A Prospective, Randomized, Double-blind, Split-face Clinical Trial Comparing the Efficacy of Two Topical Human Growth Factors for the Rejuvenation of the Aging Face

PubMed Central

Goldman, Mitchel P.

2017-01-01

Background: Cosmeceutical products represent an increasingly important therapeutic option for anti-aging and rejuvenation, either used alone or in combination with dermatologic surgical procedures. Among this group of products, topical growth factors have demonstrated efficacy in randomized, controlled clinical trials. However, comparisons between different products remain uncommon. Objective: The objective of this randomized, double-blind, split-face clinical trial was to compare two different topical growth factor formulations derived from either human fibroblasts or human adipose tissue derived mesenchymal stem cells. Methods: This was an institutional review board-approved, randomized, double-blind, split-face clinical trial involving 20 healthy subjects with moderate-to-severe facial wrinkling secondary to photodamage. One half of the face was randomized to receive topical human fibroblast growth factors and the other topical human mesenchymal stem cell growth factors. Treatment was continued for three months, and evaluations were performed in a double-blind fashion. Results: Both growth factor formulations achieved significant improvement in facial wrinkling. Blinded investigator and subject evaluations did not detect any significant differences between the two formulations in terms of efficacy, safety, or tolerability. Conclusion: Both human fibroblast growth factors and human mesenchymal stem cell growth factors are effective at facial rejuvenation. Topical growth factors represent a useful therapeutic modality. PMID:28670356

A Prospective, Randomized, Double-blind, Split-face Clinical Trial Comparing the Efficacy of Two Topical Human Growth Factors for the Rejuvenation of the Aging Face.

PubMed

Wu, Douglas C; Goldman, Mitchel P

2017-05-01

Background: Cosmeceutical products represent an increasingly important therapeutic option for anti-aging and rejuvenation, either used alone or in combination with dermatologic surgical procedures. Among this group of products, topical growth factors have demonstrated efficacy in randomized, controlled clinical trials. However, comparisons between different products remain uncommon. Objective: The objective of this randomized, double-blind, split-face clinical trial was to compare two different topical growth factor formulations derived from either human fibroblasts or human adipose tissue derived mesenchymal stem cells. Methods: This was an institutional review board-approved, randomized, double-blind, split-face clinical trial involving 20 healthy subjects with moderate-to-severe facial wrinkling secondary to photodamage. One half of the face was randomized to receive topical human fibroblast growth factors and the other topical human mesenchymal stem cell growth factors. Treatment was continued for three months, and evaluations were performed in a double-blind fashion. Results: Both growth factor formulations achieved significant improvement in facial wrinkling. Blinded investigator and subject evaluations did not detect any significant differences between the two formulations in terms of efficacy, safety, or tolerability. Conclusion: Both human fibroblast growth factors and human mesenchymal stem cell growth factors are effective at facial rejuvenation. Topical growth factors represent a useful therapeutic modality.

Treatment of toxoplasmic lymphadenitis with co-trimoxazole: double-blind, randomized clinical trial.

PubMed

Alavi, Seyed Mohammad; Alavi, Leila

2010-09-01

Lymphadenitis is one of the presenting signs of toxoplasmosis. Co-trimoxazole (CTM) has a good therapeutic effect on ocular and cerebral infections caused by Toxoplasma gondii. Since this infection is endemic in Ahvaz and because of the lack of investigations into the therapeutic effects of CTM in toxoplasmic lymphadenitis (TL), this study was performed from 2005 to 2007 to determine the therapeutic effects of CTM on TL in Ahvaz. Forty-six patients with TL were enrolled in this randomized, double-blind, placebo-controlled trial study. Diagnosis was based on clinical examination, serological tests (chemiluminescent), and histopathological examinations. Palpable lymph nodes, IgM >8IU, and follicular hyperplasia were defined as positive findings. Patients were randomly assigned to the comparison groups (23 patients in each group). The CTM patients were treated with 48 mg/kg/day CTM divided into two doses, for 1 month. The placebo patients were treated with placebo for 1 month. The primary endpoint for treatment response was 1 month. Follow-up with physical and serological examinations occurred at 6 months. The secondary endpoint was at 6 months. Clinical response was defined as no palpable lymph nodes and serological response as IgM <6IU; a patient was cured if the lymph nodes were no longer palpable and IgM was <6IU. Results were analyzed using SPSS software and the Chi-square test. At the end of treatment, a clinical response was observed in 15 (65.2%) in the CTM group and five (21.7%) in the placebo group. A serological response was seen in 65.2% of the CTM group and 13.0% of the placebo group. The cure rate was 65.2% in the CTM group and 13.1% in the placebo group. There was a significant difference in therapeutic effect between the two groups (52.2%, 95% confidence interval 32.1-72%, p<0.001). There was no difference in the site of infection between the two groups (p>0.05). CTM has a good therapeutic effect in TL and may be used in selected patients for whom

Cholecalciferol, Calcitriol, and Vascular Function in CKD: A Randomized, Double-Blind Trial.

PubMed

Kendrick, Jessica; Andrews, Emily; You, Zhiying; Moreau, Kerrie; Nowak, Kristen L; Farmer-Bailey, Heather; Seals, Douglas R; Chonchol, Michel

2017-09-07

High circulating vitamin D levels are associated with lower cardiovascular mortality in CKD, possibly by modifying endothelial function. We examined the effect of calcitriol versus cholecalciferol supplementation on vascular endothelial function in patients with CKD. We performed a prospective, double-blind, randomized trial of 128 adult patients with eGFR=15-44 ml/min per 1.73 m 2 and serum 25-hydroxyvitamin D level <30 ng/ml at the University of Colorado. Participants were randomly assigned to oral cholecalciferol (2000 IU daily) or calcitriol (0.5 μ g) daily for 6 months. The primary end point was change in brachial artery flow-mediated dilation. Secondary end points included changes in circulating markers of mineral metabolism and circulating and cellular markers of inflammation. One hundred and fifteen patients completed the study. The mean (SD) age and eGFR of participants were 58±12 years old and 33.0±10.2 ml/min per 1.73 m 2 , respectively. There were no significant differences between groups at baseline. After 6 months, neither calcitriol nor cholecalciferol treatment resulted in a significant improvement in flow-mediated dilation (mean±SD percentage flow-mediated dilation; calcitriol: baseline 4.8±3.1%, end of study 5.1±3.6%; cholecalciferol: baseline 5.2±5.2%, end of study 4.7±3.6%); 25-hydroxyvitamin D levels increased significantly in the cholecalciferol group compared with the calcitriol group (cholecalciferol: 11.0±9.5 ng/ml; calcitriol: -0.8±4.8 ng/ml; P <0.001). Parathyroid hormone levels decreased significantly in the calcitriol group compared with the cholecalciferol group (median [interquartile range]; calcitriol: -22.1 [-48.7-3.5] pg/ml; cholecalciferol: -0.3 [-22.6-16.9] pg/ml; P =0.004). Six months of therapy with calcitriol or cholecalciferol did not improve vascular endothelial function or improve inflammation in patients with CKD. Copyright © 2017 by the American Society of Nephrology.

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

Can homeopaths detect homeopathic medicines by dowsing? A randomized, double-blind, placebo-controlled trial

PubMed Central

McCarney, R; Fisher, P; Spink, F; Flint, G; van Haselen, R

2002-01-01

Dowsing is a method of problem-solving that uses a motor automatism, amplified through a pendulum or similar device. In a homeopathic context, it is used as an aid to prescribing and as a tool to identify miasm or toxin load. A randomized double-blind trial was conducted to determine whether six dowsing homeopaths were able to distinguish between Bryonia in a 12c potency and placebo by use of dowsing alone. The homeopathic medicine Bryonia was correctly identified in 48.1% of bottle pairs (n=156; 95% confidence interval 40.2%, 56.0%; P=0.689). These results, wholly negative, add to doubts whether dowsing in this context can yield objective information. PMID:11934908

Can homeopaths detect homeopathic medicines by dowsing? A randomized, double-blind, placebo-controlled trial.

PubMed

McCarney, R; Fisher, P; Spink, F; Flint, G; van Haselen, R

2002-04-01

Dowsing is a method of problem-solving that uses a motor automatism, amplified through a pendulum or similar device. In a homeopathic context, it is used as an aid to prescribing and as a tool to identify miasm or toxin load. A randomized double-blind trial was conducted to determine whether six dowsing homeopaths were able to distinguish between Bryonia in a 12c potency and placebo by use of dowsing alone. The homeopathic medicine Bryonia was correctly identified in 48.1% of bottle pairs (n=156; 95% confidence interval 40.2%, 56.0%; P=0.689). These results, wholly negative, add to doubts whether dowsing in this context can yield objective information.

Effect of Linear Low-Intensity Extracorporeal Shockwave Therapy for Erectile Dysfunction-12-Month Follow-Up of a Randomized, Double-Blinded, Sham-Controlled Study.

PubMed

Fojecki, Grzegorz Lukasz; Tiessen, Stefan; Osther, Palle Jørn Sloth

2018-03-01

Short-term data on the effect of low-intensity extracorporeal shockwave therapy (Li-ESWT) on erectile dysfunction (ED) have been inconsistent. The suggested mechanisms of action of Li-ESWT on ED include stimulation of cell proliferation, tissue regeneration, and angiogenesis, which can be processes with a long generation time. Therefore, long-term data on the effect of Li-ESWT on ED are strongly warranted. To assess the outcome at 6 and 12 months of linear Li-ESWT on ED from a previously published randomized, double-blinded, sham-controlled trial. Subjects with ED (N = 126) who scored lower than 25 points in the erectile function domain of the International Index of Erectile Function (IIEF-EF) were eligible for the study. They were allocated to 1 of 2 groups: 5 weekly sessions of sham treatment (group A) or linear Li-ESWT (group B). After a 4-week break, the 2 groups received active treatment once a week for 5 weeks. At baseline and 6 and 12 months, subjects were evaluated by the IIEF-EF, the Erectile Hardness Scale (EHS), and the Sexual Quality of Life in Men. The primary outcome measure was an increase of at least 5 points in the IIEF-EF (ΔIIEF-EF score). The secondary outcome measure was an increase in the EHS score to at least 3 in men with a score no higher than 2 at baseline. Data were analyzed by linear and logistic regressions. Linear regression of the ΔIIEF-EF score from baseline to 12 months included 95 patients (dropout rate = 25%). Adjusted for the IIEF-EF score at baseline, the difference between groups B and A was -1.30 (95% CI = -4.37 to 1.77, P = .4). The success rate based on the main outcome parameter (ΔIIEF-EF score ≥ 5) was 54% in group A vs 47% in group B (odds ratio = 0.67, P = .28). Improvement based on changes in the EHS score in groups A and B was 34% and 24%, respectively (odds ratio = 0.47, P = .82). Exposure to 2 cycles of linear Li-ESWT for ED is not superior to 1 cycle at 6- and 12-month follow-ups. Fojecki GL, Tiessen S

Efficacy and safety of aripiprazole once-monthly in Asian patients with schizophrenia: a multicenter, randomized, double-blind, non-inferiority study versus oral aripiprazole.

PubMed

Ishigooka, Jun; Nakamura, Jun; Fujii, Yasuo; Iwata, Nakao; Kishimoto, Toshifumi; Iyo, Masaomi; Uchimura, Naohisa; Nishimura, Ryoji; Shimizu, Naoaki

2015-02-01

This study was designed to evaluate efficacy and safety of aripiprazole once-monthly (AOM) by verifying non-inferiority of AOM to oral aripiprazole in Asian patients with schizophrenia. The study consisted of a screening phase and three phases: an oral conversion phase (≤12weeks), an oral stabilization phase (≤12weeks) and a 52-week double-blind phase. Patients meeting stabilization criteria for 4weeks during the oral stabilization phase were randomly assigned (1:1) to AOM (400mg) or oral aripiprazole (6-24mg/day). The primary endpoint was Kaplan-Meier estimated rate of non-exacerbation of psychotic symptoms/non-relapse at Week 26. A total of 724 patients were screened, and 502 patients entered the oral stabilization phase. Of 455 patients randomized in the double-blind phase, 228 received AOM and 227 received oral aripiprazole. The non-exacerbation of psychotic symptoms/non-relapse rates at Week 26 were 95.0% (AOM) and 94.7% (oral aripiprazole) and the difference was 0.3% (95% CI: -3.9,4.5), thus non-inferiority of AOM compared to oral aripiprazole with respect to non-exacerbation of psychotic symptoms/non-relapse rate was shown with a margin of -3.9% which is well above the pre-defined non-inferiority limit (-15%). The proportions of patients meeting exacerbation of psychotic symptoms/relapse criteria and stabilization of psychotic symptoms/maintenance criteria were 6.6% and 92.5% in both groups. Discontinuation rates due to all reasons were 25.9% (AOM) and 33.5% (oral aripiprazole). AOM was well tolerated as well as oral aripiprazole. Non-inferiority of AOM to oral aripiprazole was established. AOM is efficacious in maintenance treatment of stabilized schizophrenia, with comparable efficacy and tolerability to oral aripiprazole. JapicCTI-101175. Copyright © 2014 Elsevier B.V. All rights reserved.

EEG Neurofeedback for ADHD: Double-Blind Sham-Controlled Randomized Pilot Feasibility Trial

ERIC Educational Resources Information Center

Arnold, L. Eugene; Lofthouse, Nicholas; Hersch, Sarah; Pan, Xueliang; Hurt, Elizabeth; Bates, Bethany; Kassouf, Kathleen; Moone, Stacey; Grantier, Cara

2013-01-01

Objective: Preparing for a definitive randomized clinical trial (RCT) of neurofeedback (NF) for ADHD, this pilot trial explored feasibility of a double-blind, sham-controlled design and adherence/palatability/relative effect of two versus three treatments/week. Method: Unmedicated 6- to 12-year-olds with "Diagnostic and Statistical Manual of…

An open-label six-month extension study to investigate the safety and efficacy of an extract of Artemisia annua for managing pain, stiffness and functional limitation associated with osteoarthritis of the hip and knee.

