The range of minimum provoking doses in hazelnut-allergic patients as determined by double-blind, placebo-controlled food challenges.

PubMed

Wensing, M; Penninks, A H; Hefle, S L; Akkerdaas, J H; van Ree, R; Koppelman, S J; Bruijnzeel-Koomen, C A F M; Knulst, A C

2002-12-01

The risk for allergic reactions depends on the sensitivity of individuals and the quantities of offending food ingested. The sensitivity varies among allergic individuals, as does the threshold dose of a food allergen capable of inducing an allergic reaction. This study aimed at determining the distribution of minimum provoking doses of hazelnut in a hazelnut-allergic population. Thirty-one patients with a history of hazelnut-related allergic symptoms, a positive skin prick test to hazelnut and/or an elevated specific IgE level, were included. Double-blind, placebo-controlled food challenges (DBPCFC) were performed with seven increasing doses of dried hazelnut (1 mg to 1 g hazelnut protein) randomly interspersed with seven placebo doses. Twenty-nine patients had a positive challenge. Itching of the oral cavity and/or lips was the first symptom in all cases. Additional gastrointestinal symptoms were reported in five patients and difficulty in swallowing in one patient. Lip swelling was observed in two patients, followed by generalized urticaria in one of these. Threshold doses for eliciting subjective reactions varied from a dose of 1 mg up to 100 mg hazelnut protein (equivalent to 6.4-640 mg hazelnut meal). Extrapolation of the dose-response curve showed that 50% of our hazelnut-allergic population will suffer from an allergic reaction after ingestion of 6 mg (95% CI, 2-11 mg) of hazelnut protein. Objective symptoms were observed in two patients after 1 and 1,000 mg, respectively. DBPCFCs demonstrated threshold doses in half of the hazelnut-allergic patients similar to doses previously described to be hidden in consumer products. This stresses the need for careful labelling and strategies to prevent and detect contamination of food products with hazelnut residues.

A randomized controlled study of peanut oral immunotherapy (OIT): clinical desensitization and modulation of the allergic response

PubMed Central

Varshney, Pooja; Jones, Stacie M.; Scurlock, Amy M.; Perry, Tamara T.; Kemper, Alex; Steele, Pamela; Hiegel, Anne; Kamilaris, Janet; Carlisle, Suzanne; Yue, Xiaohong; Kulis, Mike; Pons, Laurent; Vickery, Brian; Burks, A. Wesley

2011-01-01

Background Open-label oral immunotherapy (OIT) protocols have been used to treat small numbers of patients with peanut allergy. Peanut OIT has not been evaluated in double-blind, placebo-controlled trials. Objective To investigate the safety and effectiveness of OIT for peanut allergy in a double blind, placebo-controlled study. Methods In this multicenter study, peanut-allergic children ages 1-16 years received OIT with peanut flour or placebo. Initial escalation, build-up, and maintenance phases were followed by an oral food challenge at approximately one year. Titrated skin prick tests (SPT) and laboratory studies were performed at regular intervals. Results Twenty-eight subjects were enrolled in the study. Three peanut OIT subjects withdrew early in the study due to allergic side effects. During the double-blind, placebo-controlled food challenge, all remaining peanut OIT subjects (N=16) ingested the maximum cumulative dose of 5000 mg (approximately 20 peanuts), while placebo subjects (N=9) ingested a median cumulative dose of 280 mg (range, 0-1900 mg) [p<0.001]. In contrast to the placebo group, the peanut OIT group showed reductions in SPT size (p<0.001), IL-5 (p=0.01), and IL-13 (p=0.02) and increases in peanut-specific IgG4 (p<0.001). Peanut OIT subjects had initial increases in peanut-specific IgE (p<0.01) but did not show significant change from baseline by the time of OFC. The ratio of FoxP3 hi: FoxP3 intermediate CD4+CD25+ T cells increased at the time of OFC (p=0.04) in peanut OIT subjects. Conclusion These results conclusively demonstrate that peanut OIT induces desensitization and concurrent immune modulation. The present study continues and is evaluating the hypothesis that peanut OIT causes long-term immune tolerance. PMID:21377034

Safety, clinical, and immunologic efficacy of a Chinese herbal medicine (Food Allergy Herbal Formula-2) for food allergy.

PubMed

Wang, Julie; Jones, Stacie M; Pongracic, Jacqueline A; Song, Ying; Yang, Nan; Sicherer, Scott H; Makhija, Melanie M; Robison, Rachel G; Moshier, Erin; Godbold, James; Sampson, Hugh A; Li, Xiu-Min

2015-10-01

Food Allergy Herbal Formula-2 (FAHF-2) is a 9-herb formula based on traditional Chinese medicine that blocks peanut-induced anaphylaxis in a murine model. In phase I studies FAHF-2 was found to be safe and well tolerated. We sought to evaluate the safety and effectiveness of FAHF-2 as a treatment for food allergy. In this double-blind, randomized, placebo-controlled study 68 subjects aged 12 to 45 years with allergies to peanut, tree nut, sesame, fish, and/or shellfish, which were confirmed by baseline double-blind, placebo-controlled oral food challenges (DBPCFCs), received FAHF-2 (n = 46) or placebo (n = 22). After 6 months of therapy, subjects underwent DBPCFCs. For those who demonstrated increases in the eliciting dose, a repeat DBPCFC was performed 3 months after stopping therapy. Treatment was well tolerated, with no serious adverse events. By using intent-to-treat analysis, the placebo group had a higher eliciting dose and cumulative dose (P = .05) at the end-of-treatment DBPCFC. There was no difference in the requirement for epinephrine to treat reactions (P = .55). There were no significant differences in allergen-specific IgE and IgG4 levels, cytokine production by PBMCs, or basophil activation between the active and placebo groups. In vitro immunologic studies performed on subjects' baseline PBMCs incubated with FAHF-2 and food allergen produced significantly less IL-5, greater IL-10 levels, and increased numbers of regulatory T cells than untreated cells. Notably, 44% of subjects had poor drug adherence for at least one third of the study period. FAHF-2 is a safe herbal medication for subjects with food allergy and shows favorable in vitro immunomodulatory effects; however, efficacy for improving tolerance to food allergens is not demonstrated at the dose and duration used. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Food-additive-induced urticaria: a survey of 838 patients with recurrent chronic idiopathic urticaria.

PubMed

Di Lorenzo, Gabriele; Pacor, Maria Luisa; Mansueto, Pasquale; Martinelli, Nicola; Esposito-Pellitteri, Maria; Lo Bianco, Claudia; Ditta, Vito; Leto-Barone, Maria Stefania; Napoli, Nicola; Di Fede, Gaetana; Rini, Giovambattista; Corrocher, Roberto

2005-11-01

Recurrent chronic idiopathic urticaria (RCIU) is a common skin condition that affects 0.1-3% of the population in the USA and Europe and accounts for nearly 75% of all 'ordinary' chronic urticaria (CU) cases. We studied 838 consecutive patients with RCIU referred to hospital between 1998 and 2003. Patients with known causes of CU were excluded. Clinical history, physical examination, and symptom diaries were evaluated during two periods, a diet-free period (1 week) and a food-additive-free diet (FAFD) period (4 weeks), respectively, and two double-blind placebo-controlled (DBPC) challenges of six food additives were administered. The first DBPC challenge included a mixture of the six food additives (DBPCmixed) given to all patients. The second DBPC challenge comprised the single food additives, administered at increasing doses (DBPCsingle) to patients with a positive DBPCmixed test and 105 patients with a negative DBPCmixed test, as a control. The DBPCmixed challenge was positive in 116 patients. None of the 105 control patients had a positive DBPCsingle test. Only 31 DBPCsingle tests were positive in patients with positive DBPCmixed challenge. Twenty-four of the 116 patients showing a positive DBPCmixed challenge also had a positive DBPCsingle result. Our results confirmed that food additive hypersensitivity reactions occurred in few RCIU patients using DBPCsingle challenge. The combination of the results of FAFD and DBPCmixed challenge seems to be of considerable practical interest for allergists, internists and dermatologists, rather than the data of clinical history and the results of DBPCsingle challenge, in patients with RCIU. Copyright (c) 2005 S. Karger AG, Basel.

The impact of food allergens on airway responsiveness in schoolchildren with asthma: A DBPCFC study.

PubMed

Krogulska, Aneta; Dynowski, Jarosław; Jędrzejczyk, Magdalena; Sardecka, Izabela; Małachowska, Beata; Wąsowska-Królikowska, Krystyna

2016-08-01

Despite the growing evidence of a possible link between asthma and food allergy (FA), so far, the involvement of food in inducing respiratory symptoms has not been fully evaluated. The objective of this study was to evaluate the impact of food allergens on respiratory symptoms and bronchial reactivity (BHR) in schoolchildren with asthma. The initial study group consisted of 362 children with asthma. In the end, 22 children with concomitant FA, and 18 without FA, were selected to participate in the study. Spirometry and Methacholine Inhalation Challenge (MIC) were conducted prior to and after the completion of a double blind placebo control food challenge (DBPCFC). The food-induced asthmatic reactions were observed in nine (2.5%) out of all 362 children with asthma. Mean FEV1 prior to and after allergen or placebo challenge did not differ between the groups studied. Increase of BHR after DBPCFC was seen in 17 (4.7%) children with asthma. The mean PC20 value in children with FA was 1.41 ± 1.12 mg/ml prior to the allergen challenge and 0.86 ± 0.71 mg/ml (P = 0.002) after the test, whereas these values were 1.93 ± 1.68 mg/ml and 2.02 ± 1.75 mg/ml, respectively, in children without FA (P > 0.05). Significant differences were noted after the allergen provocation in children with FA as compared to children without FA (P = 0.007). Although food allergens are a rare trigger of food-induced asthmatic reactions in schoolchildren with asthma, they could enhance BHR, despite a lack of evident clinical respiratory signs and decreased in FEV1 values after food challenge. Pediatr Pulmonol. 2016;51:787-795. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

The effects of intranasal oxytocin on smoothie intake, cortisol and attentional bias in anorexia nervosa.

PubMed

Leppanen, Jenni; Cardi, Valentina; Ng, Kah Wee; Paloyelis, Yannis; Stein, Daniel; Tchanturia, Kate; Treasure, Janet

2017-05-01

Anorexia nervosa (AN) is characterised by severe malnutrition as well as intense fear and anxiety around food and eating with associated anomalies in information processing. Previous studies have found that the neuropeptide, oxytocin, can influence eating behaviour, lower the neurobiological stress response and anxiety among clinical populations, and alter attentional processing of food and eating related images in AN. Thirty adult women with AN and twenty-nine healthy comparison (HC) women took part in the current study. The study used double blind, placebo controlled, crossover design to investigate the effects of a single dose of intranasal oxytocin (40 IU) on a standard laboratory smoothie challenge, and on salivary cortisol, anxiety, and attentional bias towards food images before and after the smoothie challenge in AN and HC participants. Attentional bias was assessed using a visual probe task. Relative to placebo intranasal oxytocin reduced salivary cortisol and altered anomalies in attentional bias towards food images in the AN group only. The oxytocin-induced reduction in attentional avoidance of food images correlated with oxytocin induced reduction in salivary cortisol in the AN group before the smoothie challenge. Intranasal oxytocin did not significantly alter subjective feelings of anxiety or intake during the smoothie challenge in the AN or HC groups. Intranasal oxytocin may moderate the automated information processing biases in AN and reduce neurobiological stress. Further investigation of the effects of repeated administration of oxytocin on these processes as well as on eating behaviour and subjective anxiety would be of interest. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

An Experimental Evaluation of Hyperactivity and Food Additives. 1977-Phase II.

ERIC Educational Resources Information Center

Harley, J. Preston; And Others

Phase II of a study on the effectiveness of B. Feingold's recommended diet for hyperactive children involved the nine children (mean age 9 years) who had shown the "best" response to diet manipulation in Phase I. Each child served as his own control and was challenged with specified amounts of placebo and artificial color containing food…

Evidence for the Presence of Non-Celiac Gluten Sensitivity in Patients with Functional Gastrointestinal Symptoms: Results from a Multicenter Randomized Double-Blind Placebo-Controlled Gluten Challenge.

PubMed

Elli, Luca; Tomba, Carolina; Branchi, Federica; Roncoroni, Leda; Lombardo, Vincenza; Bardella, Maria Teresa; Ferretti, Francesca; Conte, Dario; Valiante, Flavio; Fini, Lucia; Forti, Edoardo; Cannizzaro, Renato; Maiero, Stefania; Londoni, Claudio; Lauri, Adriano; Fornaciari, Giovanni; Lenoci, Nicoletta; Spagnuolo, Rocco; Basilisco, Guido; Somalvico, Francesco; Borgatta, Bruno; Leandro, Gioacchino; Segato, Sergio; Barisani, Donatella; Morreale, Gaetano; Buscarini, Elisabetta

2016-02-08

Non-celiac gluten sensitivity (NCGS) is characterized by the onset of symptoms after eating gluten-containing food. We aimed to single out NCGS subjects among subjects with functional gastrointestinal symptoms. Patients were enrolled in a multicenter double-blind placebo-controlled trial with crossover. Symptoms and quality of life were evaluated by means of 10-cm VAS and SF36. Iron parameters, transaminases and C reactive protein (CRP) were evaluated. After a three-week-long gluten-free diet (GFD), responsive patients were randomly assigned to gluten intake (5.6 g/day) or placebo for seven days, followed by crossover. The primary endpoint was the worsening of symptoms (VAS increase ≥3 cm) during gluten ingestion compared to placebo. One hundred and forty patients were enrolled and 134 (17 males, mean age 39.1 ± 11.7 years, BMI 22.4 ± 3.8) completed the first period. A total of 101 subjects (10 males, mean age 39.3 ± 11.0 years, BMI 22.3 ± 4.0) reported a symptomatic improvement (VAS score 2.3 ± 1.2 vs. 6.5 ± 2.2 before and after GFD, p = 0.001). 98 patients underwent the gluten challenge and 28 (all females, mean age 38.9 ± 12.7 years, BMI 22.0 ± 2.9) reported a symptomatic relapse and deterioration of quality of life. No parameters were found to be statistically associated with positivity to the challenge. However, 14 patients responded to the placebo ingestion. Taking into account this finding, about 14% of patients responding to gluten withdrawal showed a symptomatic relapse during the gluten challenge. This group is suspected to have NCGS.

Evidence for the Presence of Non-Celiac Gluten Sensitivity in Patients with Functional Gastrointestinal Symptoms: Results from a Multicenter Randomized Double-Blind Placebo-Controlled Gluten Challenge

PubMed Central

Elli, Luca; Tomba, Carolina; Branchi, Federica; Roncoroni, Leda; Lombardo, Vincenza; Bardella, Maria Teresa; Ferretti, Francesca; Conte, Dario; Valiante, Flavio; Fini, Lucia; Forti, Edoardo; Cannizzaro, Renato; Maiero, Stefania; Londoni, Claudio; Lauri, Adriano; Fornaciari, Giovanni; Lenoci, Nicoletta; Spagnuolo, Rocco; Basilisco, Guido; Somalvico, Francesco; Borgatta, Bruno; Leandro, Gioacchino; Segato, Sergio; Barisani, Donatella; Morreale, Gaetano; Buscarini, Elisabetta

2016-01-01

Non-celiac gluten sensitivity (NCGS) is characterized by the onset of symptoms after eating gluten-containing food. We aimed to single out NCGS subjects among subjects with functional gastrointestinal symptoms. Patients were enrolled in a multicenter double-blind placebo-controlled trial with crossover. Symptoms and quality of life were evaluated by means of 10-cm VAS and SF36. Iron parameters, transaminases and C reactive protein (CRP) were evaluated. After a three-week-long gluten-free diet (GFD), responsive patients were randomly assigned to gluten intake (5.6 g/day) or placebo for seven days, followed by crossover. The primary endpoint was the worsening of symptoms (VAS increase ≥3 cm) during gluten ingestion compared to placebo. One hundred and forty patients were enrolled and 134 (17 males, mean age 39.1 ± 11.7 years, BMI 22.4 ± 3.8) completed the first period. A total of 101 subjects (10 males, mean age 39.3 ± 11.0 years, BMI 22.3 ± 4.0) reported a symptomatic improvement (VAS score 2.3 ± 1.2 vs. 6.5 ± 2.2 before and after GFD, p = 0.001). 98 patients underwent the gluten challenge and 28 (all females, mean age 38.9 ± 12.7 years, BMI 22.0 ± 2.9) reported a symptomatic relapse and deterioration of quality of life. No parameters were found to be statistically associated with positivity to the challenge. However, 14 patients responded to the placebo ingestion. Taking into account this finding, about 14% of patients responding to gluten withdrawal showed a symptomatic relapse during the gluten challenge. This group is suspected to have NCGS. PMID:26867199

Allergenic components of a novel food, Micronesian nut Nangai (Canarium indicum), shows IgE cross-reactivity in pollen allergic patients.

PubMed

Sten, Eva; Stahl Skov, P; Andersen, S B; Torp, A M; Olesen, A; Bindslev-Jensen, U; Poulsen, L K; Bindslev-Jensen, C

2002-05-01

New foods may present a risk for food hypersensitive patients. Several examples exist of allergic reactions caused by cross-reactive plant-derived foods, and new foods should be scrutinised before introducing them to the market. We have evaluated the clinical and serological relevance of cross-reactivity between Nangai and pollen allergens. Cross-reactivity was examined with Maxisorp RAST (radioallergosorbent test), RAST inhibition and Western blot, using sera from patients allergic to grass, birch and mugwort pollen. None of the patients reported having seen or eaten Nangai previously. To determine the biological and clinical relevance of the cross-reactivity, histamine release (HR) test, skin prick test (SPT) and food challenge were used. There was prevalence for reactivity against Nangai in the group of pollen allergic patients. This cross-reactivity seems to be related--at least in part--to carbohydrate epitopes. Three out of 12 patients tested with Nangai were positive upon open challenge, but using double blind placebo controlled food challenge (DBPCFC) this could not be confirmed in two patients. The biological effects of Nangai on allergic patients were confirmed using HR and SPT. The Nangai specific IgE found among pollen allergic patients addresses the need for control of new or changed foods before introduction to the market.

A new model for low-dose food challenge in children with allergy to milk or egg.

PubMed

Devenney, Irene; Norrman, Gunilla; Oldaeus, Göran; Strömberg, Leif; Fälth-Magnusson, Karin

2006-09-01

Atopic eczema and food allergy are common in early childhood. Children seem to gradually develop tolerance to milk and egg, and it is a relief for families when their child can tolerate small amounts of these basic foods, even if larger doses may still cause symptoms. To develop a model for low-dose oral food challenge, facilitating re-/introduction of milk or egg. In 39 children sensitized to milk and/or egg, we performed 52 challenges using a new standardized model for low-dose oral food challenge. The recipes were validated for blinding with sensorial tests. Four children challenged to milk had a positive challenge outcome. There were no significant differences with respect to family history, associated atopic manifestations, nutritional supply, eczema severity, or skin-prick test compared with the non-reacting children, but total and specific IgE values were significantly higher. All but two of the non-reacting children were able to introduce milk and egg into their diet without problems. We report recipes and a protocol to be used for standardized open and double-blind placebo-controlled low-dose food challenge in young children, enabling the introduction of small amounts of egg and milk into the diet during tolerance development.

A mutant of the major apple allergen, Mal d 1, demonstrating hypo-allergenicity in the target organ by double-blind placebo-controlled food challenge.

PubMed

Bolhaar, S T H P; Zuidmeer, L; Ma, Y; Ferreira, F; Bruijnzeel-Koomen, C A F M; Hoffmann-Sommergruber, K; van Ree, R; Knulst, A C

2005-12-01

Allergen-specific immunotherapy for food allergy has been hindered by severe side-effects in the past. Well-characterized hypo-allergenic recombinant food allergens potentially offer a safe solution. To demonstrate hypo-allergenicity of a mutated major food allergen from apple, Mal d 1, in vitro and in vivo. A mutant of the major apple allergen, Mal d 1, was obtained by site-directed mutagenesis exchanging five amino acid residues. Fourteen patients with combined birch pollen-related apple allergy were included in the study. Hypo-allergenicity of the mutant rMal d 1 (rMal d 1mut) compared with rMal d 1 was assessed by in vitro methods, i.e. RAST (inhibition), immunoblotting and basophil histamine release (BHR) and in vivo by skin prick test and double-blind placebo-controlled food challenge (DBPCFC). RAST analysis (n = 14) revealed that IgE reactivity to rMal d 1mut was twofold lower than that of the wild-type molecule (95% confidence interval (CI): 1.7-2.4). RAST inhibition (n = 6) showed a 7.8-fold decrease in IgE-binding potency (95% CI: 3.0-12.6). In contrast to this moderate decrease in IgE-binding potency, the biological activity of rMal d 1mut assessed by SPT and BHR decreased 10-200-fold. Hypo-allergenicity was confirmed by DBPCFC (n = 2) with both recombinant molecules. A moderate decrease in IgE-binding potency translates into a potent inhibition of biological activity. This is the first study that confirms by DBPCFC that a mutated recombinant major food allergen is clinically hypo-allergenic. This paves the way towards safer immunotherapy for the treatment of food-allergic patients.

Elicitors and co-factors in food-induced anaphylaxis in adults

PubMed Central

2013-01-01

Food-induced anaphylaxis (FIA) in adults is often insufficiently diagnosed. One reason is related to the presence of co-factors like exercise, alcohol, additives and non-steroidal anti-inflammatory drugs. The objective of this analysis was to retrospectively investigate the role of co-factors in patients with FIA. 93 adult patients with suspected FIA underwent double-blind, placebo-controlled food challenges with suspected allergens and co-factors. The elicitors of anaphylaxis were identified in 44/93 patients. 27 patients reacted to food allergens upon challenge, 15 patients reacted only when a co-factor was co-exposed with the allergen. The most common identified allergens were celery (n = 7), soy, wheat (n = 4 each) and lupine (n = 3). Among the co-factors food additives (n = 8) and physical exercise (n = 6) were most frequent. In 10 patients more than one co-factor and/or more than one food allergen was necessary to elicit a positive reaction. The implementation of co-factors into the challenge protocol increases the identification rate of elicitors in adult food anaphylactic patients. PMID:24262093

Common methodologies in the evaluation of food allergy: pitfalls and prospects of food allergy prevalence studies.

PubMed

Shu, Shang-an; Chang, Christopher; Leung, Patrick S C

2014-06-01

Global and regional studies on the prevalence of food allergies are plagued by inconsistent methodologies, variations in interpretation of results, and non-standardized study design. Hence, it becomes difficult to compare the prevalence of food allergies in different communities. This information would be useful in providing critical data that will enhance research to elucidate the nature of food allergies, and the role of gene-environment interactions in the sensitization of children and adults to foods. Testing methodologies range from questionnaires to objective in vitro and in vivo testing, to the gold standard, double-blind placebo-controlled food challenge (DBPCFC). Although considered the most accurate and reliable method in detecting the prevalence of food allergy, DBPCFC is not always practical in epidemiological studies of food allergy. On the other hand, multiple logistic regression studies have been done to determine predictability of the outcome of food challenges, and it appears that skin prick testing and in vitro-specific serum IgE are the best predictors. Future studies directed towards confirming the validity of these methods as well as developing algorithms to predict the food challenge outcomes are required, as they may someday become accessory tools to complement DBPCFC.

Can conjunctival provocation test facilitate the diagnosis of food allergy in children?

PubMed

Krane Kvenshagen, B; Jacobsen, M; Halvorsen, R

2010-01-01

Food allergy is common in children, occurring in 5-7.5%. The diagnosis may, however, be difficult. Elevated IgE or positive skin prick test to a food allergen is often considered proof of allergy, but may represent sensitisation without clinical manifestations. For a precise diagnosis oral challenge is necessary, but this is often not performed because of risk of serious allergic reactions. The aim of this study was to evaluate whether conjunctival provocation test would facilitate the diagnosis of IgE-mediated food allergy. One hundred and forty-nine children with 174 possible diagnoses of food allergy were included. General examination, skin prick test and specific IgE were performed, as well as conjunctival provocation test of the suspected food allergen. Open food challenges and double-blind placebo controlled tests were performed in order to diagnose possible food allergy. Forty-six children with strongly positive conjunctival reactions (rubor, itching, oedema) to fifty food allergens were all proven to have allergy to the food in question. The children with negative conjunctival provocation tests showed no allergic reactions when challenged. We find that a strongly positive conjunctival reaction to a food allergen correlates well with true allergy. An oral challenge should be carefully performed. With a negative conjunctival test an oral challenge may safely be performed. Copyright © 2009 SEICAP. Published by Elsevier Espana. All rights reserved.

Double-blind placebo-controlled food challenges in children with alleged cow's milk allergy: prevention of unnecessary elimination diets and determination of eliciting doses.

PubMed

Dambacher, Wendy M; de Kort, Ellen H M; Blom, W Marty; Houben, Geert F; de Vries, Esther

2013-02-08

Children with cow's milk allergy (CMA) need a cow's milk protein (CMP) free diet to prevent allergic reactions. For this, reliable allergy-information on the label of food products is essential to avoid products containing the allergen. On the other hand, both overzealous labeling and misdiagnosis that result in unnecessary elimination diets, can lead to potentially hazardous health situations. Our objective was to evaluate if excluding CMA by double-blind placebo-controlled food challenge (DBPCFC) prevents unnecessary elimination diets in the long term. Secondly, to determine the minimum eliciting dose (MED) for an acute allergic reaction to CMP in DBPCFC positive children. All children with suspected CMA under our care (Oct'05-Jun'09) were prospectively enrolled in a DBPCFC. Placebo and verum feedings were administered on two randomly assigned separate days. The MED was determined by noting the 'lowest observed adverse effect level' (LOAEL) in DBPCFC-positive children. Based on the outcomes of the DBPCFC a dietary advice was given. Parents were contacted by phone several months later about the diet of their child. 116 children were available for analysis. In 76 children CMA was rejected. In 60 of them CMP was successfully reintroduced, in 2 the parents refused introduction, in another 3 the parents stopped reintroduction. In 9 children CMA symptoms reappeared. In 40 children CMA was confirmed. Infants aged ≤ 12 months in our study group have a higher cumulative distribution of MED than older children. Excluding CMA by DBPCFC successfully stopped unnecessary elimination diets in the long term in most children. The MEDs form potential useful information for offering dietary advice to patients and their caretakers.

Food protein induced enterocolitis syndrome caused by rice beverage.

PubMed

Caminiti, Lucia; Salzano, Giuseppina; Crisafulli, Giuseppe; Porcaro, Federica; Pajno, Giovanni Battista

2013-05-14

Food protein-induced enterocolitis syndrome (FPIES) is an uncommon and potentially severe non IgE-mediated gastrointestinal food allergy. It is usually caused by cow's milk or soy proteins, but may also be triggered by ingestion of solid foods. The diagnosis is made on the basis of clinical history and symptoms. Management of acute phase requires fluid resuscitation and intravenous steroids administration, but avoidance of offending foods is the only effective therapeutic option.Infant with FPIES presented to our emergency department with vomiting, watery stools, hypothension and metabolic acidosis after ingestion of rice beverage. Intravenous fluids and steroids were administered with good clinical response. Subsequently, a double blind placebo control food challenge (DBPCFC) was performed using rice beverage and hydrolyzed formula (eHF) as placebo. The "rice based formula" induced emesis, diarrhoea and lethargy. Laboratory investigations reveal an increase of absolute count of neutrophils and the presence of faecal eosinophils. The patient was treated with both intravenous hydration and steroids. According to Powell criteria, oral food challenge was considered positive and diagnosis of FPIES induced by rice beverage was made. Patient was discharged at home with the indication to avoid rice and any rice beverage as well as to reintroduce hydrolyzed formula. A case of FPIES induced by rice beverage has never been reported. The present case clearly shows that also beverage containing rice proteins can be responsible of FPIES. For this reason, the use of rice beverage as cow's milk substitute for the treatment of non IgE-mediated food allergy should be avoided.

Diagnostic Value of Tryptase in Food Allergic Reactions: A Prospective Study of 160 Adult Peanut Challenges.

PubMed

Dua, Shelley; Dowey, James; Foley, Loraine; Islam, Sabita; King, Yvonne; Ewan, Pamela; Clark, Andrew T

2018-02-27

Serum tryptase is useful in diagnosing drug and venom anaphylaxis. Its utility in food anaphylaxis is unknown. The objective of this study was to determine whether tryptase rises in food allergic reactions, optimal sampling time points, and a diagnostic cutoff for confirming a clinical reaction. Characterized peanut allergic patients were recruited and underwent up to 4 peanut challenges and 1 placebo challenge each. Tryptase was measured serially on challenge days both before (baseline) and during the challenge. The peak percentage tryptase rise (peak/baseline) was related to reaction severity. Receiver operating characteristic (ROC) curves were generated establishing an optimal diagnostic cutoff. Tryptase was analyzed in 160 reactive (9% anaphylaxis) and 45 nonreactive (placebo) challenges in 50 adults aged 18 to 39 years. Tryptase rose above the normal range (11.4 ng/mL) in 4 of 160 reactions. When compared with baseline levels, a rise was observed in 100 of 160 (62.5%) reactions and 0 of 45 placebo challenges. The median rise (95% confidence interval [CI]) for all reactions was 25% (13.3% to 33.3%) and 70.8% (33.3% to 300%) during anaphylaxis. Peak levels occurred at 2 hours and correlated with severity (P < .05). Moderate-to-severe respiratory symptoms, generalized erythema, dizziness, and hypotension were correlated with a higher peak/baseline tryptase (P < .05). ROC curve analysis demonstrated the optimal cutoff to identify a reaction as a 30% rise (sensitivity 0.53; specificity 0.85), area under the curve 0.72 (95% CI, 0.67-0.78). Serum tryptase measurement is valuable in food allergic reactions, and correlates with symptom severity. Comparing peak reaction levels at 2 hours with baseline is essential. A rise in tryptase of 30% is associated with food allergic reactions. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

The diagnosis of Brazil nut allergy using history, skin prick tests, serum-specific immunoglobulin E and food challenges.

PubMed

Ridout, S; Matthews, S; Gant, C; Twiselton, R; Dean, T; Arshad, S H

2006-02-01

Allergy to Brazil nut is a relatively common nut allergy and can be fatal. However, the evidence is lacking regarding the best approach to its diagnosis. We sought to determine the relative merits of history, skin prick testing, measurement of serum-specific IgE and challenge in the diagnosis of Brazil nut allergy. Fifty-six children and adults with a history of an allergic reaction to Brazil nut or evidence of sensitization were investigated by questionnaire (n=56), skin prick tests (SPTs) (n=53), measurement of serum-specific IgE to Brazil nut (n=54) and double-blind, placebo-controlled labial, and if necessary oral, challenges (n=19). Brazil nut allergy occurred in highly atopic individuals of any age with a strong family history of atopy. In 24 of 56 (43%), the history of an immediate reaction was sufficient to make a diagnosis with confidence and an oral challenge was considered unsafe. Of the 19 subjects undertaking the 'gold standard' test of a double-blind, placebo-controlled, food challenge, all six subjects with a SPT of at least 6 mm had a positive challenge and all three subjects with a SPT of 0 mm had a negative challenge. In the remaining 10 (53%) subjects, where SPT was between 1 and 5 mm and serum-specific IgE was less than 3.5 kU/L, an oral challenge was performed resulting in three positive and seven negative challenges. A combination of history, SPT and serum-specific IgE was adequate in achieving a diagnosis in the majority (77%) patients with suspected Brazil nut allergy. However, a doubtful history with SPT between 1 and 5 mm, or a serum-specific IgE less than 3.5 kU/L may require an oral challenge to help determine the risk of a Brazil nut allergic reaction.

Immunotherapy (oral and sublingual) for food allergy to fruits.

PubMed

Yepes-Nuñez, Juan Jose; Zhang, Yuan; Roqué i Figuls, Marta; Bartra Tomas, Joan; Reyes, Juan Manuel; Pineda de la Losa, Fernando; Enrique, Ernesto

2015-11-09

Food allergy is an abnormal immunological response following exposure (usually ingestion) to a food. Elimination of the allergen is the principle treatment for food allergy, including allergy to fruit. Accidental ingestion of allergenic foods can result in severe anaphylactic reactions. Allergen-specific immunotherapy (SIT) is a specific treatment, when the avoidance of allergenic foods is problematic. Recently, studies have been conducted on different types of immunotherapy for the treatment of food allergy, including oral (OIT) and sublingual immunotherapy (SLIT). To determine the efficacy and safety of oral and sublingual immunotherapy in children and adults with food allergy to fruits, when compared with placebo or an elimination strategy. The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, and AMED were searched for published results along with trial registries and the Journal of Negative Results in BioMedicine for grey literature. The date of the most recent search was July 2015. Randomised controlled trials (RCTs) comparing OIT or SLIT with placebo or an elimination diet were included. Participants were children or adults diagnosed with food allergy who presented immediate fruit reactions. We used standard methodological procedures expected by the Cochrane Collaboration. We assessed treatment effect through risk ratios (RRs) for dichotomous outcomes. We identified two RCTs (N=89) eligible for inclusion. These RCTs addressed oral or sublingual immunotherapy, both in adults, with an allergy to apple or peach respectively. Both studies enrolled a small number of participants and used different methods to provide these differing types of immunotherapy. Both studies were judged to be at high risk of bias in at least one domain. Overall, the quality of evidence was judged to be very low due to the small number of studies and participants and possible bias. The studies were clinically heterogeneous and hence we did not pool the results. A study comparing SLIT with placebo for allergy to peach did not detect a significant difference between the number of patients desensitised at six months following a double-blind placebo-controlled food challenge (RR 1.16, 95% confidence interval (CI) 0.49 to 2.74). The second study, comparing OIT versus no treatment for apple allergy, found an effect on desensitisation in favour of the intervention using an oral provocation test at eight months, but results were imprecise (RR 17.50, 95% CI 1.13 to 270.19). Neither study reported data on evidence of immunologic tolerance. In both studies, the incidence of mild and moderate adverse events was higher in the intervention groups than in the controls. In the study comparing SLIT with placebo, patients in the intervention group experienced significantly more local adverse reactions than participants in the control group (RR 3.21, 95% CI 1.51 to 6.82), though there was not a significant difference in the number of participants experiencing systemic adverse reactions (RR 0.81, 95% CI 0.22 to 3.02). In the study of OIT, two of the 25 participants in the intervention group reported relevant side effects, whereas no participants in the control group reported relevant side effects. There is insufficient evidence for using OIT or SLIT to treat allergy to fruit, specifically related to peach and apple. Mild or moderate adverse reactions were reported more frequently in people receiving OIT or SLIT. However, these reactions could be treated successfully with medications.

Dietary assessment in children adhering to a food allergen avoidance diet for allergy prevention.

PubMed

Vlieg-Boerstra, B J; van der Heide, S; Bijleveld, C M A; Kukler, J; Duiverman, E J; Wolt-Plompen, S A A; Dubois, A E J

2006-12-01

The purpose of this investigation was to verify if avoidance of allergenic foods in children adhering to a food allergen avoidance diet from birth was complete and feasible, and whether dietary assessment can be used as a tool in predicting the outcome of double-blind, placebo-controlled food challenges (DBPCFCs). Children adhering to an allergen avoidance diet from birth underwent DBPCFCs. The investigator-dietician verified whether the elimination was complete, using food frequency questionnaires for common allergenic foods. University Medical Centre Groningen, the Netherlands. Thiry-eight children aged 1-13 years, who were consecutively referred to the University Medical Centre Groningen for DBPCFC between January 2002 and February 2004. Among the 38 children undergoing DBPCFCs, there were 15 challenges with egg, 15 with peanut, five with hazelnut and three with soy. Fifteen food challenges (39%) were positive. Small quantities of allergenic foods were inadvertently present in the diets of 13 patients (34%), were possibly present in the diets of 14 patients (37%) and could not be identified in the diets of 11 patients (29%). Seven patients (54%) who had inadvertently ingested small quantities of allergenic foods without sequelae had a positive DBPCFC. Dietary avoidance was incomplete and not feasible in most cases. Tolerance of small amounts of allergenic foods does not preclude positive challenge reactions. Dietary assessment does not seem a useful tool in predicting the outcome of DBPCFC in children adhering to an elimination diet. The Stichting Astma Bestrijding (Foundation for the Prevention of Asthma), The Netherlands.

A Clinical Trial about a Food Supplement Containing α-Lipoic Acid on Oxidative Stress Markers in Type 2 Diabetic Patients.

PubMed

Derosa, Giuseppe; D'Angelo, Angela; Romano, Davide; Maffioli, Pamela

2016-10-28

The aim of this study was to evaluate the effect of a food supplement containing α-lipoic acid and of a placebo on glyco-metabolic control and on oxidative stress markers in type 2 diabetics. We randomized 105 diabetics to either a supplementation containing 600 mg of α-lipoic acid, 165 mg of L -carnosin, 7.5 mg of zinc, and vitamins of group B, or a placebo, for three months. We evaluated body mass index, fasting plasma glucose (FPG), post-prandial-glucose (PPG), glycated hemoglobin (HbA 1c ), fasting plasma insulin (FPI), HOMA-index (HOMA-IR), lipid profile, high sensitivity C-reactive protein (Hs-CRP), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA). There was a reduction of FPG, PPG, and HbA 1c with the food supplement containing α-lipoic acid compared with a baseline, and with the placebo. Concerning lipid profile, we observed a reduction of LDL-C, and Tg with the food supplement, compared with both the baseline, and the placebo. There was a reduction of Hs-CRP with the food supplement containing α-lipoic acid, both compared with the baseline and the placebo. An increase of SOD, and GSH-Px, and a decrease of MDA were reached by the food supplement containing α-lipoic acid, both compared with the baseline and the placebo. We can conclude that the food supplement containing α-lipoic acid, L -carnosin, zinc, and vitamins of group B improved glycemic control, lipid profile, and anti-oxidative stress markers.

A Clinical Trial about a Food Supplement Containing α-Lipoic Acid on Oxidative Stress Markers in Type 2 Diabetic Patients

PubMed Central

Derosa, Giuseppe; D’Angelo, Angela; Romano, Davide; Maffioli, Pamela

2016-01-01

The aim of this study was to evaluate the effect of a food supplement containing α-lipoic acid and of a placebo on glyco-metabolic control and on oxidative stress markers in type 2 diabetics. We randomized 105 diabetics to either a supplementation containing 600 mg of α-lipoic acid, 165 mg of L-carnosin, 7.5 mg of zinc, and vitamins of group B, or a placebo, for three months. We evaluated body mass index, fasting plasma glucose (FPG), post-prandial-glucose (PPG), glycated hemoglobin (HbA1c), fasting plasma insulin (FPI), HOMA-index (HOMA-IR), lipid profile, high sensitivity C-reactive protein (Hs-CRP), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA). There was a reduction of FPG, PPG, and HbA1c with the food supplement containing α-lipoic acid compared with a baseline, and with the placebo. Concerning lipid profile, we observed a reduction of LDL-C, and Tg with the food supplement, compared with both the baseline, and the placebo. There was a reduction of Hs-CRP with the food supplement containing α-lipoic acid, both compared with the baseline and the placebo. An increase of SOD, and GSH-Px, and a decrease of MDA were reached by the food supplement containing α-lipoic acid, both compared with the baseline and the placebo. We can conclude that the food supplement containing α-lipoic acid, L-carnosin, zinc, and vitamins of group B improved glycemic control, lipid profile, and anti-oxidative stress markers. PMID:27801825

Effects of Intranasal Oxytocin on the Blood Oxygenation Level-Dependent Signal in Food Motivation and Cognitive Control Pathways in Overweight and Obese Men.

PubMed

Plessow, Franziska; Marengi, Dean A; Perry, Sylvia K; Felicione, Julia M; Franklin, Rachel; Holmes, Tara M; Holsen, Laura M; Makris, Nikolaos; Deckersbach, Thilo; Lawson, Elizabeth A

2018-02-01

Recent research indicates that the hypothalamic neuropeptide hormone oxytocin is a key central nervous system factor in the regulation of food intake and weight. However, the mechanisms underlying the anorexigenic effects of oxytocin in humans are unknown and critical to study to consider oxytocin as a neurohormonal weight loss treatment. We performed a randomized, double-blind, placebo-controlled crossover study with single-dose intranasal oxytocin (24 IU) in ten overweight or obese, otherwise healthy men. Following oxytocin/placebo administration, participants completed an established functional magnetic resonance imaging food motivation paradigm. We hypothesized that oxytocin would reduce the blood oxygenation level-dependent (BOLD) signal to high-calorie food vs non-food visual stimuli in the ventral tegmental area (VTA), the origin of the mesolimbic dopaminergic reward system. Following oxytocin administration, compared to placebo, participants showed bilateral VTA hypoactivation to high-calorie food stimuli. A secondary exploratory whole-brain analysis revealed hypoactivation in additional hedonic (orbitofrontal cortex, insula, globus pallidus, putamen, hippocampus, and amygdala) and homeostatic (hypothalamus) food motivation and hyperactivation in cognitive control (anterior cingulate and frontopolar cortex) brain regions following oxytocin administration vs placebo. Oxytocin administration reduces the BOLD signal in reward-related food motivation brain regions, providing a potential neurobiological mechanism for the anorexigenic oxytocin effects in humans. Furthermore, our data indicate that oxytocin administration reduces activation in homeostatic and increases activation in cognitive control brain regions critically involved in regulating food intake and resolving affective conflict, respectively. Future studies are required to link these changes in brain activation to oxytocin effects on food intake and weight.

Walnut consumption increases activation of the insula to highly desirable food cues: A randomized, double-blind, placebo-controlled, cross-over fMRI study.

PubMed

Farr, Olivia M; Tuccinardi, Dario; Upadhyay, Jagriti; Oussaada, Sabrina M; Mantzoros, Christos S

2018-01-01

The use of walnuts is recommended for obesity and type 2 diabetes, although the mechanisms through which walnuts may improve appetite control and/or glycaemic control remain largely unknown. To determine whether short-term walnut consumption could alter the neural control of appetite using functional magnetic resonance imaging, we performed a randomized, placebo-controlled, double-blind, cross-over trial of 10 patients who received, while living in the controlled environment of a clinical research center, either walnuts or placebo (using a validated smoothie delivery system) for 5 days each, separated by a wash-out period of 1 month. Walnut consumption decreased feelings of hunger and appetite, assessed using visual analog scales, and increased activation of the right insula to highly desirable food cues. These findings suggest that walnut consumption may increase salience and cognitive control processing of highly desirable food cues, leading to the beneficial metabolic effects observed. © 2017 John Wiley & Sons Ltd.

The effects of a double blind, placebo controlled, artificial food colourings and benzoate preservative challenge on hyperactivity in a general population sample of preschool children

PubMed Central

Bateman, B; Warner, J; Hutchinson, E; Dean, T; Rowlandson, P; Gant, C; Grundy, J; Fitzgerald, C; Stevenson, J

2004-01-01

Aims: To determine whether artificial food colourings and a preservative in the diet of 3 year old children in the general population influence hyperactive behaviour. Methods: A sample of 1873 children were screened in their fourth year for the presence of hyperactivity at baseline (HA), of whom 1246 had skin prick tests to identify atopy (AT). Children were selected to form the following groups: HA/AT, not-HA/AT, HA/not-AT, and not-HA/not-AT (n = 277). After baseline assessment, children were subjected to a diet eliminating artificial colourings and benzoate preservatives for one week; in the subsequent three week within subject double blind crossover study they received, in random order, periods of dietary challenge with a drink containing artificial colourings (20 mg daily) and sodium benzoate (45 mg daily) (active period), or a placebo mixture, supplementary to their diet. Behaviour was assessed by a tester blind to dietary status and by parents' ratings. Results: There were significant reductions in hyperactive behaviour during the withdrawal phase. Furthermore, there were significantly greater increases in hyperactive behaviour during the active than the placebo period based on parental reports. These effects were not influenced by the presence or absence of hyperactivity, nor by the presence or absence of atopy. There were no significant differences detected based on objective testing in the clinic. Conclusions: There is a general adverse effect of artificial food colouring and benzoate preservatives on the behaviour of 3 year old children which is detectable by parents but not by a simple clinic assessment. Subgroups are not made more vulnerable to this effect by their prior levels of hyperactivity or by atopy. PMID:15155391

BASALIT trial: double-blind placebo-controlled allergen immunotherapy with rBet v 1-FV in birch-related soya allergy.

PubMed

Treudler, R; Franke, A; Schmiedeknecht, A; Ballmer-Weber, B; Worm, M; Werfel, T; Jappe, U; Biedermann, T; Schmitt, J; Brehler, R; Kleinheinz, A; Kleine-Tebbe, J; Brüning, H; Ruëff, F; Ring, J; Saloga, J; Schäkel, K; Holzhauser, T; Vieths, S; Simon, J C

2017-08-01

Conflicting results exist on the effect of allergen immunotherapy (AIT) on pollen-related food allergy. We aimed to investigate the efficacy of one-year AIT with the folding variant (FV) of recombinant (r) Bet v 1 on birch-related soya allergy. Of 138 subjects with Bet v 1 sensitization, 82 were positive at double-blind placebo-controlled food challenge (DBPCFC) with soya. A total of 56 of 82 were randomized in the ratio of 2:1 (active: placebo). Per-protocol population (PPP) had received ≥150 μg of allergen or placebo preparation. lowest observed adverse effect levels (LOAEL), postinterventional occurrence of objective signs (objS) at any dose level, sIgE/IgG4 against Bet v 1 and Gly m 4. Between-group changes were investigated (ancova, Mann-Whitney U-test, Fisher exact test). Baseline characteristics including LOAELs were comparable in both groups with objS and subjS occurring in 82% and 95% of active (n = 38) vs 78% and 83% of placebo group (n = 18). After AIT, objS occurred in 24% and 47%, respectively. LOAEL group differences showed a beneficial tendency (P = 0.081) for LOAEL objective in PPP (30 active, 15 placebo). sIgG4 raised only in active group (Bet v 1: P = 0.054, Gly m 4: P = 0.037), and no relevant changes occurred for sIgE. Only 56% of the intended sample size was recruited. For the first time, we present data on the effect of rBet v 1-FV on birch-related soya allergy. rBet v 1-FV AIT induced significant immunogenic effects. Clinical assessment showed a tendency in favour of the active group but did not reach statistical significance. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Zinc-rich oysters as well as zinc-yeast- and astaxanthin-enriched food improved sleep efficiency and sleep onset in a randomized controlled trial of healthy individuals.

PubMed

Saito, Hitomi; Cherasse, Yoan; Suzuki, Rina; Mitarai, Makoto; Ueda, Fumitaka; Urade, Yoshihiro

2017-05-01

Zinc is an essential mineral that plays an important role in the body. We previously reported that orally feeding zinc-enriched yeast to mice induces nonrapid-eye-movement sleep. In addition, astaxanthin, an antioxidant abundant in seafood such as salmon and krill, is able to chelate minerals and may promote zinc absorption, which in return may also improve sleep. The purpose of our study was to examine the effect of zinc-rich and astaxanthin-containing food on sleep in humans. We conducted a randomized, double-blinded, placebo-controlled parallel group trial of 120 healthy subjects and recorded their night activity by actigraphy for 12 weeks. These subjects were divided into four groups: placebo, zinc-rich food, zinc-, and astaxanthin-rich food, and placebo supplemented with zinc-enriched yeast and astaxanthin oil. Compared with the placebo group, the zinc-rich food group efficiently decreased the time necessary to fall asleep and improved sleep efficiency, whereas the group that ingested zinc-enriched yeast and astaxanthin oil significantly improved the sleep onset latency. Actigraphic sleep monitoring demonstrated that eating zinc-rich food improved sleep onset latency as well as improved the sleep efficiency in healthy individuals. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Role of atopy patch test for diagnosis of food allergy-related gastrointestinal symptoms in children.

PubMed

Boonyaviwat, Onsuree; Pacharn, Punchama; Jirapongsananuruk, Orathai; Vichyanond, Pakit; Visitsunthorn, Nualanong

2015-12-01

Double-blind, placebo-controlled food challenge is the gold standard for diagnosing food allergy. However, it is a time-consuming procedure and requires onsite medical supervision and resuscitating medicines and devices on hand. The objective of this study was to compare the atopy patch test (APT) with the oral food challenge test (OFC) in children with suspected food allergy-related gastrointestinal (GI) symptoms. A prospective self-controlled study enrolled children with a history of suspected food allergy-related GI symptoms. Skin prick test (SPT) and APT using lyophilized and commercial allergen extracts for cow's milk, egg, wheat, soy, and shrimp were evaluated, and OFC was performed. Thirty-nine patients (25 boys, median age 2.4 yrs) with 76 events of suspected food allergy-related GI symptoms were enrolled. SPT was positive in 11/76 events (14.5%). Sensitivity, specificity, predictive values, and likelihood ratio were calculated related to the food challenge outcome. Of 41 OFC, 30 (73.2%) were positive. APT using lyophilized allergen extracts yielded high sensitivity (80%) and high positive predictive value (85.7%). APT using commercial allergen extracts yielded low sensitivity (30%) but high specificity (90%). The negative predictive value of APT using lyophilized and commercial allergen extracts was 53.8% and 32.2%, respectively. All cases with positive APT using lyophilized allergen extracts together with positive SPT also had positive OFC. In contrast to commercial extracts, APT with lyophilized allergen extracts is reliable, safe, and maybe useful for the diagnosis of suspected food allergy-related GI symptoms in children. OFC is still needed in most of the cases. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Fructan, Rather Than Gluten, Induces Symptoms in Patients With Self-Reported Non-Celiac Gluten Sensitivity.

PubMed

Skodje, Gry I; Sarna, Vikas K; Minelle, Ingunn H; Rolfsen, Kjersti L; Muir, Jane G; Gibson, Peter R; Veierød, Marit B; Henriksen, Christine; Lundin, Knut E A

2018-02-01

Non-celiac gluten sensitivity is characterized by symptom improvement after gluten withdrawal in absence of celiac disease. The mechanisms of non-celiac gluten sensitivity are unclear, and there are no biomarkers for this disorder. Foods with gluten often contain fructans, a type of fermentable oligo-, di-, monosaccharides and polyols. We aimed to investigate the effect of gluten and fructans separately in individuals with self-reported gluten sensitivity. We performed a double-blind crossover challenge of 59 individuals on a self-instituted gluten-free diet, for whom celiac disease had been excluded. The study was performed at Oslo University Hospital in Norway from October 2014 through May 2016. Participants were randomly assigned to groups placed on diets containing gluten (5.7 g), fructans (2.1 g), or placebo, concealed in muesli bars, for 7 days. Following a minimum 7-day washout period (until the symptoms induced by the previous challenge were resolved), participants crossed over into a different group, until they completed all 3 challenges (gluten, fructan, and placebo). Symptoms were measured by Gastrointestinal Symptom Rating Scale Irritable Bowel Syndrome (GSRS-IBS) version. A linear mixed model for analysis was used. Overall GSRS-IBS scores differed significantly during gluten, fructan, and placebo challenges; mean values were 33.1 ± 13.3, 38.6 ± 12.3, and 34.3 ± 13.9, respectively (P = .04). Mean scores for GSRS-IBS bloating were 9.3 ± 3.5, 11.6 ± 3.5, and 10.1 ± 3.7, respectively, during the gluten, fructan, and placebo challenges (P = .004). The overall GSRS-IBS score for participants consuming fructans was significantly higher than for participants consuming gluten (P = .049), as was the GSRS bloating score (P = .003). Thirteen participants had the highest overall GSRS-IBS score after consuming gluten, 24 had the highest score after consuming fructan, and 22 had the highest score after consuming placebo. There was no difference in GSRS-IBS scores between gluten and placebo groups. In a randomized, double-blind, placebo-controlled crossover study of individuals with self-reported non-celiac gluten sensitivity, we found fructans to induce symptoms, measured by the GSRS-IBS. Clinicaltrials.gov no: NCT02464150. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Clinical reactivity of celery cultivars in allergic patients: Role of Api g 1.

PubMed

Dölle, S; Welter, S; Ruppel, E; Lehmann, K; Schwarz, D; Jensen-Jarolim, E; Zieglmayer, P; Franken, P; Worm, M

2018-04-01

Celery (Apium graveolens L.) is a vegetable consumed world-wide. Celery stalks and celeriac roots are often ingredients in convenient food products like spice blends and soups. In this study, we examined the allergenicity of distinct celeriac cultivars. Sixteen celery-allergic patients were identified using a double-blind, placebo-controlled food challenge. Ten different celeriac cultivars were used for skin prick testing in the patients. Two cultivars were further applied for oral food challenges; their protein composition was analysed by immunoblotting, and contents of major allergen Api g 1 were quantified. From the 10 investigated celeriac cultivars, two cultivars elicited significantly different skin reactivity ("Anita": 5.0 [2.0-12.0] mm vs "Prinz": 7.0 [3.0-9.5] mm; P = .047). Moreover, "Anita" induced fewer symptoms after a controlled oral-celeriac challenge in 14 patient (P < .001). The protein profiles on 2DE protein gels showed distinct protein patterns and higher protein amounts of Api g 1 in "Prinz" than in "Anita." Taken together, the data from this study suggest that cultivar Anita is better tolerated in celery-allergic patients than "Prinz." Differences in the protein expression profile between the cultivars, particularly the different content of Api g 1, could cause the different allergenicity. © 2018 John Wiley & Sons Ltd.

Sesame allergy: current perspectives.

PubMed

Adatia, Adil; Clarke, Ann Elaine; Yanishevsky, Yarden; Ben-Shoshan, Moshe

2017-01-01

Sesame is an important global allergen affecting ~0.1% of the North American population. It is a major cause of anaphylaxis in the Middle East and is the third most common food allergen in Israel. We conducted a systematic review of original articles published in the last 10 years regarding the diagnosis and management of sesame allergy. Skin prick testing appears to be a useful predictor of sesame allergy in infants, although data are less consistent in older children and adults. The diagnostic capacity of serum-specific immunoglobulin E is poor, especially in studies that used oral food challenges to confirm the diagnosis. Double-blind, placebo-controlled food challenge thus remains the diagnostic gold standard for sesame allergy. The cornerstone of sesame allergy management is allergen avoidance, though accidental exposures are common and patients must be prepared to treat the consequent reactions with epinephrine. Novel diagnostic and treatment options such as component-resolved diagnostics, basophil activation testing, and oral immunotherapy are under development but are not ready for mainstream clinical application.

Food-specific sublingual immunotherapy is well tolerated and safe in healthy dogs: a blind, randomized, placebo-controlled study.

PubMed

Maina, E; Pelst, M; Hesta, M; Cox, E

2017-01-18

Food allergies are increasing in prevalence but no treatment strategies are currently available to cure dogs with food allergy. Over the past decade, experimental food allergen-specific sublingual immunotherapy (FA-SLIT) has emerged as a potential treatment for food allergies in human medicine. However, FA-SLIT has not been investigated in dogs. Therefore, the objective of this study was to prospectively evaluate the safety, tolerability and dispenser sterility of FA-SLIT in healthy dogs before testing it in food allergic dogs. Eight experimental healthy beagle dogs, never orally exposed to peanut, were randomized in two groups to receive SLIT with peanut or placebo for 4 months. Subjects were monitored daily for local and systemic adverse effects. Blood samples for complete blood count and serum biochemistry, and urine for urinalysis were collected and the dogs' body weight was recorded at day 0, 35 and 119 of the SLIT treatment. Sera for the determination of peanut-specific IgG and IgE were collected at day 0, 35, 49, 70, 91, 105 and 119. Intradermal tests were performed before (day 0) and after (day 119) the experiment. The content of each dispenser used to administer treatment or placebo was tested for sterility after usage. In order to assess the presence or absence of sensitization, dogs were challenged 6 months after the end of the study with 2000 μg of peanut extract daily for 7 to 14 days. All dogs completed the study. The treatment did not provoke either local or systemic side-effects. Peanut-specific IgG significantly increased in treatment group. Even though a significant increase in peanut-specific IgE was also seen, intradermal tests were negative in all dogs before and after the experiment, and the challenge test did not trigger any adverse reactions in the treated dogs, which shows the protocol did not cause sensitization to peanut, but nevertheless primed the immune system as indicated by the humoral immune response. All dispenser solutions were sterile. Our results demonstrate that the used peanut-SLIT protocol is well tolerated and safe in healthy dogs. Further studies should evaluate tolerability, safety and efficacy in dogs with food allergy.

Challenges and Recommendations for Placebo Controls in Randomized Trials in Physical and Rehabilitation Medicine

PubMed Central

Fregni, Felipe; Imamura, Marta; Chien, Hsin Fen; Lew, Henry L.; Boggio, Paulo; Kaptchuk, Ted J; Riberto, Marcelo; Hsing, Wu Tu; Battistella, Linamara Rizzo; Furlan, Andrea

2010-01-01

Compared to other specialties, the field of Physical and Rehabilitation Medicine (PRM) has not received the deserved recognition from clinicians and researchers in the scientific community. One of the reasons is the lack of sound evidence to support the traditional PRM treatments. The best way to change this disadvantage is through well-conducted clinical research, such as the standard placebo or sham-controlled randomized clinical trials. Therefore, having placebo groups in clinical trials is essential to improve the level of evidence-based practice in PRM that ultimately translates in a better clinical care. To address the challenges for the use of placebo in PRM randomized clinical trials, and to create useful recommendations, we convened a working group during the inaugural International Symposium in Placebo (February 2009, in Sao Paulo, Brazil) in which the following topics were discussed: (1) current status of randomized clinical trials in PRM, (2) challenges for the use of placebo in PRM, (3) bioethical issues, (4) use of placebo in acupuncture trials and for the treatment of low-back pain, (5) mechanisms of placebo, and (6) insights from other specialties. The current article represents the consensus report from the working group. PMID:20090428

Two-step egg introduction for prevention of egg allergy in high-risk infants with eczema (PETIT): a randomised, double-blind, placebo-controlled trial.

PubMed

Natsume, Osamu; Kabashima, Shigenori; Nakazato, Junko; Yamamoto-Hanada, Kiwako; Narita, Masami; Kondo, Mai; Saito, Mayako; Kishino, Ai; Takimoto, Tetsuya; Inoue, Eisuke; Tang, Julian; Kido, Hiroshi; Wong, Gary W K; Matsumoto, Kenji; Saito, Hirohisa; Ohya, Yukihiro

2017-01-21

Evidence is accumulating that early consumption is more beneficial than is delayed introduction as a strategy for primary prevention of food allergy. However, allergic reactions caused by early introduction of such solid foods have been a problematic issue. We investigated whether or not early stepwise introduction of eggs to infants with eczema combined with optimal eczema treatment would prevent egg allergy at 1 year of age. In this randomised, double-blind, placebo-controlled trial, we enrolled infants 4-5 months of age with eczema from two centres in Japan. Exclusion criteria were being born before 37 weeks of gestational age, experience of ingestion of hen's eggs or egg products, history of immediate allergic reaction to hen's eggs, history of non-immediate allergic reaction to a particular type of food, and complications of any severe disease. Infants were randomly assigned (block size of four; stratified by institution and sex) to early introduction of egg or placebo (1:1). Participants in the egg group consumed orally 50 mg of heated egg powder per day from 6 months to 9 months of age and 250 mg per day thereafter until 12 months of age. We aggressively treated participants' eczema at entry and maintained control without exacerbations throughout the intervention period. Participants and physicians were masked to assignment, and allocation was concealed. The primary outcome was the proportion of participants with hen's egg allergy confirmed by open oral food challenges at 12 months of age, assessed blindly by standardised methods, in all randomly allocated participants who received the intervention. This trial is registered with the University Hospital Medical Information Network Clinical Trials Registry, number UMIN000008673. Between Sept 18, 2012, and Feb 13, 2015, we randomly allocated 147 participants (73 [50%] to the egg group and 74 [50%] to the placebo group). This trial was terminated on the basis of the results of the scheduled interim analysis of 100 participants, which showed a significant difference between the two groups (four [9%] of 47 participants had an egg allergy in the egg group vs 18 [38%] of 47 in the placebo group; risk ratio 0·222 [95% CI 0·081-0·607]; p=0·0012). In the primary analysis population, five (8%) of 60 participants had an egg allergy in the egg group compared with 23 (38%) of 61 in the placebo group (risk ratio 0·221 [0·090-0·543]; p=0·0001). The only difference in adverse events between groups was admissions to hospital (six [10%] of 60 in the egg group vs none in the placebo group; p=0·022). 19 acute events occurred in nine (15%) participants in the egg group versus 14 events in 11 (18%) participants in the placebo group after intake of the trial powder. Introduction of heated egg in a stepwise manner along with aggressive eczema treatment is a safe and efficacious way to prevent hen's egg allergy in high-risk infants. In this study, we developed a practical approach to overcome the second wave of the allergic epidemic caused by food allergy. Ministry of Health, Labour and Welfare, and National Centre for Child Health and Development, Japan. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dietary Milk-Fat-Globule Membrane Affects Resistance to Diarrheagenic Escherichia coli in Healthy Adults in a Randomized, Placebo-Controlled, Double-Blind Study.

PubMed

Ten Bruggencate, Sandra J; Frederiksen, Pernille D; Pedersen, Simon M; Floris-Vollenbroek, Esther G; Lucas-van de Bos, Elly; van Hoffen, Els; Wejse, Peter L

2016-02-01

The milk-fat-globule membrane (MFGM) contains phospholipids and membrane glycoproteins that have been shown to affect pathogen colonization and gut barrier integrity. In the present study, we determined whether commercial heat-treated MFGM can increase resistance to diarrheagenic Escherichia coli. A randomized, placebo-controlled, double-blind, 4-wk parallel-intervention study was conducted in healthy adults. Participants were randomly assigned to a milk protein concentrate rich in MFGM [10 g Lacprodan PL-20 (Arla Foods Ingredients Group P/S), twice daily; n = 30; MFGM group) or a control [10 g Miprodan 30 (sodium caseinate), twice daily; n = 28]. After 2 wk, participants were orally challenged with live, attenuated diarrheagenic E. coli (10(10) colony-forming units). Primary outcomes were infection-induced diarrhea and fecal diarrheagenic E. coli excretion. Secondary outcomes were gastrointestinal symptoms [Gastrointestinal Symptom Rating Scale (GSRS)], stool frequency, and stool consistency (Bristol Stool Scale). Diarrheagenic E. coli resulted in increased fecal output, lower relative fecal dry weight, increased fecal E. coli numbers, and an increase in stool frequency and gastrointestinal complaints at day 1 after challenge. MFGM significantly decreased the E. coli-induced changes in reported stool frequency (1.1 ± 0.1 stools/d in the MFGM group; 1.6 ± 0.2 stools/d in the control group; P = 0.04) and gastrointestinal complaints at day 2 (1.1 ± 0.5 and 2.5 ± 0.6 GSRS scores in the MFGM and control groups, respectively; P = 0.05). MFGM did not affect fecal wet weight and E. coli excretion at day 2 after challenge. The attenuated diarrheagenic E. coli strain transiently induced mild symptoms of a food-borne infection, with complete recovery of reported clinical symptoms within 2 d. The present diarrheagenic E. coli challenge trial conducted in healthy adults indicates that a milk concentrate rich in natural, bioactive phospho- and sphingolipids from the MFGM may improve in vivo resistance to diarrheagenic E. coli. This trial was registered at clinicaltrials.gov as NCT01800396. © 2016 American Society for Nutrition.

The role of food allergy in atopic dermatitis.

PubMed

Greenhawt, Matthew

2010-01-01

Atopic dermatitis (AD) affects ∼10% of children. Food allergy is a known provoking cause of AD in a subset of affected children. A literature search of PubMed and Medline was conducted to review the epidemiology and pathophysiology of AD, with special focus on the role of food allergy in the development of AD, its management, and its long-term preventive strategies. A literature search of PubMed and Medline was conducted. Food allergens readily provoke AD in ∼35% of patients, as proven through double-blind placebo-controlled food challenge studies. Milk, egg, wheat, soy, and peanut account for 75% of the cases of food-induced AD. However, the positive predictive values of the parental history, skin-prick tests, or serum tests for detecting food-specific IgE are low, making these unsuitable for use as single diagnostic modalities. Therefore, the use of a food challenge test is very helpful in objectively confirming the history or positive tests. Elimination diets are often helpful in challenge-proven cases, but care must be taken to evaluate the nutritional status of the child. There are few effective long-term strategies to prevent the development of food allergen-induced AD. Early onset of AD has been shown to be a risk factor for the development of other allergic diseases, including other food allergy/sensitization, as part of the atopic march. Treatment of other causes of AD, such as barrier dysfunction and cutaneous infection, are of equal importance to food allergen avoidance. Food allergy is an important provoking cause of AD, but it is only relevant in ∼35% of affected individuals.

Serotonin enhances the impact of health information on food choice.

PubMed

Vlaev, Ivo; Crockett, Molly J; Clark, Luke; Müller, Ulrich; Robbins, Trevor W

2017-06-01

Serotonin has been implicated in promoting self-control, regulation of hunger and physiological homeostasis, and regulation of caloric intake. However, it remains unclear whether the effects of serotonin on caloric intake reflect purely homeostatic mechanisms, or whether serotonin also modulates cognitive processes involved in dietary decision making. We investigated the effects of an acute dose of the serotonin reuptake inhibitor citalopram on choices between food items that differed along taste and health attributes, compared with placebo and the noradrenaline reuptake inhibitor atomoxetine. Twenty-seven participants attended three sessions and received single doses of atomoxetine, citalopram, and placebo in a double-blind randomised cross-over design. Relative to placebo, citalopram increased choices of more healthy foods over less healthy foods. Citalopram also increased the emphasis on health considerations in decisions. Atomoxetine did not affect decision making relative to placebo. The results support the hypothesis that serotonin may influence food choice by enhancing a focus on long-term goals. The findings are relevant for understanding decisions about food consumption and also for treating health conditions such as eating disorders and obesity.

A double blind, randomized, placebo controlled trial of the efficacy, quality of life and safety of food allergen-specific sublingual immunotherapy in client owned dogs with adverse food reactions: a small pilot study.

PubMed

Maina, Elisa; Cox, Eric

2016-10-01

Food allergen-specific sublingual immunotherapy (FA-SLIT) has emerged as a novel and successful approach for desensitizing human patients to specific food allergens. It has not been tested in dogs. To investigate the efficacy, quality of life (QoL), tolerability and safety of FA-SLIT in dogs with adverse food reactions (AFR). Dogs with proven AFR were randomized to treatment (T group; n = 7) or placebo (P group; n = 6) to receive either FA-SLIT (based on the results of a food elimination trial) or glycerinated saline, respectively. The treatment was continued daily for 6 months with fortnightly dosage escalations. To evaluate the treatment, pruritus Visual Analog Scale (pVAS), Canine Atopic Dermatitis Extent and Severity Index (CADESI-04), QoL, faecal consistency scores, owner assessment, overall tolerability scores and blood analyses were assessed. Eleven dogs completed the study, two dogs in the T group were withdrawn by the owner after FA-SLIT exacerbated clinical signs of AFR. Statistical tests showed significant protection against food challenge induced clinical signs following FA-SLIT therapy, as indicated by reduced pVAS and CADESI scores (P < 0.05). The QoL did not differ between groups. The treatment was rated as effective or quite effective by 80% of the owners, whereas placebo was rated as ineffective by all owners. FA-SLIT was effective, well tolerated and safe. No severe adverse events were recorded; erythema and pruritus were reported in association with only 0.7% of the dispensed doses. Larger clinical trials with more extended maintenance immunotherapy periods will be needed to provide more precise estimates of efficacy and frequency of adverse events. © 2016 ESVD and ACVD.

The dilemma of allergy to food additives.

PubMed

Bahna, Sami L; Burkhardt, Joshua G

2018-01-01

To provide a brief summary on food additives and to outline a practical approach for evaluating subjects suspected of having reactions to food additives. Information was derived from selected reviews and original articles published in peer-reviewed journals, supplemented by the clinical experience of the authors. Priority was given to studies that used blinded, placebo controlled, oral challenges to confirm adverse reactions to food additives. In addition, selected, appropriately evaluated case reports were included. A large number of food additives are widely used in the food industry. Allergic reactions to additives seem to be rare but are very likely underdiagnosed, primarily due to a low index of suspicion. A wide variety of symptoms to food additives have been reported, but a cause-and-effect relationship has not been well documented in the majority of cases. Reactions to food additives should be suspected in patients who report symptoms related to multiple foods or to a certain food when commercially prepared but not when home made. It is also prudent to investigate food additives in subjects considered to have "idiopathic" reactions. Except for a limited number of natural additives, there is a small role for skin tests or in vitro testing. Oral challenge, in stages, with commonly used additives is the definitive procedure for detecting the offending agent. Once the specific additive is identified, management is strict avoidance, which can be difficult.

Double-blind placebo-controlled challenges for peanut allergy the efficiency of blinding procedures and the allergenic activity of peanut availability in the recipes.

PubMed

van Odijk, J; Ahlstedt, S; Bengtsson, U; Borres, M P; Hulthén, L

2005-05-01

A firm diagnosis of double-blind placebo-controlled food challenge (DBPCFC) would facilitate the diagnosis in patients with uncertain history of reaction. Guidelines are lacking for an upper provoking dose and how to hide high concentrations of peanuts. To develop and evaluate a double-blind recipe with minimum 10% of peanut. To compare the recipe with published recipes regarding blindness, taste, texture and immunoglobulin (Ig)E antibody binding to peanut. A recipe (I) with 10% of peanut was developed evaluated and used in DBPCFC. The challenges were followed by development of a concentrated recipe (II) (15% peanut, 25% fat). Recipe II was compared with the only published recipe (III) (11% peanut, 7% fat) regarding taste, texture and availability of peanut. Recipe IV (12% peanut, 10% fat) was developed using the same methods. The binding of IgE in the recipes was measured using an inhibition method. During challenges, one patient reacted after 4 g, emphasizing the need for blinding recipes containing high doses of peanut. Evaluation between recipes II and III, only recipe II was regarded as blind by the taste panels. A tenfold lower availability of peanut protein in the recipe II was found at 50% of inhibition. Recipe IV had a better IgE binding that did not differ from the original peanut extract. The peanut taste and texture can be hidden in a challenge medium. The fat content was important for the availability of the allergenic protein in challenges. The availability of allergens must be taken into consideration when used for DBPCFC.

Clinical evaluation of liquid placebos for an herbal supplement, STW5, in healthy volunteers.

PubMed

Yoon, Saunjoo L; Grundmann, Oliver; Keane, Devan; Urbano, Theodore; Moshiree, Baharak

2012-10-01

Although clinical trials are needed to evaluate the efficacy of liquid herbal medicinal products, design of feasible placebos that mimic the appearance, taste, and smell of such products is particularly challenging. The design and feasibility of a liquid placebo for STW5, an herbal medicinal product used for various gastrointestinal problems, was explored in this study. Four sample products-STW5, a fresh and aged version of a placebo made from a seasoning mix (Maggi™), and a placebo with aged artificial flavor and food coloring-were compared in two organoleptic (sensory), single-blind trials with a total of 60 (N=60) healthy volunteers (n(1)=30, n(2)=30). The appearance, smell, and taste of each solution were evaluated using a Likert scale questionnaire. The liquid placebos evaluated were similar in regard to appearance, smell, and taste. However, participants indicated that for a clinical trial with STW5, the aged Maggi™ placebo would be more viable compared to the fresh Maggi placebo or the aged artificial food coloring placebo with licorice flavor. Participants also noted that the mint flavor and smell of STW5 was distinctly different from the placebo solutions. The trials were conducted in healthy volunteers, not in actual patients. The aged Maggi™ liquid mix may be more favorable as a placebo than the artificially created one. However, further adjustment will need to be made to the Maggi™ placebo to simulate the complex aromatic composition of STW5 for clinical studies in the future. Copyright © 2012 Elsevier Ltd. All rights reserved.

Design, formulation and sensory evaluation of a polyphenol-rich food placebo: an example of aronia juice for food intervention studies.

PubMed

Kardum, Nevena; Konic Ristic, Aleksandra; Zec, Manja; Kojadinovic, Milica; Petrovic-Oggiano, Gordana; Zekovic, Milica; Kroon, Paul A; Glibetić, Maria

2017-09-01

Products suitable for use as controls in food interventions designed to demonstrate the role of minor components are largely lacking. In the present study, we aimed to develop a formulation to be used as a placebo in a clinical trial designed to assess the effects of aronia juice polyphenols on platelet function. Three formulations with the same nutrient composition as aronia juice were prepared by mixing various nutrients, artificial colours and flavours with water. The similarity of formulations to aronia juice in terms of taste, colour, smell and texture was assessed by six food panellists. The final placebo was tested for its impact on platelet function, biochemical and anthropometric parameters in a 4-week long study. No significant changes in platelet function, or in several cardiovascular and safety markers were recorded. Formulation suitable for use as a placebo for dietary intervention studies using aronia juice has been developed and demonstrated to be well tolerated in humans.

Ige-mediated food allergy - current problems and future perspectives (review).

PubMed

Lomidze, N; Gotua, T; Gotua, M

2015-01-01

The incidence and prevalence of FA have changed over time, and many studies have indeed suggested a true rise in prevalence over the past 10-20 years. Recent studies showed that prevalence of self-reported food allergy is 17, 3%, versus challenged confirmed - 0.9%. The majority of allergic reactions to foods, particularly in children, are suggested to be caused primarily by eight foods, namely cow's milk, egg, wheat, soy, peanut, tree nuts, fish, and shellfish. Clinical symptoms of FA include skin, gastrointestinal and systemic reaction anaphylaxis that might be life-threatening and cause fatal reaction. Diagnosis of food allergy is based on SPT, sIgE measurements, component resolved diagnostics (CRD) and double-blind placebo-controlled food challenge (DBPCFC) tests. The primary therapy for food allergy is strict avoidance of the causal foods. Patients should be provided an emergency action plan, including how to administer an epinephrine autoinjector. It is recommended that all infants be exclusively breast-fed, without maternal diet restriction of allergens, until 4 to 6 months of age. Recent studies have shown that oral immunotherapy (OIT) can induce desensitization and modulate allergen-specific immune responses. Further work to evaluate the long-term effectiveness and safety of this therapy is ongoing and needed before they are used in the main-stream care of children or adults with food allergy.

Promising effects of oxytocin on social and food-related behaviour in young children with Prader-Willi syndrome: a randomized, double-blind, controlled crossover trial.

PubMed

Kuppens, R J; Donze, S H; Hokken-Koelega, A C S

2016-12-01

Prader-Willi syndrome (PWS) is known for hyperphagia with impaired satiety and a specific behavioural phenotype with stubbornness, temper tantrums, manipulative and controlling behaviour and obsessive-compulsive features. PWS is associated with hypothalamic and oxytocinergic dysfunction. In humans without PWS, intranasal oxytocin administration had positive effects on social and eating behaviour, and weight balance. To evaluate the effects of intranasal oxytocin compared to placebo administration on social behaviour and hyperphagia in children with PWS. Randomized, double-blind, placebo-controlled, crossover study in a PWS Reference Center in the Netherlands. Crossover intervention with twice daily intranasal oxytocin (dose range 24-48 IU/day) and placebo administration, both during 4 weeks, in 25 children with PWS (aged 6 to 14 years). In the total group, no significant effects of oxytocin on social behaviour or hyperphagia were found, but in the 17 children younger than 11 years, parents reported significantly less anger (P = 0·001), sadness (P = 0·005), conflicts (P = 0·010) and food-related behaviour (P = 0·011), and improvement of social behaviour (P = 0·018) during oxytocin treatment compared with placebo. In the eight children older than 11 years, the items happiness (P = 0·039), anger (P = 0·042) and sadness (P = 0·042) were negatively influenced by oxytocin treatment compared to placebo. There were no side effects or adverse events. This randomized, double-blind, placebo-controlled study suggests that intranasal oxytocin administration has beneficial effects on social behaviour and food-related behaviour in children with PWS younger than 11 years of age, but not in those older than 11 years of age. © 2016 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.

Monitoring of IgE-mediated food allergy in childhood.

PubMed

Thong, B Y H; Hourihane, J O' B

2004-06-01

The prevalence of IgE-mediated food allergy (FA) in childhood varies from 6% to 8% in the first year of life compared to 1% to 2% in adults. In contrast to adults, FA in childhood, often part of the "allergic march", resolves in more than 85% of children, especially those with hypersensitivity to cow's milk and egg. This paper explains the rationale for continuing care for childhood FA and describes how children should be monitored for resolution/persistence of FA. A clinical, multidisciplinary approach and management algorithm based on relevant, peer-reviewed original research articles and reviews using the keywords anaphylaxis, atopic eczema, children, milk allergy, double-blind placebo-controlled food challenge, egg allergy, epinephrine, failure to thrive, food allergy, food challenge, food hypersensitivity, immunoglobulin E, nutrition, natural history, paediatrics, peanut allergy, prevalence, psychosocial factors, quality of life, radioallergosorbent test, and tolerance from years 1966 to 2003 in MEDLINE. Additional studies were identified from article reference lists. A combination of outcome measures, a multidisciplinary approach involving a dietitian and allergy nurse specialist, and a management algorithm are useful tools in clinical management. Prospective studies of non-selected children, optimally from birth cohorts, are needed to evaluate the effects of such management programmes regarding FA in childhood.

Effects of once-weekly semaglutide on appetite, energy intake, control of eating, food preference and body weight in subjects with obesity.

PubMed

Blundell, John; Finlayson, Graham; Axelsen, Mads; Flint, Anne; Gibbons, Catherine; Kvist, Trine; Hjerpsted, Julie B

2017-09-01

The aim of this trial was to investigate the mechanism of action for body weight loss with semaglutide. This randomised, double-blind, placebo-controlled, two-period crossover trial investigated the effects of 12 weeks of treatment with once-weekly subcutaneous semaglutide, dose-escalated to 1.0 mg, in 30 subjects with obesity. Ad libitum energy intake, ratings of appetite, thirst, nausea and well-being, control of eating, food preference, resting metabolic rate, body weight and body composition were assessed. After a standardised breakfast, semaglutide, compared with placebo, led to a lower ad libitum energy intake during lunch (-1255 kJ; P  < .0001) and during the subsequent evening meal ( P  = .0401) and snacks ( P  = .0034), resulting in a 24% reduction in total energy intake across all ad libitum meals throughout the day (-3036 kJ; P  < .0001). Fasting overall appetite suppression scores were improved with semaglutide vs placebo, while nausea ratings were similar. Semaglutide was associated with less hunger and food cravings, better control of eating and a lower preference for high-fat foods. Resting metabolic rate, adjusted for lean body mass, did not differ between treatments. Semaglutide led to a reduction from baseline in mean body weight of 5.0 kg, predominantly from body fat mass. After 12 weeks of treatment, ad libitum energy intake was substantially lower with semaglutide vs placebo with a corresponding loss of body weight observed with semaglutide. In addition to reduced energy intake, likely mechanisms for semaglutide-induced weight loss included less appetite and food cravings, better control of eating and lower relative preference for fatty, energy-dense foods. © 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Effects of a meal replacement system alone or in combination with phentermine on weight loss and food cravings.

PubMed

Moldovan, Christina P; Weldon, Abby J; Daher, Noha S; Schneider, Louise E; Bellinger, Denise L; Berk, Lee S; Hermé, Alyson C; Aréchiga, Adam L; Davis, Willie L; Peters, Warren R

2016-11-01

To examine the effects of phentermine combined with a meal replacement program on weight loss and food cravings and to investigate the relationship between food cravings and weight loss. In a 12-week randomized, double-blind, placebo-controlled clinical trial, 77 adults with obesity received either phentermine or placebo. All participants were provided Medifast ® meal replacements, were instructed to follow the Take Shape for Life ® Optimal Weight 5&1 Plan for weight loss, and received lifestyle coaching in the Habits of Health program. The Food Craving Inventory and the General Food Cravings State and Trait Questionnaires were used to measure food cravings. The phentermine group lost 12.1% of baseline body weight compared with 8.8% in the placebo group. Cravings for all food groups decreased in both groups; however, there was a greater reduction in cravings for fats and sweets in the phentermine group compared with the placebo group. Percent weight loss correlated significantly with reduced total food cravings (r = 0.332, P = 0.009), cravings for sweets (r = 0.412, P < 0.000), and state food cravings (r = 0.320, P = 0.007). Both phentermine combined with a meal replacement program and meal replacements alone significantly reduced body weight and food cravings; however, the addition of phentermine enhanced these effects. © 2016 The Obesity Society.

Short-term effects of a green coffee extract-, Garcinia c ambogia- and L-carnitine-containing chewing gum on snack intake and appetite regulation.

PubMed

Bobillo, Cecilia; Finlayson, Graham; Martínez, Ana; Fischman, Daniela; Beneitez, Analisa; Ferrero, Alejandro J; Fernández, Belisario E; Mayer, Marcos A

2018-03-01

Different studies have assessed the influence of chewing gum to aid control of appetite and reduce food intake. The aims of the present study were to evaluate the effects of chewing gum on satiety, food hedonics and snack intake and to explore the potential effects of the combination of Garcinia c ambogia, green coffee extract and L-carnitine on satiety, when administered in a gum format. This was a prospective study in which 57 subjects randomly received three kinds of treatments, in a crossover design: (1) active gum; (2) placebo gum; and (3) no gum. Food preferences and appetite sensations were evaluated by means of the Leeds Food Preference Questionnaire and visual analog scales. There was a significant reduction in low-fat sweet snack intake with placebo gum and the active gum compared to no gum and a reduction in high-fat sweet snack intake with the active gum compared to placebo gum and no gum. Total caloric intake was only reduced in the active gum condition. Both the active and placebo gum conditions significantly reduced hunger and prospective food consumption and increased fullness compared to no gum and were associated with a reduced wanting for sweet food in the LFPQ, consistent in a reduction in the relative preference for sweet snacks versus savoury snacks. This study supports the notion that chewing gum containing nutraceutical products might aid in the control over snack intake and reduce hunger sensations.

Distinct patterns of cow's milk allergy in infancy defined by prolonged, two-stage double-blind, placebo-controlled food challenges.

PubMed

Baehler, P; Chad, Z; Gurbindo, C; Bonin, A P; Bouthillier, L; Seidman, E G

1996-03-01

The clinical manifestations of cow's milk allergy (CMA) are highly variable, and challenges usually identify only immediate, IgE mediated reactions. To clearly identify CMA of immediate and delayed types using a two-stage, double-blind, placebo-controlled food challenge (DBPCFC), and to prospectively compare the clinical history and analyses of specific IgE antibodies to milk in predicting outcome of DBPCFC. A total of 69 patients (33 girls, 36 boys) were recruited for study based on a history highly suggestive of CMA and resolution of symptoms on a bovine protein-free diet. After skin-prick tests (SPTs) and search for allergen-specific serum IgE antibodies by enzyme allergosorbent test (EAST), a two-stage DBPCFC was performed over several days. Of 16 patients (mean age 36.9 months) classified as probable immediate reactors based on the history, 10 (62.5%) had a positive DBPCFC with similar patterns to historical adverse reactions (< or = 2 h after milk exposure). The other 53 (77%) patients (17.3 months) had a history of probable delayed type CMA presenting with predominantly gastrointestimal symptoms from 2 h and up to 6 days after milk exposure. Of these, 15 (28.8%) had a positive DBPCFC, again with a symptom pattern similar to the history. Sensitivity/specificity of SPT was similar to that of EAST for both immediate (70/83% and 62/83% respectively, NS) or delayed (0/97% and 0/97%) CMA confirmed by DBPCFC. Using our two-stage, prolonged DBPCFC, we clearly identified two groups of children with CMA, reflecting different pathogenesis of either immediate-type IgE-dependent, or delayed-type IgE-independent allergy. Although useful in immediate reactors, IgE antibody determination cannot predict the outcome of DBPCFC in delayed reactors. A thorough clinical history was the most helpful tool to predict the type of response in challenge positive patients.

Gastrointestinal manifestations of cow's milk allergy.

PubMed

Magazzù, Giuseppe; Scoglio, Riccardo

2002-12-01

To review and discuss the relationship between cow's milk allergy (CMA) and some gastrointestinal manifestations, such as gastroesophageal reflux, constipation, food protein-induced enterocolitis, and food-induced eosinophilic proctocolitis, with respect to diagnostic strategies that might eliminate the need for a double-blind, placebo-controlled oral food challenge (DBPCFC). A review of pertinent PubMed articles, published during the past 10 years, was performed. To obtain positive and negative predictive values known as posterior probabilities and to calculate the likelihood ratio, only those studies including both patients and control subjects were selected for analysis. With respect to gastroesophageal reflux, a typical 24-hour esophageal pH monitoring pattern might obviate the performance of a DBPCFC in patients with symptoms of reflux suspected of having CMA, provided this pH pattern is confirmed in other studies. A relationship between CMA and constipation has been reported in only one prospective controlled study; the clinical and laboratory variables of perianal lesions, histologic abnormalities, and signs of hypersensitivity had likelihood ratios of 2.2, 2.4, and 3.7, respectively, and posttest probabilities of 83, 84, and 88%, respectively. Therefore, a DBPCFC is warranted. In reference to food protein-induced enterocolitis, clinical and laboratory criteria suggested in the literature for defining a food challenge as positive have not been prospectively evaluated in the untreated state. Some simple stool tests, such as fecal tumor necrosis factor-alpha and alpha1-antitrypsin determination, might be candidates for diagnostic studies in patients with food protein-induced enterocolitis, if prospectively evaluated. In infants with food-induced eosinophilic proctocolitis, rectal biopsy invariably shows eosinophilic infiltration and thus makes performance of a DBPCFC unnecessary. Although the current diagnosis of gastrointestinal manifestations of CMA usually depends on a DBPCFC, investigators continue to study other options for confirming the diagnosis.

Controlled trial of hyposensitisation in children with food-induced hyperkinetic syndrome.

PubMed

Egger, J; Stolla, A; McEwen, L M

1992-05-09

Food intolerance seems to be an important cause of the hyperkinetic syndrome, but restricted diets are expensive, socially disruptive, and often nutritionally inadequate. Enzyme-potentiated desensitisation (EPD) may overcome some of these difficulties. EPD was tested in a double-blind placebo-controlled trial among 40 children with food-induced hyperkinetic behaviour disorder. A total of 185 children with established hyperkinetic syndrome underwent oligoantigenic dietary treatment for four weeks. 116 whose behaviour responded had provoking foods identified by sequential reintroduction. Foods that reproducibly provoked overactivity were avoided. 40 patients who were then invited to take part in the hyposensitisation trial were randomly assigned to treated and control groups. Treated patients received three doses of EPD (beta-glucuronidase and small quantities of food antigens) intradermally at two-monthly intervals. Controls received buffer only. Thereafter, patients were allowed to eat known provoking foods. Of 20 patients who received active treatment, 16 became tolerant towards provoking foods compared with 4 of 20 who received placebo (p less than 0.001). Our results show that EPD permits children with food-induced hyperkinetic syndrome to eat foods that had previously been identified as responsible for their symptoms. These results also support the notion that food allergy is a possible mechanism of the hyperkinetic syndrome.

The role of the dopaminergic system in mood, motivation and cognition in Parkinson's disease: a double blind randomized placebo-controlled experimental challenge with pramipexole and methylphenidate.

PubMed

Drijgers, Rosa L; Verhey, Frans R J; Tissingh, Gerrit; van Domburg, Peter H M F; Aalten, Pauline; Leentjens, Albert F G

2012-09-15

In Parkinson's disease (PD) reduced dopaminergic activity in the mesocorticolimbic pathway is implied in the pathophysiology of several non-motor symptoms related to mood, motivation and cognition. Insight in the pathophysiology of these syndromes may pave the way for more rational treatments. In a double-blind, randomized, placebo controlled, crossover design with three arms, we studied the effects of a direct dopaminergic challenge with the dopamine 2 receptor agonist pramipexole, an indirect challenge with the dopamine reuptake inhibitor methylphenidate, and placebo on measures of mood, motivation and cognition in 23 agonist-naïve PD patients and 23 healthy controls. Acute challenge with pramipexole had a negative effect on mood and fatigue in both patients and controls. In addition, challenge with pramipexole led to increased anger, fatigue, vigor and tension in healthy control subjects, but not in PD patients. Challenge with methylphenidate had a positive effect on anhedonia and vigor in PD patients. Due to its side effects after a single administration, pramipexole is probably less suitable for acute challenge studies. The acute effects of a methylphenidate challenge on anhedonia and vigor in PD patients make this drug an interesting choice for further studies of the treatment of mood and motivational disorders in this population. Copyright © 2012 Elsevier B.V. All rights reserved.

Does Dapagliflozin Affect Energy Intake and Appetite? A Randomized, Controlled Exploratory Study in Healthy Subjects.

PubMed

Bertran, Elizabeth; Berlie, Helen D; Nixon, Aaron; Jaber, Linda

2018-05-03

The primary aims of this study were to assess the effects of dapagliflozin versus placebo on energy intake and appetite ratings in healthy individuals. This was a randomized, single-blind, placebo-controlled, 2-period crossover study. In each period, healthy individuals received either dapagliflozin or placebo for 2 weeks. On assessment days, participants were asked to consume a standard preload breakfast. Appetite ratings were measured with 100-mm visual analog scales immediately before and during the 4.25-hour period after breakfast. Energy intake was measured at an ad libitum lunch. Energy intake and appetite responses were assessed at the end of each 2-week treatment period by mixed-design analysis of variance. Eighteen individuals completed all assessments (44% female; mean age, 22.8 years; 44% Caucasian; mean BMI, 25.2 kg/m 2 ). There was no difference in energy intake on dapagliflozin compared to placebo (mean difference, -19.8 kcal; P = .516). Mean differences in prebreakfast desire for salty foods (11.3 mm, P = .094) and postbreakfast desire for sweet foods (8.1 mm, P = .054) trended higher with dapagliflozin relative to placebo. Our data do not support an effect of dapagliflozin on energy intake or appetite measures in young, healthy subjects. Although not statistically significant, the size of the mean differences in prebreakfast desire for salty foods and postbreakfast desire for sweet foods on dapagliflozin were larger than placebo and reflect the drug's natriuretic and glucuretic effects. These findings should be further evaluated in patients with type 2 diabetes. © 2018, The American College of Clinical Pharmacology.

Oxytocin curbs calorie intake via food-specific increases in the activity of brain areas that process reward and establish cognitive control.

PubMed

Spetter, Maartje S; Feld, Gordon B; Thienel, Matthias; Preissl, Hubert; Hege, Maike A; Hallschmid, Manfred

2018-02-09

The hypothalamic neurohormone oxytocin decreases food intake via largely unexplored mechanisms. We investigated the central nervous mediation of oxytocin's hypophagic effect in comparison to its impact on the processing of generalized rewards. Fifteen fasted normal-weight, young men received intranasal oxytocin (24 IU) or placebo before functional magnetic resonance imaging (fMRI) measurements of brain activity during exposure to food stimuli and a monetary incentive delay task (MID). Subsequently, ad-libitum breakfast intake was assessed. Oxytocin compared to placebo increased activity in the ventromedial prefrontal cortex, supplementary motor area, anterior cingulate, and ventrolateral prefrontal cortices in response to high- vs. low-calorie food images in the fasted state, and reduced calorie intake by 12%. During anticipation of monetary rewards, oxytocin compared to placebo augmented striatal, orbitofrontal and insular activity without altering MID performance. We conclude that during the anticipation of generalized rewards, oxytocin stimulates dopaminergic reward-processing circuits. In contrast, oxytocin restrains food intake by enhancing the activity of brain regions that exert cognitive control, while concomitantly increasing the activity of structures that process food reward value. This pattern points towards a specific role of oxytocin in the regulation of eating behaviour in humans that might be of relevance for potential clinical applications.

Consumption of a calcium and vitamin D-fortified food product does not affect iron status during initial military training: a randomised, double-blind, placebo-controlled trial.

PubMed

Hennigar, Stephen R; Gaffney-Stomberg, Erin; Lutz, Laura J; Cable, Sonya J; Pasiakos, Stefan M; Young, Andrew J; McClung, James P

2016-02-28

Ca/vitamin D supplementation maintains bone health and decreases stress fracture risk during initial military training (IMT); however, there is evidence that Ca may negatively affect the absorption of other critical micronutrients, particularly Fe. The objective of this randomised, double-blind, placebo-controlled trial was to determine whether providing 2000 mg/d Ca and 25 µg/d vitamin D in a fortified food product during 9 weeks of military training affects Fe status in young adults. Male (n 98) and female (n 54) volunteers enrolled in US Army basic combat training (BCT) were randomised to receive a snack bar with Ca/vitamin D (n 75) or placebo (snack bar without Ca/vitamin D; n 77) and were instructed to consume 2 snack bars/d between meals throughout the training course. Circulating ionised Ca was higher (P0·05) in markers of Fe status between placebo and Ca/vitamin D groups. Collectively, these data indicate that Ca/vitamin D supplementation through the use of a fortified food product consumed between meals does not affect Fe status during IMT.

A dietary cholesterol challenge study to assess Chlorella supplementation in maintaining healthy lipid levels in adults: a double-blinded, randomized, placebo-controlled study.

PubMed

Kim, Sangmi; Kim, Joohee; Lim, Yeni; Kim, You Jin; Kim, Ji Yeon; Kwon, Oran

2016-05-13

Previous animal studies suggested that Chlorella, a unicellular green alga, has a preventive role in maintaining serum cholesterol levels against excess dietary cholesterol intake. This study aimed to conduct a pioneering investigation to clarify this issue in healthy subjects by adopting a dietary cholesterol challenge, which has not been used previously in similar studies of Chlorella in hypercholesterolemia. In this double blind, randomized, placebo-controlled study, 34 participants ingested 510 mg of dietary cholesterol from three eggs concomitantly with a usual dose of Chlorella (5 g/d) or a matched placebo for 4 weeks. The dietary cholesterol challenge induced consistently higher concentrations of serum total cholesterol (TC, P < 0.001), LDL-C (P = 0.004), and HDL-C (P = 0.010) compared with baseline values, suggesting that the challenge was reliable. Thus, we observed a preventive action of Chlorella in maintaining serum TC versus placebo levels (3.5 % versus 9.8 %, respectively; P = 0.037) and LDL-C versus placebo levels (1.7 % versus 14.3 %, respectively; P = 0.012) against excessive dietary cholesterol intake and in augmenting HDL-C versus placebo levels (8.3 % versus 3.8 %, respectively). Furthermore, serum α-carotene showed the best separation between the placebo and Chlorella groups (R(2)X and R(2)Y > 0.5; Q(2) > 0.4). The results suggest that a fully replicated dietary cholesterol challenge may be useful in assessing the effectiveness of dietary supplements in maintaining the serum lipid profiles of adults whose habitual diets are high in cholesterol. WHO International Clinical Trials Registry Platform ( KCT0000258 ).

Aacap 2002 Research Forum: Placebo and Alternatives to Placebo in Randomized Controlled Trials in Pediatric Psychopharmacology

ERIC Educational Resources Information Center

March, John; Kratochvil, Christopher; Clarke, Gregory; Beardslee, William; Derivan, Albert; Emslie, Graham; Green, Evelyn P.; Heiligenstein, John; Hinshaw, Stephen; Hoagwood, Kimberly; Jensen, Peter; Lavori, Philip; Leonard, Henrietta; McNulty, James; Michaels, M. Alex; Mossholder, Andrew; Osher, Trina; Petti, Theodore; Prentice, Ernest; Vitiello, Benedetto; Wells, Karen

2004-01-01

Objective: The use of placebo in the pediatric age group has come under increasing scrutiny. At the 2002 Annual Meeting of the American Academy of Child and Adolescent Psychiatry, the Academy's Workgroup on Research conducted a research forum. The purpose was to identify challenges and their solutions regarding the use of placebo in randomized…

Sex differences in subjective and objective responses to a stimulant medication (methylphenidate): Comparisons between overweight/obese adults with and without binge-eating disorder.

PubMed

Davis, Caroline; Levitan, Robert D; Kaplan, Allan S; Carter-Major, Jacqueline C; Kennedy, James L

2016-05-01

The purpose of this study was to examine sex differences in response to a single dose of a psychomotor-stimulant medication (methylphenidate: MP) and to assess whether expected differences were moderated by binge-eating disorder (BED) status. It is anticipated that findings will shed light on factors that contribute to response variation in the use of stimulant pharmacotherapy to treat BED. The study employed a double-blind, drug-placebo, cross-over design in overweight/obese adults with BED (n = 90) and without BED (n = 108). Emotional/mood ratings were assessed every 15 minutes after oral administration of the drug/placebo, and appetite, cravings, and consumption were assessed during a laboratory-based snack-food challenge. Women reported earlier and more sustained "overall" effects of the drug-including "feeling high"-than the men. There was also a significantly greater suppression in appetite ratings, food cravings, and food consumption from the placebo to the drug condition among the women. Indeed, among men there were no significant differences between the two conditions on any of the food-related variables. BED status also did not moderate any of the drug-placebo differences. These findings are relevant to the use of stimulant pharmacotherapy for BED, and raise the possibility that overweight/obese men may be relatively less responsive to this form of treatment. © 2015 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:473-481). © 2015 Wiley Periodicals, Inc.

[Food allergy, food intolerance or functional disorder?].

PubMed

Wüthrich, B

2009-04-01

The term "food allergy" is widely misused for all sorts of symptoms and diseases caused by food. Food allergy (FA) is an adverse reaction to food (food hypersensitivity) occurring in susceptible individuals, which is mediated by a classical immune mechanism specific for the food itself. The best established mechanism in FA is due to the presence of IgE antibodies against the offending food. Food intolerance (FI) are all non-immune-mediated adverse reactions to food. The subgroups of FI are enzymatic (e.g. lactose intolerance due to lactase deficiency), pharmacological (reactions against biogenic amines, histamine intolerance), and undefined food intolerance (e.g. against some food additives). The diagnosis of an IgE-mediated FA is made by a carefully taken case history, supported by the demonstration of an IgE sensitization either by skin prick tests or by in vitro tests, and confirmed by positive oral provocation. For scientific purposes the only accepted test for the confirmation of FA/FI is a properly performed double-blind, placebo-controlled food challenge (DBPCFC). A panel of recombinant allergens, produced as single allergenic molecules, may in future improve the diagnosis of IgE-mediated FA. Due to a lack of causal treatment possibilities, the elimination of the culprit "food allergen" from the diet is the only therapeutic option for patients with real food allergy.

Hyperactivity: is candy causal?

PubMed

Krummel, D A; Seligson, F H; Guthrie, H A

1996-01-01

Adverse behavioral responses to ingestion of any kind of candy have been reported repeatedly in the lay press. Parents and teachers alike attribute excessive motor activity and other disruptive behaviors to candy consumption. However, anecdotal observations of this kind need to be tested scientifically before conclusions can be drawn, and criteria for interpreting diet behavior studies must be rigorous. Ingredients in nonchocolate candy (sugar, artificial food colors), components in chocolate candy (sugar, artificial food colors in coatings, caffeine), and chocolate itself have been investigated for any adverse effects on behavior. Feingold theorized that food additives (artificial colors and flavors) and natural salicylates caused hyperactivity in children and elimination of these components would result in dramatic improvement in behavior. Numerous double-blind studies of the Feingold hypothesis have led to the rejection of the idea that this elimination diet has any benefit beyond the normal placebo effect. Although sugar is widely believed by the public to cause hyperactive behavior, this has not been scientifically substantiated. Twelve double-blind, placebo-controlled studies of sugar challenges failed to provide any evidence that sugar ingestion leads to untoward behavior in children with Attention-Deficit Hyperactivity Disorder or in normal children. Likewise, none of the studies testing candy or chocolate found any negative effect of these foods on behavior. For children with behavioral problems, diet-oriented treatment does not appear to be appropriate. Rather, clinicians treating these children recommend a multidisciplinary approach. The goal of diet treatment is to ensure a balanced diet with adequate energy and nutrients for optimal growth.

Antiviral Activity of Pocapavir in a Randomized, Blinded, Placebo-Controlled Human Oral Poliovirus Vaccine Challenge Model

PubMed Central

Hincks, Jeffrey R.; Benschop, Kimberley; Duizer, Erwin; van der Avoort, Harrie; Rhoden, Eric; Liu, Hongmei; Oberste, M. Steven; McKinlay, Mark A.; Hartford, Marianne

2017-01-01

Abstract Background. Immunodeficient individuals who excrete vaccine-derived polioviruses threaten polio eradication. Antivirals address this threat. Methods. In a randomized, blinded, placebo-controlled study, adults were challenged with monovalent oral poliovirus type 1 vaccine (mOPV1) and subsequently treated with capsid inhibitor pocapavir or placebo. The time to virus negativity in stool was determined. Results. A total of 144 participants were enrolled; 98% became infected upon OPV challenge. Pocapavir-treated subjects (n = 93) cleared virus a median duration of 10 days after challenge, compared with 13 days for placebo recipients (n = 48; P = .0019). Fifty-two of 93 pocapavir-treated subjects (56%) cleared virus in 2–18 days with no evidence of drug resistance, while 41 of 93 (44%) treated subjects experienced infection with resistant virus while in the isolation facility, 3 (3%) of whom were infected at baseline, before treatment initiation. Resistant virus was also observed in 5 placebo recipients (10%). Excluding those with resistant virus, the median time to virus negativity was 5.5 days in pocapavir recipients, compared with 13 days in placebo recipients (P < .0001). There were no serious adverse events and no withdrawals from the study. Conclusions. Treatment with pocapavir was safe and significantly accelerated virus clearance. Emergence of resistant virus and transmission of virus were seen in the context of a clinical isolation facility. Clinical Trials Registration. EudraCT 2011-004804-38. PMID:27932608

The liberating effect of weight loss supplements on dietary control: a field experiment.

PubMed

Chang, Yevvon Y; Chiou, Wen-Bin

2014-09-01

Taking weight-loss supplements may create illusion of protection against weight gain and thereby loosen subsequent dietary self-control. The current study examined whether taking weight-loss supplement would increase food intake and further tested whether positive attitudes toward supplements would increase susceptibility to overeating. Participants were randomly assigned to take either a known placebo or a purported weight loss supplement (actually, the same placebo). After supplement provision, participants' actual food consumption at a reward buffet lunch was recorded. Compared with controls, participants receiving a purported weight loss supplement ate more food at the reward buffet. Perceived progress toward the goal of weight reduction mediated the connection between use of weight loss supplements and subsequent food consumption. Participants with more positive attitudes toward weight loss supplements were more susceptible to the liberating effect of taking weight loss supplements on food intake. Using weight loss supplements may produce unintended consequences on dietary self-regulation. The public should pay more attention to the notion of psychological liberation when using weight loss supplements. Copyright © 2014 Elsevier Inc. All rights reserved.

A new framework for the documentation and interpretation of oral food challenges in population-based and clinical research.

PubMed

Grabenhenrich, L B; Reich, A; Bellach, J; Trendelenburg, V; Sprikkelman, A B; Roberts, G; Grimshaw, K E C; Sigurdardottir, S; Kowalski, M L; Papadopoulos, N G; Quirce, S; Dubakiene, R; Niggemann, B; Fernández-Rivas, M; Ballmer-Weber, B; van Ree, R; Schnadt, S; Mills, E N C; Keil, T; Beyer, K

2017-03-01

The conduct of oral food challenges as the preferred diagnostic standard for food allergy (FA) was harmonized over the last years. However, documentation and interpretation of challenge results, particularly in research settings, are not sufficiently standardized to allow valid comparisons between studies. Our aim was to develop a diagnostic toolbox to capture and report clinical observations in double-blind placebo-controlled food challenges (DBPCFC). A group of experienced allergists, paediatricians, dieticians, epidemiologists and data managers developed generic case report forms and standard operating procedures for DBPCFCs and piloted them in three clinical centres. The follow-up of the EuroPrevall/iFAAM birth cohort and other iFAAM work packages applied these methods. A set of newly developed questionnaire or interview items capture the history of FA. Together with sensitization status, this forms the basis for the decision to perform a DBPCFC, following a standardized decision algorithm. A generic form including details about severity and timing captures signs and symptoms observed during or after the procedures. In contrast to the commonly used dichotomous outcome FA vs no FA, the allergy status is interpreted in multiple categories to reflect the complexity of clinical decision-making. The proposed toolbox sets a standard for improved documentation and harmonized interpretation of DBPCFCs. By a detailed documentation and common terminology for communicating outcomes, these tools hope to reduce the influence of subjective judgment of supervising physicians. All forms are publicly available for further evolution and free use in clinical and research settings. © 2016 The Authors. Allergy Published by John Wiley & Sons Ltd.

Development and piloting of a food-based intervention to increase vitamin E intake in pregnant women in a randomized controlled trial.

PubMed

Clark, Julia; Holgan, Nikki; Craig, Leone; Morgan, Heather; Danielian, Peter; Devereux, Graham

2016-11-01

Low maternal vitamin E intake during pregnancy is associated with childhood asthma and a trial is required to test whether increasing maternal vitamin E intake reduces childhood asthma. This study investigated whether such a trial is possible using food to increase vitamin E intake. Three soup varieties with enhanced vitamin E content (16-19 mg/can) from food ingredients were developed. Near identical retail versions (vitamin E 1-4 mg/can) acted as placebo. In a pilot double-blind randomized controlled trial, pregnant women were randomized 1:1 to enhanced or placebo soups (three tins/week) from 12 weeks gestation to delivery. Vitamin E intake was quantified at 12, 20, and 34 weeks gestation. Qualitative interviews were conducted. 59 women were randomized (29 enhanced, 30 placebo), 28 completed the trial, (15 enhanced, 13 placebo). In women completing the trial, vitamin E intake of the placebo group remained unchanged; 7.09 mg/d (95% CI 5.41-8.77) at 12 weeks, 6.41 mg/d (5.07-7.75) at 20 weeks, and 6.67 mg/d (5.38-7.96) at 34 weeks gestation; vitamin E intake of the enhanced group increased from 6.50 mg/d (5.21-7.79) at 12 weeks to 14.9 mg/d (13.3-16.4) at 20 weeks and 15.2 mg/d (12.9-17.5) at 34 weeks, P  < 0.001. Qualitative interviewing provided clear guidance on improving adherence. Although 31 women withdrew at median 19 weeks gestation (interquartile range 16-25), the intervention was consumed by women for 80% of weeks between 12 and 34 weeks gestation and for 63% of weeks between 12 weeks gestation and delivery. In a pilot double-blind randomized controlled trial (RCT) it is possible to increase maternal vitamin E intake using food ingredients, a further food product is required to improve adherence.

Anaphylaxis after eating Italian pizza containing buckwheat as the hidden food allergen.

PubMed

Heffler, E; Guida, G; Badiu, I; Nebiolo, F; Rolla, G

2007-01-01

A 20-year-old woman developed anaphylaxis after eating pizza on 4 different occasions in 2 restaurants. Both restaurants made their pizza dough with a mixture of wheat and buckwheat flours. A prick-to-prick test with buckwheat flour was positive. Skin prick tests and specific immunoglobulin E responses to soybean and peanut were weakly positive while the response to buckwheat was negative. We ruled out a pathogenic role for peanut and soybean because the patient usually eats both with no signs of allergic reaction. Double-blind, placebo-controlled food challenges with buckwheat flour were positive after the administration of a cumulative dose of 2.3 g of the culprit flour. To our knowledge, our report describes the first case of anaphylaxis after intake of buckwheat flour as the hidden allergen in pizza dough.

Sibutramine promotes amygdala activity under fasting conditions in obese women.

PubMed

Oltmanns, Kerstin M; Heldmann, Marcus; Daul, Susanne; Klose, Silke; Rotte, Michael; Schäfer, Michael; Heinze, Hans-Jochen; Münte, Thomas F; Lehnert, Hendrik

2012-06-01

Sibutramine, a centrally-acting selective monoamine reuptake inhibitor, has been used as an appetite suppressant drug in obesity. To gain insight into the central nervous actions of sibutramine, brain responses to pictures of food items after sibutramine vs placebo application were assessed by functional magnetic resonance imaging (fMRI) in obese women. In a randomized double-blind crossover design, 10 healthy obese women (BMI 31.8-39.9 kg/m(2)) received 15 mg/d of sibutramine vs placebo for 14 d. Obese participants, and a group of 10 age-matched normal weight controls, viewed pictures of food items and control objects in hungry and satiated states while lying in the MR scanner. The paradigm followed a block design. In obese participants, fMRI measurements were conducted prior and after two weeks of daily sibutramine or placebo administration, whereas control participants were scanned only at one point in time. Upon food item presentation, obese participants showed increased brain activity in areas related to emotional and reward processing, perceptual processing, and cognitive control as compared to normal weight controls. Sibutramine exerted a divergent satiety-dependent effect on amygdala activity in obese participants, increasing activity in the hungry state while decreasing it under conditions of satiation. Our results demonstrate a modulatory influence of sibutramine on amygdala activity in obese women which may underlie the appetite suppressant effects of the drug.

Acute effects of betahistine hydrochloride on food intake and appetite in obese women: a randomized, placebo-controlled trial1234

PubMed Central

Ali, Asem H; Yanoff, Lisa B; Stern, Elizabeth A; Akomeah, Abena; Courville, Amber; Kozlosky, Merel; Brady, Sheila M; Calis, Karim A; Reynolds, James C; Crocker, Melissa K; Barak, Nir; Yanovski, Jack A

2010-01-01

Background: Central nervous system histaminergic tone is thought to play a role in appetite regulation. In animal models, histamine receptor 1 (HRH1) agonists and histamine receptor 3 (HRH3) antagonists decrease food intake. Objective: The objective of this study was to examine the acute effects of betahistine hydrochloride (an HRH1 agonist and HRH3 antagonist) on food intakes and appetites. Design: The study was a proof-of-concept, randomized, double-blinded, placebo-controlled, dose-ranging study performed to examine the effects of betahistine in women with class I or II obesity [body mass index (BMI; in kg/m2) of 30–39.99]. After a 24-h placebo run-in period, subjects received a placebo (n = 19) or 48 (n = 19), 96 (n = 17), or 144 (n = 21) mg betahistine/d for 24 h. Treatment was followed by a buffet test meal to assess energy intake. Hunger, satiety, and desire to eat were measured after consuming the meal by using visual analog scales. Data were analyzed by using regression models with the assumption that there would be an increasing effect of betahistine doses. Analyses were adjusted for age, log fat and lean mass, food preferences, and intake during a buffet test meal obtained during the placebo run-in period. Results: Of the 79 obese women (mean ± SD age: 42 ± 11 y; BMI: 35 ± 3) enrolled in the study, 76 women completed the study. The betahistine dose did not significantly change intakes from those observed during the run-in period of the buffet test meal (P = 0.78). Hunger, fullness, and desire to eat (all P > 0.62) similarly showed no differences according to the betahistine dose. Conclusions: Betahistine did not produce an effect on food intakes or appetites. More potent histaminergic modulators may be required to elucidate the possible role of histaminergic pathways in human obesity. This trial was registered at clinicaltrials.gov as NCT00459992 PMID:20881066

Putting the brakes on the "drive to eat": Pilot effects of naltrexone and reward based eating on food cravings among obese women

PubMed Central

Mason, Ashley E.; Laraia, Barbara; Daubenmier, Jennifer; Hecht, Frederick M.; Lustig, Robert H.; Puterman, Eli; Adler, Nancy; Dallman, Mary; Kiernan, Michaela; Gearhardt, Ashley N.; Epel, Elissa S.

2015-01-01

Purpose Obese individuals vary in their experience of food cravings and tendency to engage in reward-driven eating, both of which can be modulated by the neural reward system rather than physiological hunger. We examined two predictions in a sample of obese women: (1) whether opioidergic blockade reduced food-craving intensity, and (2) whether opioidergic blockade reduced an association between food-craving intensity and reward-driven eating, which is a trait-like index of three factors (lack of control over eating, lack of satiation, preoccupation with food). Methods Forty-four obese, pre-menopausal women completed the Reward-based Eating Drive (RED) scale at study start and daily food-craving intensity on 5 days on which they ingested either a pill-placebo (2 days), a 25mg naltrexone dose (1 day), or a standard 50mg naltrexone dose (2 days). Results Craving intensity was similar under naltrexone and placebo doses. The association between food-craving intensity and reward-driven eating significantly differed between placebo and 50mg naltrexone doses. Reward-driven eating and craving intensity were significantly positively associated under both placebo doses. As predicted, opioidergic blockade (for both doses 25mg and 50mg naltrexone) reduced this positive association between reward-driven eating and craving intensity to non-significance. Conclusions Opioidergic blockade did not reduce craving intensity; however, blockade reduced an association between trait-like reward-driven eating and daily food-craving intensity, and may help identify an important endophenotype within obesity. PMID:26164674

Orange pomace improves postprandial glycemic responses: an acute, randomized, placebo-controlled, double-blind, crossover trial in overweight men

USDA-ARS?s Scientific Manuscript database

Orange pomace (OP), a fiber-rich byproduct of juice production, has the potential for being formulated into a variety of food products. We hypothesized that OP would diminish postprandial glycemic responses to a high carbohydrate/fat breakfast and lunch. We conducted an acute, randomized, placebo-co...

Position paper of the EAACI: food allergy due to immunological cross-reactions with common inhalant allergens.

PubMed

Werfel, T; Asero, R; Ballmer-Weber, B K; Beyer, K; Enrique, E; Knulst, A C; Mari, A; Muraro, A; Ollert, M; Poulsen, L K; Vieths, S; Worm, M; Hoffmann-Sommergruber, K

2015-09-01

In older children, adolescents, and adults, a substantial part of all IgE-mediated food allergies is caused by cross-reacting allergenic structures shared by inhalants and foods. IgE stimulated by a cross-reactive inhalant allergen can result in diverse patterns of allergic reactions to various foods. Local, mild, or severe systemic reactions may occur already after the first consumption of a food containing a cross-reactive allergen. In clinical practice, clinically relevant sensitizations are elucidated by skin prick testing or by the determination of specific IgE in vitro. Component-resolved diagnosis may help to reach a diagnosis and may predict the risk of a systemic reaction. Allergy needs to be confirmed in cases of unclear history by oral challenge tests. The therapeutic potential of allergen immunotherapy with inhalant allergens in pollen-related food allergy is not clear, and more placebo-controlled studies are needed. As we are facing an increasing incidence of pollen allergies, a shift in sensitization patterns and changes in nutritional habits, and the occurrence of new, so far unknown allergies due to cross-reactions are expected. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Tolerability of donkey's milk in 92 highly-problematic cow's milk allergic children.

PubMed

Monti, G; Viola, S; Baro, C; Cresi, F; Tovo, P A; Moro, G; Ferrero, M P; Conti, A; Bertino, E

2012-01-01

Not exclusively breastfed children with cow's milk allergy (CMA) require a formula or other alternative food, but past and present guidelines differ concerning the best choice. Our aim was to investigate the clinical tolerability, palatability and nutritional adequacy of donkey's milk (DM) in children with proven CMA. It was important to identify a CM replacement for these children, highly problematic from the feeding standpoint, in spite of their age. A prospective study was conducted on 92 children with CMA, diagnosed through a CM elimination diet, followed by double-blind, placebo-controlled food challenge (DBPCFC) unless contraindicated. Maternal milk was unavailable and current CM substitutes could not be used. Moreover, 89 percent were affected by multiple FA, and subjected to very restricted diets. Within 3 months after the last CM challenge, DBPCFC for DM was performed. CM or DM skin prick test and sIgE determination preceded the CM or DM challenge, respectively. Native electrophoresis and immunoblotting were used to identify CM and DM cross-reactive proteins. Z-scores of weight and length/stature for age were calculated at DM food challenge (T0) and during DM assumption. 83 children (90.2 percent) liked and tolerated DM, at challenge and during follow-up, with increased Z-score for weight and length/stature and improved nutritional parameters. Bovine beta-lactoglobulin was identified as the cross-reacting protein among the DM allergic patients. DM was found to be a valid alternative foodstuff, in terms of clinical tolerability, palatability and nutritional adequacy, in subjects with CMA who were highly problematic from the feeding standpoint.

A placebo-controlled study of the nasal decongestant effect of phenylephrine and pseudoephedrine in the Vienna Challenge Chamber.

PubMed

Horak, Friedrich; Zieglmayer, Petra; Zieglmayer, René; Lemell, Patrick; Yao, Ruji; Staudinger, Heribert; Danzig, Melvyn

2009-02-01

Studies on the efficacy of phenylephrine in the treatment of nasal congestion have yielded inconsistent results, notwithstanding its approval for this indication. To evaluate and compare the decongestant effect of a single dose of phenylephrine to placebo and pseudoephedrine in patients with seasonal allergic rhinitis. This randomized, placebo-controlled, 3-way crossover study evaluated patient-scored nasal congestion, peak nasal inspiratory flow, and rhinomanometry at more than 6 hours in 39 grass-sensitive patients exposed to grass pollen in the Vienna Challenge Chamber. Patients were dosed with immediate-release formulations of phenylephrine, 12 mg, pseudoephedrine, 60 mg, as a control, or placebo. Phenylephrine was not significantly different from placebo in the primary end point, mean change in nasal congestion score at more than 6 hours (P = .56), whereas pseudoephedrine was significantly more effective than both placebo (P < .01) and phenylephrine (P = .01). Phase 1 results showed a difference between phenylephrine and placebo that was 64% of the difference between pseudoephedrine and placebo, substantially greater than the 17% difference observed for all phases. Carryover bias due to patient recall of the pseudoephedrine effect may have influenced these results. Rhinomanometry and peak nasal inspiratory flow results were consistent with these data. Neither phenylephrine nor pseudoephedrine had an effect on the nonnasal symptoms. No adverse events were reported in this study. During a 6-hour observation period, a single dose of pseudoephedrine but not phenylephrine resulted in significant improvement in measures of nasal congestion. Neither phenylephrine nor pseudoephedrine had an effect on nonnasal symptoms.

Diagnosis of Non-Celiac Gluten Sensitivity (NCGS): The Salerno Experts' Criteria.

PubMed

Catassi, Carlo; Elli, Luca; Bonaz, Bruno; Bouma, Gerd; Carroccio, Antonio; Castillejo, Gemma; Cellier, Christophe; Cristofori, Fernanda; de Magistris, Laura; Dolinsek, Jernej; Dieterich, Walburga; Francavilla, Ruggiero; Hadjivassiliou, Marios; Holtmeier, Wolfgang; Körner, Ute; Leffler, Dan A; Lundin, Knut E A; Mazzarella, Giuseppe; Mulder, Chris J; Pellegrini, Nicoletta; Rostami, Kamran; Sanders, David; Skodje, Gry Irene; Schuppan, Detlef; Ullrich, Reiner; Volta, Umberto; Williams, Marianne; Zevallos, Victor F; Zopf, Yurdagül; Fasano, Alessio

2015-06-18

Non-Celiac Gluten Sensitivity (NCGS) is a syndrome characterized by intestinal and extra-intestinal symptoms related to the ingestion of gluten-containing food, in subjects that are not affected by either celiac disease or wheat allergy. Given the lack of a NCGS biomarker, there is the need for standardizing the procedure leading to the diagnosis confirmation. In this paper we report experts' recommendations on how the diagnostic protocol should be performed for the confirmation of NCGS. A full diagnostic procedure should assess the clinical response to the gluten-free diet (GFD) and measure the effect of a gluten challenge after a period of treatment with the GFD. The clinical evaluation is performed using a self-administered instrument incorporating a modified version of the Gastrointestinal Symptom Rating Scale. The patient identifies one to three main symptoms that are quantitatively assessed using a Numerical Rating Scale with a score ranging from 1 to 10. The double-blind placebo-controlled gluten challenge (8 g/day) includes a one-week challenge followed by a one-week washout of strict GFD and by the crossover to the second one-week challenge. The vehicle should contain cooked, homogeneously distributed gluten. At least a variation of 30% of one to three main symptoms between the gluten and the placebo challenge should be detected to discriminate a positive from a negative result. The guidelines provided in this paper will help the clinician to reach a firm and positive diagnosis of NCGS and facilitate the comparisons of different studies, if adopted internationally.

Diagnosis of Non-Celiac Gluten Sensitivity (NCGS): The Salerno Experts’ Criteria

PubMed Central

Catassi, Carlo; Elli, Luca; Bonaz, Bruno; Bouma, Gerd; Carroccio, Antonio; Castillejo, Gemma; Cellier, Christophe; Cristofori, Fernanda; de Magistris, Laura; Dolinsek, Jernej; Dieterich, Walburga; Francavilla, Ruggiero; Hadjivassiliou, Marios; Holtmeier, Wolfgang; Körner, Ute; Leffler, Dan A.; Lundin, Knut E. A.; Mazzarella, Giuseppe; Mulder, Chris J.; Pellegrini, Nicoletta; Rostami, Kamran; Sanders, David; Skodje, Gry Irene; Schuppan, Detlef; Ullrich, Reiner; Volta, Umberto; Williams, Marianne; Zevallos, Victor F.; Zopf, Yurdagül; Fasano, Alessio

2015-01-01

Non-Celiac Gluten Sensitivity (NCGS) is a syndrome characterized by intestinal and extra-intestinal symptoms related to the ingestion of gluten-containing food, in subjects that are not affected by either celiac disease or wheat allergy. Given the lack of a NCGS biomarker, there is the need for standardizing the procedure leading to the diagnosis confirmation. In this paper we report experts’ recommendations on how the diagnostic protocol should be performed for the confirmation of NCGS. A full diagnostic procedure should assess the clinical response to the gluten-free diet (GFD) and measure the effect of a gluten challenge after a period of treatment with the GFD. The clinical evaluation is performed using a self-administered instrument incorporating a modified version of the Gastrointestinal Symptom Rating Scale. The patient identifies one to three main symptoms that are quantitatively assessed using a Numerical Rating Scale with a score ranging from 1 to 10. The double-blind placebo-controlled gluten challenge (8 g/day) includes a one-week challenge followed by a one-week washout of strict GFD and by the crossover to the second one-week challenge. The vehicle should contain cooked, homogeneously distributed gluten. At least a variation of 30% of one to three main symptoms between the gluten and the placebo challenge should be detected to discriminate a positive from a negative result. The guidelines provided in this paper will help the clinician to reach a firm and positive diagnosis of NCGS and facilitate the comparisons of different studies, if adopted internationally. PMID:26096570

Fish oil in infancy protects against food allergy in Iceland-Results from a birth cohort study.

PubMed

Clausen, M; Jonasson, K; Keil, T; Beyer, K; Sigurdardottir, S T

2018-01-10

Consumption of oily fish or fish oil during pregnancy, lactation and infancy has been linked to a reduction in the development of allergic diseases in childhood. In an observational study, Icelandic children (n = 1304) were prospectively followed from birth to 2.5 years with detailed questionnaires administered at birth and at 1 and 2 years of age, including questions about fish oil supplementation. Children with suspected food allergy were invited for physical examinations, allergic sensitization tests, and a double-blind, placebo-controlled food challenge if the allergy testing or clinical history indicated food allergy. The study investigated the development of sensitization to food and confirmed food allergy according to age and frequency of postnatal fish oil supplementation using proportional hazards modelling. The incidence of diagnosed food sensitization was significantly lower in children who received regular fish oil supplementation (relative risk: 0.51, 95% confidence interval: 0.32-0.82). The incidence of challenge-confirmed food allergy was also reduced, although not statistically significant (0.57, 0.30-1.12). Children who began to receive fish oil in their first half year of life were significantly more protected than those who began later (P = .045 for sensitization, P = .018 for allergy). Indicators of allergy severity decreased with increased fish oil consumption (P = .013). Adjusting for parent education and allergic family history did not change the results. Postnatal fish oil consumption is associated with decreased food sensitization and food allergies in infants and may provide an intervention strategy for allergy prevention. © 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

The suppression of appetite and food consumption by methylphenidate: the moderating effects of gender and weight status in healthy adults.

PubMed

Davis, Caroline; Fattore, Liana; Kaplan, Allan S; Carter, Jacqueline C; Levitan, Robert D; Kennedy, James L

2012-03-01

Females typically show greater behavioural responses to stimulant drugs than males, including loss of appetite; as seen, for example, in those who use methylphenidate (MP) therapeutically for treatment of attention deficit hyperactivity disorder (ADHD). This is a relevant issue because of the strong link between ADHD and obesity. In a sample (n=132) of normal-weight (BMI <25) and obese (BMI >30) men and women we assessed appetite, cravings, and snack-food intake in response to MP (0.5 mg/kg) and placebo. Results indicated a significant three-way interaction for the three dependent variables--food-related responding diminishing in all groups from placebo to MP, except in obese males who showed no decreases to the MP challenge. These data show for the first time the existence of gender differences in the appetite response to MP, and are relevant for finding a dopamine pathway to new weight-loss medications, which would be utilized differently in males than in females.

Small Amounts of Gluten in Subjects With Suspected Nonceliac Gluten Sensitivity: A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Trial.

PubMed

Di Sabatino, Antonio; Volta, Umberto; Salvatore, Chiara; Biancheri, Paolo; Caio, Giacomo; De Giorgio, Roberto; Di Stefano, Michele; Corazza, Gino R

2015-09-01

There is debate over the existence of nonceliac gluten sensitivity (NCGS) intestinal and extraintestinal symptoms in response to ingestion of gluten-containing foods by people without celiac disease or wheat allergy. We performed a randomized, double-blind, placebo-controlled, cross-over trial to determine the effects of administration of low doses of gluten to subjects with suspected NCGS. We enrolled 61 adults without celiac disease or a wheat allergy who believed ingestion of gluten-containing food to be the cause of their intestinal and extraintestinal symptoms. Participants were assigned randomly to groups given either 4.375 g/day gluten or rice starch (placebo) for 1 week, each via gastrosoluble capsules. After a 1-week gluten-free diet, participants crossed over to the other group. The primary outcome was the change in overall (intestinal and extraintestinal) symptoms, determined by established scoring systems, between gluten and placebo intake. A secondary outcome was the change in individual symptom scores between gluten vs placebo. According to the per-protocol analysis of data from the 59 patients who completed the trial, intake of gluten significantly increased overall symptoms compared with placebo (P = .034). Abdominal bloating (P = .040) and pain (P = .047), among the intestinal symptoms, and foggy mind (P = .019), depression (P = .020), and aphthous stomatitis (P = .025), among the extraintestinal symptoms, were significantly more severe when subjects received gluten than placebo. In a cross-over trial of subjects with suspected NCGS, the severity of overall symptoms increased significantly during 1 week of intake of small amounts of gluten, compared with placebo. Clinical trial no: ISRCTN72857280. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

The effects of the dopamine D₃ receptor antagonist GSK598809 on attentional bias to palatable food cues in overweight and obese subjects.

PubMed

Nathan, Pradeep J; O'Neill, Barry V; Mogg, Karin; Bradley, Brendan P; Beaver, John; Bani, Massimo; Merlo-Pich, Emilio; Fletcher, Paul C; Swirski, Bridget; Koch, Annelize; Dodds, Chris M; Bullmore, Edward T

2012-03-01

The mesolimbic dopamine system plays a critical role in the reinforcing effects of rewards. Evidence from pre-clinical studies suggests that D₃ receptor antagonists may attenuate the motivational impact of rewarding cues. In this study we examined the acute effects of the D₃ receptor antagonist GSK598809 on attentional bias to rewarding food cues in overweight to obese individuals (n=26, BMI mean=32.7±3.7, range 27-40 kg/m²) who reported binge and emotional eating. We also determined whether individual differences in restrained eating style modulated the effects of GSK598809 on attentional bias. The study utilized a randomized, double-blind, placebo-controlled cross-over design with each participant tested following acute administration of placebo and GSK598809 (175 mg). Attentional bias was assessed by the visual probe task and modified Stroop task using food-related words. Overall GSK598809 had no effects on attentional bias in either the visual probe or food Stroop tasks. However, the effect of GSK598809 on both visual probe and food Stroop attentional bias scores was inversely correlated with a measure of eating restraint allowing the identification of two subpopulations, low- and high-restrained eaters. Low-restrained eaters had a significant attentional bias towards food cues in both tasks under placebo, and this was attenuated by GSK598809. In contrast, high-restrained eaters showed no attentional bias to food cues following either placebo or GSK598809. These findings suggest that excessive attentional bias to food cues generated by individual differences in eating traits can be modulated by D₃ receptor antagonists, warranting further investigation with measures of eating behaviour and weight loss.

A brief history of placebos and clinical trials in psychiatry.

PubMed

Shorter, Edward

2011-04-01

The history of placebos in psychiatry can be understood only in the context of randomized controlled trials (RCTs). Placebo treatments are as old as medicine itself, and are particularly effective in dealing with psychosomatic symptoms. In psychiatry, placebos have mainly been featured in clinical drug trials. The earliest controlled trial in psychiatry (not involving drugs) occurred in 1922, followed by the first crossover studies during the 1930s. Meanwhile the concept of randomization was developed during the interwar years by British statistician Ronald A Fisher, and introduced in 3 trials of tuberculosis drugs between 1947 and 1951. These classic studies established the RCT as the gold standard in pharmaceutical trials, and its status was cemented during the mid-1950s. Nevertheless, while the placebo became established as a standard measure of drug action, placebo treatments became stigmatized as unethical. This is unfortunate, as they constitute one of the most powerful therapies in psychiatry. In recent years, moreover, the dogma of the placebo-controlled trial as the only acceptable data for drug licensing is also being increasingly discredited. This backlash has had 2 sources: one is the recognition that the US Food and Drug Administration has been too lax in permitting trials controlled with placebos alone, rather than also using an active agent as a test of comparative efficacy. In addition, there is evidence that in the hands of the pharmaceutical industry, the scientific integrity of RCTs themselves has been degraded into a marketing device. The once-powerful placebo is thus threatened with extinction.

Risk of low bone mineral density and low body mass index in patients with non-celiac wheat-sensitivity: a prospective observation study.

PubMed

Carroccio, Antonio; Soresi, Maurizio; D'Alcamo, Alberto; Sciumè, Carmelo; Iacono, Giuseppe; Geraci, Girolamo; Brusca, Ignazio; Seidita, Aurelio; Adragna, Floriana; Carta, Miriam; Mansueto, Pasquale

2014-11-28

Non-celiac gluten sensitivity (NCGS) or 'wheat sensitivity' (NCWS) is included in the spectrum of gluten-related disorders. No data are available on the prevalence of low bone mass density (BMD) in NCWS. Our study aims to evaluate the prevalence of low BMD in NCWS patients and search for correlations with other clinical characteristics. This prospective observation study included 75 NCWS patients (63 women; median age 36 years) with irritable bowel syndrome (IBS)-like symptoms, 65 IBS and 50 celiac controls. Patients were recruited at two Internal Medicine Departments. Elimination diet and double-blind placebo controlled (DBPC) wheat challenge proved the NCWS diagnosis. All subjects underwent BMD assessment by Dual Energy X-Ray Absorptiometry (DXA), duodenal histology, HLA DQ typing, body mass index (BMI) evaluation and assessment for daily calcium intake. DBPC cow's milk proteins challenge showed that 30 of the 75 NCWS patients suffered from multiple food sensitivity. Osteopenia and osteoporosis frequency increased from IBS to NCWS and to celiac disease (CD) (P <0.0001). Thirty-five NCWS patients (46.6%) showed osteopenia or osteoporosis. Low BMD was related to low BMI and multiple food sensitivity. Values of daily dietary calcium intake in NCWS patients were significantly lower than in IBS controls. An elevated frequency of bone mass loss in NCWS patients was found; this was related to low BMI and was more frequent in patients with NCWS associated with other food sensitivity. A low daily intake of dietary calcium was observed in patients with NCWS.

Safety and lipid-altering efficacy of a new omega-3 fatty acid and antioxidant-containing medical food in men and women with elevated triacylglycerols.

PubMed

Maki, K C; Geohas, J G; Dicklin, M R; Huebner, M; Udani, J K

2015-08-01

This randomized, double-blind, placebo-controlled multi-center trial investigated the lipid-altering effects of a medical food (PDL-0101) providing 1.8 g/d eicosapentaenoic acid; 12 mg/d astaxanthin, a marine algae-derived carotenoid; and 100 mg/d tocopherol-free gamma/delta tocotrienols enriched with geranylgeraniol, extracted from annatto, on triacylglycerols (TAG), other lipoprotein lipids, and oxidized low-density lipoprotein (LDL) in 102 subjects with TAG 150-499 mg/dL (1.69-5.63 mmol/L) and LDL cholesterol (LDL-C) ≥70 mg/dL (1.81 mmol/L). Compared to placebo, after eight weeks of treatment, PDL-0101 significantly reduced median TAG (-9.5% vs. 10.6%, p<0.001), while not significantly altering mean LDL-C (-3.0% vs. -8.0% for PDL-0101 and placebo, respectively, p=0.071), mean high-density lipoprotein cholesterol (~3% decrease in both groups, p=0.732), or median oxidized LDL concentrations (5% vs. -5% for PDL-0101 and placebo, respectively, p=0.112). These results demonstrate that PDL-0101 is an effective medical food for the management of elevated TAG. Copyright © 2015 Elsevier Ltd. All rights reserved.

A randomized placebo controlled trial to evaluate the effects of butamirate and dextromethorphan on capsaicin induced cough in healthy volunteers

PubMed Central

Faruqi, Shoaib; Wright, Caroline; Thompson, Rachel; Morice, Alyn H

2014-01-01

Aims The examination of cough reflex sensitivity through inhalational challenge can be utilized to demonstrate pharmacological end points. Here we compare the effect of butamirate, dextromethorphan and placebo on capsaicin-induced cough in healthy volunteers. Methods In this randomized, placebo-controlled, six way crossover study the effect of dextromethrophan 30 mg, four doses of butamirate and placebo was evaluated on incremental capsaicin challenges performed at baseline and 2, 4, 6, 8, 12 and 24 h following dosing. The primary end point was the area under the curve (AUC(0,12h)) of log10 C5 from pre-dose to 12 h after dosing. Plasma butamirate metabolites were analyzed to evaluate pharmacokinetic and pharmacodynamic relationships. Results Thirty-four subjects (13 males, median age 25 years) completed the study. Cough sensitivity decreased from baseline in all arms of the study. Dextromethorphan was superior to placebo (P = 0.01) but butamirate failed to show significant activity with maximum attenuation at the 45 mg dose. There was no apparent relationship between pharmacokinetic and pharmacodynamic parameters for butamirate. Conclusions We have demonstrated for the first time that dextromethorphan attenuates capsaicin challenge confirming its broad activity on the cough reflex. The lack of efficacy of butamirate could be due to formulation issues at higher doses. PMID:24995954

A randomized placebo controlled trial to evaluate the effects of butamirate and dextromethorphan on capsaicin induced cough in healthy volunteers.

PubMed

Faruqi, Shoaib; Wright, Caroline; Thompson, Rachel; Morice, Alyn H

2014-12-01

The examination of cough reflex sensitivity through inhalational challenge can be utilized to demonstrate pharmacological end points. Here we compare the effect of butamirate, dextromethorphan and placebo on capsaicin-induced cough in healthy volunteers. In this randomized, placebo-controlled, six way crossover study the effect of dextromethrophan 30 mg, four doses of butamirate and placebo was evaluated on incremental capsaicin challenges performed at baseline and 2, 4, 6, 8, 12 and 24 h following dosing. The primary end point was the area under the curve (AUC(0,12h)) of log10 C5 from pre-dose to 12 h after dosing. Plasma butamirate metabolites were analyzed to evaluate pharmacokinetic and pharmacodynamic relationships. Thirty-four subjects (13 males, median age 25 years) completed the study. Cough sensitivity decreased from baseline in all arms of the study. Dextromethorphan was superior to placebo (P = 0.01) but butamirate failed to show significant activity with maximum attenuation at the 45 mg dose. There was no apparent relationship between pharmacokinetic and pharmacodynamic parameters for butamirate. We have demonstrated for the first time that dextromethorphan attenuates capsaicin challenge confirming its broad activity on the cough reflex. The lack of efficacy of butamirate could be due to formulation issues at higher doses. © 2014 The British Pharmacological Society.

Non-coeliac gluten or wheat sensitivity: emerging disease or misdiagnosis?

PubMed

Potter, Michael DE; Walker, Marjorie M; Talley, Nicholas J

2017-08-04

Non-coeliac gluten or wheat sensitivity (NCG/WS) is a condition characterised by adverse gastrointestinal and/or extra-intestinal symptoms associated with the ingestion of gluten- or wheat-containing foods, in the absence of coeliac disease or wheat allergy. Up to one in 100 people in Australia may have coeliac disease but many more report adverse gastrointestinal and/or extra-intestinal symptoms after eating wheat products. In the absence of validated biomarkers, a diagnosis of NCG/WS can only be made by a double-blind, placebo-controlled, dietary crossover challenge with gluten, which is difficult to apply in clinical practice. Of people self-reporting gluten or wheat sensitivity, only a small proportion (16%) will have reproducible symptoms after a blinded gluten challenge of gluten versus placebo in a crossover dietary trial and fulfil the current consensus criteria for a diagnosis of NCG/WS. A wide range of symptoms are associated with NCG/WS, including gastrointestinal, neurological, psychiatric, rheumatological and dermatological complaints. The pathogenesis of NCG/WS is not well understood, but the innate immune system has been implicated, and there is overlap with coeliac disease and the functional gastrointestinal disorders (irritable bowel syndrome and functional dyspepsia). Identification of NCG/WS is important as gluten-free diets carry risks, are socially restricting and are costlier than regular diets.

sIgE Ana o 1, 2 and 3 accurately distinguish tolerant from allergic children sensitized to cashew nuts.

PubMed

van der Valk, J P M; Gerth van Wijk, R; Vergouwe, Y; Steyerberg, E W; Reitsma, M; Wichers, H J; Savelkoul, H F J; Vlieg-Boerstra, B; de Groot, H; Dubois, A E J; de Jong, N W

2017-01-01

The double-blind, placebo-controlled food challenge test (DBPCFC) is the gold standard in cashew nut allergy. This test is costly, time consuming and not without side effects. Analysis of IgE reactivity to cashew nut components may reduce the need for food challenge tests. In a prospective and multicentre study, children with suspected cashew nut allergy underwent a DBPCFC with cashew nut. Specific IgE to cashew nut and to the components Ana o 1, 2 and 3 were determined. A skin prick test (SPT) with cashew nut extract was performed. The association between the outcome of the food challenge test and specific IgE to Ana o 1, 2 and 3 was assessed with logistic regression analyses, unadjusted and adjusted for other diagnostic variables. Discriminative ability was quantified with a concordance index (c). A total of 173 children (103 boys, 60%) with a median age of 9 years were included. About 79% had a positive challenge test outcome. A steep rise in the risk of a positive challenge was observed for specific IgE to each individual component Ana o 1, 2 and 3 with estimated risks up to approximately 100%. Median values of Ana o 1, 2, 3 were 1.29 kU/l (range 0-100 kU/l), 4.77 kU/l (range 0-100 kU/l) and 8.33 kU/l (range 0-100 kU/l) respectively and varied significantly (p < 0.001). Specific IgE to Ana o 1, 2 and 3 was better distinguished between cashew-allergic and tolerant children (c = 0.87, 0.85 and 0.89, respectively) than specific IgE to cashew nut or SPT (c = 0.76 and 0.83, respectively). The major cashew nut allergens Ana o 1, 2 and 3 are each individually predictive for the outcome of food challenge tests in cashew-allergic children. © 2016 John Wiley & Sons Ltd.

Food choice as a key management strategy for functional gastrointestinal symptoms.

PubMed

Gibson, Peter R; Shepherd, Susan J

2012-05-01

Recognition of food components that induce functional gut symptoms in patient's functional bowel disorders (FBD) has been challenging. Food directly or indirectly provides considerable afferent input into the enteric nervous system. There is an altered relationship between the afferent input and perception/efferent response in FBD. Defining the nature of food-related stimuli may provide a means of minimizing such an input and gut symptoms. Using this premise, reducing the intake of FODMAPs (fermentable oligo-, di-, and mono-saccharides and polyols)--poorly absorbed short-chain carbohydrates that, by virtue of their small molecular size and rapid fermentability, will distend the intestinal lumen with liquid and gas--improves symptoms in the majority of patients. Well-developed methodologies to deliver the diet via dietician-led education are available. Another abundant source of afferent input is natural and added food chemicals (such as salicylates, amines, and glutamates). Studies are needed to assess the efficacy of the low food chemical dietary approach. A recent placebo-controlled trial of FODMAP-poor gluten provided the first valid evidence that non-celiac gluten intolerance might actually exist, but its prevalence and underlying mechanisms require elucidation. Food choice via the low FODMAP and potentially other dietary strategies is now a realistic and efficacious therapeutic approach for functional gut symptoms.

Allergenic potential of novel foods.

PubMed

Meredith, Clive

2005-11-01

Concerns have been expressed that the introduction of novel foods into the diet might lead to the development of new food allergies in consumers. Novel foods can be conveniently divided into GM and non-GM categories. Decision-tree approaches (e.g. International Life Sciences Institute-International Food Biotechnology Council and WHO/FAO) to assess the allergenic potential of GM foods were developed following the discovery, during product development, of the allergenic potential of GM soyabean expressing a gene encoding a storage protein from Brazil nut (Bertolletia excelsa). Within these decision trees considerations include: the source of the transgene; amino acid homology with known allergens; cross-reactivity with IgE from food-allergic individuals; resistance to proteolysis; prediction using animal models of food allergy. Such decision trees are under constant review as new knowledge and improved models emerge, but they provide a useful framework for the assessment of the allergenic potential of GM foods. For novel non-GM foods the assessment of allergenic potential is more subjective; some foods or food ingredients will need no assessment other than a robust protein assay to demonstrate the absence of protein. Where protein is present in the novel non-GM food, hazard and risk assessments need to be made in terms of the quantity of protein that might be consumed, the identity of individual protein components and their relationships to known food allergens. Where necessary, this assessment would extend to serum screening for potential cross-reactivities, skin-prick tests in previously-sensitised individuals and double-blind placebo-controlled food challenges.

Does the Neuroimmune Modulator Ibudilast Alter Food Craving? Results in a Sample With Alcohol Use Disorder.

PubMed

Cummings, Jenna R; Tomiyama, A Janet; Ray, Lara A

2018-05-21

Ibudilast (IBUD) is a neuroimmune modulator that inhibits phosphodiesterase-4 and -10 and macrophage migration inhibitory factor. A randomized, placebo-control, crossover human laboratory trial advanced IBUD development for alcohol use disorder and found that IBUD reduced tonic levels of alcohol craving. Given the importance of considering medication effects on other appetitive behavior, the present study tested the effect of IBUD (50 mg bid) on food craving. The present study was a secondary data analysis of the trial of IBUD in non-treatment seekers with alcohol use disorder (N = 19). High-fat/high-sugar food craving was measured daily. Moreover, because substantial literatures show that small alcohol doses and psychological stress increase eating of high-fat/high-sugar food, craving for high-fat/high-sugar food was measured after alcohol infusion and stress reactivity. Results indicated that IBUD did not alter tonic high-fat/high-sugar food craving. Alcohol infusion did not generally increase high-fat/high-sugar food craving but psychological stress did. Likewise, IBUD did not affect high-fat/high-sugar food craving after alcohol infusion but IBUD did increase high-fat/high-sugar food craving after psychological stress. Follow-up analyses revealed that, among individuals with lower depressive symptomatology, IBUD compared to placebo heightened the effect of psychological stress on high-fat/high-sugar food craving. These results advance the development of IBUD for addiction indications by demonstrating that IBUD compared to placebo does not suppress other appetitive responses, namely craving for high-fat/high-sugar food among individuals with alcohol use disorder.

A Brief History of Placebos and Clinical Trials in Psychiatry

PubMed Central

Shorter, Edward

2013-01-01

The history of placebos in psychiatry can be understood only in the context of randomized controlled trials (RCTs). Placebo treatments are as old as medicine itself, and are particularly effective in dealing with psychosomatic symptoms. In psychiatry, placebos have mainly been featured in clinical drug trials. The earliest controlled trial in psychiatry (not involving drugs) occurred in 1922, followed by the first crossover studies during the 1930s. Meanwhile the concept of randomization was developed during the interwar years by British statistician Ronald A Fisher, and introduced in 3 trials of tuberculosis drugs between 1947 and 1951. These classic studies established the RCT as the gold standard in pharmaceutical trials, and its status was cemented during the mid-1950s. Nevertheless, while the placebo became established as a standard measure of drug action, placebo treatments became stigmatized as unethical. This is unfortunate, as they constitute one of the most powerful therapies in psychiatry. In recent years, moreover, the dogma of the placebo-controlled trial as the only acceptable data for drug licensing is also being increasingly discredited. This backlash has had 2 sources: one is the recognition that the US Food and Drug Administration has been too lax in permitting trials controlled with placebos alone, rather than also using an active agent as a test of comparative efficacy. In addition, there is evidence that in the hands of the pharmaceutical industry, the scientific integrity of RCTs themselves has been degraded into a marketing device. The once-powerful placebo is thus threatened with extinction. PMID:21507275

Prebiotic supplementation improves appetite control in children with overweight and obesity: a randomized controlled trial.

PubMed

Hume, Megan P; Nicolucci, Alissa C; Reimer, Raylene A

2017-04-01

Background: Prebiotics have been shown to improve satiety in adults with overweight and obesity; however, studies in children are limited. Objective: We examined the effects of prebiotic supplementation on appetite control and energy intake in children with overweight and obesity. Design: This study was a randomized, double-blind, placebo-controlled trial. Forty-two boys and girls, ages 7-12 y, with a body mass index (BMI) of ≥85th percentile were randomly assigned to 8 g oligofructose-enriched inulin/d or placebo (maltodextrin) for 16 wk. Objective measures of appetite included energy intake at an ad libitum breakfast buffet, 3-d food records, and fasting satiety hormone concentrations. Subjective appetite ratings were obtained from visual analog scales before and after the breakfast. Children's Eating Behavior Questionnaires were also completed by caregivers. Results: Compared with placebo, prebiotic intake resulted in significantly higher feelings of fullness ( P = 0.04) and lower prospective food consumption ( P = 0.03) at the breakfast buffet at 16 wk compared with baseline. Compared with placebo, prebiotic supplementation significantly reduced energy intake at the week 16 breakfast buffet in 11- and 12-y-olds ( P = 0.04) but not in 7- to 10-y-olds. Fasting adiponectin ( P = 0.04) and ghrelin ( P = 0.03) increased at 16 wk with the prebiotic compared with placebo. In intent-to-treat analysis, there was a trend for prebiotic supplementation to reduce BMI z score to a greater extent than placebo (-3.4%; P = 0.09) and a significant -3.8% reduction in per-protocol analysis ( P = 0.043). Conclusions: Independent of other lifestyle changes, prebiotic supplementation in children with overweight and obesity improved subjective appetite ratings. This translated into reduced energy intake in a breakfast buffet in older but not in younger children. This simple dietary change has the potential to help with appetite regulation in children with obesity. This trial was registered at clinicaltrials.gov as NCT02125955. © 2017 American Society for Nutrition.

The diagnostic value of component-resolved diagnostics in peanut allergy in children attending a Regional Paediatric Allergology Clinic.

PubMed

van Veen, Leonieke N; Heron, Michiel; Batstra, Manou; van Haard, Paul M M; de Groot, Hans

2016-06-02

To date, diagnosing food allergies in children still presents a diagnostic dilemma, leading to uncertainty concerning the definite diagnosis of peanut allergy, as well as to the need for strict diets and the potential need for adrenalin auto-injectors. This uncertainty in particular is thought to contribute to a lower quality of life. In the diagnostic process double-blind food challenges are considered the gold standard, but they are time-consuming as well as potentially hazardous. Other diagnostic tests have been extensively studied and among these component-resolved diagnostics appeared to present a promising alternative: Ara h2, a peanut storage protein in previous studies showed to have a significant predictive value. Sixty-two out of 72 children, with suspected peanut allergy were analyzed using serum specific IgE and/or skin prick tests and specific IgE to several components of peanut (Ara h 1, 2, 3, 6, 8, 9). Subsequently, double-blind food challenges were performed. The correlation between the various diagnostic tests and the overall outcome of the double-blind food challenges were studied, in particular the severity of the reaction and the eliciting dose. The double-blind provocation with peanut was positive in 33 children (53 %). There was no relationship between the eliciting dose and the severity of the reaction. A statistically significant relationship was found between the skin prick test, specific IgE directed to peanut, Ara h 1, Ara h 2 or Ara h 6, and the outcome of the food challenge test, in terms of positive or negative (P < .001). However, we did not find any relationship between sensitisation to peanut extract or the different allergen components and the severity of the reaction or the eliciting dose. There was no correlation between IgE directed to Ara h 3, Ara h 8, Ara h 9 and the clinical outcome of the food challenge. This study shows that component-resolved diagnostics is not superior to specific IgE to peanut extract or to skin prick testing. At present, it cannot replace double-blind placebo-controlled food challenges for determination of the eliciting dose or the severity of the peanut allergy in our patient group.

Differential effect of the 5-HTT gene-linked polymorphic region on emotional eating during stress exposure following tryptophan challenge.

PubMed

Markus, C Rob; Verschoor, Ellen; Smeets, Tom

2012-04-01

Stress and negative moods, which are thought to be partly mediated by reduced brain serotonin function, often increase emotional eating in dieting women (restrainers). Because the short (S) allele polymorphism in the serotonin transporter gene (5-HTTLPR) is associated with serotonin dysfunction, S allele compared to long (L) allele 5-HTTLPR genotypes may be more susceptible to stress-induced emotional eating. Consequently, serotonin challenge via tryptophan (TRP)-rich protein hydrolysate (TPH) may alleviate stress-induced emotional eating particularly in S/S allele carriers. We tested whether acute stress affects emotional eating in women with high or low dietary restraints depending on their 5-HTTLPR genotype and TPH intake. Nineteen female subjects who were homozygous for the short-allele 5-HTTLPR genotype (S'/S'=S/L(G), L(G)/L(G): restrainers vs. nonrestrainers) and 23 female subjects who were homozygous for the long-allele 5-HTTLPR genotype (L'/L'=L(A)/L(A): restrainers vs. nonrestrainers) were tested in a double-blind, placebo-controlled crossover study of stress-induced emotional eating following intake of TPH or a placebo. TPH intake significantly increased the plasma TRP/large neutral amino acid ratio (P<.0001) in the L'/L' group (70%) compared to the S'/S' group (30%). TPH reduced food intake in both groups, but in the L'/L' group, it also reduced stress-induced negative mood (P=.037) and the desire for sweet, high-fat foods (P=.011) regardless of dietary restraint. Since TPH caused a greater increase in the plasma TRP/large neutral amino acid ratio in the L'/L' group compared to S'/S' group, the exclusive beneficial effects of L'/L' genotype may be due to enhanced brain 5-HT function. Copyright © 2012 Elsevier Inc. All rights reserved.

Diagnosis of exercise-induced anaphylaxis: current insights.

PubMed

Pravettoni, Valerio; Incorvaia, Cristoforo

2016-01-01

Exercise-induced anaphylaxis (EIAn) is defined as the occurrence of anaphylactic symptoms (skin, respiratory, gastrointestinal, and cardiovascular symptoms) after physical activity. In about a third of cases, cofactors, such as food intake, temperature (warm or cold), and drugs (especially nonsteroidal anti-inflammatory drugs) can be identified. When the associated cofactor is food ingestion, the correct diagnosis is food-dependent EIAn (FDEIAn). The literature describes numerous reports of FDEIAn after intake of very different foods, from vegetables and nuts to meats and seafood. One of the best-characterized types of FDEIAn is that due to ω5-gliadin of wheat, though cases of FDEIAn after wheat ingestion by sensitization to wheat lipid transfer protien (LTP) are described. Some pathophysiological mechanisms underlying EIAn have been hypothesized, such as increase/alteration in gastrointestinal permeability, alteration of tissue transglutaminase promoting IgE cross-linking, enhanced expression of cytokines, redistribution of blood during physical exercise leading to altered mast-cell degranulation, and also changes in the acid-base balance. Nevertheless, until now, none of these hypotheses has been validated. The diagnosis of EIAn and FDEIAn is achieved by means of a challenge, with physical exercise alone for EIAn, and with the assumption of the suspected food followed by physical exercise for FDEIAn; in cases of doubtful results, a double-blind placebo-controlled combined food-exercise challenge should be performed. The prevention of this particular kind of anaphylaxis is the avoidance of the specific trigger, ie, physical exercise for EIAn, the assumption of the culprit food before exercise for FDEIAn, and in general the avoidance of the recognized cofactors. Patients must be supplied with an epinephrine autoinjector, as epinephrine has been clearly recognized as the first-line intervention for anaphylaxis.

The power of the placebo.

PubMed

Eccles, Ron

2007-05-01

The placebo is much more than a control medicine in a clinical trial. The placebo response is the largest component of any allergy treatment and consists of two components: nonspecific effects (eg, natural recovery) and a "true placebo effect" that is the psychological therapeutic effect of the treatment. Belief in the beneficial nature of the treatment is a key component of the true placebo effect, and can be enhanced by factors such as interaction with the physician and the sensory impact of the treatment. Negative beliefs can generate a nocebo effect that may explain some psychogenic illnesses; this is the basis of much research in psychoneuroimmunology. An understanding of the placebo and nocebo effects is important for general allergy practice, and harnessing the power of the true placebo effect is a major challenge to modern medicine.

Clinical spectrum of food allergies: a comprehensive review.

PubMed

Ho, Marco H-K; Wong, Wilfred H-S; Chang, Christopher

2014-06-01

Food allergy is defined as an adverse immune response towards food proteins or as a form of a food intolerance associated with a hypersensitive immune response. It should also be reproducible by a double-blind placebo-controlled food challenge. Many reported that food reactions are not allergic but are intolerances. Food allergy often presents to clinicians as a symptom complex. This review focuses on the clinical spectrum and manifestations of various forms of food allergies. According to clinical presentations and allergy testing, there are three types of food allergy: IgE mediated, mixed (IgE/Non-IgE), and non-IgE mediated (cellular, delayed type hypersensitivity). Recent advances in food allergy in early childhood have highlighted increasing recognition of a spectrum of delayed-onset non-IgE-mediated manifestation of food allergy. Common presentations of food allergy in infancy including atopic eczema, infantile colic, and gastroesophageal reflux. These clinical observations are frequently associated with food hypersensitivity and respond to dietary elimination. Non-IgE-mediated food allergy includes a wide range of diseases, from atopic dermatitis to food protein-induced enterocolitis and from eosinophilic esophagitis to celiac disease. The most common food allergies in children include milk, egg, soy, wheat, peanut, treenut, fish, and shellfish. Milk and egg allergies are usually outgrown, but peanut and treenut allergy tends to persist. The prevalence of food allergy in infancy is increasing and may affect up to 15-20 % of infants. The alarming rate of increase calls for a public health approach in the prevention and treatment of food allergy in children.

A proprietary blend of quail egg for the attenuation of nasal provocation with a standardized allergenic challenge: a randomized, double-blind, placebo-controlled study

PubMed Central

Benichou, Annie-Claude; Armanet, Marion; Bussière, Anthony; Chevreau, Nathalie; Cardot, Jean-Michel; Tétard, Jan

2014-01-01

Occasional rhinitis symptoms caused by exposure to pollution or allergens is a growing concern. Based first on empirical observation of a lesser occurrence of allergies in quail farmers and then scientific works on ovomucoids properties, we developed a dietary supplement for the relief of such occasional rhinitis symptoms. The objective of the study was to determine whether one acute oral dose of the study product attenuates nasal provocation and other allergy-related symptoms after exposure to a standardized allergenic challenge as compared to placebo. Healthy subjects were recruited to participate in a randomized, double-blind, two-arm crossover, placebo-controlled, clinical trial. One acute dose of either the active study product (proprietary blend of quail egg) or placebo was given concomitantly to the standardized allergenic challenge. The primary endpoint was peak nasal inspiratory flow (PNIF) measurement and the secondary endpoints were subjects' perceived feelings of well-being based on Visual Analog Scale (VAS) scores for allergy-related symptoms, as well as immunoglobulin E count. Forty-three healthy subjects were enrolled and evaluable in a per protocol analysis. A gradual increase in PNIF from nadir up to Time 120 reflected the normal, gradual recovery from nasal obstruction induced by allergenic challenge for both the active and the placebo groups. At all postchallenge time points, the active group had higher PNIF values compared to the placebo group, indicating that the active product was associated with fewer symptoms and reduced intensity of these symptoms. The active product resulted also in statistically significant improvements of most of the subjects' perceived feelings of well-being based on VAS scores. No adverse events occurred during the study. In conclusion, the dietary supplement consisting of proprietary blend made of quail eggs provides fast and efficient relief of allergic rhinitis symptoms caused by the most common outdoor and indoor allergens, without adverse events. PMID:25493182

Using a Human Challenge Model of Infection to Measure Vaccine Efficacy: A Randomised, Controlled Trial Comparing the Typhoid Vaccines M01ZH09 with Placebo and Ty21a.

PubMed

Darton, Thomas C; Jones, Claire; Blohmke, Christoph J; Waddington, Claire S; Zhou, Liqing; Peters, Anna; Haworth, Kathryn; Sie, Rebecca; Green, Christopher A; Jeppesen, Catherine A; Moore, Maria; Thompson, Ben A V; John, Tessa; Kingsley, Robert A; Yu, Ly-Mee; Voysey, Merryn; Hindle, Zoe; Lockhart, Stephen; Sztein, Marcelo B; Dougan, Gordon; Angus, Brian; Levine, Myron M; Pollard, Andrew J

2016-08-01

Typhoid persists as a major cause of global morbidity. While several licensed vaccines to prevent typhoid are available, they are of only moderate efficacy and unsuitable for use in children less than two years of age. Development of new efficacious vaccines is complicated by the human host-restriction of Salmonella enterica serovar Typhi (S. Typhi) and lack of clear correlates of protection. In this study, we aimed to evaluate the protective efficacy of a single dose of the oral vaccine candidate, M01ZH09, in susceptible volunteers by direct typhoid challenge. We performed a randomised, double-blind, placebo-controlled trial in healthy adult participants at a single centre in Oxford (UK). Participants were allocated to receive one dose of double-blinded M01ZH09 or placebo or 3-doses of open-label Ty21a. Twenty-eight days after vaccination, participants were challenged with 104CFU S. Typhi Quailes strain. The efficacy of M01ZH09 compared with placebo (primary outcome) was assessed as the percentage of participants reaching pre-defined endpoints constituting typhoid diagnosis (fever and/or bacteraemia) during the 14 days after challenge. Ninety-nine participants were randomised to receive M01ZH09 (n = 33), placebo (n = 33) or 3-doses of Ty21a (n = 33). After challenge, typhoid was diagnosed in 18/31 (58.1% [95% CI 39.1 to 75.5]) M01ZH09, 20/30 (66.7% [47.2 to 87.2]) placebo, and 13/30 (43.3% [25.5 to 62.6]) Ty21a vaccine recipients. Vaccine efficacy (VE) for one dose of M01ZH09 was 13% [95% CI -29 to 41] and 35% [-5 to 60] for 3-doses of Ty21a. Retrospective multivariable analyses demonstrated that pre-existing anti-Vi antibody significantly reduced susceptibility to infection after challenge; a 1 log increase in anti-Vi IgG resulting in a 71% decrease in the hazard ratio of typhoid diagnosis ([95% CI 30 to 88%], p = 0.006) during the 14 day challenge period. Limitations to the study included the requirement to limit the challenge period prior to treatment to 2 weeks, the intensity of the study procedures and the high challenge dose used resulting in a stringent model. Despite successfully demonstrating the use of a human challenge study to directly evaluate vaccine efficacy, a single-dose M01ZH09 failed to demonstrate significant protection after challenge with virulent Salmonella Typhi in this model. Anti-Vi antibody detected prior to vaccination played a major role in outcome after challenge. ClinicalTrials.gov (NCT01405521) and EudraCT (number 2011-000381-35).

Creatine Supplementation Associated or Not with Strength Training upon Emotional and Cognitive Measures in Older Women: A Randomized Double-Blind Study

PubMed Central

Alves, Christiano Robles Rodrigues; Merege Filho, Carlos Alberto Abujabra; Benatti, Fabiana Braga; Brucki, Sonia; Pereira, Rosa Maria R.; de Sá Pinto, Ana Lucia; Lima, Fernanda Rodrigues; Roschel, Hamilton; Gualano, Bruno

2013-01-01

Purpose To assess the effects of creatine supplementation, associated or not with strength training, upon emotional and cognitive measures in older woman. Methods This is a 24-week, parallel-group, double-blind, randomized, placebo-controlled trial. The individuals were randomly allocated into one of the following groups (n=14 each): 1) placebo, 2) creatine supplementation, 3) placebo associated with strength training or 4) creatine supplementation associated with strength training. According to their allocation, the participants were given creatine (4 x 5 g/d for 5 days followed by 5 g/d) or placebo (dextrose at the same dosage) and were strength trained or not. Cognitive function, assessed by a comprehensive battery of tests involving memory, selective attention, and inhibitory control, and emotional measures, assessed by the Geriatric Depression Scale, were evaluated at baseline, after 12 and 24 weeks of the intervention. Muscle strength and food intake were evaluated at baseline and after 24 weeks. Results After the 24-week intervention, both training groups (ingesting creatine supplementation and placebo) had significant reductions on the Geriatric Depression Scale scores when compared with the non-trained placebo group (p = 0.001 and p = 0.01, respectively) and the non-trained creatine group (p < 0.001 for both comparison). However, no significant differences were observed between the non-trained placebo and creatine (p = 0.60) groups, or between the trained placebo and creatine groups (p = 0.83). Both trained groups, irrespective of creatine supplementation, had better muscle strength performance than the non-trained groups. Neither strength training nor creatine supplementation altered any parameter of cognitive performance. Food intake remained unchanged. Conclusion Creatine supplementation did not promote any significant change in cognitive function and emotional parameters in apparently healthy older individuals. In addition, strength training per se improved emotional state and muscle strength, but not cognition, with no additive effects of creatine supplementation. Trial Registration Clinicaltrials.gov NCT01164020 PMID:24098469

Effects of dietary fiber with Bacillus coagulans lilac-01 on bowel movement and fecal properties of healthy volunteers with a tendency for constipation.

PubMed

Minamida, Kimiko; Nishimura, Mie; Miwa, Kazunori; Nishihira, Jun

2015-01-01

To elucidate the effects of Lilac LAB (Bacillus coagulans lilac-01 and okara [soy pulp] powder) on bowel movements/fecal properties, we conducted a double-blind placebo-controlled randomized trial with healthy Japanese volunteers with a tendency for constipation (n = 297). The subjects ingested 2 g/d placebo (okara powder) or test food (Lilac LAB, 1 × 10(8) CFU) once a day for 2 weeks. In the test group of functionally constipated subjects, the changes in the average scores of self-reported fecal size, sensation of incomplete evacuation, and defecation frequency were significantly improved compared to the placebo group (p < 0.05), and fecal color and odor tended to improve (p = 0.07). In the test food group of all subjects and among the non-functionally constipated subjects, the fecal size tended to improve compared to the placebo group (p = 0.06, p = 0.07, respectively). Lilac LAB was effective in improving bowel movements and fecal properties in functionally constipated persons.

Magnitude of blood pressure reduction in the placebo arms of modern hypertension trials: implications for trials of renal denervation.

PubMed

Patel, Hitesh C; Hayward, Carl; Ozdemir, Baris Ata; Rosen, Stuart D; Krum, Henry; Lyon, Alexander R; Francis, Darrel P; di Mario, Carlo

2015-02-01

Early phase studies of novel interventions for hypertension, such as renal sympathetic denervation, are sometimes single-armed (uncontrolled). We explored the wisdom of this by quantifying the blood pressure fall in the placebo arms of contemporary trials of hypertension. We searched Medline up to June 2014 and identified blinded, randomized trials of hypertension therapy in which the control arm received placebo medication or a sham (placebo) procedure. For nonresistant hypertension, we have identified all such trials of drugs licensed by the US Food and Drug Administration since 2000 (5 drugs). This US Food and Drug Administration-related restriction was not applied to resistant hypertension trials. This produced 7451 patients, who were allocated to a blinded control from 52 trials of nonresistant hypertension and 694 patients from 8 trials of resistant hypertension (3 drugs and 2 interventions). Systolic blood pressure fell by 5.92 mm Hg (95% confidence interval, 5.14-6.71; P<0.0001) in the nonresistant cohort and by 8.76 mm Hg (95% confidence interval, 4.83-12.70; P<0.0001) in the resistant cohort. Using metaregression, the falls were larger in trials that did not use ambulatory blood pressure monitoring as an inclusion criterion (z=2.84; P=0.0045), in those with higher baseline blood pressures (z=-0.3; P=0.0001), and in those where the patients were prescribed a continuous background of antihypertensives (z=-2.72; P=0.0065). The nontrivial magnitude of these apparent blood pressure reductions with perfectly ineffective intervention (placebo) illustrates that efficacy explorations of novel therapies for hypertension, once safety is established, should be performed with a randomized, appropriately controlled, and blinded design. © 2014 American Heart Association, Inc.

Allergenicity of mare's milk in children with cow's milk allergy.

PubMed

Businco, L; Giampietro, P G; Lucenti, P; Lucaroni, F; Pini, C; Di Felice, G; Iacovacci, P; Curadi, C; Orlandi, M

2000-05-01

Cow's milk allergy is a common disease of infancy and early childhood. If the baby is not breast-fed, a substitute for cow's milk formula is necessary. The aim of this study was to investigate, in vitro and in vivo, the allergenicity of mare's milk in a population of selected children with severe IgE-mediated cow's milk allergy. Twenty-five children (17 male and 8 female) aged 19 to 72 months (median age 34 months) with IgE-mediated cow's milk allergy were selected for this study. All the children underwent skin prick tests with cow's milk and mare's milk and double-blind placebo-controlled oral food challenge (DBPCOFC) with fresh cow's milk, fresh mare's milk, and, as placebo, a soy formula (Isomil, Abbott, Campoverde, Italy). We performed immunoblotting of cow's and mare's milk developed with IgE from allergic children. All the children showed strong positive skin test responses to cow's milk (4+); 2 children had positive skin test responses to mare's milk (2+). All children had positive DBPCOFCs to cow's milk; one child had a positive DBPCOFC to mare's milk. No children reacted to the placebo (Isomil). In the cow's milk, some proteins are able to strongly react with human IgE; when the sera are tested with mare's milk, the bands corresponding to the same proteins are recognized by a lower percentage of sera. These data suggest that mare's milk can be regarded as a good substitute of cow's milk in most children with severe IgE-mediated cow's milk allergy. It would be prudent, however, to confirm its tolerability by a supervised titrated oral challenge test.

Incidence and natural history of challenge-proven cow's milk allergy in European children--EuroPrevall birth cohort.

PubMed

Schoemaker, A A; Sprikkelman, A B; Grimshaw, K E; Roberts, G; Grabenhenrich, L; Rosenfeld, L; Siegert, S; Dubakiene, R; Rudzeviciene, O; Reche, M; Fiandor, A; Papadopoulos, N G; Malamitsi-Puchner, A; Fiocchi, A; Dahdah, L; Sigurdardottir, S Th; Clausen, M; Stańczyk-Przyłuska, A; Zeman, K; Mills, E N C; McBride, D; Keil, T; Beyer, K

2015-08-01

Cow's milk allergy (CMA) is one of the most commonly reported childhood food problems. Community-based incidence and prevalence estimates vary widely, due to possible misinterpretations of presumed reactions to milk and differences in study design, particularly diagnostic criteria. Children from the EuroPrevall birth cohort in 9 European countries with symptoms possibly related to CMA were invited for clinical evaluation including cows' milk-specific IgE antibodies (IgE), skin prick test (SPT) reactivity and double-blind, placebo-controlled food challenge. Across Europe, 12 049 children were enrolled, and 9336 (77.5%) were followed up to 2 years of age. CMA was suspected in 358 children and confirmed in 55 resulting in an overall incidence of challenge-proven CMA of 0.54% (95% CI 0.41-0.70). National incidences ranged from 1% (in the Netherlands and UK) to <0.3% (in Lithuania, Germany and Greece). Of all children with CMA, 23.6% had no cow's milk-specific IgE in serum, especially those from UK, the Netherlands, Poland and Italy. Of children with CMA who were re-evaluated one year after diagnosis, 69% (22/32) tolerated cow's milk, including all children with non-IgE-associated CMA and 57% of those children with IgE-associated CMA. This unique pan-European birth cohort study using the gold standard diagnostic procedure for food allergies confirmed challenge-proven CMA in <1% of children up to age 2. Affected infants without detectable specific antibodies to cow's milk were very likely to tolerate cow's milk one year after diagnosis, whereas only half of those with specific antibodies in serum 'outgrew' their disease so soon. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effects of Chromium Picolinate on Food Intake and Satiety

PubMed Central

Morrison, Christopher D.; Cefalu, William T.; Martin, Corby K.; Coulon, Sandra; Geiselman, Paula; Han, Hongmei; White, Christy L.; Williamson, Donald A.

2008-01-01

Abstract Background Chromium picolinate (CrPic) has been shown to attenuate weight gain, but the mechanism underlying this effect is unknown. Methods We assessed the effect of CrPic in modulating food intake in healthy, overweight, adult women who reported craving carbohydrates (Study 1) and performed confirmatory studies in Sprague-Dawley rats (Study 2). Study 1 utilized a double-blind placebo-controlled design and randomly assigned 42 overweight adult women with carbohydrate cravings to receive 1,000 μg of chromium as CrPic or placebo for 8 weeks. Food intake at breakfast, lunch, and dinner was directly measured at baseline, week 1, and week 8. For Study 2, Sprague-Dawley rats were fasted for 24 h and subsequently injected intraperitoneally with 0, 1, 10, or 50 μg/kg CrPic. Subsequently, rats were implanted with an indwelling third ventricular cannula. Following recovery, 0, 0.4, 4, or 40 ng of CrPic was injected directly into the brain via the intracerebroventricular cannula, and spontaneous 24-h food intake was measured. Results Study 1 demonstrated that CrPic, as compared to placebo, reduced food intake (P < 0.0001), hunger levels (P < 0.05), and fat cravings (P < 0.0001) and tended to decrease body weight (P = 0.08). In study 2, intraperitoneal administration resulted in a subtle decrease in food intake at only the highest dose (P = 0.03). However, when administered centrally, CrPic dose-dependently decreased food intake (P < 0.05). Conclusions These data suggest CrPic has a role in food intake regulation, which may be mediated by a direct effect on the brain. PMID:18715218

A double-blind, placebo-controlled clinical trial of the effect of chlorpheniramine on the response of the nasal airway, middle ear and eustachian tube to provocative rhinovirus challenge.

PubMed

Doyle, W J; McBride, T P; Skoner, D P; Maddern, B R; Gwaltney, J M; Uhrin, M

1988-03-01

This paper presents the results of a randomized, double-blind, placebo-controlled study of the efficacy of chlorpheniramine in relieving the symptoms and attenuating the pathophysiologic correlates of a rhinovirus "common cold." Forty healthy, adult, nonatopic subjects were randomly assigned to one of two treatment groups: active drug and placebo. On study Day 0, all subjects were challenged intranasally with rhinovirus type 39 (dose = 100 TCID50). Subjects were cloistered from Day 2 to Day 7, at which time they were treated with either chlorpheniramine or placebo. From 3 days before challenge to study Day 19, subjects had nasal patency assessed by rhinomanometry, eustachian tube function assessed by the 9-step test and sonotubometry, middle ear pressure assessed by tympanometry and nasal clearance assessed by the dyed-saccharin technique. Symptom diaries were maintained throughout the period of follow-up. During cloister, symptoms also were scored by interview, nasal secretions were quantified and nasal washings were performed for viral culture. Results showed that 19 (95%) subjects in the active-treatment group and 18 (90%) subjects in the placebo-treatment group shed virus. Symptomatic colds were observed in 63% of the active-treated and 83% of the placebo-treated subjects. Symptoms increased on Day 1 and peaked at Days 4 to 5. Detrimental changes in other measured functions consistent with those previously reported were observed. During the period of treatment, significant differences in the average symptom scores favoring the active-treatment group were observed for sneezing. Also, weight of expelled secretions was greater and mucociliary clearance rate less on some cloister days for the placebo-treated group. No significant differences between treatment groups in the objective measures of nasal congestion or the response of the middle ear and eustachian tube were documented.

Effect of Two Years of Treatment with Sublingual Grass Pollen Immunotherapy on Nasal Response to Allergen Challenge at Three Years among Patients with Moderate to Severe Seasonal Allergic Rhinitis: A Randomized Clinical Trial

PubMed Central

Scadding, Guy W.; Calderon, Moises A.; Shamji, Mohamed H.; Eifan, Aarif O.; Penagos, Martin; Dumitru, Florentina; Sever, Michelle L.; Bahnson, Henry T; Lawson, Kaitie; Harris, Kristina M.; Plough, Audrey G.; Panza, Joy Laurienzo; Qin, Tielin; Lim, Noha; Tchao, Nadia K.; Togias, Alkis; Durham, Stephen R.

2017-01-01

Importance Sublingual immunotherapy and subcutaneous immunotherapy are effective in seasonal allergic rhinitis. Three years of continuous treatment with subcutaneous immunotherapy and sublingual immunotherapy has been shown to improve symptoms for at least two years following discontinuation of treatment. Objective To assess whether 2 years of treatment with grass pollen sublingual immunotherapy compared with placebo provides improved nasal response to allergen challenge at 3 year follow-up. Design, Setting, Participants A randomized double-blind, placebo-controlled, 3-parallel group study performed in a single academic centre, Imperial College London, including adult patients with moderate-to-severe seasonal allergic rhinitis (interfering with usual daily activities or sleep). First enrolment was March 2011, last follow-up February 2015. Intervention Thirty-six participants received 2 years sublingual immunotherapy (daily tablets containing 15 microgram of major allergen Phleum p 5 and monthly placebo injections), 36 received subcutaneous immunotherapy (monthly injections containing 20 micrograms of Phleum p 5 and daily placebo tablets) and 34 received matched double-placebo. Nasal allergen challenge was performed before treatment, at 1 and 2 years and at 3 years (1 year after treatment discontinuation). Main outcomes and measures Total nasal symptom scores (TNSS, range 0 (best) to 12 (worst) were recorded during 0–10 hours after challenge. The minimum clinically important difference for change in TNSS within an individual is 1.08. The primary outcome was TNSS comparing sublingual immunotherapy to placebo at year 3. Subcutaneous immunotherapy was included as a positive control. The study was not powered to compare sublingual immunotherapy with subcutaneous immunotherapy. Results Among 106 participants who were randomized (mean age 33.5 years, 32.1% female), 92 completed the study at 3 years. Imputed TNSS scores [mean (95% confidence intervals)] pre-treatment and at 3 years for the sublingual immunotherapy group were 6.36 (5.76, 6.96) and 4.73 (3.97, 5.48) and for the placebo group, 6.06 (5.23, 6.88) and 4.81 (3.97, 5.65), respectively. The between-group difference (adjusted for baseline) (95% CIs) was −0.18 (−1.25, 0.90), p=0.75. Conclusion Among patients with moderate-to-severe seasonal allergic rhinitis, two years of sublingual grass pollen immunotherapy was not significantly different than placebo in improving the nasal response to allergen challenge at 3 year follow-up. PMID:28196255

Combining rigour with relevance: a novel methodology for testing Chinese herbal medicine.

PubMed

Flower, Andrew; Lewith, George; Little, Paul

2011-03-24

There is a need to develop an evidence base for Chinese herbal medicine (CHM) that is both rigorous and reflective of good practice. This paper proposes a novel methodology to test individualised herbal decoctions using a randomised, double blinded, placebo controlled clinical trial. A feasibility study was conducted to explore the role of CHM in the treatment of endometriosis. Herbal formulae were pre-cooked and dispensed as individual doses in sealed plastic sachets. This permitted the development and testing of a plausible placebo decoction. Participants were randomised at a distant pharmacy to receive either an individualised herbal prescription or a placebo. The trial met the predetermined criteria for good practice. Neither the participants nor the practitioner-researcher could reliably identify group allocation. Of the 28 women who completed the trial, in the placebo group (n=15) 3 women (20%) correctly guessed they were on placebo, 8 (53%) thought they were on herbs and 4 (27%) did not know which group they had been allocated to. In the active group (n=13) 2 (15%) though they were on placebo, 8 (62%) thought they were on herbs and 3 (23%) did not know. Randomisation, double blinding and allocation concealment were successful and the study model appeared to be feasible and effective. It is now possible to subject CHM to rigorous scientific scrutiny without compromising model validity. Improvement in the design of the placebo using food colourings and flavourings instead of dried food will help guarantee the therapeutic inertia of the placebo decoction. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

The EuroPrevall outpatient clinic study on food allergy: background and methodology.

PubMed

Fernández-Rivas, M; Barreales, L; Mackie, A R; Fritsche, P; Vázquez-Cortés, S; Jedrzejczak-Czechowicz, M; Kowalski, M L; Clausen, M; Gislason, D; Sinaniotis, A; Kompoti, E; Le, T-M; Knulst, A C; Purohit, A; de Blay, F; Kralimarkova, T; Popov, T; Asero, R; Belohlavkova, S; Seneviratne, S L; Dubakiene, R; Lidholm, J; Hoffmann-Sommergruber, K; Burney, P; Crevel, R; Brill, M; Fernández-Pérez, C; Vieths, S; Clare Mills, E N; van Ree, R; Ballmer-Weber, B K

2015-05-01

The EuroPrevall project aimed to develop effective management strategies in food allergy through a suite of interconnected studies and a multidisciplinary integrated approach. To address some of the gaps in food allergy diagnosis, allergen risk management and socio-economic impact and to complement the EuroPrevall population-based surveys, a cross-sectional study in 12 outpatient clinics across Europe was conducted. We describe the study protocol. Patients referred for immediate food adverse reactions underwent a consistent and standardized allergy work-up that comprised collection of medical history; assessment of sensitization to 24 foods, 14 inhalant allergens and 55 allergenic molecules; and confirmation of clinical reactivity and food thresholds by standardized double-blind placebo-controlled food challenges (DBPCFCs) to milk, egg, fish, shrimp, peanut, hazelnut, celeriac, apple and peach. A standardized methodology for a comprehensive evaluation of food allergy was developed and implemented in 12 outpatient clinics across Europe. A total of 2121 patients (22.6% <14 years) reporting 8257 reactions to foods were studied, and 516 DBPCFCs were performed. This is the largest multicentre European case series in food allergy, in which subjects underwent a comprehensive, uniform and standardized evaluation including DBPCFC, by a methodology which is made available for further studies in food allergy. The analysis of this population will provide information on the different phenotypes of food allergy across Europe, will allow to validate novel in vitro diagnostic tests, to establish threshold values for major allergenic foods and to analyse the socio-economic impact of food allergy. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Marine drug Haishengsu increases chemosensitivity to conventional chemotherapy and improves quality of life in patients with acute leukemia.

PubMed

Li, Guang-Yao; Zhang, Li; Liu, Ji-Zhu; Chen, Shou-Guo; Xiao, Tai-Wu; Liu, Guo-Zhen; Wang, Jing-Xia; Wang, Le-Xin; Hou, Ming

2016-07-01

Pharmacological management of acute leukemia remains a challenge. A seashell protein Haishengsu (HSS) has been found to exert anticancer activities in recent in vitro studies. The aim of this study was to determine whether the addition of HSS to the conventional chemotherapies would increase chemosensitivity and improves quality of life in patients with acute leukemia. Two hundred and forty-eight patients with acute leukemia were enrolled in a double-blind, and placebo-controlled study. In addition to conventional chemotherapy, 142 patients received HSS and 106 received placebo. In an in vitro study, the expression of P-gp was evaluated by flow cytometry in a drug-resistant leukemia cell line (K562/ADM cells). Sorcin was examined by Western blot. The complete remission rates in the HSS treatment group were all higher than in the placebo group with non-relapsing leukemia and relapsed leukemia (p<0.05). Less patients in the HSS group experienced gastrointestinal side effects from chemotherapy, whereas more patients had increased food take and an increase in Karnofsky performance status (KPS) score (p<0.01). In vitro, the expression of P-gp and sorcin in the HSS treated cells were lower than in the control group cells (p<0.01). When added to conventional chemotherapy, HSS improves the complete remission rates and quality of life in patients with acute leukemia. The in vitro findings indicate that suppression of P-gp and sorcin genes in leukemia cells may be involved in the beneficial effects of HSS. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Lubiprostone: a new drug for the treatment of chronic idiopathic constipation.

PubMed

Baker, Danial E

2007-01-01

Lubiprostone offers an additional alternative for patients with chronic idiopathic constipation. Lubiprostone is more efficacious than placebo in the treatment of chronic idiopathic constipation. In placebo-controlled clinical trials, lubiprostone therapy was generally well tolerated and was not associated with severe adverse effects; however, the high incidence of nausea may be problematic for some patients. The nausea may be alleviated or minimized by administering the dose with food, and some patients may require a dosage reduction to 24 mug once daily. The key limitations of the placebo-controlled clinical trials include the absence of information regarding the duration of the constipation and previous types of therapies that had been used to treat the constipation and the absence of an active control group. Comparative studies with other therapies (eg, saline laxatives, polyethylene glycol) used for constipation are necessary to determine the clinical and economic value of this agent relative to other forms of therapy.

A randomized, placebo-controlled trial of nandrolone decanoate in human immunodeficiency virus-infected men with mild to moderate weight loss with recombinant human growth hormone as active reference treatment.

PubMed

Storer, Thomas W; Woodhouse, Linda J; Sattler, Fred; Singh, Atam B; Schroeder, E Todd; Beck, Keith; Padero, MaClara; Mac, Phong; Yarasheski, Kevin E; Geurts, Paul; Willemsen, Arnold; Harms, Marloes K; Bhasin, Shalender

2005-08-01

We compared the effectiveness of a biweekly regimen of 150 mg nandrolone with placebo in HIV-infected men with mild to moderate weight loss and contrasted its effects against a Food and Drug Administration-approved regimen of recombinant human (rh)GH. In this placebo-controlled, randomized, 12-wk trial, placebo and nandrolone (150 mg im biweekly) were administered double blind, and rhGH (6 mg sc daily) was administered in an open-label manner. Participants were HIV-infected men with 5-15% weight loss over 6 months and on stable antiretroviral therapy for more than 12 wk. Lean body mass (LBM), muscle performance, physical function, endurance, hormone levels, insulin sensitivity, sexual function, quality of life, and appetite were assessed at baseline and after 12 wk. Nandrolone administration was associated with a greater increase in LBM (+1.6 +/- 0.3 kg) by dual-energy x-ray absorptiometry scan than placebo (+0.4 +/- 0.3 kg; P < 0.05); however, the change in LBMs with nandrolone was not significantly different from rhGH (+2.5 +/- 0.3 kg). Nandrolone administration was also associated with significantly greater gains in fat-free mass (+1.6 +/- 0.3 kg), body cell mass (+1.0 +/- 0.2 kg), and intracellular water (+0.9 +/- 0.2 kg) than placebo; these changes in the nandrolone group were not significantly different from the rhGH group. rhGH administration was associated with greater loss of whole body fat mass and higher frequency of drug-related adverse effects and treatment discontinuations than nandrolone and placebo and a greater increase in extracellular water than nandrolone. Nandrolone treatment was associated with greater improvements in perception of health than rhGH and sexual function than placebo. The cachexia/anorexia scores, health care resource use, and insulin sensitivity did not significantly change. We conclude that nandrolone is superior to placebo and not significantly different from a Food and Drug Administration-approved regimen of rhGH in improving lean body mass in HIV-infected men with mild to moderate weight loss.

Improvement in insulin resistance and favourable changes in plasma inflammatory adipokines after weight loss associated with two months' consumption of a combination of bioactive food ingredients in overweight subjects.

PubMed

Rondanelli, Mariangela; Opizzi, Annalisa; Perna, Simone; Faliva, Milena; Solerte, Sebastiano Bruno; Fioravanti, Marisa; Klersy, Catherine; Cava, Edda; Edda, Cava; Paolini, Maddalena; Maddalena, Paolini; Scavone, Luciano; Luciano, Scavone; Ceccarelli, Paola; Paola, Ceccarelli; Castellaneta, Emanuela; Emanuela, Castellaneta; Savina, Claudia; Claudia, Savina; Donini, Lorenzo Maria

2013-10-01

This randomized, double blind, placebo-controlled, 8 week trial assessed the efficacy on metabolic changes produced by a consumption of a combination of bioactive food ingredients (epigallocatechin gallate, capsaicins, piperine and L-carnitine) versus a placebo, as part of a therapeutic 'lifestyle change' diet, in 86 overweight subjects. Forty-one patients (2/14 F/M; age 43.7 ± 8.5; BMI 30.3 ± 3.5 kg/m(2)) were randomized to the supplemented group and 45 (29/16; age 40.7 ± 10.2; BMI 30.0 ± 2.7) to the control group. We observed that consumption of the dietary supplement was associated with a significantly greater decrease in insulin resistance, assessed by homostasis model assessment (p < 0.001), leptin/adiponectin ratio (p < 0.04), respiratory quotient (p < 0.008). LDL-cholesterol levels (p < 0.01). Moreover, statistically significant differences were recorded between the two groups in relation to urinary norepinephrine levels (p < 0.001). Leptin, ghrelin, C-reactive protein decreased and resting energy expenditure increased significantly in the supplemented group (p < 0.05, 0.03, 0.02 and 0,02 respectively), but not in the placebo group; adiponectin decreased significantly in the placebo group (0.001) but not in the supplemented group, although no statistical significance between the groups was elicited. BMI, fat mass (assessed by DXA) and vascular endothelial growth factor significantly decreased, whilst the resting energy expenditure/free fat mass significantly increased in both groups. In general, a greater change was recorded in the supplemented group compared to the placebo, although no statistically significant difference between the two groups was recorded. These results suggest that the combination of bioactive food ingredients studied might be useful for the treatment of obesity-related inflammatory metabolic dysfunctions.

Intake of kale suppresses postprandial increases in plasma glucose: A randomized, double-blind, placebo-controlled, crossover study

PubMed Central

Kondo, Sumio; Suzuki, Asahi; Kurokawa, Mihoko; Hasumi, Keiji

2016-01-01

Kale (Brassica oleracea var. acephala), a vegetable in the family Brassicaceae, has beneficial effects on health, including hypoglycemic effects. In our previous study with a limited number of subjects, intake of kale-containing food at a dose of 14 g decreased postprandial plasma glucose levels. In the present study, the effective dose of kale-containing food was investigated in a randomized, double-blind, placebo-controlled, crossover trial. The trial was conducted on 42 Japanese subjects aged 21–64 years with fasting plasma glucose levels of ≤125 mg/dl and 30-min postprandial plasma glucose levels of 140–187 mg/dl. The subjects consumed placebo or kale-containing food [7 or 14 g; low-dose (active-L) or high-dose (active-H) kale, respectively] together with a high-carbohydrate meal. At 30–120 min after the test meal intake, the plasma levels of glucose and insulin were determined. The postprandial plasma glucose levels in subjects with intake of active-L or active-H were significantly lower than those in subjects with intake of placebo, with the maximum plasma concentration (Cmax; 163±24 mg/dl for active-L and 162±23 mg/dl for active-H compared with 176±26 mg/dl for placebo [values presented as means ± standard deviation (SD); P<0.01]. The area under the plasma glucose concentration-time curve for 0–2 h (AUC0–2 h) values (means ± SD) were significantly lower for active-L (268±43 mg/h/dl) and active-H (266±42 mg/h/dl) than for the placebo (284±43 mg/h/dl; P<0.05). No significant differences were identified in the postprandial plasma insulin levels between the three conditions. No adverse events associated with intake of either dose of kale were observed. Our findings suggest that intake of kale suppresses postprandial increases in plasma glucose levels at a single dose of 7 g, and that a dose as high as 14 g is safe. PMID:27882216

Intake of kale suppresses postprandial increases in plasma glucose: A randomized, double-blind, placebo-controlled, crossover study.

PubMed

Kondo, Sumio; Suzuki, Asahi; Kurokawa, Mihoko; Hasumi, Keiji

2016-11-01

Kale ( Brassica oleracea var. acephala ), a vegetable in the family Brassicaceae, has beneficial effects on health, including hypoglycemic effects. In our previous study with a limited number of subjects, intake of kale-containing food at a dose of 14 g decreased postprandial plasma glucose levels. In the present study, the effective dose of kale-containing food was investigated in a randomized, double-blind, placebo-controlled, crossover trial. The trial was conducted on 42 Japanese subjects aged 21-64 years with fasting plasma glucose levels of ≤125 mg/dl and 30-min postprandial plasma glucose levels of 140-187 mg/dl. The subjects consumed placebo or kale-containing food [7 or 14 g; low-dose (active-L) or high-dose (active-H) kale, respectively] together with a high-carbohydrate meal. At 30-120 min after the test meal intake, the plasma levels of glucose and insulin were determined. The postprandial plasma glucose levels in subjects with intake of active-L or active-H were significantly lower than those in subjects with intake of placebo, with the maximum plasma concentration (C max ; 163±24 mg/dl for active-L and 162±23 mg/dl for active-H compared with 176±26 mg/dl for placebo [values presented as means ± standard deviation (SD); P<0.01]. The area under the plasma glucose concentration-time curve for 0-2 h (AUC 0-2 h ) values (means ± SD) were significantly lower for active-L (268±43 mg/h/dl) and active-H (266±42 mg/h/dl) than for the placebo (284±43 mg/h/dl; P<0.05). No significant differences were identified in the postprandial plasma insulin levels between the three conditions. No adverse events associated with intake of either dose of kale were observed. Our findings suggest that intake of kale suppresses postprandial increases in plasma glucose levels at a single dose of 7 g, and that a dose as high as 14 g is safe.

The administration to Indonesians of monosodium L-glutamate in Indonesian foods: an assessment of adverse reactions in a randomized double-blind, crossover, placebo-controlled study.

PubMed

Prawirohardjono, W; Dwiprahasto, I; Astuti, I; Hadiwandowo, S; Kristin, E; Muhammad, M; Kelly, M F

2000-04-01

Monosodium L-glutamate (MSG) has been suggested to cause postprandial symptoms after the ingestion of Chinese or oriental meals. Therefore, we examined whether such symptoms could be elicited in Indonesians ingesting levels of MSG typically found in Indonesian cuisine. Healthy volunteers (n = 52) were treated with capsules of placebo or MSG (1.5 and 3.0 g/person) as part of a standardized Indonesian breakfast. The study used a rigorous, randomized, double-blind, crossover design. The occurrence of symptoms after MSG ingestion did not differ from that after consumption of the placebo.

Diet and Dermatitis: Food Triggers

PubMed Central

Schlichte, Megan

2014-01-01

Given increasing awareness of the link between diet and health, many patients are concerned that dietary factors may trigger dermatitis. Research has found that dietary factors can indeed exacerbate atopic dermatitis or cause dermatitis due to systemic contact dermatitis. In atopic dermatitis, dietary factors are more likely to cause an exacerbation among infants or children with moderate-to-severe atopic dermatitis relative to other populations. Foods may trigger rapid, immunoglobulin E-mediated hypersensitivity reactions or may lead to late eczematous reactions. While immediate reactions occur within minutes to hours of food exposure, late eczematous reactions may occur anywhere from hours to two days later. Screening methods, such as food allergen-specific serum immunoglobulin E tests or skin prick tests, can identify sensitization to specific foods, but a diagnosis of food allergy requires specific signs and symptoms that occur reproducibly upon food exposure. Many patients who are sensitized will not develop clinical findings upon food exposure; therefore, these tests may result in false-positive tests for food allergy. This is why the gold standard for diagnosis remains the double-blind, placebo-controlled food challenge. In another condition, systemic contact dermatitis, ingestion of a specific food can actually cause dermatitis. Systemic contact dermatitis is a distinct T-cell mediated immunological reaction in which dietary exposure to specific allergens results in dermatitis. Balsam of Peru and nickel are well-known causes of systemic contact dermatitis, and reports have implicated multiple other allergens. This review seeks to increase awareness of important food allergens, elucidate their relationship with atopic dermatitis and systemic contact dermatitis, and review available diagnostic and treatment strategies. PMID:24688624

Can oral challenge with balsam of Peru predict possible benefit from a low-balsam diet?

PubMed

Veien, N K; Hattel, T; Laurberg, G

1996-06-01

Previous studies have shown that some patients sensitive to balsams and/or fragrances obtain long-term benefits by following a low-balsam diet, whereas others do not. This study was performed to determine whether a low-balsam diet was a helpful long-term treatment for selected patients sensitive to balsam of Peru and/or a perfume mixture and to determine whether oral challenge with balsam of Peru could predict which balsam-sensitive patients might benefit from a reduction in balsam intake. Questionnaires were sent to 46 patients with positive patch test results to balsam of Peru and/or a perfume mixture and chronic dermatitis of a morphology consistent with endogenous dermatitis who had experienced improvement after 1 to 2 months on a diet intended to reduce the intake of balsams. The questionnaires were mailed 1 to 3 years after the initiation of the diet treatment to inquire about a possible long-term benefit of the diet. Twenty-eight of the 46 patients stated in the questionnaire that they had long-term benefits from the diet treatment. These included 16 of 22 patients who had reacted to a placebo-controlled oral challenge with 1 g balsam of Peru, 3 of 10 who had no reaction or a placebo reaction to the oral challenge, and 9 of 14 who had not been challenged orally. The efficacy of the diet treatment was not correlated to whether the patient had patch test reactivity to either balsam of Peru, the perfume mixture, or both substances. Food items most commonly mentioned by patients as causing aggravation of their symptoms on at least three different occasions were wine, candy, chocolate, cinnamon, curry, citrus fruit, and flavorings. In its present form, the oral challenge procedure with balsam of Peru offers only limited assistance in selecting patients who are likely to benefit from diet treatment.

Ethical considerations in design of a study to evaluate a US Food and Drug Administration-approved indication: antivenom versus placebo for copperhead envenomation.

PubMed

Gerardo, Charles J; Lavonas, Eric J; McKinney, Ross E

2014-10-01

In 2000, the US Food and Drug Administration approved CroFab(®) Crotalidae Polyvalent Immune Fab, ovine (FabAV), which had received orphan drug designation, for use in patients with minimal to moderate North American crotaline envenomations including copperhead snakes. As existing evidence on the effectiveness of FabAV for this indication is limited, wide practice variation in its use exists. In order to provide more definitive clinical evidence as to the role of this treatment, a new randomized, placebo-controlled trial of FabAV specifically for copperhead bites was initiated. In light of the existing US Food and Drug Administration approval, ethical considerations of participation in this trial have been raised. We discuss the ethical principles pertinent to this randomized, placebo-controlled trial with placebo arm. We apply an accepted framework for ethical research to this trial. Due to the evidence gap in the literature, wide-ranging treatment recommendations by medical experts, and broad practice variation, clinical equipoise exists in the treatment of copperhead envenomation with FabAV. The impact of this clinical equipoise on the value and scientific validity of the trial is discussed. The trial's risk-benefit ratio is also considered. Potential risks to the patients are minimized as the protocol includes a plan for rescue therapy in the event that patients progress to severe envenomation symptoms. Overall, risks are further minimized by the inclusion of an interim analysis with stopping rules based on demonstrated efficacy should the therapy clearly prove to be beneficial. Although a post-marketing clinical study of this nature is unusual for an approved indication, this trial adheres to all ethical preconditions found in existing guidelines for clinical research involving human subjects. © The Author(s) 2014.

Using a Human Challenge Model of Infection to Measure Vaccine Efficacy: A Randomised, Controlled Trial Comparing the Typhoid Vaccines M01ZH09 with Placebo and Ty21a

PubMed Central

Jones, Claire; Blohmke, Christoph J.; Waddington, Claire S.; Zhou, Liqing; Peters, Anna; Haworth, Kathryn; Sie, Rebecca; Green, Christopher A.; Jeppesen, Catherine A.; Moore, Maria; Thompson, Ben A. V.; John, Tessa; Kingsley, Robert A.; Yu, Ly-Mee; Voysey, Merryn; Hindle, Zoe; Lockhart, Stephen; Sztein, Marcelo B.; Dougan, Gordon; Angus, Brian; Levine, Myron M.; Pollard, Andrew J.

2016-01-01

Background Typhoid persists as a major cause of global morbidity. While several licensed vaccines to prevent typhoid are available, they are of only moderate efficacy and unsuitable for use in children less than two years of age. Development of new efficacious vaccines is complicated by the human host-restriction of Salmonella enterica serovar Typhi (S. Typhi) and lack of clear correlates of protection. In this study, we aimed to evaluate the protective efficacy of a single dose of the oral vaccine candidate, M01ZH09, in susceptible volunteers by direct typhoid challenge. Methods and Findings We performed a randomised, double-blind, placebo-controlled trial in healthy adult participants at a single centre in Oxford (UK). Participants were allocated to receive one dose of double-blinded M01ZH09 or placebo or 3-doses of open-label Ty21a. Twenty-eight days after vaccination, participants were challenged with 104CFU S. Typhi Quailes strain. The efficacy of M01ZH09 compared with placebo (primary outcome) was assessed as the percentage of participants reaching pre-defined endpoints constituting typhoid diagnosis (fever and/or bacteraemia) during the 14 days after challenge. Ninety-nine participants were randomised to receive M01ZH09 (n = 33), placebo (n = 33) or 3-doses of Ty21a (n = 33). After challenge, typhoid was diagnosed in 18/31 (58.1% [95% CI 39.1 to 75.5]) M01ZH09, 20/30 (66.7% [47.2 to 87.2]) placebo, and 13/30 (43.3% [25.5 to 62.6]) Ty21a vaccine recipients. Vaccine efficacy (VE) for one dose of M01ZH09 was 13% [95% CI -29 to 41] and 35% [-5 to 60] for 3-doses of Ty21a. Retrospective multivariable analyses demonstrated that pre-existing anti-Vi antibody significantly reduced susceptibility to infection after challenge; a 1 log increase in anti-Vi IgG resulting in a 71% decrease in the hazard ratio of typhoid diagnosis ([95% CI 30 to 88%], p = 0.006) during the 14 day challenge period. Limitations to the study included the requirement to limit the challenge period prior to treatment to 2 weeks, the intensity of the study procedures and the high challenge dose used resulting in a stringent model. Conclusions Despite successfully demonstrating the use of a human challenge study to directly evaluate vaccine efficacy, a single-dose M01ZH09 failed to demonstrate significant protection after challenge with virulent Salmonella Typhi in this model. Anti-Vi antibody detected prior to vaccination played a major role in outcome after challenge. Trial registration ClinicalTrials.gov (NCT01405521) and EudraCT (number 2011-000381-35). PMID:27533046

[Prevalence of food allergy in Icelandic infants during first year of life].

PubMed

Kristinsdóttir, Harpa; Clausen, Michael; Ragnarsdóttir, Hildur S; Halldórsdóttir, Ingibjörg H; McBride, Doreen; Beyer, Kristen; Sigurdardóttir, Sigurveig Th

2011-01-01

This study is a part of EuroPrevall, an EU-funded European food allergy project. The aim was to evaluate the prevalence of food allergy in Icelandic infants during their first year of life. Infants (n=1,341) were followed prospectively from birth to 12 months of age. Questionnaires were obtained at birth and 12 months. Children with symptoms of possible food allergy were assessed with a skin-prick test (SPT) and specific IgE. Food allergy was confirmed with a double-blind placebo-controlled food challenge (DBPCFC). Out of 170 symptomatic children 44 infants (3.27%) had either positive SPT (n=21; 1.57%) or specific IgE (n=40; 2.98%). Food allergy was confirmed in 25 (1.86%); egg allergy 1.42%, milk 0.52%, fish 0.22%, wheat 0.15%, peanuts 0.15%, and soy 0.07%. Atopic dermatitis was diagnosed in 7.90% (n=106) and according to questionnaires 8.80% had asthma (n=118). Positive family history was the strongest risk factor for asthma (OR=2.12; p<0.001) and atopic dermatitis (OR=1.90; p=0.004). Family history influenced the relationship between predisposing factors and allergy symptoms. Our results show lower prevalence of food allergy than previously reported in a study of Icelandic children at two years of age. The prevalence was also lower than reported in some other European countries and could be explained by different genetic and environmental factors.

Efficacy of Olibra: A 12-Week Randomized Controlled Trial and a Review of Earlier Studies

PubMed Central

Rebello, Candida J; Martin, Corby K; Johnson, William D; O'Neil, Carol E; Greenway, Frank L

2012-01-01

Background Intervention strategies that harness the body's appetite and satiety regulating signals provide a means of countering excessive energy intake. Methods Eighty-two subjects were enrolled (18–60 years, body mass index: 25–40 kg/m2) in a randomized, placebo-controlled, double-blind, parallel trial. During a 12-week period, the effects of Olibra™ fat emulsion (2.1 g twice daily) on food intake, appetite, satiety, weight, and body composition were compared with those of a twice daily administered placebo (1.95 g milk fat). On days -7, 0, and 28, Olibra or the placebo added to 200 g of yogurt was served at breakfast and lunch. Food intake, appetite, and satiety were assessed after lunch and dinner. Body weight was measured on days -7, 0, 14, 28, 56, and 84. Body fat, waist circumference, and waist-hip ratio were determined on days 0 and 84. The Eating Inventory was administered at screening and on day 28. Data relating to 71 subjects were analyzed using analysis of covariance. Results At 12 weeks, body weight was reduced in the test group (2.17 ± 0.46 kg standard error of the mean, p < .0001) and the control group (1.68 ± 0.42 kg, p < .0001). Waist circumference decreased by 2.93 ± 0.85 cm in the test group (p = .001) and by 1.78 ± 0.74 cm in the control group (p = .02). Differential weight and waist circumference reductions were not significant. Hunger scores (Eating Inventory) decreased more in the test group (p = .0082). Differential group effects were not significant for body fat, waist-hip ratio, food intake, appetite, and satiety. Conclusions At this dose, Olibra did not exert a consistent effect on food intake, appetite regulation, body weight, or body composition. PMID:22768902

The Vaccine Candidate Vibrio cholerae 638 Is Protective against Cholera in Healthy Volunteers

PubMed Central

García, Luis; Jidy, Manuel Díaz; García, Hilda; Rodríguez, Boris L.; Fernández, Roberto; Año, Gemma; Cedré, Bárbara; Valmaseda, Tania; Suzarte, Edith; Ramírez, Margarita; Pino, Yadira; Campos, Javier; Menéndez, Jorge; Valera, Rodrigo; González, Daniel; González, Irma; Pérez, Oliver; Serrano, Teresita; Lastre, Miriam; Miralles, Fernando; del Campo, Judith; Maestre, Jorge Luis; Pérez, José Luis; Talavera, Arturo; Pérez, Antonio; Marrero, Karen; Ledón, Talena; Fando, Rafael

2005-01-01

Vibrio cholerae 638 is a living candidate cholera vaccine strain attenuated by deletion of the CTXΦ prophage from C7258 (O1, El Tor Ogawa) and by insertion of the Clostridium thermocellum endoglucanase A gene into the hemagglutinin/protease coding sequence. This vaccine candidate was previously found to be well tolerated and immunogenic in volunteers. This article reports a randomized, double-blind, placebo-controlled trial conducted to test short-term protection conferred by 638 against subsequent V. cholerae infection and disease in volunteers in Cuba. A total of 45 subjects were enrolled and assigned to receive vaccine or placebo. The vaccine contained 109 CFU of freshly harvested 638 buffered with 1.3% NaHCO3, while the placebo was buffer alone. After vaccine but not after placebo intake, 96% of volunteers had at least a fourfold increase in vibriocidal antibody titers, and 50% showed a doubling of at least the lipopolysaccharide-specific immunoglobulin A titers in serum. At 1 month after vaccination, five volunteers from the vaccine group and five from the placebo group underwent an exploratory challenge study with 109 CFU of ΔCTXΦ attenuated mutant strain V. cholerae 81. Only two volunteers from the vaccine group shed strain 81 in their feces, but none of them experienced diarrhea; in the placebo group, all volunteers excreted the challenge strain, and three had reactogenic diarrhea. An additional 12 vaccinees and 9 placebo recipients underwent challenge with 7 × 105 CFU of virulent strain V. cholerae 3008 freshly harvested from a brain heart infusion agar plate and buffered with 1.3% NaHCO3. Three volunteers (25%) from the vaccine group and all from the placebo group shed the challenge agent in their feces. None of the 12 vaccinees but 7 volunteers from the placebo group had diarrhea, and 2 of the latter exhibited severe cholera (>5,000 g of diarrheal stool). These results indicate that at 1 month after ingestion of a single oral dose (109 CFU) of strain 638, volunteers remained protected against cholera infection and disease provoked by the wild-type challenge agent V. cholerae 3008. We recommend that additional vaccine lots of 638 be prepared under good manufacturing practices for further evaluation. PMID:15845509

The vaccine candidate Vibrio cholerae 638 is protective against cholera in healthy volunteers.

PubMed

García, Luis; Jidy, Manuel Díaz; García, Hilda; Rodríguez, Boris L; Fernández, Roberto; Año, Gemma; Cedré, Bárbara; Valmaseda, Tania; Suzarte, Edith; Ramírez, Margarita; Pino, Yadira; Campos, Javier; Menéndez, Jorge; Valera, Rodrigo; González, Daniel; González, Irma; Pérez, Oliver; Serrano, Teresita; Lastre, Miriam; Miralles, Fernando; Del Campo, Judith; Maestre, Jorge Luis; Pérez, José Luis; Talavera, Arturo; Pérez, Antonio; Marrero, Karen; Ledón, Talena; Fando, Rafael

2005-05-01

Vibrio cholerae 638 is a living candidate cholera vaccine strain attenuated by deletion of the CTXPhi prophage from C7258 (O1, El Tor Ogawa) and by insertion of the Clostridium thermocellum endoglucanase A gene into the hemagglutinin/protease coding sequence. This vaccine candidate was previously found to be well tolerated and immunogenic in volunteers. This article reports a randomized, double-blind, placebo-controlled trial conducted to test short-term protection conferred by 638 against subsequent V. cholerae infection and disease in volunteers in Cuba. A total of 45 subjects were enrolled and assigned to receive vaccine or placebo. The vaccine contained 10(9) CFU of freshly harvested 638 buffered with 1.3% NaHCO(3), while the placebo was buffer alone. After vaccine but not after placebo intake, 96% of volunteers had at least a fourfold increase in vibriocidal antibody titers, and 50% showed a doubling of at least the lipopolysaccharide-specific immunoglobulin A titers in serum. At 1 month after vaccination, five volunteers from the vaccine group and five from the placebo group underwent an exploratory challenge study with 10(9) CFU of DeltaCTXPhi attenuated mutant strain V. cholerae 81. Only two volunteers from the vaccine group shed strain 81 in their feces, but none of them experienced diarrhea; in the placebo group, all volunteers excreted the challenge strain, and three had reactogenic diarrhea. An additional 12 vaccinees and 9 placebo recipients underwent challenge with 7 x 10(5) CFU of virulent strain V. cholerae 3008 freshly harvested from a brain heart infusion agar plate and buffered with 1.3% NaHCO(3). Three volunteers (25%) from the vaccine group and all from the placebo group shed the challenge agent in their feces. None of the 12 vaccinees but 7 volunteers from the placebo group had diarrhea, and 2 of the latter exhibited severe cholera (>5,000 g of diarrheal stool). These results indicate that at 1 month after ingestion of a single oral dose (10(9) CFU) of strain 638, volunteers remained protected against cholera infection and disease provoked by the wild-type challenge agent V. cholerae 3008. We recommend that additional vaccine lots of 638 be prepared under good manufacturing practices for further evaluation.