PubMed

Hunt, Sheena; Stebbings, Simon; McNamara, Debra

2016-10-28

This six-month single-centre open-label extension study, conducted at the University of Otago, Dunedin, follows from a previously published 12-week pilot double-blind randomised placebo-controlled study of dietary supplement, Arthrem® (ART) in patients with osteoarthritis (OA) of the hip or knee. The pilot double-blind study showed that treatment with ART 150 mg twice-daily was associated with clinically relevant pain reduction. The extension study aims were to assess longer-term safety and efficacy during six months' treatment following the pilot trial. Patients who completed the pilot double-blind study had the option to continue on open-label treatment with ART for a further six months. Safety was assessed by adverse event monitoring and laboratory tests at three and six months. Efficacy was assessed at three and six months using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC®). Thirty-four patients entered the optional extension and 28 completed six months' treatment. ART was well tolerated when taken for up to nine months. Improvements in WOMAC® efficacy parameters reported in the double-blind phase of the study were maintained over six months. ART appears to be a safe and effective alternative for managing the symptoms of OA over an extended period.

The Effect of Three-Monthly Albendazole Treatment on Malarial Parasitemia and Allergy: A Household-Based Cluster-Randomized, Double-Blind, Placebo-Controlled Trial

PubMed Central

Kaisar, Maria M. M.; May, Linda; Prasetyani, Margaretta A.; Wahyuni, Sitti; Djuardi, Yenny; Ariawan, Iwan; Wibowo, Heri; Lell, Bertrand; Sauerwein, Robert; Brice, Gary T.; Sutanto, Inge; van Lieshout, Lisette; de Craen, Anton J. M.; van Ree, Ronald; Verweij, Jaco J.; Tsonaka, Roula; Houwing-Duistermaat, Jeanine J.; Luty, Adrian J. F.; Sartono, Erliyani; Supali, Taniawati; Yazdanbakhsh, Maria

2013-01-01

Background Helminth infections are proposed to have immunomodulatory activities affecting health outcomes either detrimentally or beneficially. We evaluated the effects of albendazole treatment, every three months for 21 months, on STH, malarial parasitemia and allergy. Methods and Findings A household-based cluster-randomized, double-blind, placebo-controlled trial was conducted in an area in Indonesia endemic for STH. Using computer-aided block randomization, 481 households (2022 subjects) and 473 households (1982 subjects) were assigned to receive placebo and albendazole, respectively, every three months. The treatment code was concealed from trial investigators and participants. Malarial parasitemia and malaria-like symptoms were assessed in participants older than four years of age while skin prick test (SPT) to allergens as well as reported symptoms of allergy in children aged 5–15 years. The general impact of treatment on STH prevalence and body mass index (BMI) was evaluated. Primary outcomes were prevalence of malarial parasitemia and SPT to any allergen. Analysis was by intention to treat. At 9 and 21 months post-treatment 80.8% and 80.1% of the study subjects were retained, respectively. The intensive treatment regiment resulted in a reduction in the prevalence of STH by 48% in albendazole and 9% in placebo group. Albendazole treatment led to a transient increase in malarial parasitemia at 6 months post treatment (OR 4.16(1.35–12.80)) and no statistically significant increase in SPT reactivity (OR 1.18(0.74–1.86) at 9 months or 1.37 (0.93–2.01) 21 months). No effect of anthelminthic treatment was found on BMI, reported malaria-like- and allergy symptoms. No adverse effects were reported. Conclusions The study indicates that intensive community treatment of 3 monthly albendazole administration for 21 months over two years leads to a reduction in STH. This degree of reduction appears safe without any increased risk of malaria or allergies. Trial

A multicenter randomized double-blind study on the efficacy and safety of nicergoline in patients with multi-infarct dementia.

PubMed

Herrmann, W M; Stephan, K; Gaede, K; Apeceche, M

1997-01-01

A 6-month double-blind, randomized, placebo-controlled clinical trial preceded by a 3-week single-blind, washout/run-in placebo phase was performed in male and female patients, 55-85 years of age with a clinical diagnosis of mild to moderate multi-infarct dementia according to DSM-III to evaluate the therapeutic efficacy and safety of nicergoline 30 mg b.i.d. Primary endpoints for efficacy were the changes in the Sandoz Clinical Assessment Geriatric Scale (SCAG) and Mini-Mental State Examination (MMSE) scores at the end of the treatment with respect to baseline. Secondary endpoints were Clinical Global Impression, 3 subtests of the Weschsler Adult Intelligence Scale and Blessed A scale for activities of daily living, and all endpoints in 2-month intervals. A total of 252 patients were screened, 136 patients entered the double-blind phase and were evaluated as intent-to-treat (ITT) patients. Fifteen patients were excluded from the efficacy analyses of valid cases (VC) due to protocol violations or because they dropped out of the study prematurely. Confirmatory efficacy analysis after 6 months of treatment revealed superiority of nicergoline treatment with p < 0.01 for both SCAG and MMSE scores (ITT and VC). Subsequent descriptive efficacy analysis resulted in significant differences in favor of nicergoline, in the majority of cases as early as 2 months after start of treatment. Nicergoline was well tolerated and a similar number of adverse events were observed in both the placebo and the nicergoline group.

Tic Reduction with Risperidone Versus Pimozide in a Randomized, Double-Blind, Crossover Trial

ERIC Educational Resources Information Center

Gilbert, Donald L.; Batterson, J. Robert; Sethuraman, Gopalan; Sallee, Floyd R.

2004-01-01

Objective: To compare the tic suppression, electrocardiogram (ECG) changes, weight gain, and side effect profiles of pimozide versus risperidone in children and adolescents with tic disorders. Method: This was a randomized, double-blind, crossover (evaluable patient analysis) study. Nineteen children aged 7 to 17 years with Tourette's or chronic…

FTY720 versus mycophenolate mofetil in de novo renal transplantation: six-month results of a double-blind study.

PubMed

Tedesco-Silva, Helio; Szakaly, Peter; Shoker, Ahmed; Sommerer, Claudia; Yoshimura, Norio; Schena, Francesco Paolo; Cremer, Malika; Hmissi, Abdel; Mayer, Hartmut; Lang, Philippe

2007-10-15

FTY720 is a novel immunomodulator that was developed to produce optimal graft protection with improved safety and tolerability. Phase II studies have demonstrated the efficacy of FTY720 up to the doses of 2.5 mg with full-dose cyclosporine (FDC). This multicenter, double-blind, Phase IIb, randomized study evaluated the safety and efficacy of 5 mg FTY720 (n=87; Group 1) vs. 2.5 mg FTY720 (n=90; Group 2) vs. mycophenolate mofetil (MMF; n=94; Group 3) in de novo renal transplant patients receiving FDC and prednisone. The primary efficacy endpoint was the occurrence of treated biopsy-proven acute rejection, graft loss, death, or premature study discontinuation (composite endpoint) within 6 months. The primary endpoint was superior in Group 1 (24%) and statistically noninferior in Group 2 compared to Group 3 (24.1% vs. 29.2% vs. 39.4%; P=0.025 and 0.0039, respectively). FTY720 plus FDC was generally well tolerated, with a similar incidence of adverse events across all groups. FTY720 was associated with higher incidence of bradycardia (Group 1: 26.4%, P=0.0002 and Group 2: 15.6%, P=0.046, vs. Group 3: 6.4%), respiratory disorders (Group 1: 40.2%, not significant [P=NS] and Group 2: 34.4%, P=NS vs. Group 3: 28.7%). One macular edema occurred in Group 2. Lower creatinine clearances were observed with FTY720 versus MMF (Group 1: 52.4 ml/min, P=NS and Group 2: 51.7 ml/min, P=0.039 vs. Group 3: 62.5 ml/min). Although FTY720 with FDC provided adequate protection from acute rejection the safety profile was less favorable for adverse events than current standard immunosuppression in de novo renal transplant patients.

A randomized, double-blind, safety and tolerability study to assess the ophthalmic and renal effects of tafenoquine 200 mg weekly versus placebo for 6 months in healthy volunteers.

PubMed

Leary, Kevin J; Riel, Michael A; Roy, Michael J; Cantilena, Louis R; Bi, Daoqin; Brater, D Craig; van de Pol, Corina; Pruett, Khadeeja; Kerr, Caron; Veazey, James M; Beboso, Ronnie; Ohrt, Colin

2009-08-01

A randomized, double-blind, placebo-controlled study was conducted to assess the effect of tafenoquine, 200 mg weekly for 6 months on ophthalmic and renal safety. This trial was carried out after observations in previous clinical trials that tafenoquine may be associated with the development of corneal deposits and elevations in serum creatinine. In 120 healthy volunteers who received tafenoquine or placebo in a 2:1 randomization, there was no effect on night vision or other ophthalmic indices measured. Persons taking tafenoquine also showed no difference in mean change in glomerular filtration rate (GFR, mL/s/1.73 m(2)) after 6 months of dosing, with a treatment difference of -0.061 (95% confidence interval, -0.168, 0.045), and non-inferiority margin of -0.247 mL/s/1.73 m(2). Tafenoquine was well tolerated over the course of the study. The results of this study showed no clinically significant effects of tafenoquine on ophthalmic or renal function, and support its continued development as an antimalarial drug.

A Double-Blind Randomized Pilot Study Comparing Quetiapine and Divalproex for Adolescent Mania

ERIC Educational Resources Information Center

Delbello, Melissa P.; Kowatch, Robert A.; Adler, Caleb M.; Stanford, Kevin E.; Welge, Jeffrey A.; Barzman, Drew H.; Nelson, Erik; Strakowski, Stephen M.

2006-01-01

Objective: To determine the comparative efficacy of quetiapine and divalproex for the treatment of adolescent mania. Method: Fifty adolescents (ages 12-18 years) with bipolar I disorder, manic or mixed episode, were randomized to quetiapine (400-600 mg/day) or divalproex (serum level 80-120 [micro]g/mL) for 28 days for this double-blind study,…

Developmental Outcomes at 24 Months of Age in Toddlers Supplemented with Arachidonic Acid and Docosahexaenoic Acid: Results of a Double Blind Randomized, Controlled Trial

PubMed Central

Devlin, Angela M.; Chau, Cecil M. Y.; Matheson, Julie; McCarthy, Deanna; Yurko-Mauro, Karin; Innis, Sheila M.; Grunau, Ruth E.

2017-01-01

Little is known about arachidonic acid (ARA) and docosahexaenoic acid (DHA) requirements in toddlers. A longitudinal, double blind, controlled trial in toddlers (n = 133) age 13.4 ± 0.9 months (mean ± standard deviation), randomized to receive a DHA (200 mg/day) and ARA (200 mg/day) supplement (supplement) or a corn oil supplement (control) until age 24 months determined effects on neurodevelopment. We found no effect of the supplement on the Bayley Scales of Infant and Toddler Development 3rd Edition (Bayley-III) cognitive and language composites and Beery–Buktenica Developmental Test of Visual–Motor Integration (Beery VMI) at age 24 months. Supplemented toddlers had higher RBC phosphatidylcholine (PC), phosphatidylethanolamine (PE), and plasma DHA and ARA compared to placebo toddlers at age 24 months. A positive relationship between RBC PE ARA and Bayley III Cognitive composite (4.55 (0.21–9.00), B (95% CI), p = 0.045) in supplemented boys, but not in control boys, was observed in models adjusted for baseline fatty acid, maternal non-verbal intelligence, and BMI z-score at age 24 months. A similar positive relationship between RBC PE ARA and Bayley III Language composite was observed for supplemented boys (11.52 (5.10–17.94), p < 0.001) and girls (11.19 (4.69–17.68), p = 0.001). These findings suggest that increasing the ARA status in toddlers is associated with better neurodevelopment at age 24 months. PMID:28878181

Effect of home visit training program on growth and development of preterm infants: a double blind randomized controlled trial.

PubMed

Edraki, Mitra; Moravej, Hossian; Rambod, Masoume

2015-01-01

Home visit program can be effective in infants' growth and development. The present study aimed to investigate the effect of home visit program on preterm infants' growth and development within 6 months. It was a double-blind clinical trial study. The study was conducted in Hafez, Hazrat-e-Zeinab, and Namazee Hospitals affiliated to Shiraz University of Medical Sciences, Shiraz, Iran from 2010 to 2011. Preterm infants were divided into intervention (n=30) and control groups (n=30) through blocked randomization. The intervention group received home visit training program for 6 months, while the control group only received the hospital's routine care. Then, the infants' growth indexes, including weight, height, and head circumference, and development criteria were compared on the first day of admission in Neonatal Intensive Care Unit, and then first, second, third, and sixth months. The data were analyzed using Chi-square, independent t-test, and repeated measures ANCOVA. The mean weight of the intervention and control group infants was 7207.3±1129.74 and 6366.7±922.26 gr in the sixth month. Besides, the intervention group infants' mean weight was higher compared to the control group after six months (t=-3.05, P=0.03). Also, a significant difference was found between the two groups regarding development indexes, such as following moving objects with the head, keeping the head stable when changing the position from lying to sitting,  producing "Agha" sound, and taking objects by hand (P<0.05) during six months of age. The results showed that the home visit program was effective in preterm infants' weight gain and some development indexes at the sixth month. Considering the importance of infants' growth and development, healthcare staff is recommended to incorporate home visit training into their programs, so that steps can be taken towards improvement of preterm infants' health. IRCT2014082013690N3 

Double-blind randomized 12-month soy intervention had no effects on breast MRI fibroglandular tissue density or mammographic density

PubMed Central

Wu, Anna H.; Spicer, Darcy; Garcia, Agustin; Tseng, Chiu-Chen; Hovanessian-Larsen, Linda; Sheth, Pulin; Martin, Sue Ellen; Hawes, Debra; Russell, Christy; McDonald, Heather; Tripathy, Debu; Su, Min-Ying; Ursin, Giske; Pike, Malcolm C.