Human chorionic gonadotrophin and weight loss. A double-blind, placebo-controlled trial.

PubMed

Bosch, B; Venter, I; Stewart, R I; Bertram, S R

1990-02-17

Low-dose human chorionic gonadotrophin (HCG) combined with a severe diet remains a popular treatment for obesity, despite equivocal evidence of its effectiveness. In a double-blind, placebo-controlled study, the effects of HCG on weight loss were compared with placebo injections. Forty obese women (body mass index greater than 30 kg/m2) were placed on the same diet supplying 5,000 kJ per day and received daily intramuscular injections of saline or HCG, 6 days a week for 6 weeks. A psychological profile, hunger level, body circumferences, a fasting blood sample and food records were obtained at the start and end of the study, while body weight was measured weekly. Subjects receiving HCG injections showed no advantages over those on placebo in respect of any of the variables recorded. Furthermore, weight loss on our diet was similar to that on severely restricted intake. We conclude that there is no rationale for the use of HCG injections in the treatment of obesity.

A double-blind, randomized, placebo-controlled trial of itopride (100 and 200 mg three times daily) on gastric motor and sensory function in healthy volunteers.

PubMed

Choung, R S; Talley, N J; Peterson, J; Camilleri, M; Burton, D; Harmsen, W S; Zinsmeister, A R

2007-03-01

Itopride, a dopamine D2 antagonist and acetylcholinesterase inhibitor, significantly improved symptoms in patients with functional dyspepsia in one phase II randomized trial. However, the mechanisms by which itopride may improve symptoms are unknown. We aimed to compare the effects of two doses of itopride and placebo on gastric volumes, gastric emptying, small bowel transit and satiation in female and male healthy volunteers. Randomized, double-blind, placebo-controlled study evaluated gastric function before and after 7 days of itopride 100 mg (n = 16) or 200 mg (n = 15) or placebo (n = 15) t.i.d. Validated methods were used to study gastric accommodation (single photon emission computed tomography), gastric emptying and orocecal transit and satiation postnutrient challenge. The three arms were comparable with regard to age, gender and body mass index. There were no statistically significant effects of itopride on gastric emptying, orocecal transit, fasting gastric volume, maximum tolerated volume or aggregate symptom score with nutrient drink challenge. Postprandial (PP) change in gastric volume differed in the three groups (P = 0.019): 625[+/-28 (SEM)], 555(+/-26) and 512(+/-33) in placebo, itopride 100 and 200 mg groups, respectively. In healthy subjects, itopride reduced total PP gastric volume without accelerating gastric emptying or significantly altering gastric motor and sensory function in healthy individuals.

Ethical considerations in placebo-controlled randomised clinical trials.

PubMed

Kaufman, Kenneth R

2015-06-01

Ethical considerations in standard medical care and clinical research are underpinnings to quality medicine. Similarly, the placebo-controlled double-blind randomised clinical trial is the gold standard for medical research and fundamental to the development of evidence-based medicine. Researchers and clinicians are challenged by ethical concerns in the informed consent with a need to maximise understanding and minimise therapeutic misconception. This editorial expands on themes raised by Chen et al 's article 'Disclosing the Potential Impact of Placebo Controls in Antidepressant Trials' and serves as an invitation for further submissions to BJPsych Open on ethics, research design and informed consent. None. © The Royal College of Psychiatrists 2015. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

Enhanced tolerability of the 5-hydroxytryptophane challenge test combined with granisetron.

PubMed

Jacobs, G E; Kamerling, I M C; de Kam, M L; Derijk, R H; van Pelt, J; Zitman, F G; van Gerven, J M A

2010-01-01

A recently developed oral serotonergic challenge test consisting of 5-Hydroxytryptophane (5-HTP, 200 mg) combined with carbidopa (CBD, 100 mg + 50 mg) exhibited dose-related neuroendocrine responsiveness and predictable pharmacokinetics. However, its applicability is limited by nausea and vomiting. A randomized, double-blind, placebo-controlled, four-way crossover trial was performed in 12 healthy male volunteers. The 5-HTP/CBD-challenge was combined with two oral anti-emetics (granisetron, 2 mg or domperidone, 10 mg) to investigate its reliability when side-effects are suppressed. The neuroendocrine response (serum cortisol and prolactin), the side-effect profile [Visual Analogue Scale Nausea (VAS)] and vomiting subjects per treatment were the main outcome measures. Compared to 5-HTP/CBD/placebo, 5-HTP/CBD/ granisetron had no impact on cortisol [% change with 95% confidence interval: -7.1% (18.9; 6.5)] or prolactin levels [-9.6% (-25.1; 9.1)]; 5-HTP/CBD/domperidone increased cortisol [+13.0% (-4.2; 33.4)], and increased prolactin extensively [+336.8% (245.7; 451.9)]. Compared to placebo, VAS Nausea increased non-significantly with granisetron [+7.6 mm (-1.3; 16.5)], as opposed to domperidone [+16.2 mm (7.2; 25.2)] and 5-HTP/CBD/placebo [+14.7 mm (5.5; 23.8)]. No subjects vomited with granisetron, compared to two subjects treated with 5-HTP/CBD/placebo and five subjects with domperidone. Compared with 5-HTP/CBD/placebo, granisetron addition decreased C(max) of 5-HTP statistically significantly different (from 1483 to 1272 ng/ml) without influencing AUC(0- infinity). Addition of granisetron to the combined 5-HTP/CBD challenge suppresses nausea and vomiting without influencing the neuroendocrine response or pharmacokinetics, enhancing its clinical applicability in future psychiatric research and drug development.

Daily consumption of red grape cell powder in a dietary dose improves cardiovascular parameters: a double blind, placebo-controlled, randomized study.

PubMed

Vaisman, Nachum; Niv, Eva

2015-05-01

Consumption of polyphenol-rich food and food ingredient such as grape and grape products improved various cardiovascular parameters. In this study, we investigate the effect of dietary daily consumption of red grape cell powder (RGC) on blood pressure (BP) and flow-mediated dilatation (FMD) as well as on oxidative stress in 50 subjects with prehypertension and mild hypertension. The subjects were randomized into groups that consumed 200, 400 mg RGC or placebo daily for 12 weeks. RGC consumption was associated with an improvement of FMD (p = 0.013). There was a significant decrease in lipid peroxidation (p = 0.013) after 12 weeks in a combined RGC-treated group. The diastolic BP decreased significantly in the 200 mg RGC group compared to the placebo group (p = 0.032). Our results indicate that a daily supplementation, of red grape cell powder, for 12 weeks affects endothelial function, diastolic BP and oxidative stress without any adverse effects.

Food additives and behavior in 8- to 9-year-old children in Hong Kong: a randomized, double-blind, placebo-controlled trial.

PubMed

Lok, Kris Y W; Chan, Ruth S M; Lee, Vivian W Y; Leung, Patrick W; Leung, Cynthia; Leung, Jason; Woo, Jean

2013-01-01

To test the individual effect of artificial food colorings (AFCs) and a preservative on the behavior of the general Chinese population. One hundred thirty children (70 boys and 60 girls) in Hong Kong with a mean age of 8.64 years were enlisted to the study with a within-subject crossover between AFCs, a preservative (sodium benzoate), and a placebo capsule. Two behavior scores were used including the strengths and weaknesses of attention deficit hyperactivity disorder and normal behavior rating scale and the child behavior checklist-teacher report form. Capsule A containing AFCs and Capsule B containing sodium benzoate had no significant adverse effect compared with placebo in both behavior scores. This result persisted when analysis was restricted to children with 85% consumption of capsule (per protocol analysis). There seem to be no significant associations between AFCs and a preservative on Chinese children's behavior at the age of 8 to 9 years. Future directions and implications of this research are discussed.

Prevalence of fish and shellfish allergy: A systematic review.

PubMed

Moonesinghe, Harriet; Mackenzie, Heather; Venter, Carina; Kilburn, Sally; Turner, Paul; Weir, Kellyn; Dean, Taraneh

2016-09-01

Accurate information on the prevalence of food allergy facilitates a more evidence-based approach to planning of allergy services and can identify important geographic variations. To conduct a systematic review to assess the age-specific prevalence of fish and shellfish allergy worldwide. Searches were conducted using Web of Science and PubMed. Population-based cross-sectional studies and cohort studies that examined the prevalence of fish and shellfish allergy (IgE mediated and non-IgE mediated) at an identifiable point in time were eligible for inclusion in the study. Reviewers extracted general study information and study design, type of food allergy considered, food(s) assessed, method of diagnosis, sampling strategy, and sample characteristics. Raw data were extracted and percentage prevalence and 95% confidence intervals calculated. A total of 7,333 articles were identified of which 61 studies met the inclusion criteria and were included in this review. The prevalence of fish allergy ranged from 0% to 7% and the prevalence of shellfish allergy from 0% to 10.3%, depending on the method of diagnosis. Where food challenges were used, the prevalence for fish allergy was found to be 0% to 0.3% and for shellfish allergy was 0% to 0.9%. Few studies have established the prevalence of fish or shellfish allergy using the gold standard double-blind, placebo-controlled challenge criteria, with most instead relying on self-reported questionnaire-based methods. The limited data available suggest that fish allergy prevalence is similar worldwide; however, shellfish allergy prevalence may be higher in the Southeast Asia region. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Intraduodenal infusion of a combination of tastants decreases food intake in humans.

PubMed

van Avesaat, Mark; Troost, Freddy J; Ripken, Dina; Peters, Jelmer; Hendriks, Henk Fj; Masclee, Ad Am

2015-10-01

Taste receptors are expressed not only in taste buds but also in the gastrointestinal tract. It has been hypothesized that these receptors may play a role in satiety and food intake. This study investigated the effect of intraduodenal tastant infusions (bitter, sweet, and umami) on food intake, hunger and fullness, gastrointestinal symptoms, and gastrointestinal peptide release. Fifteen healthy volunteers [6 male; mean ± SEM age: 23.9 ± 2.0 y; mean ± SEM body mass index (in kg/m(2)): 22.4 ± 0.3] received 5 treatments in a double-blind, randomized, placebo-controlled crossover design. Test days started with the insertion of a nasoduodenal catheter followed by a standardized liquid breakfast. Participants received an intraduodenal infusion 150 min after breakfast, containing quinine (bitter), rebaudioside A (sweet), monosodium glutamate (umami), a combination of the 3 tastants, or placebo (tap water) over a period of 60 min. Food intake was measured during an ad libitum meal, and visual analog scales were used to monitor gastrointestinal complaints and hunger and fullness scores. Blood samples were drawn at regular intervals for cholecystokinin, glucagon-like peptide 1 (GLP-1), and peptide YY (PYY) analysis. Infusion of the combination of tastants substantially decreased food intake (422 ± 97 compared with 486 ± 104 kcal for placebo, P < 0.05), whereas both a combination of tastants and umami decreased hunger scores compared with placebo. No change in cholecystokinin, GLP-1, or PYY concentrations was observed during the infusions. Intraduodenal infusions of the tastants did not result in gastrointestinal symptoms. Intraduodenal infusion of umami and a combination of tastants inhibits feelings of hunger, but only the latter also reduces food intake. However, these alterations were not accompanied by changes in the plasma concentrations of the gut-derived peptides cholecystokinin, GLP-1, or PYY. This trial was registered at clinicaltrials.gov as NCT01956838. © 2015 American Society for Nutrition.

The effects of the DDS-1 strain of lactobacillus on symptomatic relief for lactose intolerance - a randomized, double-blind, placebo-controlled, crossover clinical trial.

PubMed

Pakdaman, Michael N; Udani, Jay K; Molina, Jhanna Pamela; Shahani, Michael

2016-05-20

Lactose intolerance is a form of lactose maldigestion where individuals experience symptoms such as diarrhea, abdominal cramping, flatulence, vomiting and bowel sounds following lactose consumption. Lactobacillus acidophilus is a species of bacteria known for its sugar fermenting properties. Preclinical studies have found that Lactobacillus acidophilus supplementation may assist in breaking down lactose; however, no human clinical trials exist evaluating its efficacy in alleviating symptoms related to lactose intolerance. The aim of this randomized, double-blind, placebo-controlled, crossover study was to evaluate the effect of a proprietary strain of Lactobacillus acidophilus on relieving discomfort related to lactose intolerance. The study enrolled healthy volunteers between 18 and 75 years of age who complained of lactose intolerance. Screening visits included a lactose challenge visit to confirm eligibility based on a score of 10 or higher on subjective assessment of the following symptoms after lactose challenge: diarrhea, abdominal cramping, vomiting, audible bowel sounds, flatulence, and overall symptoms. Qualified subjects participated in a 2-arm crossover design, with each arm consisting of 4 weeks of intervention of either active or placebo product, with a 2-week washout period during crossover. The study product consisted of the DDS-1 strain of Lactobacillus acidophilus (Nebraska Cultures, Walnut Creek, California). The placebo was formulated from maltodextrin. Study participants were instructed to take the product once daily for 4 weeks. Data collected included subjective symptom scores related to lactose intolerance. Longitudinal comparison between the DDS-1 group and placebo group demonstrated statistically significant reductions in abdominal symptom scores during the 6-h Lactose Challenge at week 4 for diarrhea (p = 0.033), abdominal cramping (p = 0.012), vomiting (p = 0.0002), and overall symptom score (p = 0.037). No adverse events were reported. The present study has found that this unique DDS-1 strain of Lactobacillus acidophilus, manufactured by Nebraska Cultures, is safe to consume and improves abdominal symptom scores compared to placebo with respect to diarrhea, cramping, and vomiting during an acute lactose challenge.

Evaluation of different fluoridated dentifrice formulations using an in situ erosion remineralization model.

PubMed

Barlow, A P; Sufi, F; Mason, S C

2009-01-01

The objective of these three clinical in situ studies was to investigate the relative performance of commercially available and experimental dentifrice formulations, having different fluoride sources and excipient ingredients, at remineralizing a bovine enamel surface previously softened by a dietary acid challenge. Each study utilized the same randomized, placebo-controlled, single-blind, crossover design. Subjects undertook single brushings of their natural teeth, with an in situ appliance in place, using different dentifrices in a randomly assigned order. Study A involved 58 subjects with the following dentifrices: Sensodyne Pronamel (1450 ppm F as NaF/5% KNO3); Blend-a-Med Classic (1450 ppm F as NaF); and a matched (Pronamel) placebo control (0 ppm F). Study B involved 56 subjects with the following dentifrices: Sensodyne Pronamel (1150 ppm F as NaF/5% KNO3); Crest Cavity Protection (1100 ppm F as NaF); Crest Pro-Health (0.454% SnF2 [1100 ppm F]/sodium hexametaphosphate); and a matched (Pronamel) placebo control (0 ppm F). Study C involved 56 subjects with the following dentifrices: Sensodyne Pronamel (1150 ppm F as NaF/5% KNO3); Sensodyne Pronamel Gentle Whitening (1150 ppm F as NaF/5% KNO3); Colgate Sensitive Multi Protection (1000 ppm F as NaMFP/5.53% potassium citrate/2% zinc citrate); and a matched (Pronamel) placebo control (0 ppm F). Subjects wore their palatal appliances holding eight bovine enamel blocks, previously exposed for 25 minutes to an in vitro erosive challenge with grapefruit juice, for the duration of the experiment. Five minutes after appliance insertion, subjects undertook a supervised, 90-second brush/rinse regimen with their assigned dentifrice. Surface microhardness (SMH) of the specimens was determined prior to the erosive challenge (baseline), after the in vitro erosive challenge, and were remeasured after four hours in situ remineralization following the tooth brushing event. Finally, SMH values were determined after a second in vitro erosive challenge at the end of the in situ remineralization period. Statistical analyses included ANOVA and pair-wise comparisons between treatments, testing at a 5% significance level. All three studies demonstrated significantly greater percent surface microhardness recovery (% SMHr) and percent relative erosion resistance (% RER) for dentifrices containing sodium fluoride compared to placebo controls. Overall, significantly greater % SMHr (p < 0.0001) was observed for Sensodyne Pronamel compared to Blend-a-Med Classic, Crest Pro-Health, and Colgate Sensitive Multi Protection dentifrices. Similarly, Sensodyne Pronamel delivered directionally better % RER vs. Blend-a-Med Classic (p = 0.0731), and significantly higher % RER vs. Crest Pro-Health (p = 0.0074) and Colgate Sensitive Multi Protection (p <0.0001). Crest Cavity Protection demonstrated significantly better % RER (p = 0.031) than Crest Pro-Health, which in turn demonstrated significantly better % RER than the placebo control (p < 0.0001). No other statistically significant between-product comparisons were observed. The results of these in situ studies support the effectiveness of dentifrices containing sodium fluoride to reharden enamel previously softened with an erosive challenge. Furthermore, these studies demonstrate the protective effects conferred to enamel, from erosion following the remineralization process in the presence of "ionic" fluoride. Under clinically relevant conditions, Sensodyne Pronamel and Sensodyne Pronamel Gentle Whitening offered superior anti-erosion performance compared to currently marketed dentifrice controls. These studies reinforce previous research indicating the importance of formulation effects on the relative remineralization performance of dentifrices under erosive conditions.

Explorative Placebo-Controlled Double-Blind Intervention Study with Low Doses of Inhaled Δ9-Tetrahydrocannabinol and Cannabidiol Reveals No Effect on Sweet Taste Intensity Perception and Liking in Humans.

PubMed

de Bruijn, Suzanne E M; de Graaf, Cees; Witkamp, Renger F; Jager, Gerry

2017-01-01

Introduction: The endocannabinoid system (ECS) plays an important role in food reward. For example, in humans, liking of palatable foods is assumed to be modulated by endocannabinoid activity. Studies in rodents suggest that the ECS also plays a role in sweet taste intensity perception, but it is unknown to what extent this can be extrapolated to humans. Therefore, this study aimed at elucidating whether Δ9-tetrahydrocannabinol (THC) or cannabidiol (CBD) affects sweet taste intensity perception and liking in humans, potentially resulting in alterations in food preferences. Materials and Methods: In a randomized placebo-controlled, double-blind crossover study, 10 healthy males participated in three test sessions that were 2 weeks apart. During the test sessions, participants received THC-rich, CBD-rich, or placebo Cannabis by inhalation divided over two doses (4 + 1 mg THC; 25 + 10 mg CBD). Participants tasted seven chocolate milk-like drinks that differed in sugar concentration and they rated sweet taste intensity and liking of the drinks. They were then asked to rank the seven drinks according to how much they liked the drinks and were offered ad libitum access to their favorite drink. In addition, they completed a computerized food preference task and completed an appetite questionnaire at the start, midway, and end of the test sessions. Results: Inhalation of the Cannabis preparations did not affect sweet taste intensity perception and liking, ranking order, or ad libitum consumption of the favorite drink. In addition, food preferences were not influenced by the interventions. Reported fullness was lower, whereas desire to eat was higher throughout the THC compared to the CBD condition. Conclusions: These results suggest that administration of Cannabis preparations at the low doses tested does not affect sweet taste intensity perception and liking, nor does it influence food preferences in humans.

A Randomized, Double-Blind Study of Larazotide Acetate to Prevent the Activation of Celiac Disease During Gluten Challenge

PubMed Central

Leffler, Daniel A; Kelly, C P; Abdallah, H Z; Colatrella, A M; Harris, L A; Leon, F; Arterburn, L A; Paterson, B M; Lan, Z H; Murray, J A

2012-01-01

OBJECTIVES: In patients with celiac disease, enteropathy is caused by the entry of gluten peptides into the lamina propria of the intestine, in which their immunogenicity is potentiated by tissue transglutaminase (tTG) and T-helper type 1–mediated immune responses are triggered. Tight junction disassembly and paracellular permeability are believed to have an important role in the transport of gluten peptides to the lamina propria. Larazotide acetate is a tight-junction regulator peptide that, in vitro, prevents the opening of intestinal epithelial tight junctions. The aim of this study was to evaluate the efficacy and tolerability of larazotide acetate in protecting against gluten-induced intestinal permeability and gastrointestinal symptom severity in patients with celiac disease. METHODS: In this dose-ranging, placebo-controlled study, 86 patients with celiac disease controlled through diet were randomly assigned to larazotide acetate (0.25, 1, 4, or 8 mg) or placebo three times per day with or without gluten challenge (2.4 g/day) for 14 days. The primary efficacy outcome was the urinary lactulose/mannitol (LAMA) fractional excretion ratio. Secondary endpoints included gastrointestinal symptom severity, quality-of-life measures, and antibodies to tTG. RESULTS: LAMA measurements were highly variable in the outpatient setting. The increase in LAMA ratio associated with the gluten challenge was not statistically significantly greater than the increase in the gluten-free control. Among patients receiving the gluten challenge, the difference in the LAMA ratios for the larazotide acetate and placebo groups was not statistically significant. However, larazotide acetate appeared to limit gluten-induced worsening of gastrointestinal symptom severity as measured by the Gastrointestinal Symptom Rating Scale at some lower doses but not at the higher dose. Symptoms worsened significantly in the gluten challenge–placebo arm compared with the placebo–placebo arm, suggesting that 2.4 g of gluten per day is sufficient to induce reproducible gluten toxicity. Larazotide acetate was generally well tolerated. No serious adverse events were observed. The most common adverse events were headache and urinary tract infection. CONCLUSIONS: LAMA variability in the outpatient setting precluded accurate assessment of the effect of larazotide acetate on intestinal permeability. However, some lower doses of larazotide acetate appeared to prevent the increase in gastrointestinal symptom severity induced by gluten challenge. PMID:22825365

The effect of exercise on water balance in premenopausal physically active women.

PubMed

Weinheimer, Eileen M; Martin, Berdine R; Weaver, Connie M; Welch, Jo M; Campbell, Wayne W

2008-10-01

This controlled feeding study examined the effects of exercise on daily water intake (particularly ad libitum water intake), water output, whole-body water balance, and hydration status in physically active, premenopausal women. The randomized crossover design consisted of three 8-day trials: placebo and no exercise, placebo and exercise (1-hour cycling bout per day at 65%-70% of heart rate reserve), and 800 mg calcium supplementation and exercise. During each trial, controlled quantities of the same foods and beverages were provided and ad libitum water intake was quantified. Water input included measured water from foods and beverages, measured ad libitum intake, and estimated metabolic production. Water output included measured losses in urine and stool, and estimated insensible losses from respiration and non-sweating perspiration (insensible diffusion through the skin). Participants were 26 women, age 25+/-5 years, body mass index 22+/-2, and VO(2peak) 43+/-6 mLxkg(-1)xmin(-1) (mean+/-standard deviation). Ad libitum water intake was 363 g/day more (P<0.05) for the placebo and exercise (1,940+/-654 g/day) and calcium supplementation and exercise (1,935+/-668 g/day) trials, compared with placebo and no exercise trial (1,575+/-667 g/day), and total water input was correspondingly higher in placebo and exercise and calcium supplementation and exercise trials compared with the placebo and no exercise trial. Urine, stool, and total water outputs were not different among trials. Apparent net water balance (representative of sweat water output) was 367 g/day more (P<0.05) in placebo and exercise (679+/-427 g/day) and calcium supplementation and exercise (641+/-519 g/day) trials compared with placebo and no exercise trial (293+/-419 g/day). Hydration status was clinically normal during all three trials. Calcium supplementation did not influence water balance. These results support that young, physically active women can completely compensate for exercise-induced sweat losses by increasing ad libitum water intake, and not decreasing non-sweat water outputs or impairing hydration status.

Clinical and immunological profile of children aged 5-9 years with persistent egg allergy before oral immunotherapy with egg. A multicenter, randomized controlled trial of the Spanish Society of Pediatric Allergy, Asthma and Clinical Immunology (SEICAP).

PubMed

Echeverria, L; Martin-Muñoz, M F; Martorell, C; Belver, M T; Alonso Lebrero, E; Zapatero, L; Fuentes, V; Piqué, M; Plaza, A; Muñoz, C; Martorell, A; Blasco, C; Villa, B; Gómez, C; Nevot, S; García, J M; Madero, R

2018-05-24

In children with egg protein allergy (EA), the probability of overcoming the allergy decreases with age, and the possibility of suffering severe adverse reactions as a consequence of dietetic transgressions results in worsened quality of life. One treatment option in such cases is oral immunotherapy (OIT) with foods. We present a cohort of children with EA scheduled for OIT with pasteurized raw egg white, describing their clinical and allergic characteristics before the start of OIT. The median age was six years, and 93% of the patients also suffered other allergies (58% asthma and 38.6% allergy to more than two food groups). In the last year, 14.8% had suffered a severe reaction due to dietetic transgression with egg. The median IgE specific of egg white titer was 38.5kU/l. A double-blind placebo-controlled food challenge with cooked egg white was performed, and if the test proved positive, it was repeated with pasteurized raw egg white. The mean symptoms-provoking dose was 1.26g and 0.55g for cooked egg white and raw egg white, respectively. An IgE specific of ovomucoid titer of <2.045kU/l differentiated those patients that tolerated cooked egg white. OIT with egg is regarded as an option in patients with persistent egg allergy. In the previous challenge test, an IgE specific of ovomucoid titer of <2.045kU/l differentiates those patients that tolerate cooked egg white. Copyright © 2018 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.

Ovomucoid (Gal d 1) specific IgE detected by microarray system predict tolerability to boiled hen's egg and an increased risk to progress to multiple environmental allergen sensitisation.

PubMed

Alessandri, C; Zennaro, D; Scala, E; Ferrara, R; Bernardi, M Livia; Santoro, M; Palazzo, P; Mari, A

2012-03-01

Egg allergy is a very common finding in early childhood. Detecting hen's egg (HE) allergy outgrowing and reintroduction of food containing egg is a task for the allergist. We sought to evaluate the suitability of boiled egg food challenge compared with IgE to allergenic molecules from HE white using a microarray system. Sixty-eight children referring to our centre by the family paediatricians for a suspected egg allergy were enrolled. Patients underwent double-blind, placebo-controlled food challenge with boiled and raw eggs. Challenge outcomes were compared with skin tests performed using egg white and yolk commercial extracts, to prick-prick test with boiled and raw egg white and yolk, total IgE, egg white specific IgE detected using ImmunoCAP and IgE to egg allergens available on the immunosolid phase allergen chip (ISAC) 103 microarray. Nineteen subjects (28%) were reactive to both raw and boiled egg, 14 (20.5%) to raw egg only and 35 (51.4%) tolerated both boiled and raw egg. Efficiency analysis was carried out using both raw and boiled egg challenges as gold standard. Forty four of 47 Gal d 1 negative patients tolerated boiled egg (94%). Conversely, 20 of 21 Gal d 1 positive patients reacted to raw egg (95%). None of the other tests was able to discriminate patients' response to HE challenge. Furthermore, Gal d 1 positivity seems to lead to broader environmental allergen IgE sensitization. The Gal d 1 IgE reactivity appears to be a very good predictor of HE clinical allergy. Gal d 1 positive children have a high frequency of HE allergy, whereas Gal d 1 negative children have a high frequency of tolerance to boiled egg. Multiple specific IgE detection by means of ISAC improves the diagnostic approach in HE allergic children, disclosing other food and inhalant allergic sensitizations, anyhow requiring a comprehensive clinical evaluation. © 2011 Blackwell Publishing Ltd.

Efficacy of dexpanthenol in skin protection against irritation: a double-blind, placebo-controlled study.

PubMed

Biro, Kathrin; Thaçi, Diamant; Ochsendorf, Falk R; Kaufmann, Roland; Boehncke, Wolf-Henning

2003-08-01

Dexpanthenol is popular in treating various dermatoses and in skin care, but few controlled clinical trials have been performed. We investigated the efficacy of dexpanthenol in skin protection against irritation in a randomized, prospective, double-blind, placebo-controlled study. 25 healthy volunteers (age 18-45 years) were treated for the inner aspect of both forearms with either Bepanthol Handbalsam containing 5% dexpanthenol or placebo x2 daily for 26 days. From day 15-22, sodium lauryl sulfate (SLS) 2% was applied to these areas x2 daily. Documentation comprised sebumetry, corneometry, pH value and clinical appearance (photographs). 21 volunteers completed the study, 3 were excluded because of non-compliance and 1 experienced a non-study-related, severe, adverse event. Only corneometry yielded a statistically significant difference, with decreased values following SLS challenge at the placebo sites (P < 0.05). Intraindividual comparisons showed superior results at the dexpanthenol-treated sites in 11 cases and in only 1 case at the placebo site. 6 volunteers experienced an irritant contact dermatitis, with more severe symptoms at the placebo site in 5 cases. In conclusion, dexpanthenol exhibits protective effects against skin irritation. The initiation of a study to evaluate the efficacy of dexpanthenol in preventing irritant occupational contact dermatitis under real workplace conditions is validated.

The safety of flavocoxid, a medical food, in the dietary management of knee osteoarthritis.

PubMed

Morgan, Sarah L; Baggott, Joseph E; Moreland, Larry; Desmond, Renee; Kendrach, Angela C

2009-10-01

This study was designed to determine the safety of a medical food, flavocoxid, a proprietary blend of free-B ring flavonoids and flavans from the root of Scutellaria baicalensis (Chinese skullcap) and the bark of Acacia catechu in the dietary management of knee osteoarthritis. The 12-week, randomized, double-blind, placebo-controlled trial in an academic medical center enrolled 59 patients with moderate osteoarthritis of at least one knee who were recruited who were classified as having "below average" to "a moderately above average cardiovascular risk" with a Framingham-based scoring tool. Subjects were randomized to flavocoxid 250 mg twice a day versus identical placebo. Safety measures, including recording of adverse events, incidence of serious adverse events, and results of routine laboratory values, were compared between the two groups. There were no major differences in the baseline demographic characteristics of the placebo and flavocoxid groups. With one exception no significant differences were found between the two groups with respect to adverse events by body system, blood pressure, or laboratory values. There was a significantly higher incidence of upper respiratory adverse events in the placebo group (35.4% vs. 5.8%, P = .0003). There were no intra- or inter-group differences in any of the laboratory parameters from study baseline to completion. Thus, flavocoxid is safe when used in a population with "below average" to "moderately above average cardiovascular risk" compared to placebo.

Prevalence of confirmed IgE-mediated food allergy among adolescents in Turkey.

PubMed

Kaya, Ayşenur; Erkoçoğlu, Mustafa; Civelek, Ersoy; Çakır, Banu; Kocabaş, Can N

2013-08-01

Although food allergy is an important health problem in Western countries, the prevalence varies among geographic regions. There is limited data on the prevalence of food allergy especially for adolescent age group, and the data from Turkey and Mediterranean region are even scarce. The study is a cross-sectional survey including a questionnaire followed by phone survey with families that have reported food allergy and clinical evaluation of children having a history compatible with food allergy after phone survey. The sample number of students has been calculated 9096 of a total of 210.000 students at the second stage (6th, 7th, and 8th grades) of state elementary schools in the metropolitan counties of Ankara province with the assumption of food allergy prevalence (P) = 1% and a δ value = 0.2 (α < 0.05, β = 0.8). Of 11,233 questionnaires distributed at 34 schools, 10,096 (89.4%) have been returned. The number of reported food allergy was 1139 (11.2%), and it was reduced to 133 (1.3%) after phone survey. After clinical evaluation by skin test, specific IgE and double-blind placebo-controlled food challenge (DBPCFC), proven IgE-mediated food allergy was determined in 15 (0.15%) children. The foods most commonly resulting food allergy were peanut 0.05% and treenuts 0.05%. The prevalence of food allergy among adolescent age group has been confirmed to be comparatively low in Turkey. Peanuts and treenuts were determined to be the most common causes of IgE-mediated food allergy. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Fecal Microbiome and Food Allergy in Pediatric Atopic Dermatitis: A Cross-Sectional Pilot Study.

PubMed

Fieten, Karin B; Totté, Joan E E; Levin, Evgeni; Reyman, Marta; Meijer, Yolanda; Knulst, André; Schuren, Frank; Pasmans, Suzanne G M A

2018-01-01

Exposure to microbes may be important in the development of atopic disease. Atopic diseases have been associated with specific characteristics of the intestinal microbiome. The link between intestinal microbiota and food allergy has rarely been studied, and the gold standard for diagnosing food allergy (double-blind placebo-controlled food challenge [DBPCFC]) has seldom been used. We aimed to distinguish fecal microbial signatures for food allergy in children with atopic dermatitis (AD). Pediatric patients with AD, with and without food allergy, were included in this cross-sectional observational pilot study. AD was diagnosed according to the UK Working Party criteria. Food allergy was defined as a positive DBPCFC or a convincing clinical history, in combination with sensitization to the relevant food allergen. Fecal samples were analyzed using 16S rRNA microbial analysis. Microbial signature species, discriminating between the presence and absence food allergy, were selected by elastic net regression. Eighty-two children with AD (39 girls) with a median age of 2.5 years, and 20 of whom were diagnosed with food allergy, provided fecal samples. Food allergy to peanut and cow's milk was the most common. Six bacterial species from the fecal microbiome were identified, that, when combined, distinguished between children with and without food allergy: Bifidobacterium breve, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Escherichia coli, Faecalibacterium prausnitzii, and Akkermansia muciniphila (AUC 0.83, sensitivity 0.77, specificity 0.80). In this pilot study, we identified a microbial signature in children with AD that discriminates between the absence and presence of food allergy. Future studies are needed to confirm our findings. © 2018 The Author(s) Published by S. Karger AG, Basel.

Omalizumab facilitates rapid oral desensitization for peanut allergy

PubMed Central

MacGinnitie, Andrew J.; Rachid, Rima; Gragg, Hana; Little, Sara V; Lakin, Paul; Cianferoni, Antonella; Heimall, Jennifer; Makhija, Melanie; Robison, Rachel; Chinthrajah, R. Sharon; Lee, John; Lebovidge, Jennifer; Dominguez, Tina; Rooney, Courtney; Lewis, Megan Ott; Koss, Jennifer; Burke-Roberts, Elizabeth; Chin, Kimberly; Logvinenko, Tanya; Pongracic, Jacqueline A.; Umetsu, Dale T.; Spergel, Jonathan; Nadeau, Kari C.; Schneider, Lynda C.

2017-01-01

Background Peanut oral immunotherapy (OIT) is a promising approach to peanut allergy but reactions are frequent and some patients cannot be desensitized. The anti-IgE medication omalizumab (Xolair) may allow more rapid peanut updosing and decrease reactions. Objective To evaluate if omalizumab facilitated rapid peanut desensitization in highly allergic patients. Methods Thirty-seven subjects were randomized to omalizumab (n=29) or placebo (n=8). After 12 weeks of treatment subjects underwent a rapid one-day desensitization of up to 250 mg of peanut protein, followed by weekly increases up to 2000 mg. Omalizumab was then discontinued and subjects continued on 2000 mg of peanut protein. They underwent an open challenge to 4000 mg peanut protein twelve weeks after stopping study drug. If tolerated, subjects continued on 4000 mg of peanut protein daily. Results The median peanut dose tolerated on the initial desensitization day was 250 mg for omalizumab versus 22.5 mg for placebo treated subject. Subsequently 23 of 29 (79%) subjects randomized to omalizumab tolerated 2000 mg peanut protein 6 weeks after stopping omalizumab versus 1 of 8 (12%) receiving placebo (p<0.01). Twenty-three subjects on omalizumab versus 1 on placebo passed the 4000 mg food challenge. Overall reaction rates were not significantly lower in omalizumab versus placebo treated subjects (OR=0.57 p=0.15), although omalizumab treated subjects were exposed to much higher doses of peanut. Conclusion Omalizumab allows subjects with peanut allergy to be rapidly desensitized over as little as 8 weeks of peanut OIT. In the majority of subjects, this desensitization is sustained after omalizumab is discontinued. Additional studies will help clarify which patients would benefit most from this approach. PMID:27609658

Double-blind, placebo-controlled immunotherapy with mixed grass-pollen allergoids. IV. Comparison of the safety and efficacy of two dosages of a high-molecular-weight allergoid.

PubMed

Bousquet, J; Hejjaoui, A; Soussana, M; Michel, F B

1990-02-01

Specific immunotherapy is still widely used in grass-pollen allergy, but its side effects may limit its use. We tested the safety and efficacy of a formalinized high-molecular-weight allergoid prepared from a mixed grass-pollen extract with two injection schedules in a double-blind, placebo-controlled study. Eighteen patients received placebo, 19 received the low-dose schedule (maximal dose: 2000 PNU) and 20 received the high-dose schedule (maximal dose: 10,000 PNU). Only one patient presented a systemic reaction of moderate severity for a dose of 1200 PNU. Before the onset of the pollen season, patients had a nasal challenge with orchard grass-pollen grains, a skin test titration, and the titration of serum-specific IgG. Both groups of patients presented a significant reduction in nasal and skin sensitivities and a significant increase in IgG compared to placebo. Symptoms and medications for rhinitis and asthma were studied during the season, and both groups receiving allergoids had a significant reduction of symptom-medication scores for nasal and bronchial symptoms. There was a highly significant correlation between nasal symptom-medication scores during the season and the results of nasal challenges. High-molecular-weight allergoids are safe and effective.

Important issues in the justification of a control treatment in paediatric drug trials.

PubMed

Kelly, Lauren E; Davies, Elin Haf; Saint-Raymond, Agnes; Tomasi, Paolo; Offringa, Martin

2016-10-01

The value of comparative effectiveness trials in informing clinical and policy decisions depends heavily on the choice of control arm (comparator). Our objective is to identify challenges in comparator reasoning and to determine justification criteria for selecting a control arm in paediatric clinical trials. A literature search was completed to identify existing sources of guidance on comparator selection. Subsequently, we reviewed a randomly selected sample of comparators selected for paediatric investigation plans (PIPs) adopted by the Paediatric Committee of the European Medicines Agency in 2013. We gathered descriptive information and evaluated their review process to identify challenges and compromises between regulators and sponsors with regard to the selection of the comparator. A tool to help investigators justify the selection of active controls and placebo arms was developed using the existing literature and empirical data. Justifying comparator selection was a challenge in 28% of PIPs. The following challenging paediatric issues in the decision-making process were identified: use of off-label medications as comparators, ethical and safe use of placebo, duration of placebo use, an undefined optimal dosing strategy, lack of age-appropriate safety and efficacy data, and drug dosing not supported by extrapolation of safety/efficacy evidence from other populations. In order to generate trials that will inform clinical decision-making and support marketing authorisations, researchers must systemically and transparently justify their selection of the comparator arm for their study. This report highlights key areas for justification in the choice of comparator in paediatric clinical trials. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

A double-blind, placebo-controlled oral challenge study with lyophilized larvae and antigen of the fish parasite, Anisakis simplex.

PubMed

Sastre, J; Lluch-Bernal, M; Quirce, S; Arrieta, I; Lahoz, C; Del Amo, A; Fernández-Caldas, E; Marañón, F

2000-06-01

The third-stage larvae of Anisakis simplex may be a hidden source of allergens in fish. The objective was to determine whether the ingestion of lyophilized A. simplex larvae, or antigen, induces clinical symptoms in a group of A. simplex-sensitized patients. Double-blind, placebo-controlled oral challenges were conducted in 11 individuals who had experienced allergic reactions after eating fish. Another patient had chronic urticaria unrelated to the ingestion of fish. All patients had positive skin tests and specific IgE determinations for A. simplex and negative skin tests to a battery of fish species. Conjunctival tests with A. simplex extracts were conducted in all patients and in five controls. The 12 patients received capsules containing either lactose or one, five, or 25 lyophilized larvae of A. simplex at 2-h intervals in a double-blind fashion. The highest single dose was 100 larvae. ECP and tryptase levels in serum were measured before and after the last oral challenge. Lyophilized antigen was also given to five patients. None of the 12 patients experienced a positive reaction after the ingestion of the placebo, the lyophilized larvae, or the antigen. Tryptase and ECP levels before and after challenges did not change significantly. Conjunctival provocation tests were positive in 11 out of the 12 patients and in none of the controls. The ingestion of 100 lyophilized A. simplex larvae, or its equivalent in antigen, does not induce clinical symptoms in individuals with a clinical history and laboratory findings of hypersensitivity to A. simplex. The data suggest that only the ingestion of live larvae may be capable of inducing allergic manifestations.

Prevalence of immunoglobulin E-mediated food allergy in 6-9-year-old urban schoolchildren in the eastern Black Sea region of Turkey.

PubMed

Orhan, F; Karakas, T; Cakir, M; Aksoy, A; Baki, A; Gedik, Y

2009-07-01

The prevalence of adverse reactions to food in childhood in Turkey is not known. We aimed to investigate the prevalence and characteristics of IgE-mediated food allergies (FAs) in 6-9-year-old urban schoolchildren. This cross-sectional study recruited 3500 of the randomly selected 6-9-year-old urban schoolchildren from the eastern Black Sea region of Turkey during 2006. Following a self-administered questionnaire completed by the parents and the child, consenting children were invited for skin prick tests (SPTs) and oral food challenges. Children with suspected IgE-mediated FA were skin prick tested with a predefined panel of food allergens (milk, hen's egg, soy, wheat, peanut, fish, and hazelnut), aeroallergens (Dermatophagoides pteronyssinus, Dermatophagoides farinae, cat, dog, Alternaria, grass pollen mix, weed pollen mix, and tree pollen mix), and food allergens reported in the questionnaire. All children with a positive SPT to any food were invited for a double-blind, placebo-controlled food challenge (DBPCFC). The prevalence of IgE-mediated FA was established using DBPCFCs. The response rate to the questionnaire was 78.2% (2739/3500). The estimated prevalence of parental-reported IgE-mediated FA was 5.7% (156/2739) [95% confidence interval (CI), 4.83-6.57%]. The rate of sensitization to the food allergens was 33.1% (48/145) in the parental-reported group. The confirmed prevalence of IgE-mediated FA by means of DBPCFC in 6-9-year-old urban schoolchildren living in the eastern Black Sea region of Turkey was 0.80% (22/2739) (95% CI, 0.47-1.13%). The most common allergenic foods were beef (31.8%), cow's milk (18.1%), cocoa (18.1%), hen's egg (13.6%), and kiwi (13.6%). The rate of reported IgE-mediated FA was significantly higher than clinically confirmed FA by means of DBPCFC (odds ratio, 7.46; 95% CI, 4.67-12.01; P<0.0001). The order of allergenic foods was different and somewhat unique to the eastern Black Sea region of Turkey when compared with western countries.

The Gluten-Free/Casein-Free Diet: A Double-Blind Challenge Trial in Children with Autism.

PubMed

Hyman, Susan L; Stewart, Patricia A; Foley, Jennifer; Cain, Usa; Peck, Robin; Morris, Danielle D; Wang, Hongyue; Smith, Tristram

2016-01-01

To obtain information on the safety and efficacy of the gluten-free/casein-free (GFCF) diet, we placed 14 children with autism, age 3-5 years, on the diet for 4-6 weeks and then conducted a double-blind, placebo-controlled challenge study for 12 weeks while continuing the diet, with a 12-week follow-up. Dietary challenges were delivered via weekly snacks that contained gluten, casein, gluten and casein, or placebo. With nutritional counseling, the diet was safe and well-tolerated. However, dietary challenges did not have statistically significant effects on measures of physiologic functioning, behavior problems, or autism symptoms. Although these findings must be interpreted with caution because of the small sample size, the study does not provide evidence to support general use of the GFCF diet.

The effect of Korean pine nut oil on in vitro CCK release, on appetite sensations and on gut hormones in post-menopausal overweight women.

PubMed

Pasman, Wilrike J; Heimerikx, Jos; Rubingh, Carina M; van den Berg, Robin; O'Shea, Marianne; Gambelli, Luisa; Hendriks, Henk F J; Einerhand, Alexandra W C; Scott, Corey; Keizer, Hiskias G; Mennen, Louise I

2008-03-20

Appetite suppressants may be one strategy in the fight against obesity. This study evaluated whether Korean pine nut free fatty acids (FFA) and triglycerides (TG) work as an appetite suppressant. Korean pine nut FFA were evaluated in STC-1 cell culture for their ability to increase cholecystokinin (CCK-8) secretion vs. several other dietary fatty acids from Italian stone pine nut fatty acids, oleic acid, linoleic acid, alpha-linolenic acid, and capric acid used as a control. At 50 muM concentration, Korean pine nut FFA produced the greatest amount of CCK-8 release (493 pg/ml) relative to the other fatty acids and control (46 pg/ml). A randomized, placebo-controlled, double-blind cross-over trial including 18 overweight post-menopausal women was performed. Subjects received capsules with 3 g Korean pine (Pinus koraiensis) nut FFA, 3 g pine nut TG or 3 g placebo (olive oil) in combination with a light breakfast. At 0, 30, 60, 90, 120, 180 and 240 minutes the gut hormones cholecystokinin (CCK-8), glucagon like peptide-1 (GLP-1), peptide YY (PYY) and ghrelin, and appetite sensations were measured. A wash-out period of one week separated each intervention day.CCK-8 was higher 30 min after pine nut FFA and 60 min after pine nut TG when compared to placebo (p < 0.01). GLP-1 was higher 60 min after pine nut FFA compared to placebo (p < 0.01). Over a period of 4 hours the total amount of plasma CCK-8 was 60% higher after pine nut FFA and 22% higher after pine nut TG than after placebo (p < 0.01). For GLP-1 this difference was 25% after pine nut FFA (P < 0.05). Ghrelin and PYY levels were not different between groups. The appetite sensation "prospective food intake" was 36% lower after pine nut FFA relative to placebo (P < 0.05). This study suggests that Korean pine nut may work as an appetite suppressant through an increasing effect on satiety hormones and a reduced prospective food intake.

Are we drawing the right conclusions from randomised placebo-controlled trials? A post-hoc analysis of data from a randomised controlled trial

PubMed Central

2009-01-01

Background Assumptions underlying placebo controlled trials include that the placebo effect impacts on all study arms equally, and that treatment effects are additional to the placebo effect. However, these assumptions have recently been challenged, and different mechanisms may potentially be operating in the placebo and treatment arms. The objective of the current study was to explore the nature of placebo versus pharmacological effects by comparing predictors of the placebo response with predictors of the treatment response in a randomised, placebo-controlled trial of a phytotherapeutic combination for the treatment of menopausal symptoms. A substantial placebo response was observed but no significant difference in efficacy between the two arms. Methods A post hoc analysis was conducted on data from 93 participants who completed this previously published study. Variables at baseline were investigated as potential predictors of the response on any of the endpoints of flushing, overall menopausal symptoms and depression. Focused tests were conducted using hierarchical linear regression analyses. Based on these findings, analyses were conducted for both groups separately. These findings are discussed in relation to existing literature on placebo effects. Results Distinct differences in predictors were observed between the placebo and active groups. A significant difference was found for study entry anxiety, and Greene Climacteric Scale (GCS) scores, on all three endpoints. Attitude to menopause was found to differ significantly between the two groups for GCS scores. Examination of the individual arms found anxiety at study entry to predict placebo response on all three outcome measures individually. In contrast, low anxiety was significantly associated with improvement in the active treatment group. None of the variables found to predict the placebo response was relevant to the treatment arm. Conclusion This study was a post hoc analysis of predictors of the placebo versus treatment response. Whilst this study does not explore neurobiological mechanisms, these observations are consistent with the hypotheses that 'drug' effects and placebo effects are not necessarily additive, and that mutually exclusive mechanisms may be operating in the two arms. The need for more research in the area of mechanisms and mediators of placebo versus active responses is supported. Trial Registration International Clinical Trials Registry ISRCTN98972974. PMID:19549306

Placebos in 19th century medicine: a quantitative analysis of the BMJ.

PubMed

Raicek, Jacqueline E; Stone, Bradley H; Kaptchuk, Ted J

2012-12-18

To provide the first quantitative data on the use of the term "placebo" in the 19th century. Computer search of BMJ's archival database from January 1840 (the first issue) through December 1899 for uses of the words "placebo(s)." Grounded theory was used to categorise the implications of uses of the term. 71 citations contained the term "placebo(s)." Of these, 22 (31%) used the term to mean "no effect" or as a general pejorative term, 18 (25%) portrayed placebo treatment as permitting the unfolding of the natural history (the normal waxing and waning of illness), 14 (20%) described placebo as important to satisfy patients, 7 (10%) described it as fulfilling a physician's performance role, 3 (4%) described its use to buy time, 3 (4%) described its use for financial gain, 2 (3%) used it in a manner similar to a placebo control, and only one implied that placebo could have a clinical effect. Only one citation mentioned telling the patient about his placebo treatment. Nineteenth century physicians had diverse a priori assumptions about placebos. These findings remind us that contemporary medicine needs to use rigorous science to separate fact from its own beliefs concerning the "provision of care." As in previous generations, ethical issues concerning placebos continue to challenge medicine.

The Anticaries Effect of a Food Extract (Shiitake) in a Short-Term Clinical Study

PubMed Central

Lingström, Peter; Zaura, Egija; Hassan, Haidar; Buijs, Mark J.; Hedelin, Pamie; Pratten, Jonathan; Spratt, David; Daglia, Maria; Karbowiak, Aneta; Signoretto, Caterina; Rosema, Martijn; van der Weijden, Fridus; Wilson, Michael

2012-01-01

The main objective was to investigate whether low-molecular-weight fraction of edible mushroom shiitake extract (Lentinus edodes) possesses caries-preventive properties. The study was designed as a double-blind, three-leg, cross-over, randomized, controlled clinical trial carried out on two series of volunteers at the University of Gothenburg, and the Academic Centre for Dentistry Amsterdam. Volunteers rinsed twice daily with a solution containing low-molecular-weight fraction of edible mushroom, placebo (negative control without active ingredients), or Meridol (positive control, AmF-SnF2) for two weeks, with a two-week washout period between each rinsing period. Changes in the acidogenicity of dental plaque before and after a sucrose challenge, shifts in microbial composition, and plaque scores were determined. Frequent rinses with shiitake reduced the metabolic activity of dental plaque. No reduction of plaque scores and no inhibition of the production of organic acids in plaque was found. Minor differences in microbial composition between test sessions were found. To conclude, the results indicate that shiitake extract has anticariogenic potential, but not to the same extent as the positive control. PMID:22500081

Interventions to lower the glycemic response to carbohydrate foods with a low-viscosity fiber (resistant maltodextrin): meta-analysis of randomized controlled trials.

PubMed

Livesey, Geoffrey; Tagami, Hiroyuki

2009-01-01

The glycemic response to diet has been linked with noncommunicable diseases and is reduced by low-palatable, viscous, soluble fiber (1). Whether a palatable, low-viscous, soluble fiber such as resistant maltodextrin (RMD) has the same effect is unclear. The objective was to assess evidence on the attenuation of the blood glucose response to foods by < or = 10 g RMD in healthy adults. We conducted a systematic review of randomized, placebo-controlled trials with the use of fixed- and random-effects meta-analyses and meta-regression models. We found data from 37 relevant trials to April 2007. These trials investigated the attenuation of the glycemic response to rice, noodles, pastry, bread, and refined carbohydrates that included 30-173 g available carbohydrate. RMD was administered in drinks or liquid foods or solid foods. Placebo drinks and foods excluded RMD. Percentage attenuation was significant, dose-dependent, and independent of the amount of available carbohydrate coingested. Attenuation of the glycemic response to starchy foods by 6 g RMD in drinks approached approximately 20%, but when placed directly into foods was approximately 10% -- significant (P < 0.001) by both modes of administration. Study quality analyses, funnel plots, and trim-and-fill analyses uncovered no cause of significant systematic bias. Studies from authors affiliated with organizations for-profit were symmetrical without heterogeneity, whereas marginal asymmetry and significant heterogeneity arose among studies involving authors from nonprofit organizations because of some imprecise studies. A nonviscous palatable soluble polysaccharide can attenuate the glycemic response to carbohydrate foods. Evidence of an effect was stronger for RMD in drinks than in foods.

Experience and challenges presented by a multicenter crossover study of combination analgesic therapy for the treatment of painful HIV-associated polyneuropathies.

PubMed

Harrison, Taylor; Miyahara, Sachiko; Lee, Anthony; Evans, Scott; Bastow, Barbara; Simpson, David; Gilron, Ian; Dworkin, Robert; Daar, Eric S; Wieclaw, Linda; Clifford, David B

2013-07-01

There is limited evidence for efficacy of analgesics as monotherapy for neuropathic pain associated with HIV-associated polyneuropathies, in spite of demonstrated efficacy in other neuropathic pain conditions. We evaluated the tolerability and analgesic efficacy of duloxetine, methadone, and the combination of duloxetine-methadone compared with placebo. This study was a phase II, randomized, double-blind, placebo-controlled, four-period crossover multicenter study of analgesic therapy for patients with at least moderate neuropathic pain due to HIV-associated polyneuropathy. Duloxetine, methadone, combination duloxetine-methadone, and placebo were administered in four different possible sequences. The primary outcome measure was mean pain intensity (MPI) measured daily in a study-supplied pain diary. A total of 15 patients were enrolled from eight study sites and eight patients completed the entire trial. Study treatments failed to show statistically significant change in MPI compared with placebo. Adverse events were frequent and associated with high rates of drug discontinuation and study dropout. Challenges with participant recruitment and poor retention precluded trial completion to its planned targets, limiting our evaluation of the analgesic efficacy of the study treatments. Challenges to successful completion of this study and lessons learned are discussed. Wiley Periodicals, Inc.

Experience and challenges presented by a multicenter crossover study of combination analgesic therapy for the treatment of painful HIV-associated polyneuropathies

PubMed Central

Harrison, Taylor; Miyahara, Sachiko; Lee, Anthony; Evans, Scott; Bastow, Barbara; Simpson, David; Gilron, Ian; Dworkin, Robert; Daar, Eric S.; Wieclaw, Linda; Clifford, David B.

2014-01-01

Objective There is limited evidence for efficacy of analgesics as monotherapy for neuropathic pain associated with HIV-associated polyneuropathies, in spite of demonstrated efficacy in other neuropathic pain conditions. We evaluated the tolerability and analgesic efficacy of duloxetine, methadone, and the combination of duloxetine-methadone compared to placebo. Design This study was a phase II, randomized, double blind, placebo-controlled, four-period crossover multi-center study of analgesic therapy for patients with at least moderate neuropathic pain due to HIV-associated polyneuropathy. Duloxetine, methadone, combination duloxetine-methadone, and placebo were administered in four different possible sequences. The primary outcome measure was mean pain intensity (MPI) measured daily in a study-supplied pain diary. Results A total of 15 patients were enrolled from 8 study sites and 8 patients completed the entire trial. Study treatments failed to show statistically significant change in MPI compared to placebo. Adverse events were frequent and associated with high rates of drug discontinuation and study drop-out. Conclusions Challenges with participant recruitment and poor retention precluded trial completion to its planned targets, limiting our evaluation of the analgesic efficacy of the study treatments. Challenges to successful completion of this study and lessons learned are discussed. PMID:23565581

Short-term administration of the GLP-1 analog liraglutide decreases circulating leptin and increases GIP levels and these changes are associated with alterations in CNS responses to food cues: A randomized, placebo-controlled, crossover study

PubMed Central

Farr, Olivia M.; Tsoukas, Michael A.; Triantafyllou, Georgios; Dincer, Fadime; Filippaios, Andreas; Ko, Byung-Joon; Mantzoros, Christos S.

2016-01-01

Background GLP-1 agonists, including liraglutide, have emerged as effective therapies for type 2 diabetes (DM) and obesity. Here, we attempted to delineate how liraglutide, at doses approved for DM, may impact circulating hormones influencing energy homeostasis in diabetics. Basic Procedures Using a randomized, placebo-controlled, double-blind, cross-over trial of 20 patients with type 2 diabetes, we examined the effects of liraglutide as compared to placebo on fasting levels of circulating hormones important to energy homeostasis, including leptin, ghrelin, PYY, and GIP. After 17 days (0.6 mg for 7 days, 1.2 mg for 7 days and 1.8 mg for 3 days) of treatment, we also studied changes in fMRI responses to food cues. Main Findings By design, to avoid any confounding by weight changes, subjects were studied for 17 days, i.e. before body weight changed. Participants on liraglutide had significantly increased GLP-1 levels (p<0.001), decreased percent change in leptin levels (p<0.01) and increased GIP levels (p<0.03) in comparison to placebo treated subjects. Whole brain regressions of functional activity in response to food cues reveal that increased GIP levels were associated with deactivation of the attention- and reward-related insula. Decreases in leptin levels were associated with activations in the reward-related midbrain, precuneus, and dorsolateral prefrontal cortex (DLPFC), and sensorimotor-related motor cortex and with deactivations in the attention-related parietal cortex and the cognitive control-related thalamus and pre-SMA. Principal Conclusions We demonstrate herein short-term changes to circulating levels of GIP and leptin in response to GLP-1 agonist liraglutide therapy. These findings suggest that liraglutide may alter the circulating levels of hormones important in energy homeostasis that, in turn, influence CNS perception of food cues. This could possibly lead to compensatory changes in energy homeostasis that would over time limit the efficacy of liraglutide to decrease body weight. These novel findings, which, pointing to the potential advantages of combination therapies, may have therapeutic implications, will need to be confirmed by larger and longer-term trials. PMID:27282865

Casein-specific IL-4- and IL-13-secreting T cells: a tool to implement diagnosis of cow's milk allergy.

PubMed

Michaud, B; Aroulandom, J; Baiz, N; Amat, F; Gouvis-Echraghi, R; Candon, S; Foray, A-P; Couderc, R; Bach, J-F; Chatenoud, L; Just, J

2014-11-01

Cow's milk allergy (CMA) is a frequent food allergy in young children. The oral food challenge is the gold standard for diagnosis, and there is currently no reliable biological test. Our aim was to evaluate the diagnostic potential of a functional assay quantifying allergen-specific Th2 cells in CMA children. A total of 29 children aged 2.8-10.5 years underwent a double-blind, placebo-controlled food challenge (DBPCFC) to cow's milk. Blood was collected before performing the DBPCFC, and peripheral mononuclear cells were cultured in an 18-h ELISpot assay with casein, α-lactalbumin, or β-lactoglobulin. Numbers of antigen-specific IL-4- and IL-13-secreting lymphocytes and serum-specific IgE, IgG4, and total IgE levels were assessed. Receiver operating characteristic (ROC) curves were generated. A total of 17 (59%) children reacted to cow's milk and were therefore considered as allergic to cow's milk (CMA). The mean number of casein-specific IL-4- and IL-13-secreting T cells was higher in CMA than in non-CMA children (P = 0.009, 0.004, respectively). Moreover, it was inversely correlated with the cumulative dose of cow's milk tolerated (P = 0.003, 0.0009, respectively). ROC curve of combined IL-4 and IL-13 analysis showed an area under the curve of 0.98 (95% CI 0.90-1.06). For a cutoff of 10 IL-4- and 12 IL-13-secreting T cells, sensitivity and negative predictive value were 100%. Enumeration of casein-specific IL-4- and IL-13-secreting T cells appears a promising tool to improve diagnosis and, if confirmed in larger studies, could permit less frequent use of the oral food challenge. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Fish oil supplementation in pregnancy and lactation may decrease the risk of infant allergy.

PubMed

Furuhjelm, Catrin; Warstedt, Kristina; Larsson, Johanna; Fredriksson, Mats; Böttcher, Malin Fagerås; Fälth-Magnusson, Karin; Duchén, Karel

2009-09-01

Maternal intake of omega-3 (omega-3) polyunsaturated fatty acids (PUFAs) during pregnancy has decreased, possibly contributing to a current increased risk of childhood allergy. To describe the effects of maternal omega-3 long-chain PUFA supplementation during pregnancy and lactation on the incidence of allergic disease in infancy. One hundred and forty-five pregnant women, affected by allergy themselves or having a husband or previous child with allergies, were included in a randomized placebo-controlled trial. Daily maternal supplementation with either 1.6 g eicosapentaenoic acid and 1.1 g docosahexaenoic acid or placebo was given from the 25(th) gestational week to average 3-4 months of breastfeeding. Skin prick tests, detection of circulating specific immunoglobulin E (IgE) antibodies and clinical examinations of the infants were performed. The period prevalence of food allergy was lower in the omega-3 group (1/52, 2%) compared to the placebo group (10/65, 15%, p < 0.05) as well as the incidence of IgE-associated eczema (omega-3 group: 4/52, 8%; placebo group: 15/63, 24%, p < 0.05). Maternal omega-3 fatty acid supplementation may decrease the risk of food allergy and IgE-associated eczema during the first year of life in infants with a family history of allergic disease.

Testing a Low Molecular Mass Fraction of a Mushroom (Lentinus edodes) Extract Formulated as an Oral Rinse in a Cohort of Volunteers

PubMed Central

Signoretto, Caterina; Burlacchini, Gloria; Marchi, Anna; Grillenzoni, Marcello; Cavalleri, Giacomo; Ciric, Lena; Lingström, Peter; Pezzati, Elisabetta; Daglia, Maria; Zaura, Egija; Pratten, Jonathan; Spratt, David A.; Wilson, Michael; Canepari, Pietro

2011-01-01

Although foods are considered enhancing factors for dental caries and periodontitis, laboratory researches indicate that several foods and beverages contain components endowed with antimicrobial and antiplaque activities. A low molecular mass (LMM) fraction of an aqueous mushroom extract has been found to exert these activities in in vitro experiments against potential oral pathogens. We therefore conducted a clinical trial in which we tested an LMM fraction of shiitake mushroom extract formulated in a mouthrinse in 30 young volunteers, comparing the results with those obtained in two identical cohorts, one of which received water (placebo) and the other Listerine. Plaque index, gingival index and bacterial counts in plaque samples were determined in all volunteers over the 11 days of the clinical trial. Statistically significant differences (P < 0.05) were obtained for the plaque index on day 12 in subjects treated with mushroom versus placebo, while for the gingival index significant differences were found for both mushroom versus placebo and mushroom versus Listerine. Decreases in total bacterial counts and in counts of specific oral pathogens were observed for both mushroom extract and Listerine in comparison with placebo. The data suggest that a mushroom extract may prove beneficial in controlling dental caries and/or gingivitis/periodontitis. PMID:21912481

Effects of enzyme-treated asparagus extract on heat shock protein 70, stress indices, and sleep in healthy adult men.

PubMed

Ito, Tomohiro; Goto, Kazunori; Takanari, Jun; Miura, Takehito; Wakame, Koji; Nishioka, Hiroshi; Tanaka, Aiko; Nishihira, Jun

2014-01-01

Enzyme-treated asparagus extract (ETAS) has been developed as a novel anti-stress functional food ingredient that is produced from asparagus. Two human intervention trials with ETAS were conducted in healthy adult male volunteers. Study 1 was a randomized, double-blind, placebo-controlled study to assess the effects of ETAS on expression of heat shock protein 70 (HSP70) mRNA in blood and the autonomic nervous system (ANS). The ETAS group showed a tendency to enhance HSP70 mRNA expression level compared to the placebo group. Several ANS condition parameters were significantly improved in the ETAS group when compared to the placebo group. In Study 2, a randomized, double-blind, placebo-controlled, crossover trial investigated the influence on stress-related hormones and sleep. Serum and salivary cortisol levels were significantly elevated compared to baseline during the placebo period, but remained unchanged during the ETAS period. The salivary chromogranin A level was significantly decreased in the ETAS-treated subjects compared to their baseline levels. The actual sleep time was not significantly different between ETAS and placebo. However, when the subjects were divided into two categories based on sleep efficiency or the average of night sleeping time, ETAS intake was effective to modulate the sleep state among those with low sleep efficiency or excess sleep time.

Ara h 2 and Ara 6 are the best predictors of severe peanut allergy: a double-blind placebo-controlled study.

PubMed

Kukkonen, A K; Pelkonen, A S; Mäkinen-Kiljunen, S; Voutilainen, H; Mäkelä, M J

2015-10-01

Component-resolved diagnostics offers a modern tool in peanut allergy, but studies applying consistently double-blind placebo-controlled challenges are lacking. We aimed to optimize diagnostics for moderate-to-severe peanut allergy in a birch-endemic region and to create an oral-peanut challenge with its allergen activity characterized. We performed double-blind placebo-controlled peanut challenges for a referred sample of 6- to 18-year-olds with peanut sensitization or a high suspicion of peanut allergy, including anaphylaxis. We measured specific IgE (sIgE) to Ara h 1, 2, 3, 6, 8, and 9. Testing of allergen activity of the challenge products was by IgE microarray inhibition. Of the 102 patients, 69 were challenge positive: 25 (36%) had severe, 36 (52%) moderate, and 8 (12%) mild symptoms; 38 (37%) received adrenalin. SIgE to Ara h 6 AUC 0.98 (95%CI, 0.96-1.00) was the best marker of moderate-to-severe allergy. When sIgE to Ara h 2 and Ara h 6 was measured together, all (100%) severe reactions at low doses were successfully diagnosable. SIgE to Ara h 8 had no diagnostic value, AUC 0.42 (95%CI, 0.30-0.52). Both nonroasted and roasted peanut inhibited 100% of IgE binding to Ara h 1, 2, 3, and 6. Nonroasted peanut inhibited 87% of IgE binding to Ara h 8, roasted inhibited 30%. The products lacked Ara h 9 activity. Co-sensitization to Ara h 2 and Ara h 6 was associated with severe reactions distinguishing severe allergy from mild symptoms. SIgE to Ara h 8 added no diagnostic value. Component-resolved diagnostics reduce the need for oral challenges in peanut allergy. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A diet containing whey protein, glutamine, and TGFbeta modulates gut protein metabolism during chemotherapy-induced mucositis in rats.

PubMed

Boukhettala, Nabile; Ibrahim, Ayman; Claeyssens, Sophie; Faure, Magali; Le Pessot, Florence; Vuichoud, Jacques; Lavoinne, Alain; Breuillé, Denis; Déchelotte, Pierre; Coëffier, Moïse

2010-08-01

Mucositis, a common side effect of chemotherapy, is characterized by compromised digestive function, barrier integrity and immune competence. Our aim was to evaluate the impact of a specifically designed diet Clinutren Protect (CP), which contains whey proteins, TGFbeta-rich casein, and free glutamine, on mucositis in rats. Mucositis was induced by three consecutive injections (day 0, day 1, day 2) of methotrexate (2.5 mg/kg). Rats had free access to CP or placebo diets from days -7 to 9. In the placebo diet, whey proteins and TGFbeta-rich casein were replaced by TGFbeta-free casein and glutamine by alanine. Intestinal parameters were assessed at day 3 and 9. Values, expressed as mean +/- SEM, were compared using two-way ANOVA. At day 3, villus height was markedly decreased in the placebo (296 +/- 11 microm) and CP groups (360 +/- 10 microm) compared with controls (464 +/- 27 microm), but more markedly in the placebo as compared to CP group. The intestinal damage score was also reduced in the CP compared with the placebo group. Glutathione content increased in the CP compared with the placebo group (2.2 +/- 0.2 vs. 1.7 +/- 0.2 micromol/g tissue). Gut protein metabolism was more affected in the placebo than in the CP group. The fractional synthesis rate was decreased in the placebo group (93.8 +/- 4.9%/day) compared with controls (121.5 +/- 12.1, P < 0.05), but not in the CP group (106.0 +/- 13.1). In addition, at day 9, rats exhibited improved body weight and food intake recovery in the CP compared to the placebo group. Clinutren Protect feeding reduces intestinal injury in the acute phase of methotrexate-induced mucositis in rats and improves recovery.

Comparing oxytocin and cortisol regulation in a double-blind, placebo-controlled, hydrocortisone challenge pilot study in children with autism and typical development.

PubMed

Corbett, Blythe A; Bales, Karen L; Swain, Deanna; Sanders, Kevin; Weinstein, Tamara A R; Muglia, Louis J

2016-01-01

Children with autism spectrum disorder (ASD) show marked impairment in social functioning and poor adaptation to new and changing contexts, which may be influenced by underlying regulatory processes. Oxytocin (OT) and cortisol are key neuromodulators of biological and behavioral responses, show a synergistic effect, and have been implicated in the neuropathological profile in ASD. However, they are rarely investigated together. The purpose of the pilot study was to evaluate the relationship between cortisol and OT in children with ASD under baseline and physiological stress (hydrocortisone challenge) conditions. Arginine vasopressin (AVP), structurally similar to OT, was also examined. A double-blind, placebo-controlled, randomly assigned, crossover design was employed in 25 children 8-to-12 years with ASD (N = 14) or typical development (TD, N = 11). A low dose of hydrocortisone and placebo were administered via liquid suspension. Analysis of variance (ANOVA) was used to examine the within-subject factor "Condition" (hydrocortisone/placebo) and "Time" (pre and post) and the between-subject factor "Group" (ASD vs. TD). Pearson correlations examined the relationship between hormone levels and clinical profile. There was a significant Time × Condition × Group interaction F (1.23) = 4.18, p = 0.05 showing a rise in OT during the experimental condition (hydrocortisone) and a drop during the placebo condition for the TD group but not the ASD group. There were no group differences for AVP. Hormone levels were associated with social profiles. For the TD group, an inverse relationship was observed. OT increased during physiological challenge suggesting that OT played a stress-buffering role during cortisol administration. In contrast for the ASD group, OT remained unchanged or decreased during both the physiological challenge and the placebo condition, suggesting that OT failed to serve as a stress buffer under conditions of physiological stress. While OT has been tied to the social ability of children with ASD, the diminished moderating effect of OT on cortisol may also play a contributory role in the heightened stress often observed in children with ASD. These results contribute to our understanding of the growing complexity of the effects of OT on social behavior as well as the functional interplay and differential regulation OT may have on stress modulation.

Developing a placebo-controlled trial in surgery: issues of design, acceptability and feasibility.

PubMed

Campbell, M K; Entwistle, V A; Cuthbertson, B H; Skea, Z C; Sutherland, A G; McDonald, A M; Norrie, J D; Carlson, R V; Bridgman, S

2011-02-21

Surgical placebos are controversial. This in-depth study explored the design, acceptability, and feasibility issues relevant to designing a surgical placebo-controlled trial for the evaluation of the clinical and cost effectiveness of arthroscopic lavage for the management of people with osteoarthritis of the knee in the UK. Two surgeon focus groups at a UK national meeting for orthopaedic surgeons and one regional surgeon focus group (41 surgeons); plenary discussion at a UK national meeting for orthopaedic anaesthetists (130 anaesthetists); three focus groups with anaesthetists (one national, two regional; 58 anaesthetists); two focus groups with members of the patient organisation Arthritis Care (7 participants); telephone interviews with people on consultant waiting lists from two UK regional centres (15 participants); interviews with Chairs of UK ethics committees (6 individuals); postal surveys of members of the British Association of Surgeons of the Knee (382 surgeons) and members of the British Society of Orthopaedic Anaesthetists (398 anaesthetists); two centre pilot (49 patients assessed). There was widespread acceptance that evaluation of arthroscopic lavage had to be conducted with a placebo control if scientific rigour was not to be compromised. The choice of placebo surgical procedure (three small incisions) proved easier than the method of anaesthesia (general anaesthesia). General anaesthesia, while an excellent mimic, was more intrusive and raised concerns among some stakeholders and caused extensive discussion with local decision-makers when seeking formal approval for the pilot.Patients were willing to participate in a pilot with a placebo arm; although some patients when allocated to surgery became apprehensive about the possibility of receiving placebo, and withdrew. Placebo surgery was undertaken successfully. Our study illustrated the opposing and often strongly held opinions about surgical placebos, the ethical issues underpinning this controversy, and the challenges that exist even when ethics committee approval has been granted. It showed that a placebo-controlled trial could be conducted in principle, albeit with difficulty. It also highlighted that not only does a placebo-controlled trial in surgery have to be ethically and scientifically acceptable but that it also must be a feasible course of action. The place of placebo-controlled surgical trials more generally is likely to be limited and require specific circumstances to be met. Suggested criteria are presented. The trial was assigned ISRCTN02328576 through http://controlled-trials.com/ in June 2006. The first patient was randomised to the pilot in July 2007.

Developing a placebo-controlled trial in surgery: Issues of design, acceptability and feasibility

PubMed Central

2011-01-01

Background Surgical placebos are controversial. This in-depth study explored the design, acceptability, and feasibility issues relevant to designing a surgical placebo-controlled trial for the evaluation of the clinical and cost effectiveness of arthroscopic lavage for the management of people with osteoarthritis of the knee in the UK. Methods Two surgeon focus groups at a UK national meeting for orthopaedic surgeons and one regional surgeon focus group (41 surgeons); plenary discussion at a UK national meeting for orthopaedic anaesthetists (130 anaesthetists); three focus groups with anaesthetists (one national, two regional; 58 anaesthetists); two focus groups with members of the patient organisation Arthritis Care (7 participants); telephone interviews with people on consultant waiting lists from two UK regional centres (15 participants); interviews with Chairs of UK ethics committees (6 individuals); postal surveys of members of the British Association of Surgeons of the Knee (382 surgeons) and members of the British Society of Orthopaedic Anaesthetists (398 anaesthetists); two centre pilot (49 patients assessed). Results There was widespread acceptance that evaluation of arthroscopic lavage had to be conducted with a placebo control if scientific rigour was not to be compromised. The choice of placebo surgical procedure (three small incisions) proved easier than the method of anaesthesia (general anaesthesia). General anaesthesia, while an excellent mimic, was more intrusive and raised concerns among some stakeholders and caused extensive discussion with local decision-makers when seeking formal approval for the pilot. Patients were willing to participate in a pilot with a placebo arm; although some patients when allocated to surgery became apprehensive about the possibility of receiving placebo, and withdrew. Placebo surgery was undertaken successfully. Conclusions Our study illustrated the opposing and often strongly held opinions about surgical placebos, the ethical issues underpinning this controversy, and the challenges that exist even when ethics committee approval has been granted. It showed that a placebo-controlled trial could be conducted in principle, albeit with difficulty. It also highlighted that not only does a placebo-controlled trial in surgery have to be ethically and scientifically acceptable but that it also must be a feasible course of action. The place of placebo-controlled surgical trials more generally is likely to be limited and require specific circumstances to be met. Suggested criteria are presented. Trial registration number The trial was assigned ISRCTN02328576 through http://controlled-trials.com/ in June 2006. The first patient was randomised to the pilot in July 2007. PMID:21338481

A Review of Pomegranate in Prostate Cancer

PubMed Central

Paller, Channing J.; Pantuck, Allan; Carducci, Michael A.

2017-01-01

Background Preclinical studies showing that pomegranate juice and its components inhibit prostate cancer led to multiple clinical trials to determine whether pomegranate products could slow the growth of prostate cancer. This review summarizes the preclinical data and discusses the results of the clinical trials. Methods Trials targeted patients on active surveillance, neoadjuvant patients, patients with biochemical recurrence (BCR) following local therapy for prostate cancer, and patients with metastatic castration-resistant prostate cancer (mCRPC). Results In the BCR patient population, early phase II trials of both pomegranate juice and extract showed significant lengthening of PSA doubling time (PSADT), and confirmed the safety of pomegranate products. While a placebo-controlled phase III trial determined that pomegranate extract did not significantly prolong PSADT in BCR patients, a preplanned subset analysis of patients with the manganese superoxide dismutase (MnSOD) AA genotype showed greater PSADT lengthening on the pomegranate extract arm. In the neoadjuvant population, a large trial demonstrated a significant increase in urolithin A and a non-significant reduction in 8-OHdG, a marker of oxidation in prostate cancer tissue, on the pomegranate arm vs. the placebo arm. In addition, a randomized clinical trial of a polyphenol-rich multi-component food supplement tablet, including 31.25% pomegranate extract, found significant slowing of PSA increase in the food supplement arm vs. placebo in men on active surveillance and those experiencing biochemical recurrence. Conclusions Pomegranate juice and extract are safe but did not significantly improve outcomes in BCR patients in a large placebo controlled trial. However a subset of BCR patients with the MnSOD AA genotype appear to respond positively to the antioxidant effects of pomegranate treatment. Phase II trials of 100% pomegranate products in neoadjuvant patients and patients with mCRPC were negative. A multi-component food supplement showed promising results in a phase II study in active surveillance and BCR patients. PMID:28440320

A review of pomegranate in prostate cancer.

PubMed

Paller, C J; Pantuck, A; Carducci, M A

2017-09-01

Preclinical studies showing that pomegranate juice and its components inhibit prostate cancer led to multiple clinical trials to determine whether pomegranate products could slow the growth of prostate cancer. This review summarizes the preclinical data and discusses the results of the clinical trials. Trials targeted patients on active surveillance, neoadjuvant patients, patients with biochemical recurrence (BCR) following local therapy for prostate cancer, and patients with metastatic castration-resistant prostate cancer (mCRPC). In the BCR patient population, early phase II trials of both pomegranate juice and extract showed significant lengthening of PSA doubling time (PSADT), and confirmed the safety of pomegranate products. While a placebo-controlled phase III trial determined that pomegranate extract did not significantly prolong PSADT in BCR patients, a preplanned subset analysis of patients with the manganese superoxide dismutase (MnSOD) AA genotype showed greater PSADT lengthening on the pomegranate extract arm. In the neoadjuvant population, a large trial demonstrated a significant increase in urolithin A and a non-significant reduction in 8-hydroxy-2-deoxyguanosine, a marker of oxidation in prostate cancer tissue, on the pomegranate arm vs the placebo arm. In addition, a randomized clinical trial of a polyphenol-rich multicomponent food supplement that included a 31.25% pomegranate extract found significant slowing of PSA increase in the food supplement arm vs placebo in men on active surveillance and those experiencing BCR. Pomegranate juice and extract are safe but did not significantly improve outcomes in BCR patients in a large placebo-controlled trial. However a subset of BCR patients with the MnSOD AA genotype appear to respond positively to the antioxidant effects of pomegranate treatment. Phase II trials of 100% pomegranate products in neoadjuvant patients and patients with mCRPC were negative. A multicomponent food supplement showed promising results in a phase II study in active surveillance and BCR patients.

The Safety of Flavocoxid, a Medical Food, in the Dietary Management of Knee Osteoarthritis

PubMed Central

Baggott, Joseph E.; Moreland, Larry; Desmond, Renee; Kendrach, Angela C.

2009-01-01

Abstract This study was designed to determine the safety of a medical food, flavocoxid, a proprietary blend of free-B ring flavonoids and flavans from the root of Scutellaria baicalensis (Chinese skullcap) and the bark of Acacia catechu in the dietary management of knee osteoarthritis. The 12-week, randomized, double-blind, placebo-controlled trial in an academic medical center enrolled 59 patients with moderate osteoarthritis of at least one knee who were recruited who were classified as having “below average” to “a moderately above average cardiovascular risk” with a Framingham-based scoring tool. Subjects were randomized to flavocoxid 250 mg twice a day versus identical placebo. Safety measures, including recording of adverse events, incidence of serious adverse events, and results of routine laboratory values, were compared between the two groups. There were no major differences in the baseline demographic characteristics of the placebo and flavocoxid groups. With one exception no significant differences were found between the two groups with respect to adverse events by body system, blood pressure, or laboratory values. There was a significantly higher incidence of upper respiratory adverse events in the placebo group (35.4% vs. 5.8%, P = .0003). There were no intra- or inter-group differences in any of the laboratory parameters from study baseline to completion. Thus, flavocoxid is safe when used in a population with “below average” to “moderately above average cardiovascular risk” compared to placebo. PMID:19857081

Saturated fat -a never ending story?

PubMed

Svendsen, Karianne; Arnesen, Erik; Retterstøl, Kjetil

2017-01-01

Science has no clear message regarding health effects of saturated fats, it seems. Different RCTs, prospective cohort studies and meta-analysis have led to contrasting conclusions. The aim of the present commentary is to discuss some possible reasons for an apparently never-ending fat controversy. They are of a purely scientific nature, which is important to recognize, but unfortunately hard to overcome. First is the placebo problem. In pharmaceutical science, evidence-based medicine is often synonymous with data on verified medical events from long-lasting double-blind randomized placebo controlled trials. In nutritional science the lack of double-blind design and lack of placebo food generate less conclusive data than those achieved in pharmaceutical science. Some scientists may apply the same type of scientific criteria used to evaluate the effects of drugs for foods. This leaves an impression of insufficient data since in this respect the fundamental criteria for evidence based medicine are not present. The next scientific problem is the energy balance equation. In contrast to pharmaceuticals, nutrients contain energy. An increased intake of one nutrient will lead to a decreased intake of another. The effect of change in only one nutrient is then difficult to isolate. Lastly, in nutritional science, generalizability is difficult compared to pharmaceutical science. Food culture interferes with lifestyle and food habits change over time. In conclusion, all available knowledge, from molecular experiments to population studies, must be taken in to account, to convert scientific data into dietary recommendations.

Diet and ADHD, Reviewing the Evidence: A Systematic Review of Meta-Analyses of Double-Blind Placebo-Controlled Trials Evaluating the Efficacy of Diet Interventions on the Behavior of Children with ADHD.

PubMed

Pelsser, Lidy M; Frankena, Klaas; Toorman, Jan; Rodrigues Pereira, Rob

2017-01-01

Attention-deficit/hyperactivity disorder (ADHD) is a debilitating mental health problem hampering the child's development. The underlying causes include both genetic and environmental factors and may differ between individuals. The efficacy of diet treatments in ADHD was recently evaluated in three reviews, reporting divergent and confusing conclusions based on heterogeneous studies and subjects. To address this inconsistency we conducted a systematic review of meta-analyses of double-blind placebo-controlled trials evaluating the effect of diet interventions (elimination and supplementation) on ADHD. Our literature search resulted in 14 meta-analyses, six of which confined to double-blind placebo-controlled trials applying homogeneous diet interventions, i.e. artificial food color (AFC) elimination, a few-foods diet (FFD) and poly-unsaturated fatty acid (PUFA) supplementation. Effect sizes (ES) and Confidence intervals (CI) of study outcomes were depicted in a forest plot. I2 was calculated to assess heterogeneity if necessary and additional random effects subgroup meta-regression was conducted if substantial heterogeneity was present. The AFC ESs were 0.44 (95% CI: 0.16-0.72, I2 = 11%) and 0.21 (95% CI: -0.02-0.43, I2 = 68%) [parent ratings], 0.08 (95% CI: -0.07-0.24, I2 = 0%) [teacher ratings] and 0.11 (95% CI: -0.13-0.34, I2 = 12%) [observer ratings]. The FFD ESs were 0.80 (95% CI: 0.41-1.19, I2 = 61%) [parent ratings] and 0.51 (95% CI: -0.02-1.04, I2 = 72%) [other ratings], while the PUFA ESs were 0.17 (95% CI: -0.03-0.38, I2 = 38%) [parent ratings], -0.05 (95% CI: -0.27-0.18, I2 = 0%) [teacher ratings] and 0.16 (95% CI: 0.01-0.31, I2 = 0%) [parent and teacher ratings]. Three meta-analyses (two FFD and one AFC) resulted in high I2 without presenting subgroup results. The FFD meta-analyses provided sufficient data to perform subgroup analyses on intervention type, resulting in a decrease of heterogeneity to 0% (diet design) and 37.8% (challenge design). Considering the small average ESs PUFA supplementation is unlikely to provide a tangible contribution to ADHD treatment, while further research is required for AFC elimination before advising this intervention as ADHD treatment. The average FFD ES is substantial, offering treatment opportunities in subgroups of children with ADHD not responding to or too young for medication. Further FFD research should focus on establishing the underlying mechanisms of food (e.g. incrimination of gut microbiota) to simplify the FFD approach in children with ADHD.

The effect of vilazodone on sexual function during the treatment of major depressive disorder.

PubMed

Clayton, Anita H; Kennedy, Sidney H; Edwards, John B; Gallipoli, Susan; Reed, Carol R

2013-10-01

  Sexual dysfunction is common in major depressive disorder (MDD), and many serotonergic antidepressants adversely affect sexual function. Vilazodone, a novel serotonin (5-HT) reuptake inhibitor and 5-HT1A partial agonist approved for MDD, exerts its effects at the 5-HT transporter and at both presynaptic and postsynaptic 5-HT1A receptors. This mechanism may limit sexual dysfunction.   To summarize effects of vilazodone (40 mg/day, with food) on sexual function in adults with MDD.   Data sources were three Phase III studies: two 8-week, placebo-controlled studies (NCT00285376 and NCT00683592) and a 52-week open-label study (NCT00644358). Sexual function was assessed by analyzing changes from baseline to end of treatment (EOT) using validated measures.   Arizona Sexual Experience Scale or Changes in Sexual Functioning Questionnaire.   Population included 869 patients (vilazodone, 436; placebo, 433) from placebo-controlled studies and 599 patients from the open-label study. Sexual dysfunction prevalence was high (50%, men; 68%, women) before treatment and declined during treatment in vilazodone and placebo groups, indicating improvement on average. At EOT, stable/improved sexual function was observed in ≥91% of patients in placebo-controlled studies; treatment group differences in sexual dysfunction at EOT were not statistically significant for either sex. Differences vs. placebo in changes from baseline of sexual function scores were small and were generally not statistically significant; effect sizes (Cohen's D) were generally of low magnitude. In the placebo-controlled studies, 8.0% of vilazodone-treated patients and 0.9% of placebo-treated patients reported ≥1 sexual-function-related treatment-emergent adverse event (P<0.001).   Half of men and two thirds of women with MDD had sexual dysfunction at baseline; sexual function improved on average in both vilazodone and placebo groups. Results suggest that vilazodone may have a small adverse impact on sexual function in adults with MDD relative to the high prevalence of sexual dysfunction at baseline. © 2012 International Society for Sexual Medicine.

Prophylactic Efficacy of Hyperimmune Bovine Colostral Antiadhesin Antibodies Against Enterotoxigenic Escherichia coli Diarrhea: A Randomized, Double-Blind, Placebo-Controlled, Phase 1 Trial.

PubMed

Savarino, Stephen J; McKenzie, Robin; Tribble, David R; Porter, Chad K; O'Dowd, Aisling; Cantrell, Joyce A; Sincock, Stephanie A; Poole, Steven T; DeNearing, Barbara; Woods, Colleen M; Kim, Hye; Grahek, Shannon L; Brinkley, Carl; Crabb, Joseph H; Bourgeois, A Louis

2017-07-01

Tip-localized adhesive proteins of bacterial fimbriae from diverse pathogens confer protection in animal models, but efficacy in humans has not been reported. Enterotoxigenic Escherichia coli (ETEC) commonly elaborate colonization factors comprising a minor tip adhesin and major stalk-forming subunit. We assessed the efficacy of antiadhesin bovine colostral IgG (bIgG) antibodies against ETEC challenge in volunteers. Adults were randomly assigned (1:1:1) to take oral hyperimmune bIgG raised against CFA/I minor pilin subunit (CfaE) tip adhesin or colonization factor I (CFA/I) fimbraie (positive control) or placebo. Two days before challenge, volunteers began a thrice-daily, 7-day course of investigational product administered in sodium bicarbonate 15 minutes after each meal. On day 3, subjects drank 1 × 109 colony-forming units of colonization factor I (CFA/I)-ETEC strain H10407 with buffer. The primary efficacy endpoint was diarrhea within 120 hours of challenge. After enrollment and randomization, 31 volunteers received product, underwent ETEC challenge, and were included in the per protocol efficacy analysis. Nine of 11 placebos developed diarrhea, 7 experiencing moderate to severe disease. Protective efficacy of 63% (P = .03) and 88% (P = .002) was observed in the antiadhesin bIgG and positive control groups, respectively. Oral administration of anti-CFA/I minor pilin subunit (CfaE) antibodies conferred significant protection against ETEC, providing the first clinical evidence that fimbrial tip adhesins function as protective antigens. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Effect of probiotic on innate inflammatory response and viral shedding in experimental rhinovirus infection - a randomised controlled trial.

PubMed

Turner, R B; Woodfolk, J A; Borish, L; Steinke, J W; Patrie, J T; Muehling, L M; Lahtinen, S; Lehtinen, M J

2017-04-26

Ingestion of probiotics appears to have modest effects on the incidence of viral respiratory infection. The mechanism of these effects is not clear; however, there is evidence from animal models that the probiotic may have an effect on innate immune responses to pathogens. The purpose of this randomised, placebo-controlled study was to determine the effect of administration of Bifidobacterium animalis subspecies lactis Bl-04 on innate and adaptive host responses to experimental rhinovirus challenge. The effect on the response of chemokine (C-X-C motif) ligand 8 (CXCL8) to rhinovirus infection was defined as the primary endpoint for the study. 152 seronegative volunteers who had been supplemented for 28 days, 73 with probiotic and 79 with placebo, were challenged with RV-A39. Supplement or placebo administration was then continued for five days during collection of specimens for assessment of host response, infection, and symptoms. 58 probiotic and 57 placebo-supplemented volunteers met protocol-defined criteria for analysis. Probiotic resulted in higher nasal lavage CXCL8 on day 0 prior to virus challenge (90 vs 58 pg/ml, respectively, P=0.04, ANCOVA). The CXCL8 response to rhinovirus infection in nasal lavage was significantly reduced in the probiotic treated group (P=0.03, ANCOVA). Probiotic was also associated with a reduction in nasal lavage virus titre and the proportion of subjects shedding virus in nasal secretions (76% in the probiotic group, 91% in the placebo group, P=0.04, Fisher Exact test). The administration of probiotic did not influence lower respiratory inflammation (assessed by exhaled nitric oxide), subjective symptom scores, or infection rate. This study demonstrates that ingestion of Bl-04 may have an effect on the baseline state of innate immunity in the nose and on the subsequent response of the human host to rhinovirus infection. Clinicaltrials.gov registry number: NCT01669603.

Investigations of botanicals on food intake, satiety, weight loss and oxidative stress: study protocol of a double-blind, placebo-controlled, crossover study.

PubMed

Anton, Stephen D; Shuster, Jonathan; Leeuwenburgh, Christiaan

2011-11-01

Botanicals represent an important and underexplored source of potential new therapies that may facilitate caloric restriction and thereby may produce long-term weight loss. In particular, one promising botanical that may reduce food intake and body weight by affecting neuroendocrine pathways related to satiety is hydroxycitric acid (HCA) derived from Garcinia cambogia Desr. The objective of this article is to describe the protocol of a clinical trial designed to directly test the effects of Garcinia cambogia-derived HCA on food intake, satiety, weight loss and oxidative stress levels, and to serve as a model for similar trials. A total of 48 healthy, overweight or obese individuals (with a body mass index range of 25.0 to 39.9 kg/m(2)) between the ages of 50 to 70 will participate in this double-blind, placebo-controlled, crossover study designed to examine the effects of two doses of Garcinia cambogia-derived HCA on food intake, satiety, weight loss, and oxidative stress levels. Food intake represents the primary outcome measure and is calculated based on the total calories consumed at breakfast, lunch, and dinner meals during each test meal day. This study can be completed with far fewer subjects than a parallel design. Of the numerous botanical compounds, the compound Garcinia cambogia-derived HCA is selected for testing in the present study because of its potential to safely reduce food intake, body weight, and oxidative stress levels. We will review potential mechanisms of action and safety parameters throughout this clinical trial. ClinicalTrials.gov (Identifier: NCT01238887).

Potential food allergens in wine: double-blind, placebo-controlled trial and basophil activation analysis.

PubMed

Rolland, Jennifer M; Apostolou, Effie; Deckert, Kirsten; de Leon, Maria P; Douglass, Jo A; Glaspole, Ian N; Bailey, Michael; Stockley, Creina S; O'Hehir, Robyn E

2006-09-01

Recent Australian and international legislation requires labeling of wines made by using the potentially allergenic food proteins casein, milk, egg white, or isinglass (fish-derived) where "there is a detectable residual processing aid." We investigated whether wines fined using these proteins or non-grape-derived tannins (tree-nut derived) can provoke significant clinical allergic reactions (anaphylaxis) in patients with confirmed immunoglobulin E-mediated relevant food allergy. A double-blind, placebo-controlled trial was performed to determine whether allergic reactions followed consumption of Australian commercial wines fined using one or more of the legislation-targeted food proteins. In addition, allergenicity of a larger panel of these wines was evaluated by blood basophil activation. No anaphylaxis was induced by wine consumption. Three mild clinical reactions to protein-fined wine and two mild reactions to unfined wine occurred, but there was no statistically significant difference in reaction parameters between subject groups or between processing aids. No pattern of basophil activation correlated with wine type, processing aid, or subject group. Wines fined with egg white, isinglass, or non-grape-derived tannins present an extremely low risk of anaphylaxis to fish-, egg-, or peanut-allergic consumers. Although consumption of milk protein-fined wine did not induce anaphylaxis, there were insufficient subjects to determine statistically whether wines fined with milk proteins present a risk to the very rare milk-allergic consumers. In summary, the observed lack of anaphylaxis and basophil activation induced by wines made using the legislation-targeted food proteins according to good manufacturing practice suggests negligible residual food allergens in these wines.

Lorcaserin Administration Decreases Activation of Brain Centers in Response to Food Cues and These Emotion- and Salience-Related Changes Correlate With Weight Loss Effects: A 4-Week-Long Randomized, Placebo-Controlled, Double-Blind Clinical Trial.

PubMed

Farr, Olivia M; Upadhyay, Jagriti; Gavrieli, Anna; Camp, Michelle; Spyrou, Nikolaos; Kaye, Harper; Mathew, Hannah; Vamvini, Maria; Koniaris, Anastasia; Kilim, Holly; Srnka, Alexandra; Migdal, Alexandra; Mantzoros, Christos S

2016-10-01

Lorcaserin is a serotonin 5-hydroxytryptamine 2c receptor agonist effective in treating obesity. Studies in rodents have shown that lorcaserin acts in the brain to exert its weight-reducing effects, but this has not yet been studied in humans. We performed a randomized, placebo-controlled, double-blind trial with 48 obese participants and used functional MRI to study the effects of lorcaserin on the brain. Subjects taking lorcaserin had decreased brain activations in the attention-related parietal and visual cortices in response to highly palatable food cues at 1 week in the fasting state and in the parietal cortex in response to any food cues at 4 weeks in the fed state. Decreases in emotion- and salience-related limbic activity, including the insula and amygdala, were attenuated at 4 weeks. Decreases in caloric intake, weight, and BMI correlated with activations in the amygdala, parietal, and visual cortices at baseline. These data suggest that lorcaserin exerts its weight-reducing effects by decreasing attention-related brain activations to food cues (parietal and visual cortices) and emotional and limbic activity (insula, amygdala). Results indicating that baseline activation of the amygdala relates to increased efficacy suggest that lorcaserin would be of particular benefit to emotional eaters. © 2016 by the American Diabetes Association.

Lorcaserin Administration Decreases Activation of Brain Centers in Response to Food Cues and These Emotion- and Salience-Related Changes Correlate With Weight Loss Effects: A 4-Week-Long Randomized, Placebo-Controlled, Double-Blind Clinical Trial

PubMed Central

Farr, Olivia M.; Upadhyay, Jagriti; Gavrieli, Anna; Camp, Michelle; Spyrou, Nikolaos; Kaye, Harper; Mathew, Hannah; Vamvini, Maria; Koniaris, Anastasia; Kilim, Holly; Srnka, Alexandra; Migdal, Alexandra

2016-01-01

Lorcaserin is a serotonin 5-hydroxytryptamine 2c receptor agonist effective in treating obesity. Studies in rodents have shown that lorcaserin acts in the brain to exert its weight-reducing effects, but this has not yet been studied in humans. We performed a randomized, placebo-controlled, double-blind trial with 48 obese participants and used functional MRI to study the effects of lorcaserin on the brain. Subjects taking lorcaserin had decreased brain activations in the attention-related parietal and visual cortices in response to highly palatable food cues at 1 week in the fasting state and in the parietal cortex in response to any food cues at 4 weeks in the fed state. Decreases in emotion- and salience-related limbic activity, including the insula and amygdala, were attenuated at 4 weeks. Decreases in caloric intake, weight, and BMI correlated with activations in the amygdala, parietal, and visual cortices at baseline. These data suggest that lorcaserin exerts its weight-reducing effects by decreasing attention-related brain activations to food cues (parietal and visual cortices) and emotional and limbic activity (insula, amygdala). Results indicating that baseline activation of the amygdala relates to increased efficacy suggest that lorcaserin would be of particular benefit to emotional eaters. PMID:27385157

Antipsychotic-induced insulin resistance and postprandial hormonal dysregulation independent of weight gain or psychiatric disease.

PubMed

Teff, Karen L; Rickels, Michael R; Grudziak, Joanna; Fuller, Carissa; Nguyen, Huong-Lan; Rickels, Karl

2013-09-01

Atypical antipsychotic (AAP) medications that have revolutionized the treatment of mental illness have become stigmatized by metabolic side effects, including obesity and diabetes. It remains controversial whether the defects are treatment induced or disease related. Although the mechanisms underlying these metabolic defects are not understood, it is assumed that the initiating pathophysiology is weight gain, secondary to centrally mediated increases in appetite. To determine if the AAPs have detrimental metabolic effects independent of weight gain or psychiatric disease, we administered olanzapine, aripiprazole, or placebo for 9 days to healthy subjects (n = 10, each group) under controlled in-patient conditions while maintaining activity levels. Prior to and after the interventions, we conducted a meal challenge and a euglycemic-hyperinsulinemic clamp to evaluate insulin sensitivity and glucose disposal. We found that olanzapine, an AAP highly associated with weight gain, causes significant elevations in postprandial insulin, glucagon-like peptide 1 (GLP-1), and glucagon coincident with insulin resistance compared with placebo. Aripiprazole, an AAP considered metabolically sparing, induces insulin resistance but has no effect on postprandial hormones. Importantly, the metabolic changes occur in the absence of weight gain, increases in food intake and hunger, or psychiatric disease, suggesting that AAPs exert direct effects on tissues independent of mechanisms regulating eating behavior.

Cutaneous irritancy of an ibuprofen medicated plaster in healthy volunteers.

PubMed

Maganji, Manisha; Connolly, Mark P; Bhatt, Aomesh

2018-04-01

To assess the irritation and contact sensitization potential of a 200 mg ibuprofen medicated plaster. This double-blind, phase-1 placebo controlled study had two phases; the induction phase to evaluate the irritant potential of continuous application of the plaster, and the challenge phase to assess contact sensitivity (allergy). The cumulative irritancy potential was evaluated using an adaptation of the Shelanski method. Healthy adults (≥18 years of age) (N = 210) were treated simultaneously with one ibuprofen medicated and one placebo plaster applied in a randomized fashion to either the left or right side of the lower back. During the induction phase, plasters were applied on Days 1, 3, 5, 8, 10, 12, 15, 17, and 19 and the final plaster removed on Day 22. At each scheduled visit plasters and applications sites were assessed for degree of adhesion and skin irritation (score of 1 = no irritation to 7 = strong reaction spreading beyond test sites), respectively. The challenge phase followed a two-week washout period. A plaster was applied on Day 36 for 48 h and assessment occurred on Days 38, 39, and 40. The mean cumulative irritation score during the induction phase was lower for the ibuprofen medicated plaster than the placebo plaster (0.32 vs. 1.23, respectively). Three (1.4%) subjects experience a dermal reaction of grade ≥3 for the ibuprofen medicated plaster compared with 27 (12.7%) for the placebo plaster. Following challenge with ibuprofen or placebo plasters, 12 subjects (6.2%) with the ibuprofen medicated plaster and four (2.2%) with the placebo plaster had skin reaction of assessment grade higher than the induction phase. One subject for the ibuprofen and two for the placebo plaster had reactions with grade >2. No subjects showed an increase in sensitization on Day 39 or 40 compared with Day 38. The findings indicate that the both the irritancy and contact sensitization of the ibuprofen medicated plaster is acceptable.

Exenatide has a Pronounced Effect on Energy Intake but not Energy Expenditure in Non-Diabetic Subjects with Obesity: A Randomized, Double-blind, Placebo-Controlled Trial.

PubMed

Basolo, Alessio; Burkholder, Joshua; Osgood, Kristy; Graham, Alexis; Bundrick, Sarah; Frankl, Joseph; Piaggi, Paolo; Thearle, Marie S; Krakoff, Jonathan

2018-03-26

Exenatide is a glucagon-like peptide 1 (GLP-1) mimetic which induces weight loss predominantly, it is presumed, via decreased food intake. However, circulating GLP-1 is also a determinant of energy expenditure. We sought to quantify the effect of exenatide on energy expenditure (EE) and energy intake. In this single-center, randomized double-blind placebo controlled trial, we randomized 80 healthy, non-diabetic volunteers with obesity (46 women, age: 34.4±8.7 y, body fat by DXA: 44.2±7.8%) to subcutaneous exenatide 10 μg twice daily or placebo. Subjects were admitted to our clinical research unit for measurement of 24h-EE in a whole-room indirect calorimeter and ad libitum food intake using an automated vending machine paradigm before and after randomization. Furthermore, energy expenditure and ad libitum food intake measures were repeated at 24-week after readmission for 7-day inpatient stay. Body weight was obtained weekly for up to 5 weeks and was recorded at each monthly follow up visit up to 24 weeks. Prior to randomization, participants over ate during the 3-day vending machine period in the whole study group (114.6±35.2 %), expressed as percentage of weight maintaining energy needs (WMEN) with those who were eventually randomized to exenatide overeating more (121.6±37.7 %) compared to placebo group (107.6±31.5 %). In the exenatide group, ad libitum absolute energy intake decreased by 1016.1±724.5 kcal/day (95% CI: -1250.9 to -781.2) versus a 245.1±710.5 kcal/day (95% CI: -475.4 to -14.7) decrease in placebo (Δ= -624.8 Kcal/day, p < .0001) whereas the reduction in ad libitum caloric intake relative to WMEN was a more modest 366.8±752.1 kcal/day (95% CI: -614.0 to -119.6) decrease compared to 8.0±860.1 kcal/day (95% CI: -286.8 to 270.8) reduction in placebo (Δ= -382.3 Kcal/day, p = 0.03). The decrease was uniform across all macronutrients groups. No differences in 24hEE or substrate oxidation rates were found. In the exenatide group, body weight decreased more over the 5 weeks (β = -0.039 kg/week, p = 0.02) and was lower compared to placebo at the end of fifth week (-1.48±0.77 kg; 95% CI: -3.02 to 0.05, p = 0.06). At the 24-week follow up, there was no difference in energy intake between exenatide group and placebo group and the treatment group decreased 24-h EE more compared to placebo (β = -160.6 Kcal/day, 95% CI: -307.6 to 13.6, p = 0.03) compared to their pre-randomization measurement. However, this reduction was not present after adjustment for changes in FM and FFM (β = -87 kcal/day, p = 0.14). No difference was observed in body weight (Δ = -1.72 kg, 95% CI: -5.77 to 2.30, p = 0.39) in exenatide versus placebo over 24 weeks. Compared with placebo, exenatide decreased early ad libitum energy intake but did not change 24h-EE. However, the reduction was more modest in relative versus absolute terms (i.e. below that needed for WMEN). Thus, although rate of weight change was greater in the exenatide treated subjects at 5 weeks, the absolute difference in weight was not significant. These findings indicate that although exenatide reduces food intake, it may be more beneficial in blunting overeating and thus may serve to more prevent weight regain following initial weight loss. Published by Elsevier Inc.

Effect of Chicory-derived Inulin on Abdominal Sensations and Bowel Motor Function

PubMed Central

Molne, Laura; Mendez, Sara; Nieto, Adoración; Manichanh, Chaysavanh; Mego, Marianela; Accarino, Anna; Santos, Javier; Sailer, Manuela; Theis, Stephan; Guarner, Francisco

2017-01-01

Goal: To determine the effect of a prebiotic chicory-derived inulin-type fructan on the tolerance of intestinal gas. Background: Subjects with gas-related complaints exhibit impaired handling of intestinal gas loads and we hypothesized that inulin would have a beneficial effect. Study: Placebo-controlled, parallel, randomized, double-blind trial. Subjects with abdominal symptoms and reduced tolerance of intestinal gas (selected by a pretest) received either inulin (8 g/d, n=18) or maltodextrin as a placebo (8 g/d, n=18) for 4 weeks. A gas challenge test (4 h jejunal gas infusion at 12 mL/min while measuring abdominal symptoms and gas retention for 3 h) was performed before and at the end of the intervention phase. Gastrointestinal symptoms and bowel habits (using daily questionnaires for 1 wk) and fecal bifidobacteria counts were measured before and at the end of the intervention. Results: Inulin decreased gas retention during the gas challenge test (by 22%; P=0.035 vs. baseline), while the placebo did not, but the intergroup difference was not statistically significant (P=0.343). Inulin and placebo reduced the perception of abdominal sensations in the gas challenge test to a similar extent (by 52% and 43%, respectively). Participants reported moderate gastrointestinal symptoms and normal bowel habits during baseline examination, and these findings remained unchanged in both groups during the intervention. Inulin led to a higher relative abundance of bifidobacteria counts (P=0.01 vs. placebo). Conclusions: A daily dose of inulin that promotes bifidobacteria growth and may improve gut function, is well tolerated by subjects with gastrointestinal complaints. PMID:27680592

Effect of Chicory-derived Inulin on Abdominal Sensations and Bowel Motor Function.

PubMed

Azpiroz, Fernando; Molne, Laura; Mendez, Sara; Nieto, Adoración; Manichanh, Chaysavanh; Mego, Marianela; Accarino, Anna; Santos, Javier; Sailer, Manuela; Theis, Stephan; Guarner, Francisco

2017-08-01

To determine the effect of a prebiotic chicory-derived inulin-type fructan on the tolerance of intestinal gas. Subjects with gas-related complaints exhibit impaired handling of intestinal gas loads and we hypothesized that inulin would have a beneficial effect. Placebo-controlled, parallel, randomized, double-blind trial. Subjects with abdominal symptoms and reduced tolerance of intestinal gas (selected by a pretest) received either inulin (8 g/d, n=18) or maltodextrin as a placebo (8 g/d, n=18) for 4 weeks. A gas challenge test (4 h jejunal gas infusion at 12 mL/min while measuring abdominal symptoms and gas retention for 3 h) was performed before and at the end of the intervention phase. Gastrointestinal symptoms and bowel habits (using daily questionnaires for 1 wk) and fecal bifidobacteria counts were measured before and at the end of the intervention. Inulin decreased gas retention during the gas challenge test (by 22%; P=0.035 vs. baseline), while the placebo did not, but the intergroup difference was not statistically significant (P=0.343). Inulin and placebo reduced the perception of abdominal sensations in the gas challenge test to a similar extent (by 52% and 43%, respectively). Participants reported moderate gastrointestinal symptoms and normal bowel habits during baseline examination, and these findings remained unchanged in both groups during the intervention. Inulin led to a higher relative abundance of bifidobacteria counts (P=0.01 vs. placebo). A daily dose of inulin that promotes bifidobacteria growth and may improve gut function, is well tolerated by subjects with gastrointestinal complaints.

Acute personalized habitual caffeine doses improve attention and have selective effects when considering the fractionation of executive functions.

PubMed

Lanini, Juliana; Galduróz, José Carlos Fernandes; Pompéia, Sabine

2016-01-01

Caffeine is widely used, often consumed with food, and improves simple and complex/executive attention under fasting conditions. We investigated whether these cognitive effects are observed when personalized habitual doses of caffeine are ingested by caffeine consumers, whether they are influenced by nutriments and if various executive domains are susceptible to improvement. This was a double-blind, placebo-controlled study including 60 young, healthy, rested males randomly assigned to one of four treatments: placebo fasting, caffeine fasting, placebo meal and caffeine meal. Caffeine doses were individualized for each participant based on their self-reported caffeine consumption at the time of testing (morning). The test battery included measures of simple and sustained attention, executive domains (inhibiting, updating, shifting, dual tasking, planning and accessing long-term memory), control measures of subjective alterations, glucose and insulin levels, skin conductance, heart rate and pupil dilation. Regardless of meal intake, acute habitual doses of caffeine decreased fatigue, and improved simple and sustained attention and executive updating. This executive effect was not secondary to the habitual weekly dose consumed, changes in simple and sustained attention, mood, meal ingestion and increases in cognitive effort. We conclude that the morning caffeine "fix" has positive attentional effects and selectively improved executive updating whether or not caffeine is consumed with food. Copyright © 2015 John Wiley & Sons, Ltd.

Incomplete digestion of codfish represents a risk factor for anaphylaxis in patients with allergy.

PubMed

Untersmayr, Eva; Vestergaard, Helle; Malling, Hans-Jørgen; Jensen, Louise Bjerremann; Platzer, Michael H; Boltz-Nitulescu, George; Scheiner, Otto; Skov, Per Stahl; Jensen-Jarolim, Erika; Poulsen, Lars K

2007-03-01

Fish represents one of the most important allergenic foods causing severe allergic reactions. Nevertheless, it has been shown that gastric digestion significantly reduces its allergenic capacity. In this study, we assessed the absorption kinetics of fish proteins and investigated the clinical reactivity of patients with fish allergy to codfish digested at physiological or elevated gastric pH. Healthy individuals were openly challenged with codfish and blood samples were evaluated by histamine release for absorbed fish allergens. Patients with allergy were recruited on the basis of previously diagnosed codfish allergy. Fish extracts were digested with gastric enzymes at pH 2.0 and 3.0 and used for histamine release, skin prick tests, and titrated double-blind placebo-controlled food challenges. Ingestion experiments in subjects without allergy revealed absorption of biologically active fish allergens only 10 minutes after ingestion with maximal serum levels after 1 to 2 hours. Incubation of fish proteins with digestive enzymes at pH 2.0 resulted in a fragmentation of the proteins leading to a reduced biological activity evidenced by a significantly smaller wheal reaction and reduced histamine release. Fish digested at pH 3.0 revealed comparable reactivity patterns as undigested extracts. Moreover, these test materials triggered reactions at 10-fold to 30-fold lower cumulated challenge doses in patients with allergy. Our data indicate the paramount importance of gastric digestion for fish allergens because the quantitatively significant absorption and elicitation of symptoms seemed to take place in the intestine. Hindered digestion puts patients with fish allergy at risk to develop severe allergic reactions at minute amounts of allergens.

Acute effects of a herb extract formulation and inulin fibre on appetite, energy intake and food choice.

PubMed

Harrold, J A; Hughes, G M; O'Shiel, K; Quinn, E; Boyland, E J; Williams, N J; Halford, J C G

2013-03-01

The impact of two commercially available products, a patented herb extract Yerbe Maté, Guarana and Damiana (YGD) formulation and an inulin-based soluble fermentable fibre (SFF), alone or in combination, on appetite and food intake were studied for the first time in a double blind, placebo-controlled, cross-over design. 58 normal to slightly overweight women consumed a fixed-load breakfast followed 4h later by an ad libitum lunch. They were administered YGD (3 tablets) and SFF (5g in 100ml water), YGD and water (100ml), SFF and placebo (3 tablets) or water and placebo 15min before meals. Appetite was assessed using visual analogue scales, and energy intake was measured at lunch. Significant reductions in food intake and energy intake were observed when YGD was present (59.5g, 16.3%; 112.4kcal, 17.3%) and when SFF was present (31.9g, 9.1%; 80kcal, 11.7%) compared with conditions were products were absent. The lowest intake (gram and kcal) was in the YGD+SFF condition. Significant reductions in AUC hunger and AUC desire to eat were also observed after YGD+SFF combination. The data demonstrate that YGD produces a robust short-term effect on caloric intake, an effect augmented by SFF. Caloric compensation for SFF indicates independent effects on appetite regulation. Copyright © 2012 Elsevier Ltd. All rights reserved.

U.S. Food and Drug Administration Approval Summary: Enzalutamide for the Treatment of Patients With Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer.

PubMed

Ning, Yang-Min; Brave, Michael; Maher, V Ellen; Zhang, Lijun; Tang, Shenghui; Sridhara, Rajeshwari; Kim, Geoffrey; Ibrahim, Amna; Pazdur, Richard

2015-08-01

The U.S. Food and Drug Administration approved enzalutamide for the treatment of patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC). At the prespecified interim analysis, a statistically significant improvement in overall survival was demonstrated for patients in the enzalutamide arm compared with patients in the placebo arm. The overall benefit-risk profile supports the expanded indication for enzalutamide. On September 10, 2014, the U.S. Food and Drug Administration approved enzalutamide for the treatment of patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC). Enzalutamide was initially approved in 2012 for use in patients with mCRPC who had previously received docetaxel. The current approval was based on the results of a randomized, placebo-controlled, double-blind trial conducted in 1,717 asymptomatic or minimally symptomatic patients with chemotherapy-naïve mCRPC. Patients were assigned to receive either enzalutamide 160 mg or placebo orally once daily. The coprimary endpoints were overall survival (OS) and radiographic progression-free survival (rPFS), which was assessed by independent central radiology review. At the prespecified interim analysis, a statistically significant improvement in OS was demonstrated for patients in the enzalutamide arm compared with patients in the placebo arm (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.60-0.84). The median OS was 32.4 and 30.2 months in the enzalutamide and placebo arms, respectively. A statistically significant prolongation of rPFS was observed in patients in the enzalutamide arm (HR, 0.17; 95% CI, 0.14-0.21). In addition, the time to initiation of cytotoxic chemotherapy was prolonged in the enzalutamide arm (HR, 0.35; 95% CI, 0.30-0.40), with median times of 28.0 and 10.8 months in the enzalutamide and placebo arms, respectively. The safety profile was similar to that previously reported for enzalutamide. Adverse reactions of interest included seizure, hypertension, and falls. Enzalutamide should be discontinued if a seizure occurs during treatment. The overall benefit-risk profile supports the expanded indication for enzalutamide. ©AlphaMed Press.

The Gluten-Free/Casein-Free Diet: A Double-Blind Challenge Trial in Children with Autism

ERIC Educational Resources Information Center

Hyman, Susan L.; Stewart, Patricia A.; Foley, Jennifer; Cain, Usa; Peck, Robin; Morris, Danielle D.; Wang, Hongyue; Smith, Tristram

2016-01-01

To obtain information on the safety and efficacy of the gluten-free/casein-free (GFCF) diet, we placed 14 children with autism, age 3-5 years, on the diet for 4-6 weeks and then conducted a double-blind, placebo-controlled challenge study for 12 weeks while continuing the diet, with a 12-week follow-up. Dietary challenges were delivered via weekly…

Dietary Plant Sterols Supplementation Increases In Vivo Nitrite and Nitrate Production in Healthy Adults: A Randomized, Controlled Study.

PubMed

Ho, Xing Lin; Loke, Wai Mun

2017-07-01

A randomized, double-blinded, placebo-controlled and crossover study was conducted to simultaneously measure the effects, 3 h after consumption and after 4-wk daily exposure to plant sterols-enriched food product, on in vivo nitrite and nitrate production in healthy adults. Eighteen healthy participants (67% female, 35.3 [mean] ± 9.5 [SD] years, mean body mass index 22.8 kg/m 2 ) received 2 soy milk (20 g) treatments daily: placebo and one containing 2.0 g free plant sterols equivalent of their palmityl esters (β-sitosterol, 55%; campesterol, 29%; and stigmasterol, 23%). Nitrite and nitrate concentrations were measured in the blood plasma and urine, using stable isotope-labeled gas chromatography-mass spectrometry. L-arginine and asymmetric dimethylarginine concentrations in blood serum were measured using commercially available enzyme immunoassays. Nitrite and nitrate concentrations in blood plasma (nitrite 5.83 ± 0.50 vs. 4.52 ± 0.27; nitrate 15.78 ± 0.96 vs. 13.43 ± 0.81 μmol/L) and urine (nitrite 1.12 ± 0.22 vs. 0.92 ± 0.36, nitrate 12.23 ± 1.15 vs. 9.71 ± 2.04 μmol/L) were significantly elevated after 4-wk plant sterols supplementation Placebo and 3-h treatments did not affect the blood plasma and urinary concentrations of nitrite and nitrate. Circulating levels of L-arginine and asymmetric dimethylarginine were unchanged in the placebo and treatment arms. Total plant sterols, β-Sitosterol, campesterol, and stigmasterol concentrations were significantly elevated after 4-wk treatments compared to the placebo and 3-h treatments. Blood plasma nitrite and nitrate concentrations correlated significantly with the plasma total and specific plant sterol concentrations. Our results suggest that dietary plant sterols, in the combination used, can upregulate nitrite, and nitrate production in vivo. © 2017 Institute of Food Technologists®.

The effect of OPC Factor on energy levels in healthy adults ages 45-65: a phase IIb randomized controlled trial.

PubMed

LaRiccia, Patrick J; Farrar, John T; Sammel, Mary D; Gallo, Joseph J

2008-07-01

To determine the efficacy of the food supplement OPC Factor to increase energy levels in healthy adults aged 45 to 65. Randomized, placebo-controlled, triple-blind crossover study. Twenty-five (25) healthy adults recruited from the University of Pennsylvania Health System. OPC Factor,trade mark (AlivenLabs, Lebanon, TN) a food supplement that contains oligomeric proanthocyanidins from grape seeds and pine bark along with other nutrient supplements including vitamins and minerals, was in the form of an effervescent powder. The placebo was similar in appearance and taste. Five outcome measurements were performed: (1) Energy subscale scores of the Activation-Deactivation Adjective Check List (AD ACL); (2) One (1) global question of percent energy change (Global Energy Percent Change); (3) One (1) global question of energy change measured on a Likert scale (Global Energy Scale Change); 4. One (1) global question of percent overall status change (Global Overall Status Percent Change); and (5) One (1) global question of overall status change measured on a Likert scale (Global Overall Status Scale Change). There were no carryover/period effects in the groups randomized to Placebo/Active Product sequence versus Active Product/Placebo sequence. Examination of the AD ACL Energy subscale scores for the Active Product versus Placebo comparison revealed no significant difference in the intention-to-treat (IT) analysis and the treatment received (TR) analysis. However, Global Energy Percent Change (p = 0.06) and Global Energy Scale Change (p = 0.09) both closely approached conventional levels of statistical significance for the active product in the IT analysis. Global Energy Percent Change (p = 0.05) and Global Energy Scale Change (p = 0.04) reached statistical significance in the TR analysis. A cumulative percent responders analysis graph indicated greater response rates for the active product. OPC Factor may increase energy levels in healthy adults aged 45-65 years. A larger study is recommended. Clinical Trials.gov identifier: NCT03318019.

Incidence and risk factors for food hypersensitivity in UK infants: results from a birth cohort study.

PubMed

Grimshaw, Kate E C; Bryant, Trevor; Oliver, Erin M; Martin, Jane; Maskell, Joe; Kemp, Terri; Clare Mills, E N; Foote, Keith D; Margetts, Barrie M; Beyer, Kirsten; Roberts, Graham

2015-01-01

The prevalence of food hypersensitivity in the UK is still largely open to debate. Additionally its pathogenesis is also unclear although it is known that there are differing phenotypes. Determining its prevalence, along with identifying those factors associated with its development will help to assess its clinical importance within the national setting and also add to the debate on appropriate prevention strategies. A population based birth cohort study conducted in Hampshire, UK as part of the EuroPrevall birth cohort study. 1140 infants were recruited with 823 being followed up until 2 years of age. Infants with suspected food reactions were assessed including specific IgE measurement and skin prick testing. Diagnosis of food hypersensitivity was by positive double-blind, placebo-controlled food challenge (DBPCFC) where symptoms up to 48 h after the end of the food challenge were considered indicative of a food hypersensitivity. Factors associated with food hypersensitivity and its two phenotypes of IgE-mediated and non-IgE-mediated disease were modelled in a multivariable logistic regression analysis. Cumulative incidence of food hypersensitivity by 2 years of age was 5.0 %. The cumulative incidence for individual food allergens were hens' egg 2.7 % (1.6-3.8); cows' milk 2.4 % (1.4-3.5); peanut 0.7 % (0.1-1.3); soy 0.4 % (0.0-0.8); wheat 0.2 % (0.0-0.5) and 0.1 % (0.0-0.32) for fish. The cumulative incidence of IgE-mediated food allergy was 2.6 % with 2.1 % reacting to hens' egg. For non-IgE-mediated food allergy the cumulative incidence was 2.4 % (cows' milk 1.7 %). Predictors for any food hypersensitivity were wheeze, maternal atopy, increasing gestational age, age at first solid food introduction and mean healthy dietary pattern score. Predictors for IgE mediated allergy were eczema, rhinitis and healthy dietary pattern score whereas for non-IgE-mediated food allergy the predictors were dog in the home, healthy dietary pattern score, maternal consumption of probiotics during breastfeeding and age at first solid food introduction. Just under half the infants with confirmed food hypersensitivity had no demonstrable IgE. In an exploratory analysis, risk factors for this phenotype of food hypersensitivity differed from those for IgE-mediated food allergy except for a healthy infant diet which was associated with less risk for both phenotypes.

Opposing neural effects of naltrexone on food reward and aversion: implications for the treatment of obesity.

PubMed

Murray, Elizabeth; Brouwer, Sietske; McCutcheon, Rob; Harmer, Catherine J; Cowen, Philip J; McCabe, Ciara

2014-11-01

Opioid antagonism reduces the consumption of palatable foods in humans but the neural substrates implicated in these effects are less well understood. The aim of the present study was to examine the effects of the opioid antagonist, naltrexone, on neural response to rewarding and aversive sight and taste stimuli. We used functional magnetic resonance imaging (fMRI) to examine the neural responses to the sight and taste of pleasant (chocolate) and aversive (mouldy strawberry) stimuli in 20 healthy volunteers who received a single oral dose of naltrexone (50 mg) and placebo in a double-blind, repeated-measures cross-over, design. Relative to placebo, naltrexone decreased reward activation to chocolate in the dorsal anterior cingulate cortex and caudate, and increased aversive-related activation to unpleasant strawberry in the amygdala and anterior insula. These findings suggest that modulation of key brain areas involved in reward processing, cognitive control and habit formation such as the dorsal anterior cingulate cortex (dACC) and caudate might underlie reduction in food intake with opioid antagonism. Furthermore we show for the first time that naltrexone can increase activations related to aversive food stimuli. These results support further investigation of opioid treatments in obesity.

Occupational asthma caused by exposure to asparagus: detection of allergens by immunoblotting.

PubMed

Lopez-Rubio, A; Rodriguez, J; Crespo, J F; Vives, R; Daroca, P; Reaño, M

1998-12-01

Vegetables of the Liliaceae family, such as garlic or onion, have been reported to cause occupational asthma. However, there are few data on adverse reactions to asparagus. We evaluated the role of asparagus as a cause of asthma in a patient with respiratory symptoms occurring at work (horticulture) and studied relevant allergens. A 28-year-old man complained of rhinoconjunctivitis and asthma when harvesting asparagus at work. Eating cooked asparagus did not provoke symptoms. A positive skin test reaction was observed with raw asparagus, Alternaria alternata, and grass-pollen extracts. The methacholine test demonstrated mild bronchial hyperresponsiveness. The patient had an immediate asthmatic response after challenge with raw asparagus extract. Bronchial provocation tests with boiled asparagus, A. alternata, and control extracts were negative. Two unexposed subjects with seasonal allergic asthma did not react to the raw asparagus extract. The double-blind, placebo-controlled food challenge with raw asparagus was negative. Serum asparagus-specific IgE was 13.9 kU(A)/l. By SDS-PAGE immunoblot, at least six IgE-binding components, ranging from 22 to 73 kDa, were detected only in raw asparagus. We report a case of occupational asthma caused by asparagus inhalation, confirmed by specific bronchoprovocation. Immunoblot analysis showed that asparagus allergens are very labile and quite sensitive to heat denaturation.

Pilot study: a randomised, double blind, placebo controlled trial of pancrealipase for the treatment of postprandial irritable bowel syndrome-diarrhoea

PubMed Central

Money, Mary E; Walkowiak, Jaroslaw; Virgilio, Chris; Talley, Nicholas J

2011-01-01

Objective To evaluate the efficacy of pancrealipase (PEZ) compared with placebo in the reduction of postprandial irritable bowel syndrome-diarrhoea (IBS-D). Design An intention to treat, double blind, randomised, crossover trial comparing PEZ to placebo for reduction of postprandial IBS-D. Patients had to recognise at least two different triggering foods, be willing to consume six baseline ‘trigger meals’ and again blinded with PEZ and placebo. Patients then chose which drug they preferred for another 25 meals. Setting Outpatient internal medicine practice clinic. Patients 255 patients were screened; 83 met the criteria, including 5 years of symptoms, recognised ‘food triggers’, no other identifiable cause for the symptoms, either a normal colonoscopy or barium enema while symptomatic and able to discontinue all anticholinergic medications. 69 patients were enrolled, 20 withdrew before randomisation, leaving 49 patients: 14 men, 35 women, mean age 52 years (SD 15.3). Over 60% had experienced symptoms for 11–30 years and 16% for more than 40 years. Interventions After completing six baseline meals, patients were randomised in blocks of four to receive either identical PEZ or a placebo for another six meals, and after a washout period of time received the alternative drug. Main outcome measures The primary analysis was number of patients who chose PEZ over placebo for the extended use. Results Overall, 30/49 (61%) would have chosen PEZ (p=0.078), with first drug preference for PEZ at 0.002. Among the PEZ subgroup, PEZ use compared with placebo, demonstrated improvement in all symptoms (p≤0.001) for cramping, bloating, borborygami, urge to defecate, global pain and decrease stooling with increase in stool firmness. Conclusions PEZ was found in a small group of patients to reduce postprandial IBS-D symptoms and deserves further evaluation. PMID:22095308

Omalizumab facilitates rapid oral desensitization for peanut allergy.

PubMed

MacGinnitie, Andrew J; Rachid, Rima; Gragg, Hana; Little, Sara V; Lakin, Paul; Cianferoni, Antonella; Heimall, Jennifer; Makhija, Melanie; Robison, Rachel; Chinthrajah, R Sharon; Lee, John; Lebovidge, Jennifer; Dominguez, Tina; Rooney, Courtney; Lewis, Megan Ott; Koss, Jennifer; Burke-Roberts, Elizabeth; Chin, Kimberly; Logvinenko, Tanya; Pongracic, Jacqueline A; Umetsu, Dale T; Spergel, Jonathan; Nadeau, Kari C; Schneider, Lynda C

2017-03-01

Peanut oral immunotherapy is a promising approach to peanut allergy, but reactions are frequent, and some patients cannot be desensitized. The anti-IgE medication omalizumab (Xolair; Genentech, South San Francisco, Calif) might allow more rapid peanut updosing and decrease reactions. We sought to evaluate whether omalizumab facilitated rapid peanut desensitization in highly allergic patients. Thirty-seven subjects were randomized to omalizumab (n = 29) or placebo (n = 8). After 12 weeks of treatment, subjects underwent a rapid 1-day desensitization of up to 250 mg of peanut protein, followed by weekly increases up to 2000 mg. Omalizumab was then discontinued, and subjects continued on 2000 mg of peanut protein. Subjects underwent an open challenge to 4000 mg of peanut protein 12 weeks after stopping study drug. If tolerated, subjects continued on 4000 mg of peanut protein daily. The median peanut dose tolerated on the initial desensitization day was 250 mg for omalizumab-treated subjects versus 22.5 mg for placebo-treated subject. Subsequently, 23 (79%) of 29 subjects randomized to omalizumab tolerated 2000 mg of peanut protein 6 weeks after stopping omalizumab versus 1 (12%) of 8 receiving placebo (P < .01). Twenty-three subjects receiving omalizumab versus 1 subject receiving placebo passed the 4000-mg food challenge. Overall reaction rates were not significantly lower in omalizumab-treated versus placebo-treated subjects (odds ratio, 0.57; P = .15), although omalizumab-treated subjects were exposed to much higher peanut doses. Omalizumab allows subjects with peanut allergy to be rapidly desensitized over as little as 8 weeks of peanut oral immunotherapy. In the majority of subjects, this desensitization is sustained after omalizumab is discontinued. Additional studies will help clarify which patients would benefit most from this approach. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Succinate-based preparation alleviates manifestations of the climacteric syndrome in women.

PubMed

Peskov, A B; Maevskii, E I; Uchitel', M L; Sakharova, N Yu; Vize-Khripunova, M A

2005-09-01

Clinical placebo-controlled study of Enerlit-Clima (bioactive succinate-based food additive) a showed positive effect of the preparation on general clinical and psychoemotional manifestations of the climacteric syndrome. A trend to an increase in estradiol level in early pathological climacteric and normalization of the endometrial status were observed.

76 FR 23324 - Endocrinologic and Metabolic Drugs Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-26

... for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 31, rm... Cardiovascular Risk in Diabetes-Lipid (ACCORD Lipid) trial as they relate to the efficacy and safety of the... cholesterol goal. The ACCORD Lipid study was a randomized, double-blind, placebo- controlled add-on trial...

A randomised controlled trial of a probiotic 'functional food' in the management of irritable bowel syndrome.

PubMed

Roberts, Lesley M; McCahon, Deborah; Holder, Roger; Wilson, Sue; Hobbs, F D Richard

2013-03-07

Irritable Bowel Syndrome (IBS) is a common condition characterised by pain, distension and altered bowel habit. Evidence suggests functional foods containing probiotics improve gastrointestinal transit, however, data are limited by short follow-up periods and evaluation in selected populations. A multi-centre, randomized, double blind, controlled trial to evaluate the effect of a probiotic vs non-probiotic dairy product on symptoms in IBS with a constipation element (IBS-Constipation or IBS-Mixed profile). Set in 13 general practices within central England. Individuals meeting the ROME III criteria for IBS, aged 18-65 completed a pre-study diary. Eligible individuals were randomized to consume dairy 'yoghurt' products which either did or did not contain active probiotics twice daily and to complete a daily diary. Primary outcome was subjective global assessment of symptom relief at week 4. Other outcomes comprised, IBS symptom scores, pain, bloating and flatulence levels, stool frequency, stool consistency, ease of bowel movement and quality of life. 179 were randomized (91 active, 88 placebo). 76 (43 active, 33 placebo) completed the study. No significant between group differences existed at 4 weeks (57% active vs 53% placebo, reported adequate relief (p = 0.71)). By week 8, 46% active vs 68% placebo reported adequate relief (p = 0.03). This was sustained at week 12. Significant improvements were reported for most outcomes in all trial participants but improvement did not differ by group. This trial does not provide evidence for effectiveness of a probiotic in IBS, in variance with a body of published literature and review conclusions. Differential drop out may however cloud interpretation of data. UK TRIAL REGISTRATION: ISRCTN78863629.

Biological agents for moderately to severely active ulcerative colitis: a systematic review and network meta-analysis.

PubMed

Danese, Silvio; Fiorino, Gionata; Peyrin-Biroulet, Laurent; Lucenteforte, Ersilia; Virgili, Gianni; Moja, Lorenzo; Bonovas, Stefanos

2014-05-20

Biological agents are emerging treatment options for the management of ulcerative colitis (UC). To assess the comparative efficacy and harm of biological agents in adult patients with moderately to severely active UC who are naive to biological agents. MEDLINE, EMBASE, and Cochrane Library from inception through December 2013, without language restrictions, and ClinicalTrials.gov, European Medicines Agency, and U.S. Food and Drug Administration Web sites. Randomized, placebo-controlled or head-to-head trials assessing biological agents as induction or maintenance therapy for moderately to severely active UC. Two reviewers independently abstracted study data and outcomes and rated each trial's risk of bias. There were no head-to-head trials. There were 7 double-blind, placebo-controlled trials that were rated as low risk of bias and showed that all biological agents (adalimumab, golimumab, infliximab, and vedolizumab) resulted in more clinical responses, clinical remissions, and mucosal healings than placebo for induction therapy. The results of network meta-analysis suggested that infliximab is more effective to induce clinical response (odds ratio, 2.36 [95% credible interval, 1.22 to 4.63]) and mucosal healing (odds ratio, 2.02 [95% credible interval, 1.13 to 3.59]) than adalimumab. No other indirect comparison reached statistical significance. For maintenance, 6 double-blind, placebo-controlled trials that were rated high risk of bias showed that all biological agents have greater clinical efficacy than placebo. The occurrence of adverse events was not different between biological agents and placebo. Few trials, no head-to-head comparisons, and inadequate follow-up in maintenance trials. Biological agents are effective treatments for UC, but head-to-head trials are warranted to establish the best therapeutic option.

Allergen-specific oral immunotherapy for peanut allergy.

PubMed

Nurmatov, Ulugbek; Venderbosch, Iris; Devereux, Graham; Simons, F Estelle R; Sheikh, Aziz

2012-09-12

Peanut allergy is one of the most common forms of food allergy encountered in clinical practice.  In most cases, it does not spontaneously resolve; furthermore, it is frequently implicated in acute life-threatening reactions. The current management of peanut allergy centres on meticulous avoidance of peanuts and peanut-containing foods. Allergen-specific oral immunotherapy (OIT) for peanut allergy aims to induce desensitisation and then tolerance to peanut, and has the potential to revolutionise the management of peanut allergy. However, at present there is still considerable uncertainty about the effectiveness and safety of this approach. To establish the effectiveness and safety of OIT in people with IgE-mediated peanut allergy who develop symptoms after peanut ingestion. We searched in the following databases: AMED, BIOSIS, CAB, CINAHL, The Cochrane Library, EMBASE, Global Health, Google Scholar, IndMed, ISI Web of Science, LILACS, MEDLINE, PakMediNet and TRIP. We also searched registers of on-going and unpublished trials. The date of the most recent search was January 2012. Randomised controlled trials (RCTs), quasi-RCTs or controlled clinical trials involving children or adults with clinical features indicative of IgE-mediated peanut allergy treated with allergen-specific OIT, compared with control group receiving either placebo or no treatment, were eligible for inclusion. Two review authors independently checked and reviewed titles and abstracts of identified studies and assessed risk of bias. The full text of potentially relevant trials was assessed. Data extraction was independently performed by two reviewers with disagreements resolved through discussion. We found one small RCT, judged to be at low risk of bias, that enrolled 28 children aged 1 to 16 years with evidence of sensitisation to peanut and a clinical history of reaction to peanut within 60 minutes of exposure. The study did not include children who had moderate to severe asthma or who had a history of severe peanut anaphylaxis. Randomisation was in a 2:1 ratio resulting in 19 children being randomised to the intervention arm and nine to the placebo arm. Intervention arm children received OIT with peanut flour and control arm participants received placebo comprising of oat flour. The primary outcome was assessed using a double-blind, placebo controlled oral food challenge (OFC) at approximately one year. No data were available on longer term outcomes beyond the OFC conducted at the end of the study.Because of adverse events, three patients withdrew from the intervention arm before the completion of the study. Therefore, only 16 participants received the full course of peanut OIT, whereas all nine patients receiving placebo completed the trial. The per-protocol analysis found a significant increase in the threshold dose of peanut allergen required to trigger a reaction in those in the intervention arm with all 16 participants able to ingest the maximum cumulative dose of 5000 mg of peanut protein (which the authors equate as being equivalent to approximately 20 peanuts) without developing symptoms, whereas in the placebo group they were able to ingest a median cumulative dose of 280 mg (range: 0 to 1900 mg, P < 0.001) before experiencing symptoms.  Per-protocol analyses also demonstrated that peanut OIT resulted in reductions in skin prick test size (P < 0.001), interleukin-5 (P = 0.01), interleukin-13 (P = 0.02) and an increase in peanut-specific immunoglobulin G(4) (IgG(4)) (P < 0.01).Children in the intervention arm experienced more adverse events during treatment than those in the placebo arm. In the initial day escalation phase, nine (47%) of the 19 participants initially enrolled in the OIT arm experienced clinically-relevant adverse events which required treatment with H(1)-antihistamines, two of which required additional treatment with epinephrine (adrenaline). The one small RCT we found showed that allergen-specific peanut OIT can result in desensitisation in children, and that this is associated with evidence of underlying immune-modulation. However, this treatment approach was associated with a substantial risk of adverse events, although the majority of these were mild.  In view of the risk of adverse events and the lack of evidence of long-term benefits, allergen-specific peanut OIT cannot currently be recommended as a treatment for the management of patients with IgE-mediated peanut allergy.  Larger RCTs are needed to investigate the acceptability, long-term effectiveness and cost-effectiveness of safer treatment regimens, particularly in relation to the induction of clinical and immunological tolerance.

No Acute Effects of Choline Bitartrate Food Supplements on Memory in Healthy, Young, Human Adults.

PubMed

Lippelt, D P; van der Kint, S; van Herk, K; Naber, M

2016-01-01

Choline is a dietary component and precursor of acetylcholine, a crucial neurotransmitter for memory-related brain functions. In two double-blind, placebo-controlled cross-over experiments, we investigated whether the food supplement choline bitartrate improved declarative memory and working memory in healthy, young students one to two hours after supplementation. In experiment 1, 28 participants performed a visuospatial working memory task. In experiment 2, 26 participants performed a declarative picture memorization task. In experiment 3, 40 participants performed a verbal working memory task in addition to the visuospatial working memory and declarative picture task. All tasks were conducted approximately 60 minutes after the ingestion of 2.0-2.5g of either choline bitartrate or placebo. We found that choline did not significantly enhance memory performance during any of the tasks. The null hypothesis that choline does not improve memory performance as compared to placebo was strongly supported by Bayesian statistics. These results are in contrast with animal studies suggesting that choline supplementation boosts memory performance and learning. We conclude that choline likely has no acute effects on cholinergic memory functions in healthy human participants.

No Acute Effects of Choline Bitartrate Food Supplements on Memory in Healthy, Young, Human Adults

PubMed Central

Lippelt, D. P.; van der Kint, S.; van Herk, K.; Naber, M.

2016-01-01

Choline is a dietary component and precursor of acetylcholine, a crucial neurotransmitter for memory-related brain functions. In two double-blind, placebo-controlled cross-over experiments, we investigated whether the food supplement choline bitartrate improved declarative memory and working memory in healthy, young students one to two hours after supplementation. In experiment 1, 28 participants performed a visuospatial working memory task. In experiment 2, 26 participants performed a declarative picture memorization task. In experiment 3, 40 participants performed a verbal working memory task in addition to the visuospatial working memory and declarative picture task. All tasks were conducted approximately 60 minutes after the ingestion of 2.0–2.5g of either choline bitartrate or placebo. We found that choline did not significantly enhance memory performance during any of the tasks. The null hypothesis that choline does not improve memory performance as compared to placebo was strongly supported by Bayesian statistics. These results are in contrast with animal studies suggesting that choline supplementation boosts memory performance and learning. We conclude that choline likely has no acute effects on cholinergic memory functions in healthy human participants. PMID:27341028

Single and Multiple Ascending-dose Studies of Oral Delafloxacin: Effects of Food, Sex, and Age.

PubMed

Hoover, Randall; Hunt, Thomas; Benedict, Michael; Paulson, Susan K; Lawrence, Laura; Cammarata, Sue; Sun, Eugene

2016-01-01

The objective of this report is describe the results of 2 studies that examined the pharmacokinetic parameters, safety profile, and tolerability of single and multiple ascending doses of oral delafloxacin and the effects of food, sex, and age on oral delafloxacin pharmacokinetic parameters, safety profile, and tolerability. The first study contained 3 parts and used unformulated delafloxacin in a capsule. Part 1 was a randomized, double-blind, placebo-controlled, single (50, 100, 200, 400, 800, 1200, and 1600 mg) ascending-dose study of oral delafloxacin in healthy men. Part 2 was a single-dose crossover study in which 20 men received 250 mg delafloxacin with or without food. Part 2 also included a parallel group, double-blind, placebo-controlled study in 16 women and 16 elderly men and women who were randomized (3:1) to receive 250 mg delafloxacin or placebo. Part 3 was a randomized, double-blind, placebo-controlled, multiple (100, 200, 400, 800, 1200 mg once daily for 5 days) ascending-dose study of oral delafloxacin in healthy men. The second study was a single-dose, randomized, 3-period crossover study in which participants received 900 mg delafloxacin (2 × 450-mg tablets) under fasted conditions, with a high-fat meal, or fasted with a high-fat meal 2 hours after dosing. Serial blood samples were collected, and plasma pharmacokinetic parameters of delafloxacin were determined. Delafloxacin Cmax and AUC0-∞ increased with increasing oral dose over the dose range of 50 to 1600 mg. The increases in delafloxacin AUC0-∞ were dose proportional at doses of ≥200 mg. Steady state was reached by day 3 of dosing with minimal accumulation of delafloxacin. The Cmax of delafloxacin was decreased slightly in the presence of food. No sex difference in delafloxacin pharmacokinetic parameters was observed. In the elderly men and women, mean delafloxacin Cmax and AUC0-∞ were 35% higher than observed for young adults, which could be partially explained by a decrease in the creatinine clearance in the elderly men and women. Delafloxacin was well tolerated at the tested doses, with gastrointestinal adverse effects observed more commonly at doses ≥1200 mg. Delafloxacin exhibits linear pharmacokinetic parameters that reached steady state after 3 days of daily oral dosing with minimal accumulation. Delafloxacin was well tolerated throughout both studies, with gastrointestinal effects observed at the higher doses (≥1200 mg). Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Double-blind, placebo-controlled immunotherapy with mixed grass-pollen allergoids. II. Comparison between parameters assessing the efficacy of immunotherapy.

PubMed

Bousquet, J; Maasch, H; Martinot, B; Hejjaoui, A; Wahl, R; Michel, F B

1988-09-01

Specific immunotherapy is effective in alleviating symptoms in grass pollen-induced rhinitis, but there are no clear data demonstrating a correlation between symptom-medication scores and objective parameters. Twenty-five patients taking part in a double-blind, placebo-controlled immunotherapy with mixed grass pollen-formalinized allergoids were studied. All patients had the same investigations. Symptom-medication scores were significantly (p less than 0.005, Mann-Whitney U test) reduced in the treated group by comparison to the placebo-treated patients. Nasal challenges performed with threefold increasing numbers of orchard grass-pollen grains demonstrated that patients treated with allergoid tolerated a significantly (p less than 0.005, Wilcoxon W test) greater number of grains after treatment, whereas there was no mean difference in the placebo-treated patients. There was a significant (p less than 0.005, Spearman rank-correlation) correlation between nasal challenges and symptom scores during the season. The skin prick test end point was significantly (p less than 0.001, Wilcoxon W test) reduced after treatment in the allergoid-treated group and remained unchanged in the placebo-treated group. There was a significant (p less than 0.001) correlation between the skin prick test end point and symptom scores during the season. Serum grass-pollen IgG titrated by a solid-phase radioimmunoassay with Staphylococcus A protein was significantly (p less than 0.01, Wilcoxon W test) increased after treatment with allergoid, but there was no significant correlation between IgG titer and symptom scores during the season. Serum grass-pollen IgE increased (p less than 0.04, Wilcoxon W test) in the treated group but there was no correlation with symptom scores.

Effect of a polysaccharide-rich hydrolysate from Saccharomyces cerevisiae (LipiGo®) in body weight loss: randomised, double-blind, placebo-controlled clinical trial in overweight and obese adults.

PubMed

Santas, Jonathan; Lázaro, Elisabet; Cuñé, Jordi

2017-09-01

In the present study we evaluated the weight loss effect of a polysaccharide-rich food supplement, LipiGo®, comprising a specific β-glucan-chitin-chitosan fraction (BGCC) obtained from the chemical hydrolysis of Saccharomyces cerevisiae, resulting as a by-product of the brewing process. A randomised, double-blind, placebo-controlled clinical trial was performed enrolling 56 overweight and obese subjects (body mass index, BMI, 25-35 kg m -2 ) who were not following any specific diet, and were given placebo or BGCC (3 g d -1 ) for 12 weeks. Results were analysed by intention-to-treat (ITT) and per-protocol (PP) methods. Body weight increased in the placebo group compared to baseline (ITT: 1.0 kg, P < 0.001; PP: 1.5 kg, P = 0.003), while it was slightly lowered in the BGCC group (ITT: -0.8 kg, P = 0.210; PP: -1.1 kg, P = 0.182). BGCC, but not the consumption of placebo, also resulted in a reduction of waist circumference and body fat compared to baseline. Results suggest that daily supplementation of BGCC may be useful for improving body weight and waist circumference in overweight and obese subjects, without relevant adverse effects. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Remineralisation effect of a dual-phase calcium silicate/phosphate gel combined with calcium silicate/phosphate toothpaste on acid-challenged enamel in situ.

PubMed

Joiner, Andrew; Schäfer, Fred; Naeeni, Mojgan M; Gupta, Ashok K; Zero, Domenick T

2014-06-01

To test if a novel dual-phase gel system (calcium silicate and phosphate with 1450 ppmF, as NaF/MFP; TG) combined with a toothpaste (calcium silicate and sodium phosphate with 1450 ppmF, as MFP; TG) was able to re-harden previously acid-challenged enamel to a greater extent than other toothpastes. The study consisted of a double-blind, randomised, cross-over design with four 7-day treatment legs. In each leg, subjects wearing a partial denture holding four demineralised enamel specimens (25 min in 0.3% citric acid, pH3.8) used either the test regimen (TG+TP) or one of the three controls. (placebo TG+TP; Positive Control - placebo TG+marketed 1450 ppmF toothpaste; Negative Control - placebo TG+placebo TP). Enamel specimens were removed after 1, 2, 3 and 7 days. The gel systems were applied once per day for the first three days during which subjects also brushed with the corresponding toothpaste; this was followed by four days use of the toothpastes only. Toothpastes were used in the conventional way brushing twice per day throughout the seven days. The outcome variable was %Surface Microhardness Recovery calculated after three and seven days of in situ treatment. The results showed a statistically significant (p<0.001) re-hardening effect for all treatments compared to pre-treatment hardness. After three days and after seven days of in situ treatment significantly greater hardening (p<0.05) was found in the samples treated with calcium silicate/phosphate gel system plus calcium silicate/phosphate toothpaste than in the control groups. It is concluded that the test regimen based on the novel dual-phase gel system combined with toothpaste was able to re-harden acid-challenged tooth enamel to a greater extent than a normal fluoride toothpaste. The novel oral care products containing calcium silicate, sodium phosphate salts and fluoride is a new approach to the repair of demineralised enamel. © 2014 Elsevier Ltd. All rights reserved.

Does the rising placebo response impact antihypertensive clinical trial outcomes? An analysis of data from the Food and Drug Administration 1990-2016

PubMed Central

Fahl Mar, Kaysee; Schilling, Joshua; Brown, Walter A.

2018-01-01

Background Recent studies show that placebo response has grown significantly over time in clinical trials for antidepressants, ADHD medications, antiepileptics, and antidiabetics. Contrary to expectations, trial outcome measures and success rates have not been impacted. This study aimed to see if this trend of increasing placebo response and stable efficacy outcome measures is unique to the conditions previously studied or if it occurs in trials for conditions with physiologically-measured symptoms, such as hypertension. Method For this reason, we evaluated the efficacy data reported in the US Food and Drug Administration Medical and Statistical reviews for 23 antihypertensive programs (32,022 patients, 63 trials, 142 treatment arms). Placebo and medication response, effect sizes, and drug-placebo differences were calculated for each treatment arm and examined over time using meta-regression. We also explored the relationship of sample size, trial duration, baseline blood pressure, and number of treatment arms to placebo/drug response and efficacy outcome measures. Results Like trials of other conditions, placebo response has risen significantly over time (R2 = 0.093, p = 0.018) and effect size (R2 = 0.013, p = 0.187) drug-placebo difference (R2 = 0.013, p = 0.182) and success rate (134/142, 94.4%) have remained unaffected, likely due to a significant compensatory increase in antihypertensive response (R2 = 0.086, p<0.001). Treatment arms are likely overpowered with sample sizes increasing over time (R2 = 0.387, p<0.0001) and stable, large effect sizes (0.78 ±0.37). The exploratory analysis of sample size, trial duration, baseline blood pressure, and number of treatment arms yielded mixed results unlikely to explain the pattern of placebo response and efficacy outcomes over time. The magnitude of placebo response had no relationship to effect size (p = 0.877), antihypertensive-placebo differences (p = 0.752), or p-values (p = 0.963) but was correlated with antihypertensive response (R2 = 0.347, p<0.0001). Conclusions As hypothesized, this study shows that placebo response is increasing in clinical trials for hypertension without any evidence of this increase impacting trial outcomes. Attempting to control placebo response in clinical trials for hypertension may not be necessary for successful efficacy outcomes. In exploratory analysis, we noted that despite finding significant relationships, none of the trial or patient characteristics we examined offered a clear explanation of the rise in placebo and stability in outcome measures over time. Collectively, these data suggest that the phenomenon of increasing placebo response and stable efficacy outcomes may be a general trend, occurring across trials for various psychiatric and medical conditions with physiological and non-physiological endpoints. PMID:29489874

Can soy intake affect serum uric acid level? Pooled analysis from two 6-month randomized controlled trials among Chinese postmenopausal women with prediabetes or prehypertension.

PubMed

Liu, Z M; Ho, C S; Chen, Y M; Woo, J

2015-02-01

Hyperuricemia is a recognized risk factor for cardiovascular diseases. Soy foods contain a moderate amount of purine and may predispose to raised serum uric acid (UA). However, no study has examined the long-term effect of soy intake on UA levels. We examined whether consumption of soy foods and isoflavone extracts for 6 months altered serum UA. The analysis included two randomized controlled trials (soy protein trial and whole soy trial) among total 450 postmenopausal women with either prehypertension or prediabetes. We conducted a pooled analysis by combining participants from both the soy flour and soy protein groups (combined soy foods group), participants from both the isoflavone and daidzein groups (combined isoflavone group) and participants from both milk placebo groups. Fasting venous samples were obtained at baseline and the end of the trial for serum UA analysis. In the pooled data, 417 subjects completed the study according to protocol. The baseline serum UA levels were comparable among the three combined groups. There was a lower decrease in UA levels among women in the combined soy foods group compared with women in the other two groups (p = 0.028 and 0.026). The net decrease and % decrease in UA were 14.5 μmol/L (95 % CI 1.93-25.6, p = 0.023) or 4.9 % (95 % CI 1.3-8.5 %, p = 0.023) between the combined soy foods group and placebo group. Among Chinese postmenopausal women with either prehypertension or prediabetes, soy intake did not increase urate levels.

Correlation of the turbo-MP RIA with ImmunoCAP FEIA for determination of food allergen-specific immunoglobulin E.

PubMed

Kontis, Kris J; Valcour, Andre; Patel, Ashok; Chen, Andy; Wang, Jan; Chow, Julia; Nayak, Narayan

2006-01-01

It has been reported that in vitro measurement of food-specific IgE can be used to accurately predict food allergy and reduce the risk associated with double-blinded placebo-controlled food challenges (DBPCFC). Our objective was to assess the performance characteristics of the Hycor Turbo-MP quantitative radioimmunoassay for food-specific IgE and to determine this method's comparability to another assay, the Pharmacia ImmunoCAP fluorescence enzyme immunoassay (FEIA). The dynamic range of the Turbo-MP assay is 0.05 to 100 IU/ml, compared to 0.35 to 100 IU/ml for the FEIA. Performance characteristics of the Turbo-MP assay (ie, reproducibility of the calibration curve, within-run precision, total precision, parallelism, and linearity) were determined using samples from the Hycor serum bank. The precision (CV) of IgE calibrator replicates was <10%. The total precision (CV) of the Turbo-MP assay ranged from 8.8% to 18.4% for specific IgE concentrations between 0.28 to 31.4 IU/ml. Testing of serial dilutions of sera with IgE specificities for egg white, cow's milk, codfish, wheat, peanut, and soybean showed that the assay is linear over the entire dynamic range. Serial dilution data (slopes of 1.01 to 1.10) showed parallelism to serial dilutions of the IgE calibrator (slope of 0.96). The Turbo-MP and FEIA methods were both used for quantitative assays of food-specific IgE in 457 serum samples obtained from a clinical reference laboratory. Comparison of specific IgE results by the Turbo-MP and FEIA methods for 6 major food allergens exhibited a slope of 0.99 (0.92 to 1.03) with a correlation coefficient of 0.81.

Default mode network deactivation to smoking cue relative to food cue predicts treatment outcome in nicotine use disorder.

PubMed

Wilcox, Claire E; Claus, Eric D; Calhoun, Vince D; Rachakonda, Srinivas; Littlewood, Rae A; Mickey, Jessica; Arenella, Pamela B; Goodreau, Natalie; Hutchison, Kent E

2018-01-01

Identifying predictors of treatment outcome for nicotine use disorders (NUDs) may help improve efficacy of established treatments, like varenicline. Brain reactivity to drug stimuli predicts relapse risk in nicotine and other substance use disorders in some studies. Activity in the default mode network (DMN) is affected by drug cues and other palatable cues, but its clinical significance is unclear. In this study, 143 individuals with NUD (male n = 91, ages 18-55 years) received a functional magnetic resonance imaging scan during a visual cue task during which they were presented with a series of smoking-related or food-related video clips prior to randomization to treatment with varenicline (n = 80) or placebo. Group independent components analysis was utilized to isolate the DMN, and temporal sorting was used to calculate the difference between the DMN blood-oxygen-level dependent signal during smoke cues and that during food cues for each individual. Food cues were associated with greater deactivation compared with smoke cues in the DMN. In correcting for baseline smoking and other clinical variables, which have been shown to be related to treatment outcome in previous work, a less positive Smoke - Food difference score predicted greater smoking at 6 and 12 weeks when both treatment groups were combined (P = 0.005, β = -0.766). An exploratory analysis of executive control and salience networks demonstrated that a more positive Smoke - Food difference score for executive control network predicted a more robust response to varenicline relative to placebo. These findings provide further support to theories that brain reactivity to palatable cues, and in particular in DMN, may have a direct clinical relevance in NUD. © 2017 Society for the Study of Addiction.

Daily supplementation with 15 μg vitamin D2 compared with vitamin D3 to increase wintertime 25-hydroxyvitamin D status in healthy South Asian and white European women: a 12-wk randomized, placebo-controlled food-fortification trial.

PubMed

Tripkovic, Laura; Wilson, Louise R; Hart, Kathryn; Johnsen, Sig; de Lusignan, Simon; Smith, Colin P; Bucca, Giselda; Penson, Simon; Chope, Gemma; Elliott, Ruan; Hyppönen, Elina; Berry, Jacqueline L; Lanham-New, Susan A

2017-08-01

Background: There are conflicting views in the literature as to whether vitamin D 2 and vitamin D 3 are equally effective in increasing and maintaining serum concentrations of 25-hydroxyvitamin D [25(OH)D], particularly at lower doses of vitamin D. Objective: We aimed to investigate whether vitamin D 2 or vitamin D 3 fortified in juice or food, at a relatively low dose of 15 μg/d, was effective in increasing serum total 25(OH)D and to compare their respective efficacy in South Asian and white European women over the winter months within the setting of a large randomized controlled trial. Design: A randomized, double-blind, placebo-controlled food-fortification trial was conducted in healthy South Asian and white European women aged 20-64 y ( n = 335; Surrey, United Kingdom) who consumed placebo, juice supplemented with 15 μg vitamin D 2 , biscuit supplemented with 15 μg vitamin D 2 , juice supplemented with 15 μg vitamin D 3 , or biscuit supplemented with 15 μg vitamin D 3 daily for 12 wk. Serum 25(OH)D was measured by liquid chromatography-tandem mass spectrometry at baseline and at weeks 6 and 12 of the study. Results: Postintervention in the 2 ethnic groups combined, both the vitamin D 3 biscuit and the vitamin D 3 juice groups showed a significantly greater absolute incremental change (Δ) in total 25(OH)D when compared with the vitamin D 2 biscuit group [Δ (95% CI): 15.3 nmol/L (7.4, 23.3 nmol/L) ( P < 0.0003) and 16.0 nmol/L (8.0, 23.9 nmol/L) ( P < 0.0001)], the vitamin D 2 juice group [Δ (95% CI): 16.3 nmol/L (8.4, 24.2 nmol/L) ( P < 0.0001) and 16.9 nmol/L (9.0, 24.8 nmol/L) ( P < 0.0001)], and the placebo group [Δ (95% CI): 42.3 nmol/L (34.4, 50.2 nmol/L) ( P < 0.0001) and 42.9 nmol/L (35.0, 50.8 nmol/L) ( P < 0.0002)]. Conclusions: With the use of a daily dose of vitamin D relevant to public health recommendations (15 μg) and in vehicles relevant to food-fortification strategies, vitamin D 3 was more effective than vitamin D 2 in increasing serum 25(OH)D in the wintertime. Vitamin D 3 may therefore be a preferential form to optimize vitamin D status within the general population. This trial was registered at www.controlled-trials.com as ISRCTN23421591. © 2017 American Society for Nutrition.

Efficient assessment of efficacy in post-traumatic peripheral neuropathic pain patients: pregabalin in a randomized, placebo-controlled, crossover study

PubMed Central

Jenkins, Tim M; Smart, Trevor S; Hackman, Frances; Cooke, Carol; Tan, Keith KC

2012-01-01

Background: Detecting the efficacy of novel analgesic agents in neuropathic pain is challenging. There is a critical need for study designs with the desirable characteristics of assay sensitivity, low placebo response, reliable pain recordings, low cost, short duration of exposure to test drug and placebo, and relevant and recruitable population. Methods: We designed a proof-of-concept, double-blind, randomized, placebo-controlled, crossover study in patients with post-traumatic peripheral neuropathic pain (PTNP) to evaluate whether such a study design had the potential to detect efficacious agents. Pregabalin, known to be efficacious in neuropathic pain, was used as the active analgesic. We also assessed physical activity throughout the study. Results: Twenty-five adults (20–70 years of age) with PTNP for ≥3 months entered a screening week and were then randomized to one of the two following treatment sequences: (1) pregabalin followed by placebo or (2) placebo followed by pregabalin. These 2-week treatment periods were separated by a 2-week washout period. Patients on pregabalin treatment received escalating doses to a final dosage of 300 mg/day (days 5–15). In an attempt to minimize placebo response, patients received placebo treatment during the screening week and the 2-week washout period. Average daily pain scores (primary endpoint) were significantly reduced for pregabalin versus placebo, with a mean treatment difference of −0.81 (95% confidence interval: −1.45 to −0.17; P = 0.015). Conclusion: The efficacy of pregabalin was similar to that identified in a large, parallel group trial in PTNP. Therefore, this efficient crossover study design has potential utility for future proof-of-concept studies in neuropathic pain. PMID:22888270

Acute allergic reactions in children with AEDS after prolonged cow's milk elimination diets.

PubMed

Flinterman, A E; Knulst, A C; Meijer, Y; Bruijnzeel-Koomen, C A F M; Pasmans, S G M A

2006-03-01

Food allergy is not always correctly diagnosed in children with atopic eczema dermatitis syndrome (AEDS) and treatment with an avoidance diet is not without danger. After admission to our clinic, 11 children with a prolonged cow's milk (CM) elimination diet because of AEDS and sensitization underwent double-blind placebo-controlled food challenge (DBPCFC). Retrospectively, the exposure to CM, sensitization and reactions to accidental ingestion were carefully documented. The DBPCFC was used to evaluate the childrens' current status. Before the elimination period (median 2.3 years; started before the admission) all 11 children with AEDS were sensitized and had ingested CM (four bottle-fed; seven breast-fed without CM diet of the mother) without the development of acute reactions. The diagnosis of CM allergy was not confirmed by DBPCFC previously. After elimination the AEDS had not improved, but nevertheless the diet was continued. During the elimination period, eight of 11 children developed severe acute allergic reactions to CM after accidental ingestion. In evaluation, in our clinic all 11 children experienced acute allergic reactions to CM during DBPCFC. There is a considerable chance of developing acute allergic reactions to CM after elimination in children with AEDS without previous problems after CM intake.

Clinical Trial: High-Dose Acid Suppression for Chronic Cough: A Randomized, Double-Blind, Placebo-Controlled Trial

PubMed Central

Shaheen, Nicholas J.; Crockett, Seth D.; Bright, Stephanie D.; Madanick, Ryan D.; Buckmire, Robert; Couch, Marion; Dellon, Evan S.; Galanko, Joseph A.; Sharpless, Ginny; Morgan, Douglas R.; Spacek, Melissa B.; Heidt-Davis, Paris; Henke, David

2011-01-01

Summary Background Cough may be a manifestation of gastro-esophageal reflux disease (GERD). The utility of acid suppression in GERD-related cough is uncertain. Aim To assess the impact of high-dose acid suppression with proton pump inhibitors (PPI) on chronic cough in subjects with rare or no heartburn. Methods Subjects were non-smokers without history of asthma, with chronic cough for > 8 weeks. All subjects underwent a baseline 24 hr pH/impedance study, methacholine challenge test (MCT), and laryngoscopy. Subjects were randomized to either 40 mg of esomeprazole twice daily or placebo for 12 weeks. The primary outcome measure was the Cough-Specific Quality of Life Questionnaire (CQLQ). Secondary outcomes were response on Fisman Cough Severity/Frequency scores, and change in laryngeal findings. Results 40 subjects were randomized (22 PPI, 18 placebo) and completed the study. There was no difference between PPI and placebo in CQLQ (mean improvement 9.8, vs. 5.9 in placebo, p = 0.3), or Fisman Cough Severity/Frequency scores. The proportion of patients who improved by >1 standard deviation on the CQLQ was 27.8% (5/18) and 31.8% (7/22) in the placebo and PPI groups respectively. Conclusions In subjects with chronic cough and rare or no heartburn, high-dose PPI did not improve cough-related quality of life or symptoms in this randomized controlled trial. PMID:21083673

GLP-1 receptors exist in the parietal cortex, hypothalamus and medulla of human brains and the GLP-1 analogue liraglutide alters brain activity related to highly desirable food cues in individuals with diabetes: a crossover, randomised, placebo-controlled trial

PubMed Central

Farr, Olivia M.; Sofopoulos, Michail; Tsoukas, Michael A.; Dincer, Fadime; Thakkar, Bindiya; Sahin-Efe, Ayse; Filippaios, Andreas; Bowers, Jennifer; Srnka, Alexandra; Gavrieli, Anna; Ko, Byung-Joon; Liakou, Chrysoula; Kanyuch, Nickole; Tseleni-Balafouta, Sofia; Mantzoros, Christos S.

2016-01-01

Aims/hypothesis Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue that has been demonstrated to successfully treat diabetes and promote weight loss. The mechanisms by which liraglutide confers weight loss remain to be fully clarified. Thus, we investigated whether GLP-1 receptors are expressed in human brains and whether liraglutide administration affects neural responses to food cues in diabetic individuals (primary outcome). Methods In 22 consecutively studied human brains, expression of GLP-1 receptors in the hypothalamus, medulla oblongata and parietal cortex was examined using immunohistochemistry. In a randomised (assigned by the pharmacy using a randomisation enrollment table), placebo-controlled, double-blind, crossover trial, 21 individuals with type 2 diabetes (18 included in analysis due to lack or poor quality of data) were treated with placebo and liraglutide for a total of 17 days each (0.6 mg for 7 days, 1.2 mg for 7 days and 1.8 mg for 3 days). Participants were eligible if they had type 2 diabetes and were currently being treated with lifestyle changes or metformin. Participants, caregivers, people doing measurements and/or examinations, and people assessing the outcomes were blinded to the medication assignment. We studied metabolic changes as well as neurocognitive and neuroimaging (fMRI) of responses to food cues at the clinical research centre of Beth Israel Deaconess Medical Center. Results Immunohistochemical analysis revealed the presence of GLP-1 receptors on neurons in the human hypothalamus, medulla and parietal cortex. Liraglutide decreased activation of the parietal cortex in response to highly desirable (vs less desirable) food images (p < 0.001; effect size: placebo 0.53 ± 0.24, liraglutide −0.47 ± 0.18). No significant adverse effects were noted. In a secondary analysis, we observed decreased activation in the insula and putamen, areas involved in the reward system. Furthermore, we showed that increased ratings of hunger and appetite correlated with increased brain activation in response to highly desirable food cues while on liraglutide, while ratings of nausea correlated with decreased brain activation. Conclusions/interpretation For the first time, we demonstrate the presence of GLP-1 receptors in human brains. We also observe that liraglutide alters brain activity related to highly desirable food cues. Our data point to a central mechanism contributing to, or underlying, the effects of liraglutide on metabolism and weight loss. Future studies will be needed to confirm and extend these findings in larger samples of diabetic individuals and/or with the higher doses of liraglutide (3 mg) recently approved for obesity. PMID:26831302

Low percentage of clinically relevant pistachio nut and mango co-sensitisation in cashew nut sensitised children.

PubMed

van der Valk, J P M; Bouche, R El; Gerth van Wijk, R; de Groot, H; Wichers, H J; Dubois, A E J; de Jong, N W

2017-01-01

Cashew nut, pistachio nut and mango belong to the Anacardiaceae family and are botanically related. Therefore, cashew nut sensitised children are frequently advised to eliminate cashew nuts and pistachio nuts from their diet. The 'Improvement of Diagnostic mEthods for ALlergy assessment (IDEAL trial number NTR3572) study showed that cashew nut sensitised children were co-sensitised to pistachio nut in 98% of cases and to mango in 21% of cases. The aim of this follow-up study to IDEAL is to assess the clinical relevance of co-sensitisation to pistachio nut and mango in cashew nut sensitised children. Children were recruited from the study: 'Improvement of Diagnostic mEthods for ALlergy assessment (IDEAL trial number NTR3572). Inclusion criterion for the IDEAL study was sensitization to cashew nut as demonstrated by either SPT or sIgE, and a clinical history of reactions to cashew nuts or no previous (known) exposure. Sensitized children who were tolerant to cashew nuts were excluded. Inclusion criterion for this IDEAL follow-up study was co-sensitization to pistachio nut, regardless the result of the DBPCFC with cashew nut. In this follow-up study a double-blind placebo-controlled food challenge with pistachio nut and an open food challenge with mango were performed. Twenty-nine children (mean age of 11.6 years, 62% male) were included. Pistachio nut sensitisation was clinically relevant in only 34% of cashew-sensitised children and only 31% of cashew challenge positive children. None of the children was challenge positive to mango. Although co-sensitisation between cashew nut and pistachio nut was observed in 98%, pistachio nut sensitisation was only clinically relevant in 34% of the children. Therefore, a challenge test with pistachio nut is recommended in children with cashew nut and pistachio nut sensitisation. Trial registration The study was registered in the Dutch trial register (registration number 3572) on 10 August 2012 (retrospectively registered).

Profilin desensitization: A case series

PubMed Central

Nucera, Eleonora; Aruanno, Arianna; Rizzi, Angela; Pecora, Valentina; Patriarca, Giampiero; Buonomo, Alessandro; Mezzacappa, Simona; Schiavino, Domenico

2016-01-01

The role of profilin as an allergen has long been questioned. The capacity of profilin to induce respiratory symptoms has recently been demonstrated; moreover, over 50% of patients sensitized to profilin experienced symptoms after the ingestion of plant-derived foods, suggesting that profilin should be considered as a clinically relevant food allergen. We describe the cases of seven allergic patients with oral allergy syndrome and other adverse reactions after eating plant-derived food, that have been undergone to profilin desensitization treatment. The protocol started with a drop of profilin solution (50 µg/mL) diluted 1:1018 in water until the highest dose of 10 drops of undiluted solution three times a week. At the end of the treatment we observed a decreased mean diameter of profilin wheal in skin prick test (SPT) in five of the seven participants and in profilin specific IgE values in six patients that repeated the test. Regarding basophil activation test (BAT) and the detection of IgG4, we do not have significant results because the tests have to be repeated in some patients. Regarding the double-blind placebo-controlled challenges, after about 10 months of induction phase all the patients showed tolerance to several foods that they previously did not tolerate. Moreover, the immunotherapy with profilin has proved to be safe because no serious adverse events have been reported in our patients. In summary, the results of this exploratory study of sublingual immunotherapy (SLIT) for profilin allergy show that it can be a promising therapeutic option that could modify the clinical reactivity of the patients to the intake of plant-derived food. PMID:26684620

Effects of guar gum ingestion on postprandial blood pressure in older adults.

PubMed

Jang, A L; Hwang, S K; Kim, D U

2015-03-01

The aim of this study was to investigate the effects of guar gum on postprandial blood pressure in older people. A randomized, double-blind, placebo-controlled, cross-over design. Community senior centers in B city, South Korea. Twenty-two older female adults aged 67 to 88 with postprandial hypotension. The participants were randomly assigned to guar gum (semi-fluid food with 9 gram) or placebo intervention during the first treatment phase. After a washout period of 1 week, the two interventions were switched to the other in the second treatment phase. Blood pressure was measured during both phases before having a meal and every 15 minutes during 120 minutes after a meal with automated sphygmomanometer. Change in systolic blood pressure (SBP) over time was significantly different between guar gum and placebo groups (F=4.07, p=0.001). Compared with placebo group, guar gum group had significantly low prevalence of postprandial hypotension (PPH) (guar gum group=18.2% vs. placebo group=72.7%; χ² =13.20, p<0.001). It also had significant difference in change of diastolic blood pressure (DBP) over time between guar gum and placebo groups (F=2.49, p=0.027). This findings show that guar gum could be effective on postprandial drops in blood pressure in older female adults.

Bioavailability of epicatechin and effects on nitric oxide metabolites of an apple flavanol-rich extract supplemented beverage compared to a whole apple puree: a randomized, placebo-controlled, crossover trial.

PubMed

Hollands, Wendy J; Hart, David J; Dainty, Jack R; Hasselwander, Oliver; Tiihonen, Kirsti; Wood, Richard; Kroon, Paul A

2013-07-01

Flavanol-rich foods are known to exert beneficial effects on cardiovascular health. The biological effects depend on bioavailability of flavanols which may be influenced by food matrix and dose ingested. We compared the bioavailability and dose-response of epicatechin from whole apple and an epicatechin-rich extract, and the effects on plasma and urinary nitric oxide (NO) metabolites. In a randomized, placebo-controlled, crossover trial, subjects consumed drinks containing 70 and 140 mg epicatechin from an apple extract and an apple puree containing 70 mg epicatechin. Blood and urine samples were collected for 24 h post ingestion. Maximum plasma concentration, AUC(0-24 h) , absorption and urinary excretion were all significantly higher after ingestion of both epicatechin drinks compared with apple puree (p < 0.05). Time to maximum plasma concentration was significantly later for the puree compared with the drinks (p < 0.01). Epicatechin bioavailability was >2-fold higher after ingestion of the 140 mg epicatechin drink compared to the 70 mg epicatechin drink (p < 0.05). Excretion of NO metabolites was higher for all test products compared with placebo, which was significant for the high dose drink (p = 0.016). Oral bioavailability of apple epicatechin increases at higher doses, is reduced by whole apple matrix and has the potential to increase NO bioavailability. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Sensitivity of the appetite control system in obese subjects to nutritional and serotoninergic challenges.

PubMed

Hill, A J; Blundell, J E

1990-03-01

The sensitivity of the appetite system of a group of obese individuals was assessed in response to two challenges known to reduce hunger and enhance satiety in lean people. The challenges were the presentation of a caloric (high protein) load and the activation of serotonin systems. Eight obese female adults (BMI = 38) received 2 X 15 mg d-fenfluramine or placebo daily for 3 days, the study conforming to a 2 X 2 factor (drug X lunch type), double blind, repeated measures design. Three hours after dosing on day 3 they ate either a high carbohydrate (63 percent of total energy) or high protein (54 percent) lunchtime meal (the caloric load). These fixed meal challenges were equal in energy (475 kcal), weight and fat content. Ratings of hunger motivation and food preferences were tracked over the course of lunch and for a further 3 hours, at which point subjects returned for a self-selection test meal. Intakes from this second open meal revealed significant main effects of both caloric load and drug on energy intake, with the high protein d-fenfluramine combination being the most potent anorectic pairing. These findings were supported by the profiles of hunger motivation. This study has confirmed that the appetite system of these subjects was responsive to these biologically relevant challenges. The results suggest that the combination of an appetite modulating drug with specific dietary intervention may represent an effective strategy for the management of hunger arising from caloric restriction.

Need for common internal controls when assessing the relative efficacy of pharmacologic agents using a meta-analytic approach: case study of cyclooxygenase 2-selective inhibitors for the treatment of osteoarthritis.

PubMed

Lee, Chin; Hunsche, Elke; Balshaw, Robert; Kong, Sheldon X; Schnitzer, Thomas J

2005-08-15

To evaluate the role of common internal controls in a meta-analysis of the relative efficacy of cyclooxygenase 2-selective inhibitors (coxibs) in the treatment of osteoarthritis (OA). A systematic search of Medline and US Food and Drug Administration electronic databases was performed to identify randomized, placebo-controlled clinical trials of coxibs (etoricoxib, celecoxib, rofecoxib, valdecoxib) in patients with hip and/or knee OA. The effect size for coxibs and common active internal controls (nonsteroidal antiinflammatory drugs [NSAIDs], naproxen) were determined by the mean changes from baseline in Western Ontario and McMaster Universities Osteoarthritis Index pain subscores as compared with placebo. The effect size for all coxib groups combined (0.44) indicated greater efficacy as compared with placebo, but significant heterogeneity (P < 0.0001) was observed. Rofecoxib at dosages of 12.5 mg/day and 25 mg/day and etoricoxib at a dosage of 60 mg/day had similar effect sizes (0.68 and 0.73, respectively), but these effect sizes were comparatively greater than those for both celecoxib at dosages of 200 mg/day and 100 mg twice daily or valdecoxib at a dosage of 10 mg/day (0.26 and 0.16, respectively). The effect sizes for NSAIDs or naproxen versus placebo, as determined using data from rofecoxib/etoricoxib trials, were consistently higher than the effect sizes derived from trials of celecoxib/valdecoxib. Significant heterogeneity was present in the overall effect size for NSAIDs (P = 0.007) and naproxen (P = 0.04) groups based on data available from all coxib trials. Coxibs and common active internal controls showed larger effect sizes versus placebo in the rofecoxib/etoricoxib trials than in the celecoxib/valdecoxib trials. These findings suggest systematic differences among published coxib trials and emphasize the need for direct-comparison trials. In the absence of such trials, common internal controls should be assessed when performing indirect meta-analytic comparisons.

A Synthetic Influenza Virus Vaccine Induces a Cellular Immune Response That Correlates with Reduction in Symptomatology and Virus Shedding in a Randomized Phase Ib Live-Virus Challenge in Humans

PubMed Central

Pleguezuelos, Olga; Robinson, Stuart; Fernández, Ana; Stoloff, Gregory A.; Mann, Alex; Gilbert, Anthony; Balaratnam, Ganesh; Wilkinson, Tom; Lambkin-Williams, Rob; Oxford, John

2015-01-01

Current influenza vaccines elicit primarily antibody-based immunity. They require yearly revaccination and cannot be manufactured until the identification of the circulating viral strain(s). These issues remain to be addressed. Here we report a phase Ib trial of a vaccine candidate (FLU-v) eliciting cellular immunity. Thirty-two males seronegative for the challenge virus by hemagglutination inhibition assay participated in this single-center, randomized, double-blind study. Volunteers received one dose of either the adjuvant alone (placebo, n = 16) or FLU-v (500 μg) and the adjuvant (n = 16), both in saline. Twenty-one days later, FLU-v (n = 15) and placebo (n = 13) volunteers were challenged with influenza virus A/Wisconsin/67/2005 (H3N2) and monitored for 7 days. Safety, tolerability, and cellular responses were assessed pre- and postvaccination. Virus shedding and clinical signs were assessed postchallenge. FLU-v was safe and well tolerated. No difference in the prevaccination FLU-v-specific gamma interferon (IFN-γ) response was seen between groups (average ± the standard error of the mean [SEM] for the placebo and FLU-v, respectively, 1.4-fold ± 0.2-fold and 1.6-fold ± 0.5-fold higher than the negative-control value). Nineteen days postvaccination, the FLU-v group, but not the placebo group, developed FLU-v-specific IFN-γ responses (8.2-fold ± 3.9-fold versus 1.3-fold ± 0.1-fold higher than the negative-control value [average ± SEM] for FLU-v versus the placebo [P = 0.0005]). FLU-v-specific cellular responses also correlated with reductions in both viral titers (P = 0.01) and symptom scores (P = 0.02) postchallenge. Increased cellular immunity specific to FLU-v correlates with reductions in both symptom scores and virus loads. (This study has been registered at ClinicalTrials.gov under registration no. NCT01226758 and at hra.nhs.uk under EudraCT no. 2009-014716-35.) PMID:25994549

A Synthetic Influenza Virus Vaccine Induces a Cellular Immune Response That Correlates with Reduction in Symptomatology and Virus Shedding in a Randomized Phase Ib Live-Virus Challenge in Humans.

PubMed

Pleguezuelos, Olga; Robinson, Stuart; Fernández, Ana; Stoloff, Gregory A; Mann, Alex; Gilbert, Anthony; Balaratnam, Ganesh; Wilkinson, Tom; Lambkin-Williams, Rob; Oxford, John; Caparrós-Wanderley, Wilson

2015-07-01

Current influenza vaccines elicit primarily antibody-based immunity. They require yearly revaccination and cannot be manufactured until the identification of the circulating viral strain(s). These issues remain to be addressed. Here we report a phase Ib trial of a vaccine candidate (FLU-v) eliciting cellular immunity. Thirty-two males seronegative for the challenge virus by hemagglutination inhibition assay participated in this single-center, randomized, double-blind study. Volunteers received one dose of either the adjuvant alone (placebo, n = 16) or FLU-v (500 μg) and the adjuvant (n = 16), both in saline. Twenty-one days later, FLU-v (n = 15) and placebo (n = 13) volunteers were challenged with influenza virus A/Wisconsin/67/2005 (H3N2) and monitored for 7 days. Safety, tolerability, and cellular responses were assessed pre- and postvaccination. Virus shedding and clinical signs were assessed postchallenge. FLU-v was safe and well tolerated. No difference in the prevaccination FLU-v-specific gamma interferon (IFN-γ) response was seen between groups (average ± the standard error of the mean [SEM] for the placebo and FLU-v, respectively, 1.4-fold ± 0.2-fold and 1.6-fold ± 0.5-fold higher than the negative-control value). Nineteen days postvaccination, the FLU-v group, but not the placebo group, developed FLU-v-specific IFN-γ responses (8.2-fold ± 3.9-fold versus 1.3-fold ± 0.1-fold higher than the negative-control value [average ± SEM] for FLU-v versus the placebo [P = 0.0005]). FLU-v-specific cellular responses also correlated with reductions in both viral titers (P = 0.01) and symptom scores (P = 0.02) postchallenge. Increased cellular immunity specific to FLU-v correlates with reductions in both symptom scores and virus loads. (This study has been registered at ClinicalTrials.gov under registration no. NCT01226758 and at hra.nhs.uk under EudraCT no. 2009-014716-35.). Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Infrared therapy for chronic low back pain: A randomized, controlled trial

PubMed Central

Gale, George D; Rothbart, Peter J; Li, Ye

2006-01-01

OBJECTIVE The objective of the present study was to assess the degree of pain relief obtained by applying infrared (IR) energy to the low back in patients with chronic, intractable low back pain. METHODS Forty patients with chronic low back pain of over six years’ duration were recruited from patients attending the Rothbart Pain Management Clinic, North York, Ontario. They came from the patient lists of three physicians at the clinic, and were randomly assigned to IR therapy or placebo treatment. One patient dropped out of the placebo group; as a result, 21 patients received IR therapy and 18 recieved placebo therapy. The IR therapy was provided by two small, portable units in a sturdy waistband powered by small, rechargeable batteries made by MSCT Infrared Wraps Inc (Canada). These units met safety standards for Food and Drug Administration portability, and are registered with the Food and Drug Administration as a therapeutic device. The unit converted electricity to IR energy at 800 nm to 1200 nm wavelength. The treated group received IR therapy. The placebo group had identical units, but the power was not connected to the circuit-board within the IR pad. Patients attended seven weekly sessions. One baseline and six weekly sets of values were recorded. The principle measure of outcome was pain rated on the numerical rating scale (NRS). The pain was assessed overall, then rotating and bending in different directions. RESULTS The mean NRS scores in the treatment group fell from 6.9 of 10 to 3 of 10 at the end of the study. The mean NRS in the placebo group fell from 7.4 of 10 to 6 of 10. CONCLUSION The IR therapy unit used was demonstrated to be effective in reducing chronic low back pain, and no adverse effects were observed. PMID:16960636

Echocardiographic assessment of cardiac valvular regurgitation with lorcaserin from analysis of 3 phase 3 clinical trials.

PubMed

Weissman, Neil J; Sanchez, Matilde; Koch, Gary G; Smith, Steven R; Shanahan, William R; Anderson, Christen M

2013-07-01

Lorcaserin is a selective 5-HT2C agonist evaluated for weight management in clinical trials. Echocardiographic monitoring was conducted to test the hypothesis that selective 5-HT2C agonism would avoid valvular heart disease. Echocardiographic and weight change data from 5249 obese and overweight patients in 3 phase 3 trials were integrated. Treatment duration with 10 mg lorcaserin twice daily or placebo was 52 weeks. The proportions of patients who developed Food and Drug Administration-defined valvulopathy (≥ mild aortic or ≥ moderate mitral regurgitation) and changes in regurgitant grade at each heart valve were evaluated. Possible associations between weight or body mass index change and valvulopathy were explored. New valvulopathy was present in 2.04% of placebo and 2.37% of lorcaserin recipients at 52 weeks (risk difference, 0.33%; 95% confidence interval, -0.46 to 1.13; risk ratio, 1.16 [all patients with sufficient echocardiographic data, last-observation-carried-forward imputation] or 1.03 [patients who completed 52 weeks]). Changes in weight and body mass index were negatively associated with presence of valvulopathy at week 52 (P=0.02 and P=0.04, respectively); a 5% decrease in weight was associated with an odds ratio of 1.15 for Food and Drug Administration-defined valvulopathy. Most changes in regurgitation were ±1 grade in both treatment groups at all heart valves. In 3 prospective placebo-controlled trials with integrated data for 5249 patients, the rate of echocardiographic valvulopathy was similar with lorcaserin and placebo. Point estimates for risk ratios ranged from 1.03 to 1.16 and may be at least partially influenced by greater weight loss in the lorcaserin group than in the placebo group. URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00395135, NCT00603291, NCT00603902.

Antiobesity Effect of Caraway Extract on Overweight and Obese Women: A Randomized, Triple-Blind, Placebo-Controlled Clinical Trial

PubMed Central

Radzi, Che Wan Jasimah Bt wan Mohamed; Hajifaraji, Majid; Haerian, Batoul Sadat; Mosaddegh, Mohammad Hossein; Cordell, Geoffrey A.

2013-01-01

Caraway (Carum carvi L.), a potent medicinal plant, is traditionally used for treating obesity. This study investigates the weight-lowering effects of caraway extract (CE) on physically active, overweight and obese women through a randomized, triple-blind, placebo-controlled clinical trial. Seventy overweight and obese, healthy, aerobic-trained, adult females were randomly assigned to two groups (n = 35 per group). Participants received either 30 mL/day of CE or placebo without changing their diet or physical activity. Subjects were examined at baseline and after 90 days for changes in body composition, anthropometric indices, and clinical and paraclinical variables. The treatment group, compared with placebo, showed a significant reduction of weight, body mass index, body fat percentage, and waist-to-hip ratio. No changes were observed in lipid profile, urine-specific gravity, and blood pressure of subjects. The results suggest that a dietary CE with no restriction in food intake, when combined with exercise, is of value in the management of obesity in women wishing to lower their weight, BMI, body fat percentage, and body size, with no clinical side effects. In conclusion, results of this study suggest a possible phytotherapeutic approach for caraway extract in the management of obesity. This trial is registered with NCT01833377. PMID:24319489

The role of histamine degradation gene polymorphisms in moderating the effects of food additives on children's ADHD symptoms.

PubMed

Stevenson, Jim; Sonuga-Barke, Edmund; McCann, Donna; Grimshaw, Kate; Parker, Karen M; Rose-Zerilli, Matthew J; Holloway, John W; Warner, John O

2010-09-01

Food additives can exacerbate ADHD symptoms and cause non-immunoglobulin E-dependent histamine release from circulating basophils. However, children vary in the extent to which their ADHD symptoms are exacerbated by the ingestion of food additives. The authors hypothesized that genetic polymorphisms affecting histamine degradation would explain the diversity of responses to additives. In a double-blind, placebo-controlled crossover trial, challenges involving two food color additive and sodium benzoate (preservative) mixtures in a fruit drink were administered to a general community sample of 3-year-old children (N = 153) and 8/9-year-old children (N = 144). An aggregate ADHD symptom measure (based on teacher and parent blind ratings of behavior, blind direct observation of behavior in the classroom, and--for 8/9-year-old children only--a computerized measure of attention) was the main outcome variable. The adverse effect of food additives on ADHD symptoms was moderated by histamine degradation gene polymorphisms HNMT T939C and HNMT Thr105Ile in 3- and 8/9-year-old children and by a DAT1 polymorphism (short versus long) in 8/9-year-old children only. There was no evidence that polymorphisms in catecholamine genes COMT Val108Met, ADRA2A C1291G, and DRD4-rs7403703 moderated the effect on ADHD symptoms. Histamine may mediate the effects of food additives on ADHD symptoms, and variations in genes influencing the action of histamine may explain the inconsistency between previous studies. Genes influencing a range of neurotransmitter systems and their interplay with environmental factors, such as diet, need to be examined to understand genetic influences on ADHD symptoms.

Incomplete digestion of codfish represents a risk factor for anaphylaxis in patients with allergy

PubMed Central

Untersmayr, Eva; Vestergaard, Helle; Malling, Hans-Jørgen; Jensen, Louise Bjerremann; Platzer, Michael H.; Boltz-Nitulescu, George; Scheiner, Otto; Skov, Per Stahl; Jensen-Jarolim, Erika; Poulsen, Lars K.

2010-01-01

Background Fish represents one of the most important allergenic foods causing severe allergic reactions. Nevertheless, it has been shown that gastric digestion significantly reduces its allergenic capacity. Objective In this study, we assessed the absorption kinetics of fish proteins and investigated the clinical reactivity of patients with fish allergy to codfish digested at physiological or elevated gastric pH. Methods Healthy individuals were openly challenged with codfish and blood samples were evaluated by histamine release for absorbed fish allergens. Patients with allergy were recruited on the basis of previously diagnosed codfish allergy. Fish extracts were digested with gastric enzymes at pH 2.0 and 3.0 and used for histamine release, skin prick tests, and titrated double-blind placebo-controlled food challenges. Results Ingestion experiments in subjects without allergy revealed absorption of biologically active fish allergens only 10 minutes after ingestion with maximal serum levels after 1 to 2 hours. Incubation of fish proteins with digestive enzymes at pH 2.0 resulted in a fragmentation of the proteins leading to a reduced biological activity evidenced by a significantly smaller wheal reaction and reduced histamine release. Fish digested at pH 3.0 revealed comparable reactivity patterns as undigested extracts. Moreover, these test materials triggered reactions at 10-fold to 30-fold lower cumulated challenge doses in patients with allergy. Conclusion Our data indicate the paramount importance of gastric digestion for fish allergens because the quantitatively significant absorption and elicitation of symptoms seemed to take place in the intestine. Clinical implications Hindered digestion puts patients with fish allergy at risk to develop severe allergic reactions at minute amounts of allergens. PMID:17215033

A Randomized, Placebo-Controlled, Crossover Trial of Cannabis Cigarettes in Neuropathic Pain

PubMed Central

Wilsey, Barth; Marcotte, Thomas; Tsodikov, Alexander; Millman, Jeanna; Bentley, Heather; Gouaux, Ben; Fishman, Scott

2016-01-01

The Food and Drug Administration (FDA), Substance Abuse and Mental Health Services Administration (SAMHSA), and the National Institute for Drug Abuse (NIDA) report that no sound scientific studies support the medicinal use of cannabis. Despite this lack of scientific validation, many patients routinely use “medical marijuana,” and in many cases this use is for pain related to nerve injury. We conducted a double-blinded, placebo-controlled, crossover study evaluating the analgesic efficacy of smoking cannabis for neuropathic pain. Thirty-eight patients with central and peripheral neuropathic pain underwent a standardized procedure for smoking either high-dose (7%), low-dose (3.5%), or placebo cannabis. In addition to the primary outcome of pain intensity, secondary outcome measures included evoked pain using heat-pain threshold, sensitivity to light touch, psychoactive side effects, and neuropsychological performance. A mixed linear model demonstrated an analgesic response to smoking cannabis. No effect on evoked pain was seen. Psychoactive effects were minimal and well-tolerated, with some acute cognitive effects, particularly with memory, at higher doses. PMID:18403272

Mammalian milk allergy: clinical suspicion, cross-reactivities and diagnosis.

PubMed

Järvinen, Kirsi M; Chatchatee, Pantipa

2009-06-01

Cow's milk allergy affects 2-3% of young children, the economic impact of which necessitates search for simple diagnostic tools and affordable milk substitutes. This review examines recent studies on the diagnosis of cow's milk allergy as well as on the allergenicity of milk from other mammalian species. Resolution of symptoms during strict milk avoidance and their re-appearance during the double-blind, placebo-controlled milk challenge remains the gold standard for the diagnosis of cow's milk allergy. Allergic eosinophilic esophagitis/gastroenteritis requires confirmatory endoscopic biopsy. There are increasing data in various populations on cut-off points based on positive predictive values for skin prick test and milk-specific IgE measurements to aid in the diagnosis of cow's milk allergy and to decrease the number of unnecessary food challenges. For non-IgE-mediated manifestations, noninvasive diagnostic tests are still largely lacking. The significant homology between milk from cow, sheep and goat results in clinical cross-reactivity. However, mare's or donkey's milk may be tolerated by some individuals. Data have been accumulating on the utility of diagnostic tools for mostly IgE-mediated milk allergy and allergenicity of milk from other mammalian species, although further studies are sought.

Oxytocin enhances cognitive control of food craving in women.

PubMed

Striepens, Nadine; Schröter, Franziska; Stoffel-Wagner, Birgit; Maier, Wolfgang; Hurlemann, René; Scheele, Dirk

2016-12-01

In developed countries, obesity has become an epidemic resulting in enormous health care costs for society and serious medical complications for individuals. The homeostatic regulation of food intake is critically dependent on top-down control of reward-driven food craving. There is accumulating evidence from animal studies that the neuropeptide oxytocin (OXT) is involved in regulating hunger states and eating behavior, but whether OXT also contributes to cognitive control of food craving in humans is still unclear. We conducted a counter-balanced, double-blind, within-subject, pharmacological magnetic resonance imaging experiment involving 31 healthy women who received 24 IU of intranasal OXT or placebo and were scanned twice while they were exposed to pictures of palatable food. The participants were instructed either to imagine the immediate consumption or to cognitively control the urge to eat the food. Our results show a trend that OXT specifically reduced food craving in the cognitive control condition. On the neural level, these findings were paralleled by an increase of activity in the middle and superior frontal gyrus, precuneus, and cingulate cortex under OXT. Interestingly, the behavioral OXT effect correlated with the OXT-induced changes in the prefrontal cortex and precuneus. Collectively, the present study provides first evidence that OXT plays a key role in the cognitive regulation of food craving in women by strengthening activity in a broad neurocircuitry implicated in top-down control and self-referential processing. Hum Brain Mapp 37:4276-4285, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Effect of fat on serum 25-hydroxyvitamin D levels after a single oral dose of vitamin D in young healthy adults: a double-blind randomized placebo-controlled study.

PubMed

Raimundo, Fabiana Viegas; Lang, Maria Augusta Britto; Scopel, Luciano; Marcondes, Natália Aydos; Araújo, Mirna Griselda Anocibar; Faulhaber, Gustavo Adolpho Moreira; Furlanetto, Tania Weber

2015-04-01

This double-blind placebo-controlled trial evaluated serum 25-hydroxyvitamin D [25(OH)D] levels after the oral intake of a single dose of cholecalciferol during one of the three meals, containing different amounts of fat or placebo. Sixty-four healthy medical residents or students of a university hospital in Porto Alegre, latitude 30° S, Brazil, were divided into four groups. Three groups received a single 50,000 IU oral dose of cholecalciferol during a meal containing 0 g (Group 1), 15 g (Group 2) or 30 g (Group 3) of fat, and one group received placebo (Group 4), according to randomization. Serum 25(OH)D, parathyroid hormone, total calcium, albumin, magnesium, and creatinine levels, and urinary calcium, magnesium, and creatinine levels were measured at baseline and after 14 days. Baseline mean serum 25(OH)D levels were low in all groups. Vitamin D given during breakfast increased the mean change of serum 25(OH)D levels, when compared to placebo. Furthermore, the intake of fat with vitamin D increased the mean change of serum 25(OH)D levels. A single oral dose of vitamin D given with food increased mean serum 25(OH)D levels, after 2 weeks, and the mean increase was larger, when the meal had at least 15 g of fat. These findings can have important implications to oral vitamin D supplementation.

Consumption of cranberry beverage improved endogenous antioxidant status and protected against bacteria adhesion in healthy humans: a randomized controlled trial.

PubMed

Mathison, Bridget D; Kimble, Lindsey L; Kaspar, Kerrie L; Khoo, Christina; Chew, Boon P

2014-05-01

Consumption of polyphenol-rich foods is associated with lower risk from many chronic diseases. We hypothesized that a single dose of cranberry beverage would improve indices of oxidative stress, inflammation, and urinary antibacterial adhesion activity in healthy humans. Six males and 6 females (18-35 years; body mass index, 19-25 kg/m(2)) consumed placebo, cranberry leaf extract beverage, or low-calorie cranberry juice cocktail (LCJC) once in a randomized, double-blind, placebo-controlled cross-over experimental design trial. The washout period between beverages was 1 week. Blood was collected 0, 2, 4, 8, and 24 hours after beverage consumption for measuring oxidative and inflammatory biomarkers. Urine was collected at 0, 0 to 3, 3 to 6, 6 to 9, 9 to 12, and 24 hours postintervention to assess antibacterial adhesion activity. Consumption of cranberry leaf extract beverage elevated (P < .05) blood glutathione peroxidase activity, whereas LCJC consumption increased (P < .05) glutathione concentrations and superoxide dismutase activity compared with placebo. Cranberry leaf extract beverage and LCJC consumption had no effect on the inflammatory biomarkers measured as compared with placebo. At 0 to 3 hours postconsumption, urine from participants who consumed cranberry beverages had higher (P < .05) ex vivo antiadhesion activity against P-fimbriated Escherichia coli compared with placebo. An acute dose of cranberry beverages improved biomarkers of antioxidant status and inhibition of bacterial adhesion in urine. Copyright © 2014 Elsevier Inc. All rights reserved.

High-Fiber Orange Juice as a Nutrition Supplement in Women: A Randomized, Double-Blind, Placebo-Controlled Study of Tolerance and Effectiveness.

PubMed

Bergamasco, Christiane; Horie, Lilian Mika; Torrinhas, Raquel Susana; Waitzberg, Dan L

2015-11-01

The daily consumption of dietary fiber is frequently below suggested recommendations. Using a double-blind, controlled, randomized study, we assessed the efficiency and tolerance of a fiber-enriched orange juice to supplement fiber intake in women. After 1 week of noninterventional observation, 192 healthy adult women ingested 400 mL of orange juice for 21 days, which either was not (placebo group) or was enriched with fiber (fiber group). Orange juice ingestion was registered daily and controlled for each week during the study period. Macronutrient, fiber, and energy intake were determined using a 3-day food record, validated food chemical composition databases, and the "Pro Diet" software. Gastrointestinal symptoms were self-evaluated daily by scoring 4 grades of symptom intensity and using a visual analog scale to grade pain severity. No changes were observed for macronutrient and energy ingestion. For the placebo group (n = 97), the total fiber intake record was under the daily recommended value. In contrast, the fiber group (n = 95) displayed higher comparative values of total and soluble fiber consumption (P ≤ .001), achieving the daily recommended values of fiber intake. Both groups reported an increased frequency of slight bloating and rumbles over time (P ≤ .05). The fiber group also experienced a higher frequency of slight flatulence over time (P = .002). Consumption of fiber-enriched orange juice was efficient to achieve the daily fiber intake recommendation for women, was not accompanied by intense adverse events, and may represent a suitable method to supplement fiber intake in woman. © 2014 American Society for Parenteral and Enteral Nutrition.

In vitro testing to diagnose venom allergy and monitor immunotherapy: a placebo-controlled, crossover trial.

PubMed

Brown, S G A; Haas, M A; Black, J A; Parameswaran, A; Woods, G M; Heddle, R J

2004-05-01

In people with a history of sting allergy, only prior reaction severity and older age are known to predict subsequent reaction risk. Furthermore, no diagnostic test other than a deliberate sting challenge has been found to identify people in whom venom immunotherapy (VIT) has been unsuccessful. We aimed to assess the utility of a number of in vitro tests to diagnose venom allergy and to monitor immunotherapy. During a double-blind randomized placebo-controlled crossover trial of Myrmecia pilosula ant VIT the following venom-specific tests were performed at enrolment, and at completion of treatment prior to a diagnostic sting challenge; leucocyte stimulation index (SI), IL-4 production, IgE RAST, histamine release test (HRT), leukotriene release test (LRT) and basophil activation test (BAT). Intradermal venom skin testing (VST) was also performed at trial entry. Only VST and HRT identified those at risk of sting anaphylaxis in the placebo group. Although IgE RAST, leucocyte SI and IL-4 production, LRT and BAT all correlated well with intradermal VSTs, they did not predict sting challenge outcome. After successful VIT, venom-induced leucocyte IL-4 production tended to fall, whereas IgE RAST increased and a natural decline in HRT reactivity was reversed. A confounding seasonal affect on laboratory results was suspected. The HRT warrants further assessment for diagnosis of venom allergy. Uninformative performance of the commercially available LRT and BAT tests may be due to pre-incubation with IL-3. None of the tests evaluated appear to be reliable markers of successful VIT.

Postprandial effects of a polyphenolic grape extract (PGE) supplement on appetite and food intake: a randomised dose-comparison trial.

PubMed

Shin, Hyun-San; Kindleysides, Sophie; Yip, Wilson; Budgett, Stephanie C; Ingram, John R; Poppitt, Sally D

2015-09-14

There is recent evidence that glucose delivered to the distal small intestine (SI) may stimulate the ileal brake and inhibit appetite. High polyphenolic grape extract (PGE) has been shown to inhibit α-amylase and α-glucosidase activity, two key enzymes required for starch digestion, in vitro. It is hypothesised to slow digestion and absorption of starch in the proximal SI such that glucose may be delivered distally into the ileum and suppress appetite. This study investigated the safety and efficacy of a PGE supplement, delivered within a capsule and consumed with a high-starch breakfast, on appetite ratings and ad libitum energy intake (EI) at a subsequent lunch meal. Twenty healthy, non-obese (BMI 18-28 kg/m(2)) male volunteers participated in a randomised, double blind, placebo controlled, three arm, cross-over study. Participants were administered (i) low dose PGE500 (500 mg), (ii) high dose PGE1500 (1500 mg), and (iii) matched placebo with a 2 MJ high-starch breakfast (white bread); followed 3 h later by a single item buffet-style lunch meal (pasta and meat sauce). Outcome variables were feelings of hunger, fullness, prospective thoughts of food (TOF) and satisfaction assessed using visual analogue scales (VAS); and ad lib energy and macronutrient intake at the lunch meal. There was no detectable effect of PGE500 or PGE1500 compared with placebo (all, time*supplement interaction, P > 0.05) on VAS-assessed hunger, fullness, TOF or satisfaction. There was also no evidence that PGE significantly altered ad lib energy or macronutrient intake at the lunch meal relative to placebo (P > 0.05). EI following PGE500 was +164 kJ higher than placebo (+5.3%, P > 0.05); and EI following PGE1500 was -51 kJ lower than placebo (-1.7%, P > 0.05). Whilst well tolerated, there was no evidence that encapsulated low dose PGE500 or high dose PGE1500 consumed with a high starch breakfast meal altered postprandial hunger, fullness, TOF or satisfaction relative to a matched placebo. Nor was there evidence that either dose altered ad lib energy or macronutrient intake at an outcome meal. ACTRN12614000041651.

On Suggestibility and Placebo: A Follow-Up Study.

PubMed

Lifshitz, Michael; Sheiner, Eli O; Olson, Jay A; Thériault, Rémi; Raz, Amir

2017-04-01

Identifying what makes some people respond well to placebos remains a major challenge. Here, we attempt to replicate an earlier study in which we found a relationship between hypnotic suggestibility and subjective ratings of relaxation following the ingestion of a placebo sedative (Sheiner, Lifshitz, & Raz, 2016). To assess the reliability of this effect, we tested 34 participants using a similar design. Participants ingested a placebo capsule in one of two conditions: (1) relaxation, wherein we described the capsule as a herbal sedative, or (2) control, wherein we described the capsule as inert. To index placebo response, we collected measures of blood pressure and heart rate, as well as self-report ratings of relaxation and drowsiness. Despite using a similar experimental design as in our earlier study, we were unable to replicate the correlation between hypnotic suggestibility and placebo response. Furthermore, whereas in our former experiment we observed a change in subjective ratings of relaxation but no change in physiological measures, here we found that heart rate dropped in the relaxation condition while subjective ratings remained unchanged. Even within a consistent context of relaxation, therefore, our present results indicate that placebos may induce effects that are fickle, tenuous, and unreliable. Although we had low statistical power, our findings tentatively accord with the notion that placebo response likely involves a complex, multifaceted interaction between traits, expectancies, and contexts.

Determining bioavailability of food folates in a controlled intervention study.

PubMed

Hannon-Fletcher, Mary P; Armstrong, Nicola C; Scott, John M; Pentieva, Kristina; Bradbury, Ian; Ward, Mary; Strain, J J; Dunn, Adele A; Molloy, Anne M; Kerr, Maeve A; McNulty, Helene

2004-10-01

The concept of dietary folate equivalents (DFEs) in the United States recognizes the differences in bioavailability between natural food folates and the synthetic vitamin, folic acid. However, many published reports on folate bioavailability are problematic because of several confounding factors. We compared the bioavailability of food folates with that of folic acid under controlled conditions. To broadly represent the extent to which natural folates are conjugated in foods, we used 2 natural sources of folate, spinach (50% polyglutamyl folate) and yeast (100% polyglutamyl folate). Ninety-six men were randomly assigned according to their screening plasma homocysteine (tHcy) concentration to 1 of 4 treatment groups for an intervention period of 30 d. Each subject received (daily under supervision) either a folate-depleted "carrier" meal or a drink plus 1) placebo tablet, 2) 200 microg folic acid in a tablet, 3) 200 microg natural folate provided as spinach, or 4) 200 microg natural folate provided as yeast. Among the subjects who completed the intervention, responses (increase in serum folate, lowering of tHcy) relative to those in the placebo group (n = 18) were significant in the folic acid group (n = 18) but not in the yeast folate (n = 19) or the spinach folate (n = 18) groups. Both natural sources of folate were significantly less bioavailable than was folic acid. Overall estimations of folate bioavailability relative to that of folic acid were found to be between 30% (spinach) and 59% (yeast). Relative bioavailability estimates were consistent with the estimates from the metabolic study that were used as a basis to derive the US DFE value.

Effects of a novel sodium channel blocker, GSK2339345, in patients with refractory chronic cough
.

PubMed

Smith, Jaclyn A; McGarvey, Lorcan P A; Badri, Huda; Satia, Imran; Warren, Francis; Siederer, Sarah; Liefaard, Lia; Murdoch, Robert D; Povey, Kathryn; Marks-Konczalik, Joanna

2017-09-01

Voltage-gated sodium channels (VGSC) are important in the initiation and propagation of action potentials in afferent sensory nerve fibers responsible for evoking cough. This study investigated the efficacy of GSK2339345, a VGSC inhibitor, in the treatment of refractory chronic cough (RCC). A three-part randomized, double-blind, placebo-controlled, cross-over study was conducted in the UK. In part A, patients with RCC received two inhaled doses of either GSK2339345 or placebo, 4 hours apart during three study periods. Patients were monitored for cough for 8 hours post-first dose using the VitaloJAK, ambulatory cough monitor. In parts B and C, patients underwent full dose-response cough challenges with capsaicin and citric acid respectively following single doses of randomly assigned GSK2339345 or placebo (4 study days). Part A was analyzed using a mixed effects model and parts B and C using population non-linear mixed effects models. Of 16 enrolled patients, 11 completed the study. 8-hour cough counts increased following GSK2339345 treatment compared with placebo (GSK2339345/placebo ratio of adjusted geometric means: 1.26 (90% credible interval 1.10, 1.44), associated with GSK2339345-evoked coughing, recorded during the 2 minutes post-dose. This was not observed with placebo. The effect of GSK2339345 on cough responses during cough challenges was inconclusive. GSK2339345 was well tolerated. While these data could not determine if GSK2339345 reached the target VGSC, they strongly suggest that GSK2339345 has no anti-tussive effect despite reaching airway sensory nerves as evidenced by the evoked transient cough.
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Challenges in conducting psychiatry studies in India

PubMed Central

Kharawala, Saifuddin; Dalal, Jeroze

2011-01-01

A large number of psychiatry studies are conducted in India. Psychiatry studies are complex and present unique challenges in the Indian setting. Ethical issues pertaining to the risk of worsening of illness, use of placebo and validity of informed consents are commonly faced. Site selection can be difficult due to the relative paucity of ICH-GCP (International Conference on Harmonisation - Good Clinical Practice) trained psychiatry investigators in India. Recruitment can be challenging due to issues such as strict eligibility criteria, (lack of) availability of caregiver, illness-related considerations, etc. Assessment of the consent capacity of patients is not simple, while structured assessments are not commonly employed. As the illness fluctuates, the consent capacity may change, thus requiring continued assessment of consent capacity. Study patients run the risk of worsening of illness and suicide due to exposure to inactive treatments; this risk is counterbalanced by use of appropriate study designs, as well as the indirect psychotherapeutic support received. Psychiatry studies are associated with a high placebo response. This necessitates conduct of placebo-controlled studies despite the attendant difficulties. Also, the high placebo response is often the cause of failed trials. Rating scales are essential for assessment of drug response. Some rating instruments as well as some rater training procedures may not be suitable for the Indian setting. Technological advancements may increase the procedural complexity but improve the quality of ratings. Psychiatry studies present monitors and auditors with unique scenarios too. Utilization of psychiatry specific training and expertise is recommended to ensure successful conduct of these studies in India. PMID:21584176

Treatment with a nicotine vaccine does not lead to changes in brain activity during smoking cue exposure or a working memory task.

PubMed

Havermans, Anne; Vuurman, Eric F; van den Hurk, Job; Hoogsteder, Philippe; van Schayck, Onno C P

2014-08-01

To assess whether immunization attenuates nicotinic stimulation of the brain and elucidate brain and behavioural responses during exposure to smoking cues and a working memory task. Randomized, placebo-controlled parallel-group, repeated-measures design. Maastricht University, the Netherlands. Forty-eight male smokers were randomized to receive five injections with either 400 μg/ml of the 3'-aminomethylnicotine Pseudomonas aeruginosa r-Exoprotein-conjugated vaccine or placebo. Subjects were tested on two occasions, once after a nicotine challenge and once after a placebo challenge, and were asked to refrain from smoking 10 hours before testing. Reaction-times and accuracies were recorded during an n-back task. Moreover, regional blood oxygenated level-dependent (BOLD) response was measured during this task and during smoking cue exposure. Greater activation was found in response to smoking cues compared to neutral cues in bilateral trans-occipital sulcus (P < 0.005); however, this effect did not survive correction for multiple comparisons. There was no difference in brain activity to smoking cues between the treatment groups and no effects of acute nicotine challenge were established. For the n-back task we found working memory load-sensitive increases in brain activity in several frontal and parietal areas (P < 0.0025). However, no effects of immunization or nicotine challenge were observed. No significant effects of immunization on brain activity in response to a nicotine challenge were established. Therefore this vaccine is not likely to be an effective aid in smoking cessation. © 2014 Society for the Study of Addiction.