2015-01-01

Soy supplementation by breast cancer patients remains controversial. No controlled intervention studies have investigated the effects of soy supplementation on mammographic density in breast cancer patients. We conducted a double-blind, randomized, placebo-controlled intervention study in previously treated breast cancer patients (n=66) and high-risk women (n=29). We obtained digital mammograms and breast magnetic resonance imaging (MRI) scans at baseline and after 12 months of daily soy (50 mg isoflavones per day) (n=46) or placebo (n=49) tablet supplementation. The total breast area (MA) and the area of mammographic density (MD) on the mammogram was measured using a validated computer-assisted method, and mammographic density percent (MD% = 100 × MD/MA) was determined. A well-tested computer algorithm was used to quantitatively measure the total breast volume (TBV) and fibroglandular tissue volume (FGV) on the breast MRI, and the FGV percent (FGV% = 100 × FGV/TBV) was calculated. On the basis of plasma soy isoflavone levels, compliance was excellent. Small decreases in MD% measured by the ratios of month 12 to baseline levels, were seen in the soy (0.95) and the placebo (0.87) groups; these changes did not differ between the treatments (P=0.38). Small decreases in FGV% were also found in both the soy (0.90) and the placebo (0.92) groups; these changes also did not differ between the treatments (P=0.48). Results were comparable in breast cancer patients and high-risk women. We found no evidence that soy supplementation would decrease mammographic density and that MRI might be more sensitive to changes in density than mammography. PMID:26276750

Visual field protective effect of Erigeron breviscapus (vant.) Hand. Mazz. extract on glaucoma with controlled intraocular pressure: a randomized, double-blind, clinical trial.

PubMed

Zhong, Yisheng; Xiang, Minhong; Ye, Wen; Cheng, Yu; Jiang, Youqin

2010-01-01

To evaluate the visual field protective effect of Erigeron breviscapus (vant.) Hand. Mazz. (EBHM) extract on glaucoma with controlled intraocular pressure (IOP). Forty patients (40 eyes) with primary open-angle glaucoma, visual field defects and a postsurgical IOP of <18 mmHg were enrolled. The EBHM and placebo tablets were given orally according to the randomized and double-blind principle. Two tablets (of either EBHM or placebo) were taken three times a day for a period of 6 months. Patients were examined every 2 months after treatment commenced. At the end of the study, the results were given to the drug manufacturer. All patients completed the prospective, randomized, double-blind, clinical trial. No obvious adverse effects were found in patients during the treatment period. In the placebo group, no significant difference was found in mean defect (MD) or mean sensitivity (MS) between the values at pre-treatment and after 2, 4, and 6 months of treatment. After 6 months of EBHM treatment, the MD was significantly decreased and the MS was significantly increased compared with pre-treatment (p < 0.05). In the patients with moderate and late glaucoma, the MD was significantly decreased and the MS was significantly increased after 2, 4, and 6 months of EBHM treatment compared with pre-treatment. EBHM extract may have a partial protective effect on the visual field of glaucoma patients with controlled IOP. Further studies are needed to determine the safety and effectiveness of long-term EBHM treatment.

Prospective, multicentre, randomized, double-blind study of the efficacy of escitalopram versus citalopram in outpatient treatment of major depressive disorder.

PubMed

Moore, Nicholas; Verdoux, Hélène; Fantino, Bruno

2005-05-01

Pre-clinical studies, active-control clinical trials and meta-analyses indicate that escitalopram (S-citalopram) might be more effective than citalopram, the racemic mixture of S- and R-citalopram. The present study aimed to confirm the superior efficacy of escitalopram over citalopram. A double-blind, randomized clinical trial was performed in which general practitioners and psychiatrists compared fixed doses of escitalopram (20 mg/day) with citalopram (40 mg/day) over 8 weeks in outpatients with major depressive disorder (MDD) [baseline Montgomery-Asberg Depression Rating Scale (MADRS) score > or =30]. Primary efficacy parameter was change from baseline to last assessment in the MADRS total score. Out of 138 (aged 44.1+/-10.9 years; initial MADRS score 36.3+/-4.8) and 142 (aged 46.2+/-11.1 years; initial MADRS score 35.7+/-4.4) evaluable patients who were randomized to escitalopram and citalopram, respectively, six and 15 withdrew prematurely (P=0.05). The MADRS score decreased more in the escitalopram than in the citalopram arm (-22.4+/-12.9 versus -20.3+/-12.7; P<0.05). There were more treatment responders with escitalopram (76.1%) than with citalopram (61.3%, P<0.01). Adjusted remitter rates were 56.1% and 43.6%, respectively (P<0.05). Tolerability was similar in both groups. This randomized double-blind trial confirms that escitalopram has a superior effect to citalopram in MDD.

Effects of Low Dose Metformin in Adolescents with Type I Diabetes Mellitus: A Randomized, Double-Blinded Placebo-Controlled Study

PubMed Central

Nadeau, Kristen; Chow, Kelsey; Alam, Lyla; Lindquist, Kara; Cambell, Sarah; McFann, Kim; Klingensmith, Georgeanna; Walravens, Phillipe

2014-01-01

Background Insulin resistance increases during adolescence in those with type 1 diabetes (T1DM), complicating glycemic control and potentially increasing cardiovascular disease (CVD) risk. Metformin, typically used in type 2 diabetes (T2DM), is a possible adjunct therapy in T1DM to help improve glycemic control and insulin sensitivity. Objective We hypothesized that metformin would improve metabolic parameters in adolescents with T1DM. Design, Setting, and Participants This randomized, double-blinded, placebo-controlled trial included 74 pubertal adolescents (ages 13–20 years) with T1DM. Participants were randomized to receive either metformin or placebo for six months. HbA1c, insulin dose, waist circumference, BMI, and blood pressure were measured at baseline, 3 and 6 months, with fasting lipids measured at baseline and 6 months. Results Total daily insulin dose, BMI Z-score and waist circumference significantly decreased at 3 and 6 months compared to baseline within the metformin group, even among normal-weight participants. In placebo group, total insulin dose and systolic blood pressure increased significantly at 3 months and total insulin dose increased significantly at 6 months. No significant change was observed in HbA1c at any time point between metformin and placebo groups or within either group. Conclusions Low-dose metformin likely improves BMI as well as insulin sensitivity in T1DM adolescents, as indicated by a decrease in total daily insulin dose. The decrease in waist circumference indicates that fat distribution is also likely impacted by metformin in T1DM. Further studies with higher metformin doses and more detailed measurements are needed to confirm these results, their underlying mechanisms, and potential impact on CVD in T1DM youth. PMID:24698216

Renal denervation in treatment-resistant essential hypertension. A randomized, SHAM-controlled, double-blinded 24-h blood pressure-based trial.

PubMed

Mathiassen, Ole N; Vase, Henrik; Bech, Jesper N; Christensen, Kent L; Buus, Niels H; Schroeder, Anne P; Lederballe, Ole; Rickers, Hans; Kampmann, Ulla; Poulsen, Per L; Hansen, Klavs W; Btker, Hans E; Peters, Christian D; Engholm, Morten; Bertelsen, Jannik B; Lassen, Jens F; Langfeldt, Sten; Andersen, Gratien; Pedersen, Erling B; Kaltoft, Anne

2016-08-01

Renal denervation (RDN), treating resistant hypertension, has, in open trial design, been shown to lower blood pressure (BP) dramatically, but this was primarily with respect to office BP. We conducted a SHAM-controlled, double-blind, randomized, single-center trial to establish efficacy data based on 24-h ambulatory BP measurements (ABPM). Inclusion criteria were daytime systolic ABPM at least 145 mmHg following 1 month of stable medication and 2 weeks of compliance registration. All RDN procedures were carried out by an experienced operator using the unipolar Medtronic Flex catheter (Medtronic, Santa Rosa, California, USA). We randomized 69 patients with treatment-resistant hypertension to RDN (n = 36) or SHAM (n = 33). Groups were well balanced at baseline. Mean baseline daytime systolic ABPM was 159 ± 12 mmHg (RDN) and 159 ± 14 mmHg (SHAM). Groups had similar reductions in daytime systolic ABPM compared with baseline at 3 months [-6.2 ± 18.8 mmHg (RDN) vs. -6.0 ± 13.5 mmHg (SHAM)] and at 6 months [-6.1 ± 18.9 mmHg (RDN) vs. -4.3 ± 15.1 mmHg (SHAM)]. Mean usage of antihypertensive medication (daily defined doses) at 3 months was equal [6.8 ± 2.7 (RDN) vs. 7.0 ± 2.5 (SHAM)].RDN performed at a single center and by a high-volume operator reduced ABPM to the same level as SHAM treatment and thus confirms the result of the HTN3 trial. Further, clinical use of RDN for treatment of resistant hypertension should await positive results from double-blinded, SHAM-controlled trials with multipolar ablation catheters or novel denervation techniques.

Lidocaine for systemic sclerosis: a double-blind randomized clinical trial

PubMed Central

2011-01-01

Background Systemic sclerosis (scleroderma; SSc) is an orphan disease with the highest case-specific mortality of any connective-tissue disease. Excessive collagen deposit in affected tissues is a key for the disease's pathogenesis and comprises most of the clinical manifestations. Lidocaine seems to be an alternative treatment for scleroderma considering that: a) the patient's having excessive collagen deposits in tissues affected by scleroderma; b) the patient's demonstrating increased activity of the enzyme prolyl hydroxylase, an essential enzyme for the biosynthesis of collagen; and c) lidocaine's reducing the activity of prolyl hydroxylase. The aim of this study was to evaluate the efficacy and safety of lidocaine in treating scleroderma. Methods A randomized double-blind clinical trial included 24 patients with scleroderma randomized to receive lidocaine or placebo intravenously in three cycles of ten days each, with a one-month interval between them. Outcomes: cutaneous (modified Rodnan skin score), oesophageal (manometry) and microvascular improvement (nailfold capillaroscopy); improvement in subjective self-assessment and in quality of life (HAQ). Results There was no statistically significant difference between the groups for any outcome after the treatment and after 6-months follow-up. Improvement in modified Rodnan skin score occurred in 66.7% and 50% of placebo and lidocaine group, respectively (p = 0.408). Both groups showed an improvement in subjective self-assessment, with no difference between them. Conclusions Despite the findings of a previous cohort study favouring the use of lidocaine, this study demonstrated that lidocaine at this dosage and means of administration showed a lack of efficacy for treating scleroderma despite the absence of significant adverse effects. However, further similar clinical trials are needed to evaluate the efficacy of lidocaine when administered in different dosages and by other means. PMID:21299861

Hormone therapy in menopausal women with cognitive complaints: a randomized, double-blind trial.

PubMed

Maki, P M; Gast, M J; Vieweg, A J; Burriss, S W; Yaffe, K

2007-09-25

To evaluate the effects of hormone therapy (HT) on cognition and subjective quality of life (QoL) in recently postmenopausal women with cognitive complaints. Cognitive Complaints in Early Menopause Trial (COGENT) was a randomized, double-blind, placebo-controlled, multicenter, pilot study of 180 healthy postmenopausal women aged 45 to 55 years, randomly assigned to receive either placebo or conjugated equine estrogen 0.625 mg/medroxyprogesterone acetate 2.5 mg for 4 months. Outcome measures included memory, subjective cognition, QoL, sexuality, and sleep, which were assessed at baseline and month 4. The study was terminated before the expected final sample size of 275 due to a decrease in enrollment coinciding with the publication of findings from the Women's Health Initiative. There were no differences between groups on any cognitive or QoL measures, except for an increase in sexual interest and thoughts with HT. Modest negative effects on short- and long-term verbal memory approached significance (p < 0.10). Women with baseline vasomotor symptoms (VMS) showed a decrease in VMS and an improvement in general QoL, but no cognitive benefit vs placebo. With the power to detect an effect size of >or=0.45, this study suggests potential modest negative effects on verbal memory that are consistent with previous hormone therapy trials in older women.

Human norovirus inactivation in oysters by high hydrostatic pressure processing: A randomized double-blinded study

USDA-ARS?s Scientific Manuscript database

This randomized, double-blinded, clinical trial assessed the effect of high hydrostatic pressure processing (HPP) on genogroup I.1 human norovirus (HuNoV) inactivation in virus-seeded oysters when ingested by subjects. The safety and efficacy of HPP treatments were assessed in three study phases wi...

Iron supplementation in HIV-infected Malawian children with anemia: a double-blind, randomized, controlled trial.

PubMed

Esan, Michael O; van Hensbroek, Michael Boele; Nkhoma, Ernest; Musicha, Crispin; White, Sarah A; Ter Kuile, Feiko O; Phiri, Kamija S

2013-12-01

It is unknown whether iron supplementation in human immunodeficiency virus (HIV)-infected children living in regions with high infection pressure is safe or beneficial. A 2-arm, double-blind, randomized, controlled trial was conducted to examine the effects of iron supplementation on hemoglobin, HIV disease progression, and morbidity. HIV-infected Malawian children aged 6-59 months with moderate anemia (hemoglobin level, 7.0-9.9 g/dL) were randomly assigned to receive 3 mg/kg/day of elemental iron and multivitamins (vitamins A, C, and D) or multivitamins alone for 3 months. Participants were followed for 6 months. A total of 209 children were randomly assigned to treatment, and 196 (93.8%) completed 6 months of follow-up. Iron supplementation was associated with greater increases in hemoglobin concentrations (adjusted mean difference [aMD], 0.60; 95% confidence interval [CI], .06-1.13; P = .03) and reduced the risk of anemia persisting for up to 6 months follow-up (adjusted prevalence ratio, 0.59; 95% CI, .38-.92; P = .02). Children who received iron had a better CD4 percentage response at 3 months (aMD, 6.00; 95% CI, 1.84-10.16; P = .005) but an increased incidence of malaria at 6 months (incidence rate, 120.2 vs 71.7; adjusted incidence rate ratio [aIRR], 1.81 [95% CI, 1.04-3.16]; P = .04), especially during the first 3 months (incidence rate, 78.1 vs 36.0; aIRR, 2.68 [95% CI, 1.08-6.63]; P = .03). Iron supplementation in anemic HIV-infected children has beneficial effects on hemoglobin, anemia, and immunity but increases the risk of malaria. Thus, iron supplementation in HIV-infected children living in malaria-endemic areas should only be provided in combination with adequate protection from malaria. ISRCTN-62947977.

A randomized, double-blind, placebo-controlled trial of coenzyme Q10 in Huntington disease.

PubMed

McGarry, Andrew; McDermott, Michael; Kieburtz, Karl; de Blieck, Elisabeth A; Beal, Flint; Marder, Karen; Ross, Christopher; Shoulson, Ira; Gilbert, Peter; Mallonee, William M; Guttman, Mark; Wojcieszek, Joanne; Kumar, Rajeev; LeDoux, Mark S; Jenkins, Mary; Rosas, H Diana; Nance, Martha; Biglan, Kevin; Como, Peter; Dubinsky, Richard M; Shannon, Kathleen M; O'Suilleabhain, Padraig; Chou, Kelvin; Walker, Francis; Martin, Wayne; Wheelock, Vicki L; McCusker, Elizabeth; Jankovic, Joseph; Singer, Carlos; Sanchez-Ramos, Juan; Scott, Burton; Suchowersky, Oksana; Factor, Stewart A; Higgins, Donald S; Molho, Eric; Revilla, Fredy; Caviness, John N; Friedman, Joseph H; Perlmutter, Joel S; Feigin, Andrew; Anderson, Karen; Rodriguez, Ramon; McFarland, Nikolaus R; Margolis, Russell L; Farbman, Eric S; Raymond, Lynn A; Suski, Valerie; Kostyk, Sandra; Colcher, Amy; Seeberger, Lauren; Epping, Eric; Esmail, Sherali; Diaz, Nancy; Fung, Wai Lun Alan; Diamond, Alan; Frank, Samuel; Hanna, Philip; Hermanowicz, Neal; Dure, Leon S; Cudkowicz, Merit

2017-01-10

To test the hypothesis that chronic treatment of early-stage Huntington disease (HD) with high-dose coenzyme Q10 (CoQ) will slow the progressive functional decline of HD. We performed a multicenter randomized, double-blind, placebo-controlled trial. Patients with early-stage HD (n = 609) were enrolled at 48 sites in the United States, Canada, and Australia from 2008 to 2012. Patients were randomized to receive either CoQ 2,400 mg/d or matching placebo, then followed for 60 months. The primary outcome variable was the change from baseline to month 60 in Total Functional Capacity score (for patients who survived) combined with time to death (for patients who died) analyzed using a joint-rank analysis approach. An interim analysis for futility revealed a conditional power of <5% for the primary analysis, prompting premature conclusion in July 2014. No statistically significant differences were seen between treatment groups for the primary or secondary outcome measures. CoQ was generally safe and well-tolerated throughout the study. These data do not justify use of CoQ as a treatment to slow functional decline in HD. NCT00608881. This article provides Class I evidence that CoQ does not slow the progressive functional decline of patients with HD. © 2016 American Academy of Neurology.

A Double-Blind, Randomized, Placebo-Controlled Trial of Escitalopram in the Treatment of Pediatric Depression

ERIC Educational Resources Information Center

Wagner, Karen Dineen; Jonas, Jeffrey; Findling, Robert L.; Ventura, Daniel; Saikali, Khalil

2006-01-01

Objective: Escitalopram is a selective serotonin reuptake inhibitor antidepressant indicated for use in adults. This trial examined the efficacy and safety of escitalopram in pediatric depression. Method: Patients (6-17 years old) with major depressive disorder were randomized to receive 8 weeks of double-blind flexibly dosed treatment with…

Efficacy of Trimetazidine Dihydrochloride for Relieving Chronic Tinnitus: A Randomized Double-Blind Study

PubMed Central

Kumral, Tolgar Lütfi; Yıldırım, Güven; Berkiten, Güler; Saltürk, Ziya; Ataç, Enes; Atar, Yavuz; Uyar, Yavuz

2016-01-01

Objectives. To evaluate the efficacy of trimetazidine dihydrochloride as a treatment for chronic tinnitus. Methods. A total of 97 chronic tinnitus patients were evaluated in this randomized, prospective, double-blind, placebo-controlled trial. After assessing for eligibility, 82 patients were randomly assigned into placebo or trimetazidine groups according to the medication. The trimetazidine group received 20×3 mg/day per oral trimetazidine dihydrochloride and the placebo group received 20×3 mg/day per oral placebo for 3 months. Tinnitus handicap inventory (THI), visual analogue scale (VAS) questionnaires and audiometric results were used to determine the effectiveness of trimetazidine treatment. Results. The study group comprised 82 tinnitus subjects, 42 (51%) of whom received trimetazidine dihydrochloride and 40 (49%) who received placebo. There was no significant difference between placebo and trimetazidine groups in THI grade and VAS (both pre- and posttreatment scores) (P>0.05) and no significant improvement was observed in subjective loudness score in either group (P>0.05). Additionally there was no significant difference between groups in pre- and posttreatment pure tone hearing thresholds at all measured frequencies (P>0.05). Conclusion. Trimetazidine dihydrochloride therapy was ineffective for relieving chronic tinnitus. PMID:27230273

Clozapine and risperidone in moderately refractory schizophrenia: a 6-month randomized double-blind comparison.

PubMed

Schooler, Nina R; Marder, Stephen R; Chengappa, K N R; Petrides, Georgios; Ames, Donna; Wirshing, William C; McMeniman, Marjorie; Baker, Robert W; Parepally, Haranath; Umbricht, Daniel; Kane, John M

2016-05-01

Clozapine remains the only medication indicated for refractory schizophrenia. As new antipsychotic drugs become available, their efficacy compared to clozapine, particularly in moderately ill patients, is of great clinical interest. We compared risperidone, the first of these, to clozapine in partially responsive patients. Further, since participation of patients usually excluded from clinical trials is increasingly important, we broadened inclusion to a wider patient population. We compared clozapine (n = 53) to risperidone (n = 54) in a randomized, double-blind, 29-week trial in schizophrenia patients (diagnosed using DSM-IV) at 3 research outpatient clinics. Randomization was stratified by "narrow" or "broad" inclusion criteria. The study was conducted between December 1995 and October 1999. Time to treatment discontinuation for lack of efficacy and time to 20% improvement in the Brief Psychiatric Rating Scale psychotic symptom cluster were the primary outcome measures. There were no differences in all-cause discontinuation; clozapine-treated participants were significantly less likely to discontinue for lack of efficacy (15%) than risperidone-treated participants (38%) (Wilcoxon χ(2)1 = 6.10, P = .01). Clozapine resulted in significantly more global improvement (F2,839 = 6.07, P < .01) and asociality improvement (F2,315 = 6.64, P < .01) than risperidone. There was no difference in proportions meeting an a priori criterion of psychosis improvement (risperidone: 57%; clozapine: 71%). Significant adverse effect differences in salivation (F1 = 4.05, P < .05) (F1 = 12.13, P < .001), sweating (F1 = 5.07, P < .05), and tachycardia (F1 = 6.51, P < .05) favored risperidone. Clozapine-treated partially responsive patients were less likely to discontinue treatment for lack of efficacy and improved more globally than those treated with risperidone, although psychotic symptoms did not differ. These findings suggest that clozapine should not be restricted to the most

Effect of Two or Six Doses 800 mg of Albendazole Every Two Months on Loa loa Microfilaraemia: A Double Blind, Randomized, Placebo-Controlled Trial.

PubMed

Kamgno, Joseph; Nguipdop-Djomo, Patrick; Gounoue, Raceline; Téjiokem, Mathurin; Kuesel, Annette C

2016-03-01

Loiasis is a parasitic infection endemic in the African rain forest caused by the filarial nematode Loa loa. Loiasis can be co-endemic with onchocerciasis and/or lymphatic filariasis. Ivermectin, the drug used in the control of these diseases, can induce serious adverse reactions in patients with high L loa microfilaraemia (LLM). A drug is needed which can lower LLM below the level that represents a risk so that ivermectin mass treatment to support onchocerciasis and lymphatic filariasis elimination can be implemented safely. Sixty men and women from a loiasis endemic area in Cameroon were randomized after stratification by screening LLM (≤ 30000, 30001-50000, >50000) to three treatment arms: two doses albendazole followed by 4 doses matching placebo (n = 20), six doses albendazole (n = 20) albendazole or 6 doses matching placebo (n = 20) administered every two months. LLM was measured before each treatment and 14, 18, 21 and 24 months after the first treatment. Monitoring for adverse events occurred three and seven days as well as 2 months after each treatment. None of the adverse events recorded were considered treatment related. The percentages of participants with ≥ 50% decrease in LLM from pre-treatment for ≥ 4 months were 53%, 17% and 11% in the 6-dose, 2-dose and placebo treatment arms, respectively. The difference between the 6-dose and the placebo arm was significant (p = 0.01). The percentages of participants with LLM < 8100 mf/ml for ≥ 4 months were 21%, 11% and 0% in the 6-dose, 2-dose and placebo treatment arms, respectively. The 6-dose regimen reduced LLM significantly, but the reduction was insufficient to eliminate the risk of severe and/or serious adverse reactions during ivermectin mass drug administration in loiasis co-endemic areas.

Effect of Two or Six Doses 800 mg of Albendazole Every Two Months on Loa loa Microfilaraemia: A Double Blind, Randomized, Placebo-Controlled Trial

PubMed Central

Kamgno, Joseph; Nguipdop-Djomo, Patrick; Gounoue, Raceline; Téjiokem, Mathurin; Kuesel, Annette C.

2016-01-01

Background Loiasis is a parasitic infection endemic in the African rain forest caused by the filarial nematode Loa loa. Loiasis can be co-endemic with onchocerciasis and/or lymphatic filariasis. Ivermectin, the drug used in the control of these diseases, can induce serious adverse reactions in patients with high L loa microfilaraemia (LLM). A drug is needed which can lower LLM below the level that represents a risk so that ivermectin mass treatment to support onchocerciasis and lymphatic filariasis elimination can be implemented safely. Methodology Sixty men and women from a loiasis endemic area in Cameroon were randomized after stratification by screening LLM (≤30000, 30001–50000, >50000) to three treatment arms: two doses albendazole followed by 4 doses matching placebo (n = 20), six doses albendazole (n = 20) albendazole or 6 doses matching placebo (n = 20) administered every two months. LLM was measured before each treatment and 14, 18, 21 and 24 months after the first treatment. Monitoring for adverse events occurred three and seven days as well as 2 months after each treatment. Principal Findings None of the adverse events recorded were considered treatment related. The percentages of participants with ≥ 50% decrease in LLM from pre-treatment for ≥ 4 months were 53%, 17% and 11% in the 6-dose, 2-dose and placebo treatment arms, respectively. The difference between the 6-dose and the placebo arm was significant (p = 0.01). The percentages of participants with LLM < 8100 mf/ml for ≥4 months were 21%, 11% and 0% in the 6-dose, 2-dose and placebo treatment arms, respectively. Conclusions/ Significance The 6-dose regimen reduced LLM significantly, but the reduction was insufficient to eliminate the risk of severe and/or serious adverse reactions during ivermectin mass drug administration in loiasis co-endemic areas. PMID:26967331

A randomized, double-blind, placebo controlled, parallel group, efficacy study of alpha BRAIN® administered orally.

PubMed

Solomon, Todd M; Leech, Jarrett; deBros, Guy B; Murphy, Cynthia A; Budson, Andrew E; Vassey, Elizabeth A; Solomon, Paul R

2016-03-01

Alpha BRAIN® is a nootropic supplement that purports to enhance cognitive functioning in healthy adults. The goal of this study was to investigate the efficacy of this self-described cognitive enhancing nootropic on cognitive functioning in a group of healthy adults by utilizing a randomized, double blind, placebo-controlled design. A total of 63-treatment naïve individuals between 18 and 35 years of age completed the randomized, double-blind, placebo controlled trial. All participants completed a 2-week placebo run in before receiving active product, Alpha BRAIN® or new placebo, for 6 weeks. Participants undertook a battery of neuropsychological tests at randomization and at study completion. Primary outcome measures included a battery of neuropsychological tests and measures of sleep. Compared with placebo, Alpha BRAIN® significantly improved on tasks of delayed verbal recall and executive functioning. Results also indicated significant time-by-group interaction in delayed verbal recall for the Alpha BRAIN® group. The use of Alpha BRAIN® for 6 weeks significantly improved recent verbal memory when compared with controls, in a group of healthy adults. While the outcome of the study is encouraging, this is the first randomized controlled trial of Alpha BRAIN®, and the results merit further study. Copyright © 2016 John Wiley & Sons, Ltd.