Dietary supplementation with rice bran fermented with Lentinus edodes increases interferon-γ activity without causing adverse effects: a randomized, double-blind, placebo-controlled, parallel-group study.

PubMed

Choi, Ji-Young; Paik, Doo-Jin; Kwon, Dae Young; Park, Yongsoon

2014-04-22

The purpose of this study was to investigate the hypothesis that dietary supplementation with rice bran fermented with Lentinus edodes (rice bran exo-biopolymer, RBEP), a substance known to contain arabinoxylan, enhances natural killer (NK) cell activity and modulates cytokine production in healthy adults. This study was designed in a randomized, double-blind, placebo-controlled, and parallel-group format. Eighty healthy participants with white blood cell counts of 4,000-8,000 cells/μL were randomly assigned to take six capsules per day of either 3 g RBEP or 3 g placebo for 8 weeks. Three participants in the placebo group were excluded after initiation of the protocol; no severe adverse effects from RBEP supplementation were reported. NK cell activity of peripheral blood mononuclear cells was measured using nonradioactive cytotoxicity assay kits and serum cytokine concentrations included interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-2, IL-4, IL-10, and IL-12 were measured by Bio-Plex cytokine assay kit. This study was registered with the Clinical Research Information Service (KCT0000536). Supplementation of RBEP significantly increased IFN-γ production compared with the placebo group (P = 0.012). However, RBEP supplementation did not affect either NK cell activity or cytokine levels, including IL-2, IL-4, IL-10, IL-12, and TNF-α, compared with the placebo group. The data obtained in this study indicate that RBEP supplementation increases IFN-γ secretion without causing significant adverse effects, and thus may be beneficial to healthy individuals. This new rice bran-derived product may therefore be potentially useful to include in the formulation of solid and liquid foods designed for treatment and prevention of pathological states associated with defective immune responses.

Effect of a traditional syrup from Citrus medica L. fruit juice on migraine headache: A randomized double blind placebo controlled clinical trial.

PubMed

Jafarpour, Mehrnaz; Yousefi, Gholamhossein; Hamedi, Azadeh; Shariat, Abdolhamid; Salehi, Alireza; Heydari, Mojtaba

2016-02-17

In Persian ethnomedicine several herbal remedies and functional foods have been used to treat migraine headache which are mostly summarized in Qarabadin-e-kabir (Aghili-Shirazi MH, 1773). One of them is Citron syrup (Sharbat-e-Balang) containing edible Citrus medica L. fruit juice and sugar. The present study was designed to assess the efficacy and safety of Citron syrup on patients with migraine headache. Citron syrup was prepared as described in Qarabadin-e-kabir. In this double blind randomized placebo-controlled clinical trial, ninety patients with migraine headache were allocated to three parallel groups (Citron syrup, propranolol or placebo). Patients received 15ml of Citron syrup, placebo syrup or 20mg of propranolol tablet three times daily after a meal for 4 weeks. Primary outcomes were obtained from three measures: the frequency (per month), mean duration (hour) and mean intensity (visual analogue scale "VAS" 0-10 score) of headache attacks evaluated prior to and following 4 weeks of the intervention. Citron syrup was superior to placebo in reduction of headache attacks intensity (P<0.01) and duration (p<0.0001) and as effective as propranolol in patients with migraine headache (P>0.05). However, unlike propranolol, Citron syrup could not significantly reduce the frequency of attacks compared to placebo. No indication of any serious side effects from Citron syrup was observed. According to obtained results, Citron syrup as a traditional Persian remedy can be suggested as an effective treatment for decreasing pain intensity and duration of attacks in migraine headache and the effectiveness is comparable to propranolol. However, the syrup did not show significant effect on frequency of attacks. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Comparison of two modes of vitamin B12 supplementation on neuroconduction and cognitive function among older people living in Santiago, Chile: a cluster randomized controlled trial. a study protocol [ISRCTN 02694183

PubMed Central

2011-01-01

Background Older people have a high risk of vitamin B12 deficiency; this can lead to varying degrees of cognitive and neurological impairment. CBL deficiency may present as macrocytic anemia, subacute combined degeneration of the spinal cord, or as neuropathy, but is often asymptomatic in older people. Less is known about subclinical vitamin B12 deficiency and concurrent neuroconduction and cognitive impairment. A Programme of Complementary Feeding for the Older Population (PACAM) in Chile delivers 2 complementary fortified foods that provide approximately 1.4 μg/day of vitamin B12 (2.4 μg/day elderly RDA). The aim of the present study is to assess whether supplementation with vitamin B12 will improve neuroconduction and cognitive function in older people who have biochemical evidence of vitamin B12 insufficiency in the absence of clinical deficiency. Methods We designed a cluster double-blind placebo-controlled trial involving community dwelling people aged 70-79 living in Santiago, Chile. We randomized 15 clusters (health centers) involving 300 people (20 per cluster). Each cluster will be randomly assigned to one of three arms: a) a 1 mg vitamin B12 pill taken daily and a routine PACAM food; b) a placebo pill and the milk-PACAM food fortified to provide 1 mg of vitamin B12; c) the routine PACAM food and a placebo pill. The study has been designed as an 18 month follow up period. The primary outcomes assessed at baseline, 4, 9 and 18 months will be: serum levels of vitamin B12, neuroconduction and cognitive function. Conclusions In view of the high prevalence of vitamin B12 deficiency in later life, the present study has potential public health interest because since it will measure the impact of the existing program of complementary feeding as compared to two options that provide higher vitamin B12 intakes that might potentially may contribute in preserving neurophysiologic and cognitive function and thus improve quality of life for older people in Chile. Trial registration ISRCTN: ISRCTN02694183 PMID:21952034

More pain, more gain: Blocking the opioid system boosts adaptive cognitive control.

PubMed

van Steenbergen, Henk; Weissman, Daniel H; Stein, Dan J; Malcolm-Smith, Susan; van Honk, Jack

2017-06-01

The ability to adaptively increase cognitive control in response to cognitive challenges is crucial for goal-directed behavior. Recent findings suggest that aversive arousal triggers adaptive increases of control, but the neurochemical mechanisms underlying these effects remain unclear. Given the known contributions of the opioid system to hedonic states, we investigated whether blocking this system increases adaptive control modulations. To do so, we conducted a double-blind, placebo-controlled psychopharmacological study (n=52 females) involving a Stroop-like task. Specifically, we assessed the effect of naltrexone, an opioid blocker most selective to the mu-opioid system, on two measures of adaptive control that are thought to depend differentially on aversive arousal: post-error slowing and conflict adaptation. Consistent with our hypothesis, relative to placebo, naltrexone increased post-error slowing without influencing conflict adaptation. This finding not only supports the view that aversive arousal triggers adaptive control but also reveals a novel role for the opioid system in modulating such effects. Copyright © 2017 Elsevier Ltd. All rights reserved.

An intervention study on the effect of matcha tea, in drink and snack bar formats, on mood and cognitive performance.

PubMed

Dietz, Christina; Dekker, Matthijs; Piqueras-Fiszman, Betina

2017-09-01

Matcha tea is gaining popularity throughout the world in recent years and is frequently referred to as a mood-and-brain food. Previous research has demonstrated that three constituents present in matcha tea, l-theanine, epigallocatechin gallate (EGCG), and caffeine, affect mood and cognitive performance. However, to date there are no studies assessing the effect of matcha tea itself. The present study investigates these effects by means of a human intervention study administering matcha tea and a matcha containing product. Using a randomized, placebo-controlled, single-blind study, 23 consumers participated in four test sessions. In each session, participants consumed one of the four test products: matcha tea, matcha tea bar (each containing 4g matcha tea powder), placebo tea, or placebo bar. The assessment was performed at baseline and 60min post-treatment. The participants performed a set of cognitive tests assessing attention, information processing, working memory, and episodic memory. The mood state was measured by means of a Profile of Mood States (POMS). After consuming the matcha products compared to placebo versions, there were mainly significant improvements in tasks measuring basic attention abilities and psychomotor speed in response to stimuli over a defined period of time. In contrast to expectations, the effect was barely present in the other cognitive tasks. The POMS results revealed no significant changes in mood. The influence of the food matrix was demonstrated by the fact that on most cognitive performance measures the drink format outperformed the bar format, particularly in tasks measuring speed of spatial working memory and delayed picture recognition. This study suggests that matcha tea consumed in a realistic dose can induce slight effects on speed of attention and episodic secondary memory to a low degree. Further studies are required to elucidate the influences of the food matrix. Copyright © 2017 Elsevier Ltd. All rights reserved.

A high polymerized grass pollen extract is efficacious and safe in a randomized double-blind, placebo-controlled study using a novel up-dosing cluster-protocol

PubMed Central

Klimek, L; Uhlig, J; Mösges, R; Rettig, K; Pfaar, O

2014-01-01

Background Cluster immunotherapy represents an interesting alternative to conventional up-dosing schedules because it allows achieving the maintenance dose within a shorter time interval. In this study, the efficacy and safety of cluster immunotherapy with a high polymerized allergen extract of a grass/rye pollen mixture have been evaluated in a randomized, double-blind, placebo-controlled, multicenter study. Methods In total, 121 patients with allergic rhinoconjunctivitis due to grass pollen were randomized 1 : 1 to verum or placebo group. A short cluster up-dosing schedule of only 1 week was applied to achieve the maintenance dose which was administered monthly during the study period of 1 year. Total combined symptom and medication score (TCS) was defined as primary outcome parameter. Secondary outcome parameters were individual symptom and medication scores, ‘well days,’ global improvement as well as immunological effects and nasal allergen challenge. The safety profile was evaluated based on the European academy of allergy and clinical immunology grading system. Results Significant reduction in the verum compared to the placebo group (intention-to-treat, population, verum: n = 55; placebo: n = 47) was found regarding TCS (P = 0.005), rhinoconjunctivitis total symptom score (RTSS, P = 0.006), and total rescue medication score (TRMS, P = 0.002). Additionally, secondary outcomes such as ‘well days,’ nasal challenge results, and increase of specific IgG4 were in favor of the active treatment. All systemic adverse reactions (0.8% of all injections in the verum group) were of mild intensity. No severe reactions related to the study medication were observed. Conclusion Cluster immunotherapy with high polymerized grass pollen extracts resulted in significant clinical efficacy and has been shown to be a safe treatment for grass pollen-allergic patients. PMID:25130503

GLP-1 receptors exist in the parietal cortex, hypothalamus and medulla of human brains and the GLP-1 analogue liraglutide alters brain activity related to highly desirable food cues in individuals with diabetes: a crossover, randomised, placebo-controlled trial.

PubMed

Farr, Olivia M; Sofopoulos, Michail; Tsoukas, Michael A; Dincer, Fadime; Thakkar, Bindiya; Sahin-Efe, Ayse; Filippaios, Andreas; Bowers, Jennifer; Srnka, Alexandra; Gavrieli, Anna; Ko, Byung-Joon; Liakou, Chrysoula; Kanyuch, Nickole; Tseleni-Balafouta, Sofia; Mantzoros, Christos S

2016-05-01

Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue that has been demonstrated to successfully treat diabetes and promote weight loss. The mechanisms by which liraglutide confers weight loss remain to be fully clarified. Thus, we investigated whether GLP-1 receptors are expressed in human brains and whether liraglutide administration affects neural responses to food cues in diabetic individuals (primary outcome). In 22 consecutively studied human brains, expression of GLP-1 receptors in the hypothalamus, medulla oblongata and parietal cortex was examined using immunohistochemistry. In a randomised (assigned by the pharmacy using a randomisation enrolment table), placebo-controlled, double-blind, crossover trial, 21 individuals with type 2 diabetes (18 included in analysis due to lack or poor quality of data) were treated with placebo and liraglutide for a total of 17 days each (0.6 mg for 7 days, 1.2 mg for 7 days, and 1.8 mg for 3 days). Participants were eligible if they had type 2 diabetes and were currently being treated with lifestyle changes or metformin. Participants, caregivers, people doing measurements and/or examinations, and people assessing the outcomes were blinded to the medication assignment. We studied metabolic changes as well as neurocognitive and neuroimaging (functional MRI) of responses to food cues at the clinical research centre of Beth Israel Deaconess Medical Center. Immunohistochemical analysis revealed the presence of GLP-1 receptors on neurons in the human hypothalamus, medulla and parietal cortex. Liraglutide decreased activation of the parietal cortex in response to highly desirable (vs less desirable) food images (p < 0.001; effect size: placebo 0.53 ± 0.24, liraglutide -0.47 ± 0.18). No significant adverse effects were noted. In a secondary analysis, we observed decreased activation in the insula and putamen, areas involved in the reward system. Furthermore, we showed that increased ratings of hunger and appetite correlated with increased brain activation in response to highly desirable food cues while on liraglutide, while ratings of nausea correlated with decreased brain activation. For the first time, we demonstrate the presence of GLP-1 receptors in human brains. We also observe that liraglutide alters brain activity related to highly desirable food cues. Our data point to a central mechanism contributing to, or underlying, the effects of liraglutide on metabolism and weight loss. Future studies will be needed to confirm and extend these findings in larger samples of diabetic individuals and/or with the higher doses of liraglutide (3 mg) recently approved for obesity. ClinicalTrials.gov NCT01562678 FUNDING : The study was funded by Novo Nordisk, NIH UL1 RR025758 and 5T32HD052961.

Lubiprostone: chloride channel activator for chronic constipation.

PubMed

Rivkin, Anastasia; Chagan, Larisa

2006-12-01

Chronic constipation is a common and costly health problem occurring in approximately 4.5 million Americans. Current management of constipation is suboptimal and requires a stepwise approach using a combination of laxatives to decrease symptoms. The objective of this review was to describe the efficacy and safety of a new therapeutic entity, lubiprostone, recently approved by the US Food and Drug Administration for the treatment of chronic idiopathic constipation. Computerized searches of MEDLINE and International Pharmaceutical Abstracts were conducted (1966-July 10, 2006). Search terms utilized were lubiprostone, RU-0211, and chronic constipation. References of selected articles were searched for additional articles or abstracts. All relevant published literature regarding lubiprostone was included in this review. Pertinent abstracts presented at meetings of the American College of Gastroenterology and Digestive Diseases Week were also included. Lubiprostone activates a chloride channel (ie, subtype 2) and increases chloride and fluid secretion into the intestines, resulting in relief of constipation. It is poorly absorbed after oral administration, and its metabolism occurs primarily in the stomach and jejunum. Lubiprostone was evaluated in 6 placebo-controlled, double-blind, randomized Phase II or III clinical trials. Overall, in clinical trials, >1400 patients were exposed to 24 mug of lubiprostone BID for up to 48 weeks. It improved the number of bowel movements, stool consistency, bloating, and global assessment of constipation compared with placebo (P < 0.05). Nausea was the most common adverse effect reported in clinical trials, occurring in 30.9% of patients. However, nausea was dose dependent and decreased when lubiprostone was given with food. Lubiprostone is the first in its class of chloride channel activators that results in improvement of symptoms of constipation. It has not been compared with other laxatives but, based on the available placebo-controlled studies, its efficacy is superior to placebo and its safety is acceptable. Considering the currently available laxatives, lubiprostone will become an additional option for the treatment of patients with chronic constipation.

Gastrointestinal tract recovery in patients undergoing bowel resection: results of a randomized trial of alvimopan and placebo with a standardized accelerated postoperative care pathway.

PubMed

Ludwig, Kirk; Enker, Warren E; Delaney, Conor P; Wolff, Bruce G; Du, Wei; Fort, John G; Cherubini, Maryann; Cucinotta, James; Techner, Lee

2008-11-01

To investigate the efficacy and safety of alvimopan, 12 mg, administered orally 30 to 90 minutes preoperatively and twice daily postoperatively in conjunction with a standardized accelerated postoperative care pathway for managing postoperative ileus after bowel resection. This multicenter, randomized, placebo-controlled, double-blind, phase 3 trial enrolled adult patients undergoing partial bowel resection with primary anastomosis by laparotomy and scheduled to receive intravenous, opioid-based, patient-controlled analgesia. A standardized accelerated postoperative care pathway including early ambulation, oral feeding, and postoperative nasogastric tube removal was used to facilitate gastrointestinal (GI) tract recovery in all of the patients. The primary end point was time to GI-2 recovery (toleration of solid food and first bowel movement). Secondary end points included time to GI-3 recovery (toleration of solid food and first flatus or bowel movement), hospital discharge order written, and actual hospital discharge. Postoperative length of hospital stay based on calendar day of hospital discharge order written, opioid consumption, and overall postoperative ileus-related morbidity were recorded. Alvimopan, 12 mg, was well tolerated and significantly accelerated GI-2 recovery, GI-3 recovery, and actual hospital discharge compared with a standardized accelerated postoperative care pathway alone (hazard ratio = 1.5, 1.5, and 1.4, respectively; P < .001 for all). Time to hospital discharge order written as measured by hazard ratio (1.4) and by postoperative calendar days (mean for alvimopan, 5.2 days; mean for placebo, 6.2 days) was also accelerated. Opioid consumption was comparable between groups, and alvimopan was associated with reduced postoperative ileus-related morbidity compared with placebo. Alvimopan, 12 mg, administered 30 to 90 minutes before and twice daily after bowel resection is well tolerated, accelerates GI tract recovery, and reduces postoperative ileus-related morbidity without compromising opioid analgesia.

Acute effect on satiety, resting energy expenditure, respiratory quotient, glucagon-like peptide-1, free fatty acids, and glycerol following consumption of a combination of bioactive food ingredients in overweight subjects.

PubMed

Rondanelli, Mariangela; Opizzi, Annalisa; Perna, Simone; Faliva, Milena; Solerte, Sebastiano Bruno; Fioravanti, Marisa; Klersy, Catherine; Edda, Cava; Maddalena, Paolini; Luciano, Scavone; Paola, Ceccarelli; Emanuela, Castellaneta; Claudia, Savina; Donini, Lorenzo Maria

2013-01-01

A combination of bioactive food ingredients (capsaicinoids, epigallocatechin gallate, piperin, and l-carnitine, CBFI) may promote satiety and thermogenesis. The study was conducted in order to assess whether there is any effect on satiety, resting energy expenditure (REE), respiratory quotient, glucagon-like peptide-1 (GLP-1), free fatty acids (FFA) and glycerol release, following a standardized mixed meal with or without single consumption of a CBFI. An 8-week randomized double-blind placebo-controlled trial. Dietetic and Metabolic Unit, Azienda di Servizi alla Persona, University of Pavia and "Villa delle Querce" Clinical Rehabilitation Institute, Rome, Italy. Thirty-seven overweight adults (body mass index [BMI]: 25-35). Nineteen overweight subjects were included in the supplemented group (14 women, 5 men; age 46.4 ± 6.4; BMI: 30.5 ± 3.3) and 18 in the placebo group (13 women, 5 men; age 40.8 ± 11.5; BMI: 30.1 ± 2.6). Satiety was assessed using 100-mm visual analogue scales (VAS) and the area under the curve was calculated. All measured parameters increased significantly in comparison with baseline in response to meal, both with CBFI and with placebo. However, throughout the study day, the supplemented group experienced a significantly greater increase than the placebo group in their sensation of satiety following acute administration of the supplement. CBFI may therefore be of great value in the treatment of overweight patients by increasing satiety and stimulating thermogenesis.

Measurement of allergen-specific IgG in serum is of limited value for the management of dogs diagnosed with cutaneous adverse food reactions.

PubMed

Hagen-Plantinga, E A; Leistra, M H G; Sinke, J D; Vroom, M W; Savelkoul, H F J; Hendriks, W H

2017-02-01

Conflicting results have been reported in the literature in terms of the usefulness of serological testing for IgG against food allergens in dogs with cutaneous adverse food reaction (CAFR). The aim of the present study was to evaluate the suitability of a commercially available IgG ELISA for identifying food allergens in dogs, by challenging dogs with specific food ingredients, selected on the basis of IgG reactivity in serum samples. A total of 24 adult dogs with CAFR were enrolled into the study and 16 healthy dogs were included as a control group. Blood samples were obtained for measurement of specific IgG antibodies against 39 commonly used pet food ingredients by ELISA. Participating owners were surveyed to obtain information on their pet's dietary history. Eleven healthy control dogs and 12 dogs with CAFR were subsequently challenged in a blinded cross-over design experiment with both positive and negative food ingredients, selected on the basis of the ELISA test results. There was substantial individual variation in ELISA test results to the various food allergens, but no significant difference in IgG reactivity comparing the CAFR and control groups. None of the control dogs developed any clinical signs of an allergic reaction during the dietary challenge study. In the CAFR group, six of 12 dogs developed clinical signs after the negative challenge, and two of nine dogs developed clinical signs after the positive challenge. It was concluded that the ELISA test for dietary allergen-specific IgG is of limited value in the management of dogs with CAFR. Copyright © 2017 Elsevier Ltd. All rights reserved.

Efficacy and safety of 4 months of sublingual immunotherapy with recombinant Mal d 1 and Bet v 1 in patients with birch pollen-related apple allergy.

PubMed

Kinaciyan, Tamar; Nagl, Birgit; Faustmann, Sandra; Frommlet, Florian; Kopp, Stephan; Wolkersdorfer, Martin; Wöhrl, Stefan; Bastl, Katharina; Huber, Hans; Berger, Uwe; Bohle, Barbara

2018-03-01

Birch pollen-related apple allergy is among the most prevalent food allergies in adolescent/adult subjects and mainly results from sensitization to the major birch pollen allergen Bet v 1 and subsequent cross-reaction with the apple protein Mal d 1. However, specific immunotherapy with birch pollen has inconsistent effects on apple allergy. We sought to compare the safety and efficacy of sublingual immunotherapy (SLIT) with 2 formulations containing either rMal d 1 or rBet v 1 on birch pollen-related apple allergy. Sixty participants with birch pollen-related apple allergy were randomized to daily sublingual application of placebo (n = 20) or 25 μg of rMal d 1 (n = 20) or rBet v 1 (n = 20) for 16 weeks. Adverse events were regularly recorded. Sublingual challenges with standardized doses of rMal d 1, skin prick tests with recombinant allergens, and measurements of allergen-specific IgE and IgG 4 antibodies were performed before and after treatment. Both formulations caused comparable, mainly local adverse events. No systemic reactions occurred. Compared with the placebo and rBet v 1-treated groups, SLIT with rMal d 1 reduced rMal d 1-induced oral symptoms (P = .001 and P = .038) accompanied by longitudinally reduced rMal d 1-specific cutaneous reactions (P = .022) and enhanced IgG 4 /IgE ratios (P = .012). SLIT with rBet v 1 neither improved the clinical reactivity to rMal d 1 nor enhanced rMal d 1-specific IgG 4 /IgE ratios. Participants receiving placebo showed no allergen-specific changes. Sublingual treatment with a recombinant food allergen was safe and clinically effective, as determined by using standardized challenges. We present a promising approach for the effective treatment of birch pollen-related apple allergy. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Allergen-specific responses of CD19(+)CD5(+)Foxp3(+) regulatory B cells (Bregs) and CD4(+)Foxp3(+) regulatory T cell (Tregs) in immune tolerance of cow milk allergy of late eczematous reactions.

PubMed

Noh, Joonyong; Noh, Geunwoong; Kim, Hyuk Soon; Kim, A-Ram; Choi, Wahn Soo

2012-01-01

Foxp3-expressing cells among CD19(+)CD5(+) B cells were identified as regulatory B cells. Food allergy manifesting as late eczematous reactions is regarded as a non-IgE-mediated food allergy. The diagnosis for milk allergy manifesting as late eczematous reactions was made on the basis of the findings obtained from a double-blind placebo-controlled food challenge in patients with atopic dermatitis. Twelve patients with milk allergy and 12 patients who could tolerate milk were selected. On casein stimulation, the CD19(+)CD5(+)Foxp3(+) B cell (Breg) fraction in CD5(+) B cells decreased from 4.4±1.1% to 3.1±0.7% (P=0.047, n=12) in the milk allergy group and increased from 4.4±1.3% to 5.2±1.4% (P=0.001, n=10) in the milk-tolerant group. On the other hand, on allergen stimulation, the number of CD4(+)Foxp3(+) regulatory T cells (Tregs) in the milk allergy group and milk-tolerant group increased from 2.6±0.7% to 3.4±0.6% (P=0.014, n=9) and from 2.7±1.0% to 3.5±1.0% (P=0.038, n=10), respectively. In conclusion, allergen-specific responses of Bregs, rather than those of Tregs, seem to influence the immune responses (i.e., allergy or tolerance) to a food allergen. Copyright © 2012 Elsevier Inc. All rights reserved.

Quantitative Assessment of the Safety Benefits Associated with Increasing Clinical Peanut Thresholds Through Immunotherapy.

PubMed

Baumert, Joseph L; Taylor, Steve L; Koppelman, Stef J

Peanut immunotherapy studies are conducted with the aim to decrease the sensitivity of patients to peanut exposure with the outcome evaluated by testing the threshold for allergic response in a double-blind placebo-controlled food challenge. The clinical relevance of increasing this threshold is not well characterized. We aimed to quantify the clinical benefit of an increased threshold for peanut-allergic patients. Quantitative risk assessment was performed by matching modeled exposure to peanut protein with individual threshold levels. Exposure was modeled by pairing US consumption data for various food product categories with potential contamination levels of peanut that have been demonstrated to be present on occasion in such food products. Cookies, ice cream, doughnuts/snack cakes, and snack chip mixes were considered in the risk assessment. Increasing the baseline threshold before immunotherapy from 100 mg or less peanut protein to 300 mg peanut protein postimmunotherapy reduces the risk of experiencing an allergic reaction by more than 95% for all 4 food product categories that may contain trace levels of peanut residue. Further increase in the threshold to 1000 mg of peanut protein had an additional quantitative benefit in risk reduction for all patients reacting to 300 mg or less at baseline. We conclude that achieving thresholds of 300 mg and 1000 mg of peanut protein by peanut immunotherapy is clinically relevant, and that the risk for peanut-allergic patients who have achieved this increased threshold to experience an allergic reaction is reduced in a clinically meaningful way. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Effects of subtle cognitive manipulations on placebo analgesia - An implicit priming study.

PubMed

Rosén, A; Yi, J; Kirsch, I; Kaptchuk, T J; Ingvar, M; Jensen, K B

2017-04-01

Expectancy is widely accepted as a key contributor to placebo effects. However, it is not known whether non-conscious expectancies achieved through semantic priming may contribute to placebo analgesia. In this study, we investigated if an implicit priming procedure, where participants were unaware of the intended priming influence, affected placebo analgesia. In a double-blind experiment, healthy participants (n = 36) were randomized to different implicit priming types; one aimed at increasing positive expectations and one neutral control condition. First, pain calibration (thermal) and a credibility demonstration of the placebo analgesic device were performed. In a second step, an independent experimenter administered the priming task; Scrambled Sentence Test. Then, pain sensitivity was assessed while telling participants that the analgesic device was either turned on (placebo) or turned off (baseline). Pain responses were recorded on a 0-100 Numeric Response Scale. Overall, there was a significant placebo effect (p < 0.001), however, the priming conditions (positive/neutral) did not lead to differences in placebo outcome. Prior experience of pain relief (during initial pain testing) correlated significantly with placebo analgesia (p < 0.001) and explained 34% of placebo variance. Trait neuroticism correlated positively with placebo analgesia (p < 0.05) and explained 21% of placebo variance. Priming is one of many ways to influence behaviour, and non-conscious activation of positive expectations could theoretically affect placebo analgesia. Yet, we found no SST priming effect on placebo analgesia. Instead, our data point to the significance of prior experience of pain relief, trait neuroticism and social interaction with the treating clinician. Our findings challenge the role of semantic priming as a behavioural modifier that may shape expectations of pain relief, and affect placebo analgesia. © 2016 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC®.

Double-blind, placebo-controlled study with alginate suspension for laryngopharyngeal reflux disease.

PubMed

Tseng, Wen-Hsuan; Tseng, Ping-Huei; Wu, Jia-Feng; Hsu, Ya-Chin; Lee, Ting-Yi; Ni, Yen-Hsuan; Wang, Hsiu-Po; Hsiao, Tzu-Yu; Hsu, Wei-Chung

2018-02-05

Treatment for laryngopharyngeal reflux disease (LPRD) is challenging because of delays in recognition and poor responsiveness to proton-pump inhibitor therapy. The aim of this study was to determine the efficacy and safety of liquid alginate suspension for treating LPRD. A double-blind, placebo-controlled, prospective study comparing 8 weeks of treatment with Alginos Oral Suspension (TTY Biopharm Co. Ltd., Taipei, Taiwan) (sodium alginate 1,000 mg three times daily) with a placebo was conducted on patients who fulfilled the criteria of at least one symptom consistent with LPRD, a total reflux symptom index (RSI) score of > 10, and a total reflux finding score (RFS) of > 5. Those with erosive gastroesophageal reflux disease, as evidenced through screened transnasal upper gastrointestinal endoscopy, were excluded. Efficacy was assessed by RSI, RFS, and ambulatory multichannel intraluminal impedance and pH (MII-pH) monitoring. A total of 80 patients aged 22 to 72 years were enrolled. Compared with baseline, both Alginos (TTY Biopharm Co. Ltd.) and the placebo significantly reduced the total RSI (P < 0.001) and the total number of reflux episodes shown by MII-pH monitoring (P < 0.05) after 8 weeks of treatment. However, liquid alginate suspension was unable to show superiority over the placebo. The incidence of various adverse events from Alginos (TTY Biopharm Co. Ltd.) was relatively low (7.7%) and mild. This study showed that liquid alginate suspension was well tolerated by LPRD patients. It effectively improved symptoms and reflux numbers but was unable to show superiority over placebo. As observed in previous studies, a great placebo effect was present. The importance of lifestyle modification could not be overlooked. 2. Laryngoscope, 00:000-000, 2018. © 2018 The American Laryngological, Rhinological and Otological Society, Inc.

Milk-induced eczema is associated with the expansion of T cells expressing cutaneous lymphocyte antigen.

PubMed Central

Abernathy-Carver, K J; Sampson, H A; Picker, L J; Leung, D Y

1995-01-01

The extravasation of T cells at sites of inflammation is critically dependent on the activity of homing receptors (HR) involved in endothelial cell recognition and binding. Two such HR (the cutaneous lymphocyte antigen [CLA] and L-selectin) have been shown to be selectively involved in T cell migration to skin and peripheral lymph nodes, respectively. This study was designed to assess the relationship between the organ specificity of an allergic reaction to food and the expression of HR on T cells activated in vitro by the relevant food allergen. Peripheral blood mononuclear cells were isolated from seven milk allergic children with a history of eczema when exposed to milk. All patients had a positive prick skin test and double-blind placebo-controlled food challenge to milk. 10 children with either allergic eosinophilic gastroenteritis or milk-induced enterocolitis and 8 nonatopic adults served as controls. Five-parameter flow cytometry using monoclonal antibodies was used for detection of the specific HR on freshly isolated T cells versus T cell blasts induced by a 6-d incubation with casein, as compared with Candida albicans. After in vitro stimulation with casein, but not C. albicans, patients with milk allergy and atopic dermatitis had a significantly greater percentage of CLA+ T cells (P < 0.01) than controls with milk-induced enterocolitis, allergic eosinophilic gastroenteritis, or nonatopic healthy controls. In contrast, the percentage of L-selectin-expressing T cells did not differ significantly between these groups. These data suggest that after casein stimulation allergic patients with milk-induced skin disease have an expanded population of CLA+ T cells, as compared with nonatopics or allergic patients without skin involvement. We postulate that heterogeneity in the regulation of HR expression on antigen-specific T cells may play a role in determining sites of involvement in tissue-directed allergic responses. Images PMID:7532192

Milk-induced eczema is associated with the expansion of T cells expressing cutaneous lymphocyte antigen.

PubMed

Abernathy-Carver, K J; Sampson, H A; Picker, L J; Leung, D Y

1995-02-01

The extravasation of T cells at sites of inflammation is critically dependent on the activity of homing receptors (HR) involved in endothelial cell recognition and binding. Two such HR (the cutaneous lymphocyte antigen [CLA] and L-selectin) have been shown to be selectively involved in T cell migration to skin and peripheral lymph nodes, respectively. This study was designed to assess the relationship between the organ specificity of an allergic reaction to food and the expression of HR on T cells activated in vitro by the relevant food allergen. Peripheral blood mononuclear cells were isolated from seven milk allergic children with a history of eczema when exposed to milk. All patients had a positive prick skin test and double-blind placebo-controlled food challenge to milk. 10 children with either allergic eosinophilic gastroenteritis or milk-induced enterocolitis and 8 nonatopic adults served as controls. Five-parameter flow cytometry using monoclonal antibodies was used for detection of the specific HR on freshly isolated T cells versus T cell blasts induced by a 6-d incubation with casein, as compared with Candida albicans. After in vitro stimulation with casein, but not C. albicans, patients with milk allergy and atopic dermatitis had a significantly greater percentage of CLA+ T cells (P < 0.01) than controls with milk-induced enterocolitis, allergic eosinophilic gastroenteritis, or nonatopic healthy controls. In contrast, the percentage of L-selectin-expressing T cells did not differ significantly between these groups. These data suggest that after casein stimulation allergic patients with milk-induced skin disease have an expanded population of CLA+ T cells, as compared with nonatopics or allergic patients without skin involvement. We postulate that heterogeneity in the regulation of HR expression on antigen-specific T cells may play a role in determining sites of involvement in tissue-directed allergic responses.

Effects of Capsaicin on Older Patients with Oropharyngeal Dysphagia: A Double-Blind, Placebo-Controlled, Crossover Study.

PubMed

Nakato, Rui; Manabe, Noriaki; Shimizu, Sayako; Hanayama, Kozo; Shiotani, Akiko; Hata, Jiro; Haruma, Ken

2017-01-01

The standard of care for older patients with oropharyngeal dysphagia (OD) is poor. Stimulation of transient receptor potential vanilloid 1 might become a pharmacological strategy for these patients. This study aimed to compare the therapeutic effect of film food containing 0.75 µg of capsaicin in these patients. In a crossover, randomized trial, 49 patients with OD were provided capsaicin or identical placebo at least 7 days apart. Patients' reported symptoms during repeated swallowing, the volume, pH and substance P (SP) concentrations in saliva, and cervical esophageal wall motion evaluated by ultrasonographic tissue Doppler imaging were obtained before and after capsaicin or placebo administration. Significantly more patients with OD who took capsaicin experienced improvement in symptoms than those who took placebo. Salivary SP levels were significantly increased after capsaicin administration compared with placebo in the effective group. The duration of cervical esophageal wall opening was significantly shorter in capsaicin administration in the effective group. Furthermore, a significant negative correlation was found between the duration of cervical esophageal wall opening and salivary SP levels. Elevated salivary SP concentrations stimulated by capsaicin greatly improve the safety and efficacy of swallowing, and shorten the swallow response in older patients with OD. © 2017 S. Karger AG, Basel.

A randomized, double-blind, placebo-controlled trial to assess the efficacy of topiramate in the treatment of post-traumatic stress disorder.

PubMed

Mello, Marcelo Feijó; Yeh, Mary Sau Ling; Barbosa Neto, Jair; Braga, Luciana Lorens; Fiks, Jose Paulo; Mendes, Daniela Deise; Moriyama, Tais S; Valente, Nina Leão Marques; Costa, Mariana Caddrobi Pupo; Mattos, Patricia; Bressan, Rodrigo Affonseca; Andreoli, Sergio Baxter; Mari, Jair Jesus

2009-05-29

Topiramate might be effective in the treatment of posttraumatic stress disorder (PTSD) because of its antikindling effect and its action in both inhibitory and excitatory neurotransmitters. Open-label studies and few controlled trials have suggested that this anticonvulsant may have therapeutic potential in PTSD. This 12-week randomized, double-blind, placebo-controlled clinical trial will compare the efficacy of topiramate with placebo and study the tolerability of topiramate in the treatment of PTSD. Seventy-two adult outpatients with DSM-IV-diagnosed PTSD will be recruited from the violence program of Federal University of São Paulo Hospital (UNIFESP). After informed consent, screening, and a one week period of wash out, subjects will be randomized to either placebo or topiramate for 12 weeks. The primary efficacy endpoint will be the change in the Clinician-administered PTSD scale (CAPS) total score from baseline to the final visit at 12 weeks. The development of treatments for PTSD is challenging due to the complexity of the symptoms and psychiatric comorbidities. The selective serotonin reuptake inhibitors (SSRIs) are the mainstream treatment for PTSD, but many patients do not have a satisfactory response to antidepressants. Although there are limited clinical studies available to assess the efficacy of topiramate for PTSD, the findings of prior trials suggest this anticonvulsant may be promising in the management of these patients. NCT 00725920.

Investigations of botanicals on food intake, satiety, weight loss, and oxidative stress: a study protocol of a double-blind, placebo-controlled, crossover study

PubMed Central

Anton, Stephen D.; Shuster, Jonathan; Leeuwenburgh, Christiaan

2013-01-01

Background Botanicals represent an important and underexplored source of potential new therapies that may facilitate caloric restriction and thereby produce long-term weight loss. In particular, one promising botanical that may reduce food intake and body weight by affecting neuroendocrine pathways related to satiety is Garcinia cambogia (Garcinia cambogia Desr.)-derived (−)-hydroxycitric acid (HCA). Methods and Design The objective of this article is to describe the protocol of a clinical trial designed to directly test the effect that Garcinia cambogia-derived HCA has on food intake, satiety, weight loss, and oxidative stress levels, and to serve as a model for similar trials. A total of 48 healthy, overweight and obese individuals (body mass index; BMI range = 25.0 – 39.9) between the ages of 50 to 70 will participate in this double-blind, placebo-controlled, crossover study designed to examine the effects of two doses of Garcinia cambogia-derived HCA on food intake, satiety, weight loss, and oxidative stress levels. This trial will take place at the University of Florida (UF)’s Aging and Rehabilitation Research Center (ARRC) and UF Clinical Research Center (CRC). Food intake represents the primary outcome measure and is calculated based on the total calories consumed at breakfast, lunch, and dinner meals during each test meal day at the CRC. This study can be completed with far fewer subjects than a parallel design. Discussion Of the numerous botanical compounds, the compound Garcinia cambogia-derived HCA was selected for testing in the present study because of its potential to safely reduce food intake, body weight, and oxidative stress levels. We will review potential mechanisms of action and safety parameters throughout this clinical trial, which is registered at ClinicalTrials.gov under NCT01238887. Trial registration ClinicalTrials.gov (Identifier: NCT01238887). PMID:22088584

Specific oral desensitization in children with IgE-mediated cow's milk allergy. Evolution in one year.

PubMed

Alvaro, Montserrat; Giner, Ma Teresa; Vázquez, Marta; Lozano, Jaime; Domínguez, Olga; Piquer, Mónica; Días, Marcia; Jiménez, Rosa; Martín, Ma Anunciación; Alsina, Laia; Plaza, Ana Ma

2012-09-01

Cow's milk allergy is the most frequent childhood food allergy. Children older than 5 who have not become tolerant have less probabilities of natural tolerance. Specific oral desensitization methods are being investigated in reference centres. The aims of our study were to assess the efficacy of our guideline of specific oral desensitization to cow's milk in children and to know its suitability for anaphylactic children. Both clinical and specific IgE outcomes were evaluated. Eighty-seven children aged 5 to 16 years with a history of cow's milk allergy were included. Prior to desensitization, skin prick test, specific IgE to cow's milk proteins and a double-blind placebo control food challenge were performed in all. Of the 87 patients, 21 had a negative challenge; they were considered tolerant, and they were told to follow a free diet. Of the positive, 44 were anaphylactic and 22 non-anaphylactic. All of them were included. In non-anaphylactic patients, 6 achieved partial and 16 maximum desensitization after 23.1 weeks. In the anaphylactic group, 7 achieved partial and 35 maximum desensitization after 26.4 weeks. Cow's milk-specific IgE levels and casein-specific IgE levels were significantly lower in the tolerant patients at baseline. One year after desensitization, the medium specific cow's milk levels and casein IgE levels had dropped significantly. Our guideline for specific oral desensitization to cow's milk is efficacious even in patients with anaphylactic reactions to cow's milk and represents a significant life change. Immunological changes in 1 year show a drop in cow's milk protein-specific IgE.

Use of Specific IgE and Skin Prick Test to Determine Clinical Reaction Severity

PubMed Central

Ta, Von; Weldon, Brittany; Yu, Grace; Humblet, Olivier; Neale-May, Susan; Nadeau, Kari

2012-01-01

Aims To determine whether specific IgE and skin prick test correlate better in predicting reaction severity during a double-blinded placebo controlled food challenge (DBPCFC) for egg, milk, and multiple tree nut allergens. Study design Prospective study. Place and Duration of Study Department of Pediatrics, Stanford University School of Medicine, August 2009 and ongoing. Methodology We examined the reaction severity of twenty-four subjects to nine possible food allergens: milk, egg, almond, cashew, hazelnut, peanut, sesame, pecan and walnut. Specific IgE and SPT were performed before each DBPCFC. DBPCFC results were classified into mild (1), moderate (2), or severe (3) reactions using a modified Bock’s criteria. Results Twenty four subjects underwent a total of 80 DBPCFC. Eighty percent of all DBPCFCs resulted in a positive reaction. A majority, 71%, were classified as mild. No reactions occurred with a SPT of zero mm while three reactions occurred with a negative specific IgE. All reactions were reversible with medication. Conclusion These data suggest that SPT and specific IgE levels are not associated with reaction severity (p<0.64 and 0.27, respectively). We also found that combining specific IgE and SPT improved specificity but did not help to achieve clinically useful sensitivity. For instance, an SPT > 5mm had a sensitivity of 91% and specificity of 50%. Combining SPT > 5mm and IgE > 7 resulted in a reduced sensitivity of 64%. Unexpectedly, a history of anaphylaxis 70% (n=17) was not predictive of anaphylaxis on challenge 4% (n=2). PMID:22993721

Harnessing adolescent values to motivate healthier eating.

PubMed

Bryan, Christopher J; Yeager, David S; Hinojosa, Cintia P; Chabot, Aimee; Bergen, Holly; Kawamura, Mari; Steubing, Fred

2016-09-27

What can be done to reduce unhealthy eating among adolescents? It was hypothesized that aligning healthy eating with important and widely shared adolescent values would produce the needed motivation. A double-blind, randomized, placebo-controlled experiment with eighth graders (total n = 536) evaluated the impact of a treatment that framed healthy eating as consistent with the adolescent values of autonomy from adult control and the pursuit of social justice. Healthy eating was suggested as a way to take a stand against manipulative and unfair practices of the food industry, such as engineering junk food to make it addictive and marketing it to young children. Compared with traditional health education materials or to a non-food-related control, this treatment led eighth graders to see healthy eating as more autonomy-assertive and social justice-oriented behavior and to forgo sugary snacks and drinks in favor of healthier options a day later in an unrelated context. Public health interventions for adolescents may be more effective when they harness the motivational power of that group's existing strongly held values.

Sensitization to Food Additives in Patients with Allergy: A Study Based on Skin Test and Open Oral Challenge.

PubMed

Moghtaderi, Mozhgan; Hejrati, Zinatosadat; Dehghani, Zahra; Dehghani, Faranak; Kolahi, Niloofar

2016-06-01

There has been a great increase in the consumption of various food additives in recent years. The purpose of this study was to identify the incidence of sensitization to food additives by using skin prick test in patients with allergy and to determine the concordance rate between positive skin tests and oral challenge in hypersensitivity to additives. This cross-sectional study included 125 (female 71, male 54) patients aged 2-76 years with allergy and 100 healthy individuals. Skin tests were performed in both patient and control groups with 25 fresh food additives. Among patients with allergy, 22.4% showed positive skin test at least to one of the applied materials. Skin test was negative to all tested food additives in control group. Oral food challenge was done in 28 patients with positive skin test, in whom 9 patients showed reaction to culprit (Concordance rate=32.1%). The present study suggested that about one-third of allergic patients with positive reaction to food additives showed positive oral challenge; it may be considered the potential utility of skin test to identify the role of food additives in patients with allergy.

Safety and efficacy of ebselen for the prevention of noise-induced hearing loss: a randomised, double-blind, placebo-controlled, phase 2 trial.

PubMed

Kil, Jonathan; Lobarinas, Edward; Spankovich, Christopher; Griffiths, Scott K; Antonelli, Patrick J; Lynch, Eric D; Le Prell, Colleen G

2017-09-02

Noise-induced hearing loss is a leading cause of occupational and recreational injury and disease, and a major determinant of age-related hearing loss. No therapeutic agent has been approved for the prevention or treatment of this disorder. In animal models, glutathione peroxidase 1 (GPx1) activity is reduced after acute noise exposure. Ebselen, a novel GPx1 mimic, has been shown to reduce both temporary and permanent noise-induced hearing loss in preclinical studies. We assessed the safety and efficacy of ebselen for the prevention of noise-induced hearing loss in young adults in a phase 2 clinical trial. In this single-centre, randomised, double-blind, placebo-controlled phase 2 trial, healthy adults aged 18-31 years were randomly assigned (1:1:1:1) at the University of Florida (Gainsville, FL, USA) to receive ebselen 200 mg, 400 mg, or 600 mg, or placebo orally twice daily for 4 days, beginning 2 days before a calibrated sound challenge (4 h of pre-recorded music delivered by insert earphones). Randomisation was done with an allocation sequence generated by an independent third party. The primary outcome was mean temporary threshold shift (TTS) at 4 kHz measured 15 min after the calibrated sound challenge by pure tone audiometry; a reduction of 50% in an ebselen dose group compared with the placebo group was judged to be clinically relevant. All participants who received the calibrated sound challenge and at least one dose of study drug were included in the efficacy analysis. All randomly assigned patients were included in the safety analysis. This trial is registered with ClinicalTrials.gov, number NCT01444846. Between Jan 11, 2013, and March 24, 2014, 83 participants were enrolled and randomly assigned to receive ebselen 200 mg (n=22), 400 mg (n=20), or 600 mg (n=21), or placebo (n=20). Two participants in the 200 mg ebselen group were discontinued from the study before the calibrated sound challenge because they no longer met the inclusion criteria; these participants were excluded from the efficacy analysis. Mean TTS at 4 kHz was 1·32 dB (SE 0·91) in the 400 mg ebselen group compared with 4·07 dB (0·90) in the placebo group, representing a significant reduction of 68% (difference -2·75 dB, 95% CI -4·54 to -0·97; p=0·0025). Compared with placebo, TTS at 4 kHz was non-significantly reduced by 21% in the 200 mg ebselen group (3·23 dB [SE 0·91] vs 4·07 dB [0·90] in the placebo group; difference -0·84 dB, 95% CI -2·63 to 0·94; p=0·3542) and by 7% in the 600 mg ebselen group (3·81 dB [0·90] vs 4·07 dB [0·90] in the placebo group; difference -0·27, 95% CI -2·03 to 1·50; p=0·7659). Ebselen treatment was well tolerated across all doses and no significant differences were seen in any haematological, serum chemistry, or radiological assessments between the ebselen groups and the placebo group. Treatment with ebselen was safe and effective at a dose of 400 mg twice daily in preventing a noise-induced TTS. These data lend support to a role of GPx1 activity in acute noise-induced hearing loss. Sound Pharmaceuticals. Copyright © 2017 Elsevier Ltd. All rights reserved.

A review of escitalopram and citalopram in child and adolescent depression.

PubMed

Carandang, Carlo; Jabbal, Rekha; Macbride, Angela; Elbe, Dean

2011-11-01

To review the basic pharmacology and published literature regarding escitalopram and citalopram in child and adolescent depression. A LITERATURE REVIEW WAS CONDUCTED USING THE SEARCH TERMS: 'escitalopram', 'citalopram', 'depression', 'randomized controlled trial', 'open label trial' and limits set to: Human trials, English Language and All Child (Age 0-18). Additional articles were identified from reference information and poster presentation data. Three prospective, randomized controlled trials (RCT) were found for escitalopram in pediatric depression, and two RCTs were found for citalopram. One RCT each for escitalopram and citalopram showed superiority over placebo on the primary out come measure. Adverse effects in escitalopram and citalopram trials were generally mild to moderate. Suicidality was not assessed systematically in all RCTs reviewed, but did not appear to be elevated over placebo in escitalopram RCTs. One trial reported numerically higher suicide related events for citalopram compared to placebo (14 vs. 5, p=0.06). At present, escitalopram and citalopram should be considered a second-line option for adolescent depression. The US Food and Drug Administration approval of escitalopram for treatment of adolescent depression was based on a single positive RCT. This is less evidence than typically required for approval of a drug for a new indication.

Perceptual training effects on anticipation of direct and deceptive 7-m throws in handball.

PubMed

Alsharji, Khaled E; Wade, Michael G

2016-01-01

We examined the effectiveness of perceptual training on the performance of handball goalkeepers when anticipating the direction of both direct and deceptive 7-m throws. Skilled goalkeepers were assigned equally to three matched-ability groups based on their pre-test performance: a perceptual training group (n = 14) received video-based perceptual training, a placebo training group (n = 14) received video-based regular training and a control group received no training. Participants in the perceptual training group significantly improved their performance compared to both placebo and control groups; however, anticipation of deceptive throws improved less than for direct throws. The results confirm that although anticipating deception in handball is a challenging task for goalkeepers, task-specific perceptual training can minimise its effect and improve performance.

Relevance of casual contact with peanut butter in children with peanut allergy.

PubMed

Simonte, Steven J; Ma, Songhui; Mofidi, Shideh; Sicherer, Scott H

2003-07-01

Casual skin contact or inhalation of peanut butter fumes is reported and feared to cause allergic reactions in highly sensitive children with peanut allergy but has not been systematically studied. We sought to determine the clinical relevance of exposure to peanut butter by means of inhalation and skin contact in children with peanut allergy. Children with significant peanut allergy (recent peanut-specific IgE antibody concentration >50 kIU/L or evidence of peanut-specific IgE antibody and one of the following: clinical anaphylaxis, a reported inhalation-contact reaction, or positive double-blind, placebo-controlled oral challenge result to peanut) underwent double-blind, placebo-controlled, randomized exposures to peanut butter by means of contact with intact skin (0.2 mL pressed flat for 1 minute) and inhalation (surface area of 6.3 square inches 12 inches from the face for 10 minutes). Placebo challenges were performed by using soy butter mixed with histamine (contact), and scent was masked with soy butter, tuna, and mint (inhalation). Thirty children underwent the challenges (median age, 7.7 years; median peanut IgE level, >100 kIU/L; 13 with prior history of contact and 11 with inhalation reactions). None experienced a systemic or respiratory reaction. Erythema (3 subjects), pruritus without erythema (5 subjects), and wheal-and-flare reactions (2 subjects) developed only at the site of skin contact with peanut butter. From this number of participants, it can be stated with 96% confidence that at least 90% of highly sensitive children with peanut allergy would not experience a systemic-respiratory reaction from casual exposure to peanut butter. Casual exposure to peanut butter is unlikely to elicit significant allergic reactions. The results cannot be generalized to larger exposures or to contact with peanut in other forms (flour and roasted peanuts).

Pharmacodynamic correlations using fresh and cryopreserved tissue following use of vaginal rings containing dapivirine and/or maraviroc in a randomized, placebo controlled trial

PubMed Central

Dezzutti, Charlene S.; Richardson-Harman, Nicola; Rohan, Lisa C.; Marzinke, Mark A.; Hoesley, Craig J.; Panther, Lori; Johnson, Sherri; Nuttall, Jeremy P.; Nel, Annalene; Chen, Beatrice A.

2016-01-01

Abstract Background: The ex vivo challenge assay is a bio-indicator of drug efficacy and was utilized in this randomized, placebo controlled trial as one of the exploratory endpoints. Fresh and cryopreserved tissues were evaluated for human immunodeficiency virus (HIV) infection and pharmacokinetic (PK)/pharmacodynamic (PD) relationships. Methods: HIV-negative women used vaginal rings containing 25 mg dapivirine (DPV)/100 mg maraviroc (MVC) (n = 12), DPV only (n = 12), MVC only (n = 12), or placebo (n = 12) for 28 days. Blood plasma, cervicovaginal fluid (CVF), and cervical biopsies were collected for drug quantification and the ex vivo challenge assay; half (fresh) were exposed immediately to HIV while the other half were cryopreserved, thawed, then exposed to HIV. HIV replication was monitored by p24 enzyme-linked immunosorbent assay from culture supernatant. Data were log-transformed and analyzed by linear least squared regression, nonlinear Emax dose–response model and Satterthwaite t test. Results: HIV replication was greater in fresh compared to cryopreserved tissue (P = 0.04). DPV was detected in all compartments, while MVC was consistently detected only in CVF. Significant negative correlations between p24 and DPV levels were observed in fresh cervical tissue (P = 0.01) and CVF (P = 0.03), but not plasma. CVF MVC levels showed a significant negative correlation with p24 levels (P = 0.03); drug levels in plasma and tissue were not correlated with HIV suppression. p24 levels from cryopreserved tissue did not correlate to either drug from any compartment. Conclusion: Fresh tissue replicated HIV to greater levels and defined PK/PD relationships while cryopreserved tissue did not. The ex vivo challenge assay using fresh tissue could prioritize drugs being considered for HIV prevention. PMID:27428211

Pharmacodynamic correlations using fresh and cryopreserved tissue following use of vaginal rings containing dapivirine and/or maraviroc in a randomized, placebo controlled trial.

PubMed

Dezzutti, Charlene S; Richardson-Harman, Nicola; Rohan, Lisa C; Marzinke, Mark A; Hoesley, Craig J; Panther, Lori; Johnson, Sherri; Nuttall, Jeremy P; Nel, Annalene; Chen, Beatrice A

2016-07-01

The ex vivo challenge assay is a bio-indicator of drug efficacy and was utilized in this randomized, placebo controlled trial as one of the exploratory endpoints. Fresh and cryopreserved tissues were evaluated for human immunodeficiency virus (HIV) infection and pharmacokinetic (PK)/pharmacodynamic (PD) relationships. HIV-negative women used vaginal rings containing 25 mg dapivirine (DPV)/100 mg maraviroc (MVC) (n = 12), DPV only (n = 12), MVC only (n = 12), or placebo (n = 12) for 28 days. Blood plasma, cervicovaginal fluid (CVF), and cervical biopsies were collected for drug quantification and the ex vivo challenge assay; half (fresh) were exposed immediately to HIV while the other half were cryopreserved, thawed, then exposed to HIV. HIV replication was monitored by p24 enzyme-linked immunosorbent assay from culture supernatant. Data were log-transformed and analyzed by linear least squared regression, nonlinear Emax dose-response model and Satterthwaite t test. HIV replication was greater in fresh compared to cryopreserved tissue (P = 0.04). DPV was detected in all compartments, while MVC was consistently detected only in CVF. Significant negative correlations between p24 and DPV levels were observed in fresh cervical tissue (P = 0.01) and CVF (P = 0.03), but not plasma. CVF MVC levels showed a significant negative correlation with p24 levels (P = 0.03); drug levels in plasma and tissue were not correlated with HIV suppression. p24 levels from cryopreserved tissue did not correlate to either drug from any compartment. Fresh tissue replicated HIV to greater levels and defined PK/PD relationships while cryopreserved tissue did not. The ex vivo challenge assay using fresh tissue could prioritize drugs being considered for HIV prevention.

Impact of maternal probiotic-supplemented dietary counseling during pregnancy on colostrum adiponectin concentration: a prospective, randomized, placebo-controlled study.

PubMed

Luoto, Raakel; Laitinen, Kirsi; Nermes, Merja; Isolauri, Erika

2012-06-01

The breast milk bioactive substances such as adiponectin, have a presumably long-term impact upon the health and well-being of a child. To determine the impact of probiotic-supplemented dietary counseling during pregnancy on colostrum adiponectin concentration. Altogether 256 pregnant women were randomized into three study groups: dietary intervention with probiotics (diet/probiotics) or with placebo (diet/placebo) and a control group (control/placebo). The intervention group received dietary counseling provided by a nutritionist, the main focus being the amount and the type of dietary fat. The probiotics used were Lactobacillus rhamnosus GG and Bifidobacterium lactis in combination. Dietary intake was evaluated by food records at every trimester of pregnancy. Breast milk samples were collected after birth (colostrum) for adiponectin concentration analysis (n=181). The dietary intervention increased the colostrum adiponectin concentration (ng/mL, geometric mean [95% CI]), the difference being significant when comparing to the control group; 12.7 [10.6-29.7] vs. 10.2 [9.9-13.2], P=0.024. Maternal weight gain during pregnancy (kg) correlated inversely with colostrum adiponectin concentration; β (SE)=-1.7 (0.1), P=0.020, and gestational diabetes mellitus was associated with the likelihood of adiponectin concentration falling into the lowest quartile; OR 2.36, 95% CI 1.1-3.2, P=0.028. In showing that the colostrum adiponectin concentration is markedly dependent on maternal diet and nutritional status during pregnancy, and considering that colostrum adiponectin has potential effects on metabolism, nutrition, and immune function in the neonates, the results of this study underscore the importance of the metabolic homeostasis of the mother for the child's initial nutritional environment. Copyright © 2011 Elsevier Ltd. All rights reserved.

The Effect of Acclydine in Chronic Fatigue Syndrome: A Randomized Controlled Trial

PubMed Central

The, Gerard K. H; Bleijenberg, Gijs; van der Meer, Jos W. M

2007-01-01

Objectives: It is unclear whether insulin-like growth factor (IGF) function is involved in the pathophysiology of chronic fatigue syndrome (CFS). Unpublished data and reports in patient organization newsletters suggest that Acclydine, a food supplement, could be effective in the treatment of CFS by increasing biologically active IGF1 levels. Here we aimed to measure the IGF1 and IGF binding protein (IGFBP) 3 status of CFS patients compared to age- and gender-matched neighborhood controls, and to assess the effect of Acclydine on fatigue severity, functional impairment, and biologically active IGF1 level (IGFBP3/IGF1 ratio). Design: A randomized, placebo-controlled, double-blind clinical trial. Setting: Radboud University Nijmegen Medical Centre, The Netherlands. Participants: Fifty-seven adult patients who fulfilled the US Centers for Disease Control and Prevention criteria for CFS. IGF status of 22 CFS patients was compared to that of 22 healthy age- and gender-matched neighborhood control individuals. Intervention: Acclydine or placebo for 14 wk. Outcome measures: Outcomes were fatigue severity (Checklist Individual Strength, subscale fatigue severity [CIS-fatigue]), functional impairment (Sickness Impact Profile-8 [SIP-8]), and biologically active IGF1 serum concentrations. Analyses were on an intention-to-treat basis. Results: There was no difference in IGF status in 22 CFS patients compared to healthy age- and gender-matched control individuals. Treatment with Acclydine did not result in significant differences compared with the placebo group on any of the outcome measures: CIS-fatigue +1.1 (95% CI −4.4 to +6.5, p = 0.70), SIP-8 +59.1 (95% CI −201.7 to +319.8, p = 0.65), and IGFBP3/IGF1 ratio −0.5 (95% CI −2.8 to +1.7, p = 0.63). Conclusion: We found no differences in IGF1 status in CFS patients compared to healthy matched neighborhood controls. In addition, the results of this clinical trial do not demonstrate any benefit of Acclydine over placebo in the treatment of CFS. PMID:17525791

The effect of acclydine in chronic fatigue syndrome: a randomized controlled trial.

PubMed

The, Gerard K H; Bleijenberg, Gijs; van der Meer, Jos W M

2007-05-18

It is unclear whether insulin-like growth factor (IGF) function is involved in the pathophysiology of chronic fatigue syndrome (CFS). Unpublished data and reports in patient organization newsletters suggest that Acclydine, a food supplement, could be effective in the treatment of CFS by increasing biologically active IGF1 levels. Here we aimed to measure the IGF1 and IGF binding protein (IGFBP) 3 status of CFS patients compared to age- and gender-matched neighborhood controls, and to assess the effect of Acclydine on fatigue severity, functional impairment, and biologically active IGF1 level (IGFBP3/IGF1 ratio). A randomized, placebo-controlled, double-blind clinical trial. Radboud University Nijmegen Medical Centre, The Netherlands. Fifty-seven adult patients who fulfilled the US Centers for Disease Control and Prevention criteria for CFS. IGF status of 22 CFS patients was compared to that of 22 healthy age- and gender-matched neighborhood control individuals. Acclydine or placebo for 14 wk. Outcomes were fatigue severity (Checklist Individual Strength, subscale fatigue severity [CIS-fatigue]), functional impairment (Sickness Impact Profile-8 [SIP-8]), and biologically active IGF1 serum concentrations. Analyses were on an intention-to-treat basis. There was no difference in IGF status in 22 CFS patients compared to healthy age- and gender-matched control individuals. Treatment with Acclydine did not result in significant differences compared with the placebo group on any of the outcome measures: CIS-fatigue +1.1 (95% CI -4.4 to +6.5, p = 0.70), SIP-8 +59.1 (95% CI -201.7 to +319.8, p = 0.65), and IGFBP3/IGF1 ratio -0.5 (95% CI -2.8 to +1.7, p = 0.63). We found no differences in IGF1 status in CFS patients compared to healthy matched neighborhood controls. In addition, the results of this clinical trial do not demonstrate any benefit of Acclydine over placebo in the treatment of CFS.

Noni juice reduces lipid peroxidation-derived DNA adducts in heavy smokers.

PubMed

Wang, Mian-Ying; Peng, Lin; Jensen, Claude J; Deng, Shixin; West, Brett J

2013-03-01

Food plants provide important phytochemicals which help improve or maintain health through various biological activities, including antioxidant effects. Cigarette smoke-induced oxidative stress leads to the formation of lipid hydroperoxides (LOOHs) and their decomposition product malondialdehyde (MDA), both of which cause oxidative damage to DNA. Two hundred forty-five heavy cigarette smokers completed a randomized, double-blind, placebo-controlled clinical trial designed to investigate the effect of noni juice on LOOH- and MDA-DNA adducts in peripheral blood lymphocytes (PBLs). Volunteers drank noni juice or a fruit juice placebo every day for 1 month. DNA adducts were measured by (32)P postlabeling analysis. Drinking 29.5-118 mL of noni juice significantly reduced adducts by 44.6-57.4%. The placebo, which was devoid of iridoid glycosides, did not significantly influence LOOH- and MDA-DNA adduct levels in current smokers. Noni juice was able to mitigate oxidative damage of DNA in current heavy smokers, an activity associated with the presence of iridoids.

Short-Term Safety and Efficacy of Calcium Montmorillonite Clay (UPSN) in Children

PubMed Central

Mitchell, Nicole J.; Kumi, Justice; Aleser, Mildred; Elmore, Sarah E.; Rychlik, Kristal A.; Zychowski, Katherine E.; Romoser, Amelia A.; Phillips, Timothy D.; Ankrah, Nii-Ayi

2014-01-01

Recently, an association between childhood growth stunting and aflatoxin (AF) exposure has been identified. In Ghana, homemade nutritional supplements often consist of AF-prone commodities. In this study, children were enrolled in a clinical intervention trial to determine the safety and efficacy of Uniform Particle Size NovaSil (UPSN), a refined calcium montmorillonite known to be safe in adults. Participants ingested 0.75 or 1.5 g UPSN or 1.5 g calcium carbonate placebo per day for 14 days. Hematological and serum biochemistry parameters in the UPSN groups were not significantly different from the placebo-controlled group. Importantly, there were no adverse events attributable to UPSN treatment. A significant reduction in urinary metabolite (AFM1) was observed in the high-dose group compared with placebo. Results indicate that UPSN is safe for children at doses up to 1.5 g/day for a period of 2 weeks and can reduce exposure to AFs, resulting in increased quality and efficacy of contaminated foods. PMID:25135766

Noni juice reduces lipid peroxidation–derived DNA adducts in heavy smokers

PubMed Central

Wang, Mian-Ying; Peng, Lin; Jensen, Claude J; Deng, Shixin; West, Brett J

2013-01-01

Food plants provide important phytochemicals which help improve or maintain health through various biological activities, including antioxidant effects. Cigarette smoke–induced oxidative stress leads to the formation of lipid hydroperoxides (LOOHs) and their decomposition product malondialdehyde (MDA), both of which cause oxidative damage to DNA. Two hundred forty-five heavy cigarette smokers completed a randomized, double-blind, placebo-controlled clinical trial designed to investigate the effect of noni juice on LOOH- and MDA-DNA adducts in peripheral blood lymphocytes (PBLs). Volunteers drank noni juice or a fruit juice placebo every day for 1 month. DNA adducts were measured by 32P postlabeling analysis. Drinking 29.5–118 mL of noni juice significantly reduced adducts by 44.6–57.4%. The placebo, which was devoid of iridoid glycosides, did not significantly influence LOOH- and MDA-DNA adduct levels in current smokers. Noni juice was able to mitigate oxidative damage of DNA in current heavy smokers, an activity associated with the presence of iridoids. PMID:24804023

Effects of an Antisense Oligonucleotide Inhibitor of C‐Reactive Protein Synthesis on the Endotoxin Challenge Response in Healthy Human Male Volunteers

PubMed Central

Noveck, Robert; Stroes, Erik S. G.; Flaim, JoAnn D.; Baker, Brenda F.; Hughes, Steve; Graham, Mark J.; Crooke, Rosanne M.; Ridker, Paul M

2014-01-01

Background C‐reactive protein (CRP) binds to damaged cells, activates the classical complement pathway, is elevated in multiple inflammatory conditions, and provides prognostic information on risk of future atherosclerotic events. It is controversial, however, as to whether inhibiting CRP synthesis would have any direct anti‐inflammatory effects in humans. Methods and Results A placebo‐controlled study was used to evaluate the effects of ISIS 329993 (ISIS‐CRPRx) on the acute‐phase response after endotoxin challenge in 30 evaluable subjects. Healthy adult males were randomly allocated to receive 6 injections over a 22‐day period of placebo or active therapy with ISIS 329993 at 400‐ or 600‐mg doses. Eligible subjects were subsequently challenged with a bolus of endotoxin (2 ng/kg). Inflammatory and hematological biomarkers were measured before and serially after the challenge. ISIS‐CRPRx was well tolerated with no serious adverse events. Median CRP levels increased more than 50‐fold from baseline 24 hours after endotoxin challenge in the placebo group. In contrast, the median increase in CRP levels was attenuated by 37% (400 mg) and 69% (600 mg) in subjects pretreated with ISIS‐CRPRx (P<0.05 vs. placebo). All other aspects of the acute inflammatory response were similar between treatment groups. Conclusion Pretreatment of subjects with ISIS‐CRPRx selectively reduced the endotoxin‐induced increase in CRP levels in a dose‐dependent manner, without affecting other components of the acute‐phase response. These data demonstrate the specificity of antisense oligonucleotides and provide an investigative tool to further define the role of CRP in human pathological conditions. PMID:25012289

Immunomodulatory Effects of ResistAid™: A Randomized, Double-Blind, Placebo-Controlled, Multidose Study

PubMed Central

Udani, Jay K.

2013-01-01

Objective To evaluate the ability of a proprietary arabinogalactan extract from the larch tree (ResistAid, Lonza Ltd., Basel, Switzerland) to change the immune response in healthy adults to a standardized antigenic challenge (tetanus and influenza vaccines) in a dose-dependent manner compared to placebo. Methods This randomized, double-blind, placebo-controlled trial included 75 healthy adults (18–61 years old). Subjects were randomized to receive either 1.5 or 4.5 g/day of ResistAid or placebo for 60 days. At day 30, subjects were administered both tetanus and influenza vaccines. Serum antigenic response (tetanus immunoglobulin G [IgG], influenza A and B IgG and immunoglobulin M [IgM]) was measured at days 45 (15 days after vaccination) and 60 (30 days after vaccination) of the study and compared to baseline antibody levels. Frequency and intensity of adverse events were monitored throughout the study. Results As expected, all 3 groups demonstrated an expected rise in tetanus IgG levels 15 and 30 days following the vaccine. There was a strongly significant difference in the rise in IgG levels at day 60 in the 1.5 g/day group compared to placebo (p = 0.008). In the 4.5 g/day group, there was significant rise in tetanus IgG at days 45 and 60 compared to baseline (p < 0.01) but these values were not significant compared to placebo. Neither group demonstrated any significant elevations in IgM or IgG antibodies compared to placebo following the influenza vaccine. There were no clinically or statistically significant or serious adverse events. Conclusions ResistAid at a dose of 1.5 g/day significantly increased the IgG antibody response to tetanus vaccine compared to placebo. In conjunction with earlier studies, this validates the effect of ResistAid on the augmentation of the response to bacterial antigens (in the form of vaccine). PMID:24219376

Immunomodulatory effects of ResistAid™: A randomized, double-blind, placebo-controlled, multidose study.

PubMed

Udani, Jay K

2013-01-01

To evaluate the ability of a proprietary arabinogalactan extract from the larch tree (ResistAid, Lonza Ltd., Basel, Switzerland) to change the immune response in healthy adults to a standardized antigenic challenge (tetanus and influenza vaccines) in a dose-dependent manner compared to placebo. This randomized, double-blind, placebo-controlled trial included 75 healthy adults (18-61 years old). Subjects were randomized to receive either 1.5 or 4.5 g/day of ResistAid or placebo for 60 days. At day 30, subjects were administered both tetanus and influenza vaccines. Serum antigenic response (tetanus immunoglobulin G [IgG], influenza A and B IgG and immunoglobulin M [IgM]) was measured at days 45 (15 days after vaccination) and 60 (30 days after vaccination) of the study and compared to baseline antibody levels. Frequency and intensity of adverse events were monitored throughout the study. As expected, all 3 groups demonstrated an expected rise in tetanus IgG levels 15 and 30 days following the vaccine. There was a strongly significant difference in the rise in IgG levels at day 60 in the 1.5 g/day group compared to placebo (p = 0.008). In the 4.5 g/day group, there was significant rise in tetanus IgG at days 45 and 60 compared to baseline (p < 0.01) but these values were not significant compared to placebo. Neither group demonstrated any significant elevations in IgM or IgG antibodies compared to placebo following the influenza vaccine. There were no clinically or statistically significant or serious adverse events. ResistAid at a dose of 1.5 g/day significantly increased the IgG antibody response to tetanus vaccine compared to placebo. In conjunction with earlier studies, this validates the effect of ResistAid on the augmentation of the response to bacterial antigens (in the form of vaccine).

A Rosa canina - Urtica dioica - Harpagophytum procumbens/zeyheri Combination Significantly Reduces Gonarthritis Symptoms in a Randomized, Placebo-Controlled Double-Blind Study.

PubMed

Moré, Margret; Gruenwald, Joerg; Pohl, Ute; Uebelhack, Ralf

2017-12-01

The special formulation MA212 (Rosaxan) is composed of rosehip ( Rosa canina L.) puree/juice concentrate, nettle ( Urtica dioica L.) leaf extract, and devil's claw ( Harpagophytum procumbens DC. ex Meisn. or Harpagophytum zeyheri Decne.) root extract and also supplies vitamin D. It is a food for special medical purposes ([EU] No 609/2013) for the dietary management of pain in patients with gonarthritis.This 12-week randomized, placebo-controlled double-blind parallel-design study aimed to investigate the efficacy and safety of MA212 versus placebo in patients with gonarthritis.A 3D-HPLC-fingerprint (3-dimensional high pressure liquid chromatography fingerprint) of MA212 demonstrated the presence of its herbal ingredients. Ninety-two randomized patients consumed 40 mL of MA212 (n = 46) or placebo (n = 44) daily. The Western Ontario and McMaster Universities Arthritis Index (WOMAC), quality-of-life scores at 0, 6, and 12 weeks, and analgesic consumption were documented. Statistically, the initial WOMAC subscores/scores did not differ between groups. During the study, their means significantly improved in both groups. The mean pre-post change of the WOMAC pain score (primary endpoint) was 29.87 in the MA212 group and 10.23 in the placebo group. The group difference demonstrated a significant superiority in favor of MA212 (p U  < 0.001; p t  < 0.001). Group comparisons of all WOMAC subscores/scores at 6 and 12 weeks reached same significances. Compared to placebo, both physical and mental quality of life significantly improved with MA212. There was a trend towards reduced analgesics consumption with MA212, compared to placebo. In the final efficacy evaluation, physicians (p Chi  < 0.001) and patients (p Chi  < 0.001) rated MA212 superior to placebo. MA212 was well tolerated.This study demonstrates excellent efficacy for MA212 in gonarthritis patients. Georg Thieme Verlag KG Stuttgart · New York.

Roflumilast attenuates allergen-induced inflammation in mild asthmatic subjects.

PubMed

Gauvreau, Gail M; Boulet, Louis-Philippe; Schmid-Wirlitsch, Christine; Côté, Johanne; Duong, Mylinh; Killian, Kieran J; Milot, Joanne; Deschesnes, Francine; Strinich, Tara; Watson, Richard M; Bredenbröker, Dirk; O'Byrne, Paul M

2011-10-26

Phosphodiesterase 4 (PDE4) inhibitors increase intracellular cyclic adenosine monophosphate (cAMP), leading to regulation of inflammatory cell functions. Roflumilast is a potent and targeted PDE4 inhibitor. The objective of this study was to evaluate the effects of roflumilast on bronchoconstriction, airway hyperresponsiveness (AHR), and airway inflammation in mild asthmatic patients undergoing allergen inhalation challenge. 25 subjects with mild allergic asthma were randomized to oral roflumilast 500 mcg or placebo, once daily for 14 days in a double-blind, placebo-controlled, crossover study. Allergen challenge was performed on Day 14, and FEV1 was measured until 7 h post challenge. Methacholine challenge was performed on Days 1 (pre-dose), 13 (24 h pre-allergen), and 15 (24 h post-allergen), and sputum induction was performed on Days 1, 13, 14 (7 h post-allergen), and 15. Roflumilast inhibited the allergen-induced late phase response compared to placebo; maximum % fall in FEV1 (p = 0.02) and the area under the curve (p = 0.01). Roflumilast had a more impressive effect inhibiting allergen-induced sputum eosinophils, neutrophils, and eosinophil cationic protein (ECP) at 7 h post-allergen (all p = 0.02), and sputum neutrophils (p = 0.04), ECP (p = 0.02), neutrophil elastase (p = 0.0001) and AHR (p = 0.004) at 24 h post-allergen. This study demonstrates a protective effect of roflumilast on allergen-induced airway inflammation. The observed attenuation of sputum eosinophils and neutrophils demonstrates the anti-inflammatory properties of PDE4 inhibition and supports the roles of both cell types in the development of late phase bronchoconstriction and AHR. ClinicalTrials.gov: NCT01365533.

Blood fatty acid changes in healthy young Americans in response to a 10-week diet that increased n-3 and reduced n-6 fatty acid consumption: a randomised controlled trial.

PubMed

Young, Andrew J; Marriott, Bernadette P; Champagne, Catherine M; Hawes, Michael R; Montain, Scott J; Johannsen, Neil M; Berry, Kevin; Hibbeln, Joseph R

2017-05-01

Military personnel generally under-consume n-3 fatty acids and overconsume n-6 fatty acids. In a placebo-controlled, double-blinded study, we investigated whether a diet suitable for implementation in military dining facilities and civilian cafeterias could benefit n-3/n-6 fatty acid status of consumers. Three volunteer groups were provided different diets for 10 weeks. Control (CON) participants consumed meals from the US Military's Standard Garrison Dining Facility Menu. Experimental, moderate (EXP-Mod) and experimental-high (EXP-High) participants consumed the same meals, but high n-6 fatty acid and low n-3 fatty acid containing chicken, egg, oils and food ingredients were replaced with products having less n-6 fatty acids and more n-3 fatty acids. The EXP-High participants also consumed smoothies containing 1000 mg n-3 fatty acids per serving, whereas other participants received placebo smoothies. Plasma and erythrocyte EPA and DHA in CON group remained unchanged throughout, whereas EPA, DHA and Omega-3 Index increased in EXP-Mod and EXP-High groups, and were higher than in CON group after 5 weeks. After 10 weeks, Omega-3 Index in EXP-High group had increased further. No participants exhibited changes in fasting plasma TAG, total cholesterol, LDL, HDL, mood or emotional reactivity. Replacing high linoleic acid (LA) containing foods in dining facility menus with similar high oleic acid/low LA and high n-3 fatty acid foods can improve n-6/n-3 blood fatty acid status after 5 weeks. The diets were well accepted and suitable for implementation in group feeding settings like military dining facilities and civilian cafeterias.

Short-term digestive tolerance of different doses of NUTRIOSE FB, a food dextrin, in adult men.

PubMed

van den Heuvel, E G H M; Wils, D; Pasman, W J; Bakker, M; Saniez, M-H; Kardinaal, A F M

2004-07-01

To determine the tolerance of increasing dosages of an incompletely hydrolysed and/or incompletely absorbed food dextrin coming from wheat starch, NUTRIOSE FB, at daily levels of 10 and 15 g up to 60 and 80 g, respectively. A randomized, double-blind, multiple dose, placebo-controlled, combined crossover and parallel trial. The metabolic ward of TNO Nutrition and Food Research. A total of 20 healthy men (age 31.7 +/- 9.1 y; BMI 24.5 +/- 2.9 kg/m2). One group of 10 subjects consumed on top of their diet 10, 30 and 60 g of NUTRIOSE FB or maltodextrin (placebo) daily. The other group of 10 subjects consumed 15, 45 and 80 g daily. Each dose was consumed for 7 days. Compared with placebo, flatulence occurred more frequently over the last 6 days on 30, 60 or 80 g/day of NUTRIOSE FB (P < 0.05). During the last 24 h, that is, days 6-7, of 60 and 80 g/day of NUTRIOSE FB, the frequency of flatulence was even higher (P < 0.05). During the last 24 h on a daily dose of 60 g NUTRIOSE FB, the frequency of defecation decreased (P < 0.05). Bloating occurred more often during the last 24 h on 80 g/day of NUTRIOSE FB (P < 0.05). None of the doses of NUTRIOSE FB resulted in diarrhoea. Compared to baseline levels, breath H2 excretion, which was only measured after a week with 10 and 15 g of NUTRIOSE FB daily, increased (P < 0.05). However, no difference in area under the curve was found. NUTRIOSE FB is a fermentable carbohydrate and is well tolerated up to a dose of 45 g daily. Higher daily dosages (60 and 80 g) may result in flatulence, but does not result in diarrhoea. TNO Nutrition and Food Research was assigned by Roquette Frères to perform the study.

Preliminary study on the time-related changes of the infrared thermal images of the human body

NASA Astrophysics Data System (ADS)

Li, Ziru; Zhang, Xusheng; Lin, Gang; Chen, Zhigang

2009-08-01

It is of great importance to study the manifestations and the influencing factors of the time-related changes of infrared thermal images (ITI) of human body since the variable body surface temperature distribution seriously affected the application of ITI in medicine. In this paper, manifestations of time-related changes of the ITI of human body from three double-blind randomized trials and their correlation with meteorological factors (e.g. temperature, pressure, humidity, cold front passage and tropical cyclone landing) were studied. The trials were placebo or drug controlled studying the influences of Chinese medicine health food (including Shengsheng capsule with immunity adjustment function, Shengan capsule with sleep improvement function and Shengyi capsule with the function of helping to decrease serum lipid) on the ITI of human body. In the first thirty-six days of the trials images were scanned every six days and image data in the seven observation time spots (including the 0, 6, 12, 18, 24, 30, 36 day of the trial) were used for the time-related study. For every subject the scanned time was fixed in the day within two hours. The ITI features which could reflect the functions of the health foods were studied. The indexes of the features were relative magnitude (temperature difference between the viewing area and the reference area). Results showed that the variation tendencies of the trial group and control group were basically the same in placebo controlled trials and some of the long-term effects of Chinese medicine health food could be reflected significantly in certain time spots in the first thirty-six days. Time-related changes of the ITI of human body were closely related with meteorological factors but there were other influencing factors still need to be studied. As the ITI of human body could reflect the influences of Chinese medicine health foods and are closely related with meteorology, there are bright prospects for the application of ITI in health monitor.

Bioactive food stimulants of sympathetic activity: effect on 24-h energy expenditure and fat oxidation.

PubMed

Belza, A; Jessen, A B

2005-06-01

Bioactive food ingredients influence energy balance by exerting weak thermogenic effects. We studied whether the thermogenic effect of a combination of capsaicin, green tea extract (catechins and caffeine), tyrosine, and calcium was maintained after 7-day treatment and whether local effects in the gastric mucosa were involved in the efficacy. The present study was designed as a 3-way crossover, randomised, placebo-controlled, double-blinded intervention. Department of Human Nutrition, RVAU, Denmark. A total of 19 overweight to obese men (BMI: 28.0+/-2.7 kg/m2) were recruited by advertising locally. The subjects took the supplements for a period of 7 days. The supplements were administrated as a simple supplement with the bioactive ingredients, a similar enterocoated version, or placebo. In all, 24-h energy expenditure (EE), substrate oxidations, spontaneous physical activity (SPA), and heart rate were measured in respiration chambers on the seventh day of each test period. After adjustment for changes in body weight and SPA, 24-h EE was increased by 160 kJ/day (95% CI: 15-305) by the simple preparation as compared to placebo, whereas the enterocoated preparation had no such effect (53 kJ/day, -92 to 198); simple vs enterocoated versions (P=0.09). The simple preparation produced a deficit in 24-h energy balance of 193 kJ/day (49-338, P=0.03). Fat and carbohydrate oxidation were equally increased by the supplements. A supplement containing bioactive food ingredients increased daily EE by approximately 200 kJ or 2%, without raising the heart rate or any observed adverse effects. The lack of effect of the enterocoated preparation suggests that a local action of capsaicin in the gastric mucosa is a prerequisite for exerting the thermogenic effect.

Preventing necrotizing enterocolitis by food additives in neonates: A network meta-analysis revealing the efficacy and safety.

PubMed

Yu, Wentao; Sui, Wu; Mu, Linsong; Yi, Wenying; Li, Haijuan; Wei, Liqin; Yin, Weihong

2017-05-01

Necrotizing enterocolitis (NEC) is a serious multifactorial gastrointestinal disease which is often discovered in premature infants. Various additives have been used to prevent NEC; yet, their relative efficacy and safety remain disputed. This study aims to compare the efficacy and safety of 5 food additives, namely, probiotics, probiotics + fructo-oligosaccharides, pentoxifylline, arginine, and lactoferrin in preventing NEC in neonates. Embase, PubMed, and Cochrane Library had been searched for all eligible randomized control trials. Odds ratios (ORs) were estimated for dichotomous data and mean differences with 95% credible intervals (CrIs) were estimated for continuous data. Surface under the cumulative ranking curve was used to rank efficacy and safety of the prevention methods on each endpoint. A total of 27 eligible studies with 4649 preterm infants were included in this network meta-analysis (NMA), and the efficacy and safety of 5 food additives were evaluated. Probiotic and arginine exhibited better preventive efficacy compared with placebo (OR = 0.50, 95% CrIs: 0.32-0.73; OR = 0.30, 95% CrIs: 0.12-0.73, respectively). Only probiotic achieved a considerable decrease in the risk of mortality compared to placebo (OR = 0.68, 95% CrIs: 0.46-0.98). NEC patients with lactoferrin appeared to have lower incidence of sepsis than those of placebo (OR = 0.13, 95% CrIs: 0.03-0.61) or probiotic (OR = 0.18, 95% CrIs: 0.03-0.83). Based on this NMA, probiotics had the potential to be the most preferable additive, since it exhibited a significant superiority for NEC and mortality as well as a relatively balanced performance in safety.

Alcohol's acute effect on food intake is mediated by inhibitory control impairments.

PubMed

Christiansen, Paul; Rose, Abigail; Randall-Smith, Laura; Hardman, Charlotte A

2016-05-01

There is a strong association between alcohol misuse and excess weight. Although alcohol is highly calorific and may directly contribute to weight gain, it is also likely to have indirect effects on weight. Indeed, alcohol primes have been found to stimulate appetite and increase energy intake in experimental taste tests. The current study investigated whether the effects of alcohol on energy intake are the result of inhibitory control impairments and whether this effect is moderated by individual differences in dietary restraint. Sixty undergraduate females completed measures of dietary restraint and the Food Craving Questionnaire-State (FCQS). Following this, they were given an alcohol prime (0.6 g of alcohol per kg of body weight) or a placebo drink manipulated to smell and taste alcoholic. Participants then completed another FCQS and a color conflict Stroop to measure inhibitory control. Finally, participants were asked to taste cookies for 15 minutes. Participants in the alcohol condition performed worse on the Stroop (d = .61) and consumed more cookie calories (d = .61) than participants in the placebo condition. Notably, the effect of the experimental condition on the amount of cookies consumed was mediated by Stroop performance (Κ2 = .08), although this effect was not evident under high levels of restraint. There was no effect of experimental condition on any subscale of craving. The current study suggests that increased energy intake after alcohol administration may be the product of inhibitory control impairments. However, the most restrained eaters are able to maintain control over their eating behavior. (c) 2016 APA, all rights reserved).

The Impact of Oxytocin on Food Intake and Emotion Recognition in Patients with Eating Disorders: A Double Blind Single Dose Within-Subject Cross-Over Design.

PubMed

Kim, Youl-Ri; Eom, Jin-Sup; Yang, Jae-Won; Kang, Jiwon; Treasure, Janet

2015-01-01

Social difficulties and problems related to eating behaviour are common features of both anorexia nervosa (AN) and bulimia nervosa (BN). The aim of this study was to examine the impact of intranasal oxytocin on consummatory behaviour and emotional recognition in patients with AN and BN in comparison to healthy controls. A total of 102 women, including 35 patients with anorexia nervosa (AN), 34 patients with bulimia nervosa (BN), and 33 healthy university students of comparable age and intelligence, participated in a double-blind, single dose placebo-controlled cross-over study. A single dose of intranasal administration of oxytocin (40 IU) (or a placebo) was followed by an emotional recognition task and an apple juice drink. Food intake was then recorded for 24 hours post-test. Oxytocin produced no significant change in appetite in the acute or 24 hours free living settings in healthy controls, whereas there was a decrease in calorie consumption over 24 hours in patients with BN. Oxytocin produced a small increase in emotion recognition sensitivity in healthy controls and in patients with BN, In patients with AN, oxytocin had no effect on emotion recognition sensitivity or on consummatory behaviour. The impact of oxytocin on appetite and social cognition varied between people with AN and BN. A single dose of intranasal oxytocin decreased caloric intake over 24 hours in people with BN. People with BN showed enhanced emotional sensitivity under oxytocin condition similar to healthy controls. Those effects of oxytocin were not found in patients with AN. ClinicalTrials.gov KCT00000716.

The Combined Effect of Caffeine and Ornithine on the Mood of Healthy Office Workers

PubMed Central

Misaizu, Akane; Kokubo, Takeshi; Tazumi, Kyoko; Kanayama, Masaya; Miura, Yutaka

2014-01-01

Caffeine is widely consumed and well known for stimulating the central nervous system. When developing new foods and beverages that contain caffeine, it is important to explore the potential synergistic effects of consuming amino acids and other food ingredients with caffeine on humans. Given the physiological pathways affected by the amino acid ornithine, consumption of ornithine with caffeine may have synergistic effects. The purpose of the present study was to examine the effect of consuming caffeine with ornithine in humans. The study used a randomized, placebo-controlled, double-blinded crossover design. The subjects were all healthy office workers who ingested the placebo, 100 mg caffeine, or 100 mg caffeine plus 200 mg ornithine in the morning and completed questionnaires about their mood. Office workers who consumed the combination of caffeine and ornithine had higher mood ratings 8 h after consumption than office workers who consumed caffeine alone. The results of the present study suggest that there is a unique synergistic effect between caffeine and ornithine on the mood of healthy office workers and that ornithine may potentiate the effects of caffeine. PMID:25580405

Should we reconsider the routine use of placebo controls in clinical research?

PubMed

Avins, Andrew L; Cherkin, Daniel C; Sherman, Karen J; Goldberg, Harley; Pressman, Alice

2012-04-27

Modern clinical-research practice favors placebo controls over usual-care controls whenever a credible placebo exists. An unrecognized consequence of this preference is that clinicians are more limited in their ability to provide the benefits of the non-specific healing effects of placebos in clinical practice. We examined the issues in choosing between placebo and usual-care controls. We considered why placebo controls place constraints on clinicians and the trade-offs involved in the choice of control groups. We find that, for certain studies, investigators should consider usual-care controls, even if an adequate placebo is available. Employing usual-care controls would be of greatest value for pragmatic trials evaluating treatments to improve clinical care and for which threats to internal validity can be adequately managed without a placebo-control condition. Intentionally choosing usual-care controls, even when a satisfactory placebo exists, would allow clinicians to capture the value of non-specific therapeutic benefits that are common to all interventions. The result could be more effective, patient-centered care that makes the best use of both specific and non-specific benefits of medical interventions.

The effectiveness of fermented turmeric powder in subjects with elevated alanine transaminase levels: a randomised controlled study.

PubMed

Kim, Sang-Wook; Ha, Ki-Chan; Choi, Eun-Kyung; Jung, Su-Young; Kim, Min-Gul; Kwon, Dae-Young; Yang, Hye-Jung; Kim, Min-Jung; Kang, Hee-Joo; Back, Hyang-Im; Kim, Sun-Young; Park, Soo-Hyun; Baek, Hum-Young; Kim, Yong-Jae; Lee, Joon-Yeol; Chae, Soo-Wan

2013-03-08

Previous animal studies have shown that Curcuma longa (turmeric) improves liver function. Turmeric may thus be a promising ingredient in functional foods aimed at improving liver function. The purpose of the study is to investigate the hepatoprotective effect of fermented turmeric powder (FTP) on liver function in subjects with elevated alanine transaminase (ALT) levels. A randomised, double-blind, placebo-controlled trial was conducted between November 2010 and April 2012 at the clinical trial center for functional foods of the Chonbuk National University Hospital. The trial included 60 subjects, 20 years old and above, who were diagnosed mild to moderate elevated ALT levels between 40 IU/L and 200 IU/L. Sixty subjects were randomised to receive FTP 3.0 g per day or placebo 3.0 g per day for 12 weeks. The treatment group received two capsules of FTP three times a day after meals, for 12 weeks. The primary efficacy endpoint was change in the ALT levels in the two groups. The secondary efficacy endpoints included its effect on aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), total bilirubin (TB), and lipid profiles. Safety was assessed throughout the study using ongoing laboratory tests. Adverse events (AEs) were also recorded. Sixty subjects were randomised in the study (30 into the FTP group, 30 into the placebo group), and among them, twelve subjects were excluded from the analysis for protocol violation, adverse events or consent withdrawal. The two groups did not differ in baseline characteristics. After 12 weeks of treatment, 48 subjects were evaluated. Of the 48 subjects, 26 randomly received FTP capsules and 22 received placebo. The FTP group showed a significant reduction in ALT levels after 12 weeks of treatment compared with the placebo group (p = 0.019). There was also observed that the serum AST levels were significantly reduce in the FTP group than placebo group (p = 0.02). The GGT levels showed a tendency to decrease, while the serum alkaline phosphatase (ALP), TB, and lipids levels were not modified. There were no reported severe AEs during this study, or abnormalities observed on blood glucose, total protein, albumin, blood urea nitrogen (BUN), and creatinine levels. The data of this trial indicate that FTP is effective and safe, generally well-tolerated without severe AEs, in the treatment of subjects with elevated ALT levels over a 12 weeks period. ClinicalTrials.gov: NCT01634256

The effectiveness of fermented turmeric powder in subjects with elevated alanine transaminase levels: a randomised controlled study

PubMed Central

2013-01-01

Background Previous animal studies have shown that Curcuma longa (turmeric) improves liver function. Turmeric may thus be a promising ingredient in functional foods aimed at improving liver function. The purpose of the study is to investigate the hepatoprotective effect of fermented turmeric powder (FTP) on liver function in subjects with elevated alanine transaminase (ALT) levels. Methods A randomised, double-blind, placebo-controlled trial was conducted between November 2010 and April 2012 at the clinical trial center for functional foods of the Chonbuk National University Hospital. The trial included 60 subjects, 20 years old and above, who were diagnosed mild to moderate elevated ALT levels between 40 IU/L and 200 IU/L. Sixty subjects were randomised to receive FTP 3.0 g per day or placebo 3.0 g per day for 12 weeks. The treatment group received two capsules of FTP three times a day after meals, for 12 weeks. The primary efficacy endpoint was change in the ALT levels in the two groups. The secondary efficacy endpoints included its effect on aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), total bilirubin (TB), and lipid profiles. Safety was assessed throughout the study using ongoing laboratory tests. Adverse events (AEs) were also recorded. Results Sixty subjects were randomised in the study (30 into the FTP group, 30 into the placebo group), and among them, twelve subjects were excluded from the analysis for protocol violation, adverse events or consent withdrawal. The two groups did not differ in baseline characteristics. After 12 weeks of treatment, 48 subjects were evaluated. Of the 48 subjects, 26 randomly received FTP capsules and 22 received placebo. The FTP group showed a significant reduction in ALT levels after 12 weeks of treatment compared with the placebo group (p = 0.019). There was also observed that the serum AST levels were significantly reduce in the FTP group than placebo group (p = 0.02). The GGT levels showed a tendency to decrease, while the serum alkaline phosphatase (ALP), TB, and lipids levels were not modified. There were no reported severe AEs during this study, or abnormalities observed on blood glucose, total protein, albumin, blood urea nitrogen (BUN), and creatinine levels. Conclusion The data of this trial indicate that FTP is effective and safe, generally well-tolerated without severe AEs, in the treatment of subjects with elevated ALT levels over a 12 weeks period. Trial registration ClinicalTrials.gov: http://NCT01634256 PMID:23497020

Does Glycine max leaves or Garcinia Cambogia promote weight-loss or lower plasma cholesterol in overweight individuals: a randomized control trial.

PubMed

Kim, Ji-Eun; Jeon, Seon-Min; Park, Ki Hun; Lee, Woo Song; Jeong, Tae-Sook; McGregor, Robin A; Choi, Myung-Sook

2011-09-21

Natural food supplements with high flavonoid content are often claimed to promote weight-loss and lower plasma cholesterol in animal studies, but human studies have been more equivocal. The aim of this study was firstly to determine the effectiveness of natural food supplements containing Glycine max leaves extract (EGML) or Garcinia cambogia extract (GCE) to promote weight-loss and lower plasma cholesterol. Secondly to examine whether these supplements have any beneficial effect on lipid, adipocytokine or antioxidant profiles. Eighty-six overweight subjects (Male:Female = 46:40, age: 20~50 yr, BMI > 23 < 29) were randomly assigned to three groups and administered tablets containing EGML (2 g/day), GCE (2 g/day) or placebo (starch, 2 g/day) for 10 weeks. At baseline and after 10 weeks, body composition, plasma cholesterol and diet were assessed. Blood analysis was also conducted to examine plasma lipoproteins, triglycerides, adipocytokines and antioxidants. EGML and GCE supplementation failed to promote weight-loss or any clinically significant change in %body fat. The EGML group had lower total cholesterol after 10 weeks compared to the placebo group (p < 0.05). EGML and GCE had no effect on triglycerides, non-HDL-C, adipocytokines or antioxidants when compared to placebo supplementation. However, HDL-C was higher in the EGML group (p < 0.001) after 10 weeks compared to the placebo group. Ten weeks of EGML or GCE supplementation did not promote weight-loss or lower total cholesterol in overweight individuals consuming their habitual diet. Although, EGML did increase plasma HDL-C levels which is associated with a lower risk of atherosclerosis.

Does Glycine max leaves or Garcinia Cambogia promote weight-loss or lower plasma cholesterol in overweight individuals: a randomized control trial

PubMed Central

2011-01-01

Background Natural food supplements with high flavonoid content are often claimed to promote weight-loss and lower plasma cholesterol in animal studies, but human studies have been more equivocal. The aim of this study was firstly to determine the effectiveness of natural food supplements containing Glycine max leaves extract (EGML) or Garcinia cambogia extract (GCE) to promote weight-loss and lower plasma cholesterol. Secondly to examine whether these supplements have any beneficial effect on lipid, adipocytokine or antioxidant profiles. Methods Eighty-six overweight subjects (Male:Female = 46:40, age: 20~50 yr, BMI > 23 < 29) were randomly assigned to three groups and administered tablets containing EGML (2 g/day), GCE (2 g/day) or placebo (starch, 2 g/day) for 10 weeks. At baseline and after 10 weeks, body composition, plasma cholesterol and diet were assessed. Blood analysis was also conducted to examine plasma lipoproteins, triglycerides, adipocytokines and antioxidants. Results EGML and GCE supplementation failed to promote weight-loss or any clinically significant change in %body fat. The EGML group had lower total cholesterol after 10 weeks compared to the placebo group (p < 0.05). EGML and GCE had no effect on triglycerides, non-HDL-C, adipocytokines or antioxidants when compared to placebo supplementation. However, HDL-C was higher in the EGML group (p < 0.001) after 10 weeks compared to the placebo group. Conclusions Ten weeks of EGML or GCE supplementation did not promote weight-loss or lower total cholesterol in overweight individuals consuming their habitual diet. Although, EGML did increase plasma HDL-C levels which is associated with a lower risk of atherosclerosis. PMID:21936892

Pregabalin versus tramadol for postoperative pain management in patients undergoing lumbar laminectomy: a randomized, double-blinded, placebo-controlled study

PubMed Central

Kumar, Koramutla Pradeep; Kulkarni, Dilip Kumar; Gurajala, Indira; Gopinath, Ramachandran

2013-01-01

Prevention and treatment of postoperative pain continues to be a major challenge in postoperative care. Opioid analgesics, with their well-known side effects, continue to represent a cornerstone in postoperative pain control. Anticonvulsant medications are established treatments for neuropathic pain. Pregabalin (S-[+]-3-isobutylgaba), a structural analog of gamma-Aminobutyric acid, has been used for the treatment of various neuropathic pain and also as an adjunctive therapy for adults with partial onset seizures. This study was thus taken up to primarily assess and compare the analgesic and anxiolytic effects of administering pregabalin and tramadol preoperatively for patients undergoing elective decompressive lumbar laminectomy. The study group included 75 patients between the ages of 20–60 years belonging to American Society of Anesthesiology-1 (ASA) and ASA-2 patients. The patients were randomly allocated into three groups of 25 patients each. The placebo group received a placebo capsule, the tramadol group received a 100 mg capsule, while the pregabalin group received a 150 mg capsule orally 1 hour before anesthetic induction. Pregabalin showed statistically significant analgesic effects compared to placebo, but the effect was found to be less prevalent compared to tramadol. The need for rescue analgesia was the least prevalent in tramadol patients followed by pregabalin patients, and reached a maximum in the control group. Pregabalin showed statistically significant anxiolytic effects compared to placebo, and this was associated with less sedation in comparison to tramadol. Pregabalin had fewer numbers of postoperative complications of nausea, vomiting, and drowsiness in comparison to tramadol. The results of this study support the clinical use of pregabalin in the postsurgical setting for pain relief, as it is well tolerated, and usually presents with transient adverse effects. PMID:23837006

Time-dependent interactions of the hypotensive effects of sildenafil citrate and sublingual glyceryl trinitrate

PubMed Central

Oliver, James J; Kerr, Debra M; Webb, David J

2009-01-01

AIM To investigate the time course of the hypotensive interaction between sildenafil and glyceryl trinitrate (GTN). METHODS Two double-blind, placebo-controlled, randomized, crossover studies were performed. Subjects were challenged with sublingual GTN 400 µg at different times after oral sildenafil 100 mg. After each GTN challenge frequent measures of blood pressure (BP) were made. In the first study GTN was given 1–48 h after sildenafil/placebo to 33 healthy men. In the second study GTN was given 1–8 h after sildenafil/placebo to 20 men with stable angina. RESULTS In healthy men there was a greater mean maximum reduction in BP with sildenafil/GTN than with placebo/GTN only at 1 h. In angina patients, there was a greater mean maximum reduction in BP with sildenafil/GTN than with placebo/GTN for up to 8 h. The mean (95% confidence interval) differences in maximum systolic BP reduction (mmHg) at 1, 4, 6 and 8 h were −16 (−12, −21), −12 (−4, −20), −6 (1, −12) and −9 (−3, −15), all P < 0.05 except at 6 h (NS). At 6 and 8 h the interaction was not more than additive, and hypotensive symptoms did not occur. CONCLUSIONS In men with angina there is an interaction on BP reduction between sildenafil and GTN for ≥ 8 h after sildenafil administration, but this is no more than additive from 6 h. These data may be helpful to clinicians who are considering the use of GTN in patients presenting with angina who have received sildenafil within 24 h. PMID:19371313

Genetic variation at the Th2 immune gene IL13 is associated with IgE-mediated paediatric food allergy.

PubMed

Ashley, S E; Tan, H-T T; Peters, R; Allen, K J; Vuillermin, P; Dharmage, S C; Tang, M L K; Koplin, J; Lowe, A; Ponsonby, A-L; Molloy, J; Matheson, M C; Saffery, R; Ellis, J A; Martino, D

2017-08-01

Food allergies pose a considerable world-wide public health burden with incidence as high as one in ten in 12-month-old infants. Few food allergy genetic risk variants have yet been identified. The Th2 immune gene IL13 is a highly plausible genetic candidate as it is central to the initiation of IgE class switching in B cells. Here, we sought to investigate whether genetic polymorphisms at IL13 are associated with the development of challenge-proven IgE-mediated food allergy. We genotyped nine IL13 "tag" single nucleotide polymorphisms (tag SNPs) in 367 challenge-proven food allergic cases, 199 food-sensitized tolerant cases and 156 non-food allergic controls from the HealthNuts study. 12-month-old infants were phenotyped using open oral food challenges. SNPs were tested using Cochran-Mantel-Haenszel test adjusted for ancestry strata. A replication study was conducted in an independent, co-located sample of four paediatric cohorts consisting of 203 food allergic cases and 330 non-food allergic controls. Replication sample phenotypes were defined by clinical history of reactivity, 95% PPV or challenge, and IL13 genotyping was performed. IL13 rs1295686 was associated with challenge-proven food allergy in the discovery sample (P=.003; OR=1.75; CI=1.20-2.53). This association was also detected in the replication sample (P=.03, OR=1.37, CI=1.03-1.82) and further supported by a meta-analysis (P=.0006, OR=1.50). However, we cannot rule out an association with food sensitization. Carriage of the rs1295686 variant A allele was also associated with elevated total plasma IgE. We show for the first time, in two independent cohorts, that IL13 polymorphism rs1295686 (in complete linkage disequilibrium with functional variant rs20541) is associated with challenge-proven food allergy. © 2017 John Wiley & Sons Ltd.

Oral food desensitization in children with IgE-mediated hen's egg allergy: a new protocol with raw hen's egg.

PubMed

Meglio, Paolo; Giampietro, Paolo G; Carello, Rossella; Gabriele, Ida; Avitabile, Simona; Galli, Elena

2013-02-01

Hen's egg allergy affects young children and can cause severe allergic reactions. Avoidance results in dietary limitations and can affect the quality of life, especially in cases where potentially life-threatening reactions exist. Our objective was to desensitize children with moderate-severe IgE-mediated hen's egg allergy over a 6-month period, by introducing increasing and very gradual daily doses of raw hen's egg in order to enable the children to assume 25ml of this food, or to induce tolerance to the highest possible dose. The protocol foresaw the egg reintroduction in the home setting. In this randomized, controlled open study, 20 hen's egg allergic children (10 in the active group) were admitted. A convincing history or a positive double-blind placebo-controlled food challenge confirmed the diagnosis. Oral desensitization was performed with increasing doses starting from 0.27 mg of hen's egg proteins (1 drop of raw hen's egg diluted 1:100). We adopted an original, mathematically calculated protocol in order to ensure a constant, daily increment of doses. 8/10 children (80%) in the active group achieved the daily intake of 25ml over a 6-month period. One child (10%) could tolerate up to 2ml/day while another child (10%) failed the desensitization. Six months after enrolment only 2 children in the control group (20%) could tolerate hen's egg. We successfully desensitized 8/10 children with IgE-mediated hen's egg allergy in a 6-month period. The partial outcome in the child who could tolerate 2ml/day reduced the risk of severe reactions after unnoticed introduction of egg. A regular protocol that ensures a daily constant increase of doses helps to reduce possible adverse events, thus improving safety and effectiveness. © 2012 John Wiley & Sons A/S.

Dietary sorbitol and mannitol: food content and distinct absorption patterns between healthy individuals and patients with irritable bowel syndrome.

PubMed

Yao, C K; Tan, H-L; van Langenberg, D R; Barrett, J S; Rose, R; Liels, K; Gibson, P R; Muir, J G

2014-04-01

Sorbitol and mannitol are naturally-occurring polyol isomers. Although poor absorption and induction of gastrointestinal symptoms by sorbitol are known, the properties of mannitol are poorly described. We aimed to expand data on food composition of these polyols, and to compare their absorptive capacities and symptom induction in patients with irritable bowel syndrome (IBS) and healthy individuals. Food samples were analysed for sorbitol and mannitol content. The degree of absorption measured by breath hydrogen production and gastrointestinal symptoms (visual analogue scales) was evaluated in a randomised, double-blinded, placebo-controlled study in 21 healthy and 20 IBS subjects after challenges with 10 g of sorbitol, mannitol or glucose. Certain fruits and sugar-free gum contained sorbitol, whereas mannitol content was higher in certain vegetables. Similar proportions of patients with IBS (40%) and healthy subjects (33%) completely absorbed sorbitol, although more so with IBS absorbed mannitol (80% versus 43%; P = 0.02). Breath hydrogen production was similar in both groups after lactulose but was reduced in patients with IBS after both polyols. No difference in mean (SEM) hydrogen production was found in healthy controls after sorbitol [area-under-the-curve: 2766 (591) ppm 4 h(-1) ] or mannitol [2062 (468) ppm 4 h(-1) ] but, in patients with IBS, this was greater after sorbitol [1136 (204) ppm 4 h(-1) ] than mannitol [404 (154) ppm 4 h(-1) ; P = 0.002]. Overall gastrointestinal symptoms increased significantly after both polyols in patients with IBS only, although they were independent of malabsorption of either of the polyols. Increased and discordant absorption of mannitol and sorbitol occurs in patients with IBS compared to that in healthy controls. Polyols induced gastrointestinal symptoms in patients with IBS independently of their absorptive patterns, suggesting that the dietary restriction of polyols may be efficacious. © 2013 The British Dietetic Association Ltd.

Applying Disruptive Preference Test Protocols to Increase the Number of "No Preference" Responses in the Placebo Pair, Using Chinese Consumers.

PubMed

Xia, Yixun; Zhong, Fang; O'Mahony, Michael

2016-09-01

One form of paired preference test protocol requires consumers to assess 2 pairs of products. One is the target pair under consideration, while the other is a putatively identical pair named the "placebo pair" which is also presented as a control. Counterintuitively, the majority of consumers report preferences when presented with the placebo pair. Their response frequencies are hypothesized to be those of consumers having "no preference" and are compared with the response frequencies elicited by a target pair, to determine whether the target pair elicits significant preferences. The primary goal of this paper was to study the robustness of 2 new so called disruptive protocols that reduced the proportion of consumers, who reported preferences when assessing a putatively identical pair of products. For this task, the tests were performed in a different language, in a different country, using different products from before. The results showed that the proportion of consumers reporting preferences for the placebo pair was reduced, confirming earlier work. Also, comparison of d' values showed a lack of significant overall differences between the placebo and target pairs, while chi-squared analyses indicated significant differences in the response frequencies. This indicated that the sample was segmented into 2 balanced groups with opposing preferences. © 2016 Institute of Food Technologists®

Integrating nutrition and early child-development interventions among infants and preschoolers in rural India.

PubMed

Fernandez-Rao, Sylvia; Hurley, Kristen M; Nair, Krishnapillai Madhavan; Balakrishna, Nagalla; Radhakrishna, Kankipati V; Ravinder, Punjal; Tilton, Nicholas; Harding, Kimberly B; Reinhart, Greg A; Black, Maureen M

2014-01-01

This article describes the development, design, and implementation of an integrated randomized double-masked placebo-controlled trial (Project Grow Smart) that examines how home/preschool fortification with multiple micronutrient powder (MNP) combined with an early child-development intervention affects child development, growth, and micronutrient status among infants and preschoolers in rural India. The 1-year trial has an infant phase (enrollment age: 6-12 months) and a preschool phase (enrollment age: 36-48 months). Infants are individually randomized into one of four groups: placebo, placebo plus early learning, MNP alone, and MNP plus early learning (integrated intervention), conducted through home visits. The preschool phase is a cluster-randomized trial conducted in Anganwadi centers (AWCs), government-run preschools sponsored by the Integrated Child Development System of India. AWCs are randomized into MNP or placebo, with the MNP or placebo mixed into the children's food. The evaluation examines whether the effects of the MNP intervention vary by the quality of the early learning opportunities and communication within the AWCs. Study outcomes include child development, growth, and micronutrient status. Lessons learned during the development, design, and implementation of the integrated trial can be used to guide large-scale policy and programs designed to promote the developmental, educational, and economic potential of children in developing countries. © 2013 New York Academy of Sciences.

Impact of a Specific Amino Acid Composition with Micronutrients on Well-Being in Subjects with Chronic Psychological Stress and Exhaustion Conditions: A Pilot Study

PubMed Central

Armborst, Deborah; Metzner, Christine; Alteheld, Birgit; Bitterlich, Norman; Rösler, Daniela; Siener, Roswitha

2018-01-01

Chronic work-life stress leads to dysfunction of the hypothalamus–pituitary–adrenal axis, the autonomic nervous system, and the serotonergic system, with resultant impairment of overall well-being. Aim of the study was to improve perceived stress by a specific amino acid composition with micronutrients in the verum versus placebo group. A total of 59 participants (18–65 years) with self-reported perceived chronic stress and exhaustion conditions participated in this randomized, double-blind, placebo-controlled study. The Perceived Stress Questionnaire (PSQ30), amino acid profile, anthropometric, clinical, blood, urine parameters, and dietary intake were assessed. After 12 weeks, the verum group achieved significantly greater improvements in the total PSQ30 score compared with the placebo group. In the verum group, serum taurine concentration, folic acid concentration, urinary magnesium excretion, and the ratio of l-tryptophan to the sum of competing amino acids rose significantly. In the placebo group, serum concentrations of serotonin, protein, and magnesium decreased significantly, whereas the cardiometabolic risk parameters body weight, body mass index, waist circumference, and waist-to-height ratio increased significantly. Compared with placebo, the verum supplementation resulted in a higher improvement in perceived stress. Beneficial effects on the serotonergic system and preventive effects on magnesium homeostasis and some cardiometabolic risk factors were supposed. Additional effects might be caused by the optimized food intake. PMID:29710825

Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial

PubMed Central

Buchbinder, Susan P.; Mehrotra, Devan V.; Duerr, Ann; Fitzgerald, Daniel W.; Mogg, Robin; Li, David; Gilbert, Peter B.; Lama, Javier R.; Marmor, Michael; Rio, Carlos del; McElrath, M. Juliana; Casimiro, Danilo R.; Gottesdiener, Keith M.; Chodakewitz, Jeffrey A.; Corey, Lawrence; Robertson, Michael N.

2009-01-01

Background Observational data and non-human primate challenge studies suggest that cell-mediated immune (CMI) responses may provide control of HIV replication. The Step Study is the first direct assessment of the efficacy of a CMI vaccine to protect against HIV infection or alter early plasma HIV levels in humans. Method HIV-seronegative participants (3000) were randomized (1:1) to receive 3 injections of MRKAd5 HIV-1 gag/pol/nef vaccine or placebo. Randomization was pre-stratified by gender, baseline adenovirus type 5 (Ad5) titer, and study site. Participants were tested ~every 6 months for HIV acquisition; early plasma HIV RNA was measured ~3 months post-HIV diagnosis. Findings The vaccine elicited IFN-γ ELISPOT responses in 75% of vaccinees. In a pre-specified interim analysis among participants with baseline Ad5 ≤200, 24 of 741 vaccinees became HIV infected, versus 21 of 762 placebo recipients. All but one infection occurred in men. The early geometric mean plasma HIV RNA was comparable in infected vaccine and placebo recipients. In exploratory multivariate analyses, HIV incidence was higher in vaccinees versus placebo recipients among Ad5 seropositive men (5.1% versus 2.2% per year, respectively) and uncircumcised men (5.2% versus 1.4% per year, respectively). HIV incidence was similar in vaccinees versus placebo recipients among Ad5 seronegative men and circumcised men. Interpretation This CMI vaccine did not prevent HIV infection or lower early viral level. Mechanisms for failure of the vaccine to protect and for the increased HIV infection rates in subgroups of vaccinees are being explored. Additional follow-up will determine if elevated HIV incidence in vaccinee subgroups persists. PMID:19012954

A randomized controlled trial of methotrexate for patients with generalized myasthenia gravis.

PubMed

Pasnoor, Mamatha; He, Jianghua; Herbelin, Laura; Burns, Ted M; Nations, Sharon; Bril, Vera; Wang, Annabel K; Elsheikh, Bakri H; Kissel, John T; Saperstein, David; Shaibani, J Aziz; Jackson, Carlayne; Swenson, Andrea; Howard, James F; Goyal, Namita; David, William; Wicklund, Matthew; Pulley, Michael; Becker, Mara; Mozaffar, Tahseen; Benatar, Michael; Pazcuzzi, Robert; Simpson, Ericka; Rosenfeld, Jeffrey; Dimachkie, Mazen M; Statland, Jeffrey M; Barohn, Richard J

2016-07-05

To determine the steroid-sparing effect of methotrexate (MTX) in patients with symptomatic generalized myasthenia gravis (MG). We performed a 12-month multicenter, randomized, double-blind, placebo-controlled trial of MTX 20 mg orally every week vs placebo in 50 acetylcholine receptor antibody-positive patients with MG between April 2009 and August 2014. The primary outcome measure was the prednisone area under the dose-time curve (AUDTC) from months 4 to 12. Secondary outcome measures included 12-month changes of the Quantitative Myasthenia Gravis Score, the Myasthenia Gravis Composite Score, Manual Muscle Testing, the Myasthenia Gravis Quality of Life, and the Myasthenia Gravis Activities of Daily Living. Fifty-eight patients were screened and 50 enrolled. MTX did not reduce the month 4-12 prednisone AUDTC when compared to placebo (difference MTX - placebo: -488.0 mg, 95% confidence interval -2,443.4 to 1,467.3, p = 0.26); however, the average daily prednisone dose decreased in both groups. MTX did not improve secondary measures of MG compared to placebo over 12 months. Eight participants withdrew during the course of the study (1 MTX, 7 placebo). There were no serious MTX-related adverse events. The most common adverse event was nonspecific pain (19%). We found no steroid-sparing benefit of MTX in MG over 12 months of treatment, despite being well-tolerated. This study demonstrates the challenges of conducting clinical trials in MG, including difficulties with recruitment, participants improving on prednisone alone, and the need for a better understanding of outcome measure variability for future clinical trials. This study provides Class I evidence that for patients with generalized MG MTX does not significantly reduce the prednisone AUDTC over 12 months of therapy. © 2016 American Academy of Neurology.

Chronic consumption of a low calorie, high polyphenol cranberry beverage attenuates inflammation and improves glucoregulation and HDL cholesterol in healthy overweight humans: a randomized controlled trial.

PubMed

Chew, Boon; Mathison, Bridget; Kimble, Lindsey; McKay, Diane; Kaspar, Kerrie; Khoo, Christina; Chen, C-Y Oliver; Blumberg, Jeffrey

2018-02-23

We studied the health benefits of low calorie cranberry beverage consumption on glucoregulation, oxidative damage, inflammation, and lipid metabolism in overweight but otherwise healthy humans. 78 overweight or obese men and women (30-70 years; BMI 27-35 kg/m 2 ) with abdominal adiposity (waist: hip > 0.8 for women and > 0.9 for men; waist: height ≥ 0.5) consumed 450 mL placebo or low calorie, high polyphenol cranberry extract beverage (CEB) daily for 8 week in a randomized, double-blind, placebo-controlled, parallel design trial. Blood and urine samples were collected after overnight fast at baseline and after 8 weeks of daily beverage consumption. Blood and urine samples were also collected during 3 oral glucose tolerance test (OGTT) challenges: (1) pre-intervention without the test beverages, (2) following a single dose of placebo or CEB at baseline (week 0), and (3) following a single dose of placebo or CEB at 8 week. Compared to placebo, a single CEB dose at baseline lowered endothelin-1 and elevated nitric oxide and the reduced:oxidized glutathione ratio (P < 0.05). Interferon-γ was elevated (P < 0.05) after a single CEB dose at baseline; however, after 8 week of CEB intervention, fasting C-reactive protein was lower (P < 0.05). CEB consumption for 8 week also reduced serum insulin and increased HDL cholesterol compared to placebo (P < 0.05). An acute dose of low calorie, high polyphenol cranberry beverage improved antioxidant status, while 8 week daily consumption reduced cardiovascular disease risk factors by improving glucoregulation, downregulating inflammatory biomarkers, and increasing HDL cholesterol.

Efficacy and safety of lorcaserin in obese adults: a meta-analysis of 1-year randomized controlled trials (RCTs) and narrative review on short-term RCTs.

PubMed

Chan, E W; He, Y; Chui, C S L; Wong, A Y S; Lau, W C Y; Wong, I C K

2013-05-01

Lorcaserin is a new anti-obesity drug recently approved by US Food and Drug Administration. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the association of lorcaserin therapy with weight loss and adverse events in obese adults (18-65 years old). Weight loss of 3.23 kg (95% confidence interval [CI]: 2.70, 3.75) and body mass index reduction of 1.16 kg m⁻² (95% CI: 0.98, 1.34) was observed compared with placebo in RCTs of 1 year duration. The use of lorcaserin for 8 and 12 weeks reduced weight of 1.60 kg (95% CI: 0.34, 2.86) and 2.9 kg (95% CI: 2.2, 3.5), respectively. In comparison to placebo, lorcaserin decreased waist circumference, blood pressure, total cholesterol, low-density lipoprotein-cholesterol and triglycerides, however did not statistically affect heart rate or high-density lipoprotein-cholesterol. Headache, nausea and dizziness were found to be significantly higher in the patients receiving lorcaserin than patients receiving placebo, whereas diarrhoea is no more likely than in patients receiving placebo. In conclusion, lorcaserin achieves modest weight loss and appears to be well tolerated. Clinical and pharmacovigilance studies with longer study duration are needed to inform of the long-term efficacy and safety of lorcaserin. © 2013 The Authors. obesity reviews © 2013 International Association for the Study of Obesity.

Fulranumab in Patients With Pain Associated With Postherpetic Neuralgia and Postraumatic Neuropathy

PubMed Central

Wang, Hao; Romano, Gary; Fedgchin, Margaret; Russell, Lucille; Sanga, Panna; Kelly, Kathleen M.; Frustaci, Mary Ellen

2017-01-01

Objective: Fulranumab is an antibody that specifically neutralizes the biological activity of human nerve growth factor. This multicenter, phase-2, randomized, double-blind (DB), placebo-controlled study evaluated the analgesic efficacy and safety of fulranumab in postherpetic neuralgia (PHN) and posttraumatic neuropathy (PTN) patients. Methods: Patients (18 to 80 y) with inadequately controlled moderate-to-severe pain received study medication (subcutaneous injection) every 4 weeks. PHN patients were randomized (3:2:2:3) to receive either placebo or one of 3 doses of fulranumab: 1 mg (1 mgQ4 wk), 3 mg (3 mgQ4 wk), or 10 mg (10 mgQ4 wk). PTN patients were randomized (1:1) to receive either placebo or fulranumab 10 mgQ4 wk. Results: The US Food and Drug Administration placed a clinical hold (December 23, 2010) on all trials of antinerve growth factor drugs, including fulranumab, due to identified risks of osteonecrosis or rapidly progressing osteoarthritis; therefore, only 49 (of 150 planned) PHN patients and 34 (of 50 planned) PTN patients completed the DB efficacy evaluation. There was no significant difference (P>0.05, fulranumab vs. placebo) for change in 7-day average of daily pain intensity scores from DB baseline to end of 12-week DB efficacy phase in PHN or PTN patients (primary endpoint). No significant difference was found with fulranumab versus placebo (P>0.05) in other efficacy measures in either PHN or PTN patients. The most common treatment-emergent adverse events (>10% incidence) in PTN patients were sinusitis, carpal tunnel syndrome, and headache, whereas in PHN patients it was arthralgia. Discussion: Fulranumab did not demonstrate efficacy in either PHN or PTN patients, but was generally well-tolerated in this small underpowered and abbreviated study. PMID:27153360

Effect of herbal medicine daikenchuto on oral and enteral caloric intake after liver transplantation: A multicenter, randomized controlled trial.

PubMed

Kaido, Toshimi; Shinoda, Masahiro; Inomata, Yukihiro; Yagi, Takahito; Akamatsu, Nobuhisa; Takada, Yasutsugu; Ohdan, Hideki; Shimamura, Tsuyoshi; Ogura, Yasuhiro; Eguchi, Susumu; Eguchi, Hidetoshi; Ogata, Satoshi; Yoshizumi, Tomoharu; Ikegami, Toshihiko; Yamamoto, Michio; Morita, Satoshi; Uemoto, Shinji

2018-03-20

Postoperative early oral or enteral intake is a crucial element of the Enhanced Recovery After Surgery (ERAS) protocol. However, normal food intake or enteral feeding cannot be started early in the presence of coexisting bowel dysfunction in patients undergoing liver transplantation (LT). The aim of this multicenter, randomized, double-blinded, placebo-controlled trial was to determine the enhancement effects of the Japanese herbal medicine Daikenchuto (DKT) on oral/enteral caloric intake in patients undergoing LT. A total of 112 adult patients undergoing LT at 14 Japanese centers were enrolled. The patients were randomly assigned to receive either DKT or placebo from postoperative day (POD) 1 to 14. The primary endpoints were total oral/enteral caloric intake, abdominal distension, and pain on POD 7. The secondary endpoints included sequential changes in total oral/enteral caloric intake after LT, and portal venous flow volume and velocity in the graft. A total of 104 patients (DKT, n = 55; placebo, n = 49) were included in the analyses. There were no significant differences between the two groups in terms of primary endpoints. However, postoperative total oral/enteral caloric intake was significantly accelerated in the DKT group compared with the placebo group (P = 0.023). Moreover, portal venous flow volume (POD 10, 14) and velocity (POD 14) were significantly higher in the DKT group than in the placebo group (P = 0.047, P = 0.025, P = 0.014, respectively). Postoperative administration of DKT may enhance total oral/enteral caloric intake and portal venous flow volume and velocity after LT and favorably contribute to the performance of the ERAS protocol. Copyright © 2018 Elsevier Inc. All rights reserved.

The effects of soy milk and isoflavone supplements on cognitive performance in healthy, postmenopausal women.

PubMed

Fournier, L R; Ryan Borchers, T A; Robison, L M; Wiediger, M; Park, J S; Chew, B P; McGuire, M K; Sclar, D A; Skaer, T L; Beerman, K A

2007-01-01

The decline in estrogen concentrations in women after menopause can contribute to health related changes including impairments in cognition, especially memory. Because of the health concerns related to hormone replacement therapy (HRT), alternative approaches to treat menopausal symptoms, such as nutritional supplements and/or diet containing isoflavones, are of interest. This study investigated whether soy isoflavones (soy milk and supplement) could improve cognitive functioning in healthy, postmenopausal women. PARTICIPANTS, INTERVENTION AND DESIGN: A total of 79 postmenopausal women, 48-65 years of age, completed a double-blind, placebo-controlled trial in which they were randomly assigned to one of three experimental groups: cow's milk and a placebo supplement (control); soy milk and placebo supplement (soy milk, 72 mg isoflavones/day); or cow's milk and isoflavone supplement (isoflavone supplement, 70 mg isoflavones/day). Cognitive functioning was assessed using various cognitive tasks before the intervention (baseline) and after the intervention (test). In contrast to predictions, soy isoflavones did not improve selective attention (Stroop task), visual long-term memory (pattern recognition), short-term visuospatial memory (Benton Visual Retention Test), or visuo-spatial working memory (color match task). Also, the soy milk group showed a decline in verbal working memory (Digit Ordering Task) compared to the soy supplement and control groups. Soy isoflavones consumed as a food or supplement over a 16-week period did not improve or appreciably affect cognitive functioning in healthy, postmenopausal women.

Nasal Ketorolac Challenge Using Acoustic Rhinometry in Patients With Aspirin-Exacerbated Respiratory Disease.

PubMed

Quiralte-Castillo, J; Ávila-Castellano, M R; Cimbollek, S; Benaixa, P; Leguisamo, S; Baynova, K; Labella, M; Quiralte, J

Safer and less time-consuming alternatives to single-blind placebo-controlled oral challenge (SBPCOC) have been sought for the diagnosis of aspirin-exacerbated respiratory disease (AERD). Nasal challenges with various nonsteroidal anti-inflammatory drugs and assessment methods have been developed. Objective: Our objective was to evaluate the utility and safety of nasal ketorolac challenge (NKC) using acoustic rhinometry in patients with suspected AERD. The study population comprised 36 patients with suspected AERD. NKC was performed with placebo (saline) and 13 mg of ketorolac sprayed as aerosol into both nostrils. A positive challenge result was defined as an increase of ≥30% in nasal symptoms (recorded using a visual analog scale) and a 30% drop in the sum of the volumes of both nasal cavities at 2-8 cm. Patients with a negative NKC result underwent SBPCOC with aspirin (cumulative dose of 750 mg). A naso-ocular reaction during NKC was detected in 21 patients. Four patients also developed mild asthma exacerbations (although only 1 experienced a decrease in FEV1 >15%). No other significant adverse events occurred. The remaining 15 patients with a negative NKC result had a negative response during aspirin SBPCOC. NKC assessed using acoustic rhinometry is a reliable method for the study of patients with AERD. We suggest that NKC assessed with acoustic rhinometry was useful and safe for selection of candidates for safe oral aspirin challenge.

No appetite efficacy of a commercial structured lipid emulsion in minimally processed drinks.

PubMed

Smit, H J; Keenan, E; Kovacs, E M R; Wiseman, S A; Mela, D J; Rogers, P J

2012-09-01

Fabuless (Olibra) is a commercially structured lipid emulsion, claimed to be a food ingredient that is effective for food intake and appetite reduction. The present study assessed its efficacy in a yoghurt-based mini-drink undergoing low or minimal food manufacturing (thermal and shear) processes. Study 1: Twenty-four healthy volunteers (16 female, 8 male; age: 18-47 years; body mass index (BMI): 17-28 kg m(-2)) took part in a randomised, placebo-controlled, double-blind parallel crossover trial. Consumption of a minimally processed 'preload' mini-drink (containing two different doses of Fabuless or a control fat) at 2 h after breakfast was followed by appetite and mood ratings, and food intake measured in ad libitum meals at 3 and 7 h post consumption of the preload. Study 2: As Study 1 (16 female, 8 male; age: 20-54 years; BMI: 21-30 kg m(-2)). A chilled, virtually unprocessed, preload breakfast mini-drink (containing minimally processed Fabuless or a control fat) was provided 5 min after a standardised breakfast, followed by appetite and mood ratings, and food intake measured in ad libitum meals at 4 and 8 h post consumption of the preload. The structured lipid emulsion tested had no significant effect on the primary measures of food intake or appetite. Even when exposed to minimal food-manufacturing conditions, Fabuless showed no efficacy on measures of appetite and food intake.

Effects of Silybum marianum (L.) Gaertn. (silymarin) extract supplementation on antioxidant status and hs-CRP in patients with type 2 diabetes mellitus: a randomized, triple-blind, placebo-controlled clinical trial.

PubMed

Ebrahimpour Koujan, Soraiya; Gargari, Bahram Pourghassem; Mobasseri, Majid; Valizadeh, Hadi; Asghari-Jafarabadi, Mohammad

2015-02-15

Diabetes is a serious metabolic disorder and oxidative stress and inflammation contribute to its pathogenesis and complications. Since Silybum marianum (L.) Gaertn. (silymarin) extract is an antioxidant with anti-inflammatory properties, this randomized clinical trial was conducted to evaluate the effects of silymarin supplementation on oxidative stress indices and hs-CRP in type 2 diabetes mellitus patients. For the present paralleled, randomized, triple-blinded, placebo-controlled clinical trial, 40 type 2 diabetes patients aged 25-50 yr old and on stable medication were recruited from the Iranian Diabetes Society and endocrinology clinics in East Azarbayjan (Tabriz, Iran) and randomly assigned into two groups. Patients in the silymarin treatment group received 140 mg, thrice daily of dried extracts of Silybum marianum (n = 20) and those in the placebo group (n = 20) received identical placebos for 45 days. Data pertaining to height, weight, waist circumference and BMI, as well as food consumption, were collected at base line and at the conclusion of the study. Fasting blood samples were obtained and antioxidant indices and hs-CRP were assessed at baseline, as well as at the end of the trial. All 40 patients completed the study and did not report any adverse effects or symptoms with the silymarin supplementation. Silymarin supplementation significantly increased superoxide dismutase (SOD), glutathione peroxidase (GPX) activity and total antioxidant capacity (TAC) compared to patients taking the placebo, by 12.85%, 30.32% and 8.43%, respectively (p < 0.05). There was a significant reduction in hs-CRP levels by 26.83% (p < 0.05) in the silymarin group compared to the placebo group. Malondialdehyde (MDA) concentration significantly decreased by 12.01% (p < 0.05) in the silymarin group compared to the baseline. Silymarin supplementation improves some antioxidant indices (SOD, GPX and TAC) and decrease hs-CRP levels in T2DM patients. Copyright © 2015. Published by Elsevier GmbH.

A randomized, double-blind, placebo-controlled, cross-over study to assess the efficacy of tadalafil (Cialis[reg]) in the treatment of erectile dysfunction following three-dimensional conformal external-beam radiotherapy for prostatic carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Incrocci, Luca; Slagter, Cleo; Slob, A. Koos

2006-10-01

Purpose: Erectile dysfunction after three-dimensional conformal external-beam radiotherapy (3DCRT) for prostatic carcinoma is reported in as many as 64% of those patients. The purpose of this study was to determine the efficacy of the oral drug tadalafil (Cialis (registered) ) in patients with erectile dysfunction after radiotherapy for prostatic carcinoma. Methods and Materials: Patients (N = 358) who completed radiotherapy at least 12 months before the study were approached by mail. All patients had been treated by 3DCRT; 60 patients were included and entered a double-blind, placebo-controlled, cross-over study lasting 12 weeks. They received 20 mg of tadalafil or placebomore » for 6 weeks. Drug or placebo was taken on demand at patient's discretion, with no restrictions regarding the consumption of alcohol or food, at least once a week and no more than once daily. At 6 weeks patients crossed over to the alternative treatment. Data were collected using the Sexual Encounter Profile (SEP) and the International Index of Erectile Function (IIEF) questionnaires. Side effects were also recorded. Results: Mean age at study entry was 69 years. All patients completed the study. For almost all questions of the IIEF questionnaire there was a significant increase in mean scores from baseline with tadalafil, but not with placebo. Sixty-seven percent of the patients reported an improvement of erectile function with tadalafil (placebo: 20%), and 48% reported successful intercourse with tadalafil (placebo: 9%) (p < 0.0001). Side effects were mild or moderate. Conclusions: Tadalafil is an effective treatment for erectile dysfunction after 3DCRT for prostatic carcinoma with successful intercourse reported in almost 50% of the patients, and it is well tolerated.« less

Neurophysiological effects of modafinil on cue-exposure in cocaine dependence: a randomized placebo-controlled cross-over study using pharmacological fMRI.

PubMed

Goudriaan, Anna E; Veltman, Dick J; van den Brink, Wim; Dom, Geert; Schmaal, Lianne

2013-02-01

Enhanced reactivity to substance related cues is a central characteristic of addiction and has been associated with increased activity in motivation, attention, and memory related brain circuits and with a higher probability of relapse. Modafinil was promising in the first clinical trials in cocaine dependence, and was able to reduce craving in addictive disorders. However, its mechanism of action remains to be elucidated. In this functional magnetic resonance imaging (fMRI) study therefore, cue reactivity in cocaine dependent patients was compared to cue reactivity in healthy controls (HCs) under modafinil and placebo conditions. An fMRI cue reactivity study, with a double-blind, placebo-controlled cross-over challenge with a single dose of modafinil (200mg) was employed in 13 treatment seeking cocaine dependent patients and 16 HCs. In the placebo condition, watching cocaine-related pictures (versus neutral pictures) resulted in higher brain activation in the medial frontal cortex, anterior cingulate cortex, angular gyrus, left orbitofrontal cortex, and ventral tegmental area (VTA) in the cocaine dependent group compared to HCs. However, in the modafinil condition, no differences in brain activation patterns were found between cocaine dependent patients and HCs. Group interactions revealed decreased activity in the VTA and increased activity in the right ACC and putamen in the modafinil condition relative to the placebo condition in cocaine dependent patients, whereas such changes were not present in healthy controls. Decreases in self-reported craving when watching cocaine-related cues after modafinil administration compared to the placebo condition were associated with modafinil-induced increases in ACC and putamen activation. Enhanced cue reactivity in the cocaine dependent group compared to healthy controls was found in brain circuitries related to reward, motivation, and autobiographical memory processes. In cocaine dependent patients, these enhanced brain responses were attenuated by modafinil, mainly due to decreases in cue- reactivity in reward-related brain areas (VTA) and increases in cue reactivity in cognitive control areas (ACC). These modafinil-induced changes in brain activation in response to cocaine-related visual stimuli were associated with diminished self-reported craving. These findings imply that in cocaine dependent patients, modafinil, although mainly known as a cognitive enhancer, acts on both the motivational and the cognitive brain circuitry. Copyright © 2012 Elsevier Ltd. All rights reserved.

Insights from Preclinical Choice Models on Treating Drug Addiction

PubMed Central

Banks, Matthew L.; Negus, S. Stevens

2016-01-01

Substance-use disorders are a global public health problem that arises from behavioral misallocation between drug use and more adaptive behaviors maintained by nondrug alternatives (e.g., food or money). Preclinical drug self-administration procedures that incorporate a concurrently available nondrug reinforcer (e.g., food) provide translationally relevant and distinct dependent measures of behavioral allocation (i.e., to assess the relative reinforcing efficacy of the drug) and behavioral rate (i.e., to assess motor competence). In particular, preclinical drug versus food ‘choice’ procedures have produced increasingly concordant results with both human laboratory drug self-administration studies and double-blind placebo-controlled clinical trials. Accordingly, here we provide a heuristic framework of substance-use disorders based on a behavioral-centric perspective and recent insights from these preclinical choice procedures. PMID:27916279

Comparison of the clinical efficacy and tolerability of olopatadine hydrochloride 0.1% ophthalmic solution and loteprednol etabonate 0.2% ophthalmic suspension in the conjunctival allergen challenge model.

PubMed

Berdy, Gregg J; Stoppel, Juan O; Epstein, Arthur B

2002-06-01

Olopatadine hydrochloride 0.1% ophthalmic solution and loteprednol etabonate 0.2% ophthalmic suspension are topical antiallergic agents indicated for treatment of the signs and symptoms of allergic conjunctivitis and seasonal allergic conjunctivitis (SAC), respectively. The purpose of this study was to compare the efficacy and tolerability of olopatadine, loteprednol, and placebo in inhibiting the early-phase allergic reaction (within 30 minutes) after conjunctival allergen challenge (CAC). This was a single-center, randomized, double-masked, parallel-controlled CAC study. It consisted of 3 visits, with CAC performed at visit 1, confirmation and randomization at visit 2, and evaluation of the treatments at visit 3. Subjects with a history of allergic conjunctivitis were randomized to receive olopatadine, loteprednol, or placebo in a 2:2:1 ratio. Because loteprednol requires a loading period to achieve maximum efficacy, subjects assigned to this treatment received loteprednol QID bilaterally for a 14-day period; the olopatadine and placebo groups received placebo QID bilaterally during this period. At the evaluation visit, subjects received 1 drop of the assigned treatment in each eye. Fifteen minutes later, they were challenged with allergen. Subjects evaluated itching at 3, 5, and 10 minutes after challenge using a standardized 5-point scale; the investigator evaluated redness at 10, 15, and 20 minutes after challenge. Intraocular pressure (IOP) was measured at baseline and after the 14-day loading period. Nonparametric analyses were performed on the change from visit 2 to visit 3 in mean itching and redness scores for each time point, and on the change in mean IOP from visit 1 to visit 3. Fifty subjects (86% white; 42% male, 58% female; age range, 21-71 years) were enrolled and completed the study (20 olopatadine, 20 loteprednol, 10 placebo). The allergens to which subjects reacted were ragweed pollen (40%), cat hair or dander (30%), grass pollen (24%), and tree pollen (6%). The difference in inhibition of itching and redness was clinically significant (> or =1 unit difference) and statistically significant (P < 0.05) in favor of olopatadine compared with loteprednol at all 3 time points. The loteprednol group had a statistically significant increase in IOP after 2 weeks of treatment (P < 0.001). In the population studied, olopatadine was more efficacious than loteprednol in reducing the acute signs and symptoms of SAC during the early phase of the ocular allergic reaction and appeared to be better tolerated.

Intra-articular Autologous Conditioned Plasma Injections Provide Safe and Efficacious Treatment for Knee Osteoarthritis: An FDA-Sanctioned, Randomized, Double-blind, Placebo-controlled Clinical Trial.

PubMed

Smith, Patrick A

2016-04-01

Platelet-rich plasma (PRP) injections have become an intriguing treatment option for osteoarthritis (OA), particularly OA of the knee. Despite the plethora of PRP-related citations, there is a paucity of high-level evidence that is comparable, cohort specific, dose controlled, injection protocol controlled, and double-blinded. To determine the safety and efficacy of leukocyte-poor PRP autologous conditioned plasma (ACP) for knee OA treatment through a feasibility trial regulated by the US Food and Drug Administration (FDA). Randomized controlled trial; Level of evidence, 1. In accordance with FDA protocol, patient selection was based on strict inclusion/exclusion criteria; 114 patients were screened, and 30 were ultimately included in the study. These patients were randomized to receive either ACP (n = 15) or saline placebo (n = 15) for a series of 3 weekly injections. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores served as the primary efficacy outcome measure. Patients were followed for 1 year. No adverse events were reported for ACP administration. Furthermore, the results demonstrated no statistically significant difference in baseline WOMAC scores between the 2 groups. However, in the ACP group, WOMAC scores at 1 week were significantly decreased compared with baseline scores, and the scores for this group remained significantly lower throughout the study duration. At the study conclusion (12 months), subjects in the ACP group had improved their overall WOMAC scores by 78% from their baseline score, compared with 7% for the placebo group. ACP is safe and provides quantifiable benefits for pain relief and functional improvement with regard to knee OA. No adverse events were reported for ACP administration. After 1 year, WOMAC scores for the ACP subjects had improved by 78% from their baseline score, whereas scores for the placebo control group had improved by only 7%. Other joints affected with OA may also benefit from this treatment. © 2016 The Author(s).

AZP-531, an unacylated ghrelin analog, improves food-related behavior in patients with Prader-Willi syndrome: A randomized placebo-controlled trial.

PubMed

Allas, Soraya; Caixàs, Assumpta; Poitou, Christine; Coupaye, Muriel; Thuilleaux, Denise; Lorenzini, Françoise; Diene, Gwenaëlle; Crinò, Antonino; Illouz, Frédéric; Grugni, Graziano; Potvin, Diane; Bocchini, Sarah; Delale, Thomas; Abribat, Thierry; Tauber, Maithé

2018-01-01

Prader-Willi syndrome (PWS) is characterized by early-onset hyperphagia and increased circulating levels of the orexigenic Acylated Ghrelin (AG) hormone with a relative deficit of Unacylated Ghrelin (UAG). AZP-531, a first-in-class UAG analog, was shown to inhibit the orexigenic effect of AG in animals, to improve glycemic control and decrease body weight in humans. We aimed to investigate the safety and efficacy of AZP-531 in patients with PWS for whom no approved treatment for hyperphagia is currently available. Multi-center, randomized, double-blind, placebo-controlled trial. Forty-seven patients with genetically confirmed PWS and evidence of hyperphagia received daily subcutaneous injections of AZP-531 (3 and 4 mg for 50-70 kg and >70 kg body weight, respectively) or matching placebo for 14 days. Assessments included adverse events, vital signs, safety laboratory tests, the Hyperphagia Questionnaire (HQ), patient-reported appetite, body composition and glycemic measures. AZP-531 was well tolerated. There was a significant improvement with AZP-531 versus placebo in the mean total score, the 9-item score and the severity domain score of the HQ (p < .05). The highest reduction in the total and 9-item scores was observed in AZP-531 subjects with the highest hyperphagia score at baseline. Findings were supported by a reduction in appetite scores observed with AZP-531 only. Body weight did not change in both groups while a significant reduction in waist circumference and fat mass was observed only with AZP-531. AZP-531 significantly decreased post-prandial glucose levels in a baseline glucose dependent fashion. AZP-531 may constitute a new treatment strategy to improve hyperphagia and metabolic issues in patients with PWS. These findings support further investigation in longer-term clinical trials.

Tolerability of a Fully Maturated Cheese in Cow’s Milk Allergic Children: Biochemical, Immunochemical, and Clinical Aspects

PubMed Central

Alessandri, Claudia; Sforza, Stefano; Palazzo, Paola; Lambertini, Francesca; Paolella, Sara; Zennaro, Danila; Rafaiani, Chiara; Ferrara, Rosetta; Bernardi, Maria Livia; Santoro, Mario; Zuzzi, Sara; Giangrieco, Ivana; Dossena, Arnaldo; Mari, Adriano

2012-01-01

Background From patients’ reports and our preliminary observations, a fully maturated cheese (Parmigiano-Reggiano; PR) seems to be well tolerated by a subset of cow’s milk (CM) allergic patients. Objective and Methods To biochemically and immunologically characterize PR samples at different maturation stage and to verify PR tolerability in CM allergic children. Seventy patients, with suspected CM allergy, were enrolled. IgE to CM, α-lactalbumin (ALA), β-lactoglobulin (BLG) and caseins (CAS) were tested using ImmunoCAP, ISAC103 and skin prick test. Patients underwent a double-blind, placebo-controlled food challenge with CM, and an open food challenge with 36 months-maturated PR. Extracts obtained from PR samples were biochemically analyzed in order to determine protein and peptide contents. Pepsin and trypsin-chymotrypsin-pepsin simulated digestions were applied to PR extracts. Each PR extract was investigated by IgE Single Point Highest Inhibition Achievable assay (SPHIAa). The efficiency analysis was carried out using CM and PR oral challenges as gold standards. Results The IgE binding to milk allergens was 100% inhibited by almost all PR preparations; the only difference was for CAS, mainly αS1-CAS. Sixteen patients sensitized to CM tolerated both CM and PR; 29 patients tolerated PR only; 21 patients, reacted to both CM and PR, whereas 4 patients reactive to CM refused to ingest PR. ROC analysis showed that the absence of IgE to BLG measured by ISAC could be a good marker of PR tolerance. The SPHIAa using digested PR preparations showed a marked effect on IgE binding to CAS and almost none on ALA and BLG. Conclusions 58% of patients clinically reactive to CM tolerated fully maturated PR. The preliminary digestion of CAS induced by PR maturation process, facilitating a further loss of allergenic reactivity during gut digestion, might explain the tolerance. This hypothesis seems to work when no IgE sensitization to ISAC BLG is detected. PMID:22829901

A Review of Escitalopram and Citalopram in Child and Adolescent Depression

PubMed Central

Carandang, Carlo; Jabbal, Rekha; MacBride, Angela; Elbe, Dean

2011-01-01

Objective: To review the basic pharmacology and published literature regarding escitalopram and citalopram in child and adolescent depression. Methods: A literature review was conducted using the search terms: ‘escitalopram’, ‘citalopram’, ‘depression’, ‘randomized controlled trial’, ‘open label trial’ and limits set to: Human trials, English Language and All Child (Age 0–18). Additional articles were identified from reference information and poster presentation data. Results: Three prospective, randomized controlled trials (RCT) were found for escitalopram in pediatric depression, and two RCTs were found for citalopram. One RCT each for escitalopram and citalopram showed superiority over placebo on the primary out come measure. Adverse effects in escitalopram and citalopram trials were generally mild to moderate. Suicidality was not assessed systematically in all RCTs reviewed, but did not appear to be elevated over placebo in escitalopram RCTs. One trial reported numerically higher suicide related events for citalopram compared to placebo (14 vs. 5, p=0.06). Conclusion: At present, escitalopram and citalopram should be considered a second-line option for adolescent depression. The US Food and Drug Administration approval of escitalopram for treatment of adolescent depression was based on a single positive RCT. This is less evidence than typically required for approval of a drug for a new indication. PMID:22114615

Evaluation of safety and tolerance of microencapsulated Lactobacillus reuteri NCIMB 30242 in a yogurt formulation: a randomized, placebo-controlled, double-blind study.

PubMed

Jones, Mitchell L; Martoni, Christopher J; Tamber, Sandeep; Parent, Mathieu; Prakash, Satya

2012-06-01

Probiotic organisms have shown promise in treating diseases. Previously, we have reported on the efficacy of microencapsulated Lactobacillus reuteri NCIMB 30242 in a yogurt formulation at lowering serum cholesterol levels in otherwise healthy hypercholesterolemic adults. This study investigates the safety and toxicology of oral ingestion of microencapsulated L. reuteri NCIMB 30242 in a yogurt formulation. A randomized group of 120 subjects received a dose of 5 × 10(10) CFU microencapsulated L. reuteri NCIMB 30242 in yogurt (n=59) or placebo yogurt (n=61) twice/day for 6 weeks. Clinical chemistry and hematological parameters of safety were analyzed. Fecal samples were collected at these time points for the analysis of deconjugated bile acids. The frequency, duration and intensity of adverse events (AEs) and clinical significance of safety parameters were recorded for both groups. No clinically significant differences between the probiotic yogurt and placebo yogurt treated groups were detected in either the blood clinical chemistry or hematology results and there was no significant increase in fecal deconjugated bile acids (P>0.05) between treated and control groups. The frequency and intensity of AEs was similar in the two groups. These results demonstrate the safe use of this formulation in food. Copyright © 2012 Elsevier Ltd. All rights reserved.

Placebo-like response in absence of treatment in children with Autism.

PubMed

Jones, Rebecca M; Carberry, Caroline; Hamo, Amarelle; Lord, Catherine

2017-09-01

Caregiver report is the most common measure of change in pediatric psychiatry. Yet, placebo response rates pose significant challenges to reliably detect a treatment response. The present study simulated an eight-week clinical trial protocol for Autism Spectrum Disorder (ASD) for the purpose of testing the feasibility and validity of several outcome measures. Twenty caregivers answered questions about their child's behavior on their smartphone each week and completed a battery of paper questionnaires during weeks one and eight. No treatment was administered. Caregivers reported a significant decrease in problem behaviors on the Aberrant Behavior Checklist (ABC) (29% decrease) and general ASD behaviors on the Social Responsiveness Scale (SRS) (7% decrease). There was also a trend of behavior improvement from smartphone questions but no significant changes in clinical ratings of core diagnostic features of ASD. Participation in a comprehensive protocol in the absence of a particular treatment significantly influenced how caregivers perceived the severity of their children's problem behaviors. These placebo-like effects represent substantial challenges for randomized controlled trials (RCTs) that use treatment as usual and have implications for future behavioral and pharmacological treatment trial designs. Autism Res 2017, 10: 1567-1572. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

Effect of tryptophan-rich egg protein hydrolysate on brain tryptophan availability, stress and performance.

PubMed

Markus, C Rob; Verschoor, E; Firk, C; Kloek, J; Gerhardt, C C

2010-10-01

Reduced brain serotonin function is involved in stress-related disturbances and may particularly occur under chronic stress. Although serotonin production directly depends on the availability of its plasma dietary amino acid precursor tryptophan (TRP), previously described effects of tryptophan-rich food sources on stress-related behavior are rather modest. Recently, an egg protein hydrolysate (EPH) was developed that showed a much greater effect on brain TRP availability than pure TRP and other TRP-food sources and therefore may be more effective for performance under stress. The aim of the present study was to investigate the effects of EPH compared to placebo protein on plasma amino acids, stress coping and performance in subjects with high and low chronic stress vulnerabilities. In a placebo-controlled, double-blind, crossover study, 17 participants with high and 18 participants with low chronic stress vulnerabilities were monitored for mood and performance under acute stress exposure either following intake of EPH or placebo. EPH significantly increased plasma TRP availability for uptake into the brain, decreased depressive mood in all subjects and improved perceptual-motor and vigilance performance only in low chronic stress-vulnerable subjects. The acute use of a TRP-rich egg protein hydrolysate (EPH) is an adequate method to increase plasma TRP for uptake into the brain and may be beneficial for perceptual-motor and vigilance performance in healthy volunteers. Copyright © 2010 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Serotoninergic manipulation, meal-induced satiety and eating pattern: effect of fluoxetine in obese female subjects.

PubMed

Lawton, C L; Wales, J K; Hill, A J; Blundell, J E

1995-07-01

Twelve nondepressed healthy female obese subjects (BMI > 30 kg/m2) took part in a study which conformed to a double-blind randomized crossover design. Each subject acted as her own control across 2 weeks of treatment with either 60 mg of the 5-HT reuptake inhibitor fluoxetine or matching placebo. On days 7 and 14 of both treatment phases subjects were provided with fixed energy lunch meals high in either CHO or fat. The effect of these meals on satiety during the fluoxetine and placebo phases was assessed by a battery of procedures. Subjects felt less hungry after consuming the high CHO meal than after consuming the high-fat meal. They also felt less hungry when taking fluoxetine than when taking the placebo. Analysis of energy intake from the test meal revealed a main effect of prior lunch meal type (high CHO or high fat) and a main effect of drug treatment. Subjects consumed an average of 574 kcal following the high CHO meal compared to 689 kcal following the high-fat meal. Subjects also consumed an average of 532 kcal when taking fluoxetine compared to 730 kcal when taking the placebo. Fluoxetine did not exert any significant effects on macronutrient selection. Mean daily energy intake, calculated from food diary records, was 1881 kcal when subjects were taking the placebo compared to 1460 kcal when taking fluoxetine (a reduction of 22.4%). Fluoxetine treatment produced a significant weight loss of 1.97 kg over the two weeks of treatment compared to a weight loss of only 0.04 kg on placebo.

Traumeel S® for pain relief following hallux valgus surgery: a randomized controlled trial

PubMed Central

2010-01-01

Background In spite of recent advances in post-operative pain relief, pain following orthopedic surgery remains an ongoing challenge for clinicians. We examined whether a well known and frequently prescribed homeopathic preparation could mitigate post-operative pain. Method We performed a randomized, double blind, placebo-controlled trial to evaluate the efficacy of the homeopathic preparation Traumeel S® in minimizing post-operative pain and analgesic consumption following surgical correction of hallux valgus. Eighty consecutive patients were randomized to receive either Traumeel tablets or an indistinguishable placebo, and took primary and rescue oral analgesics as needed. Maximum numerical pain scores at rest and consumption of oral analgesics were recorded on day of surgery and for 13 days following surgery. Results Traumeel was not found superior to placebo in minimizing pain or analgesic consumption over the 14 days of the trial, however a transient reduction in the daily maximum post-operative pain score favoring the Traumeel arm was observed on the day of surgery, a finding supported by a treatment-time interaction test (p = 0.04). Conclusions Traumeel was not superior to placebo in minimizing pain or analgesic consumption over the 14 days of the trial. A transient reduction in the daily maximum post-operative pain score on the day of surgery is of questionable clinical importance. Trial Registration This study was registered at ClinicalTrials.gov. # NCT00279513 PMID:20380750

Treatment with grass allergen peptides improves symptoms of grass pollen-induced allergic rhinoconjunctivitis.

PubMed

Ellis, Anne K; Frankish, Charles W; O'Hehir, Robyn E; Armstrong, Kristen; Steacy, Lisa; Larché, Mark; Hafner, Roderick P

2017-08-01

Synthetic peptide immunoregulatory epitopes are a new class of immunotherapy to treat allergic rhinoconjunctivitis (ARC). Grass allergen peptides, comprising 7 synthetic T-cell epitopes derived from Cyn d 1, Lol p 5, Dac g 5, Hol l 5, and Phl p 5, is investigated for treatment of grass pollen-induced ARC. We sought to evaluate the efficacy, safety, and tolerability of intradermally administered grass allergen peptides. A multicenter, randomized, double-blind, placebo-controlled study evaluated 3 regimens of grass allergen peptides versus placebo in patients with grass pollen-induced allergy (18-65 years). After a 4-day baseline challenge to rye grass in the environmental exposure unit (EEU), subjects were randomized to receive grass allergen peptides at 6 nmol at 2-week intervals for a total of 8 doses (8x6Q2W), grass allergen peptides at 12 nmol at 4-week intervals for a total of 4 doses (4x12Q4W), or grass allergen peptides at 12 nmol at 2-week intervals for a total of 8 doses (8x12Q2W) or placebo and treated before the grass pollen season. The primary efficacy end point was change from baseline in total rhinoconjunctivitis symptom score across days 2 to 4 of a 4-day posttreatment challenge (PTC) in the EEU after the grass pollen season. Secondary efficacy end points and safety were also assessed. Two hundred eighty-two subjects were randomized. Significantly greater improvement (reduction of total rhinoconjunctivitis symptom score from baseline to PTC) occurred across days 2 to 4 with grass allergen peptide 8x6Q2W versus placebo (-5.4 vs -3.8, respectively; P = .0346). Greater improvement at PTC also occurred for grass allergen peptide 8x6Q2W versus placebo (P = .0403) in patients with more symptomatic ARC. No safety signals were detected. Grass allergen peptide 8x6Q2W significantly improved ARC symptoms after rye grass allergen challenge in an EEU with an acceptable safety profile. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Whole body vibration training improves vibration perception threshold in healthy young adults: A randomized clinical trial pilot study.

PubMed

Hernandez-Mocholi, M A; Dominguez-Muñoz, F J; Corzo, H; Silva, S Cs; Adsuar, J C; Gusi, N

2016-03-01

Loss of foot sensitivity is a relevant parameter to assess and prevent in several diseases. It is crucial to determine the vibro-tactile sensitivity threshold response to acute conditions to explore innovative monitor tools and interventions to prevent and treat this challenge. The aims were: 1) to analyze the acute effects of a single whole body vibration session (4min-18Hz-4mm) on vibro-tactile perception threshold in healthy young adults. 2) to analyze the 48 hours effects of 3 whole body vibration sessions on vibro-tactile perception threshold in healthy young adults. A randomized controlled clinical trial over 3 sessions of whole body vibration intervention or 3 sessions of placebo intervention. Twenty-eight healthy young adults were included: 11 experimental group and 12 placebo group. The experimental group performed 3 sessions of WBV while the placebo group performed 3 sessions of placebo intervention. The vibro-tactile threshold increased right after a single WBV session in comparison with placebo. Nevertheless, after 3 whole body vibration sessions and 48 hours, the threshold decreased to values lower than the initial. The acute response of the vibro-tactile threshold to one whole body vibration session increased, but the 48 hours short-term response of this threshold decreased in healthy young adults.

Effects of oxcarbazepine versus carbamazepine on tinnitus: A randomized double-blind placebo-controlled clinical trial.

PubMed

Gerami, Hooshang; Saberi, Alia; Nemati, Shadman; Kazemnejad, Ehsan; Aghajanpour, Mohammad

2012-01-01

It is still a challenge to find an effective treatment for tinnitus. The aim of this study was the evaluation of carbamazepine and oxcarbazepine effects on tinnitus. In a randomized double-blind clinical trial, 57 patients who were visited in a university hospital due to chronic non-pulsatile tinnitus, were randomized in three groups and treated with carbamazepine (300-600 mg/day), oxcarbazepine (450-900 mg/day) and placebo for 12 weeks. Visual analogue scale (VAS) and tinnitus severity index (TSI) were measured in all subjects in the beginning and at the end of the 8(th) and 12(th) weeks of the trial. Data was analyzed by repeated measure analysis, paired and independent t-test. Among 51 participants who completed the trial course (28 men, 23 women), carbamazepine, oxcarbazepine and placebo decreased tinnitus severity in 56.6%, 46.2% and 38.5% of patients according to VAS, and in 61.1%, 58.8% and 50% of patients according to TSI, respectively. The effects of carbamazepine and oxcarbazepine were better in the first 8 weeks of treatment. However, their effect on tinnitus did not show any statistical difference in comparison with placebo (P = 0.34, P = 0.28). Carbamazepine and oxcarbazepine are not more effective than placebo in decreasing tinnitus severity.

Harnessing adolescent values to motivate healthier eating

PubMed Central

Bryan, Christopher J.; Yeager, David S.; Hinojosa, Cintia P.; Chabot, Aimee; Bergen, Holly; Kawamura, Mari; Steubing, Fred

2016-01-01

What can be done to reduce unhealthy eating among adolescents? It was hypothesized that aligning healthy eating with important and widely shared adolescent values would produce the needed motivation. A double-blind, randomized, placebo-controlled experiment with eighth graders (total n = 536) evaluated the impact of a treatment that framed healthy eating as consistent with the adolescent values of autonomy from adult control and the pursuit of social justice. Healthy eating was suggested as a way to take a stand against manipulative and unfair practices of the food industry, such as engineering junk food to make it addictive and marketing it to young children. Compared with traditional health education materials or to a non–food-related control, this treatment led eighth graders to see healthy eating as more autonomy-assertive and social justice-oriented behavior and to forgo sugary snacks and drinks in favor of healthier options a day later in an unrelated context. Public health interventions for adolescents may be more effective when they harness the motivational power of that group’s existing strongly held values. PMID:27621440

Phase 2 Randomized Trial of the Safety and Efficacy of MHAA4549A, a Broadly Neutralizing Monoclonal Antibody, in a Human Influenza A Virus Challenge Model.

PubMed

McBride, Jacqueline M; Lim, Jeremy J; Burgess, Tracy; Deng, Rong; Derby, Michael A; Maia, Mauricio; Horn, Priscilla; Siddiqui, Omer; Sheinson, Daniel; Chen-Harris, Haiyin; Newton, Elizabeth M; Fillos, Dimitri; Nazzal, Denise; Rosenberger, Carrie M; Ohlson, Maikke B; Lambkin-Williams, Rob; Fathi, Hosnieh; Harris, Jeffrey M; Tavel, Jorge A

2017-11-01

MHAA4549A, a human monoclonal antibody targeting the hemagglutinin stalk region of influenza A virus (IAV), is being developed as a therapeutic for patients hospitalized with severe IAV infection. The safety and efficacy of MHAA4549A were assessed in a randomized, double-blind, placebo-controlled, dose-ranging study in a human IAV challenge model. One hundred healthy volunteers were inoculated with A/Wisconsin/67/2005 (H3N2) IAV and, 24 to 36 h later, administered a single intravenous dose of either placebo, MHAA4549A (400, 1,200, or 3,600 mg), or a standard oral dose of oseltamivir. Subjects were assessed for safety, pharmacokinetics (PK), and immunogenicity. The intent-to-treat-infected (ITTI) population was assessed for changes in viral load, influenza symptoms, and inflammatory biomarkers. MHAA4549A was well tolerated in all IAV challenge subjects. The 3,600-mg dose of MHAA4549A significantly reduced the viral burden relative to that of the placebo as determined by the area under the curve (AUC) of nasopharyngeal virus infection, quantified using quantitative PCR (98%) and 50% tissue culture infective dose (TCID 50 ) (100%) assays. Peak viral load, duration of viral shedding, influenza symptom scores, mucus weight, and inflammatory biomarkers were also reduced. Serum PK was linear with a half-life of ∼23 days. No MHAA4549A-treated subjects developed anti-drug antibodies. In conclusion, MHAA4549A was well tolerated and demonstrated statistically significant and substantial antiviral activity in an IAV challenge model. (This study has been registered at ClinicalTrials.gov under identifier NCT01980966.). Copyright © 2017 American Society for Microbiology.

Sex Differences in Depressive and Socioemotional Responses to an Inflammatory Challenge: Implications for Sex Differences in Depression

PubMed Central

Moieni, Mona; Irwin, Michael R; Jevtic, Ivana; Olmstead, Richard; Breen, Elizabeth C; Eisenberger, Naomi I

2015-01-01

Substantial evidence demonstrates that inflammatory processes may underlie depression for a subset of patients, including work showing that healthy subjects exposed to an inflammatory challenge show increases in depressed mood and feelings of social disconnection. However, despite the fact that depression is two times as likely to occur in females than males, the vast majority of this work has been carried out in males. Thus, the objective of this study was to determine whether females (vs males) would show greater increases in proinflammatory cytokines, depressed mood, and social disconnection in response to an inflammatory challenge. One hundred and fifteen healthy participants (69 female) completed this double-blind, placebo-controlled, randomized clinical trial in which participants were randomly assigned to receive either a single infusion of low-dose endotoxin (derived from Escherichia coli; 0.8 ng/kg of body weight) or placebo (same volume of 0.9% saline). Interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), depressed mood, and feelings of social disconnection were assessed hourly. Results showed that endotoxin (vs placebo) led to increases in proinflammatory cytokines (TNF-α, IL-6), depressed mood, and feelings of social disconnection. Females exposed to endotoxin showed greater increases in depressed mood and feelings of social disconnection. Furthermore, increases in TNF-α and IL-6 were correlated with increases in social disconnection for females but not for males. These sex differences in the relationships between inflammatory and socioemotional responses to an inflammatory challenge may be particularly important for understanding why females are two times as likely as males to develop depressive disorders. PMID:25598426

Anticholinergic versus botulinum toxin A comparison trial for the treatment of bothersome urge urinary incontinence: ABC trial.

PubMed

Visco, Anthony G; Brubaker, Linda; Richter, Holly E; Nygaard, Ingrid; Paraiso, Marie Fidela; Menefee, Shawn A; Schaffer, Joseph; Wei, John; Chai, Toby; Janz, Nancy; Spino, Cathie; Meikle, Susan

2012-01-01

This trial compares the change in urgency urinary incontinence episodes over 6 months, tolerability and cost effectiveness between women receiving daily anticholinergic therapy plus a single intra-detrusor injection of saline versus a single intra-detrusor injection of 100 U of botulinum toxin A plus daily oral placebo tablets. We present the rationale and design of a randomized-controlled trial, Anticholinergic versus Botulinum Toxin, Comparison Trial for the Treatment of Bothersome Urge Urinary Incontinence: ABC trial, conducted by the NICHD-funded Pelvic Floor Disorders Network. We discuss the innovative nature of this trial and the challenges related to choice of patient population, maintaining masking, cost effectiveness, ethical considerations, measuring adherence, and placebo development and testing. Enrollment began in April, 2010. 242 participants will be randomized and primary outcome data analysis is anticipated to begin in mid 2012. Several challenges in the trial design are discussed. Randomization to placebo intra-detrusor injections may limit recruitment, potentially impacting generalizability. Other challenges included the heavy marketing of drugs for overactive bladder which could impact recruitment of drug-naïve women. In addition, anticholinergic medications often cause dry mouth, making masking difficult. Finally, adverse reporting of transient urinary retention is challenging as there is no standardized definition; yet this is the most common adverse event following intra-detrusor botulinum toxin injection. The ABC trial will help women with urgency urinary incontinence balance efficacy, side effects and cost of anticholinergic medication versus botulinum toxin intra-detrusor injection. The results have the potential to fundamentally change the therapeutic approach to this condition. Copyright © 2011 Elsevier Inc. All rights reserved.

Acute Cocoa Supplementation Increases Postprandial HDL Cholesterol and Insulin in Obese Adults with Type 2 Diabetes after Consumption of a High-Fat Breakfast.

PubMed

Basu, Arpita; Betts, Nancy M; Leyva, Misti J; Fu, Dongxu; Aston, Christopher E; Lyons, Timothy J

2015-10-01

Dietary cocoa is an important source of flavonoids and is associated with favorable cardiovascular disease effects, such as improvements in vascular function and lipid profiles, in nondiabetic adults. Type 2 diabetes (T2D) is associated with adverse effects on postprandial serum glucose, lipids, inflammation, and vascular function. We examined the hypothesis that cocoa reduces metabolic stress in obese T2D adults after a high-fat fast-food-style meal. Adults with T2D [n = 18; age (mean ± SE): 56 ± 3 y; BMI (in kg/m(2)): 35.3 ± 2.0; 14 women; 4 men] were randomly assigned to receive cocoa beverage (960 mg total polyphenols; 480 mg flavanols) or flavanol-free placebo (110 mg total polyphenols; <0.1 mg flavanols) with a high-fat fast-food-style breakfast [766 kcal, 50 g fat (59% energy)] in a crossover trial. After an overnight fast (10-12 h), participants consumed the breakfast with cocoa or placebo, and blood sample collection [glucose, insulin, lipids, and high-sensitivity C-reactive protein (hsCRP)] and vascular measurements were conducted at 0.5, 1, 2, 4, and 6 h postprandially on each study day. Insulin resistance was evaluated by homeostasis model assessment. Over the 6-h study, and specifically at 1 and 4 h, cocoa increased HDL cholesterol vs. placebo (overall Δ: 1.5 ± 0.8 mg/dL; P ≤ 0.01) but had no effect on total and LDL cholesterol, triglycerides, glucose, and hsCRP. Cocoa increased serum insulin concentrations overall (Δ: 5.2 ± 3.2 mU/L; P < 0.05) and specifically at 4 h but had no overall effects on insulin resistance (except at 4 h, P < 0.05), systolic or diastolic blood pressure, or small artery elasticity. However, large artery elasticity was overall lower after cocoa vs. placebo (Δ: -1.6 ± 0.7 mL/mm Hg; P < 0.05), with the difference significant only at 2 h. Acute cocoa supplementation showed no clear overall benefit in T2D patients after a high-fat fast-food-style meal challenge. Although HDL cholesterol and insulin remained higher throughout the 6-h postprandial period, an overall decrease in large artery elasticity was found after cocoa consumption. This trial was registered at clinicaltrials.gov as NCT01886989. © 2015 American Society for Nutrition.

Probiotic-enriched foods and dietary supplement containing SYNBIO positively affects bowel habits in healthy adults: an assessment using standard statistical analysis and Support Vector Machines.

PubMed

Silvi, Stefania; Verdenelli, M Cristina; Cecchini, Cinzia; Coman, M Magdalena; Bernabei, M Simonetta; Rosati, Jessica; De Leone, Renato; Orpianesi, Carla; Cresci, Alberto

2014-12-01

A randomised, double-blind, placebo-controlled, parallel group study assessed in healthy adults how daily consumption of the probiotic combination SYNBIO®, administered in probiotic-enriched foods or in a dietary supplement, affected bowel habits. Primary and secondary outcomes gave the overall assessment of bowel well-being, while a Psychological General Well-Being Index compiled by participants estimated the health-related quality of life as well as the gastrointestinal tolerance determined with the Gastrointestinal Symptom Rating Scale. Support Vector Machine models for classification problems were used to validate the total outcomes on bowel well-being. SYNBIO® consumption improved bowel habits of volunteers consuming the probiotic foods or capsules, while the same effects were not registered in the control groups. The recovery of probiotic bacteria from the faeces of a cohort of 100 subjects for each supplemented group showed the persistence of strains in the gastrointestinal tract.

Effects of Dietary Supplementation of Astaxanthin and Sesamin on Daily Fatigue: A Randomized, Double-Blind, Placebo-Controlled, Two-Way Crossover Study

PubMed Central

Imai, Ayano; Oda, Yuriko; Seki, Shinobu; Nakagawa, Kiyotaka; Miyazawa, Teruo; Ueda, Fumitaka

2018-01-01

Severe fatigue can negatively affect quality of life, and oxidative stress may play a role in its mechanism. The aim of this study was to evaluate the effect of dietary supplementation of astaxanthin and sesamin (AS), strong food-derived antioxidants, on fatigue. Twenty-four healthy volunteers were supplemented with AS and placebo, each for four weeks. After each supplementation period, participants underwent tasks inducing mental and physical fatigue (visual display terminal task and ergometer task, respectively). Subjective fatigue was evaluated using a visual analogue scale during and after the mental and physical tasks, and daily subjective fatigue was evaluated by the Chalder fatigue questionnaire. Secondary outcomes included other subjective feelings, work efficiency, autonomic nerve activity, levels of an oxidative stress marker (plasma phosphatidylcholine hydroperoxide (PCOOH)) and safety. AS supplementation was associated with significantly improved recovery from mental fatigue compared with placebo. Increased PCOOH levels during mental and physical tasks were attenuated by AS supplementation. No differences between AS and placebo were detected in secondary outcomes, and no adverse effects of AS supplementation were observed. In conclusion, AS supplementation may be a candidate to promote recovery from mental fatigue which is experienced by many healthy people. PMID:29495607

Probiotic With or Without Fiber Controls Body Fat Mass, Associated With Serum Zonulin, in Overweight and Obese Adults-Randomized Controlled Trial.

PubMed

Stenman, Lotta K; Lehtinen, Markus J; Meland, Nils; Christensen, Jeffrey E; Yeung, Nicolas; Saarinen, Markku T; Courtney, Michael; Burcelin, Rémy; Lähdeaho, Marja-Leena; Linros, Jüri; Apter, Dan; Scheinin, Mika; Kloster Smerud, Hilde; Rissanen, Aila; Lahtinen, Sampo

2016-11-01

The gut microbiota is interlinked with obesity, but direct evidence of effects of its modulation on body fat mass is still scarce. We investigated the possible effects of Bifidobacterium animalisssp. lactis 420 (B420) and the dietary fiber Litesse® Ultra polydextrose (LU) on body fat mass and other obesity-related parameters. 225 healthy volunteers (healthy, BMI 28-34.9) were randomized into four groups (1:1:1:1), using a computer-generated sequence, for 6months of double-blind, parallel treatment: 1) Placebo, microcrystalline cellulose, 12g/d; 2) LU, 12g/d; 3) B420, 10 10 CFU/d in microcrystalline cellulose, 12g/d; 4) LU+B420, 12g+10 10 CFU/d. Body composition was monitored with dual-energy X-ray absorptiometry, and the primary outcome was relative change in body fat mass, comparing treatment groups to Placebo. Other outcomes included anthropometric measurements, food intake and blood and fecal biomarkers. The study was registered in Clinicaltrials.gov (NCT01978691). There were marked differences in the results of the Intention-To-Treat (ITT; n=209) and Per Protocol (PP; n=134) study populations. The PP analysis included only those participants who completed the intervention with >80% product compliance and no antibiotic use. In addition, three participants were excluded from DXA analyses for PP due to a long delay between the end of intervention and the last DXA measurement. There were no significant differences between groups in body fat mass in the ITT population. However, LU+B420 and B420 seemed to improve weight management in the PP population. For relative change in body fat mass, LU+B420 showed a-4.5% (-1.4kg, P=0.02, N=37) difference to the Placebo group, whereas LU (+0.3%, P=1.00, N=35) and B420 (-3.0%, P=0.28, N=24) alone had no effect (overall ANOVA P=0.095, Placebo N=35). A post-hoc factorial analysis was significant for B420 (-4.0%, P=0.002 vs. Placebo). Changes in fat mass were most pronounced in the abdominal region, and were reflected by similar changes in waist circumference. B420 and LU+B420 also significantly reduced energy intake compared to Placebo. Changes in blood zonulin levels and hsCRP were associated with corresponding changes in trunk fat mass in the LU+B420 group and in the overall population. There were no differences between groups in the incidence of adverse events. This clinical trial demonstrates that a probiotic product with or without dietary fiber controls body fat mass. B420 and LU+B420 also reduced waist circumference and food intake, whereas LU alone had no effect on the measured outcomes. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

The effect of probiotics as a treatment for constipation in elderly people: A systematic review.

PubMed

Martínez-Martínez, Maria Isabel; Calabuig-Tolsá, Raquel; Cauli, Omar

2017-07-01

Treating constipation in elderly people remains a challenge; the administration of probiotics may be a valid therapy for this problem as an alternative to traditional drug-based treatments. The objective of this systematic review was to evaluate the efficiency of probiotics in treating constipation in elderly people. Articles related to this topic and published, without any time limitations, in the Medline, Embase, Scopus, Lilacs, or Cochrane databases were systematically reviewed according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. The primary search terms were 'constipation' and 'probiotics'. The main inclusion criteria were: 1) the article was original and the whole text was published in English or Spanish and 2) included the primary search terms in the title, summary, or body text; 3) the studies had to have included 60 or more participants defined as 'elderly' and 4) have specifically evaluated the effect of the administration of probiotics. Of the 475 articles consulted, 9 met the inclusion criteria. Among the selected studies, there were four randomised and placebo-controlled trials and the remaining five reports were observational. Overall, our analysis of the randomised and placebo-controlled trials suggests that administration of probiotics significantly improved constipation in elderly individuals by 10-40% compared to placebo controls in which no probiotic was administered. The strain of bacteria most commonly tested was Bifidobacterium longum. However, caution is needed when interpreting these reports because of the heterogeneity of the original study designs, populations, and the risk of bias. Therefore, further placebo-controlled trials are necessary to determine the most efficient strains, doses, and the optimal treatment duration. Copyright © 2017 Elsevier B.V. All rights reserved.

A randomized controlled trial of green tea catechins in protection against ultraviolet radiation-induced cutaneous inflammation.

PubMed

Farrar, Mark D; Nicolaou, Anna; Clarke, Kayleigh A; Mason, Sarah; Massey, Karen A; Dew, Tristan P; Watson, Rachel E B; Williamson, Gary; Rhodes, Lesley E

2015-09-01

Safe systemic protection from the health hazards of ultraviolet radiation (UVR) in sunlight is desirable. Green tea is consumed globally and is reported to have anti-inflammatory properties, which may be mediated through the impact on cyclooxygenase and lipoxygenase pathways. Recent data suggest that green tea catechins (GTCs) reduce acute UVR effects, but human trials examining their photoprotective potential are scarce. We performed a double-blind, randomized, placebo-controlled trial to examine whether GTCs protect against clinical, histologic, and biochemical indicators of UVR-induced inflammation. Healthy adults (aged 18-65 y, phototypes I-II) were randomly allocated to 1350 mg encapsulated green tea extract (540 mg GTC) with 50 mg vitamin C or placebo twice daily for 3 mo. Impact on skin erythema, dermal leukocytic infiltration, and concentrations of proinflammatory eicosanoids was assessed after solar-simulated UVR challenge, and subject compliance was determined through assay of urinary GTC metabolite epigallocatechin glucuronide. Volunteers were assigned to the active (n = 25) or the placebo (n = 25) group. After supplementation, median (IQR) sunburn threshold (minimal erythema dose) was 28 (20-28) and 20 (20-28) mJ/cm(2) in the active and placebo groups, respectively (nonsignificant), with no difference in AUC analysis for measured erythema index after a geometric series of 10 UVR doses. Skin immunohistochemistry showed increased neutrophil and CD3(+) T-lymphocyte numbers post-UVR in both groups (P < 0.01) with no statistically significant differences between groups after supplementation. Cyclooxygenase and lipoxygenase metabolites prostaglandin E2 (vasodilator) and 12-hydroxyeicosatetraenoicacid (chemoattractant), respectively, increased after UVR (P < 0.05), with no differences between supplementation groups. Oral GTC (1080 mg/d) with vitamin C over 3 mo did not significantly reduce skin erythema, leukocyte infiltration, or eicosanoid response to UVR inflammatory challenge. This trial was registered at clinicaltrials.gov as NCT01032031.

A randomized controlled trial of green tea catechins in protection against ultraviolet radiation–induced cutaneous inflammation12

PubMed Central

Farrar, Mark D; Nicolaou, Anna; Clarke, Kayleigh A; Mason, Sarah; Massey, Karen A; Dew, Tristan P; Watson, Rachel EB; Williamson, Gary; Rhodes, Lesley E

2015-01-01

Background: Safe systemic protection from the health hazards of ultraviolet radiation (UVR) in sunlight is desirable. Green tea is consumed globally and is reported to have anti-inflammatory properties, which may be mediated through the impact on cyclooxygenase and lipoxygenase pathways. Recent data suggest that green tea catechins (GTCs) reduce acute UVR effects, but human trials examining their photoprotective potential are scarce. Objective: We performed a double-blind, randomized, placebo-controlled trial to examine whether GTCs protect against clinical, histologic, and biochemical indicators of UVR-induced inflammation. Design: Healthy adults (aged 18–65 y, phototypes I–II) were randomly allocated to 1350 mg encapsulated green tea extract (540 mg GTC) with 50 mg vitamin C or placebo twice daily for 3 mo. Impact on skin erythema, dermal leukocytic infiltration, and concentrations of proinflammatory eicosanoids was assessed after solar-simulated UVR challenge, and subject compliance was determined through assay of urinary GTC metabolite epigallocatechin glucuronide. Results: Volunteers were assigned to the active (n = 25) or the placebo (n = 25) group. After supplementation, median (IQR) sunburn threshold (minimal erythema dose) was 28 (20–28) and 20 (20–28) mJ/cm2 in the active and placebo groups, respectively (nonsignificant), with no difference in AUC analysis for measured erythema index after a geometric series of 10 UVR doses. Skin immunohistochemistry showed increased neutrophil and CD3+ T-lymphocyte numbers post-UVR in both groups (P < 0.01) with no statistically significant differences between groups after supplementation. Cyclooxygenase and lipoxygenase metabolites prostaglandin E2 (vasodilator) and 12-hydroxyeicosatetraenoicacid (chemoattractant), respectively, increased after UVR (P < 0.05), with no differences between supplementation groups. Conclusion: Oral GTC (1080 mg/d) with vitamin C over 3 mo did not significantly reduce skin erythema, leukocyte infiltration, or eicosanoid response to UVR inflammatory challenge. This trial was registered at clinicaltrials.gov as NCT01032031. PMID:26178731

Is there any association between secretory IgA and lactoferrin concentration in mature human milk and food allergy in breastfed children.

PubMed

Hogendorf, Anna; Stańczyk-Przyłuska, Anna; Sieniwicz-Luzeńczyk, Katarzyna; Wiszniewska, Magdalena; Arendarczyk, Jerzy; Banasik, Małgorzata; Fendler, Wojciech; Kowalski, Marek; Zeman, Krzysztof

2013-01-01

Breastfeeding is recommended as a protective method against the development of allergy. However, some studies have reported an increased risk of allergies development in breastfed infants of atopic mothers, which implies that atopic mothers may have an altered composition of breast milk. The aim of the study was to determine the concentration of secretory immunoglobulin A (S-IgA) and lactoferrin in human mature milk and to evaluate the association between the levels of these proteins in breast milk with food allergy in children, depending on the allergy status of the breastfeeding mother. Medical data was collected from birth to 24 months of age from 84 mother-child pairs participating in an EU-funded project "EuroPrevall - The prevalence, cost and basis of food allergy across Europe". The diagnosis of food allergy in children was based on the positive result of a double-blind placebo-controlled food challenge (DBPCFC). S-IgA and lactoferrin levels were measured in the whey of mature breast milk with commercial enzyme-linked immunosorbent assay (ELISA) kits. Statistical analysis (the U Mann-Whitney and Kruskal-Wallis tests as well as the Spearman's rank correlation coefficient) was performed using STATISTICA 8.0 PL (Statsoft, Tulsa, USA). Ten out of eighty four participating children had positive skin prick tests (SPT) and/or sIgE to food antigens and in 7 (8.4%) DBPCFC confirmed food allergy. the median concentration of S-IgA was 476,83 μg/ml (range 6.51-1359.61 μg/ml). the median concentration of Lf was 15.68 μg/ml (range 11.68-36.43 μg/ml). The concentrations of S-IgA and Lf showed a moderate, negative, correlation R=-0.28; p=0.05. Mature breast milk of mothers of children with food allergy and of healthy children showed similar concentrations of both proteins. The level of S-IgA in the mature milk of mothers with atopic allergy was significantly lower, compared to non-atopic mothers. More studies are needed to reveal the mystery of the lack of protective effect of breastfeeding on allergy development in children.

Non-invasive Prefrontal/Frontal Brain Stimulation Is Not Effective in Modulating Food Reappraisal Abilities or Calorie Consumption in Obese Females

PubMed Central

Grundeis, Felicitas; Brand, Cristin; Kumar, Saurabh; Rullmann, Michael; Mehnert, Jan; Pleger, Burkhard

2017-01-01

Background/Objectives: Previous studies suggest that non-invasive transcranial direct current stimulation (tDCS) applied to the prefrontal cortex modulates food choices and calorie intake in obese humans. Participants/Methods: In the present fully randomized, placebo-controlled, within-subject and double-blinded study, we applied single sessions of anodal, cathodal, and sham tDCS to the left dorsolateral prefrontal cortex (DLPFC) and contralateral frontal operculum in 25 hungry obese women and investigated possible influences on food reappraisal abilities as well as calorie intake. We hypothesized that tDCS, (i) improves the ability to regulate the desire for visually presented foods and, (ii) reduces their consumption. Results: We could not confirm an effect of anodal or cathodal tDCS, neither on the ability to modulate the desire for visually presented foods, nor on calorie consumption. Conclusions: The present findings do not support the notion of prefrontal/frontal tDCS as a promising treatment option for obesity. PMID:28676735

Link Between Increased Satiety Gut Hormones and Reduced Food Reward After Gastric Bypass Surgery for Obesity.

PubMed

Goldstone, Anthony P; Miras, Alexander D; Scholtz, Samantha; Jackson, Sabrina; Neff, Karl J; Pénicaud, Luc; Geoghegan, Justin; Chhina, Navpreet; Durighel, Giuliana; Bell, Jimmy D; Meillon, Sophie; le Roux, Carel W

2016-02-01

Roux-en-Y gastric bypass (RYGB) surgery is an effective long-term intervention for weight loss maintenance, reducing appetite, and also food reward, via unclear mechanisms. To investigate the role of elevated satiety gut hormones after RYGB, we examined food hedonic-reward responses after their acute post-prandial suppression. These were randomized, placebo-controlled, double-blind, crossover experimental medicine studies. Two groups, more than 5 months after RYGB for obesity (n = 7-11), compared with nonobese controls (n = 10), or patients after gastric banding (BAND) surgery (n = 9) participated in the studies. Studies were performed after acute administration of the somatostatin analog octreotide or saline. In one study, patients after RYGB, and nonobese controls, performed a behavioral progressive ratio task for chocolate sweets. In another study, patients after RYGB, and controls after BAND surgery, performed a functional magnetic resonance imaging food picture evaluation task. Octreotide increased both appetitive food reward (breakpoint) in the progressive ratio task (n = 9), and food appeal (n = 9) and reward system blood oxygen level-dependent signal (n = 7) in the functional magnetic resonance imaging task, in the RYGB group, but not in the control groups. Octreotide suppressed postprandial plasma peptide YY, glucagon-like peptide-1, and fibroblast growth factor-19 after RYGB. The reduction in plasma peptide YY with octreotide positively correlated with the increase in brain reward system blood oxygen level-dependent signal in RYGB/BAND subjects, with a similar trend for glucagon-like peptide-1. Enhanced satiety gut hormone responses after RYGB may be a causative mechanism by which anatomical alterations of the gut in obesity surgery modify behavioral and brain reward responses to food.

Guar sprinkled on food: effect on glycaemic control, plasma lipids and gut hormones in non-insulin dependent diabetic patients.

PubMed

Fuessl, H S; Williams, G; Adrian, T E; Bloom, S R

1987-01-01

The effects of guar granules sprinkled over food on carbohydrate and lipid metabolism were studied in a double-blind cross-over trial in 18 patients with non-insulin-dependent diabetes mellitus (mean +/- SEM age 61.3 +/- 2.5 years). Five-gram guar granules (Guarem, Rybar Laboratories, Amersham, Bucks) were sprinkled over food at each main meal for 4 weeks, and during a 4-week placebo period (separated by a 2-week 'wash-out' period), 5 g wheat bran was taken in the same way. Diabetic treatment was not changed during the study. Mean fasting plasma glucose (FPG) concentration and glycosylated haemoglobin (HbA1) concentration after treatment were significantly lower than after the placebo period (FPG 8.29 +/- 0.47 vs 8.78 +/- 0.53 mmol/l, p less than 0.05; HbA1: 8.70 +/- 0.39 vs 9.09 +/- 0.39%, p less than 0.05). There was a 50% reduction in the incremental area under the postprandial glycaemic curve when guar was eaten with a standardized test meal. Total plasma cholesterol decreased from 5.79 +/- 0.29 to 5.19 +/- 0.22 mmol/l (p less than 0.05) after the guar treatment period. Guar ingestion reduced postprandial insulin and enteroglucagon responses, the latter significantly so, but had no apparent effect on gastric inhibitory polypeptide, pancreatic glucagon, gastrin, and pancreatic polypeptide.

Increased repetitive behaviours and prolactin responsivity to oral m-chlorophenylpiperazine in adults with autism spectrum disorders.

PubMed

Novotny, Sherie; Hollander, Eric; Phillips, Ann; Allen, Andrea; Wasserman, Stacey; Iyengar, Rupa

2004-09-01

Autism is a neurodevelopmental disorder characterized by dysfunction in three primary behavioural domains: repetitive behaviours, social deficits, and language abnormalities. There is evidence that abnormalities exist in the serotonin (5-HT) system in autism spectrum patients. Furthermore, 5-HT is known to play a role in repetitive and social behaviours. This study examined the effect of m-chlorophenylpiperazine (m-CPP) on repetitive behaviours and prolactin response in 11 adults with autism or Aspergers disorder and 8 age- and gender-matched healthy controls via randomized double-blind, m-CPP and placebo challenges. The primary outcome measure was an instrument rating six repetitive behaviours: need to know, repeating, ordering, need to tell/ask, self-injury, and touching. Patients with autism spectrum disorders showed a significant increase in repetitive behaviours at end-point following oral m-CPP in comparison to placebo. Additionally subjects with autism spectrum disorders showed a significantly increased prolactin response to m-CPP compared to normal controls, with neither group responding to placebo. This study provides further evidence for altered 5-HT sensitivity in individuals with autism spectrum disorders, as well as a possible relationship between repetitive behaviours in autism spectrum disorders and abnormalities in the 5-HT system.

Safety and efficacy of ranirestat in patients with mild-to-moderate diabetic sensorimotor polyneuropathy.

PubMed

Polydefkis, Michael; Arezzo, Joseph; Nash, Marshall; Bril, Vera; Shaibani, Aziz; Gordon, Robert J; Bradshaw, Kate L; Junor, Roderick W J

2015-12-01

We examined the efficacy and safety of ranirestat in patients with diabetic sensorimotor polyneuropathy (DSPN). Patients (18-75 years) with stable type 1/2 diabetes mellitus and DSPN were eligible for this global, double-blind, phase II/III study (ClinicalTrials.gov NCT00927914). Patients (n = 800) were randomized 1 : 1 : 1 to placebo, ranirestat 40 mg/day or 80 mg/day (265 : 264 : 271). Change in peroneal motor nerve conduction velocity (PMNCV) from baseline to 24 months was the primary endpoint with a goal improvement vs. placebo ≥1.2 m/s. Other endpoints included symptoms, quality-of-life, and safety. Six hundred thirty-three patients completed the study. The PMNCV difference from placebo was significant at 6, 12, and 18 months in both ranirestat groups, but <1.2 m/s. The mean improvement from baseline at 24 months was +0.49, +0.95, and +0.90 m/s for placebo, ranirestat 40 mg and 80 mg, respectively (NS). The treatment difference vs. placebo reached significance when ranirestat groups were combined in a post hoc analysis (+0.44 m/s; p = 0.0237). There was no effect of ranirestat on safety assessments, secondary or exploratory endpoints vs. placebo. Ranirestat was well tolerated and improved PMNCV, but did not achieve any efficacy endpoints. The absence of PMNCV worsening in the placebo group underscores the challenges of DSPN studies in patients with well-controlled diabetes. © 2015 Peripheral Nerve Society.

Effects of acarbose treatment on markers of insulin sensitivity and systemic inflammation.

PubMed

Rudovich, Natalia N; Weickert, Martin O; Pivovarova, Olga; Bernigau, Wolfgang; Pfeiffer, Andreas F H

2011-06-01

This study assessed the effect of postprandial glucose reduction by acarbose on insulin sensitivity and biomarkers of systemic inflammation. This was a single-center, double-blind, randomized, placebo-controlled, crossover study <40 weeks in duration, involving 66 subjects with varying degrees of glucose tolerance. Eligible patients completed a 3-week run-in period and were randomized to receive either 100 mg of acarbose three times daily followed by placebo, or vice versa, lasting 12 weeks each with a 12-week washout between interventions. Liquid meal challenges and hyperinsulinemic-euglycemic glucose clamp were performed at weeks 0, 12, 24, and 36. Fasting proinsulin levels and proinsulin-to-adiponectin ratios but not fasting adiponectin levels were significantly lower during acarbose versus placebo treatment. Clamp-derived insulin sensitivity index and body weight were unchanged by the intervention. Levels of fasting insulin, fasting glucose, monocyte chemoattractant protein-1, interleukin-6, and interleukin-1β were comparable between treatments. In the liquid meal challenge tests, postprandial glucose and insulin responses were significantly lower during acarbose versus placebo treatment. The effects of acarbose on the reduction of fasting proinsulin was most pronounced in subjects with impaired fasting glucose/impaired glucose tolerance (n = 24). Reduction of the glycemic load by acarbose decreased fasting levels of proinsulin but had no effect on adiponectin and whole-body insulin sensitivity as well as biomarkers reflecting inflammation. The preventive effects of acarbose on type 2 diabetes mellitus and cardiovascular risk need further investigation and cannot be explained by changes of insulin resistance and inflammatory biomarkers.

Hyperandrogenism sensitizes mononuclear cells to promote glucose-induced inflammation in lean reproductive-age women

PubMed Central

Nair, K. Sreekumaran; Daniels, Janice K.; Basal, Eati; Schimke, Jill M.

2012-01-01

Hyperandrogenism and chronic low-grade inflammation are related in polycystic ovary syndrome (PCOS), but it is unknown whether hyperandrogenemia can activate inflammation. We determined the effect of oral androgen administration on fasting and glucose-stimulated nuclear factor-κB (NF-κB) activation and expression and related markers of inflammation in mononuclear cells (MNC) of lean reproductive-age women. Sixteen lean, ovulatory reproductive-age women were treated with 130 mg of DHEA or placebo (n = 8 each) for 5 days in a randomized, controlled, double-blind fashion. Nuclear activation of NF-κB, p65 and p105 NF-κB subunit RNA, TNFα and IL-1β mRNA, and NF-κB p65 and inhibitory-κB (IκB) protein were quantified from MNC obtained while fasting and 2 h after glucose ingestion, before and after DHEA or placebo administration. Before treatment, subjects receiving DHEA or placebo exhibited no differences in androgens or any inflammatory markers while fasting and after glucose ingestion. Compared with placebo, DHEA administration raised levels of testosterone, androstenedione, and DHEA-S, increased the percent change in fasting and glucose-challenged activated NF-κB, p65, p105, TNFα, and IL-1β RNA and p65 protein, and decreased the percent change in fasting and glucose-challenged IκB protein. We conclude that elevation of circulating androgens to the range observed in PCOS upregulates the NF-κB inflammation pathway in lean reproductive-age women. Thus, hyperandrogenemia activates and sensitizes MNC to glucose in this population. PMID:22045316

Hyperandrogenism sensitizes mononuclear cells to promote glucose-induced inflammation in lean reproductive-age women.

PubMed

González, Frank; Nair, K Sreekumaran; Daniels, Janice K; Basal, Eati; Schimke, Jill M

2012-02-01

Hyperandrogenism and chronic low-grade inflammation are related in polycystic ovary syndrome (PCOS), but it is unknown whether hyperandrogenemia can activate inflammation. We determined the effect of oral androgen administration on fasting and glucose-stimulated nuclear factor-κB (NF-κB) activation and expression and related markers of inflammation in mononuclear cells (MNC) of lean reproductive-age women. Sixteen lean, ovulatory reproductive-age women were treated with 130 mg of DHEA or placebo (n = 8 each) for 5 days in a randomized, controlled, double-blind fashion. Nuclear activation of NF-κB, p65 and p105 NF-κB subunit RNA, TNFα and IL-1β mRNA, and NF-κB p65 and inhibitory-κB (IκB) protein were quantified from MNC obtained while fasting and 2 h after glucose ingestion, before and after DHEA or placebo administration. Before treatment, subjects receiving DHEA or placebo exhibited no differences in androgens or any inflammatory markers while fasting and after glucose ingestion. Compared with placebo, DHEA administration raised levels of testosterone, androstenedione, and DHEA-S, increased the percent change in fasting and glucose-challenged activated NF-κB, p65, p105, TNFα, and IL-1β RNA and p65 protein, and decreased the percent change in fasting and glucose-challenged IκB protein. We conclude that elevation of circulating androgens to the range observed in PCOS upregulates the NF-κB inflammation pathway in lean reproductive-age women. Thus, hyperandrogenemia activates and sensitizes MNC to glucose in this population.

Treatment of moderate to severe premenstrual syndrome with Vitex agnus castus (BNO 1095) in Chinese women.

PubMed

Ma, Linlin; Lin, Shouqing; Chen, Rong; Wang, Xiuli

2010-08-01

To assess efficacy of the extract of Vitex agnus castus (VAC, BNO 1095) in the treatment of Chinese women suffering from moderate to severe premenstrual syndrome (PMS). It was a prospective randomised double-blind placebo-controlled study conducted in Chinese women. Eligible patients were randomly assigned into VAC or placebo group. Symptoms were documented with a daily rating scale with four symptom factors (negative affect, water retention, food cravings and pain). Sixty-seven patients were enrolled and randomly assigned to receive one tablet of VAC or placebo once a day. The premenstrual syndrome diary (PMSD) sum score decreased from 29.38 +/- 7.63 score points at baseline to 4.28 +/- 5.76 at the 3rd cycle in the treatment group, while it decreased from 28.76 +/- 8.23 to 11.79 +/- 11.78 in the placebo group. All the four symptom factor scores were significantly reduced by the 3rd treatment cycle. There was significant difference in PMSD sum score, score of negative affect and water retention between two groups at cycle 3 (P < 0.05). PMSD sum scores decreased 60% was defined as efficacy, and the efficacy rate in treatment group was significantly higher than that in placebo group at the 3rd treatment cycle. Vitex agnus castus extract BNO 1095 shows effective in treating moderate to severe PMS in Chinese women, especially in symptoms of negative affect and water retention.

Short-term effects of a novel fat emulsion on appetite and food intake.

PubMed

Diepvens, Kristel; Steijns, Jan; Zuurendonk, Peter; Westerterp-Plantenga, Margriet S

2008-09-03

The objective of the study was to confirm the satiety/energy intake effect of a novel fat emulsion (Olibra) versus placebo in the short term. A randomized, double-blind, placebo-controlled, crossover design was used. 41 subjects participated in the study (n=21: junior-normal weight: age 23.7+/-2.8 years; BMI: 22.0+/-1.6 kg/m(2); n = 20: senior-overweight: age 43.6+/-4.9 years; BMI: 27.7+/-1.6 kg/m(2)). An energy intake and satiety test (with questionnaires) took place on 2 occasions, with placebo or test yoghurt as breakfast. In the junior-normal weight subjects, consumption of test yoghurt reduced hunger and desire to eat during the morning (area under curve, p<0.05) and increased the time elapsed between consumption of the yoghurt and the point at which hunger scores returned to baseline; 234+/-79 min in the test condition compared to 174+/-58 min in the placebo condition (p<0.05). No significant differences in appetite scores between the test and placebo yoghurt were seen for the senior-overweight subjects. No effect on energy intake was seen in the total group, in the junior-normal weight and senior-overweight subjects. In conclusion, the Olibra emulsion exerted a suppressive effect on the area under the curve of appetite ratings over 3 h in normal weight women aged 18 to 30 years. The Olibra emulsion did not affect subsequent energy intake in either group.

Effect of misoprostol on patients with aspirin-exacerbated respiratory disease undergoing aspirin challenge and desensitization.

PubMed

Walters, Kristen M; Simon, Ronald A; Woessner, Katharine M; Wineinger, Nathan E; White, Andrew A

2017-07-01

Prostaglandin E 2 (PGE 2 ) is an anti-inflammatory compound that inhibits 5-lipoxygenase activity. Diminished PGE 2 regulation in aspirin-exacerbated respiratory disease (AERD) leads to respiratory reactions on cyclooxygenase 1 inhibition. In vitro studies have found that exogenous PGE 2 stabilizes inflammatory mediator release. To examine whether misoprostol (oral prostaglandin E 1 analogue) use during aspirin challenge and desensitization might decrease the severity of aspirin-induced symptoms and make desensitization safer for patients with AERD. Forty-five patients undergoing aspirin challenge and/or desensitization were randomized to misoprostol (n = 30) or placebo (n = 15) and compared with a group of historical controls (n = 31). Misoprostol (200 μg) was administered at 30 minutes, 90 minutes, and 4 hours after the first dose of nasal ketorolac. Measured end points included change in forced expiratory volume in 1 second (FEV 1 ), peak nasal inspiratory flow rate (PNIF), number of treatments received for induced reactions, and adverse gastrointestinal effects. A difference in FEV 1 and PNIF reduction was detected between misoprostol and placebo (P = .03) and misoprostol and historical controls (P = .01), respectively, during nasal ketorolac challenge. No difference was detected among aspirin reactors. Among all reactors, no difference in magnitude was found for FEV 1 (P = .13) or PNIF (P = .07) reduction across all 3 groups. Total treatment requirement was similar (P = .14). Patients receiving misoprostol were more likely to report adverse gastrointestinal effects (P = .02). The addition of misoprostol to current aspirin challenge and/or desensitization protocols reveals no protective effect in reducing the intensity of nonsteroidal anti-inflammatory drug-induced symptoms and is not recommended based on the findings in this study. Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Expectancies and memory for an emotional film fragment: a placebo study.

PubMed

Van Oorsouw, Kim; Merckelbach, Harald

2007-01-01

This study investigated whether positive ("memory-enhancing") and negative ("memory-impairing") placebos may enhance and undermine, respectively, memory of a film fragment. After watching an emotional film fragment, participants were assigned to a "memory-enhancing" placebo group (n = 30), control group (n = 30), or "memory-impairing" placebo group (n = 30). Only participants who believed in the placebo effect were included in the analyses. In the positive placebo group, memory for the film fragment was better than that of participants who received negative placebos or control participants. Participants in the negative placebo group made more distortion errors than participants in the positive placebo or control group. Our findings show that people's expectancies about their memory may affect their memory performance. These results may have implications for both clinical practice and the legal domain.

Oxytocin administration suppresses hypothalamic activation in response to visual food cues.

PubMed

van der Klaauw, Agatha A; Ziauddeen, Hisham; Keogh, Julia M; Henning, Elana; Dachi, Sekesai; Fletcher, Paul C; Farooqi, I Sadaf

2017-06-27

The aim of this study was to use functional neuroimaging to investigate whether oxytocin modulates the neural response to visual food cues in brain regions involved in the control of food intake. Twenty-four normal weight volunteers received intranasal oxytocin (24 IU) or placebo in a double-blind, randomized crossover study. Measurements were made forty-five minutes after dosing. On two occasions, functional MRI (fMRI) scans were performed in the fasted state; the blood oxygen level-dependent (BOLD) response to images of high-calorie foods versus low-calorie foods was measured. Given its critical role in eating behaviour, the primary region of interest was the hypothalamus. Secondary analyses examined the parabrachial nuclei and other brain regions involved in food intake and food reward. Intranasal oxytocin administration suppressed hypothalamic activation to images of high-calorie compared to low-calorie food (P = 0.0125). There was also a trend towards suppression of activation in the parabrachial nucleus (P = 0.0683). No effects of intranasal oxytocin were seen in reward circuits or on ad libitum food intake. Further characterization of the effects of oxytocin on neural circuits in the hypothalamus is needed to establish the utility of targeting oxytocin signalling in obesity.

Insights from Preclinical Choice Models on Treating Drug Addiction.

PubMed

Banks, Matthew L; Negus, S Stevens

2017-02-01

Substance-use disorders are a global public health problem that arises from behavioral misallocation between drug use and more adaptive behaviors maintained by nondrug alternatives (e.g., food or money). Preclinical drug self-administration procedures that incorporate a concurrently available nondrug reinforcer (e.g., food) provide translationally relevant and distinct dependent measures of behavioral allocation (i.e., to assess the relative reinforcing efficacy of the drug) and behavioral rate (i.e., to assess motor competence). In particular, preclinical drug versus food 'choice' procedures have produced increasingly concordant results with both human laboratory drug self-administration studies and double-blind placebo-controlled clinical trials. Accordingly, here we provide a heuristic framework of substance-use disorders based on a behavioral-centric perspective and recent insights from these preclinical choice procedures. Copyright © 2016 Elsevier Ltd. All rights reserved.

A critical overview of homeopathy.

PubMed

Jonas, Wayne B; Kaptchuk, Ted J; Linde, Klaus

2003-03-04

Homeopathy is a 200-year-old therapeutic system that uses small doses of various substances to stimulate autoregulatory and self-healing processes. Homeopathy selects substances by matching a patient's symptoms with symptoms produced by these substances in healthy individuals. Medicines are prepared by serial dilution and shaking, which proponents claim imprints information into water. Although many conventional physicians find such notions implausible, homeopathy had a prominent place in 19th-century health care and has recently undergone a worldwide revival. In the United States, patients who seek homeopathic care are more affluent and younger and more often seek treatment for subjective symptoms than those who seek conventional care. Homeopathic remedies were allowed by the 1939 Pure Food and Drug Act and are available over the counter. Some data--both from randomized, controlled trials and laboratory research--show effects from homeopathic remedies that contradict the contemporary rational basis of medicine. Three independent systematic reviews of placebo-controlled trials on homeopathy reported that its effects seem to be more than placebo, and one review found its effects consistent with placebo. There is also evidence from randomized, controlled trials that homeopathy may be effective for the treatment of influenza, allergies, postoperative ileus, and childhood diarrhea. Evidence suggests that homeopathy is ineffective for migraine, delayed-onset muscle soreness, and influenza prevention. There is a lack of conclusive evidence on the effectiveness of homeopathy for most conditions. Homeopathy deserves an open-minded opportunity to demonstrate its value by using evidence-based principles, but it should not be substituted for proven therapies.

Soy proteins and isoflavones affect bone mineral density in older women: a randomized controlled trial.

PubMed

Kenny, Anne M; Mangano, Kelsey M; Abourizk, Robin H; Bruno, Richard S; Anamani, Denise E; Kleppinger, Alison; Walsh, Stephen J; Prestwood, Karen M; Kerstetter, Jane E

2009-07-01

Soy foods contain several components (isoflavones and amino acids) that potentially affect bone. Few long-term, large clinical trials of soy as a means of improving bone mineral density (BMD) in late postmenopausal women have been conducted. Our goal was to evaluate the long-term effect of dietary soy protein and/or soy isoflavone consumption on skeletal health in late postmenopausal women. We conducted a randomized, double-blind, placebo-controlled clinical trial in 131 healthy ambulatory women aged >60 y. Ninety-seven women completed the trial. After a 1-mo baseline period, subjects were randomly assigned into 1 of 4 intervention groups: soy protein (18 g) + isoflavone tablets (105 mg isoflavone aglycone equivalents), soy protein + placebo tablets, control protein + isoflavone tablets, and control protein + placebo tablets. Consumption of protein powder and isoflavone pills did not differ between groups, and compliance with the study powder and pills was 80-90%. No significant differences in BMD were observed between groups from baseline to 1 y after the intervention or in BMD change between equol and non-equol producers. However, there were significant negative correlations between total dietary protein (per kg) and markers of bone turnover (P < 0.05). Because soy protein and isoflavones (either alone or together) did not affect BMD, they should not be considered as effective interventions for preserving skeletal health in older women. The negative correlation between dietary protein and bone turnover suggests that increasing protein intakes may suppress skeletal turnover. This trial was registered at ClinicalTrials.gov as NCT00668447.

Development of the food supplement Nyaditum resae as a new tool to reduce the risk of tuberculosis development

PubMed Central

Tukvadze, Nestani; Cardona, Paula; Vashakidze, Sergo; Shubladze, Natalia; Avaliani, Zaza; Vilaplana, Cris; Cardona, Pere-Joan

2017-01-01

Nyaditum resae (NR) is a galenic preparation of heat-killed Mycobacterium manresensis (hkMn). This is a new species that belongs to the Mycobacterium fortuitum complex, and it is present in drinking water—thus, regulatorily speaking, it is considered a food supplement. Preclinical studies in the murine model of active tuberculosis (TB) in the C3HeB/FeJ strain have demonstrated that daily administration of NR containing 103–106 hkMn for 14 days was able to stop the progression toward active TB [1]. The mechanism of action was linked to the induction of low dose tolerance and was related to the increase of Tuberculin Purified Protein Derivative (PPD) memory-specific Tregs (CD4+CD25+CD39+ cells) after ex vivo incubation of splenocytes for 7 days. This increase of Tregs was related to the increase of inter-leukin (IL)-10 in the spleen and in the reduction of IL-17 in the lungs, where there was also a reduction in bacillary load and the pathology caused by a reduction of neutrophiles’ infiltration [2]. Two randomized, double-blind placebo-controlled clinical trials (CTs) have been conducted in humans. The NYADATREG study (Clinicaltrials.gov identifier NCT02076139; 2013–2014) was aimed to evaluate the safety and the immunogenicity of two concentrations of NR (containing 104 hkMn and 105 hkMn) versus placebo (all administered orally everyday for 14 days) in tuberculin-positive and tuberculin-negative volunteers (total n = 51). The results demonstrated an excellent safety record, with no differences between groups in terms of adverse effects. A significant increase in PPD-specific memory regulatory T cells was also detected in both NR groups [3]. The NYADAPETRICS study (Clinicaltrials.gov identifier NCT02581579) is evaluating the safety and immunogenicity of NR 105 hkMn (capsule format, orally) in the pediatric population. Currently, an efficacy study (randomized, double-blinded, placebo-controlled CT) is being conducted in Georgia. This NYADAGEORG trial includes close contacts of active TB cases with positive sputum not tributaries of chemoprophylaxis (<5-year-old children and HIV-positive individuals), which will receive NR (containing 105 hkMn) or placebo (orally, every day for 14 days). A total of 3300 participants will be recruited in four medical centers around Tbilissi. The participants are monitored by telephone for up to 2 years to evaluate the incidence of active TB. The hypothesis is that the NR group will exhibit a 40% reduction in expected TB incidence. Thus, the anticipated TB incidence will be 3% in the NR group versus 5% in the placebo group. The CT is projected to end by 2021 (Clinicaltrials.gov identifier NCT02897180). The administration of the food supplement NR appears to be a new, easy, safe, and reliable method for reducing the risk of developing active TB, and new CTs must be encouraged to discern the particular efficacy power according to different population characteristics. PMID:28043488

Are There Scenarios When the Use of Non-Placebo-Control Groups in Experimental Trial Designs Increase Expected Value to Society?