Hypercaloric enteral nutrition in Amyotrophic Lateral Sclerosis: a randomized double-blind placebo-controlled trial

PubMed Central

Wills, Anne-Marie; Hubbard, Jane; Macklin, Eric A.; Glass, Jonathan; Tandan, Rup; Simpson, Ericka P; Brooks, Benjamin; Gelinas, Deborah; Mitsumoto, Hiroshi; Mozaffar, Tahseen; Hanes, Gregory P.; Ladha, Shafeeq S.; Heiman-Patterson, Terry; Katz, Jonathan; Lou, Jau-Shin; Mahoney, Katy; Grasso, Daniela; Lawson, Robert; Yu, Hong; Cudkowicz, Merit

2014-01-01

Background Amyotrophic Lateral Sclerosis (ALS) is a rapidly fatal neurodegenerative disease with few therapeutic options. Mild obesity is associated with greater survival in ALS patients and calorie-dense diets increase survival in an ALS mouse model. We therefore hypothesized that hypercaloric diets might lead to weight gain and slow ALS disease progression. Methods In this double-blind, placebo-controlled, multi-center clinical trial, we enrolled adults with ALS without a history of diabetes, significant liver or cardiovascular disease, who were already receiving percutaneous enteral nutrition. We randomly assigned participants to one of three dietary interventions: replacement calories using an isocaloric diet (controls) vs. a high-carbohydrate hypercaloric diet (HC/HC), vs. a high-fat hypercaloric diet (HF/HC). Participants received the intervention diets for four months and were followed for five months. The primary outcomes were safety and tolerability. Secondary outcomes included measures of disease progression, survival, and metabolism. This trial is registered with Clinicaltrials.gov, number NCT00983983. Findings A total of 24 participants were enrolled of whom 20 initiated study diet (six control, eight HC/HC, six HF/HC). Baseline demographics were similar among the three study arms. The HC/HC diet was better tolerated with fewer serious adverse events than the control diet (zero vs. nine, p<0·001) and fewer dose discontinuations due to adverse events (0% vs. 50%). There were no deaths in the HC/HC arm vs. three deaths (43%) in the control arm (logrank p = 0·03). The HF/HC arm was not statistically different from the controls in adverse events, tolerability, deaths or disease progression. Interpretation Our results suggest that hypercaloric enteral nutrition is safe and tolerable in ALS and support the study of nutritional interventions at earlier stages of the disease. Funding The Muscular Dystrophy Association with additional support from the National

A Randomized, Double-Blinded, Placebo-Controlled Clinical Trial Evaluating the Effectiveness of Daily Vibration After Arthroscopic Rotator Cuff Repair.

PubMed

Lam, Patrick H; Hansen, Kaitlyn; Keighley, Geffrey; Hackett, Lisa; Murrell, George A C

2015-11-01

Rotator cuff repair is a common method to treat rotator cuff tears; however, retear rates remain high. High-frequency, low-magnitude vibration has been demonstrated to promote new bone formation in both animal models and in humans. This type of mechanical stimulation applied postoperatively will enhance tendon-to-bone healing and reduce postoperative retear rates. Randomized controlled trial; Level of evidence, 1. A randomized, double-blinded, placebo-controlled clinical trial was conducted to investigate the effects of 5 minutes of 80-Hz vibration applied daily after arthroscopic rotator cuff repair for 6 months on postoperative rotator cuff healing. The primary outcome was ultrasound-assessed repair integrity at 6 months after repair. Recruited patients were randomized into 2 groups: one group received a vibration device that oscillated at 80 Hz, and the other group received a placebo device. The postoperative retear rates of both groups were similar (9.1% [5/55] in the vibration group, and 9.3% [5/54] in the placebo group) at 6 months as determined by ultrasound imaging. Vibration did provide acute pain relief at 6 weeks after surgery (visual analog scale [VAS] score, 2.24 ± 0.29 cm) compared with placebo (VAS score, 3.67 ± 0.48 cm) (P < .003). Six months after surgery, both groups had significant reductions in pain during overhead activities, at rest, and during sleep and overall shoulder pain compared with before surgery (P < .001). Both the vibration and placebo groups had significant increases in shoulder strength with abduction in the scapular plane, adduction, liftoff, internal rotation, and external rotation 6 months after surgery. Statistical analysis showed that vibration was not a contributing factor at improving these parameters in these periods. High-frequency, low-magnitude vibration did provide acute pain relief on application 6 weeks after arthroscopic rotator cuff repair surgery. However, vibration did not improve tendon-to-bone healing

Randomized, double-blind, placebo-controlled clinical trial on the efficacy of 0.5% indomethacin eye drops in uveitic macular edema.

PubMed

Allegri, Pia; Murialdo, Ugo; Peri, Simona; Carniglia, Rosanna; Crivelli, Maria Grazia; Compiano, Silvia; Autuori, Silvia; Mastromarino, Antonio; Zurria, Monia; Marrazzo, Giuseppina

2014-03-10

The aim of the present randomized, double-blind, placebo-controlled clinical trial was to assess the efficacy and tolerability of 0.5% indomethacin (INDOM) eye drops in adult patients suffering from macular edema (ME) related to different etiology uveitis. Forty-six eyes of 31 adult patients (20 females and 11 males) mean age 39 years, affected by inflammatory ME, were randomized to receive a dose of commercial 0.5% INDOM eye-drops four times per day (16 subjects = 23 eyes) or placebo (the vehicle of INDOM, 15 subjects = 23 eyes) during a 6-month active therapy follow-up. Study assessment at each visit included visual acuity testing (VA), slit-lamp examination, IOP evaluation, and Heidelberg Spectralis optical coherence tomography (OCT) central foveal thickness (CFT) measurement. Any variation in subjective symptoms and tolerability was also detected. Statistical analysis showed, from baseline to the 6-month visit, a significant reduction in CFT (P < 0.0001) and a significant improvement in VA only in the 0.5% INDOM-treated group; a global reduction of discomfort symptoms was present in both groups (P < 0.001). The four times per day administration of 0.5% INDOM eye drops in eyes affected with uveitic ME from different etiologies, compared with placebo, is associated with a significant reduction in ME at the 6-month follow-up visit, as measured by spectral-domain optical coherence tomography (SD-OCT). However, not all eyes showed a complete resolution of ME because of vitreoretinal traction. (https://eudract.ema.europa.eu/index.html number, EUDRACT 2011-001522-20.).

A Phase III randomized, double-blind, clinical trial of an investigational hexavalent vaccine given at 2, 4, and 11-12 months.

PubMed

Silfverdal, Sven-Arne; Icardi, Giancarlo; Vesikari, Timo; Flores, Sheryl A; Pagnoni, Marco F; Xu, Jin; Liu, G Frank; Stek, Jon E; Boisnard, Florence; Thomas, Stéphane; Ziani, Eddy; Lee, Andrew W

2016-07-19

Combination vaccines simplify vaccination visits and improve coverage and timeliness. DTaP5-HB-IPV-Hib is a new investigational, fully-liquid, combination vaccine designed to protect against 6 infectious diseases, including 5 pertussis antigens and OMPC instead of PT as conjugated protein for Hib component. In this multicenter, double-blind, comparator-controlled, Phase III study (NCT01480258) conducted in Sweden, Italy, and Finland, healthy infants were randomized 1:1 to receive one two immunization regimens. The DTaP5-HB-IPV-Hib Group received the investigational hexavalent vaccine (DTaP5-HB-IPV-Hib) and the Control Group received Infanrix-hexa (DTPa3-HBV-IPV/Hib) at 2, 4 and 11-12months of age. Both groups received concomitantly Prevnar 13 (PCV13) and Rotateq (RV5) or Rotarix (RV1) at 2, 4months of age and PCV13 at 11-12months. Subjects administered RV5 received a 3rd dose at 5months of age. A total of 656 subjects were randomized to the DTaP5-HB-IPV-Hib Group and 659 subjects to Control Group. Immune responses to all vaccine antigens post-toddler dose were non-inferior in the DTaP5-HB-IPV-Hib Group as compared to the Control Group. Additionally, the post-dose 2 and pre-toddler DTaP5-HB-IPV-Hib anti-PRP responses were superior. The DTaP5-HB-IPV-Hib Group responses to concomitant RV1 were non-inferior compared to the Control Group. Solicited adverse event rates after any dose were similar in both groups, except for higher rates of pyrexia (6.4% difference; 95% CI: 1.5,11.3) and somnolence (5.8% difference; 95% CI: 1.7,9.8) in the DTaP5-HB-IPV-Hib Group. Vaccine-related serious adverse events occurred infrequently in the DTaP5-HB-IPV-Hib Group (0.3%) and the Control Group (0.5%). The safety and immunogenicity of DTaP5-HB-IPV-Hib is generally comparable to Control when administered in the 2, 4, 11-12month schedule. Early Hib responses were superior versus Control. DTaP5-HB-IPV-Hib could provide a new hexavalent option for pediatric combination vaccines, aligned

Randomized, double-blind, placebo-controlled trial of orlistat for weight loss in adolescents.

PubMed

Maahs, David; de Serna, Daniela Gonzalez; Kolotkin, Ronette L; Ralston, Shawn; Sandate, Jeffrey; Qualls, Clifford; Schade, David S

2006-01-01

To evaluate the efficacy of orlistat to enhance weight loss in obese adolescents. The study was a 6-month randomized, double-blind, placebo-controlled trial to compare the effects of orlistat (120 mg orally 3 times a day) and placebo on reduction of body mass index (BMI). Forty adolescents between 14 and 18 years of age with a mean BMI of 40 kg/m2 entered the protocol between December 2002 and February 2003. Study subjects stayed overnight in the General Clinical Research Center, during which dietary records were reviewed and lifestyle recommendations were given. The study participants received either orlistat (120 mg orally 3 times a day) or placebo and were assessed monthly for 6 months. At 0, 3, and 6 months, fasting laboratory tests were performed. The primary end point was the change in BMI from baseline to 6 months. Secondary outcomes included changes in weight, lean body mass, and results of blood chemistry studies. No statistically significant difference was noted between the 2 study groups for decrease in BMI from baseline to 6 months (P = 0.39). The decrease in BMI within the orlistat group (-1.3 +/- 1.6 kg/m2; P = 0.04) and within the placebo group (-0.8 +/- 3.0 kg/m2; P = 0.02), however, was statistically significant. Laboratory measurements did not differ between the 2 groups. In comparison with the placebo group, the orlistat group had increased adverse events, primarily gastrointestinal symptoms and findings. In this study of obese adolescents, orlistat did not significantly reduce BMI in comparison with placebo at 6 months.

C2 Nerve Field Stimulation for the Treatment of Fibromyalgia: A Prospective, Double-blind, Randomized, Controlled Cross-over Study.

PubMed

Plazier, Mark; Ost, Jan; Stassijns, Gaëtane; De Ridder, Dirk; Vanneste, Sven

2015-01-01

Fibromyalgia is a condition characterized by widespread chronic pain. Due to the high prevalence and high costs, it has a substantial burden on society. Treatment results are diverse and only help a small subset of patients. C2 nerve field stimulation, aka occipital nerve stimulation, is helpful and a minimally invasive treatment for primary headache syndromes. Small C2 pilot studies seem to be beneficial in fibromyalgia. Forty patients were implanted with a subcutaneous electrode in the C2 dermatoma as part of a prospective, double-blind, randomized, controlled cross-over study followed by an open label follow up period of 6 months. The patients underwent 2 week periods of different doses of stimulation consisting of minimal (.1 mA), subthreshold, and suprathreshold (for paresthesias) in a randomized order. Twenty seven patients received a permanent implant and 25 completed the 6 month open label follow up period. During the 6 week trial phase of the study, patients had an overall decrease of 36% on the fibromyalgia impact questionnaire (FIQ), a decrease of 33% fibromyalgia pain and improvement of 42% on the impact on daily life activities and quality. These results imply an overall improvement in the disease burden, maintained at 6 months follow up, as well as an improvement in life quality of 50%. Seventy six percent of patients were satisfied or very satisfied with their treatment. There seems to be a dose-response curve, with increasing amplitudes leading to better clinical outcomes. Subcutaneous C2 nerve field stimulation seems to offer a safe and effective treatment option for selected medically intractable patients with fibromyalgia. Copyright © 2015 Elsevier Inc. All rights reserved.

Short-term outcomes of local infiltration anaesthetic in total knee arthroplasty: a randomized controlled double-blinded controlled trial.

PubMed

Mulford, Jonathan S; Watson, Anna; Broe, David; Solomon, Michael; Loefler, Andreas; Harris, Ian

2016-03-01

The primary objective of the study was to determine if local infiltration anaesthetic (LIA) reduced total length of hospital stay in total knee arthroplasty (TKA) patients. The study also examined whether LIA improves early pain management, patient satisfaction and range of motion in TKA patients. We conducted a randomized controlled double-blinded study. Fifty patients undergoing TKA were randomized to receive either placebo or LIA at the time of surgery and on the first day post-operatively. Pain scores, level of satisfaction and range of motion were recorded preoperatively and post-operatively. There was no statistical difference between the groups for length of stay, post-operative pain scores, satisfaction scores or range of motion 6 weeks post-operatively. This randomized double-blinded trial did not demonstrate a decrease in pain or reduction of length of stay due to local infiltration analgesia. © 2015 Royal Australasian College of Surgeons.