PubMed

Uyei, Jennifer; Braithwaite, R Scott

2016-01-01

Despite the benefits of the placebo-controlled trial design, it is limited by its inability to quantify total benefits and harms. Such trials, for example, are not designed to detect an intervention's placebo or nocebo effects, which if detected could alter the benefit-to-harm balance and change a decision to adopt or reject an intervention. In this article, we explore scenarios in which alternative experimental trial designs, which differ in the type of control used, influence expected value across a range of pretest assumptions and study sample sizes. We developed a decision model to compare 3 trial designs and their implications for decision making: 2-arm placebo-controlled trial ("placebo-control"), 2-arm intervention v. do nothing trial ("null-control"), and an innovative 3-arm trial design: intervention v. do nothing v. placebo trial ("novel design"). Four scenarios were explored regarding particular attributes of a hypothetical intervention: 1) all benefits and no harm, 2) no biological effect, 3) only biological effects, and 4) surreptitious harm (no biological benefit or nocebo effect). Scenario 1: When sample sizes were very small, the null-control was preferred, but as sample sizes increased, expected value of all 3 designs converged. Scenario 2: The null-control was preferred regardless of sample size when the ratio of placebo to nocebo effect was >1; otherwise, the placebo-control was preferred. Scenario 3: When sample size was very small, the placebo-control was preferred when benefits outweighed harms, but the novel design was preferred when harms outweighed benefits. Scenario 4: The placebo-control was preferred when harms outweighed placebo benefits; otherwise, preference went to the null-control. Scenarios are hypothetical, study designs have not been tested in a real-world setting, blinding is not possible in all designs, and some may argue the novel design poses ethical concerns. We identified scenarios in which alternative experimental study designs would confer greater expected value than the placebo-controlled trial design. The likelihood and prevalence of such situations warrant further study. © The Author(s) 2015.

Decline in placebo-controlled trial results suggests new directions for comparative effectiveness research.

PubMed

Olfson, Mark; Marcus, Steven C

2013-06-01

The Affordable Care Act offers strong support for comparative effectiveness research, which entails comparisons among active treatments, to provide the foundation for evidence-based practice. Traditionally, a key form of research into the effectiveness of therapeutic treatments has been placebo-controlled trials, in which a specified treatment is compared to placebo. These trials feature high-contrast comparisons between treatments. Historical trends in placebo-controlled trials have been evaluated to help guide the comparative effectiveness research agenda. We investigated placebo-controlled trials reported in four leading medical journals between 1966 and 2010. We found that there was a significant decline in average effect size or average difference in efficacy (the ability to produce a desired effect) between the active treatment and placebo. On average, recently studied treatments offered only small benefits in efficacy over placebo. A decline in effect sizes in conventional placebo-controlled trials supports an increased emphasis on other avenues of research, including comparative studies on the safety, tolerability, and cost of treatments with established efficacy.

Effect of Multi-Ingredient Supplement Containing Satiereal, Naringin, and Vitamin D on Body Composition, Mood, and Satiety in Overweight Adults.

PubMed

Gonzalez, Adam M; Sell, Katie M; Ghigiarelli, Jamie J; Spitz, Robert W; Accetta, Matthew R; Mangine, Gerald T

2018-01-16

The purpose of this investigation was to examine the effects of 28 days of a dietary supplement on body composition, mood, and satiety in overweight adults. Twenty healthy adults (25.5 ± 3.8 years; 87.3 ± 20.7 kg; 169.9 ± 10.6 cm; 29.9 ± 5.1 body mass index) participated in this randomized, double-blind, placebo-controlled investigation. Ten participants were provided with a dietary supplement containing 178 mg satiereal, 100 mg naringin, and 2,000 IU vitamin D3 daily (SUPP), and ten participants were provided a placebo (PL) for 28 days. Baseline (PRE) and post (POST) assessments included body mass, BMI, and waist circumference measures. In addition, participants provided self-reported food records and completed study questionnaires twice weekly. Questionnaires consisted of profile of mood states, visual analog scales, modified trait food-cravings questionnaire, and a modified state food-cravings questionnaire. No significant differences were noted between groups for total calorie or macronutrient intake (p = 0.65-0.92), body mass (p = 0.34), BMI (p = 0.24), or waist circumference measures (p = 0.56-0.94). In addition, no significant differences between groups were observed for mood states, subjective measures of food cravings, or feelings of anxiety, fullness, bloating, hunger, craving, and stress (p >.05). In conclusion, 28 days of a dietary supplement containing satiereal, naringin, and vitamin D3 did not have any detectable beneficial effects on body-weight management.

External cues challenging the internal appetite control system-Overview and practical implications.

PubMed

Bilman, Els; van Kleef, Ellen; van Trijp, Hans

2017-09-02

Inadequate regulation of food intake plays an important role in the development of overweight and obesity, and is under the influence of both the internal appetite control system and external environmental cues. Especially in environments where food is overly available, external cues seem to override and/or undermine internal signals, which put severe challenges on the accurate regulation of food intake. By structuring these external cues around five different phases in the food consumption process this paper aims to provide an overview of the wide range of external cues that potentially facilitate or hamper internal signals and with that influence food intake. For each of the five phases of the food consumption process, meal initiation, meal planning, consumption phase, end of eating episode and time till next meal, the most relevant internal signals are discussed and it is explained how specific external cues exert their influence.

Positive effects of soy lecithin-derived phosphatidylserine plus phosphatidic acid on memory, cognition, daily functioning, and mood in elderly patients with Alzheimer's disease and dementia.

PubMed

Moré, Margret I; Freitas, Ulla; Rutenberg, David

2014-12-01

We report previously unpublished, early pilot studies performed with a brain-health food supplement containing a proprietary blend of 100 mg phosphatidylserine (PS) and 80 mg phosphatidic acid (PA) produced from soy lecithin. Serum analysis after single PS+PA ingestion was performed in healthy volunteers. A 3-month double-blind, placebo-controlled study assessed the influence of three PS+PA capsules/day, (300 mg PS + 240 mg PA/day) or placebo on memory and mood in functioning, non-depressive elderly people with memory problems, using the Wechsler Memory Scale and the List of Depressive Symptoms. Furthermore, a 2-month randomized, double-blind, placebo-controlled trial assessed the effect of three PS+PA capsules/day (300 mg PS + 240 mg PA/day) or placebo on daily functioning, mental health, emotional state, and self-reported general condition in patients with Alzheimer's disease (AD). Serum PS peaked 90 min after ingestion, returning to baseline after 180 min. In the elderly, PS+PA [per protocol (PP) n = 31], unlike placebo (PP n = 26), significantly improved memory and prevented "winter blues" in a pre-post comparison. In the patients with AD, daily functioning (i.e., 7 activities of daily living) under PS+PA (PP n = 53) remained unchanged, but declined from 5.62 to 4.90 under placebo (PP n = 39; P = 0.035), with significant group difference (P = 0.021). The PS+PA group had 3.8% deterioration and 90.6% stability in daily functioning, compared to 17.9% and 79.5% under placebo, respectively (P = 0.066). Forty-nine percent of the PS+PA patients reported an improved general condition, compared to 26.3% under placebo (P = 0.084). Approximately, 43% of the PS+PA patients, but none under placebo, continued post-trial supplementation (while double-blinded). No negative side effects were observed. PS is efficiently absorbed after oral consumption. A positive influence of PS+PA on memory, mood, and cognition was demonstrated among elderly test subjects. Short-term supplementation with PS+PA in patients with AD showed a stabilizing effect on daily functioning, emotional state and self-reported general condition. The data encourage long-term studies with PS+PA in AD patients and other elderly with memory or cognition problems.

Benefits of foods supplemented with vegetable oils rich in α-linolenic, stearidonic or docosahexaenoic acid in hypertriglyceridemic subjects: a double-blind, randomized, controlled trail.

PubMed

Dittrich, Manja; Jahreis, Gerhard; Bothor, Kristin; Drechsel, Carina; Kiehntopf, Michael; Blüher, Matthias; Dawczynski, Christine

2015-09-01

The aim of the study was to investigate the influence of foods enriched with vegetable oils varying in their n-3 polyunsaturated fatty acids profile on cardiovascular risk factors for hypertriglyceridemic subjects. Fifty-nine hypertriglyceridemic subjects (triglycerides ≥ 1.5 mmol/L) were included in the randomized, double-blind, placebo-controlled, crossover study. The placebo group received sunflower oil [linoleic acid (LA) group; 10 g LA/day]. The intervention groups received linseed oil [α-linolenic acid (ALA) group; 7 g ALA/day], echium oil [stearidonic acid (SDA) group; 2 g SDA/day] or microalgae oil [docosahexaenoic acid (DHA) group; 2 g DHA/day] over 10 weeks. Blood samples were collected at baseline and at the end of each period. Total cholesterol (TC) and low-density-lipoprotein cholesterol decreased significantly in the LA and ALA groups (LA: P ≤ 0.01, ALA: P ≤ 0.05). No changes in blood lipids were observed in the SDA group. Significant increases in TC and high-density-lipoprotein cholesterol occurred in the DHA group (P ≤ 0.05). In the ALA and SDA groups, the content of eicosapentaenoic acid in erythrocyte lipids increased significantly (P ≤ 0.05) after 10 weeks (ALA group: 38 ± 37 %, SDA group: 73  ± 59 %). Foods enriched with different vegetable oils rich in ALA or SDA are able to increase the n-3 long-chain polyunsaturated fatty acids content in erythrocyte lipids; echium oil is more potent in comparison with linseed oil. Blood lipids were beneficially modified through the consumption of food products enriched with sunflower, linseed and microalgae oils, whereas echium oil did not affect blood lipids. ClinicalTrials.gov: NCT01437930.

A renewed, ethical defense of placebo-controlled trials of new treatments for major depression and anxiety disorders.

PubMed

Dunlop, B W; Banja, J

2009-06-01

The use of placebo as a control condition in clinical trials of major depressive disorder and anxiety disorders continues to be an area of ethical concern. Typically, opponents of placebo controls argue that they violate the beneficent-based, "best proven diagnostic and therapeutic method" that the original Helsinki Declaration of 1964 famously asserted participants are owed. A more consequentialist, oppositional argument is that participants receiving placebo might suffer enormously by being deprived of their usual medication(s). Nevertheless, recent findings of potential for suicidality in young people treated with antidepressants, along with meta-analyses suggesting that antidepressants add no significant clinical benefit over placebos, warrant a re-evaluation of the arguments against placebo. Furthermore, the nature of placebo treatment in short-term clinical trials is often not well understood, and lack of understanding can foster opposition to it. This paper will show how scientific justifications for placebo use are morally relevant. The fundamental ethical importance of placebo controls is discussed in relation to several aspects of clinical trials, including detection of adverse events, accurate assessment of clinical benefit, advancing understanding of the heterogeneity of depression and anxiety disorders and respecting informed consent requirements. Prohibiting the use of placebo controls is morally concerning in that such prohibitions allow for the possibility of serious adverse public health consequences. Moral worries that research participants receiving placebo are being unduly jeopardised will be shown to be exaggerated, especially in relation to the net benefits for end-users to be gained from the quality of data resulting from using placebo controls.

A randomized double-blinded placebo-controlled study to evaluate an effective ciclosporin dose for the treatment of feline hypersensitivity dermatitis.

PubMed

King, Stephen; Favrot, Claude; Messinger, Linda; Nuttall, Tim; Steffan, Jean; Forster, Sophie; Seewald, Wolfgang

2012-10-01

Hypersensitivity dermatitides (HD) are frequently suspected in cats, but there are few clinical studies on safe and effective treatments in the published literature. To establish a safe and effective dose of ciclosporin in the treatment of feline HD. One hundred client-owned cats with feline HD. Double-blind study, with cats randomly assigned to receive ciclosporin at either 7.0 mg/kg once daily (n = 33) or 2.5 mg/kg once daily (n = 32) or a placebo (n = 35) for 6 weeks. Mean Total Lesion Scores with 7.0 mg/kg ciclosporin were significantly lower than with 2.5 mg/kg ciclosporin (P = 0.0047) or placebo (P = 0.0003) at study end. Individual Total Lesion Scores improved by >50% in 70% of the 7.0 mg/kg group, compared with 47% in the 2.5 mg/kg group and 23% in the placebo group (P = 0.0006). The investigators' Global Assessment of Improvement was 'excellent' or 'good' in 61% of cats treated with 7.0 mg/kg ciclosporin, compared with 47% of cats given 2.5 mg/kg and 23% given placebo. The improvement in Investigator Pruritus Scores was significantly greater in cats treated with 7.0 mg/kg ciclosporin (54%) compared with both 2.5 mg/kg ciclosporin (32%; P = 0.0232) and placebo (21%; P = 0.0063). Mild gastrointestinal disorders were the most common adverse events, but these did not require cessation of therapy. Results suggest that 7.0 mg/kg ciclosporin once daily in food or per os for 6 weeks is effective and well tolerated in feline HD. © 2012 The Authors. Veterinary Dermatology © 2012 ESVD and ACVD.

Acute EGCG supplementation reverses endothelial dysfunction in patients with coronary artery disease.

PubMed

Widlansky, Michael E; Hamburg, Naomi M; Anter, Elad; Holbrook, Monika; Kahn, David F; Elliott, James G; Keaney, John F; Vita, Joseph A

2007-04-01

Epidemiological studies demonstrate an inverse relation between dietary flavonoid intake and cardiovascular risk. Recent studies with flavonoid-containing beverages suggest that the benefits of these nutrients may relate, in part, to improved endothelial function. We hypothesized that dietary supplementation with epigallocatechin gallate (EGCG), a major catechin in tea, would improve endothelial function in humans. We examined the effects of EGCG on endothelial function in a double blind, placebo-controlled, crossover design study. We measured brachial artery flow-mediated dilation by vascular ultrasound at six time points: prior to treatment with EGCG or placebo, two hours after an initial dose of EGCG (300 mg) or placebo, and after two weeks of treatment with EGCG (150 mg twice daily) or placebo. The order of treatments (EGCG or placebo) was randomized and there was a one-week washout period between treatments. A total of 42 subjects completed the study, and brachial artery flow-mediated dilation improved from 7.1 +/- 4.1 to 8.6 +/- 4.7% two hours after the first dose of 300 mg of EGCG (P = 0.01), but was similar to baseline (7.8 +/- 4.2%, P = 0.12) after two weeks of treatment with the final measurements made approximately 14 hours after the last dose. Placebo treatment had no significant effect, and there were no changes in reactive hyperemia or the response to sublingual nitroglycerin. The changes in vascular function paralleled plasma EGCG concentrations, which increased from 2.6 +/- 10.9 to 92.8 +/- 78.7 ng/ml after acute EGCG (P < 0.001), but were unchanged from baseline after two weeks of treatment (3.4 +/- 13.1 ng/ml). EGCG acutely improves endothelial function in humans with coronary artery disease, and may account for a portion of the beneficial effects of flavonoid-rich food on endothelial function.

Effect of permethrin-impregnated underwear on body lice in sheltered homeless persons: a randomized controlled trial.

PubMed

Benkouiten, Samir; Drali, Rezak; Badiaga, Sékéné; Veracx, Aurélie; Giorgi, Roch; Raoult, Didier; Brouqui, Philippe

2014-03-01

The control of body lice in homeless persons remains a challenge. To determine whether the use of long-lasting insecticide-treated underwear provides effective long-term protection against body lice in homeless persons. A randomized, double-blind, placebo-controlled trial was conducted in February and December 2011 in 2 homeless shelters (Madrague Ville and Forbin) in Marseille, France. Of the 125 homeless persons screened for eligibility, 73 body lice-infested homeless persons, 18 years or older, were enrolled. Body lice-infested homeless persons were randomly assigned to receive 0.4% permethrin-impregnated underwear or an identical-appearing placebo for 45 days, in a 1:1 ratio, with a permuted block size of 10. Visits were scheduled at days 14 and 45. Data regarding the presence or absence of live body lice were collected. The primary and secondary end points were the proportions of homeless persons free of body lice on days 14 and 45, respectively. Mutations associated with permethrin resistance in the body lice were also identified. Significantly more homeless persons receiving permethrin-impregnated underwear than homeless persons receiving the placebo were free of body lice on day 14 in the intent-to-treat population (28% vs 9%; P = .04), with a between-group difference of 18.4 percentage points (95% CI, 1.4-35.4), and in the per-protocol population (34% vs 11%; P = .03), with a between-group difference of 23.7 percentage points (95% CI, 3.6-43.7). This difference was not sustained on day 45. At baseline, the prevalence of the permethrin-resistant haplotype was 51% in the permethrin group and 44% in the placebo group. On day 45, the permethrin-resistant haplotype was significantly more frequent in the permethrin group than in the placebo group (73% vs 45%, P < .001). Permethrin-impregnated underwear is more efficient than placebo at eliminating body louse infestations by day 14; however, this difference was not sustained on day 45. The use of permethrin may have increased the resistance to permethrin in body lice and thus must be avoided. clinicaltrials.gov Identifier: NCT01287663.

A randomized, placebo-controlled trial of repetitive spinal magnetic stimulation in lumbosacral spondylotic pain.

PubMed

Lo, Yew L; Fook-Chong, Stephanie; Huerto, Antonio P; George, Jane M

2011-07-01

Lumbar spondylosis is a degenerative disorder of the spine, whereby pain is a prominent feature that poses therapeutic challenges even after surgical intervention. There are no randomized, placebo-controlled studies utilizing repetitive spinal magnetic stimulation (SMS) in pain associated with lumbar spondylosis. In this study, we utilize SMS technique for patients with this condition in a pilot clinical trial. We randomized 20 patients into SMS treatment or placebo arms. All patients must have clinical and radiological evidence of lumbar spondylosis. Patients should present with pain in the lumbar region, localized or radiating down the lower limbs in a radicular distribution. SMS was delivered with a Medtronic R30 repetitive magnetic stimulator (Medtronic Corporation, Skovlunde, Denmark) connected to a C-B60 figure of eight coil capable of delivering a maximum output of 2 Tesla per pulse. The coil measured 90 mm in each wing and was centered over the surface landmark corresponding to the cauda equina region. The coil was placed flat over the back with the handle pointing cranially. Each patient on active treatment received 200 trains of five pulses delivered at 10 Hz, at an interval of 5 seconds between each train. "Sham" SMS was delivered with the coil angled vertically and one of the wing edges in contact with the stimulation point. All patients tolerated the procedure well and no side effects of SMS were reported. In the treatment arm, SMS had resulted in significant pain reduction immediately and at Day 4 after treatment (P < 0.05). In the placebo arm, however, no significant pain reduction was seen immediately and at Day 4 after SMS. SMS in the treatment arm had resulted in mean pain reduction of 62.3% postprocedure and 17.4% at Day 4. The placebo arm only achieved pain reduction of 6.1% postprocedure and 4.5% at Day 4. This is the first study to show that a single session of SMS resulted in significant improvement of pain associated with lumbar spondylosis in a randomized, double-blind, placebo-controlled setting. The novel findings support the potential of this technique for future studies pertaining to neuropathic pain. Wiley Periodicals, Inc.

Attitudes toward placebo-controlled clinical trials among depressed patients in Japan.

PubMed

Sugawara, Norio; Ishioka, Masamichi; Tsuchimine, Shoko; Tsuruga, Koji; Sato, Yasushi; Tarakita, Natsumi; Furukori, Hanako; Kudo, Shuhei; Tomita, Tetsu; Nakagami, Taku; Yasui-Furukori, Norio

2018-01-01

Placebo-controlled clinical trials are the standard in the design of clinical studies for the licensing of new drugs. Medical and ethical concerns regarding placebo use still exist in clinical trials of depressed patients. The aim of this study was to investigate the attitudes toward placebo-controlled clinical trials and to assess factors related to the willingness to participate in such trials among depressed patients in Japan. A total of 206 depressed patients aged 49.5 ± 15.7 years (mean ± SD) who were admitted to three psychiatric hospitals were recruited for a cross-sectional study from June 2015 to March 2016. After a thorough explanation of the placebo, the study participants completed a brief 14-item questionnaire developed to evaluate patients' attitudes regarding possible participation in placebo-controlled clinical trials. The Quick Inventory of Depressive Symptomatology was also administered to assess depressive symptoms. The results indicated that 47% of the patients would be willing to participate in a placebo-controlled clinical trial. Expectations for the improvement of disease, desire to receive more medical care, encouragement by family or friends, and desire to support the development of new drugs were associated with the willingness to participate in such trials, whereas a belief that additional time would be required for medical examinations and fear of exacerbation of symptoms due to placebo use were associated with non-participation. Patients were asked about possible participation in placebo-controlled clinical trials. Less than half of the respondents were willing to participate in placebo-controlled clinical trials. Attitudes toward participation in a placebo-controlled clinical trial need to be considered when deciding whether to conduct such a trial. Copyright © 2017. Published by Elsevier B.V.

The Effect of the Type and Colour of Placebo Stimuli on Placebo Effects Induced by Observational Learning.

PubMed

Świder, Karolina; Bąbel, Przemysław

2016-01-01

Research shows that placebo analgesia and nocebo hyperalgesia can be induced through observational learning. Our aim was to replicate and extend these results by studying the influence of the type and colour of stimuli used as placebos on the placebo effects induced by observational learning. Three experimental and two control groups were tested. All participants received pain stimuli of the same intensity preceded by colour lights (green and red) or geometric shapes (circles and squares). Before receiving pain stimuli, participants in the experimental groups, but not in the control groups, observed a model who rated pain stimuli that were preceded by either green lights (green placebo group), red lights (red placebo group), or circles (circle placebo group) as being less painful than those preceded by either red lights (green placebo group), green lights (red placebo group), or squares (circle placebo group). As a result participants in the experimental groups rated pain stimuli preceded by either green lights (green placebo group), red lights (red placebo group), or circles (circle placebo group) as being less painful than the participants in the control groups did, indicating that placebo effect was induced. No statistically significant differences were found in the magnitudes of the placebo effects between the three experimental groups (green placebo, red placebo, and circle placebo groups), indicating that neither the type nor the colour of placebo stimuli affected the placebo effects induced by observational learning. The placebo effects induced by observational learning were found to be unrelated to the individual differences in pain anxiety, fear of pain, and empathy.

The Effect of the Type and Colour of Placebo Stimuli on Placebo Effects Induced by Observational Learning

PubMed Central

Świder, Karolina; Bąbel, Przemysław

2016-01-01

Research shows that placebo analgesia and nocebo hyperalgesia can be induced through observational learning. Our aim was to replicate and extend these results by studying the influence of the type and colour of stimuli used as placebos on the placebo effects induced by observational learning. Three experimental and two control groups were tested. All participants received pain stimuli of the same intensity preceded by colour lights (green and red) or geometric shapes (circles and squares). Before receiving pain stimuli, participants in the experimental groups, but not in the control groups, observed a model who rated pain stimuli that were preceded by either green lights (green placebo group), red lights (red placebo group), or circles (circle placebo group) as being less painful than those preceded by either red lights (green placebo group), green lights (red placebo group), or squares (circle placebo group). As a result participants in the experimental groups rated pain stimuli preceded by either green lights (green placebo group), red lights (red placebo group), or circles (circle placebo group) as being less painful than the participants in the control groups did, indicating that placebo effect was induced. No statistically significant differences were found in the magnitudes of the placebo effects between the three experimental groups (green placebo, red placebo, and circle placebo groups), indicating that neither the type nor the colour of placebo stimuli affected the placebo effects induced by observational learning. The placebo effects induced by observational learning were found to be unrelated to the individual differences in pain anxiety, fear of pain, and empathy. PMID:27362552

Prospective, randomized, controlled, proof-of-concept study of the Ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients.

PubMed

Beck, David E; Sweeney, W Brian; McCarter, Martin D

2014-12-01

Postoperative ileus is a significant clinical challenge lacking effective management strategies. Ghrelin-receptor stimulation has promotility effects in the upper and lower gastrointestinal tract. This proof-of-concept, phase 2, randomized study evaluated the safety and efficacy of the ghrelin-receptor agonist ipamorelin in the treatment of postoperative ileus following abdominal surgery (ClinicalTrials.gov NCT00672074). The design was a multicenter, double-blind, placebo-controlled, clinical trial. The settings include hospital inpatients. The patients were adults undergoing small and large bowel resection by open or laparoscopic surgery. The intervention was intravenous infusions of 0.03-mg/kg ipamorelin vs placebo twice daily, on postoperative day 1 to 7 or hospital discharge. Safety was assessed by monitoring adverse events and laboratory tests. The key efficacy endpoint was time from first dose of study drug to tolerance of a standardized solid meal. One hundred seventeen patients were enrolled, of whom 114 patients composed the safety and modified intent-to-treat populations. Demographic and disease characteristics were balanced between groups. Overall incidence of any treatment-emergent adverse events was 87.5 % in the ipamorelin group and 94.8 % in placebo group. Median time to first tolerated meal was 25.3 and 32.6 h in the ipamorelin and placebo groups, respectively (p = 0.15). This proof of concept study was small and enrolled patients with a broad range of underlying conditions. Ipamorelin 0.03-mg/kg twice daily for up to 7 days was well tolerated. There were no significant differences between ipamorelin and placebo in the key and secondary efficacy analyses.

Evaluation of the use of Swedish integrated electronic health records and register health care data as support clinical trials in severe asthma: the PACEHR study.

PubMed

Franzén, Stefan; Janson, Christer; Larsson, Kjell; Petzold, Max; Olsson, Urban; Magnusson, Gunnar; Telg, Gunilla; Colice, Gene; Johansson, Gunnar; Sundgren, Mats

2016-11-15

In the development of new drugs for severe asthma, it is a challenge from an ethical point of view to randomize severe asthma patients to placebo, and to obtain long-term safety data due to discontinuations. The aim of this study was to evaluate the feasibility of using electronic health record (EHR) data to create a real-world reference population of uncontrolled asthmatic patients to supplement the concurrent control/placebo group in long-term studies of asthma. EHR data from 36 primary care centres and a University hospital in Sweden were linked to Swedish mandatory health registers (2005-2013), creating a population covering 33 890 asthma patients, including data on co-morbidities, risk factors and laboratory/respiratory measurements. A severe asthma EHR reference cohort was established. We used logistic regression to estimate the propensity score (probability) of each RCT or EHR patient existing in the EHR cohort given their covariates. We created an EHR-derived reference cohort of 240 patients, matching the placebo group (N = 151) in an RCT of severe asthma. The exacerbation rate during follow-up in the EHR study population was 1.24 (weighted) compared to 0.9 in the RCT placebo group. Patients in the EHR cohort were of similar age as in the RCT placebo group, 50.6 years versus 50.1 years; had slightly higher body mass index 27.0 kg/m 2 versus 27.3 kg/m 2 ; and consisted of 40% versus 34% males. The results indicate that EHRs provide an opportunity to supplement the control group in RCTs of severe diseases.

Importance of maternal diet in the training of the infant's immune system during gestation and lactation.

PubMed

Jeurink, P V; Knipping, K; Wiens, F; Barańska, K; Stahl, B; Garssen, J; Krolak-Olejnik, B

2018-02-02

Latest forecasts predict that half of the European population will be allergic within the coming 15 years, with food allergies contributing substantially to the total burden; preventive measures are urgently needed. Unfortunately, all attempted alimentary strategies for primary prevention of allergic diseases through allergen avoidance so far have failed. This also holds true for the prevention of food allergies in breastfed infants by the common practice of excluding certain foods with allergenic potential from the maternal diet. As a preventive measure, therefore, exclusion diets should be discouraged. They can exhaust nursing mothers and negatively impact both their nutritional status as well as their motivation to breastfeed. A prolonged exclusion diet may be indicated solely in cases of doctor-diagnosed food allergy following rigid medical tests (e.g. double-blind placebo-controlled food challenges). Indicated cases usually involve exclusion of only a few food items. Continued breastfeeding is generally important for many aspects of the infant's health, including the training of the infant's immune responses to foreign compounds and avoidance of overshooting inflammatory responses. Recent studies suggest that the presence of maternal dietary proteins in amniotic fluid, cord blood, and human milk might support the induction of tolerance towards solid foods in infants. These are exactly the same species of proteins or remnants thereof that, in comparatively few cases, trigger allergic responses. However, the insight that the proteins of maternal dietary origin in human milk are more likely to be cure (or, more precise, directing prevention) than curse has still largely evaded the attention of health care professionals consulted by worried breastfeeding mothers. In this paper, we summarize recent literature on the importance of exposure to dietary proteins in the establishment of immunological tolerance and hence prevention of allergic disease. Multiple organizations have used the scientific knowledge to build (local) guidelines (e.g. AAAAI, EAACI, BSACI) that can support health care professionals to provide the best strategy to prevent the onset of allergic diseases. We thus hope to clarify existing confusion about the allergenic propensities of dietary proteins during early life, which has contributed to exaggerated fears around the diet of pregnant and breastfeeding mothers.

Importance of placebo effect in cough clinical trials.

PubMed

Eccles, Ron

2010-01-01

Cough is a unique symptom because, unlike sneeze and other symptoms, it can be under voluntary control and this complicates clinical trials on cough medicines. All over-the-counter cough medicines (OTC) are very effective treatments because of their placebo effect. The placebo effect is enhanced by expectancy related to advertising, brand, packaging, and formulation. This placebo effect creates a problem for the conduct of clinical trials on OTC cough medicines that attempt to demonstrate the efficacy of a pharmacological agent above that of any placebo effect. Up to 85% of the efficacy of some cough medicines can be attributed to a placebo effect. The placebo effect apparent in clinical trials consists of several components: natural recovery, regression of cough response toward mean, demulcent effect, effect of sweetness, voluntary control, and effects related to expectancy and meaning of the treatment. The placebo effect has been studied most in the pain model, and placebo analgesia is reported to depend on the activation of endogenous opioid systems in the brain; this model may be applicable to cough. A balanced placebo design may help to control for the placebo effect, but this trial design may not be acceptable due to deception of patients. The placebo effect in clinical trials may be controlled by use of a crossover design, where feasible, and the changes in the magnitude of the placebo effect in this study design are discussed.

Patient Expectancy as a Mediator of Placebo Effects in Antidepressant Clinical Trials.

PubMed

Rutherford, Bret R; Wall, Melanie M; Brown, Patrick J; Choo, Tse-Hwei; Wager, Tor D; Peterson, Bradley S; Chung, Sarah; Kirsch, Irving; Roose, Steven P

2017-02-01

Causes of placebo effects in antidepressant trials have been inferred from observational studies and meta-analyses, but their mechanisms have not been directly established. The goal of this study was to examine in a prospective, randomized controlled trial whether patient expectancy mediates placebo effects in antidepressant studies. Adult outpatients with major depressive disorder were randomly assigned to open or placebo-controlled citalopram treatment. Following measurement of pre- and postrandomization expectancy, participants were treated with citalopram or placebo for 8 weeks. Independent samples t tests determined whether patient expectancy differed between the open and placebo-controlled groups, and mixed-effects models assessed group effects on Hamilton Depression Rating Scale (HAM-D) scores over time while controlling for treatment assignment. Finally, mediation analyses tested whether between-group differences in patient expectancy mediated the group effect on HAM-D scores. Postrandomization expectancy scores were significantly higher in the open group (mean=12.1 [SD=2.1]) compared with the placebo-controlled group (mean=11.0 [SD=2.0]). Mixed-effects modeling revealed a significant week-by-group interaction, indicating that HAM-D scores for citalopram-treated participants declined at a faster rate in the open group compared with the placebo-controlled group. Patient expectations postrandomization partially mediated group effects on week 8 HAM-D. Patient expectancy is a significant mediator of placebo effects in antidepressant trials. Expectancy-related interventions should be investigated as a means of controlling placebo responses in antidepressant clinical trials and improving patient outcome in clinical treatment.

Efficacy of itraconazole in the treatment of patients with chronic cough whose sputa yield basidiomycetous fungi-fungus-associated chronic cough (FACC).

PubMed

Ogawa, Haruhiko; Fujimura, Masaki; Takeuchi, Yasuo; Makimura, Koichi

2009-05-01

This controlled study was performed to clarify the therapeutic benefit of itraconazole for the treatment of patients with chronic cough, wherein a sputum culture yielded basidiomycetous (BM) fungi. Of the 171 patients who visited our hospital for the diagnosis and treatment of chronic cough, BM was detected in the sputum of 39 patients. Informed consents were obtained from 21 patients who were subsequently enrolled in this trial. After the administration of the standard therapy, all the patients were enrolled in a randomized placebo-controlled study with 2 weeks of treatment with a low dose of itraconazole (50 mg/day) (n = 10) in comparison with a corresponding period of treatment with matched placebo (ambroxol hydrochloride 45 mg/day) (n = 11). Coughing was assessed using subjective cough symptom scale and capsaicin cough challenging. The treatment with itraconazole, but not placebo (p = 0.17), was associated with a significant improvement in the cough scale (p = 0.0051); moreover, the improvement achieved with itraconazole was significant (p < 0.001) when compared with that of the placebo. Low-dose itraconazole was shown to be an effective antitussive in patients with chronic cough in which sputum examination yielded BM fungi. The 21 patients described here entailed the following manifestations: (1) chronic cough; (2) the presence of environmental fungi, particularly basidiomycetous (BM) fungi, in the sputum; and (3) good clinical response to antifungal drugs. These clinical features may constitute a unique disease concept called fungus-associated chronic cough (FACC).

Whole body vibration training improves vibration perception threshold in healthy young adults: A randomized clinical trial pilot study

PubMed Central

Hernandez-Mocholi, M.A.; Dominguez-Muñoz, F.J.; Corzo, H.; Silva, S.C.S.; Adsuar, J.C.; Gusi, N.

2016-01-01

Objectives: Loss of foot sensitivity is a relevant parameter to assess and prevent in several diseases. It is crucial to determine the vibro-tactile sensitivity threshold response to acute conditions to explore innovative monitor tools and interventions to prevent and treat this challenge. The aims were: 1) to analyze the acute effects of a single whole body vibration session (4min-18Hz-4mm) on vibro-tactile perception threshold in healthy young adults. 2) to analyze the 48 hours effects of 3 whole body vibration sessions on vibro-tactile perception threshold in healthy young adults. Methods: A randomized controlled clinical trial over 3 sessions of whole body vibration intervention or 3 sessions of placebo intervention. Twenty-eight healthy young adults were included: 11 experimental group and 12 placebo group. The experimental group performed 3 sessions of WBV while the placebo group performed 3 sessions of placebo intervention. Results: The vibro-tactile threshold increased right after a single WBV session in comparison with placebo. Nevertheless, after 3 whole body vibration sessions and 48 hours, the threshold decreased to values lower than the initial. Conclusions: The acute response of the vibro-tactile threshold to one whole body vibration session increased, but the 48 hours short-term response of this threshold decreased in healthy young adults. PMID:26944818

Introduction of Complementary Foods to Infants.

PubMed

West, Christina

2017-01-01

While earlier food allergy prevention strategies implemented avoidance of allergenic foods in infancy, the current paradigm is shifting from avoidance to controlled exposure. This review focuses on the outcome of recent randomized controlled trials, which have examined the early introduction of allergenic foods for allergy prevention, and discusses the implementation of results in clinical practice. In infants at high risk of allergic disease, there is now direct evidence that regular early peanut consumption will reduce the prevalence of peanut allergy, compared to avoidance. Many international infant feeding guidelines already recommend complementary foods, including allergenic foods, to be introduced from 4 to 6 months of age irrespective of family history risk. Interim guidelines from 10 International Pediatric Allergy Associations state that healthcare providers should recommend the introduction of peanut-containing products into the diets of infants at high risk of allergic disease in countries where peanut allergy is prevalent. Direct translation of the results obtained from a cohort of high-risk infants to the general population has proved difficult, and issues regarding feasibility, safety, and cost-effectiveness have been raised. Five randomized placebo-controlled trials have assessed the effects of early egg exposure in infancy with varying results. In a recent comprehensive meta-analysis, there was moderate-certainty evidence that early versus late introduction of egg was associated with a reduced egg allergy risk. Although promising, optimal timing, doses, and if the feeding regimen should be stratified according to infant allergy risk remain to be determined. The single study that assessed introduction of multiple foods from 3 months whilst breastfeeding compared with exclusive breastfeeding until 6 months of age showed no reduction in food allergy prevalence. Future research should aim at optimizing infant feeding regimens and support a tolerogenic gastrointestinal microenvironment during the period of food allergen introduction. © 2017 S. Karger AG, Basel.

Effects of metformin on energy intake and satiety in obese children.

PubMed

Adeyemo, M A; McDuffie, J R; Kozlosky, M; Krakoff, J; Calis, K A; Brady, S M; Yanovski, J A

2015-04-01

To investigate the effects of metformin on appetite and energy intake in obese children with hyperinsulinaemia. We conducted a 6-month randomized, double-blind, placebo-controlled trial to evaluate the effects of metformin 1000 mg twice daily on body weight and energy balance in 100 obese children with hyperinsulinaemia aged 6-12 years. The children ate ad libitum from standardized food arrays on two separate occasions before and after 6 months of study medication. The first test meal was consumed after an overnight fast. The second was preceded by a pre-meal load. For each test meal, energy intake was recorded, and the children completed scales of hunger, fullness and desire to eat. Data from the meal studies at baseline and after treatment with study medication were available for 84 children (metformin-treated, n = 45; placebo-treated, n = 39). Compared with placebo, metformin treatment elicited significant reductions from baseline in adjusted mean ± standard error of the mean energy intake after the pre-meal load (metformin: -104.7 ± 83.8 kcal vs. placebo: +144.2 ± 96.9 kcal; p = 0.034) independently of changes in body composition. Metformin also significantly decreased ratings of hunger (-1.5 ± 5.6 vs. +18.6 ± 6.3; p = 0.013) and increased ratings of fullness (+10.1 ± 6.2 vs. -12.8 ± 7.0; p = 0.01) after the pre-meal load. These data suggest that decreased perceived hunger resulting in diminished food intake are among the mechanisms by which metformin treatment reduces body weight in overweight children with hyperinsulinaemia. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

A Six-Month Randomized Controlled Trial of Whole Soy and Isoflavones Daidzein on Body Composition in Equol-Producing Postmenopausal Women with Prehypertension

PubMed Central

Liu, Zhao-min; Ho, Suzanne C.; Chen, Yu-ming; Woo, Jean

2013-01-01

Objectives. This paper reported the effects of commonly used whole soy foods (soy flour) and purified daidzein (one of the major isoflavones and the precursor of equol) on changes in anthropometric measurements and body composition in a 6-month double-blind, randomized, placebo-controlled trial among prehypertensive postmenopausal women who are also equol producers. Methods. 270 eligible women were randomized to either one of the three treatments: 40 g soy flour (whole soy group), 40 g low-fat milk powder + 63 mg daidzein (daidzein group), or 40 g low-fat milk powder (placebo group) daily each for 6 months. Anthropometric indicators and body composition were measured before and after intervention. Results. 253 subjects completed the study with good compliance. Urinary isoflavones levels suggested good compliance of subjects with supplementation. Whole soy and purified daidzein had no significant effect on body weight, body mass index (BMI), waist and hip circumferences, waist to hip ratio (WHR), body fat percentage, fat mass, and free fat mass. Conclusion. Six-month consumption of whole soy and purified daidzein at provided dosage had no improvement on body weight and composition compared with isocaloric milk placebo among prehypertensive equol-producing postmenopausal women. This trial is registered with ClinicalTrials.gov NCT01270737. PMID:23984051

Toward evidence-based medical statistics: a Bayesian analysis of double-blind placebo-controlled antidepressant trials in the treatment of anxiety disorders.

PubMed

Monden, Rei; de Vos, Stijn; Morey, Richard; Wagenmakers, Eric-Jan; de Jonge, Peter; Roest, Annelieke M

2016-12-01

The Food and Drug Administration (FDA) uses a p < 0.05 null-hypothesis significance testing framework to evaluate "substantial evidence" for drug efficacy. This framework only allows dichotomous conclusions and does not quantify the strength of evidence supporting efficacy. The efficacy of FDA-approved antidepressants for the treatment of anxiety disorders was re-evaluated in a Bayesian framework that quantifies the strength of the evidence. Data from 58 double-blind placebo-controlled trials were retrieved from the FDA for the second-generation antidepressants for the treatment of anxiety disorders. Bayes factors (BFs) were calculated for all treatment arms compared to placebo and were compared with the corresponding p-values and the FDA conclusion categories. BFs ranged from 0.07 to 131,400, indicating a range of no support of evidence to strong evidence for the efficacy. Results also indicate a varying strength of evidence between the trials with p < 0.05. In sum, there were large differences in BFs across trials. Among trials providing "substantial evidence" according to the FDA, only 27 out of 59 dose groups obtained strong support for efficacy according to the typically used cutoff of BF ≥ 20. The Bayesian framework can provide valuable information on the strength of the evidence for drug efficacy. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Acute Garcinia mangostana (mangosteen) supplementation does not alleviate physical fatigue during exercise: a randomized, double-blind, placebo-controlled, crossover trial.

PubMed

Chang, Chih-Wei; Huang, Tzu-Zung; Chang, Wen-Hsin; Tseng, Yi-Chun; Wu, Yu-Tse; Hsu, Mei-Chich

2016-01-01

The purple mangosteen (Garcinia mangostana), known as the "queen of fruit," is widely consumed and unique not only because of its outstanding appearance and flavor but also its remarkable and diverse pharmacological effects. The aim of the present study is to evaluate the effect of acute mangosteen supplementation on physical fatigue during exercise. A randomized, double-blind, placebo-controlled, crossover study was carried out by 12 healthy adults. The participants were randomly assigned to receive acute oral administration of either 250 mL of the mangosteen-based juice (supplementation treatment; 305 mg of α-mangostin and 278 mg of hydroxycitric acid) or a placebo (control treatment) 1 h before cycle ergometer exercise. Time to exhaustion, heart rate, Borg Rating of Perceived Exertion score, blood biochemical markers (namely ammonia, cortisol, creatine kinase, aspartate aminotransferase, alanine aminotransferase, glucose, and lactate), muscle dynamic stiffness, and Profile of Mood States (POMS) were evaluated and recorded. The results showed all parameters we examined were significantly altered by the exercise challenge, which demonstrated they directly reflected the condition of fatigue. However, there were no differences between the two treatments besides a positive impact on the POMS examination. The occurrence of physical fatigue depends on multiple underlying mechanisms. We concluded that acute mangosteen supplementation had no impact on alleviating physical fatigue during exercise.

Narcolepsy: current treatment options and future approaches

PubMed Central

Billiard, Michel

2008-01-01

The management of narcolepsy is presently at a turning point. Three main avenues are considered in this review: 1) Two tendencies characterize the conventional treatment of narcolepsy. Modafinil has replaced methylphenidate and amphetamine as the first-line treatment of excessive daytime sleepiness (EDS) and sleep attacks, based on randomized, double blind, placebo-controlled clinical trials of modafinil, but on no direct comparison of modafinil versus traditional stimulants. For cataplexy, sleep paralysis, and hypnagogic hallucinations, new antidepressants tend to replace tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) in spite of a lack of randomized, double blind, placebo-controlled clinical trials of these compounds; 2) The conventional treatment of narcolepsy is now challenged by sodium oxybate, the sodium salt of gammahydroxybutyrate, based on a series of randomized, double-blind, placebo-controlled clinical trials and a long-term open label study. This treatment has a fairly good efficacy and is active on all symptoms of narcolepsy. Careful titration up to an adequate level is essential both to obtain positive results and avoid adverse effects; 3) A series of new treatments are currently being tested, either in animal models or in humans, They include novel stimulant and anticataplectic drugs, endocrine therapy, and, more attractively, totally new approaches based on the present state of knowledge of the pathophysiology of narcolepsy with cataplexy, hypocretine-based therapies, and immunotherapy. PMID:18830438

How Placebo Needles Differ From Placebo Pills?

PubMed Central

Chae, Younbyoung; Lee, Ye-Seul; Enck, Paul

2018-01-01

Because acupuncture treatment is defined by the process of needles penetrating the body, placebo needles were originally developed with non-penetrating mechanisms. However, whether placebo needles are valid controls in acupuncture research is subject of an ongoing debate. The present review provides an overview of the characteristics of placebo needles and how they differ from placebo pills in two aspects: (1) physiological response and (2) blinding efficacy. We argue that placebo needles elicit physiological responses similar to real acupuncture and therefore provide similar clinical efficacy. We also demonstrate that this efficacy is further supported by ineffective blinding (even in acupuncture-naïve patients) which may lead to opposite guesses that will further enhances efficacy, as compared to no-treatment, e.g., with waiting list controls. Additionally, the manner in which placebo needles can exhibit therapeutic effects relative to placebo pills include enhanced touch sensations, direct stimulation of the somatosensory system and activation of multiple brain systems. We finally discuss alternative control strategies for the placebo effects in acupuncture therapy.

Effects of Kivia powder on gut health in patients with occasional constipation: a randomized, double-blind, placebo-controlled study.

PubMed

Udani, Jay K; Bloom, David W

2013-06-08

To evaluate the efficacy of Kivia powder on supporting overall gut health through the relief of the discomfort of occasional constipation. Randomized, double-blind, placebo-controlled, parallel-group trial. The investigational product for this study was Kivia powder (Vital Food Processors Ltd., Auckland, New Zealand), containing the active ingredient Zyactinase™, 5.5 g taken daily for four weeks. One hundred thirty-eight subjects reporting occasional constipation were screened and 87 were randomized to placebo (n = 44) and product (n = 43). Bowel movement frequency, as measured by both average daily spontaneous bowel movements (SBM) and complete spontaneous bowel movements (CSBM), were the same in both groups at baseline. There were significant increases in spontaneous bowel movements at week 1 (p = 0.001), week 2 (p = 0.001), week 3 (p = 0.000), and week 4 (p = 0.000) compared to baseline. SBM demonstrated significant differences between the treatment group and the placebo group at week 3 (p = 0.000), and week 4 (p = 0.020). The treatment group demonstrated a significantly higher rate of SBM at week 3 (p = 000) and from baseline to week 4 (p = 0.019). Significant increases in complete spontaneous bowel movements were observed at week 1 (p = 0.000), week 2 (p = 0.000), week 3 (p = 0.000), and week 4 (p = 0.000) compared to baseline. Moreover, CSBM was significantly higher for the treatment group compared to placebo at week 2 (p = 0.001). The change in average daily CSBM from baseline to week 2 was significantly higher in the treatment group than in the placebo group (p = 0.004).Abdominal discomfort or pain demonstrated significant differences between groups at week 1 (p = 0.044) and week 3 (p = 0.026). Flatulence was significantly lower for active group compared to placebo at week 2 (p = 0.047) and week 3 (p = 0.023). The number of bowel movements associated with urgency was significantly lower in the treatment group compared to the placebo group at week 3 (p = 0.048). In addition, it was decreased from baseline to week 1 (p = 0.040) and from baseline to week 3 (p = 0.024) in the treatment group, while the placebo group did not report any reductions in bowel urgency. Bowel movements in the treatment arm were significantly smoother and softer by week 2 (p = 0.020) and week 3 (p = 0.041). Treatment with Kivia powder, an extract of kiwifruit containing Zyactinase™, for four weeks was well tolerated and more effective than placebo in gently enhancing bowel movement frequency and reducing abdominal pain and flatulence in subjects with occasional constipation. ISRCTN: ISRCTN49036618.

Vasculoprotective Effects of Dietary Cocoa Flavanols in Patients on Hemodialysis: A Double-Blind, Randomized, Placebo-Controlled Trial.

PubMed

Rassaf, Tienush; Rammos, Christos; Hendgen-Cotta, Ulrike B; Heiss, Christian; Kleophas, Werner; Dellanna, Frank; Floege, Jürgen; Hetzel, Gerd R; Kelm, Malte

2016-01-07

Hemodialysis (HD) per se entails vascular dysfunction in patients with ESRD. Endothelial dysfunction is a key step in atherosclerosis and is characterized by impaired flow-mediated dilation (FMD). Interventional studies have shown that cocoa flavanol (CF)-rich supplements improve vascular function. Aim of this study was to investigate the effect of flavanol-rich bioactive food ingredients on acute and chronic HD-induced vascular dysfunction in ESRD. We conducted a randomized, double-blind, placebo-controlled trial from 2012 to 2013. Fifty-seven participants were enrolled, ingested CF-rich beverages (900 mg CF per study day), and were compared with those ingesting CF-free placebo. This included (1) a baseline cross-over acute study to determine safety and efficacy of CF and (2) a subsequent chronic parallel group study with a 30-day follow-up period to study effects of CF on HD-mediated vascular dysfunction entailing (3) an acute substudy during HD in flavanol-naive patients and (4) an acute on chronic study during HD. Primary and secondary outcome measures included changes in FMD and hemodynamics. CF ingestion was well tolerated. Acute ingestion improved FMD by 53% (3.2±0.6% to 4.8±0.9% versus placebo, 3.2±0.7% to 3.3±0.8%; P<0.001), with no effects on BP or heart rate. A 30-day ingestion of CF led to an increase in baseline FMD by 18% (3.4±0.9% to 3.9±0.8% versus placebo, 3.5±0.7% to 3.5±0.7%; P<0.001), with reduced diastolic BP (73±12 to 69±11 mmHg versus placebo, 70±11 to 73±13 mmHg; P=0.03) and increased heart rate (70±12 to 74±13 bpm versus placebo, 75±15 to 74±13 bpm; P=0.01). No effects were observed for placebo. Acute ingestion of CF during HD alleviated HD-induced vascular dysfunction (3.4±0.9% to 2.7±0.6% versus placebo, 3.5±0.7% to 2.0±0.6%; P<0.001). This effect was sustained throughout the study (acute on chronic, 3.9±0.9% to 3.0±0.7% versus placebo, 3.5±0.7% to 2.2±0.6; P=0.01). Dietary CF ingestion mitigates acute HD-induced and chronic endothelial dysfunction in patients with ESRD and thus, improves vascular function in this high-risk population. Larger clinical trials are warranted to test whether this translates into an improved cardiovascular prognosis in patients with ESRD. Copyright © 2016 by the American Society of Nephrology.

Use of placebo controls in the evaluation of surgery: systematic review

PubMed Central

Judge, Andrew; Hopewell, Sally; Collins, Gary S; Dean, Benjamin J F; Rombach, Ines; Brindley, David; Savulescu, Julian; Beard, David J; Carr, Andrew J

2014-01-01

Objective To investigate whether placebo controls should be used in the evaluation of surgical interventions. Design Systematic review. Data sources We searched Medline, Embase, and the Cochrane Controlled Trials Register from their inception to November 2013. Study selection Randomised clinical trials comparing any surgical intervention with placebo. Surgery was defined as any procedure that both changes the anatomy and requires a skin incision or use of endoscopic techniques. Data extraction Three reviewers (KW, BJFD, IR) independently identified the relevant trials and extracted data on study details, outcomes, and harms from included studies. Results In 39 out of 53 (74%) trials there was improvement in the placebo arm and in 27 (51%) trials the effect of placebo did not differ from that of surgery. In 26 (49%) trials, surgery was superior to placebo but the magnitude of the effect of the surgical intervention over that of the placebo was generally small. Serious adverse events were reported in the placebo arm in 18 trials (34%) and in the surgical arm in 22 trials (41.5%); in four trials authors did not specify in which arm the events occurred. However, in many studies adverse events were unrelated to the intervention or associated with the severity of the condition. The existing placebo controlled trials investigated only less invasive procedures that did not involve laparotomy, thoracotomy, craniotomy, or extensive tissue dissection. Conclusions Placebo controlled trial is a powerful, feasible way of showing the efficacy of surgical procedures. The risks of adverse effects associated with the placebo are small. In half of the studies, the results provide evidence against continued use of the investigated surgical procedures. Without well designed placebo controlled trials of surgery, ineffective treatment may continue unchallenged. PMID:24850821

The safety and efficacy of sublingual and oral immunotherapy for milk allergy.

PubMed

Keet, Corinne A; Frischmeyer-Guerrerio, Pamela A; Thyagarajan, Ananth; Schroeder, John T; Hamilton, Robert G; Boden, Stephen; Steele, Pamela; Driggers, Sarah; Burks, A Wesley; Wood, Robert A

2012-02-01

Oral immunotherapy (OIT) and sublingual immunotherapy (SLIT) are potential therapies for food allergy, but the optimal method of administration, mechanism of action, and duration of response remain unknown. We sought to explore the safety and efficacy of OIT and SLIT for the treatment of cow's milk (CM) allergy. We randomized children with CM allergy to SLIT alone or SLIT followed by OIT. After screening double-blind, placebo-controlled food challenges and initial SLIT escalation, subjects either continued SLIT escalation to 7 mg daily or began OIT to either 1000 mg (the OITB group) or 2000 mg (the OITA group) of milk protein. They were challenged with 8 g of milk protein after 12 and 60 weeks of maintenance. If they passed the 60-week challenge, therapy was withdrawn, with challenges repeated 1 and 6 weeks later. Mechanistic correlates included end point titration skin prick testing and measurement of CM-specific IgE and IgG(4) levels, basophil histamine release, constitutive CD63 expression, CD203c expression, and intracellular spleen tyrosine kinase levels. Thirty subjects with CM allergy aged 6 to 17 years were enrolled. After therapy, 1 of 10 subjects in the SLIT group, 6 of 10 subjects in the SLIT/OITB group, and 8 of 10 subjects in the OITA group passed the 8-g challenge (P = .002, SLIT vs OIT). After avoidance, 6 of 15 subjects (3 of 6 subjects in the OITB group and 3 of 8 subjects in the OITA group) regained reactivity, 2 after only 1 week. Although the overall reaction rate was similar, systemic reactions were more common during OIT than during SLIT. By the end of therapy, titrated CM skin prick test results and CD63 and CD203c expression decreased and CM-specific IgG(4) levels increased in all groups, whereas CM-specific IgE and spontaneous histamine release values decreased in only the OIT group. OIT was more efficacious for desensitization to CM than SLIT alone but was accompanied by more systemic side effects. Clinical desensitization was lost in some cases within 1 week off therapy. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Placebo - More hatred than love.

PubMed

Zhang, Hong-Liang

2011-01-01

A placebo is a sham medical intervention that can produce a placebo effect. Laboratory evidence supports the existence of several mechanisms of placebo effects in both healthy population and patients with a variety of medical conditions. The ethics of placebos have long been debated. However, accumulating ethical concern has arisen from the worldwide use of placebo in randomized control trials (RCTs), which may render their participants without early and optimal treatment. Although the pilgrimage of placebo is still on the way, refinement of controls in RCTs is worth paying new attention to.

A randomized, Phase IIb study investigating oliceridine (TRV130), a novel µ-receptor G-protein pathway selective (μ-GPS) modulator, for the management of moderate to severe acute pain following abdominoplasty.

PubMed

Singla, Neil; Minkowitz, Harold S; Soergel, David G; Burt, David A; Subach, Ruth Ann; Salamea, Monica Y; Fossler, Michael J; Skobieranda, Franck

2017-01-01

Oliceridine (TRV130), a novel μ-receptor G-protein pathway selective (μ-GPS) modulator, was designed to improve the therapeutic window of conventional opioids by activating G-protein signaling while causing low β-arrestin recruitment to the μ receptor. This randomized, double-blind, patient-controlled analgesia Phase IIb study was conducted to investigate the efficacy, safety, and tolerability of oliceridine compared with morphine and placebo in patients with moderate to severe pain following abdominoplasty (NCT02335294; oliceridine is an investigational agent not yet approved by the US Food and Drug Administration). Patients were randomized to receive postoperative regimens of intravenous oliceridine (loading/patient-controlled demand doses [mg/mg]: 1.5/0.10 [regimen A]; 1.5/0.35 [regimen B]), morphine (4.0/1.0), or placebo with treatment initiated within 4 hours of surgery and continued as needed for 24 hours. Two hundred patients were treated (n=39, n=39, n=83, and n=39 in the oliceridine regimen A, oliceridine regimen B, morphine, and placebo groups, respectively). Patients were predominantly female (n=198 [99%]) and had a mean age of 38.2 years, weight of 71.2 kg, and baseline pain score of 7.7 (on 11-point numeric pain rating scale). Patients receiving the oliceridine regimens had reductions in average pain scores (model-based change in time-weighted average versus placebo over 24 hours) of 2.3 and 2.1 points, respectively ( P =0.0001 and P =0.0005 versus placebo); patients receiving morphine had a similar reduction (2.1 points; P <0.0001 versus placebo). A lower prevalence of adverse events (AEs) related to nausea, vomiting, and respiratory function was observed with the oliceridine regimens than with morphine ( P <0.05). Other AEs with oliceridine were generally dose-related and similar in nature to those observed with conventional opioids; no serious AEs were reported with oliceridine. These results suggest that oliceridine may provide effective, rapid analgesia in patients with moderate to severe postoperative pain, with an acceptable safety/tolerability profile and potentially wider therapeutic window than morphine.

Evaluation of the efficacy of Ajuga decumbens extract supplement in individuals with knee discomfort associated with physical activity: A randomized, double-blind, placebo-controlled study

PubMed Central

Sawada, Yoko; Sugimoto, Atsushi; Hananouchi, Takehito; Sato, Norimasa; Nagaoka, Isao

2017-01-01

The aim of the present study was to assess the efficacy and safety of the oral administration of Ajuga decumbens extract (ADE) supplement to individuals with knee discomfort associated with physical activity. A randomized, double-blind, placebo-controlled study was conducted using 48 subjects. The subjects were randomly allocated to an ADE diet group (oral administration of ADE-containing diet, n=24) or a placebo group (n=24), and the intervention was conducted for 12 weeks. A total of 22 subjects in the placebo group and 22 subjects in the ADE diet group were assessed to be eligible for assessment of the efficacy of supplement. Knee function was assessed by changes in the scores of the Japanese Knee Osteoarthritis Measure (JKOM) questionnaire and the scores of the Japan Orthopedic Association (JOA) criteria, as well as by analyzing the levels of type II collagen synthesis and degradation biomarkers (procollagen II C-terminal propeptide, cross-linked C-telopeptide of type II collagen, collagen type II cleavage and matrix metalloproteinase-13). Outcomes were measured at the baseline and at 4, 8 and 12 weeks from the start of administration. Subscale II (joint flexion/stiffness) of the JOA criteria was markedly improved in the ADE diet group compared with the placebo group at 8 and 12 weeks during the intervention. Furthermore, in the subgroup analyses using subjects with mild knee discomfort, subscale II (pain/stiffness) and IV (general activities) scores of JKOM were significantly improved (P<0.05) and total JKOM score was markedly improved in the ADE diet group compared with the placebo group at week 8 of the intervention. No adverse effects were identified for the administration of ADE. In conclusion, these observations suggest that the administration of an ADE-containing diet is safe and improves joint function (flexion and stiffness) and general activity in subjects with mild knee discomfort. Therefore, ADE could be a promising candidate as a functional food that is beneficial to joint health. PMID:29109757

Preventive Effect of Korean Red Ginseng for Acute Respiratory Illness: A Randomized and Double-Blind Clinical Trial

PubMed Central

Lee, Ju-Hyung; Oh, Mira; Choi, Kyung-Min; Jeong, Mi Ran; Park, Jong-Dae; Kwon, Dae Young; Ha, Ki-Chan; Park, Eun-Ock; Lee, Nuri; Kim, Sun-Young; Choi, Eun-Kyung; Kim, Min-Gul; Chae, Soo-Wan

2012-01-01

Korean Red Ginseng (KRG) is a functional food and has been well known for keeping good health due to its anti-fatigue and immunomodulating activities. However, there is no data on Korean red ginseng for its preventive activity against acute respiratory illness (ARI). The study was conducted in a randomized, double-blinded, placebo-controlled trial in healthy volunteers (Clinical Trial Number: NCT01478009). Our primary efficacy end point was the number of ARI reported and secondary efficacy end point was severity of symptoms, number of symptoms, and duration of ARI. A total of 100 volunteers were enrolled in the study. Fewer subjects in the KRG group reported contracting at least 1 ARI than in the placebo group (12 [24.5%] vs 22 [44.9%], P = 0.034), the difference was statistically significant between the two groups. The symptom duration of the subjects who experienced the ARI, was similar between the two groups (KRG vs placebo; 5.2 ± 2.3 vs 6.3 ± 5.0, P = 0.475). The symptom scores were low tendency in KRG group (KRG vs placebo; 9.5 ± 4.5 vs 17.6 ± 23.1, P = 0.241). The study suggests that KRG may be effective in protecting subjects from contracting ARI, and may have the tendency to decrease the duration and scores of ARI symptoms. PMID:23255845

SkQ1 Ophthalmic Solution for Dry Eye Treatment: Results of a Phase 2 Safety and Efficacy Clinical Study in the Environment and During Challenge in the Controlled Adverse Environment Model.

PubMed

Petrov, Anton; Perekhvatova, Natalia; Skulachev, Maxim; Stein, Linda; Ousler, George

2016-01-01

This Phase 2 clinical trial assessed the efficacy and safety of the novel antioxidative, renewable compound SkQ1 for topical treatment of dry eye signs and symptoms. In a single-center, randomized, double-masked, placebo-controlled, 29-day study, 91 subjects with mild to moderate dry eye instilled the study drug twice daily and recorded dry eye symptoms daily. Subjects were randomized 1:1:1 into one of three ophthalmic solution treatment groups: SkQ1 1.55 µg/mL, SkQ1 0.155 µg/mL, or 0.0 µg/mL (placebo). Subjects were exposed to a controlled adverse environment chamber at 3 of the 4 study visits (Day -7, Day 1, and Day 29). Investigator assessments occurred at all study visits. SkQ1 was safe and efficacious in treating dry eye signs and symptoms. Statistically significant improvements with SkQ1 compared to placebo occurred for the dry eye signs of corneal fluorescein staining and lissamine green staining in the central region and lid margin redness, and for the dry eye symptoms of ocular discomfort, dryness, and grittiness. In addition, SkQ1 demonstrated greater efficacy compared to placebo, although the differences were not statistically significant, for corneal fluorescein staining in other regions and/or time points (total staining score, central region, corneal sum score, and temporal region), lissamine green staining for the central and nasal regions, and blink rate scores. This Phase 2 study indicated that SkQ1 is safe and efficacious for the treatment of dry eye signs and symptoms and supported previous study results. Clinicaltrials.gov identifier: NCT02121301. Miotech S.A.

The 2012 Chitranjan Ranawat award: intraarticular analgesia after TKA reduces pain: a randomized, double-blinded, placebo-controlled, prospective study.

PubMed

Goyal, Nitin; McKenzie, James; Sharkey, Peter F; Parvizi, Javad; Hozack, William J; Austin, Matthew S

2013-01-01

Postoperative pain after total knee arthroplasty remains one of the most important challenges facing patients undergoing this surgery. Providing a balance of adequate analgesia while limiting the functional impact of regional anesthesia and minimizing opioid side effects is critical to minimize adverse events and improve patient satisfaction. We asked whether bupivacaine delivered through an elastomeric device decreases the (1) patients' perception of pain after TKA; (2) narcotic consumption; and (3) narcotic-related side effects as compared with a placebo. In this prospective, double-blind, placebo-controlled study, all patients received standardized regional anesthesia, a preemptive and multimodal analgesic protocol, and a continuous intraarticular infusion at 5 mL/hour through an elastomeric infusion pump. The patients were randomized to receive either an infusion pump filled with (1) 300 mL of 0.5% bupivacaine, the experimental group (n = 75); or (2) 300 mL of 0.9% normal saline solution, the control group (n = 75). Data concerning postoperative pain levels through a visual analog scale, postoperative opioid consumption, opioid-related side effects, and complications were collected and analyzed. Patients in the experimental group receiving the bupivacaine reported a reduction in pain levels in highest, lowest, and current visual analog scale scores compared with the placebo group on the first postoperative day and highest visual analog scale score on postoperative Day 2 along with a 33% reduction in opioid consumption on postoperative Day 2 and a 54% reduction on postoperative Day 3. In patients undergoing TKA, continuous intraarticular analgesia provided an effective adjunct for pain relief in the immediate postoperative period without the disadvantages encountered with other analgesic methods.

Feeling smart: Effects of caffeine and glucose on cognition, mood and self-judgment.

PubMed

Ullrich, Susann; de Vries, Yfke C; Kühn, Simone; Repantis, Dimitris; Dresler, Martin; Ohla, Kathrin

2015-11-01

During education and early career, young adults often face examinations and assessment centers. Coffee and energy drinks are convenient and commonly used to enhance or maintain performance in these situations. Whether these macronutrients improve performance in a demanding and drawn-out multi-task situation is not clear. Using double-blind, placebo-controlled studies, we set out to examine the effects of caffeine and glucose in an assessment center-like situation, under natural consumption conditions, in a group of young adults who were heterogeneous with respect to consumption patterns. We measured multi-task performance including logical thinking, processing speed, numeric and verbal memory, attention and the ability to concentrate, and mood over a two-hour period. Caffeine and glucose were administered in common beverages with appropriate placebo controls allowing the assessment of psychological effects of expectancy. Importantly, and in contrast to most previous studies, participants retained their habitual caffeine and sugar intake (studies 1 and 2) as this represents common behavior. Based on the bulk of literature, we hypothesized that (i) caffeine enhances attentional performance and mood, while performance in more complex tasks will remain unchanged, and that (ii) glucose enhances performance on memory tasks accompanied with negative mood. Our results provide evidence that neither caffeine nor glucose significantly influence cognitive performance when compared with placebo, water, or no treatment controls in a multi-task setting. Yet, caffeine and, by trend, placebo improve dispositions such that participants perceive preserved mental energy throughout the test procedure. These subjective effects were stronger after 24 h caffeine abstinence (study 3). Future studies will have to address whether these mood changes actually result in increased motivation during a challenging task.

Studying cerebral hemodynamics and metabolism using simultaneous near-infrared spectroscopy and transcranial Doppler ultrasound: a hyperventilation and caffeine study

PubMed Central

Yang, Runze; Brugniaux, Julien; Dhaliwal, Harinder; Beaudin, Andrew E; Eliasziw, Misha; Poulin, Marc J; Dunn, Jeff F

2015-01-01

Caffeine is one of the most widely consumed psycho-stimulants in the world, yet little is known about its effects on brain oxygenation and metabolism. Using a double-blind, placebo-controlled, randomized cross-over study design, we combined transcranial Doppler ultrasound (TCD) and near-infrared spectroscopy (NIRS) to study caffeine's effect on middle cerebral artery peak blood flow velocity (Vp), brain tissue oxygenation (StO2), total hemoglobin (tHb), and cerebral oxygen metabolism (CMRO2) in five subjects. Hyperventilation-induced hypocapnia served as a control to verify the sensitivity of our measurements. During hypocapnia (∼16 mmHg below resting values), Vp decreased by 40.0 ± 2.4% (95% CI, P < 0.001), while StO2 and tHb decreased by 2.9 ± 0.3% and 2.6 ± 0.4%, respectively (P = 0.003 and P = 0.002, respectively). CMRO2, calculated using the Fick equation, was reduced by 29.3 ± 9% compared to the isocapnic-euoxia baseline (P < 0.001). In the pharmacological experiments, there was a significant decrease in Vp, StO2, and tHb after ingestion of 200 mg of caffeine compared with placebo. There was no significant difference in CMRO2 between caffeine and placebo. Both showed a CMRO2 decline compared to baseline showing the importance of a placebo control. In conclusion, this study showed that profound hypocapnia impairs cerebral oxidative metabolism. We provide new insight into the effects of caffeine on cerebral hemodynamics. Moreover, this study showed that multimodal NIRS/TCD is an excellent tool for studying brain hemodynamic responses to pharmacological interventions and physiological challenges. PMID:25907789

Nutrient and nontraditional food intakes by Zambian children in a controlled feeding trial.

PubMed

Schmaelzle, Samantha; Kaliwile, Chisela; Arscott, Sara A; Gannon, Bryan; Masi, Cassim; Tanumihardjo, Sherry A

2014-03-01

Many programs aim to alleviate vitamin A deficiency. Biofortification is an approach to improve provitamin A carotenoid concentrations of staple crops in some developing countries. In rural Zambia, maize accounts for the majority of energy intake. Provitamin A-biofortified (orange) maize has been released in Zambia. This study quantified food intake of Zambian children from records collected in a feeding trial in 2012 in order to compare adoption of orange maize and a new vegetable (green beans) with white maize and traditional foods. One hundred thirty-six children with a mean age of 71.5 +/- 6.9 months were fed three meals a day for 6 days a week for 15 weeks at four feeding centers. Breakfast consisted of maize porridge, and lunch and dinner were stiff porridge (nshima) with various side dishes (relishes). There were three treatment groups, which received orange maize and placebo oil, white maize and placebo oil, or white maize and a daily vitamin A supplement. Food was weighed before and after consumption. Nutritionists were trained to interview the children's caregivers about the previous day's intake using dietary recalls. Nine dietary recalls for each child were recorded and analyzed. Total food intake did not differ among the groups (p = .31) and energy intakes on Sundays (< or = 880 kcal) were below recommendations. Nshima intake was lower in the orange-maize group (p = .008), largely due to a genotype effect. Intakes of relish, green bean, and porridge did not differ among the groups (p > .19). Dietary recalls revealed that children living in sites closer to the main road consumed more on Sundays than children living about 8 km from the main road, but less in the evenings when children were off site. The intakes of energy of these Zambian children were low. Implementation and adoption of new and biofortified foods is possible with promotion.

Designing a definitive trial for adjuvant targeted therapy in genotype defined lung cancer: the ALCHEMIST trials.

PubMed

Alden, Ryan S; Mandrekar, Sumithra J; Oxnard, Geoffrey R

2015-09-01

Genotype-directed targeted therapies have revolutionized the treatment of metastatic non-small cell lung cancer (NSCLC) but they have not yet been comprehensively studied in the adjuvant setting. Previous trials of adjuvant targeted therapy in unselected early stage NSCLC patients showed no benefit versus placebo, however retrospective data suggests improved disease free survival (DFS) with epidermal growth factor receptor (EGFR) inhibitors in patients with appropriate molecular alterations. A definitive prospective, randomized, placebo-controlled trial of targeted therapies for NSCLC is needed to determine the efficacy of targeted therapy following surgical resection and standard adjuvant therapy. The principal challenges facing such a trial are (I) identification of actionable alterations in early stage patients; and (II) realization of sufficient enrollment to power definitive analyses. The ALCHEMIST trial (Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial) was designed to overcome these challenges. Using the national clinical trials network (NCTN) of the National Cancer Institute (NCI), several thousand patients with operable NSCLC will undergo tumor genotyping for EGFR mutations or rearrangement of anaplastic lymphoma kinase (ALK). Following resection and completion of standard adjuvant therapy, patients with EGFR-mutant NSCLC will be randomized to erlotinib versus placebo (1:1), those with ALK-rearranged NSCLC will be randomized to crizotinib versus placebo (1:1), while those not enrolled onto the adjuvant trials will continue to be followed on the screening trial. ALCHEMIST also provides for the collection of tissue at baseline and at recurrence (if available) to characterize mechanisms of recurrence and of resistance to targeted therapy. Thus, ALCHEMIST is a platform for validation of targeted therapy as part of curative care in NSCLC and creates an opportunity to advance our understanding of disease biology.

Pharmacokinetics and Safety Assessment of l-Tetrahydropalmatine in Cocaine Users: A Randomized, Double-Blind, Placebo-Controlled Study.

PubMed

Hassan, Hazem E; Kelly, Deanna; Honick, Moshe; Shukla, Sagar; Ibrahim, Ahmed; Gorelick, David A; Glassman, Matthew; McMahon, Robert P; Wehring, Heidi J; Kearns, Ann Marie; Feldman, Stephanie; Yu, Mingming; Bauer, Ken; Wang, Jia Bei

2017-02-01

Cocaine use disorder (CUD) remains a significant public health challenge. l-Tetrahydropalmatine (l-THP), a well-tolerated and nonaddictive compound, shows promise for the management of CUD. Its pharmacologic profile includes blockade at dopamine and other monoamine receptors and attenuation of cocaine self-administration, reinstatement, and rewarding properties in rats. This study evaluated the safety of l-THP in human cocaine users and its influence on the safety and pharmacokinetics (PK) of cocaine. Twenty-four cocaine-using adult men were randomized to receive l-THP (30 mg twice a day orally) or placebo double-blind for 4 days, with an intranasal cocaine (40 mg) challenge on the fourth day. Safety and tolerability were evaluated using vital signs, ECG, clinical laboratory tests, and standardized self-report instruments. Peripheral venous blood was collected periodically and later assayed for l-THP and cocaine using highly sensitive and specific ultraperformance liquid chromatography-fluorescence detection (UPLC-FLD) methods. Twenty subjects completed the study, of whom 19 provided complete PK data. The short 3.5-day course of l-THP was safe and well tolerated and did not affect cocaine's PK or its acute cardiovascular effects. The cocaine AUC 0→∞ was 211.5 and 261.4 h·ng/mL, and the C max was 83.3 and 104.5 ng/mL for the l-THP and placebo groups, respectively. In addition there were no significant differences in the number of side effects reported in each group (l-THP group 22 [48%], placebo group 24 [52%]) or vital signs including, heart rate, blood pressure, complete blood count, or ECG. These findings suggest that oral THP has promise for further development as a treatment for CUD. © 2016, The American College of Clinical Pharmacology.

Reduced neophobia: a potential mechanism explaining the emergence of self-medicative behavior in sheep.

PubMed

Egea, A Vanina; Hall, Jeffery O; Miller, James; Spackman, Casey; Villalba, Juan J

2014-08-01

Gastrointestinal helminths challenge ruminants in ways that reduce their fitness. In turn, ruminants have evolved physiological and behavioral adaptations that counteract this challenge. For instance, emerging behavioral evidence suggests that ruminants self-select medicinal compounds and foods that reduce parasitic burdens. However, the mechanism/s leading to self-medicative behaviors in sick animals is still unknown. We hypothesized that when homeostasis is disturbed by a parasitic infection, consumers should respond by increasing the acceptability of novel foods relative to healthy individuals. Three groups of lambs (N=10) were dosed with 0 (Control-C), 5000 (Medium-M) and 15000 (High-H) L3 stage larvae of Haemonchus contortus. When parasites had reached the adult stage, all animals were offered novel foods and flavors in pens and then novel forages at pasture. Ingestive responses by parasitized lambs were different from non-parasitized Control animals and they varied with the type of food and flavor on offer. Parasitized lambs consumed initially more novel beet pulp and less novel beet pulp mixed with tannins than Control lambs, but the pattern reversed after 9d of exposure to these foods. Parasitized lambs ingested more novel umami-flavored food and less novel bitter-flavored food than Control lambs. When offered choices of novel unflavored and bitter-flavored foods or different forage species to graze, parasitized lambs selected a more diverse array of foods than Control lambs. Reductions in food neophobia or selection of a more diverse diet may enhance the likelihood of sick herbivores encountering novel medicinal plants and nutritious forages that contribute to restore health. Published by Elsevier Inc.

Controlled Human Malaria Infection of Tanzanians by Intradermal Injection of Aseptic, Purified, Cryopreserved Plasmodium falciparum Sporozoites

PubMed Central

Shekalaghe, Seif; Rutaihwa, Mastidia; Billingsley, Peter F.; Chemba, Mwajuma; Daubenberger, Claudia A.; James, Eric R.; Mpina, Maximillian; Ali Juma, Omar; Schindler, Tobias; Huber, Eric; Gunasekera, Anusha; Manoj, Anita; Simon, Beatus; Saverino, Elizabeth; Church, L. W. Preston; Hermsen, Cornelus C.; Sauerwein, Robert W.; Plowe, Christopher; Venkatesan, Meera; Sasi, Philip; Lweno, Omar; Mutani, Paul; Hamad, Ali; Mohammed, Ali; Urassa, Alwisa; Mzee, Tutu; Padilla, Debbie; Ruben, Adam; Lee Sim, B. Kim; Tanner, Marcel; Abdulla, Salim; Hoffman, Stephen L.

2014-01-01

Controlled human malaria infection (CHMI) by mosquito bite has been used to assess anti-malaria interventions in > 1,500 volunteers since development of methods for infecting mosquitoes by feeding on Plasmodium falciparum (Pf) gametocyte cultures. Such CHMIs have never been used in Africa. Aseptic, purified, cryopreserved Pf sporozoites, PfSPZ Challenge, were used to infect Dutch volunteers by intradermal injection. We conducted a double-blind, placebo-controlled trial to assess safety and infectivity of PfSPZ Challenge in adult male Tanzanians. Volunteers were injected intradermally with 10,000 (N = 12) or 25,000 (N = 12) PfSPZ or normal saline (N = 6). PfSPZ Challenge was well tolerated and safe. Eleven of 12 and 10 of 11 subjects, who received 10,000 and 25,000 PfSPZ respectively, developed parasitemia. In 10,000 versus 25,000 PfSPZ groups geometric mean days from injection to Pf positivity by thick blood film was 15.4 versus 13.5 (P = 0.023). Alpha-thalassemia heterozygosity had no apparent effect on infectivity. PfSPZ Challenge was safe, well tolerated, and infectious. PMID:25070995

Motivation and placebos: do different mechanisms occur in different contexts?

PubMed

Hyland, Michael E

2011-06-27

This paper challenges the common assumption that the mechanisms underlying short-term placebo paradigms (where there is no motivation for health improvement) and long-term placebo paradigms (where patients value improvement in their health) are the same. Three types of motivational theory are reviewed: (i) classical placebo motivation theory that the placebo response results from the desire for therapeutic improvement; (ii) goal activation model that expectancy-driven placebo responses are enhanced when the placebo response satisfies an activated goal; and (iii) motivational concordance model that the placebo response is the consequence of concordance between the placebo ritual and significant intrinsic motives. It is suggested that current data are consistent with the following theory: response expectancy, conditioning and goal activation are responsible for short-term placebo effects but long-term therapeutic change is achieved through the effects of goal satisfaction and affect on the inflammatory response system and hypothalamic-pituitary-adrenal axis. Empirical predictions of this new theory are outlined, including ways in which placebo effects can be combined with other psychologically mediated effects on short-term and long-term psychological and physiological state.

Motivation and placebos: do different mechanisms occur in different contexts?

PubMed Central

Hyland, Michael E.

2011-01-01

This paper challenges the common assumption that the mechanisms underlying short-term placebo paradigms (where there is no motivation for health improvement) and long-term placebo paradigms (where patients value improvement in their health) are the same. Three types of motivational theory are reviewed: (i) classical placebo motivation theory that the placebo response results from the desire for therapeutic improvement; (ii) goal activation model that expectancy-driven placebo responses are enhanced when the placebo response satisfies an activated goal; and (iii) motivational concordance model that the placebo response is the consequence of concordance between the placebo ritual and significant intrinsic motives. It is suggested that current data are consistent with the following theory: response expectancy, conditioning and goal activation are responsible for short-term placebo effects but long-term therapeutic change is achieved through the effects of goal satisfaction and affect on the inflammatory response system and hypothalamic–pituitary–adrenal axis. Empirical predictions of this new theory are outlined, including ways in which placebo effects can be combined with other psychologically mediated effects on short-term and long-term psychological and physiological state. PMID:21576140

Assessing adherence in the CAPRISA 004 tenofovir gel HIV prevention trial: results of a nested case-control study.

PubMed

MacQueen, Kathleen M; Weaver, Mark A; van Loggerenberg, Francois; Succop, Stacey; Majola, Nelisle; Taylor, Doug; Karim, Quarraisha Abdool; Karim, Salim Abdool

2014-05-01

Adherence undeniably impacts product effectiveness in microbicide trials, but the connection has proven challenging to quantify using routinely collected behavioral data. We explored this relationship using a nested case-control study in the CAPRISA 004 Tenofovir (TFV) gel HIV prevention trial. Detailed 3-month recall data on sex events, condom and gel use were collected from 72 incident cases and 205 uninfected controls. We then assessed how the relationship between self-reported adherence and HIV acquisition differed between the TFV and placebo gel groups, an interaction effect that should exist if effectiveness increases with adherence. The CAPRISA 004 trial determined that randomization to TFV gel was associated with a significant reduction in risk of HIV acquisition. In our nested case-control study, however, we did not observe a meaningful decrease in the relative odds of infection-TFV versus placebo-as self-reported adherence increased. To the contrary, exploratory sub-group analysis of the case-control data identified greater evidence for a protective effect of TFV gel among participants reporting less than 80 % adherence to the protocol-defined regimen (odds ratio (OR) 0.30; 95 % CI 0.11-0.78) than among those reporting ≥ 80 % adherence (Odds Ratio 0.81; 95 % CI 0.34-1.92). The small number of cases may have inhibited our ability to detect the hypothesized interaction between adherence and effectiveness. Nonetheless, our results re-emphasize the challenges faced by investigators when adherence may be miss-measured, miss-reported, or confounded with the risk of HIV.

The antidepressant debate and the balanced placebo trial design: an ethical analysis.

PubMed

Waring, Duff R

2008-12-01

There is ongoing debate about whether randomized, placebo-controlled trials under a double-blind have reliably established the pharmacological efficacy of antidepressants. Numerous meta-analyses of antidepressant efficacy trials, e.g., Kirsch et al. [Kirsch, I., Moore, T. J., Scoboria, A., & Nicholls, S. (2002). The emperor's new drugs: An analysis of antidepressant medication data submitted to the U.S. food and drug administration. Prevention and Treatment, 5, Article 23. (Retrieved July 19, 2007 from http://journals.apa.org/prevention/volume5)], have shown a modest drug-placebo difference but methodological problems with standard trial design preclude a definitive conclusion that this difference results from specific biological effects of antidepressants or the nonspecific factors that have not been adequately excluded. Standard trial design assumes the additivity thesis of pharmacological efficacy, being the assumption that the specific or "true" magnitude of the pharmacological effect is limited to the difference between the drug and placebo responses in a standard trial. If the drug effects are as small as these meta-analyses suggest, then their clinical effectiveness is questionable. If the drug effects are actually larger but masked by placebo effects, then the additivity thesis is not valid and we risk false negative results with standard trial design. Kirsch et al. propose an alternative, four arm balanced placebo trial design (BPTD) that can accurately test the additivity thesis. The BPTD uses antidepressants, active placebos and the intentional deception of research subjects. My focal question is whether the BPTD is ethically defensible. I will explore two objections that can be raised against it: 1) lying to BPTD research subjects violates their autonomy and exploits their illness and 2) the BPTD may not enable us to test the additivity thesis with accuracy, i.e., it may contribute to the masking of drug effects that it aims to avoid. I argue that these objections support the conclusion that the BPTD is ethically indefensible.

Dangshen (Codonopsis pilosula) and Bai guo (Gingko biloba) enhance learning and memory.

PubMed

Singh, Betsy; Song, Howin; Liu, Xiao-Dong; Hardy, Mary; Liu, Gan-Zhong; Vinjamury, Sivarama P; Martirosian, Claudia Der

2004-01-01

An exploration of the usefulness of several common Chinese herbs used for Acquisition and Retention singly or in combination is required. To test (1) whether Gingko biloba (Bai guo) in combination with Codonopsis pilosula (Dangshen) or Gingko biloba (GB) alone could enhance memory acquisition and retention of normal human subjects, better than a placebo and (2) to investigate whether the overall health status can be affected by these supplements. A double blind randomized placebo controlled trial design was used to determine the efficacy of these two products compared to placebo. Sixty participants, aged 21- 60 years, who were either students or faculty of the Southern California University of Health Sciences. Each combination capsule was made up of 75mg of Codonopsis pilosula total glycosides and 40mg GB extract. Each GB capsule consisted of 40mg of Gingko biloba as an aqueous extract and. The placebo pill was similar in shape and color to that of the other two capsules. All the participants regardless of the group were instructed to take one pill twice a day with food. The primary outcome measure was a computerized, standardized acquisition and retention test provided by Digital Acumen, Inc. The secondary outcome measures were the SF-12 and the Medical Symptom Questionnaire ( 1997 healthcomm International, Inc. And Immuno Laboratories, Inc.) Mean age was 28 years; almost two thirds of the sample were males. The study adopted repeated measure analysis using data from three measurement points for between group analysis. GB group was compared to placebo, and CPG/GB group was also compared to placebo. These individual comparisons were made to determine whether the active products produced better results than chance. The between groups findings indicate that both products are better than placebo at producing improvements in acquisition and retention and overall health status. In our participant population, the combination product seems to be better than GB alone in improving the cognitive function and overall health.

The ethics of placebo-controlled trials: methodological justifications.

PubMed

Millum, Joseph; Grady, Christine

2013-11-01

The use of placebo controls in clinical trials remains controversial. Ethical analysis and international ethical guidance permit the use of placebo controls in randomized trials when scientifically indicated in four cases: (1) when there is no proven effective treatment for the condition under study; (2) when withholding treatment poses negligible risks to participants; (3) when there are compelling methodological reasons for using placebo, and withholding treatment does not pose a risk of serious harm to participants; and, more controversially, (4) when there are compelling methodological reasons for using placebo, and the research is intended to develop interventions that can be implemented in the population from which trial participants are drawn, and the trial does not require participants to forgo treatment they would otherwise receive. The concept of methodological reasons is essential to assessing the ethics of placebo controls in these controversial last two cases. This article sets out key considerations relevant to considering whether methodological reasons for a placebo control are compelling. © 2013.

Opiate-sensitivity: clinical characteristics and the role of skin prick testing.

PubMed

Nasser, S M; Ewan, P W

2001-07-01

The value of skin prick testing in opiate-sensitive individuals is uncertain as opiates cause non-specific weals by direct degranulation of mast cells. To define whether skin prick test (SPT) responses to opiates in opiate-sensitive individuals are different to those seen in the normal population and to describe the clinical characteristics of this group of subjects. The SPT responses of eight opiate-sensitive subjects to morphine 10 mg/mL, pethidine (meperidine) 50 mg/mL and papaveretum 15.4 mg/mL at four different concentrations (undiluted, 1/10, 1/50 and 1/100) were compared with the responses of 100 (32 atopic) non-opiate-sensitive control subjects. Four of the opiate-sensitive subjects had a clinical history of asthma, rhinitis or urticaria on occupational exposure to morphine. One subject developed urticaria with codeine, one developed urticaria and asthma with morphine and diamorphine and two subjects reacted to intravenous papaveretum with anaphylaxis or urticaria. Five out of the eight cases had opiate sensitivity confirmed by single-blind placebo-controlled oral challenge. Skin prick tests to all three opiates were not significantly different when the eight opiate-sensitive subjects were compared with either the entire normal control group or the subgroup of 47 definite opiate-tolerant controls that had previously received opiates for clinical indications. Furthermore, there were no significant differences in size of opiate SPT responses between atopic and non-atopic control subjects. In the control subjects, there was a positive correlation in SPT weal size between the three opiates. Skin prick testing is not useful in the diagnosis of opiate sensitivity and placebo-controlled challenge should be considered.

Eotaxin, but not IL-8, is increased in upper and lower airways of allergic rhinitis subjects after nasal allergen challenge.

PubMed

Semik-Orzech, Aleksandra; Barczyk, Adam; Wiaderkiewicz, Ryszard; Pierzchała, Władysław

2011-01-01

The aim of this study was to assess the impact of a single nasal allergen challenge (NAC) on levels of eotaxin and IL-8 and the inflammatory cells in upper and lower airways of allergic rhinitis (AR) patients. Twenty-four AR patients and 12 control subjects entered a sequential nasal placebo challenge and NAC study, out of the pollen season. Nasal lavage fluid (NLF) was obtained at baseline, 15 minutes, and 1, 5, and 24 hours postchallenge. Before and 24 hours after placebo/allergen challenge induced sputum was performed. NLF and induced sputum were evaluated for total cell count (TCC) and differential cell count and analyzed for concentrations of eotaxin and IL-8 using ELISA method. NAC in AR subjects was associated with significantly increased sputum (p = 0.008) and NLF (p < 0.001) eotaxin levels. Post-NAC IL-8 levels were significantly increased in NLF (p < 00001) but not in sputum (p = 0.080) of AR subjects. Increased eotaxin levels in NLF positively correlated with the increased TCC and eosinophils. Positive correlations were also found between NLF increased eotaxin level and sputum TCC, eosinophils, and macrophages. NAC is associated with the increased levels of eotaxin in lower airways of AR subjects. Allergen-induced secretion of eotaxin in nasal mucosa of AR subjects is involved in determining the cellular character of both upper and lower airway inflammation.

Effect of Baseline Nutritional Status on Long-term Multivitamin Use and Cardiovascular Disease Risk

PubMed Central

Rautiainen, Susanne; Gaziano, J. Michael; Christen, William G.; Bubes, Vadim; Kotler, Gregory; Glynn, Robert J.; Manson, JoAnn E.; Buring, Julie E.

2017-01-01

Importance Long-term multivitamin use had no effect on risk of cardiovascular disease (CVD) in the Physicians’ Health Study II. Baseline nutritional status may have modified the lack of effect. Objective To investigate effect modification by various baseline dietary factors on CVD risk in the Physicians’ Health Study II. Design, Setting, and Participants The Physicians’ Health Study II was a randomized, double-blind, placebo-controlled trial testing multivitamin use (multivitamin [Centrum Silver] or placebo daily) among US male physicians. The Physicians’ Health Study II included 14 641 male physicians 50 years or older, 13 316 of whom (91.0%) completed a baseline 116-item semiquantitative food frequency questionnaire and were included in the analyses. This study examined effect modification by baseline intake of key foods, individual nutrients, dietary patterns (Alternate Healthy Eating Index and Alternate Mediterranean Diet Score), and dietary supplement use. The study began in 1997, with continued treatment and follow-up through June 1, 2011. Interventions Multivitamin or placebo daily. Main Outcomes and Measures Major cardiovascular events, including nonfatal myocardial infarction, nonfatal stroke, and CVD mortality. Secondary outcomes included myocardial infarction, total stroke, CVD mortality, and total mortality individually. Results In total, 13 316 male physicians (mean [SD] age at randomization, 64.0 [9.0] years in those receiving the active multivitamin and 64.0 [9.1] years in those receiving the placebo) were observed for a mean (SD) follow-up of 11.4 (2.3) years. There was no consistent evidence of effect modification by various foods, nutrients, dietary patterns, or baseline supplement use on the effect of multivitamin use on CVD end points. Statistically significant interaction effects were observed between multivitamin use and vitamin B6 intake on myocardial infarction, between multivitamin use and vitamin D intake on CVD mortality, and between multivitamin use and vitamin B12 intake on CVD mortality and total mortality. However, there were inconsistent patterns in hazard ratios across tertiles of each dietary factor that are likely explained by multiple testing. Conclusions and Relevance The results suggest that baseline nutritional status does not influence the effect of randomized long-term multivitamin use on major CVD events. Future studies are needed to investigate the role of baseline nutritional biomarkers on the effect of multivitamin use on CVD and other outcomes. Trial Registration clinicaltrials.gov Identifier: NCT00270647 PMID:28384735

Meta-analysis of suicidality in placebo-controlled clinical trials of adults taking bupropion.

PubMed

Wightman, Donna S; Foster, Vicki J; Krishen, Alok; Richard, Nathalie E; Modell, Jack G

2010-01-01

To assess a possible relationship between treatment with bupropion (vs placebo) and expressed suicidal ideation and behavior. This analysis, based on the US Food and Drug Administration's (FDA's) analysis of antidepressant suicidality data, included 8,953 adult subjects receiving bupropion and 6,520 adult subjects receiving placebo from randomized, placebo-controlled trials with bupropion conducted between 1976 and 2006 across multiple indications, including major depressive disorder (MDD). A text string search of the adverse event database and case report form comments was performed to identify potential suicidal events. FDA search criteria included the following text strings: accident-, injur-, suic-, or overdos-, including all events coded as accidental overdose, attempt, cut, gas, hang, hung, jump, mutilat-, self damag-, self harm, self inflict-, shoot, slash, poison, asphyxiation, suffocation, firearm, burn, drown, gun, immolat-, and monoxide, and the following terms were added by GlaxoSmithKline to the search criteria: accident, lacerat-, MVA, and hospital. The database search included data beginning from the first dose of study medication through 1 day following the last dose. Suicidal event narratives were classified using the Columbia Classification Algorithm for Suicide Assessment. Additionally, changes on rating scale items for depressed mood and suicidality were analyzed. In the MDD population, the incidence of suicidal behavior or ideation was 17/3,179 (0.53%) versus 11/2,310 (0.48%) for the bupropion and placebo groups, respectively (OR = 1.28; 95% CI, 0.59-2.86). For suicidal behavior, the incidence was 8/3,179 (0.25%) versus 2/2,310 (0.09%), respectively (OR = 3.52; 95% CI, 0.81-24.48). No suicidal behavior event was noted in the other indications, and no completed suicides were reported during treatment. No significant worsening was observed for bupropion relative to placebo on the rating scale items. No differential treatment effects were observed by gender or age; regardless of treatment, however, the 18- to 24-year-old group had the greatest odds of having a suicide event. Although no statistically significant differences were observed between bupropion and placebo in expressed suicidal ideation or behavior, we believe that all patients treated with antidepressants should receive careful monitoring for clinical worsening, suicidality, or unusual changes in behavior.

Blood cells transcriptomics as source of potential biomarkers of articular health improvement: effects of oral intake of a rooster combs extract rich in hyaluronic acid.

PubMed

Sánchez, Juana; Bonet, M Luisa; Keijer, Jaap; van Schothorst, Evert M; Mölller, Ingrid; Chetrit, Carles; Martinez-Puig, Daniel; Palou, Andreu

2014-09-01

The aim of the study was to explore peripheral blood gene expression as a source of biomarkers of joint health improvement related to glycosaminoglycan (GAG) intake in humans. Healthy individuals with joint discomfort were enrolled in a randomized, double-blind, placebo-controlled intervention study in humans. Subjects ate control yoghurt or yoghurt supplemented with a recently authorized novel food in Europe containing hyaluronic acid (65 %) from rooster comb (Mobilee™ as commercial name) for 90 days. Effects on functional quality-of-life parameters related to joint health were assessed. Whole-genome microarray analysis of peripheral blood samples from a subset of 20 subjects (10 placebo and 10 supplemented) collected pre- and post-intervention was performed. Mobilee™ supplementation reduced articular pain intensity and synovial effusion and improved knee muscular strength indicators as compared to placebo. About 157 coding genes were differentially expressed in blood cells between supplemented and placebo groups post-intervention, but not pre-intervention (p < 0.05; fold change ≥1.2). Among them, a reduced gene expression of glucuronidase-beta (GUSB), matrix metallopeptidase 23B (MMP23B), xylosyltransferase II (XYLT2), and heparan sulfate 6-O-sulfotransferase 1 (HS6ST1) was found in the supplemented group. Correlation analysis indicated a direct relationship between blood cell gene expression of MMP23B, involved in the breakdown of the extracellular matrix, and pain intensity, and an inverse relationship between blood cell gene expression of HS6ST1, responsible for 6-O-sulfation of heparan sulfate, and indicators of knee muscular strength. Expression levels of specific genes in blood cells, in particular genes related to GAG metabolism and extracellular matrix dynamics, are potential biomarkers of beneficial effects on articular health.

The study to investigate the potential benefits of probiotics in yogurt, a patient-oriented, double-blind, cluster-randomised, placebo-controlled, clinical trial.

PubMed

Merenstein, D J; Smith, K H; Scriven, M; Roberts, R F; Sanders, M E; Petterson, S

2010-07-01

Probiotic functional foods are widely advertised to consumers primarily based on probiotic supplements. Determine if consumption of yogurt containing a high dose of probiotics improves health in children ages 1-3 years attending daycare/school centers. Double-blinded, randomized, placebo-controlled, allocation concealment clinical trial. Outpatient participants in the Washington, DC area. 182 healthy children between the age of 1 and 3 years attending daycare/school at least 3 days a week. Active was a strawberry yogurt-based drink supplemented with Bifidobacterium animalis ssp. lactis (B. lactis) BB-12. The placebo was indistinguishable from the active drink, differing only in absence of the probiotic BB-12. Primary objective was to determine if consumption of a probiotic-containing yogurt-based drink decreases absences due to illnesses from daycare for children ages 1-3 years. Secondary was to determine if probiotic-containing yogurt-based drink improves overall parental satisfaction due to decreased absences from work and an overall healthier child. There were no significant differences in the days of missed school per group, with 51.9% in the active group and 47.1% in the placebo group missing at least 1 day of school throughout the study. Additionally, there were no differences in any secondary outcomes among the groups. Consumption of a yogurt-based drink delivering 10(10) CFU of Bifidobacterium animalis ssp. lactis (B. lactis) BB-12 per day did not decrease the number of days missed of school due to an illness. Additional independent research on the potential of BB-12 to reduce illness in children needs to be conducted.

Pilot, double-blind, randomized, placebo-controlled clinical trial of the supplement food Nyaditum resae® in adults with or without latent TB infection: Safety and immunogenicity

PubMed Central

Montané, Eva; Barriocanal, Ana Maria; Arellano, Ana Lucía; Valderrama, Angelica; Sanz, Yolanda; Perez-Alvarez, Nuria; Cardona, Paula; Vilaplana, Cristina

2017-01-01

Background Nyaditum resae® (NR) is a galenic preparation of heat-killed Mycobacterium manresensis, a new species of the fortuitum complex, that is found in drinkable water, and that has demonstrated to protect against the development of active TB in a murine experimental model that develop human-like lesions. Methods Double-blind, randomized, placebo-controlled Clinical Trial (51 volunteers included). Two different doses of NR and a placebo were tested, the randomization was stratified by Latent Tuberculosis Infection (LTBI)-positive (n = 21) and LTBI-negative subjects (n = 30). Each subject received 14 drinkable daily doses for 2 weeks. Results All patients completed the study. The 46.3% of the overall reported adverse events (AE) were considered related to the investigational treatment. None of them were severe (94% were mild and 6% moderate). No statistical differences were found when comparing the median number of AE between the placebo group and both treatment groups. The most common AE reported were gastrointestinal events, most frequently mild abdominal pain and increase in stool frequency. Regarding the immunogenic response, both LTBI-negative and LTBI-positive volunteers treated with NR experienced a global increase on the Treg response, showed both in the population of CD25+CD39-, mainly effector Treg cells, or CD25+CD39+ memory PPD-specific Treg cells. Conclusion This clinical trial demonstrates an excellent tolerability profile of NR linked to a significant increase in the population of specific effector and memory Tregs in the groups treated with NR in both LTBI-positive and negative subjects. NR shows a promising profile to be used to reduce the risk of active TB. PMID:28182700

Pilot, double-blind, randomized, placebo-controlled clinical trial of the supplement food Nyaditum resae® in adults with or without latent TB infection: Safety and immunogenicity.

PubMed

Montané, Eva; Barriocanal, Ana Maria; Arellano, Ana Lucía; Valderrama, Angelica; Sanz, Yolanda; Perez-Alvarez, Nuria; Cardona, Paula; Vilaplana, Cristina; Cardona, Pere-Joan

2017-01-01

Nyaditum resae® (NR) is a galenic preparation of heat-killed Mycobacterium manresensis, a new species of the fortuitum complex, that is found in drinkable water, and that has demonstrated to protect against the development of active TB in a murine experimental model that develop human-like lesions. Double-blind, randomized, placebo-controlled Clinical Trial (51 volunteers included). Two different doses of NR and a placebo were tested, the randomization was stratified by Latent Tuberculosis Infection (LTBI)-positive (n = 21) and LTBI-negative subjects (n = 30). Each subject received 14 drinkable daily doses for 2 weeks. All patients completed the study. The 46.3% of the overall reported adverse events (AE) were considered related to the investigational treatment. None of them were severe (94% were mild and 6% moderate). No statistical differences were found when comparing the median number of AE between the placebo group and both treatment groups. The most common AE reported were gastrointestinal events, most frequently mild abdominal pain and increase in stool frequency. Regarding the immunogenic response, both LTBI-negative and LTBI-positive volunteers treated with NR experienced a global increase on the Treg response, showed both in the population of CD25+CD39-, mainly effector Treg cells, or CD25+CD39+ memory PPD-specific Treg cells. This clinical trial demonstrates an excellent tolerability profile of NR linked to a significant increase in the population of specific effector and memory Tregs in the groups treated with NR in both LTBI-positive and negative subjects. NR shows a promising profile to be used to reduce the risk of active TB.

Challenges in obesity research.

PubMed

Palou, Andreu; Bonet, M Luisa

2013-09-01

Obesity is the main nutritional problem and one of the most important health problems in developed societies. Central to the challenge of obesity prevention and management is a thoroughly understanding of its determinants. Multiple socio-cultural, socio-economic, behavioural and biological factors--often interrelated and many of them still unknown or poorly understood--can contribute to the establishment and perpetuation of obese phenotypes. Here, we address current research challenges regarding basic aspects of obesity and emerging science for its control, including brown adipose tissue thermogenesis and browning of white fat as possible therapeutic targets for obesity, the influence of the microbioma, and genetics, epigenetics, nutrigenomics and nutrigenetics of obesity. We also highlight hot topics in relation to food and lifestyle as determinants of obesity, including the brain mechanisms underlying environmental motivation to eat, the biological control of spontaneous physical activity, the possible role of concrete foods and food components, and the importance of early life nutrition and environment. Challenges regarding the connections of obesity with other alterations and pathologies are also briefly addressed, as well as social and economical challenges in relation to healthy food production and lifestyle for the prevention of obesity, and technological challenges in obesity research and management. The objective is to give a panoramic of advances accomplished and still ahead relevant to the different stakeholders engaged in understanding and combating obesity. Copyright © AULA MEDICA EDICIONES 2013. Published by AULA MEDICA. All rights reserved.

Pressor response to intravenous tyramine in healthy subjects after safinamide, a novel neuroprotectant with selective, reversible monoamine oxidase B inhibition.

PubMed

Cattaneo, Carlo; Caccia, Carla; Marzo, Antonio; Maj, Roberto; Fariello, Ruggero G

2003-01-01

Safinamide is a novel neuroprotectant combining sodium and calcium channel blocking properties with selective, reversible monoamine oxidase type B (MAO B) inhibition. Phase 1 studies have demonstrated that in healthy volunteers, the ED50 (a dose that inhibits enzyme activity by 50% in 50% of treated subjects) for MAO B inhibition is 87.5 microg/kg/day orally, and that no MAO A inhibition occurs after 10-mg/kg oral dosing. To assess the risk of inducing the "cheese effect," the effect of safinamide and placebo on the pressor response to tyramine was investigated in a group of healthy male volunteers. The study was an open, single-dose placebo-controlled trial with the 2 treatments in sequence. An increase of 30 mm Hg systolic blood pressure was obtained by intravenous tyramine administered by 0.5-mg incremental boluses injected at 15-minute intervals. The amount of tyramine necessary to achieve such a blood pressure increase was the same after the safinamide 2-mg/kg oral load compared with placebo. These results suggest that dietary restrictions for food with high tyramine content should not be required under safinamide treatment.

Intravenous Acetaminophen in Multimodal Pain Management for Patients Undergoing Total Knee Arthroplasty: A Randomized, Double-Blind, Placebo-Controlled Trial.

PubMed

Murata-Ooiwa, Minako; Tsukada, Sachiyuki; Wakui, Motohiro

2017-10-01

Although multimodal pain management including periarticular multidrug injection can provide excellent pain relief in the early postoperative period after total knee arthroplasty (TKA), rebounding pain remains an important challenge. A randomized, double-blind, placebo-controlled trial was performed to investigate the efficacy of adding intravenous acetaminophen to multimodal pain management for TKA. We enrolled 67 patients scheduled for unilateral TKA. Patients were randomly assigned to receive either 1000 mg of intravenous acetaminophen at 6-hour intervals or normal saline at the same intervals. All patients were treated with intraoperative periarticular multidrug injection and intravenous and oral nonsteroidal anti-inflammatory drugs. The primary outcome was the postoperative 100-mm visual analog pain scale at the time of administration of study drugs. In the intention-to-treat analysis, the pain score was significantly better in the intravenous acetaminophen group than the placebo group at 17:00 one day after TKA (15.3 ± 17.0 mm vs 26.8 ± 19.0 mm; P = .013). There were no significant differences in terms of the rate of complications between groups. Even in the setting of multimodal pain management including periarticular multidrug injection, intravenous acetaminophen provided better pain relief for patients undergoing unilateral TKA. Copyright © 2017 Elsevier Inc. All rights reserved.

Adjunctive Use of Olanzapine in the Treatment of Avoidant Restrictive Food Intake Disorder in Children and Adolescents in an Eating Disorders Program.

PubMed

Brewerton, Timothy D; D'Agostino, Meredith

2017-12-01

There is little information about the pharmacological treatment of avoidant and restrictive food intake disorder (ARFID), a challenging feeding disorder associated with marked impairment and developmental arrest. This brief clinical report seeks to fill this gap. A retrospective chart review of nine patients with ARFID treated in an eating disorder (ED) program (residential, partial hospital, and intensive outpatient levels of care) with adjunctive olanzapine was undertaken. The mean initial and final olanzapine doses were 0.9 + 0.63 mg/day and 2.8 + 1.47 mg/day, respectively. There was a statistically significant difference in weight gain pre- versus post-olanzapine treatment (3.3 ± 7.3 lbs vs. 13.1 ± 7.9 lbs [2.99 ± 6.62 lb SI vs. 11.88 ± 7.17 lb SI], paired t-test (p < 0.04, t = -2.48). Clinically, adjunctive olanzapine was helpful for not only weight gain but also reduction of associated anxious, depressive, and cognitive symptoms. Clinical Global Impressions scale scores indicated marked improvement in patients receiving adjunctive olanzapine. These cases illustrate that judicious use of low-dose olanzapine, when used as an adjunct to other treatment modalities, may facilitate eating, weight gain, and the reduction of anxious, depressive, and cognitive symptoms in ARFID patients. Future randomized, placebo-controlled studies in ARFID are warranted.

Activated leucocyte cell adhesion molecule (ALCAM/CD166) regulates T cell responses in a murine model of food allergy.

PubMed

Kim, Y S; Kim, M N; Lee, K E; Hong, J Y; Oh, M S; Kim, S Y; Kim, K W; Sohn, M H

2018-05-01

Food allergy is a major public health problem. Studies have shown that long-term interactions between activated leucocyte cell adhesion molecule (ALCAM/CD166) on the surface of antigen-presenting cells, and CD6, a co-stimulatory molecule, influence immune responses. However, there are currently no studies on the functions of ALCAM in food allergy. Therefore, we aimed to identify the functions of ALCAM in ovalbumin (OVA)-induced food allergy using ALCAM-deficient mice. Wild-type (WT) and ALCAM-deficient (ALCAM -/- ) mice were sensitized intraperitoneally and with orally fed OVA. The mice were killed, and parameters related to food allergy and T helper type 2 (Th2) immune responses were analysed. ALCAM serum levels increased and mRNA expression decreased in OVA-challenged WT mice. Serum immunoglobulin (Ig)E levels, Th2 cytokine mRNA and histological injuries were higher in OVA-challenged WT mice than in control mice, and these were attenuated in ALCAM -/- mice. T cell proliferation of total cells, CD3 + CD4 + T cells and activated T cells in immune tissues were diminished in OVA-challenged ALCAM -/- mice. Proliferation of co-cultured T cells and dendritic cells (DCs) was decreased by the anti-CD6 antibody. In addition, WT mice sensitized by adoptive transfer of OVA-pulsed ALCAM -/- BM-derived DCs showed reduced immune responses. Lastly, serum ALCAM levels were higher in children with food allergy than in control subjects. In this study, serum levels of ALCAM were elevated in food allergy-induced WT mice and children with food allergy. Moreover, immune responses and T cell activation were attenuated in OVA-challenged ALCAM -/- mice. These results indicate that ALCAM regulates food allergy by affecting T cell activation. © 2018 British Society for Immunology.

The motilin agonist erythromycin increases hunger by modulating homeostatic and hedonic brain circuits in healthy women: a randomized, placebo-controlled study.

PubMed

Zhao, Dongxing; Meyer-Gerspach, Anne Christin; Deloose, Eveline; Iven, Julie; Weltens, Nathalie; Depoortere, Inge; O'daly, Owen; Tack, Jan; Van Oudenhove, Lukas

2018-01-29

The motilin agonist, erythromycin, induces gastric phase III of the migrating motor complex, which in turn generates hunger peaks. To identify the brain mechanisms underlying these orexigenic effects, 14 healthy women participated in a randomized, placebo-controlled crossover study. Functional magnetic resonance brain images were acquired for 50 minutes interprandially. Intravenous infusion of erythromycin (40 mg) or saline started 10 minutes after the start of scanning. Blood samples (for glucose and hormone levels) and hunger ratings were collected at fixed timepoints. Thirteen volunteers completed the study, without any adverse events. Brain regions involved in homeostatic and hedonic control of appetite and food intake responded to erythromycin, including pregenual anterior cingulate cortex, anterior insula cortex, orbitofrontal cortex, amygdala, caudate, pallidum and putamen bilaterally, right accumbens, hypothalamus, and midbrain. Octanoylated ghrelin levels decreased, whereas both glucose and insulin increased after erythromycin. Hunger were higher after erythromycin, and these differences covaried with the brain response in most of the abovementioned regions. The motilin agonist erythromycin increases hunger by modulating neurocircuitry related to homeostatic and hedonic control of appetite and feeding. These results confirm recent behavioural findings identifying motilin as a key orexigenic hormone in humans, and identify the brain mechanisms underlying its effect.

Multicenter, placebo-controlled trial of lorcaserin for weight management.

PubMed

Smith, Steven R; Weissman, Neil J; Anderson, Christen M; Sanchez, Matilde; Chuang, Emil; Stubbe, Scott; Bays, Harold; Shanahan, William R

2010-07-15

Lorcaserin is a selective serotonin 2C receptor agonist that could be useful in reducing body weight. In this double-blind clinical trial, we randomly assigned 3182 obese or overweight adults (mean body-mass index [the weight in kilograms divided by the square of the height in meters] of 36.2) to receive lorcaserin at a dose of 10 mg, or placebo, twice daily for 52 weeks. All patients also underwent diet and exercise counseling. At week 52, patients in the placebo group continued to receive placebo but patients in the lorcaserin group were randomly reassigned to receive either placebo or lorcaserin. Primary outcomes were weight loss at 1 year and maintenance of weight loss at 2 years. Serial echocardiography was used to identify patients in whom valvulopathy (as defined by the Food and Drug Administration) developed. At 1 year, 55.4% of patients (883 of 1595) receiving lorcaserin and 45.1% of patients (716 of 1587) receiving placebo remained in the trial; 1553 patients continued into year 2. At 1 year, 47.5% of patients in the lorcaserin group and 20.3% in the placebo group had lost 5% or more of their body weight (P<0.001), corresponding to an average loss of 5.8+/-0.2 kg with lorcaserin and 2.2+/-0.1 kg with placebo during year 1 (P<0.001). Among the patients who received lorcaserin during year 1 and who had lost 5% or more of their baseline weight at 1 year, the loss was maintained in more patients who continued to receive lorcaserin during year 2 (67.9%) than in patients who received placebo during year 2 (50.3%, P<0.001). Among 2472 patients evaluated at 1 year and 1127 evaluated at 2 years, the rate of cardiac valvulopathy was not increased with the use of lorcaserin. Among the most frequent adverse events reported with lorcaserin were headache, dizziness, and nausea. The rates of serious adverse events in the two groups were similar. In conjunction with behavioral modification, lorcaserin was associated with significant weight loss and improved maintenance of weight loss, as compared with placebo. (Funded by Arena Pharmaceuticals; ClinicalTrials.gov number, NCT00395135.) 2010 Massachusetts Medical Society

Effects of vitamin D2-fortified bread v. supplementation with vitamin D2 or D3 on serum 25-hydroxyvitamin D metabolites: an 8-week randomised-controlled trial in young adult Finnish women.

PubMed

Itkonen, Suvi T; Skaffari, Essi; Saaristo, Pilvi; Saarnio, Elisa M; Erkkola, Maijaliisa; Jakobsen, Jette; Cashman, Kevin D; Lamberg-Allardt, Christel

2016-04-14

There is a need for food-based solutions for preventing vitamin D deficiency. Vitamin D3 (D3) is mainly used in fortified food products, although the production of vitamin D2 (D2) is more cost-effective, and thus may hold opportunities. We investigated the bioavailability of D2 from UV-irradiated yeast present in bread in an 8-week randomised-controlled trial in healthy 20-37-year-old women (n 33) in Helsinki (60°N) during winter (February-April) 2014. Four study groups were given different study products (placebo pill and regular bread=0 µg D2 or D3/d; D2 supplement and regular bread=25 µg D2/d; D3 supplement and regular bread=25 µg D3/d; and placebo pill and D2-biofortified bread=25 µg D2/d). Serum 25-hydroxyvitamin D2 (S-25(OH)D2) and serum 25-hydroxyvitamin D3 (S-25(OH)D3) concentrations were measured at baseline, midpoint and end point. The mean baseline total serum 25-hydroxyvitamin D (S-25(OH)D=S-25(OH)D2+S-25(OH)D3) concentration was 65·1 nmol/l. In repeated-measures ANCOVA (adjusted for baseline S-25(OH)D as total/D2/D3), D2-bread did not affect total S-25(OH)D (P=0·707) or S-25(OH)D3 (P=0·490), but increased S-25(OH)D2 compared with placebo (P<0·001). However, the D2 supplement was more effective than bread in increasing S-25(OH)D2 (P<0·001). Both D2 and D3 supplementation increased total S-25(OH)D compared with placebo (P=0·030 and P=0·001, respectively), but D2 supplementation resulted in lower S-25(OH)D3 (P<0·001). Thus, D2 from UV-irradiated yeast in bread was not bioavailable in humans. Our results support the evidence that D2 is less potent in increasing total S-25(OH)D concentrations than D3, also indicating a decrease in the percentage contribution of S-25(OH)D3 to the total vitamin D pool.

Effect of supplementation during pregnancy with L-arginine and antioxidant vitamins in medical food on pre-eclampsia in high risk population: randomised controlled trial

PubMed Central

Perichart-Perera, Otilia; Espino, Salvador; Avila-Vergara, Marco Antonio; Ibarra, Isabel; Ahued, Roberto; Godines, Myrna; Parry, Samuel; Macones, George; Strauss, Jerome F

2011-01-01

Objective To test the hypothesis that a relative deficiency in L-arginine, the substrate for synthesis of the vasodilatory gas nitric oxide, may be associated with the development of pre-eclampsia in a population at high risk. Design Randomised, blinded, placebo controlled clinical trial. Setting Tertiary public hospital in Mexico City. Participants Pregnant women with a history of a previous pregnancy complicated by pre-eclampsia, or pre-eclampsia in a first degree relative, and deemed to be at increased risk of recurrence of the disease were studied from week 14-32 of gestation and followed until delivery. Interventions Supplementation with a medical food—bars containing L-arginine plus antioxidant vitamins, antioxidant vitamins alone, or placebo—during pregnancy. Main outcome measure Development of pre-eclampsia/eclampsia. Results 222 women were allocated to the placebo group, 228 received L-arginine plus antioxidant vitamins, and 222 received antioxidant vitamins alone. Women had 4-8 prenatal visits while receiving the bars. The incidence of pre-eclampsia was reduced significantly (χ2=19.41; P<0.001) in women randomised to L-arginine plus antioxidant vitamins compared with placebo (absolute risk reduction 0.17 (95% confidence interval 0.12 to 0.21). Antioxidant vitamins alone showed an observed benefit, but this effect was not statistically significant compared with placebo (χ2=3.76; P=0.052; absolute risk reduction 0.07, 0.005 to 0.15). L-arginine plus antioxidant vitamins compared with antioxidant vitamins alone resulted in a significant effect (P=0.004; absolute risk reduction 0.09, 0.05 to 0.14). Conclusions Supplementation during pregnancy with a medical food containing L-arginine and antioxidant vitamins reduced the incidence of pre-eclampsia in a population at high risk of the condition. Antioxidant vitamins alone did not have a protective effect for prevention of pre-eclampsia. Supplementation with L-arginine plus antioxidant vitamins needs to be evaluated in a low risk population to determine the generalisability of the protective effect, and the relative contributions of L-arginine and antioxidant vitamins to the observed effects of the combined treatment need to be determined. Trial registration Clinical trials NCT00469846. PMID:21596735

Impact of Multi-Micronutrient Fortified Rice on Hemoglobin, Iron and Vitamin A Status of Cambodian Schoolchildren: a Double-Blind Cluster-Randomized Controlled Trial.

PubMed

Perignon, Marlène; Fiorentino, Marion; Kuong, Khov; Dijkhuizen, Marjoleine A; Burja, Kurt; Parker, Megan; Chamnan, Chhoun; Berger, Jacques; Wieringa, Frank T

2016-01-07

In Cambodia, micronutrient deficiencies remain a critical public health problem. Our objective was to evaluate the impact of multi-micronutrient fortified rice (MMFR) formulations, distributed through a World Food Program school-meals program (WFP-SMP), on the hemoglobin concentrations and iron and vitamin A (VA) status of Cambodian schoolchildren. The FORISCA-UltraRice+NutriRice study was a double-blind, cluster-randomized, placebo-controlled trial. Sixteen schools participating in WFP-SMP were randomly assigned to receive extrusion-fortified rice (UltraRice Original, UltraRice New (URN), or NutriRice) or unfortified rice (placebo) six days a week for six months. Four additional schools not participating in WFP-SMP were randomly selected as controls. A total of 2440 schoolchildren (6-16 years old) participated in the biochemical study. Hemoglobin, iron status, estimated using inflammation-adjusted ferritin and transferrin receptors concentrations, and VA status, assessed using inflammation-adjusted retinol-binding protein concentration, were measured at the baseline, as well as at three and six months. Baseline prevalence of anemia, depleted iron stores, tissue iron deficiency, marginal VA status and VA deficiency were 15.6%, 1.4%, 51.0%, 7.9%, and 0.7%, respectively. The strongest risk factors for anemia were hemoglobinopathy, VA deficiency, and depleted iron stores (all p < 0.01). After six months, children receiving NutriRice and URN had 4 and 5 times less risk of low VA status, respectively, in comparison to the placebo group. Hemoglobin significantly increased (+0.8 g/L) after three months for the URN group in comparison to the placebo group; however, this difference was no longer significant after six months, except for children without inflammation. MMFR containing VA effectively improved the VA status of schoolchildren. The impact on hemoglobin and iron status was limited, partly by sub-clinical inflammation. MMFR combined with non-nutritional approaches addressing anemia and inflammation should be further investigated.

AZP-531, an unacylated ghrelin analog, improves food-related behavior in patients with Prader-Willi syndrome: A randomized placebo-controlled trial

PubMed Central

Caixàs, Assumpta; Poitou, Christine; Coupaye, Muriel; Thuilleaux, Denise; Lorenzini, Françoise; Diene, Gwenaëlle; Crinò, Antonino; Illouz, Frédéric; Grugni, Graziano; Potvin, Diane; Bocchini, Sarah; Delale, Thomas; Abribat, Thierry; Tauber, Maithé

2018-01-01

Context and objective Prader-Willi syndrome (PWS) is characterized by early-onset hyperphagia and increased circulating levels of the orexigenic Acylated Ghrelin (AG) hormone with a relative deficit of Unacylated Ghrelin (UAG). AZP-531, a first-in-class UAG analog, was shown to inhibit the orexigenic effect of AG in animals, to improve glycemic control and decrease body weight in humans. We aimed to investigate the safety and efficacy of AZP-531 in patients with PWS for whom no approved treatment for hyperphagia is currently available. Methods and design Multi-center, randomized, double-blind, placebo-controlled trial. Forty-seven patients with genetically confirmed PWS and evidence of hyperphagia received daily subcutaneous injections of AZP-531 (3 and 4 mg for 50–70 kg and >70 kg body weight, respectively) or matching placebo for 14 days. Assessments included adverse events, vital signs, safety laboratory tests, the Hyperphagia Questionnaire (HQ), patient-reported appetite, body composition and glycemic measures. Results AZP-531 was well tolerated. There was a significant improvement with AZP-531 versus placebo in the mean total score, the 9-item score and the severity domain score of the HQ (p < .05). The highest reduction in the total and 9-item scores was observed in AZP-531 subjects with the highest hyperphagia score at baseline. Findings were supported by a reduction in appetite scores observed with AZP-531 only. Body weight did not change in both groups while a significant reduction in waist circumference and fat mass was observed only with AZP-531. AZP-531 significantly decreased post-prandial glucose levels in a baseline glucose dependent fashion. Conclusions AZP-531 may constitute a new treatment strategy to improve hyperphagia and metabolic issues in patients with PWS. These findings support further investigation in longer-term clinical trials. PMID:29320575

Assessment of the effeCt of lIfestyle iNtervention plus water-soluble ciNnAMon extract On loweriNg blood glucose in pre-diabetics, a randomized, double-blind, multicenter, placebo controlled trial: study protocol for a randomized controlled trial.

PubMed

Crawford, Paul; Thai, Chuong; Obholz, Joshua; Schievenin, Jeffrey; True, Mark; Shah, Sachin A; Hallgren, John; Clark, Jill; Sharon, Danny

2016-01-05

The World Health Organization predicts that by 2030 diabetes will be the seventh leading cause of death in the world. Multiple studies have tried to determine if cinnamon is an effective treatment for diabetes. Cinnamon extract is an insulin sensitizer, protects mesangial cells, decreases inflammatory markers, and lowers glucose, lipids, and blood pressure in patients with type 2 diabetes, so we developed a protocol to study whether ingestion of water-soluble cinnamon extract prevents progression from pre-diabetes to diabetes. This is a randomized, double-blind, placebo-controlled trial comparing cinnamon extract versus placebo in subjects with pre-diabetes who have committed to participate in a lifestyle change program. The trial will be conducted at five sites and will include 428 subjects who take cinnamon extract or placebo for 1 year. Follow-up for these subjects will be for a total of 2 years (nine study visits). The primary outcomes to be assessed are 1) conversion of patients from pre-diabetes to diabetes and 2) impact of water-soluble cinnamon extract on hepatic transaminases, renal function, and QT interval on electrocardiogram. Secondary outcomes include changes in HbA1c, lipids, waist circumference, weight, blood pressure, and fasting plasma glucose. The trial protocol has been approved by the Institutional Review Board of the US Air Force 59th Medical Wing, Wilford Hall Ambulatory Surgical Center (Protocol FWH20110035H). Investigator-sponsored Investigational New Drug status (114078) was granted by the US Food and Drug Administration. This study will provide high-quality evidence of the efficacy of water-soluble cinnamon extract in conjunction with lifestyle intervention for preventing patients with pre-diabetes from converting to diabetes. Additionally, it will provide important safety information about water-soluble cinnamon extract. ClinicalTrials.gov Identifier: NCT01301521 , 18 February 2011.

Cyclic cidofovir (cHPMPC) prevents congenital cytomegalovirus infection in a guinea pig model

PubMed Central

Schleiss, Mark R; Anderson, Jodi L; McGregor, Alistair

2006-01-01

Background Congenital cytomegalovirus (CMV) infection is a major public health problem. Antiviral therapies administered during pregnancy might prevent vertical CMV transmission and disease in newborns, but these agents have not been evaluated in clinical trials. The guinea pig model of congenital CMV infection was therefore used to test the hypothesis that antiviral therapy, using the agent agent cyclic cidofovir (cHPMPC), could prevent congenital CMV infection. Results Pregnant outbred Hartley guinea pigs were challenged in the early-third trimester with guinea pig CMV (GPCMV) and treated with placebo, or the antiviral agent, cyclic cidofovir. To optimize detection of vertical infection, an enhanced green fluorescent protein (eGFP)-tagged virus was employed. Compared to placebo, cyclic cidofovir-treated dams and pups had reduced mortality following GPCMV challenge. The magnitude of GPCMV-induced maternal and fetal mortality in this study was reduced from 5/25 animals in the placebo group to 0/21 animals in the treatment group (p = 0.05, Fisher's exact test). By viral culture assay, antiviral therapy was found to completely prevent GPCMV transmission to the fetus. In control pups, 5/19 (26%) were culture-positive for GPCMV, compared to 0/16 of pups in the cyclic cidofovir treatment group (p < 0.05, Fisher's exact test). Conclusion Antiviral therapy with cyclic cidofovir improves pregnancy outcomes in guinea pigs, and eliminates congenital CMV infection, following viral challenge in the third trimester. This study also demonstrated that an eGFP-tagged recombinant virus, with the reporter gene inserted into a dispensable region of the viral genome, retained virulence, including the potential for congenital transmission, facilitating tissue culture-based detection of congenital infection. These observations provide support for clinical trials of antivirals for reduction of congenital CMV infection. PMID:16509982

An efficient early phase 2 procedure to screen medications for efficacy in smoking cessation.

PubMed

Perkins, Kenneth A; Lerman, Caryn

2014-01-01

Initial screening of new medications for potential efficacy (i.e., Food and Drug Administration (FDA) early phase 2), such as in aiding smoking cessation, should be efficient in identifying which drugs do, or do not, warrant more extensive (and expensive) clinical testing. This focused review outlines our research on development, evaluation, and validation of an efficient crossover procedure for sensitivity in detecting medication efficacy for smoking cessation. First-line FDA-approved medications of nicotine patch, varenicline, and bupropion were tested as model drugs, in three separate placebo-controlled studies. We also tested specificity of our procedure in identifying a drug that lacks efficacy, using modafinil. This crossover procedure showed sensitivity (increased days of abstinence) during week-long "practice" quit attempts with each of the active cessation medications (positive controls) versus placebo, but not with modafinil (negative control) versus placebo, as hypothesized. Sensitivity to medication efficacy signal was observed only in smokers high in intrinsic quit motivation (i.e., already preparing to quit soon) and not smokers low in intrinsic quit motivation, even if monetarily reinforced for abstinence (i.e., given extrinsic motivation). A crossover procedure requiring less time and fewer subjects than formal trials may provide an efficient strategy for a go/no-go decision whether to advance to subsequent phase 2 randomized clinical trials with a novel drug. Future research is needed to replicate our results and evaluate this procedure with novel compounds, identify factors that may limit its utility, and evaluate its applicability to testing efficacy of compounds for treating other forms of addiction.

A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity to sad mood.

PubMed

Steenbergen, Laura; Sellaro, Roberta; van Hemert, Saskia; Bosch, Jos A; Colzato, Lorenza S

2015-08-01

Recent insights into the role of the human microbiota in cognitive and affective functioning have led to the hypothesis that probiotic supplementation may act as an adjuvant strategy to ameliorate or prevent depression. Heightened cognitive reactivity to normal, transient changes in sad mood is an established marker of vulnerability to depression and is considered an important target for interventions. The present study aimed to test if a multispecies probiotic containing Bifidobacterium bifidum W23, Bifidobacterium lactis W52, Lactobacillus acidophilus W37, Lactobacillus brevis W63, Lactobacillus casei W56, Lactobacillus salivarius W24, and Lactococcus lactis (W19 and W58) may reduce cognitive reactivity in non-depressed individuals. In a triple-blind, placebo-controlled, randomized, pre- and post-intervention assessment design, 20 healthy participants without current mood disorder received a 4-week probiotic food-supplement intervention with the multispecies probiotics, while 20 control participants received an inert placebo for the same period. In the pre- and post-intervention assessment, cognitive reactivity to sad mood was assessed using the revised Leiden index of depression sensitivity scale. Compared to participants who received the placebo intervention, participants who received the 4-week multispecies probiotics intervention showed a significantly reduced overall cognitive reactivity to sad mood, which was largely accounted for by reduced rumination and aggressive thoughts. These results provide the first evidence that the intake of probiotics may help reduce negative thoughts associated with sad mood. Probiotics supplementation warrants further research as a potential preventive strategy for depression. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Design of clinical trials of antidepressants: should a placebo control arm be included?

PubMed

Fritze, J; Möller, H J

2001-01-01

There is no doubt that available antidepressants are efficacious and effective. Nevertheless, more effective drugs with improved tolerability are needed. With this need in mind, some protagonists claim that future antidepressants should be proved superior to, or at least as effective as, established antidepressants, making placebo control methodologically dispensable in clinical trials. Moreover, the use of placebo control is criticised as unethical because it might result in effective treatment being withheld. There are, however, a number of methodological reasons why placebo control is indispensable for the proof of efficacy of antidepressants. Comparing investigational antidepressants only with standard antidepressants and not placebo yields ambiguous results that are difficult to interpret, be it in superiority or equivalence testing, and this method of assessment requires larger sample sizes than those required with the use of placebo control. Experimental methodology not adhering to the optimal study design is ethically questionable. Restricting the testing of investigational antidepressants only to superiority over standard antidepressants is an obstacle to therapeutic progress in terms of tolerability and the detection of innovative mechanisms of action from which certain subgroups of future patients might benefit. The use of a methodology that requires larger samples for testing of superiority or equivalence is also ethically questionable. In view of the high placebo response rates in trials of antidepressants, placebo treatment does not mean withholding effective treatment. Accepting the necessity of the clinical evaluation of new, potentially ineffective antidepressants implicitly means accepting placebo control as ethically justified. Three- or multi-arm comparisons including placebo and an active reference represent the optimal study design.

Oligofructose promotes satiety in healthy human: a pilot study.

PubMed

Cani, P D; Joly, E; Horsmans, Y; Delzenne, N M

2006-05-01

The administration of a fermentable dietary fibre (oligofructose) in rats increases satietogenic gut peptides and lowered spontaneous energy intake. The aim of the study was to assess the relevance of those effects of oligofructose on satiety and energy intake in humans. Single-blinded, crossover, placebo-controlled design, pilot study. Volunteers included five men and five women aged 21-39 years, BMI ranging from 18.5 to 27.4 kg/m(2), were randomly assigned as described below. Subjects were included in two 2-week experimental phases during which they received either fibre (oligofructose (OFS)) or placebo (dextrine maltose (DM)); a 2-week washout period was included between crossover phases. In total, 8 g OFS or 8 g DM were ingested twice daily (16 g/day in total). Energy intake, hunger, satiety, fullness and prospective food consumption were assessed with analogue scales at the end of each experimental phase. During breakfast, OFS significantly increases the satiety (P=0.04) without any difference on other sensations as compared to DM treatment periods. After lunch, no significant differences are observed between treatment period. At dinner, OFS significantly increases satiety (P=0.04), reduces hunger (P=0.04) and prospective food consumption (P=0.05). The energy intake at breakfast and lunch are significantly lower (P=0.01, 0.03, respectively) after OFS treatment than after DM treatment. Total energy intake per day is 5% lower during OFS than in DM period. Oligofructose treatment increases satiety following breakfast and dinner, reduces hunger and prospective food consumption following dinner. This pilot study presents a rationale to propose oligofructose supplements in the management of food intake in overweight and obese patients.

Effects of 7.5% CO2 challenge in generalized anxiety disorder.

PubMed

Seddon, Kate; Morris, Kelly; Bailey, Jayne; Potokar, John; Rich, Ann; Wilson, Sue; Bettica, Paolo; Nutt, David J

2011-01-01

We have previously developed a putative model of generalized anxiety disorder in healthy volunteers using a 20-minute 7.5% carbon dioxide (CO(2)) inhalation challenge. The aim of this study was to validate the 7.5% CO(2) paradigm by assessing its effects in patients with generalized anxiety disorder in a test-retest design. Twelve medication-free generalized anxiety disorder patients attended our lab for two study days. On each study day placebo (compressed air) and 7.5% CO(2) mixture were randomly administered over 20 min, at least 30 min apart, in a single blind, randomized, placebo-controlled cross-over design. Subjective ratings, cardiovascular measures and cortisol levels were collected throughout. CO(2) challenge significantly increased ratings for anxiety and other subjective symptoms associated with generalized anxiety disorder, compared with air. It also significantly increased systolic blood pressure on day 2, indicating increased autonomic arousal. There was no change between the two test days in mean anxiety rating scores, and there also appeared to be a correlation for individual scores on a number of the subjective measures. In conclusion, 20 min of 7.5% CO(2) gas inhalation increases anxiety responses in patients with generalized anxiety disorder, and this is reliable over time.

Fel d 1-derived synthetic peptide immuno-regulatory epitopes show a long-term treatment effect in cat allergic subjects.

PubMed

Couroux, P; Patel, D; Armstrong, K; Larché, M; Hafner, R P

2015-05-01

Cat-PAD, the first in a new class of synthetic peptide immuno-regulatory epitopes (SPIREs), was shown to significantly improve rhinoconjunctivitis symptoms in subjects with cat allergy up to 1 year after the start of a short course of treatment. To evaluate the long-term effects of Cat-PAD on rhinoconjunctivitis symptoms following standardized allergen challenge 2 years after treatment. In a randomized, double-blind, placebo-controlled, parallel group study, subjects were exposed to cat allergen in an environmental exposure chamber (EEC) before and after treatment with two regimens of Cat-PAD (either eight doses of 3 nmol or four doses of 6 nmol) given intradermally over a 3-month period. In this follow-up study, changes from baseline in rhinoconjunctivitis symptoms were reassessed 2 years after the start of treatment. The primary endpoint showed a mean reduction in total rhinoconjunctivitis symptom scores of 3.85 units in the 4 × 6 nmol Cat-PAD group compared to placebo 2 years after the start of treatment (P = 0.13), and this difference was statistically significant in the secondary endpoint at the end of day 4 when the cumulative allergen challenge was greatest (P = 0.02). Consistent reductions in nasal symptoms of between 2 and 3 units were observed for 4 × 6 nmol Cat-PAD compared to placebo between the 2 and 3 h time points on days 1-4 of EEC challenge at 2 years (P < 0.05). The 8 × 3 nmol dose did not show a meaningful effect in this study. A persistent, clinically meaningful reduction in rhinoconjunctivitis symptoms was observed on EEC challenge 2 years after the start of a short course of treatment with 4 × 6 nmol Cat-PAD. This study is the first to provide evidence of a long-term therapeutic effect with this new class of SPIREs. © 2015 The Authors. Clinical & Experimental Allergy Published by John Wiley & Sons Ltd.

Effect of dehydroepiandrosterone administration on recovery from mix-type exercise training-induced muscle damage.

PubMed

Liao, Yi-Hung; Liao, Kun-Fu; Kao, Chung-Lan; Chen, Chung-Yu; Huang, Chih-Yang; Chang, Wei-Hsiang; Ivy, John L; Bernard, Jeffrey R; Lee, Shin-Da; Kuo, Chia-Hua

2013-01-01

This study aimed to determine the role of DHEA-S in coping against the exercise training mixing aerobic and resistance components. During 5-day successive exercise training, 16 young male participants (19.2 ± 1.2 years) received either a placebo (flour capsule) or DHEA (100 mg/day) in a double-blinded and placebo-controlled design. Oral DHEA supplementation significantly increased circulating DHEA-S by 2.5-fold, but a protracted drop (~35 %) was observed from Day 3 during training. In the Placebo group, only a minimal DHEA-S reduction (~17 %) was observed. Changes in testosterone followed a similar pattern as DHEA-S. Muscle soreness was elevated significantly on Day 2 for both groups to a similar extent. Lower muscle soreness was observed in the DHEA-supplemented group on Day 3 and Day 6. In the Placebo group, training increased circulating creatine kinase (CK) levels by approximately ninefold, while only a threefold increase was observed in the DHEA-supplemented group. This mix-type exercise training improved glucose tolerance in both groups, while lowering the insulin response to the glucose challenge, but no difference between treatments was observed. Our results suggest that DHEA-S may play a role in protecting skeletal muscle from exercise training-induced muscle damage.

Effect of quetiapine vs. placebo on response to two virtual public speaking exposures in individuals with social phobia.

PubMed

Donahue, Christopher B; Kushner, Matt G; Thuras, Paul D; Murphy, Tom G; Van Demark, Joani B; Adson, David E

2009-04-01

Clinical practice and open-label studies suggest that quetiapine (an atypical anti-psychotic) might improve symptoms for individuals with social anxiety disorder (SAD). The purpose of this study was to provide a rigorous test of the acute impact of a single dose of quetiapine (25mg) on SAD symptoms. Individuals with SAD (N=20) were exposed to a 4-min virtual reality (VR) public speaking challenge after having received quetiapine or placebo (double-blind) 1h earlier. A parallel VR challenge occurred 1 week later using a counter-balanced cross-over (within subject) design for the medication-placebo order between the two sessions. There was no significant drug effect for quetiapine on the primary outcome measures. However, quetiapine was associated with significantly elevated heart rate and sleepiness compared with placebo. Study findings suggest that a single dose of 25mg quetiapine is not effective in alleviating SAD symptoms in individuals with fears of public speaking.

Caffeinated Tube Food Effect on Pilot Performance During a 9-Hour, Simulated Nighttime U-2 Mission

DTIC Science & Technology

2006-10-01

Tube foods are the only foods that can be consumed during a U-2 mission due to the confining and encapsulating nature of required support equipment...Caffeinated (200 mg each) or placebo tube food was consumed at 00:00 and 04:00. Dependent measures assessed included standardized tests of cognitive...performance decrements were attenuated by 200 mg of caffeine in tube food consumed every 4 h, and in some cases, performance was improved beyond

Development of the food supplement Nyaditum resae as a new tool to reduce the risk of tuberculosis development.

PubMed

Tukvadze, Nestani; Cardona, Paula; Vashakidze, Sergo; Shubladze, Natalia; Avaliani, Zaza; Vilaplana, Cris; Cardona, Pere-Joan

2016-12-01

Nyaditum resae (NR) is a galenic preparation of heat-killed Mycobacterium manresensis (hkMn). This is a new species that belongs to the Mycobacterium fortuitum complex, and it is present in drinking water-thus, regulatorily speaking, it is considered a food supplement. Preclinical studies in the murine model of active tuberculosis (TB) in the C3HeB/FeJ strain have demonstrated that daily administration of NR containing 10 3 -10 6 hkMn for 14days was able to stop the progression toward active TB [1]. The mechanism of action was linked to the induction of low dose tolerance and was related to the increase of Tuberculin Purified Protein Derivative (PPD) memory-specific Tregs (CD4 + CD25 + CD39 + cells) after ex vivo incubation of splenocytes for 7days. This increase of Tregs was related to the increase of interleukin (IL)-10 in the spleen and in the reduction of IL-17 in the lungs, where there was also a reduction in bacillary load and the pathology caused by a reduction of neutrophiles' infiltration [2]. Two randomized, double-blind placebo-controlled clinical trials (CTs) have been conducted in humans. The NYADATREG study (Clinicaltrials.gov identifier NCT02076139; 2013-2014) was aimed to evaluate the safety and the immunogenicity of two concentrations of NR (containing 10 4 hkMn and 10 5 hkMn) versus placebo (all administered orally everyday for 14days) in tuberculin-positive and tuberculin-negative volunteers (total n=51). The results demonstrated an excellent safety record, with no differences between groups in terms of adverse effects. A significant increase in PPD-specific memory regulatory T cells was also detected in both NR groups [3]. The NYADAPETRICS study (Clinicaltrials.gov identifier NCT02581579) is evaluating the safety and immunogenicity of NR 10 5 hkMn (capsule format, orally) in the pediatric population. Currently, an efficacy study (randomized, double-blinded, placebo-controlled CT) is being conducted in Georgia. This NYADAGEORG trial includes close contacts of active TB cases with positive sputum not tributaries of chemoprophylaxis (<5-year-old children and HIV-positive individuals), which will receive NR (containing 10 5 hkMn) or placebo (orally, every day for 14days). A total of 3300 participants will be recruited in four medical centers around Tbilissi. The participants are monitored by telephone for up to 2years to evaluate the incidence of active TB. The hypothesis is that the NR group will exhibit a 40% reduction in expected TB incidence. Thus, the anticipated TB incidence will be 3% in the NR group versus 5% in the placebo group. The CT is projected to end by 2021 (Clinicaltrials.gov identifier NCT02897180). The administration of the food supplement NR appears to be a new, easy, safe, and reliable method for reducing the risk of developing active TB, and new CTs must be encouraged to discern the particular efficacy power according to different population characteristics. Copyright © 2016.

Synbiotics could not reduce the scoring of childhood atopic dermatitis (SCORAD): a randomized double blind placebo-controlled trial.

PubMed

Shafiei, Alireza; Moin, Mostafa; Pourpak, Zahra; Gharagozlou, Mohammad; Aghamohammadi, Asghar; Aghamohamadi, Asghar; Sajedi, Vahid; soheili, Habib; Sotoodeh, Soheila; Movahedi, Masoud

2011-03-01

Despite preliminary evidence, the role of probiotic and synbiotic in treatment of the atopic dermatitis has shown varying results. We aimed to evaluate whether synbiotic supplementation decrease severity of atopic dermatitis (AD) in childhood. In a randomized double blind-placebo controlled trial, we evaluated the synbiotic supplementation efficiency on the treatment of atopic dermatitis. Infants aged 1-36 months with moderate to severe atopic dermatitis were randomized (n=41) and received either synbiotic (probiotic plus prebiotic) (n=20) or placebo (n=21) daily as a powder for two months. Emollient (Eucerin) and topical corticosteroid (Hydrocortisone) were permitted. Children were scored for severity of atopic dermatitis (SCORAD). Also allergen Skin Prick Tests (SPT), IgE blood level and eosinophil count were measured at first visit. Patients' SCORAD were reevaluated at the end of intervention. We followed 36 out of 41 subjects for two months (drop out rate = 9%). In the whole group, the mean Total SCORAD (at base line 40.93) decreased by 56% (p=0.00). The mean Objective SCORAD (at base line 31.29) decreased by 53% (p=0.00). There was no significant difference in the mean decrease of total SCORAD between placebo (22.3) and synbiotic groups (24.2). There was also no difference between two intervention groups in the mean decrease of total SCORAD regarding to different demographic, clinical and para clinical subgroups. This study could not confirm synbiotic as an effective treatment for childhood atopic dermatitis and further studies are needed. These findings challenge the role of synbiotics in the treatment of childhood atopic dermatitis.

A double blind placebo controlled randomized trial of the effect of acute uric acid changes on inflammatory markers in humans: A pilot study

PubMed Central

Milaneschi, Yuri; Zhang, Yongqing; Becker, Kevin G.; Zukley, Linda; Ferrucci, Luigi

2017-01-01

Uric acid has been linked with increased risk of chronic disease such as cardiovascular disease and this association has been attributed to a pro-inflammatory effect. Indeed, observational studies have shown that high uric acid is associated with high level of pro-inflammatory cytokines in the blood. However, whether high uric acid directly affects inflammation or rather represents a parallel defensive antioxidant mechanism in response to pathology that causes inflammation is unknown. To determine whether acute increase or decrease uric acid levels affects inflammation in healthy individuals, a randomized, placebo-controlled, double blind clinical study of uric acid or rasburicase with 20 healthy volunteers in each treatment-placebo group was conducted at the National Institute on Aging (NIA) Clinical Research Unit (CRU) at Harbor Hospital in Baltimore, MD. Change in inflammatory response was assessed by administering an oral lipid tolerance before and after the treatment of uric acid, rasburicase and placebo. Following uric acid administration, there was an accentuated increase in IL-6 during the oral lipid tolerance test (P<0.001). No significant differences were observed after lowering of uric acid with rasburicase. No side effects were reported throughout the trial. In health individuals, acute increase in uric acid results in an increased IL-6 response when challenged with lipid load. Such effect of amplification of inflammatory response may explain the higher risk of chronic diseases observed in subclinical hyperuricemia in observational studies. Trial Registration: ClinicalTrials.gov NCT01323335 PMID:28786993

Sodium 4-phenylbutyrate reduces myofiber damage in a mouse model of Duchenne muscular dystrophy.

PubMed

Begam, Morium; Abro, Valerie M; Mueller, Amber L; Roche, Joseph A

2016-10-01

We performed a placebo-controlled pre-clinical study to determine if sodium 4-phenylbutyrate (4PB) can reduce contraction-induced myofiber damage in the mdx mouse model of Duchenne muscular dystrophy (DMD). At 72 h post-eccentric contractions, 4PB significantly increased contractile torque and reduced myofiber damage and macrophage infiltration. We conclude that 4PB, which is approved by Health Canada (Pheburane) and the United States Food and Drug Administration (Buphenyl) for urea cycle disorders, might modify disease severity in patients with DMD.

Preventing the common cold with a vitamin C supplement: a double-blind, placebo-controlled survey.

PubMed

Van Straten, Michael; Josling, Peter

2002-01-01

One hundred sixty-eight volunteers were randomized to receive a placebo or a vitamin C supplement, two tablets daily, over a 60-day period between November and February. They used a five-point scale to assess their health and recorded any common cold infections and symptoms in a daily diary. Compared with the placebo group, the active-treatment group had significantly fewer colds (37 vs 50, P<.05), fewer days challenged virally (85 vs 178), and a significantly shorter duration of severe symptoms (1.8 vs 3.1 days, P<.03). Consequently, volunteers in the active group were less likely to get a cold and recovered faster if infected. Few side effects occurred with the active treatment, and volunteers reported greatly increased satisfaction with the study supplement compared with any previous form of vitamin C. This well-tolerated vitamin C supplement may prevent the common cold and shorten the duration of symptoms. Volunteers were generally impressed by the protection afforded them during the winter months and the general acceptability of the study medication.

The diagnosis of food allergy: a systematic review and meta-analysis.

PubMed

Soares-Weiser, K; Takwoingi, Y; Panesar, S S; Muraro, A; Werfel, T; Hoffmann-Sommergruber, K; Roberts, G; Halken, S; Poulsen, L; van Ree, R; Vlieg-Boerstra, B J; Sheikh, A

2014-01-01

We investigated the accuracy of tests used to diagnose food allergy. Skin prick tests (SPT), specific-IgE (sIgE), component-resolved diagnosis and the atopy patch test (APT) were compared with the reference standard of double-blind placebo-controlled food challenge. Seven databases were searched and international experts were contacted. Two reviewers independently identified studies, extracted data, and used QUADAS-2 to assess risk of bias. Where possible, meta-analysis was undertaken. Twenty-four (2831 participants) studies were included. For cows' milk allergy, the pooled sensitivities were 53% (95% CI 33-72), 88% (95 % CI 76-94), and 87% (95% CI 75-94), and specificities were 88% (95% CI 76-95), 68% (95% CI 56-77), and 48% (95% CI 36-59) for APT, SPT, and sIgE, respectively. For egg, pooled sensitivities were 92% (95% CI 80-97) and 93% (95% CI 82-98), and specificities were 58% (95% CI 49-67) and 49% (40-58%) for skin prick tests and specific-IgE. For wheat, pooled sensitivities were 73% (95% CI 56-85) and 83% (95% CI 69-92), and specificities were 73% (95% CI 48-89) and 43% (95% CI 20-69%) for SPT and sIgE. For soy, pooled sensitivities were 55% (95% CI 33-75) and 83% (95% CI 64-93), and specificities were 68% (95% CI 52-80) and 38% (95% CI 24-54) for SPT and sIgE. For peanut, pooled sensitivities were 95% (95% CI 88-98) and 96% (95% CI 92-98), and specificities were 61% (95% CI 47-74), and 59% (95% CI 45-72) for SPT and sIgE. The evidence base is limited and weak and is therefore difficult to interpret. Overall, SPT and sIgE appear sensitive although not specific for diagnosing IgE-mediated food allergy. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, g.j.; Wang, G.-J.; Geliebter, A.

Subjects with binge eating disorder (BED) regularly consume large amounts of food in short time periods. The neurobiology of BED is poorly understood. Brain dopamine, which regulates motivation for food intake, is likely to be involved. We assessed the involvement of brain dopamine in the motivation for food consumption in binge eaters. Positron emission tomography (PET) scans with [{sup 11}C]raclopride were done in 10 obese BED and 8 obese subjects without BED. Changes in extracellular dopamine in the striatum in response to food stimulation in food-deprived subjects were evaluated after placebo and after oral methylphenidate (MPH), a drug that blocksmore » the dopamine reuptake transporter and thus amplifies dopamine signals. Neither the neutral stimuli (with or without MPH) nor the food stimuli when given with placebo increased extracellular dopamine. The food stimuli when given with MPH significantly increased dopamine in the caudate and putamen in the binge eaters but not in the nonbinge eaters. Dopamine increases in the caudate were significantly correlated with the binge eating scores but not with BMI. These results identify dopamine neurotransmission in the caudate as being of relevance to the neurobiology of BED. The lack of correlation between BMI and dopamine changes suggests that dopamine release per se does not predict BMI within a group of obese individuals but that it predicts binge eating.« less

Prevalence and factors associated with use of placebo control groups in randomized controlled trials in psoriasis: a cross-sectional study.

PubMed

Katz, Kenneth A; Karlawish, Jason H; Chiang, David S; Bognet, Rachel A; Propert, Katherine J; Margolis, David J

2006-11-01

The ethics and science of using placebo control groups in clinical trials have been widely debated. Few studies, however, have examined factors associated with choice of control group. Our aim was to assess the prevalence of use of placebo controls in randomized controlled trials in psoriasis and to identify factors associated with use of placebo controls in these trials. This is a cross-sectional study of randomized controlled trials in psoriasis published from January 1, 2001 to December 20, 2005 and indexed in the Cochrane Central Register of Controlled Trials. We extracted data on types of control groups used, design issues (number of patients enrolled, primary end point), disease characteristics (psoriasis type and severity), and extrascientific issues (trial location, funding source, and year of publication). We used bivariable and multivariable logistic regression to determine factors associated with use of a placebo control group. Of 194 citations, 187 were available for review. One hundred thirty-five trials from 134 articles in 38 journals met inclusion criteria. Eighty-three trials (61.5%) enrolling 8171 subjects (41.7%) used active controls only, and 52 trials (38.5%) enrolling 11,406 subjects (58.3%) used placebo controls. Adjusted for trial location and funding source, trials significantly more likely to have used placebo controls included those conducted in the United States (odds ratio [OR], 5.79; 95% confidence interval [CI], 2.45-13.68; P < .001) and those funded by pharmaceutical companies (OR, 2.61; 95% CI, 1.19-5.73; P = .02). Predicted frequencies of placebo use ranged from 77.6% (industry-funded, conducted trials in the United States) to 18.6% (non-industry-funded trials not conducted in the United States). Our searches may not have identified all published trials, and we did not have access to data from unpublished trials. Use of placebo controls has been more common in psoriasis trials conducted in the United States and funded by pharmaceutical companies. The findings suggest that ethical and scientific issues related to choice of control group in psoriasis trials are interpreted markedly differently depending on trial location and funding source.

Active placebo control groups of pharmacological interventions were rarely used but merited serious consideration: a methodological overview.

PubMed

Jensen, Jakob Solgaard; Bielefeldt, Andreas Ørsted; Hróbjartsson, Asbjørn

2017-07-01

Active placebos are control interventions that mimic the side effects of the experimental interventions in randomized trials and are sometimes used to reduce the risk of unblinding. We wanted to assess how often randomized clinical drug trials use active placebo control groups; to provide a catalog, and a characterization, of such trials; and to analyze methodological arguments for and against the use of active placebo. An overview consisting of three thematically linked substudies. In an observational substudy, we assessed the prevalence of active placebo groups based on a random sample of 200 PubMed indexed placebo-controlled randomized drug trials published in October 2013. In a systematic review, we identified and characterized trials with active placebo control groups irrespective of publication time. In a third substudy, we reviewed publications with substantial methodological comments on active placebo groups (searches in PubMed, The Cochrane Library, Google Scholar, and HighWirePress). The prevalence of trials with active placebo groups published in 2013 was 1 out of 200 (95% confidence interval: 0-2), 0.5% (0-1%). We identified and characterized 89 randomized trials (published 1961-2014) using active placebos, for example, antihistamines, anticholinergic drugs, and sedatives. Such trials typically involved a crossover design, the experimental intervention had noticeable side effects, and the outcomes were patient-reported. The use of active placebos was clustered in specific research settings and did not appear to reflect consistently the side effect profile of the experimental intervention, for example, selective serotonin reuptake inhibitors were compared with active placebos in pain trials but not in depression trials. We identified and analyzed 25 methods publications with substantial comments. The main argument for active placebo was to reduce risk of unblinding; the main argument against was the risk of unintended therapeutic effect. Pharmacological active placebo control interventions are rarely used in randomized clinical trials, but they constitute a methodological tool which merits serious consideration. We suggest that active placebos are used more often in trials of drugs with noticeable side effects, especially in situations where the expected therapeutic effects are modest and the risk of bias due to unblinding is high. Copyright © 2017 Elsevier Inc. All rights reserved.

Neurodevelopmental outcome and growth at 18 to 22 months' corrected age in extremely low birth weight infants treated with early erythropoietin and iron.

PubMed

Ohls, Robin K; Ehrenkranz, Richard A; Das, Abhik; Dusick, Anna M; Yolton, Kimberly; Romano, Elaine; Delaney-Black, Virginia; Papile, Lu-Ann; Simon, Neal P; Steichen, Jean J; Lee, Kimberly G

2004-11-01

Clinical trials evaluating the use of erythropoietin (Epo) have demonstrated a limited reduction in transfusions; however, long-term developmental follow-up data are scarce. We compared anthropometric measurements, postdischarge events, need for transfusions, and developmental outcomes at 18 to 22 months' corrected age in extremely low birth weight (ELBW) infants treated with early Epo and supplemental iron therapy with that of placebo/control infants treated with supplemental iron alone. The National Institute of Child Health and Human Development Neonatal Research Network completed a randomized, controlled trial of early Epo and iron therapy in preterm infants < or =1250 g. A total of 172 ELBW (< or =1000-g birth weight) infants were enrolled (87 Epo and 85 placebo/control). Of the 72 Epo-treated and 70 placebo/control ELBW infants surviving to discharge, follow-up data (growth, development, rehospitalization, transfusions) at 18 to 22 months' corrected age were collected on 51 of 72 Epo-treated infants (71%) and 51 of 70 placebo/controls (73%) by certified examiners masked to the treatment group. Statistical significance was determined using chi2 analysis. There were no significant differences between treatment groups in weight or length or in the percentage of infants weighing <10th percentile either at the time of discharge or at follow-up, and no difference was found in the mean head circumference between groups. A similar percentage of infants in each group was rehospitalized (38% Epo and 35% placebo/control) for similar reasons. There were no differences between groups with respect to the percentage of infants with Bayley-II Mental Developmental Index <70 (34% Epo and 36% placebo/control), blindness (0% Epo and 2% placebo/control), deafness or hearing loss requiring amplification (2% Epo and 2% placebo/control), moderate to severe cerebral palsy (16% Epo and 18% placebo/control) or the percentage of infants with any of the above-described neurodevelopmental impairments (42% Epo and 44% placebo/control). Treatment of ELBW infants with early Epo and iron does not significantly influence anthropometric measurements, need for rehospitalization, transfusions after discharge, or developmental outcome at 18 to 22 months' corrected age.

U.S. Food and Drug Administration Approval: Neratinib for the Extended Adjuvant Treatment of Early Stage HER2-Positive Breast Cancer.

PubMed

Singh, Harpreet; Walker, Amanda J; Amiri-Kordestani, Laleh; Cheng, Joyce; Tang, Shenghui; Balcazar, Pamela; Barnett-Ringgold, Kimberly; Palmby, Todd R; Cao, Xianhua; Zheng, Nan; Liu, Qi; Yu, Jingyu; Pierce, William F; Daniels, Selena R; Sridhara, Rajeshwari; Ibrahim, Amna; Kluetz, Paul G; Blumenthal, Gideon M; Beaver, Julia A; Pazdur, Richard

2018-03-09

On July 17, 2017, the Food and Drug Administration (FDA) approved neratinib (NERLYNX, Puma Biotechnology, Inc) for the extended adjuvant treatment of adult patients with early-stage HER2-overexpressed/amplified breast cancer, to follow adjuvant trastuzumab-based therapy. Approval was based on data from ExteNET, a randomized, double-blind, placebo-controlled multicenter trial. Women with early-stage HER2-positive breast cancer and within two years of completing adjuvant trastuzumab were randomized to neratinib (n=1420) or placebo (n=1420) for one year. The primary endpoint was invasive disease-free survival (iDFS) defined as the time between randomization date to first occurrence of invasive recurrence (local/regional, ipsilateral or contralateral breast cancer), distance recurrence, or death from any cause, with two years and 28 days of follow up. The trial showed a statistically significant treatment effect favoring neratinib with a stratified hazard ratio of 0.66 (95% CI: 0.49, 0.90, p=0.008). Estimated iDFS rate at 2-years was 94.2% (95% CI: 92.6%, 95.4%) in patients treated with neratinib vs. 91.9% (95% CI: 90.2%, 93.2%) in those receiving placebo. Diarrhea was the most common adverse event (AE) with a 40% incidence of Grade 3 or 4 diarrhea and represents the most common AE leading to treatment discontinuation. Other frequent AEs (>10% incidence) were nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, and muscle spasms. Other than diarrhea, neratinib is associated with a low incidence of severe AEs; toxicities are generally reversible and manageable with dose interruptions, dose reductions, and/or standard medical care. This article summarizes FDA decision-making and data supporting the neratinib approval. Copyright ©2018, American Association for Cancer Research.

Long-term gastrointestinal tolerance of NUTRIOSE FB in healthy men.

PubMed

Pasman, W; Wils, D; Saniez, M-H; Kardinaal, A

2006-08-01

To determine the gastrointestinal (GI) tolerance of NUTRIOSE FB in men. A randomized, placebo-controlled, parallel, double-blind study. The metabolic ward of TNO Quality of Life. Forty-eight subjects started the study: 16 men participated in one of the three treatments. SUBJECTS consumed either 22.5 g of pure maltodextrin (Glucidex 6), or 30 or 45 g of the dextrin NUTRIOSE FB daily for 4-5 weeks. Forty-three subjects completed the study (age: 34.7 +/- 8.2 years; BMI 24.9 +/- 3.3 kg m2). Tolerance of NUTRIOSE FB was examined with a GI complaints questionnaire; effectiveness on colonic flora was examined by faecal analysis; fermentation by breath hydrogen excretion measurement. Furthermore, the effect on body weight (BW), energy intake and blood parameters were examined in the study. Both doses of NUTRIOSE FB were very well tolerated and GI complaints hardly differed from the placebo treatment. No diarrhoea was reported due to NUTRIOSE FB supplementation. In the course of the study, some habituation and adaptation of GI symptoms were found. Fermentation and faecal characteristics (pH and enzyme activity) were significantly positively affected with NUTRIOSE FB treatment. Body weight in both NUTRIOSE FB groups remained stable over time, although the placebo-treated group showed a small increase in BW (Deltaday35-1 0.8 +/- 1.0 kg) (P = 0.07). However, total food intake and macronutrient composition of the diet remained the same throughout the study. No significant differences were found between the three treatment groups in hunger and satiety scores and food preferences. Long-term supplementation of 30 or 45 g of the dextrin NUTRIOSE FB per day was well tolerated, and may act as a pre-biotic supplement. TNO Quality of Life was assigned by Roquette Frères to perform the study.

Antihypertensive and cardioprotective effects of the dipeptide isoleucine-tryptophan and whey protein hydrolysate.

PubMed

Martin, M; Kopaliani, I; Jannasch, A; Mund, C; Todorov, V; Henle, T; Deussen, A

2015-12-01

Angiotensin-converting enzyme inhibitors are treatment of choice in hypertensive patients. Clinically used inhibitors exhibit a structural similarity to naturally occurring peptides. This study evaluated antihypertensive and cardioprotective effects of ACE-inhibiting peptides derived from food proteins in spontaneously hypertensive rats. Isoleucine-tryptophan (in vitro IC50 for ACE = 0.7 μm), a whey protein hydrolysate containing an augmented fraction of isoleucine-tryptophan, or captopril was given to spontaneously hypertensive rats (n = 60) over 14 weeks. Two further groups, receiving either no supplement (Placebo) or intact whey protein, served as controls. Systolic blood pressure age-dependently increased in the Placebo group, whereas the blood pressure rise was effectively blunted by isoleucine-tryptophan, whey protein hydrolysate and captopril (-42 ± 3, -38 ± 5, -55 ± 4 mm Hg vs. Placebo). At study end, myocardial mass was lower in isoleucine-tryptophan and captopril groups but only partially in the hydrolysate group. Coronary flow reserve (1 μm adenosine) was improved in isoleucine-tryptophan and captopril groups. Plasma ACE activity was significantly decreased in isoleucine-tryptophan, hydrolysate and captopril groups, but in aortic tissue only after isoleucine-tryptophan or captopril treatment. This was associated with lowered expression and activity of matrix metalloproteinase-2. Following isoleucine-tryptophan and captopril treatments, gene expression of renin was significantly increased indicating an active feedback within renin-angiotensin system. Whey protein hydrolysate and isoleucine-tryptophan powerfully inhibit plasma ACE resulting in antihypertensive effects. Moreover, isoleucine-tryptophan blunts tissue ACE activity, reduces matrix metalloproteinase-2 activity and improves coronary flow reserve. Thus, whey protein hydrolysate and particularly isoleucine-tryptophan may serve as innovative food additives with the goal of attenuating hypertension. © 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

The effects of sibutramine on the microstructure of eating behaviour and energy expenditure in obese women.

PubMed

Halford, J C G; Boyland, E J; Cooper, S J; Dovey, T M; Huda, M S B; Dourish, C T; Dawson, G R; Wilding, J P H

2010-01-01

Given the suggestion that many potential anti-obesity drugs may enhance within-meal satiation, few studies have directly measured the effects of any drug on the microstructure of human eating behaviour. The effects of 7 days dosing with sibutramine 10 mg and 15 mg a day on appetite and energy balance were determined in 30 obese women (BMI 34.6 +/- 3.3 kg/m2, age 46.0 +/- 12.9 years) using a Universal Eating Monitor (UEM) and indirect calorimetry, in a double-blind, placebo-controlled crossover study. At day 7, sibutramine 10 mg and 15 mg reduced food intake by 16.6% and 22.3%, respectively (p < 0.001), compared with placebo. Sibutramine reduced eating rate compared with placebo rather than meal length (10 mg p < 0.05; 15 mg p < 0.001). In addition, sibutramine 10 mg significantly reduced hunger later in the meal (p < 0.05) and sibutramine 15 mg increased fullness early in the meal (p < 0.01), both of which are consistent with enhanced within-meal satiation. Sibutramine had little effect on resting metabolic rate, although 15 mg did significantly reduce respiratory quotient at several time points during the test day. These results provide novel evidence that decreased consumption of a test meal induced by sibutramine is primarily because of reduced eating rate, enhancing the deceleration in cumulative food intake within a meal associated with the development of satiety. Changes in within-meal appetite ratings appear particularly sensitive to drug-induced enhancement of satiation, and may provide key indices for assessing the therapeutic potential of novel anti-obesity drugs.

Glucose-lowering effect of whey protein depends upon clinical characteristics of patients with type 2 diabetes.

PubMed

Almario, Rogelio U; Buchan, Wendy M; Rocke, David M; Karakas, Sidika E

2017-01-01

Whey protein (WP) intake has been shown to reduce postprandial glycemia. Majority of WP research in type 2 diabetes (T2DM) involved acute challenge or weight loss studies. It is not known if WP supplementation can provide sustained glucose lowering. Our goal was to investigate the effects of WP on glycemia comprehensively by using continuous glucose monitoring (CGM) while avoiding the confounding effects of variable food intake through controlled feeding. This double-blinded and placebo (PL)-controlled study included 22 patients with T2DM patients (11 male, 11 female; age 57.1±12.6 years) on diet or metformin monotherapy. First, one serving (21 g) of WP was compared with PL in parallel-armed acute challenge studies. Next, in a crossover design, each patient underwent CGM twice, over 2 consecutive weeks, 3.5 days each week. Identical diets were provided by the study during both CGM periods. During the first CGM, one serving of either WP or PL was consumed before breakfast and another before dinner. During the second CGM, participants switched to the alternate supplement. Order of the supplements was randomized. During acute challenge studies, WP stimulated insulin and glucagon-like peptide (GLP)-1 secretion; suppressed ghrelin (all p<0.05), while PL had no effect. During CGM, glucose response to WP varied depending on the baseline characteristics of the patients. When evaluated using linear regression, the most predictive baseline variables were body mass index (BMI) (p=0.0006), triglycerides (p=8.3×10 -5 ) and GLP-1 (p=0.006). Lower BMI, triglyceride and GLP-1 predicted decreased glucose levels on WP. Obesity, hypertriglyceridemia and high fasting GLP-1 concentrations predicted increased glucose levels. Effects of WP supplementation on glycemia in T2DM depend on the baseline characteristics. Lower body weight, normal triglyceride and lower GLP-1 levels predict glucose lowering. In contrast, obesity, hypertriglyceridemia and high baseline GLP-1 predict increased glucose response.

Placebo effects in psychiatry: mediators and moderators

PubMed Central

Weimer, Katja; Colloca, Luana; Enck, Paul

2015-01-01

A strong placebo response in psychiatric disorders has been noted for the past 50 years and various attempts have been made to identify predictors of it, by use of meta-analyses of randomised controlled trials and laboratory studies. We reviewed 31 meta-analyses and systematic reviews of more than 500 randomised placebo-controlled trials across psychiatry (depression, schizophrenia, mania, attention-deficit hyperactivity disorder, autism, psychosis, binge-eating disorder, and addiction) for factors identified to be associated with increased placebo response. Of 20 factors discussed, only three were often linked to high placebo responses: low baseline severity of symptoms, more recent trials, and unbalanced randomisation (more patients randomly assigned to drug than placebo). Randomised controlled trials in non-drug therapy have not added further predictors, and laboratory studies with psychological, brain, and genetic approaches have not been successful in identifying predictors of placebo responses. This comprehensive Review suggests that predictors of the placebo response are still to be discovered, the response probably has more than one mediator, and that different and distinct moderators are probably what cause the placebo response within psychiatry and beyond. PMID:25815249

Increased mental slowing associated with the APOE epsilon4 allele after trihexyphenidyl oral anticholinergic challenge in healthy elderly.

PubMed

Pomara, Nunzio; Belzer, Ken; Hernando, Raymundo; De La Pena, Corazon; Sidtis, John J

2008-02-01

The objectives of this study were to examine the relationship between APOE epsilon4 and subjective effects of trihexyphenidyl on measures reflecting sedation and confusion and to investigate the relationship between trihexyphenidyl-induced subjective effects and objective memory performance. This study comprised 24 cognitively intact, health elderly adults (12 APOE epsilon4 carriers) at an outpatient geriatric psychiatry research clinic. This was a randomized, double blind, placebo-controlled, three-way, crossover experimental design. All participants received 1.0 mg or 2.0 mg trihexyphenidyl or placebo administered in counterbalanced sequences over a period of three consecutive weeks. Bond and Lader's visual analog scales and alternate versions of the Buschke Selective Reminding Test were administered in a repeated measures design at baseline, 1, 2.5, and 5 hours postdrug administration. A 2.0-mg oral dose of trihexyphenidyl resulted in increased subjective ratings of mental slowness in carriers of the APOE epsilon4 allele only. Drug effects as determined by difference scores between 2.0 mg trihexyphenidyl and placebo on ratings of mental slowness significantly correlated with total and delayed recall on the Buschke Selective Reminding Test in carriers of the APOE epsilon4 allele only. However, no significant effects were found with other visual analog scales reflecting subjective sedation and clear-headedness. The epsilon4 allele in healthy elderly was associated with increased subjective mental slowing after trihexyphenidyl anticholinergic challenge.

Early improvement in food cravings are associated with long-term weight loss success in a large clinical sample

PubMed Central

Dalton, M; Finlayson, G; Walsh, B; Halseth, A E; Duarte, C; Blundell, J E

2017-01-01

Background: Food cravings are associated with dysregulated eating behaviour and obesity, and may impede successful weight loss attempts. Gaining control over food craving is therefore a component in the management of obesity. The current paper examined whether early changes in control over food craving (assessed using the Craving Control subscale on the Control of Eating Questionnaire (CoEQ)) was predictive of weight loss in four phase 3 clinical trials investigating a sustained-release combination of naltrexone/bupropion (NB) in obese adults. The underlying component structure of the CoEQ was also examined. Method: In an integrated analysis of four 56-week phase 3 clinical trials, subjects completed the CoEQ and had their body weight measured at baseline and at weeks 8, 16, 28 and 56. All analyses were conducted on subjects who had complete weight and CoEQ measurements at baseline and week 56, and had completed 56 weeks of NB (n=1310) or placebo (n=736). A latent growth curve model was used to examine whether early changes in the CoEQ subscales were associated with decreases in weight loss over time. Confirmatory factor analysis (CFA) was used to determine the psychometric properties of the CoEQ. Results: The factor structure of the CoEQ was consistent with previous findings with a four-factor solution being confirmed: Craving Control, Positive Mood, Craving for Sweet and Craving for Savoury with good internal consistency (Cronbach’s α=0.72–0.92). Subjects with the greatest improvement in Craving Control at week 8 exhibited a greater weight loss at week 56. Conclusions: These findings highlight the importance of the experience of food cravings in the treatment of obesity and support the use of the CoEQ as a psychometric tool for the measurement of food cravings in research and the pharmacological management of obesity. PMID:28373674

Randomised controlled trial of the effects of L-ornithine on stress markers and sleep quality in healthy workers

PubMed Central

2014-01-01

Background L-ornithine is a non-essential, non-protein amino acid. Although L-ornithine is contained in various foods, the amount is usually small. Recently, studies have shown that orally administered L-ornithine reduced the stress response in animals. From these findings, we speculated that L-ornithine may play a role in the relieve of stress and improve sleep and fatigue symptoms in humans. Through a randomised, double-blind, placebo-controlled clinical study, we asked if L-ornithine could be beneficial to stress and sleep in healthy workers. Method Fifty-two apparently healthy Japanese adults who had previously felt slight stress as well as fatigue were recruited to be study participants and were randomly divided into either the L-ornithine (400 mg/day) or placebo group. They orally consumed the respective test substance every day for 8 weeks. Serum was collected for the assessment of cortisol and dehydroepiandrosterone-sulphate (DHEA-S). Perceived mood and quality of sleep were measured by the Profile of Mood States (POMS), Athens Insomnia Scale (AIS), and Ogri-Shirakawa-Azumi sleep inventory MA version (OSA-MA). Results Serum cortisol levels and the cortisol/DHEA-S ratio were significantly decreased in the L-ornithine group in comparison with the placebo group. Also, anger was reduced and perceived sleep quality was improved in the L-ornithine group. Conclusion L-ornithine supplementation has the potential to relieve stress and improve sleep quality related to fatigue, both objectively and subjectively. PMID:24889392

Psyllium supplementation in adolescents improves fat distribution & lipid profile: a randomized, participant-blinded, placebo-controlled, crossover trial.

PubMed

de Bock, Martin; Derraik, José G B; Brennan, Christine M; Biggs, Janene B; Smith, Greg C; Cameron-Smith, David; Wall, Clare R; Cutfield, Wayne S

2012-01-01

We aimed to assess the effects of psyllium supplementation on insulin sensitivity and other parameters of the metabolic syndrome in an at risk adolescent population. This study encompassed a participant-blinded, randomized, placebo-controlled, crossover trial. Subjects were 47 healthy adolescent males aged 15-16 years, recruited from secondary schools in lower socio-economic areas with high rates of obesity. Participants received 6 g/day of psyllium or placebo for 6 weeks, with a two-week washout before crossing over. Fasting lipid profiles, ambulatory blood pressure, auxological data, body composition, activity levels, and three-day food records were collected at baseline and after each 6-week intervention. Insulin sensitivity was measured by the Matsuda method using glucose and insulin values from an oral glucose tolerance test. 45 subjects completed the study, and compliance was very high: 87% of participants took >80% of prescribed capsules. At baseline, 44% of subjects were overweight or obese. 28% had decreased insulin sensitivity, but none had impaired glucose tolerance. Fibre supplementation led to a 4% reduction in android fat to gynoid fat ratio (p = 0.019), as well as a 0.12 mmol/l (6%) reduction in LDL cholesterol (p = 0.042). No associated adverse events were recorded. Dietary supplementation with 6 g/day of psyllium over 6 weeks improves fat distribution and lipid profile (parameters of the metabolic syndrome) in an at risk population of adolescent males. Australian New Zealand Clinical Trials Registry ACTRN12609000888268.

Efficacy of a Standardized Extract of Prunus mume in Liver Protection and Redox Homeostasis: A Randomized, Double-Blind, Placebo-Controlled Study.

PubMed

Beretta, Alberto; Accinni, Roberto; Dellanoce, Cinzia; Tonini, Annamaria; Cardot, Jean-Michel; Bussière, Anthony

2016-06-01

The antioxidant, anti-inflammatory and hepatoprotective effects of Prunus mume (PM) have previously been demonstrated. This double-blind, placebo-controlled study was designed to evaluate the influence of two doses of a food supplement, made of 150 mg of a standardized PM extract on liver transaminases, lipid profile, glycemia, neopterin and reduced and oxidized thiols in plasma and erythrocytes, during a 3-month treatment period, in healthy subjects with transaminases levels between 20 and 40 UI/L. Forty-five subjects (56.0 ± 11.6 years) were enrolled. The results showed a beneficial and statistically significant effect versus placebo of PM extract on liver function, with a decrease versus baseline in alanine aminotransferase (47%), aspartate aminotransferase (7%), gamma-glutamyl transpeptidase (15%) and glycemia (11%). The lipid profile modification was also positive with an increase versus baseline in HDL cholesterol (13%), and a decrease in LDL/HDL ratio (12%) and triglycerides (8%). The antioxidant action of PM translated into a decrease in oxidized glutathione, reduced/oxidized cysteine-glycine, oxidized cysteine (intracellular pro-oxidant) and neopterin (inflammation biomarker), was associated with an increase in reduced glutathione. These results are in favor of the use of a standardized extract of P. mume for the support of liver health and prevention of common metabolic and inflammation-based diseases. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Randomised controlled trial of the effects of L-ornithine on stress markers and sleep quality in healthy workers.

PubMed

Miyake, Mika; Kirisako, Takayoshi; Kokubo, Takeshi; Miura, Yutaka; Morishita, Koji; Okamura, Hisayoshi; Tsuda, Akira

2014-06-03

L-ornithine is a non-essential, non-protein amino acid. Although L-ornithine is contained in various foods, the amount is usually small.Recently, studies have shown that orally administered L-ornithine reduced the stress response in animals.From these findings, we speculated that L-ornithine may play a role in the relieve of stress and improve sleep and fatigue symptoms in humans. Through a randomised, double-blind, placebo-controlled clinical study, we asked if L-ornithine could be beneficial to stress and sleep in healthy workers. Fifty-two apparently healthy Japanese adults who had previously felt slight stress as well as fatigue were recruited to be study participants and were randomly divided into either the L-ornithine (400 mg/day) or placebo group. They orally consumed the respective test substance every day for 8 weeks. Serum was collected for the assessment of cortisol and dehydroepiandrosterone-sulphate (DHEA-S). Perceived mood and quality of sleep were measured by the Profile of Mood States (POMS), Athens Insomnia Scale (AIS), and Ogri-Shirakawa-Azumi sleep inventory MA version (OSA-MA). Serum cortisol levels and the cortisol/DHEA-S ratio were significantly decreased in the L-ornithine group in comparison with the placebo group. Also, anger was reduced and perceived sleep quality was improved in the L-ornithine group. L-ornithine supplementation has the potential to relieve stress and improve sleep quality related to fatigue, both objectively and subjectively.

Antagonism of NMDA receptors as a potential treatment for Down syndrome: a pilot randomized controlled trial

PubMed Central

Boada, R; Hutaff-Lee, C; Schrader, A; Weitzenkamp, D; Benke, T A; Goldson, E J; Costa, A C S

2012-01-01

Down syndrome (DS) is the most common genetic cause of intellectual disability. The N-methyl-D-aspartate (NMDA) receptor uncompetitive antagonist, memantine hydrochloride (memantine), has been shown to improve learning/memory and rescue one form of hippocampus synaptic plasticity dysfunction in the best-studied mouse model of DS available, the Ts65Dn mouse. Given the status of memantine as a treatment for Alzheimer's disease (AD) approved by the Food and Drug Administration, the preclinical evidence of potential efficacy in Ts65Dn mice, and the favorable safety profile of memantine, we designed a study to investigate whether the findings in the mouse model could be translated to individuals with DS. In this pilot, proof-of-principle study we hypothesized that memantine therapy would improve test scores of young adults with DS on measures of episodic and spatial memory, which are generally considered to be hippocampus dependent. Accordingly, in this randomized, double-blind, placebo-controlled trial, we compared the effect of 16-week treatment with either memantine or placebo on cognitive and adaptive functions of 40 young adults with DS using a carefully selected set of neuropsychological outcome measures. Safety and tolerability were also monitored. Although no significant differences were observed between the memantine and placebo groups on the two primary outcome measures, we found a significant improvement in the memantine group in one of the secondary measures associated with the primary hypothesis. Only infrequent and mild adverse events were noted. PMID:22806212

Effect of clinical response to active drugs and placebo on antipsychotics and mood stabilizers relative efficacy for bipolar depression and mania: A meta-regression analysis.

PubMed

Bartoli, Francesco; Clerici, Massimo; Di Brita, Carmen; Riboldi, Ilaria; Crocamo, Cristina; Carrà, Giuseppe

2018-04-01

Randomised placebo-controlled trials investigating treatments for bipolar disorder have been hampered by wide variations of active drugs and placebo clinical response rates. It is important to estimate whether the active drug or placebo response has a greater influence in determining the relative efficacy of drugs for psychosis (antipsychotics) and relapse prevention (mood stabilisers) for bipolar depression and mania. We identified 53 randomised, placebo-controlled trials assessing antipsychotic or mood stabiliser monotherapy ('active drugs') for bipolar depression or mania. We carried out random-effects meta-regressions, estimating the influence of active drugs and placebo response rates on treatment relative efficacy. Meta-regressions showed that treatment relative efficacy for bipolar mania was influenced by the magnitude of clinical response to active drugs ( p=0.002), but not to placebo ( p=0.60). On the other hand, treatment relative efficacy for bipolar depression was influenced by response to placebo ( p=0.047), but not to active drugs ( p=0.98). Despite several limitations, our unexpected findings showed that antipsychotics / mood stabilisers relative efficacy for bipolar depression seems unrelated to active drugs response rates, depending only on clinical response to placebo. Future research should explore strategies to reduce placebo-related issues in randomised, placebo-controlled trials for bipolar depression.

Improved Tolerance to a New Amino Acid-Based Formula by Infants With Cow's Milk Protein Allergy.

PubMed

Jirapinyo, Pipop; Densupsoontorn, Narumon; Kangwanpornsiri, Channagan; Wongarn, Renu; Tirapongporn, Hathaichanok; Chotipanang, Kwanjai; Phuangphan, Phakkanan

2016-12-01

Prevalence and severity of cow's milk protein allergy (CMA) in infants are increasing. A proportion of infants with CMA still elicit signs and symptoms of CMA while ingesting commercial amino acid-based formulas (AAFs). We propose that protein in glucose polymers (GPs) derived from corn starch in the AAFs might be the cause of intolerance to AAF in some infants. We thus have produced small molecules of GPs from rice starch, eliminating the protein fraction from them, and subsequently used them as the sole source of carbohydrate in a new amino acid-based formula (NAAF). The efficacy of the NAAF was compared with that of an AAF in a double-blind, placebo-controlled food challenge (DBPCFC) in young infants with CMA aged <4 months. Infants consumed each formula for 14 days before switching to the other one. If no respiratory, dermatologic, and gastrointestinal symptom occurred, it was considered tolerance. After the challenge, infants consumed the tolerated formula for 4 weeks to prove real tolerance to that formula. Of 46 infants, 23 were intolerant to the AAF, of whom 7 (30.4%) were also intolerant to the NAAF. Sixteen of the 23 infants who were intolerant to the AAF could tolerate the NAAF ( P < .05). The minimal important difference of decreasing percentage of intolerance to the NAAF was 34.8% compared with the infants who were intolerant to the AAF. The NAAF is better tolerated than a commercially available AAF for the management of infants with CMA.

Effects of kivia powder on Gut health in patients with occasional constipation: a randomized, double-blind, placebo-controlled study

PubMed Central

2013-01-01

Objective To evaluate the efficacy of Kivia powder on supporting overall gut health through the relief of the discomfort of occasional constipation. Design Randomized, double-blind, placebo-controlled, parallel-group trial. Interventions The investigational product for this study was Kivia powder (Vital Food Processors Ltd., Auckland, New Zealand), containing the active ingredient Zyactinase™, 5.5 g taken daily for four weeks. Results One hundred thirty-eight subjects reporting occasional constipation were screened and 87 were randomized to placebo (n = 44) and product (n = 43). Bowel movement frequency, as measured by both average daily spontaneous bowel movements (SBM) and complete spontaneous bowel movements (CSBM), were the same in both groups at baseline. There were significant increases in spontaneous bowel movements at week 1 (p = 0.001), week 2 (p = 0.001), week 3 (p = 0.000), and week 4 (p = 0.000) compared to baseline. SBM demonstrated significant differences between the treatment group and the placebo group at week 3 (p = 0.000), and week 4 (p = 0.020). The treatment group demonstrated a significantly higher rate of SBM at week 3 (p = 000) and from baseline to week 4 (p = 0.019). Significant increases in complete spontaneous bowel movements were observed at week 1 (p = 0.000), week 2 (p = 0.000), week 3 (p = 0.000), and week 4 (p = 0.000) compared to baseline. Moreover, CSBM was significantly higher for the treatment group compared to placebo at week 2 (p = 0.001). The change in average daily CSBM from baseline to week 2 was significantly higher in the treatment group than in the placebo group (p = 0.004). Abdominal discomfort or pain demonstrated significant differences between groups at week 1 (p = 0.044) and week 3 (p = 0.026). Flatulence was significantly lower for active group compared to placebo at week 2 (p = 0.047) and week 3 (p = 0.023). The number of bowel movements associated with urgency was significantly lower in the treatment group compared to the placebo group at week 3 (p = 0.048). In addition, it was decreased from baseline to week 1 (p = 0.040) and from baseline to week 3 (p = 0.024) in the treatment group, while the placebo group did not report any reductions in bowel urgency. Bowel movements in the treatment arm were significantly smoother and softer by week 2 (p = 0.020) and week 3 (p = 0.041). Conclusions Treatment with Kivia powder, an extract of kiwifruit containing Zyactinase™, for four weeks was well tolerated and more effective than placebo in gently enhancing bowel movement frequency and reducing abdominal pain and flatulence in subjects with occasional constipation. Trial registration ISRCTN: ISRCTN49036618 PMID:23758673

Food safety systems in a small dairy factory: implementation, major challenges, and assessment of systems' performances.

PubMed

Cusato, Sueli; Gameiro, Augusto H; Corassin, Carlos H; Sant'ana, Anderson S; Cruz, Adriano G; Faria, José de Assis F; de Oliveira, Carlos Augusto F

2013-01-01

The present study describes the implementation of a food safety system in a dairy processing plant located in the State of São Paulo, Brazil, and the challenges found during the process. In addition, microbiological indicators have been used to assess system's implementation performance. The steps involved in the implementation of a food safety system included a diagnosis of the prerequisites, implementation of the good manufacturing practices (GMPs), sanitation standard operating procedures (SSOPs), training of the food handlers, and hazard analysis and critical control point (HACCP). In the initial diagnosis, conformity with 70.7% (n=106) of the items analyzed was observed. A total of 12 critical control points (CCPs) were identified: (1) reception of the raw milk, (2) storage of the raw milk, (3 and 4) reception of the ingredients and packaging, (5) milk pasteurization, (6 and 7) fermentation and cooling, (8) addition of ingredients, (9) filling, (10) storage of the finished product, (11) dispatching of the product, and (12) sanitization of the equipment. After implementation of the food safety system, a significant reduction in the yeast and mold count was observed (p<0.05). The main difficulties encountered for the implementation of food safety system were related to the implementation of actions established in the flow chart and to the need for constant training/adherence of the workers to the system. Despite this, the implementation of the food safety system was shown to be challenging, but feasible to be reached by small-scale food industries.

Enhanced Striatal Dopamine Release During Food Stimulation in Binge Eating Disorder

PubMed Central

Wang, Gene-Jack; Geliebter, Allan; Volkow, Nora D.; Telang, Frank W.; Logan, Jean; Jayne, Millard C.; Galanti, Kochavi; Selig, Peter A.; Han, Hao; Zhu, Wei; Wong, Christopher T.; Fowler, Joanna S.

2011-01-01

Subjects with binge eating disorder (BED) regularly consume large amounts of food in short time periods. The neurobiology of BED is poorly understood. Brain dopamine, which regulates motivation for food intake, is likely to be involved. We assessed the involvement of brain dopamine in the motivation for food consumption in binge eaters. Positron emission tomography (PET) scans with [11C]raclopride were done in 10 obese BED and 8 obese subjects without BED. Changes in extracellular dopamine in the striatum in response to food stimulation in food-deprived subjects were evaluated after placebo and after oral methylphenidate (MPH), a drug that blocks the dopamine reuptake transporter and thus amplifies dopamine signals. Neither the neutral stimuli (with or without MPH) nor the food stimuli when given with placebo increased extracellular dopamine. The food stimuli when given with MPH significantly increased dopamine in the caudate and putamen in the binge eaters but not in the nonbinge eaters. Dopamine increases in the caudate were significantly correlated with the binge eating scores but not with BMI. These results identify dopamine neurotransmission in the caudate as being of relevance to the neurobiology of BED. The lack of correlation between BMI and dopamine changes suggests that dopamine release per se does not predict BMI within a group of obese individuals but that it predicts binge eating. PMID:21350434

The effect of vitamin D supplement on the score and quality of sleep in 20-50 year-old people with sleep disorders compared with control group.

PubMed

Majid, Mohammad Shahi; Ahmad, Hosseini Seyed; Bizhan, Helli; Mohammad Hosein, Haghighi Zade; Mohammad, Abolfathi

2017-05-05

Sleep quality may be directly related with vitamin D serum level. Some studies found that people with lower vitamin D serum level experienced a lower sleep quality. Consequently, this study aimed at determining the effect of vitamin D supplements on sleep score and quality in 20-50 year-old people with sleep disorders. This double blind, clinical trial was performed in November 2015-February 2016 on 89 people with sleep disorders based on Petersburg's Sleep Index. Patient samples were divided randomly into two groups: intervention and placebo. At the end of the study, the data on 89 subjects (44 in intervention group and 45 people in placebo group) were examined. Intervention group received a 50 000-unit vitamin D supplement, one in a fortnight for 8 weeks. Meanwhile, placebo group received placebo. Before and after intervention, Petersburg's Sleep Quality Questionnaire, International Physical Activity Questionnaire, general information questionnaire, sun exposure, vitamin D serum level and 3-day food record questionnaire were assessed and recorded for all participants. To analyze data, t-test, chi square, ANCOVA, U-Mann-Whitney and Wilcoxon statistical tests were used. Based on the results of the present study, at the end of the study sleep score (PSQI) reduced significantly in vitamin recipients as compared with placebo recipients (P < 0.05). This difference was significant even after modifying confounding variables (P < 0.05). This study shows that the use of vitamin D supplement improves sleep quality, reduces sleep latency, raises sleep duration and improves subjective sleep quality in people of 20-50 year-old with sleep disorder.

Serum IGF-1 Concentrations Change With Soy and Seaweed Supplements in Healthy Postmenopausal American Women

PubMed Central

Teas, Jane; Irhimeh, Mohammad R.; Druker, Susan; Hurley, Thomas G.; Hébert, James R.; Savarese, Todd M.; Kurzer, Mindy S.

2011-01-01

Insulin-like growth factor 1 (IGF-1) is an anabolic hormone important for growth and development. However, high-circulating serum concentrations in adults are associated with increased risk of postmenopausal breast cancer. Nutritional status and specific foods influence serum IGF-1 concentrations. Breast cancer incidence is typically low in Asian countries where soy is commonly consumed. Paradoxically, soy supplement trials in American women have reported significant increases in IGF-1. Seaweed also is consumed regularly in Asian countries where breast cancer risk is low. We investigated the possibility that seaweed could modify soy-associated increases in IGF-1 in American women. Thirty healthy postmenopausal women (mean age 58 yr) participated in this 14-wk double-blinded, randomized, placebo-controlled crossover clinical trial. Participants consumed 5 g/day placebo or seaweed (Alaria esculenta) in capsules for 7 wk. During the 7th wk, a high-soy protein isolate powder was added (2 mg/kg body weight aglycone equivalent isoflavones). Overnight fasting blood samples were collected after each intervention period. Soy significantly increased serum IGF-1 concentrations compared to the placebo (21.2 nmol/L for soy vs. 16.9 nmol/L for placebo; P = 0.0001). The combination of seaweed and soy significantly reduced this increase by about 40% (21.2 nmol/L for soy alone vs. 19.4 nmol/L; P = 0.01). Concurrent seaweed and soy consumption may be important in modifying the effect of soy on IGF-1 serum concentrations. PMID:21711174

Serum IGF-1 concentrations change with soy and seaweed supplements in healthy postmenopausal American women.

PubMed

Teas, Jane; Irhimeh, Mohammad R; Druker, Susan; Hurley, Thomas G; Hébert, James R; Savarese, Todd M; Kurzer, Mindy S

2011-01-01

Insulin-like growth factor 1 (IGF-1) is an anabolic hormone important for growth and development. However, high-circulating serum concentrations in adults are associated with increased risk of postmenopausal breast cancer. Nutritional status and specific foods influence serum IGF-1 concentrations. Breast cancer incidence is typically low in Asian countries where soy is commonly consumed. Paradoxically, soy supplement trials in American women have reported significant increases in IGF-1. Seaweed also is consumed regularly in Asian countries where breast cancer risk is low. We investigated the possibility that seaweed could modify soy-associated increases in IGF-1 in American women. Thirty healthy postmenopausal women (mean age 58 yr) participated in this 14-wk double-blinded, randomized, placebo-controlled crossover clinical trial. Participants consumed 5 g/day placebo or seaweed (Alaria esculenta) in capsules for 7 wk. During the 7th wk, a high-soy protein isolate powder was added (2 mg/kg body weight aglycone equivalent isoflavones). Overnight fasting blood samples were collected after each intervention period. Soy significantly increased serum IGF-1 concentrations compared to the placebo (21.2 nmol/L for soy vs. 16.9 nmol/L for placebo; P = 0.0001). The combination of seaweed and soy significantly reduced this increase by about 40% (21.2 nmol/L for soy alone vs. 19.4 nmol/L; P = 0.01). Concurrent seaweed and soy consumption may be important in modifying the effect of soy on IGF-1 serum concentrations.

Randomized trial of the effect of drug presentation on asthma outcomes: the American Lung Association Asthma Clinical Research Centers.

PubMed

Wise, Robert A; Bartlett, Susan J; Brown, Ellen D; Castro, Mario; Cohen, Rubin; Holbrook, Janet T; Irvin, Charles G; Rand, Cynthia S; Sockrider, Marianna M; Sugar, Elizabeth A

2009-09-01

Information that enhances expectations about drug effectiveness improves the response to placebos for pain. Although asthma symptoms often improve with placebo, it is not known whether the response to placebo or active treatment can be augmented by increasing expectation of benefit. The study objective was to determine whether response to placebo or a leukotriene antagonist (montelukast) can be augmented by messages that increase expectation of benefit. A randomized 20-center controlled trial enrolled 601 asthmatic patients with poor symptom control who were assigned to one of 5 study groups. Participants were randomly assigned to one of 4 treatment groups in a factorial design (ie, placebo with enhanced messages, placebo with neutral messages, montelukast with enhanced messages, or montelukast with neutral messages) or to usual care. Assignment to study drug was double masked, assignment to message content was single masked, and usual care was not masked. The enhanced message aimed to increase expectation of benefit from the drug. The primary outcome was mean change in daily peak flow over 4 weeks. Secondary outcomes included lung function and asthma symptom control. Peak flow and other lung function measures were not improved in participants assigned to the enhanced message groups versus the neutral messages groups for either montelukast or placebo; no differences were noted between the neutral placebo and usual care groups. Placebo-treated participants had improved asthma control with the enhanced message but not montelukast-treated participants; the neutral placebo group did have improved asthma control compared with the usual care group after adjusting for baseline difference. Headaches were more common in participants provided messages that mentioned headache as a montelukast side effect. Optimistic drug presentation augments the placebo effect for patient-reported outcomes (asthma control) but not lung function. However, the effect of montelukast was not enhanced by optimistic messages regarding treatment effectiveness.

Heartburn treatment in primary care: randomised, double blind study for 8 weeks

PubMed Central

Hatlebakk, Jan G; Hyggen, Arild; Madsen, Per H; Walle, Per O; Schulz, Tom; Mowinckel, Petter; Bernklev, Tomm; Berstad, Arnold

1999-01-01

Objective To compare the effects and tolerability of omeprazole and cisapride with that of placebo for control of heartburn in primary care patients. Design Randomised, double blind, placebo controlled study. Setting 65 primary care practices in Norway. Participants 483 untreated patients with complaints of heartburn ⩾3 days a week, with at most grade 1 reflux oesophagitis. Interventions Omeprazole 20 mg once daily, cisapride 20 mg twice daily, or placebo for 8 weeks. Main outcome measures Adequate control of heartburn, defined as ⩽1 day of the past 7 days with no more than mild heartburn, after 4 weeks of treatment. Results In the all patients treated analysis, adequate control of heartburn was achieved in 71% of patients taking omeprazole, 22% taking cisapride, and 18% taking placebo after 4 weeks of treatment (omeprazole v cisapride and placebo, P<0.0001; cisapride v placebo, non-significant). Results were comparable in patients with or without reflux oesophagitis. In patients treated with omeprazole only, symptom control was achieved significantly more often in patients positive for Helicobacter pylori. Antacid use was 2-3 times greater in patients taking cisapride or placebo than in those taking omeprazole. Relief of non-reflux symptoms did not significantly differ between the three groups. Significantly more patients taking cisapride reported adverse events than those taking omeprazole or placebo. Conclusions Omeprazole 20 mg once daily was highly effective in relieving heartburn whereas cisapride 20 mg twice daily was not significantly more effective than placebo. Key messagesIn primary care patients, heartburn is commonly treated empiricallyMost randomised clinical trials of treatment for heartburn have been conducted in specialist care, and documentation for empirical treatment is limitedOmeprazole was significantly more effective than cisapride or placebo in controlling heartburn and other symptoms of gastro-oesophageal reflux after 2, 4, and 8 weeks, whereas cisapride did not differ significantly from placeboOmeprazole should be considered as a first choice for empirical treatment of heartburn in primary care PMID:10463897

Olanzapine versus Placebo in Adolescents with Schizophrenia; a 6-Week, Randomized Double-Blind, Placebo-Controlled Trial

ERIC Educational Resources Information Center

Kryzhanovskaya, Ludmila; Schulz, Charles; McDougle, Christopher; Frazier, Jean; Dittman, Ralf; Robertson-Plouch, Carol; Bauer, Theresa; Xu, Wen; Wang, Wei; Carlson, Janice; Tohen, Mauricio

2009-01-01

The efficacy of olanzapine in treating schizophrenia was tested through a placebo-controlled trial involving one hundred seven inpatient and outpatients adolescents. Patients who took olanzapine experienced significant symptom improvement.

Lithium Treatment of Acute Mania in Adolescents: A Placebo-Controlled Discontinuation Study

ERIC Educational Resources Information Center

Kafantaris, Vivian; Coletti, Daniel J.; Dicker, Robert; Padula, Gina; Pleak, Richard R.; Alvir, Jose Ma. J.; Kane, John M.

2004-01-01

Objective: There are no published placebo-controlled studies of any agent in the treatment of acute mania in children or adolescents. This is the first placebo-controlled study of lithium's efficacy in the treatment of acute mania in adolescents. Method: In this discontinuation study, participants received open treatment with lithium at…

Ethics of placebo-controlled clinical trials in multiple sclerosis: a reassessment.

PubMed

Polman, C H; Reingold, S C; Barkhof, F; Calabresi, P A; Clanet, M; Cohen, J A; Cutter, G R; Freedman, M S; Kappos, L; Lublin, F D; McFarland, H F; Metz, L M; Miller, A E; Montalban, X; O'Connor, P W; Panitch, H; Richert, J R; Petkau, J; Schwid, S R; Sormani, M P; Thompson, A J; Weinshenker, B G; Wolinsky, J S

2008-03-25

The increasing number of established effective therapies for relapsing multiple sclerosis (MS) and emerging consensus for early treatment raise practical concerns and ethical dilemmas for placebo-controlled clinical trials in this disease. An international group of clinicians, ethicists, statisticians, regulators, and representatives from the pharmaceutical industry convened to reconsider prior recommendations regarding the ethics of placebo-controlled trials in MS. The group concluded that placebo-controlled trials can still be done ethically, with restrictions. For patients with relapsing MS for which established effective therapies exist, placebo-controlled trials should only be offered with rigorous informed consent if the subjects refuse to use these treatments, have not responded to them, or if these treatments are not available to them for other reasons (e.g., economics). Suggestions are provided to protect subject autonomy and improve informed consent procedures. Recommendations are tighter than previously suggested for placebo-controlled trials in "resource-restricted" environments where established therapies may not be available. Guidance is also provided on the ethics of alternative trial designs and the balance between study subject burden and risk, scientific rationale and interpretability of trial outcomes.

Randomized controlled ferret study to assess the direct impact of 2008-09 trivalent inactivated influenza vaccine on A(H1N1)pdm09 disease risk.

PubMed

Skowronski, Danuta M; Hamelin, Marie-Eve; De Serres, Gaston; Janjua, Naveed Z; Li, Guiyun; Sabaiduc, Suzana; Bouhy, Xavier; Couture, Christian; Leung, Anders; Kobasa, Darwyn; Embury-Hyatt, Carissa; de Bruin, Erwin; Balshaw, Robert; Lavigne, Sophie; Petric, Martin; Koopmans, Marion; Boivin, Guy

2014-01-01

During spring-summer 2009, several observational studies from Canada showed increased risk of medically-attended, laboratory-confirmed A(H1N1)pdm09 illness among prior recipients of 2008-09 trivalent inactivated influenza vaccine (TIV). Explanatory hypotheses included direct and indirect vaccine effects. In a randomized placebo-controlled ferret study, we tested whether prior receipt of 2008-09 TIV may have directly influenced A(H1N1)pdm09 illness. Thirty-two ferrets (16/group) received 0.5 mL intra-muscular injections of the Canadian-manufactured, commercially-available, non-adjuvanted, split 2008-09 Fluviral or PBS placebo on days 0 and 28. On day 49 all animals were challenged (Ch0) with A(H1N1)pdm09. Four ferrets per group were randomly selected for sacrifice at day 5 post-challenge (Ch+5) and the rest followed until Ch+14. Sera were tested for antibody to vaccine antigens and A(H1N1)pdm09 by hemagglutination inhibition (HI), microneutralization (MN), nucleoprotein-based ELISA and HA1-based microarray assays. Clinical characteristics and nasal virus titers were recorded pre-challenge then post-challenge until sacrifice when lung virus titers, cytokines and inflammatory scores were determined. Baseline characteristics were similar between the two groups of influenza-naïve animals. Antibody rise to vaccine antigens was evident by ELISA and HA1-based microarray but not by HI or MN assays; virus challenge raised antibody to A(H1N1)pdm09 by all assays in both groups. Beginning at Ch+2, vaccinated animals experienced greater loss of appetite and weight than placebo animals, reaching the greatest between-group difference in weight loss relative to baseline at Ch+5 (7.4% vs. 5.2%; p = 0.01). At Ch+5 vaccinated animals had higher lung virus titers (log-mean 4.96 vs. 4.23pfu/mL, respectively; p = 0.01), lung inflammatory scores (5.8 vs. 2.1, respectively; p = 0.051) and cytokine levels (p>0.05). At Ch+14, both groups had recovered. Findings in influenza-naïve, systematically-infected ferrets may not replicate the human experience. While they cannot be considered conclusive to explain human observations, these ferret findings are consistent with direct, adverse effect of prior 2008-09 TIV receipt on A(H1N1)pdm09 illness. As such, they warrant further in-depth investigation and search for possible mechanistic explanations.

Predicting reactivity threshold in children with anaphylaxis to peanut.

PubMed

Reier-Nilsen, T; Michelsen, M M; Lødrup Carlsen, K C; Carlsen, K-H; Mowinckel, P; Nygaard, U C; Namork, E; Borres, M P; Håland, G

2018-04-01

Peanut allergy necessitates dietary restrictions, preferably individualized by determining reactivity threshold through an oral food challenge (OFC). However, risk of systemic reactions often precludes OFC in children with severe peanut allergy. We aimed to determine whether clinical and/or immunological characteristics were associated with reactivity threshold in children with anaphylaxis to peanut and secondarily, to investigate whether these characteristics were associated with severity of the allergic reaction during OFC. A double-blinded placebo-controlled food challenge (DBPCFC) with peanut was performed in 96 5- to 15-year-old children with a history of severe allergic reactions to peanut and/or sensitization to peanut (skin prick test [SPT] ≥3 mm or specific immunoglobulin E [s-IgE] ≥0.35 kUA/L). Investigations preceding the DBPCFC included a structured interview, SPT, lung function measurements, serological immunology assessment (IgE, IgG and IgG 4 ), basophil activation test (BAT) and conjunctival allergen provocation test (CAPT). International standards were used to define anaphylaxis and grade the allergic reaction during OFC. During DBPCFC, all 96 children (median age 9.3, range 5.1-15.2) reacted with anaphylaxis (moderate objective symptoms from at least two organ systems). Basophil activation (CD63 + basophils ≥15%), peanut SPT and the ratio of peanut s-IgE/total IgE were significantly associated with reactivity threshold and lowest observed adverse events level (LOAEL) (all P < .04). Basophil activation best predicted very low threshold level (<3 mg of peanut protein), with an optimal cut-off of 75.8% giving a 93.5% negative predictive value. None of the characteristics were significantly associated with the severity of allergic reaction. In children with anaphylaxis to peanut, basophil activation, peanut SPT and the ratio of peanut s-IgE/total IgE were associated with reactivity threshold and LOAEL, but not with allergy reaction severity. © 2017 John Wiley & Sons Ltd.

Libertas: rationale and study design of a multicentre, Phase II, double-blind, randomised, placebo-controlled investigation to evaluate the efficacy, safety and tolerability of locally applied NRL001 in patients with faecal incontinence.

PubMed

Siproudhis, L; Jones, D; Shing, R Ng Kwet; Walker, D; Scholefield, J H

2014-03-01

Faecal incontinence affects up to 8% of adults. Associated social isolation and subsequent depression can have devastating effects on quality of life (QoL). Faecal incontinence is an underreported health problem as the social isolation and stigma that patients experience makes it difficult for sufferers to discuss their condition with a physician. There have been few well-designed, placebo-controlled clinical trials of treatment for faecal incontinence and little clinical evidence is available to inform the most appropriate management strategies. Libertas, a robustly designed study will investigate the efficacy and safety of NRL001 (1R,2S-methoxamine), an α1 -adrenoceptor agonist, in the treatment of faecal incontinence. Libertas is a multicentre, Phase II, double-blind, randomised, placebo-controlled, parallel group study. Patient recruitment took place across 55 study centres in Europe. Patients suffering with faecal incontinence were randomised into four groups (approximately 110 each) to receive once daily self-administered doses of NRL001 (5, 7.5 or 10 mg or placebo in a suppository formulation) for 8 weeks. The primary objective of Libertas is to assess the impact of once daily administration of NRL001 on the severity and frequency of incontinence episodes as assessed by the Wexner score at 4 weeks, compared with placebo. Secondary outcomes include measures of efficacy of NRL001 compared with placebo following 8 weeks treatment; safety and tolerability; evaluation of plasma pharmacokinetics; establishment of any pharmacokinetic/pharmacodynamic relationship to adverse events; dose-response relationship; the efficacy of NRL001 therapy at 4 and 8 weeks assessed by the Vaizey score; and QoL using the Faecal Incontinence Quality of Life and the EQ-5D-5L Healthcare Questionnaires following 4 and 8 weeks NRL001 therapy. Overall patient satisfaction with the treatment will also be evaluated. This is the first randomised controlled study to investigate the efficacy and safety of a selective α1 -adrenoceptor agonist for the treatment of faecal incontinence. Furthermore, this is the first time the impact of NRL001 on assessments of QoL, health outcomes and patient satisfaction will be assessed. Innovative strategies were developed to meet the challenge of recruiting patients for this study, for example, media advertising, posters and mailshots as allowed by each study centre. Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.

A process-based approach to characterizing the effect of acute alprazolam challenge on visual paired associate learning and memory in healthy older adults.

PubMed

Pietrzak, Robert H; Scott, James Cobb; Harel, Brian T; Lim, Yen Ying; Snyder, Peter J; Maruff, Paul

2012-11-01

Alprazolam is a benzodiazepine that, when administered acutely, results in impairments in several aspects of cognition, including attention, learning, and memory. However, the profile (i.e., component processes) that underlie alprazolam-related decrements in visual paired associate learning has not been fully explored. In this double-blind, placebo-controlled, randomized cross-over study of healthy older adults, we used a novel, "process-based" computerized measure of visual paired associate learning to examine the effect of a single, acute 1-mg dose of alprazolam on component processes of visual paired associate learning and memory. Acute alprazolam challenge was associated with a large magnitude reduction in visual paired associate learning and memory performance (d = 1.05). Process-based analyses revealed significant increases in distractor, exploratory, between-search, and within-search error types. Analyses of percentages of each error type suggested that, relative to placebo, alprazolam challenge resulted in a decrease in the percentage of exploratory errors and an increase in the percentage of distractor errors, both of which reflect memory processes. Results of this study suggest that acute alprazolam challenge decreases visual paired associate learning and memory performance by reducing the strength of the association between pattern and location, which may reflect a general breakdown in memory consolidation, with less evidence of reductions in executive processes (e.g., working memory) that facilitate visual paired associate learning and memory. Copyright © 2012 John Wiley & Sons, Ltd.

Differential effects of tri-allelic 5-HTTLPR polymorphisms in healthy subjects on mood and stress performance after tryptophan challenge.

PubMed

Markus, C Rob; Firk, Christine

2009-12-01

Earlier data suggest that a polymorphism at the serotonin (5-HT) transporter gene (5-HTTLPR) may affect depression particularly in the face of stress due to interactions between 5-HT vulnerability and stress exposure. However, this interaction between 5-HT transporter-linked transcriptional promoter region (5-HTTLPR), 5-HT vulnerability and the affective effects of stress exposure has not yet been investigated. As participants with short-allele 5-HTTLPR genotypes may exhibit enhanced 5-HT vulnerability, this study examines the effects of tryptophan challenge on stress reactivity and performance in healthy participants with S'/S' vs L'/L' genotypes. Sixteen healthy subjects with homozygotic short alleles (S'/S'=S/L(G,) L(G)/L(G)) and 14 subjects with homozygotic long alleles (L'/L'=L(A)/L(A)) of the 5-HTTLPR were tested in a double-blind placebo-controlled design under acute stress exposure following tryptophan challenge or placebo. Although there were no 5-HTTLPR-related differences in stress responses, significant beneficial effects of tryptophan challenge on mood and stress performance were exclusively found in participants with S'/S' genotypes. These findings suggest greater brain 5-HT vulnerability to tryptophan manipulations in participants with S'/S' as compared with L'/L' 5-HTTLPR genotypes. This apparent genetic 5-HT vulnerability may become a meaningful risk factor for depression when brain 5-HT falls below functional need in the face of real severe stressful life events.