Long-Term Nightly Treatment with Indiplon in Adults with Primary Insomnia: Results of a Double-Blind, Placebo-Controlled, 3-Month Study

PubMed Central

Scharf, Martin B.; Black, Jed; Hull, Steven; Landin, Rick; Farber, Robert

2007-01-01

Objectives: To evaluate the efficacy and safety of indiplon in primary insomnia. Design: Randomized, double-blind, placebo-controlled, 3-month study. Setting: Multi-center outpatient setting. Patients: N=702 (61% female; mean age 46 years) who met DSM-IV criteria for primary insomnia of at least 3 months' duration. Interventions: Indiplon 10 mg (n=236), indiplon 20 mg (n=233), or placebo (n=233). Measurements: Subjective assessment of each of the following: latency to sleep onset (sLSO), total sleep time (sTST), number of awakenings after sleep onset (sNAASO), wake time after sleep onset (sWASO), sleep quality, Insomnia Severity Index (ISI), and global improvement. Results: Treatment with indiplon resulted in significant improvement relative to placebo at all time points for the primary endpoint, sLSO. Mean sLSO at Month 1 for each treatment group was: 10 mg (34.0 ± 1.3 mins), 20 mg (33.0 ± 1.3 mins), and placebo (48.7 ± 1.9 mins; P <0.0001 for both comparisons); efficacy was sustained through Month 3. Both doses of indiplon resulted in significant improvement in sleep maintenance and duration endpoints, sTST and sWASO, as well as sleep quality, ISI, and global improvement at all assessment time points. Conclusions: In patients with chronic insomnia, long-term nightly treatment with 10 mg and 20 mg doses of indiplon resulted in significant and sustained efficacy in sleep onset, maintenance, and duration, and significant associated improvement in both daytime functioning and quality of life. Citation: Scharf MB; Black J; Hull S et al. Long-term nightly treatment with indiplon in adults with primary insomnia: Results of a double-blind, placebo-controlled, 3-month study. SLEEP 2007;30(6):743-752. PMID:17580596

Effect of Home Visit Training Program on Growth and Development of Preterm Infants: A Double Blind Randomized Controlled Trial

PubMed Central

Edraki, Mitra; Moravej, Hossian; Rambod, Masoume

2015-01-01

Background: Home visit program can be effective in infants’ growth and development. The present study aimed to investigate the effect of home visit program on preterm infants’ growth and development within 6 months. Methods: It was a double-blind clinical trial study. The study was conducted in Hafez, Hazrat-e-Zeinab, and Namazee Hospitals affiliated to Shiraz University of Medical Sciences, Shiraz, Iran from 2010 to 2011. Preterm infants were divided into intervention (n=30) and control groups (n=30) through blocked randomization. The intervention group received home visit training program for 6 months, while the control group only received the hospital’s routine care. Then, the infants’ growth indexes, including weight, height, and head circumference, and development criteria were compared on the first day of admission in Neonatal Intensive Care Unit, and then first, second, third, and sixth months. The data were analyzed using Chi-square, independent t-test, and repeated measures ANCOVA. Results: The mean weight of the intervention and control group infants was 7207.3±1129.74 and 6366.7±922.26 gr in the sixth month. Besides, the intervention group infants’ mean weight was higher compared to the control group after six months (t=-3.05, P=0.03). Also, a significant difference was found between the two groups regarding development indexes, such as following moving objects with the head, keeping the head stable when changing the position from lying to sitting,  producing “Agha” sound, and taking objects by hand (P<0.05) during six months of age. Conclusion: The results showed that the home visit program was effective in preterm infants’ weight gain and some development indexes at the sixth month. Considering the importance of infants’ growth and development, healthcare staff is recommended to incorporate home visit training into their programs, so that steps can be taken towards improvement of preterm infants’ health. Trial Registration Number

Efficacy, tolerability, and safety of aripiprazole once-monthly versus other long-acting injectable antipsychotic therapies in the maintenance treatment of schizophrenia: a mixed treatment comparison of double-blind randomized clinical trials.

PubMed

Majer, Istvan M; Gaughran, Fiona; Sapin, Christophe; Beillat, Maud; Treur, Maarten

2015-01-01

Treatment with long-acting injectable (LAI) antipsychotic medication is an important element of relapse prevention in schizophrenia. Recently, the intramuscular once-monthly formulation of aripiprazole received marketing approval in Europe and the United States for schizophrenia. This study aimed to compare aripiprazole once-monthly with other LAI antipsychotics in terms of efficacy, tolerability, and safety. A systematic literature review was conducted to identify relevant double-blind randomized clinical trials of LAIs conducted in the maintenance treatment of schizophrenia. MEDLINE, MEDLINE In-Process, Embase, the Cochrane Library, PsycINFO, conference proceedings, clinical trial registries, and the reference lists of key review articles were searched. The literature search covered studies dating from January 2002 to May 2013. Studies were required to have ≥24 weeks of follow-up. Patients had to be stable at randomization. Studies were not eligible for inclusion if efficacy of acute and maintenance phase treatment was not reported separately. Six trials were identified (0.5% of initially identified studies), allowing comparisons of aripiprazole once-monthly, risperidone LAI, paliperidone palmitate, olanzapine pamoate, haloperidol depot, and placebo. Data extracted included study details, study duration, the total number of patients in each treatment arm, efficacy, tolerability, and safety outcomes. The efficacy outcome contained the number of patients that experienced a relapse, tolerability outcomes included the number of patients that discontinued treatment due to treatment-related adverse events (AEs), and that discontinued treatment due to reasons other than AEs (e.g., loss to follow-up). Safety outcomes included the incidence of clinically relevant weight gain and extrapyramidal symptoms. Data were analyzed by applying a mixed treatment comparison competing risks model (efficacy) and using binary models (safety). There was no statistically significant

Cannabis for dyskinesia in Parkinson disease: a randomized double-blind crossover study.

PubMed

Carroll, C B; Bain, P G; Teare, L; Liu, X; Joint, C; Wroath, C; Parkin, S G; Fox, P; Wright, D; Hobart, J; Zajicek, J P

2004-10-12

The long-term treatment of Parkinson disease (PD) may be complicated by the development of levodopa-induced dyskinesia. Clinical and animal model data support the view that modulation of cannabinoid function may exert an antidyskinetic effect. The authors conducted a randomized, double-blind, placebo-controlled crossover trial to examine the hypothesis that cannabis may have a beneficial effect on dyskinesia in PD. A 4-week dose escalation study was performed to assess the safety and tolerability of cannabis in six PD patients with levodopa-induced dyskinesia. Then a randomized placebo-controlled crossover study (RCT) was performed, in which 19 PD patients were randomized to receive oral cannabis extract followed by placebo or vice versa. Each treatment phase lasted for 4 weeks with an intervening 2-week washout phase. The primary outcome measure was a change in Unified Parkinson's Disease Rating Scale (UPDRS) (items 32 to 34) dyskinesia score. Secondary outcome measures included the Rush scale, Bain scale, tablet arm drawing task, and total UPDRS score following a levodopa challenge, as well as patient-completed measures of a dyskinesia activities of daily living (ADL) scale, the PDQ-39, on-off diaries, and a range of category rating scales. Seventeen patients completed the RCT. Cannabis was well tolerated, and had no pro- or antiparkinsonian action. There was no evidence for a treatment effect on levodopa-induced dyskinesia as assessed by the UPDRS, or any of the secondary outcome measures. Orally administered cannabis extract resulted in no objective or subjective improvement in dyskinesias or parkinsonism.

Abatacept in children with juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled withdrawal trial.

PubMed

Ruperto, Nicolino; Lovell, Daniel J; Quartier, Pierre; Paz, Eliana; Rubio-Pérez, Nadina; Silva, Clovis A; Abud-Mendoza, Carlos; Burgos-Vargas, Ruben; Gerloni, Valeria; Melo-Gomes, Jose A; Saad-Magalhães, Claudia; Sztajnbok, Flavio; Goldenstein-Schainberg, Claudia; Scheinberg, Morton; Penades, Immaculada Calvo; Fischbach, Michael; Orozco, Javier; Hashkes, Philip J; Hom, Christine; Jung, Lawrence; Lepore, Loredana; Oliveira, Sheila; Wallace, Carol A; Sigal, Leonard H; Block, Alan J; Covucci, Allison; Martini, Alberto; Giannini, Edward H

2008-08-02

Some children with juvenile idiopathic arthritis either do not respond, or are intolerant to, treatment with disease-modifying antirheumatic drugs, including anti-tumour necrosis factor (TNF) drugs. We aimed to assess the safety and efficacy of abatacept, a selective T-cell costimulation modulator, in children with juvenile idiopathic arthritis who had failed previous treatments. We did a double-blind, randomised controlled withdrawal trial between February, 2004, and June, 2006. We enrolled 190 patients aged 6-17 years, from 45 centres, who had a history of active juvenile idiopathic arthritis; at least five active joints; and an inadequate response to, or intolerance to, at least one disease-modifying antirheumatic drug. All 190 patients were given 10 mg/kg of abatacept intravenously in the open-label period of 4 months. Of the 170 patients who completed this lead-in course, 47 did not respond to the treatment according to predefined American College of Rheumatology (ACR) paediatric criteria and were excluded. Of the patients who did respond to abatacept, 60 were randomly assigned to receive 10 mg/kg of abatacept at 28-day intervals for 6 months, or until a flare of the arthritis, and 62 were randomly assigned to receive placebo at the same dose and timing. The primary endpoint was time to flare of arthritis. Flare was defined as worsening of 30% or more in at least three of six core variables, with at least 30% improvement in no more than one variable. We analysed all patients who were treated as per protocol. This trial is registered, number NCT00095173. Flares of arthritis occurred in 33 of 62 (53%) patients who were given placebo and 12 of 60 (20%) abatacept patients during the double-blind treatment (p=0.0003). Median time to flare of arthritis was 6 months for patients given placebo (insufficient events to calculate IQR); insufficient events had occurred in the abatacept group for median time to flare to be assessed (p=0.0002). The risk of flare in patients

Chemoprevention of Nonmelanoma Skin Cancer With Celecoxib: A Randomized, Double-Blind, Placebo-Controlled Trial

PubMed Central

Viner, Jaye L.; Pentland, Alice P.; Cantrell, Wendy; Bailey, Howard; Kang, Sewon; Linden, Kenneth G.; Heffernan, Michael; Duvic, Madeleine; Richmond, Ellen; Elewski, Boni E.; Umar, Asad; Bell, Walter; Gordon, Gary B.

2010-01-01

Background Preclinical studies indicate that the enzyme cyclooxygenase 2 plays an important role in ultraviolet-induced skin cancers. We evaluated the efficacy and safety of celecoxib, a cyclooxygenase 2 inhibitor, as a chemopreventive agent for actinic keratoses, the premalignant precursor of nonmelanoma skin cancers, and for nonmelanoma skin cancers, including cutaneous squamous cell carcinomas (SCCs) and basal cell carcinomas (BCCs). Methods A double-blind placebo-controlled randomized trial involving 240 subjects aged 37–87 years with 10–40 actinic keratoses was conducted at eight US academic medical centers. Patients were randomly assigned to receive 200 mg of celecoxib or placebo administered orally twice daily for 9 months. Subjects were evaluated at 3, 6, 9 (ie, completion of treatment), and 11 months after randomization. The primary endpoint was the number of new actinic keratoses at the 9-month visit as a percentage of the number at the time of randomization. In an intent-to-treat analysis, the incidence of actinic keratoses was compared between the two groups using t tests. In exploratory analyses, we evaluated the number of nonmelanoma skin cancers combined and SCCs and BCCs separately per patient at 11 months after randomization using Poisson regression, after adjustment for patient characteristics and time on study. The numbers of adverse events in the two treatment arms were compared using χ2 or Fisher exact tests. All statistical tests were two-sided. Results There was no difference in the incidence of actinic keratoses between the two groups at 9 months after randomization. However, at 11 months after randomization, there were fewer nonmelanoma skin cancers in the celecoxib arm than in the placebo arm (mean cumulative tumor number per patient 0.14 vs 0.35; rate ratio [RR] = .43, 95% confidence interval [CI] = 0.24 to 0.75; P = .003). After adjusting for age, sex, Fitzpatrick skin type, history of actinic keratosis at randomization, nonmelanoma

A double blind multicentre study of OM-8980 and auranofin in rheumatoid arthritis.

PubMed Central

Vischer, T L

1988-01-01

The therapeutic efficacy of the immunomodulator OM-8980 in rheumatoid arthritis was compared with that of auranofin, an oral gold salt, in a double blind, randomised multicentre study lasting six months. Seventy patients were treated with auranofin and 75 with OM-8980. The patients of both groups improved significantly at three and six months for all the clinical parameters observed: Ritchie index, number of swollen joints, morning stiffness, pain, grip strength, intake of non-steroidal anti-inflammatory drugs, and erythrocyte sedimentation rate. No serious side effects were observed in either group. The patients receiving auranofin had more adverse reactions, mainly affecting the gastrointestinal system. PMID:3041924

Efficacy of Febuxostat for Slowing the GFR Decline in Patients With CKD and Asymptomatic Hyperuricemia: A 6-Month, Double-Blind, Randomized, Placebo-Controlled Trial.

PubMed

Sircar, Dipankar; Chatterjee, Soumya; Waikhom, Rajesh; Golay, Vishal; Raychaudhury, Arpita; Chatterjee, Suparna; Pandey, Rajendra

2015-12-01

Hyperuricemia is a putative risk factor for the progression of chronic kidney disease (CKD). We hypothesized that control of asymptomatic hyperuricemia may slow disease progression in CKD. This was a single-center, double-blind, randomized, parallel-group, placebo-controlled study. Eligible participants were adults from Eastern India aged 18 to 65 years with CKD stages 3 and 4, with asymptomatic hyperuricemia. The intervention group received febuxostat, 40mg, once daily for 6 months, while the placebo group received placebo; both groups were followed up for 6 months. The primary outcome was the proportion of patients showing a >10% decline in estimated glomerular filtration rate (eGFR) from baseline in the febuxostat and placebo groups. Secondary outcomes included changes in eGFRs in the 2 groups from baseline and at the end of the study period. 45 patients in the febuxostat group and 48 in the placebo group were analyzed. Mean eGFR in the febuxostat group showed a nonsignificant increase from 31.5±13.6 (SD) to 34.7±18.1mL/min/1.73m(2) at 6 months. With placebo, mean eGFR decreased from a baseline of 32.6±11.6 to 28.2±11.5mL/min/1.73m(2) (P=0.003). The difference between groups was 6.5 (95% CI, 0.08-12.81) mL/min/1.73m(2) at 6 months (P=0.05). 17 of 45 (38%) participants in the febuxostat group had a >10% decline in eGFR over baseline compared with 26 of 48 (54%) from the placebo group (P<0.004). Limitations of this study included small numbers of patients and short follow-up, and ∼10% of the randomly assigned population dropped out prior to completion. Febuxostat slowed the decline in eGFR in CKD stages 3 and 4 compared to placebo. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Risperidone in children with autism: randomized, placebo-controlled, double-blind study.

PubMed

Nagaraj, Ravishankar; Singhi, Pratibha; Malhi, Prahbhjot

2006-06-01

Some open-label studies suggest that risperidone can be useful in the treatment of certain target symptoms in children with autism. We aimed to study whether the use of risperidone in comparison with placebo improved functioning in children with autism with regard to behavior (aggressiveness, hyperactivity, irritability), social and emotional responsiveness, and communication skills. We conducted a randomized, double-blind, placebo-controlled trial with 40 consecutive children with autism, whose ages ranged from 2 to 9 years, who were receiving either risperidone or placebo given orally at a dose of 1 mg/day for 6 months. Autism symptoms were monitored periodically. The outcome variables were total scores on the Childhood Autism Rating Scale (CARS) and the Children's Global Assessment Scale (CGAS) after 6 months. Of the 40 children enrolled, 39 completed the trial over a period of 18 months; 19 received risperidone, and 20 received placebo. In the risperidone group, 12 of 19 children showed improvement in the total Childhood Autism Rating Scale score and 17 of 19 children in the Children's Global Assessment Scale score compared with 0 of 20 children for the Childhood Autism Rating Scale score and 2 of 20 children for the Children's Global Assessment Scale score in the placebo group (P < .001 and P = .035, respectively). Risperidone also improved social responsiveness and nonverbal communication and reduced the symptoms of hyperactivity and aggression. Risperidone was associated with increased appetite and a mild weight gain, mild sedation in 20%, and transient dyskinesias in three children. Risperidone improved global functioning and social responsiveness while reducing hyperactivity and aggression in children with autism and was well tolerated.

Effects of creatine supplementation on renal function: a randomized, double-blind, placebo-controlled clinical trial.

PubMed

Gualano, Bruno; Ugrinowitsch, Carlos; Novaes, Rafael Batista; Artioli, Guilherme Gianini; Shimizu, Maria Heloisa; Seguro, Antonio Carlos; Harris, Roger Charles; Lancha, Antonio Herbert

2008-05-01

Creatine (CR) supplementation is commonly used by athletes. However, its effects on renal function remain controversial. The aim of this study was to evaluate the effects of creatine supplementation on renal function in healthy sedentary males (18-35 years old) submitted to exercise training. A randomized, double-blind, placebo-controlled trial was performed. Subjects (n = 18) were randomly allocated to receive treatment with either creatine (CR) ( approximately 10 g day(-1) over 3 months) or placebo (PL) (dextrose). All subjects undertook moderate intensity aerobic training, in three 40-min sessions per week, during 3 months. Serum creatinine, serum and urinary sodium and potassium were determined at baseline and at the end of the study. Cystatin C was assessed prior to training (PRE), after 4 (POST 4) and 12 weeks (POST 12). Cystatin C levels (mg L(-1)) (PRE CR: 0.82 +/- 0.09; PL: 0.88 +/- 0.07 vs. POST 12 CR: 0.71 +/- 0.06; PL: 0.75 +/- 0.09, P = 0.0001) were decreased over time, suggesting an increase in glomerular filtration rate. Serum creatinine decreased with training in PL but was unchanged with training in CR. No significant differences were observed within or between groups in other parameters investigated. The decrease in cystatin C indicates that high-dose creatine supplementation over 3 months does not provoke any renal dysfunction in healthy males undergoing aerobic training. In addition, the results suggest that moderate aerobic training per se may improve renal function.

Prevention of colonic neoplasia with polyethylene glycol: A short term randomized placebo-controlled double-blinded trial.

PubMed

Wali, Ramesh K; Bianchi, Laura; Kupfer, Sonia; De La Cruz, Mart; Jovanovic, Borko; Weber, Christopher; Goldberg, Michael J; Rodriguez, L M; Bergan, Raymond; Rubin, David; Tull, Mary Beth; Richmond, Ellen; Parker, Beth; Khan, Seema; Roy, Hemant K

2018-01-01

Chemoprevention represents an attractive modality against colorectal cancer (CRC) although widespread clinical implementation of promising agents (e.g. aspirin/NSAIDS) have been stymied by both suboptimal efficacy and concerns over toxicity. This highlights the need for better agents. Several groups, including our own, have reported that the over-the-counter laxative polyethylene glycol (PEG) has remarkable efficacy in rodent models of colon carcinogenesis. In this study, we undertook the first randomized human trial to address the role of PEG in prevention of human colonic neoplasia. This was a double-blind, placebo-controlled, three-arm trial where eligible subjects were randomized to 8g PEG-3350 (n = 27) or 17g PEG-3350 (n = 24), or placebo (n = 24; maltodextrin) orally for a duration of six months. Our initial primary endpoint was rectal aberrant crypt foci (ACF) but this was changed during protocol period to rectal mucosal epidermal growth factor receptor (EGFR). Of the 87 patients randomized, 48 completed study primary endpoints and rectal EGFR unchanged PEG treatment. Rectal ACF had a trend suggesting potentially reduction with PEG treatment (pre-post change 1.7 in placebo versus -0.3 in PEG 8+ 17g doses, p = 0.108). Other endpoints (proliferation, apoptosis, expression of SNAIL and E-cadherin), previously noted to be modulated in rodent models, appeared unchanged with PEG treatment in this clinical trial. We conclude that PEG was generally well tolerated with the trial failing to meet primary efficacy endpoints. However, rectal ACFs demonstrated a trend (albeit statistically insignificant) for suppression with PEG. Moreover, all molecular assays including EGFR were unaltered with PEG underscoring issues with lack of translatability of biomarkers from preclinical to clinical trials. This data may provide the impetus for future clinical trials on PEG using more robust biomarkers of chemoprevention. ClinicalTrials.gov NCT00828984.

Prevention of colonic neoplasia with polyethylene glycol: A short term randomized placebo-controlled double-blinded trial

PubMed Central

Wali, Ramesh K.; Bianchi, Laura; Kupfer, Sonia; De La Cruz, Mart; Jovanovic, Borko; Weber, Christopher; Goldberg, Michael J.; Rodriguez, L. M.; Bergan, Raymond; Rubin, David; Tull, Mary Beth; Richmond, Ellen; Parker, Beth; Khan, Seema

2018-01-01

Chemoprevention represents an attractive modality against colorectal cancer (CRC) although widespread clinical implementation of promising agents (e.g. aspirin/NSAIDS) have been stymied by both suboptimal efficacy and concerns over toxicity. This highlights the need for better agents. Several groups, including our own, have reported that the over-the-counter laxative polyethylene glycol (PEG) has remarkable efficacy in rodent models of colon carcinogenesis. In this study, we undertook the first randomized human trial to address the role of PEG in prevention of human colonic neoplasia. This was a double-blind, placebo-controlled, three-arm trial where eligible subjects were randomized to 8g PEG-3350 (n = 27) or 17g PEG-3350 (n = 24), or placebo (n = 24; maltodextrin) orally for a duration of six months. Our initial primary endpoint was rectal aberrant crypt foci (ACF) but this was changed during protocol period to rectal mucosal epidermal growth factor receptor (EGFR). Of the 87 patients randomized, 48 completed study primary endpoints and rectal EGFR unchanged PEG treatment. Rectal ACF had a trend suggesting potentially reduction with PEG treatment (pre-post change 1.7 in placebo versus -0.3 in PEG 8+ 17g doses, p = 0.108). Other endpoints (proliferation, apoptosis, expression of SNAIL and E-cadherin), previously noted to be modulated in rodent models, appeared unchanged with PEG treatment in this clinical trial. We conclude that PEG was generally well tolerated with the trial failing to meet primary efficacy endpoints. However, rectal ACFs demonstrated a trend (albeit statistically insignificant) for suppression with PEG. Moreover, all molecular assays including EGFR were unaltered with PEG underscoring issues with lack of translatability of biomarkers from preclinical to clinical trials. This data may provide the impetus for future clinical trials on PEG using more robust biomarkers of chemoprevention. Trial registration: ClinicalTrials.gov NCT00828984 PMID

Paliperidone palmitate once-monthly reduces risk of relapse of psychotic, depressive, and manic symptoms and maintains functioning in a double-blind, randomized study of schizoaffective disorder.

PubMed

Fu, Dong-Jing; Turkoz, Ibrahim; Simonson, R Bruce; Walling, David P; Schooler, Nina R; Lindenmayer, Jean-Pierre; Canuso, Carla M; Alphs, Larry

2015-03-01

Schizoaffective disorder is a complex illness for which optimal treatment is not well established. Results of the first controlled, relapse-prevention study of paliperidone palmitate once-monthly injectable (paliperidone monthly) in schizoaffective disorder are presented. The study was conducted between September 20, 2010, and October 22, 2013. Patients with schizoaffective disorder (confirmed by the Structured Clinical Interview for DSM-IV Axis I Disorders) experiencing acute exacerbation of psychotic and depressive/manic symptoms were stabilized with paliperidone monthly as monotherapy or as adjunctive therapy to mood stabilizers or antidepressants and randomly assigned (1:1) to paliperidone monthly or placebo in a 15-month, double-blind, relapse-prevention phase. Randomization was stratified by administration as monotherapy or adjunctive therapy and by study center. The primary endpoint was time to relapse. 334 patients were evaluated. Paliperidone monthly significantly delayed time to relapse for psychotic, depressive, and manic symptoms compared with placebo (P < .001, log-rank test). Relapse risk was 2.49 times greater for placebo (hazard ratio = 2.49; 95% CI, 1.55 to 3.99; P < .001, Cox proportional hazards model). Overall relapse rates were 33.5% for placebo and 15.2% for paliperidone monthly. For monotherapy, relapse risk was 3.38 times greater with placebo (P = .002), and for adjunctive treatment it was 2.03 times greater with placebo (P = .021). Paliperidone monthly was superior to placebo in maintaining functioning as measured by the Personal and Social Performance scale (P = .014, mixed-model repeated-measures analysis). The most common adverse events (placebo, paliperidone monthly) were increased weight (4.7%, 8.5%), insomnia (7.1%, 4.9%), schizoaffective disorder (5.9%, 3.0%), headache (3.5%, 5.5%), and nasopharyngitis (3.5%, 5.5%). Incidence of any extrapyramidal-related adverse event was 7.1% for placebo and 8.5% for paliperidone monthly

Cyclosporin treatment for rheumatoid arthritis: a placebo controlled, double blind, multicentre study.

PubMed Central

van Rijthoven, A W; Dijkmans, B A; Goei The, H S; Hermans, J; Montnor-Beckers, Z L; Jacobs, P C; Cats, A

1986-01-01

The efficacy and safety of cyclosporin for patients with rheumatoid arthritis (RA) were assessed in a six month double blind, placebo controlled, multicentre study. The initial dosage of the drug was 10 mg/kg daily for two months. There were many discontinuations in both the cyclosporin group (eight out of 17) and the placebo group (six out of 19). Of the patients who completed the six months of therapy, those who had received cyclosporin showed a significant improvement in the number of swollen joints, the Ritchie articular index, and pain at active movement and at rest, compared not only with their condition at the start of the study, but also with the end results of the placebo group. Major adverse reactions to the drug were gastrointestinal disturbances and nephrotoxicity, which were probably due to the relatively high dosages of cyclosporin given in combination with non-steroidal anti-inflammatory drugs. PMID:3532966

Double-blind, randomized, controlled trial of rasagiline as monotherapy in early Parkinson's disease patients.

PubMed

Stern, Matthew B; Marek, Kenneth L; Friedman, Joseph; Hauser, Robert A; LeWitt, Peter A; Tarsy, Daniel; Olanow, C Warren

2004-08-01

Rasagiline (N-propargyl-1(R)-aminoindan) mesylate is a potent, selective, and irreversible monoamine oxidase-B inhibitor. This study was designed to evaluate the safety, tolerability, and preliminary efficacy of rasagiline monotherapy in early Parkinson's disease (PD) patients not receiving levodopa. The study was performed as a multicenter, parallel-group, double-blind, randomized, placebo-controlled, 10-week study. Fifty-six PD patients were randomly assigned to rasagiline mesylate 1, 2, or 4 mg once daily, or placebo. A 3-week dose-escalation period was followed by a 7-week maintenance phase. At week 10, the mean (+/-SE) changes from baseline in total Unified Parkinson's Disease Rating Scale (UPDRS) score were -1.8 (+/-1.3), -3.6 (+/-1.7), -3.6 (+/-1.2), and -0.5 (+/-0.8) in the rasagiline 1, 2, and 4 mg/day and placebo groups, respectively. Analysis of responders showed that 28% of patients (12 of 43) receiving rasagiline had an improvement in total UPDRS score of greater than 30%, compared with none of the patients receiving placebo (P < 0.05, Fisher's exact test). The frequency and types of adverse events reported by rasagiline-treated and placebo-treated patients were similar. These results suggest that rasagiline monotherapy is well tolerated and efficacious in early PD. Copyright 2004 Movement Disorder Society

A Double-Blind, Double-Dummy, Flexible-Design Randomized Multicenter Trial: Early Safety of Single- Versus Divided-Dose Rabbit Anti-Thymocyte Globulin Induction in Renal Transplantation.

PubMed

Stevens, R B; Wrenshall, L E; Miles, C D; Farney, A C; Jie, T; Sandoz, J P; Rigley, T H; Osama Gaber, A

2016-06-01

A previous nonblinded, randomized, single-center renal transplantation trial of single-dose rabbit anti-thymocyte globulin induction (SD-rATG) showed improved efficacy compared with conventional divided-dose (DD-rATG) administration. The present multicenter, double-blind/double-dummy STAT trial (Single dose vs. Traditional Administration of Thymoglobulin) evaluated SD-rATG versus DD-rATG induction for noninferiority in early (7-day) safety and tolerability. Ninety-five patients (randomized 1:1) received 6 mg/kg SD-rATG or 1.5 mg/kg/dose DD-rATG, with tacrolimus-mycophenolate maintenance immunosuppression. The primary end point was a composite of fever, hypoxia, hypotension, cardiac complications, and delayed graft function. Secondary end points included 12-month patient survival, graft survival, and rejection. Target enrollment was 165 patients with an interim analysis scheduled after 80 patients. Interim analysis showed primary end point noninferiority of SD-rATG induction (p = 0.6), and a conditional probability of <1.73% of continued enrollment producing a significant difference (futility analysis), leading to early trial termination. Final analysis (95 patients) showed no differences in occurrence of primary end point events (p = 0.58) or patients with no, one, or more than one event (p = 0.81), or rejection, graft, or patient survival (p = 0.78, 0.47, and 0.35, respectively). In this rigorously blinded trial in adult renal transplantation, we have shown SD-rATG induction to be noninferior to DD-rATG induction in early tolerability and equivalent in 12-month safety. (Clinical Trials.gov #NCT00906204.). © Copyright 2016 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of the American Society of Transplantation and the American Society of Transplant Surgeons.

Repeated tender point injections of granisetron alleviate chronic myofascial pain--a randomized, controlled, double-blinded trial.

PubMed

Christidis, Nikolaos; Omrani, Shahin; Fredriksson, Lars; Gjelset, Mattias; Louca, Sofia; Hedenberg-Magnusson, Britt; Ernberg, Malin

2015-01-01

Serotonin (5-HT) mediates pain by peripheral 5-HT3-receptors. Results from a few studies indicate that intramuscular injections of 5-HT3-antagonists may reduce musculoskeletal pain. The aim of this study was to investigate if repeated intramuscular tender-point injections of the 5-HT3-antagonist granisetron alleviate pain in patients with myofascial temporomandibular disorders (M-TMD). This prospective, randomized, controlled, double blind, parallel-arm trial (RCT) was carried out during at two centers in Stockholm, Sweden. The randomization was performed by a researcher who did not participate in data collection with an internet-based application ( www.randomization.com ). 40 patients with a diagnose of M-TMD according to the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) were randomized to receive repeated injections, one week apart, with either granisetron (GRA; 3 mg) or isotonic saline as control (CTR). The median weekly pain intensities decreased significantly at all follow-ups (1-, 2-, 6-months) in the GRA-group (Friedman test; P < 0.05), but not in the CTR-group (Friedman-test; P > 0.075). The numbers needed to treat (NNT) were 4 at the 1- and 6-month follow-ups, and 3.3 at the 2-month follow-up in favor of granisetron. Repeated intramuscular tender-point injections with granisetron provide a new pharmacological treatment possibility for myofascial pain patients with repeated intramuscular tender-point injections with the serotonin type 3 antagonist granisetron. It showed a clinically relevant pain reducing effect in the temporomandibular region, both in a short- and long-term aspect. European Clinical Trials Database 2005-006042-41 as well as at Clinical Trials NCT02230371 .

A randomized double-blind trial of two low dose combined oral contraceptives.

PubMed

Bounds, W; Vessey, M; Wiggins, P

1979-04-01

Fifty-five women using Loestrin-20 (20 microgram ethinyl oestradiol and 1 mg norethisterone acetate) as an oral contraceptive have been compared with a like number using Microgynon-30 (30 microgram ethinyl oestradiol and 150 microgram levonorgestrel) in a randomized, double-blind trial. Despite the small sample size, the main finding in the trial is clear-cut; Loestrin-20 provides poor cycle control and is thus less acceptable as an oral contraceptive than Microgynon-30. Although there is also a suggestion that Loestrin-20 may be less effective than Microgynon-30, the difference in the accidental pregnancy rates is not statistically significant.

Concomitant or sequential administration of live attenuated Japanese encephalitis chimeric virus vaccine and yellow fever 17D vaccine: randomized double-blind phase II evaluation of safety and immunogenicity.

PubMed

Nasveld, Peter E; Marjason, Joanne; Bennett, Sonya; Aaskov, John; Elliott, Suzanne; McCarthy, Karen; Kanesa-Thasan, Niranjan; Feroldi, Emmanuel; Reid, Mark

2010-11-01

A randomized, double-blind, study was conducted to evaluate the safety, tolerability and immunogenicity of a live attenuated Japanese encephalitis chimeric virus vaccine (JE-CV) co-administered with live attenuated yellow fever vaccine (YF-17D strain; Stamaril®, Sanofi Pasteur) or administered successively. Participants (n = 108) were randomized to receive: YF followed by JE-CV 30 days later, JE followed by YF 30 days later, or the co-administration of JE and YF followed or preceded by placebo 30 days later or earlier. Placebo was used in a double-dummy fashion to ensure masking. Neutralizing antibody titers against JE-CV, YF-17D and selected wild-type JE strains was determined using a 50% serum-dilution plaque reduction neutralization test. Seroconversion was defined as the appearance of a neutralizing antibody titer above the assay cut-off post-immunization when not present pre-injection at day 0, or a least a four-fold rise in neutralizing antibody titer measured before the pre-injection day 0 and later post vaccination samples. There were no serious adverse events. Most adverse events (AEs) after JE vaccination were mild to moderate in intensity, and similar to those reported following YF vaccination. Seroconversion to JE-CV was 100% and 91% in the JE/YF and YF/JE sequential vaccination groups, respectively, compared with 96% in the co-administration group. All participants seroconverted to YF vaccine and retained neutralizing titers above the assay cut-off at month six. Neutralizing antibodies against JE vaccine were detected in 82-100% of participants at month six. These results suggest that both vaccines may be successfully co-administered simultaneously or 30 days apart.

Intrathecal Baclofen in Children with Spastic Cerebral Palsy: A Double-Blind, Randomized, Placebo-Controlled, Dose-Finding Study

ERIC Educational Resources Information Center

Hoving, Marjanke A.; van Raak, Elisabeth P. M.; Spincemaille, Geert H. J. J.; Palmans, Liesbeth J.; Sleypen, Frans A. M.; Vles, Johan S. H.

2007-01-01

Intrathecal baclofen (ITB) therapy can be very effective in the treatment of intractable spasticity, but its effectiveness and safety have not yet been thoroughly studied in children with cerebral palsy (CP). The aims of this double-blind, randomized, placebo-controlled, dose-finding study were to select children eligible for continuous ITB…

Is ginger effective for the treatment of irritable bowel syndrome? A double blind randomized controlled pilot trial.

PubMed

van Tilburg, Miranda A L; Palsson, Olafur S; Ringel, Yehuda; Whitehead, William E

2014-02-01

Ginger is one of the most commonly used herbal medicines for irritable bowel syndrome (IBS) but no data exists about its effectiveness. Double blind randomized controlled trial. University of North Carolina, Chapel Hill, North Carolina, USA. Forty-five IBS patients were randomly assigned to three groups: placebo, 1g of ginger, and 2g of ginger daily for 28 days. The IBS severity scale (IBS-SS) was administered, as well as adequate relief of symptoms scale. A responder was defined as having at least 25% reduction in IBS-SS post-treatment. There were 57.1% responders to placebo, 46.7% to 1g and 33.3% to 2g of ginger. Adequate relief was reported by 53.3% on placebo and 53.3% in both ginger groups combined. Side effects were mild and reported by 35.7% in the placebo and 16.7% in the ginger groups. This double blind randomized controlled pilot study suggests ginger is well tolerated but did not perform better than placebo. Larger trials are needed before any definitive conclusions can be drawn. Copyright © 2014 Elsevier Ltd. All rights reserved.

Randomized, Double-Blind, Placebo-Controlled Trial of Asenapine Maintenance Therapy in Adults With an Acute Manic or Mixed Episode Associated With Bipolar I Disorder.

PubMed

Szegedi, Armin; Durgam, Suresh; Mackle, Mary; Yu, Sung Yun; Wu, Xiao; Mathews, Maju; Landbloom, Ronald P

2018-01-01

The authors determined the efficacy and safety of asenapine in preventing recurrence of any mood episode in adults with bipolar I disorder. Adults with an acute manic or mixed episode per DSM-IV-TR criteria were enrolled in this randomized, placebo-controlled trial consisting of an initial 12- to 16-week open-label period and a 26-week double-blind randomized withdrawal period. The target asenapine dosage was 10 mg b.i.d. in the open-label period but could be titrated down to 5 mg b.i.d. After completing the open-label period, subjects meeting stabilization/stable-responder criteria were randomized to asenapine or placebo treatment in the double-blind period. The primary efficacy endpoint was time to recurrence of any mood event during the double-blind period. Kaplan-Meier estimation was performed, and 95% confidence intervals were determined. Safety was assessed throughout. A total of 549 subjects entered the open-label period, of whom 253 enrolled in the double-blind randomized withdrawal period (127 in the placebo group; 126 in the asenapine group). Time to recurrence of any mood episode was statistically significantly longer for asenapine- than placebo-treated subjects. In post hoc analyses, significant differences in favor of asenapine over placebo were seen in time to recurrence of manic and depressive episodes. The most common treatment-emergent adverse events were somnolence (10.0%), akathisia (7.7%), and sedation (7.7%) in the open-label period and mania (11.9% of the placebo group compared with 4.0% of the asenapine group) and bipolar I disorder (6.3% compared with 1.6%) in the double-blind period. Long-term treatment with asenapine was more effective than placebo in preventing recurrence of mood events in adults with bipolar I disorder and was generally well-tolerated.

A randomized, double-blind, placebo-controlled trial of infliximab in refractory polymyositis and dermatomyositis.

PubMed

Schiffenbauer, Adam; Garg, Megha; Castro, Christine; Pokrovnichka, Angelina; Joe, Galen; Shrader, Joseph; Cabalar, Imelda Victoria; Faghihi-Kashani, Sara; Harris-Love, Michael O; Plotz, Paul H; Miller, Frederick W; Gourley, Mark

2018-06-01

To investigate in a pilot study the safety and efficacy of infliximab in patients with refractory dermatomyositis (DM) and polymyositis (PM). A randomized, double-blind, placebo-controlled trial including subjects with active DM or PM. Participants had stable doses of immunosuppressive medication and prednisone (≤0.5mg/kg/day), and exhibited clinical signs of muscle weakness for at least 4 weeks prior to study entry. Participants received infusions of either placebo or infliximab 5mg/kg at 0, 2, 6, and 14 weeks in blinded manner. The primary outcome was a ≥15% manual muscle strength (MMT) improvement at week 16 compared to week 0. The secondary outcome measures were improvement defined by the International Myositis Assessment and Clinical Studies Group (IMACS) criteria. At week 16, responders in each arm had the option of either continuing the same treatment or changing to the non-responder treatment for that study arm. Non-responders in the 5mg/kg infliximab arm were increased to infliximab 7.5mg/kg for weeks 22, 30, and 38. Non-responders in the placebo arm at week 16 received infliximab 5mg/kg at weeks 16, 18, 22, 30, and 38. Outcomes were reassessed at week 40. Twelve subjects completed the study to week 16. Six of the 12 subjects received infliximab treatment at the dose of 5mg/kg with only one subject meeting the responder criteria at that dose. Of the remaining five subjects on infliximab, three crossed over to the infliximab 7.5mg/kg dose. One of those three subjects responded. All six patients in the placebo arm crossed over to the 5mg/kg dosing regimen after week 16, and two of those responded to infliximab. Infliximab therapy for patients with refractory PM and DM was well tolerated and may benefit a subset of patients. Published by Elsevier Inc.

A 6-Month, Double-Blind, Maintenance Trial of Lithium Monotherapy Versus the Combination of Lithium and Divalproex for Rapid-Cycling Bipolar Disorder and Co-Occurring Substance Abuse or Dependence

PubMed Central

Kemp, David E.; Gao, Keming; Ganocy, Stephen J.; Rapport, Daniel J.; Elhaj, Omar; Bilali, Sarah; Conroy, Carla; Findling, Robert L.; Calabrese, Joseph R.

2011-01-01

Objective To assess whether combination treatment with lithium and divalproex is more effective than lithium monotherapy in prolonging the time to mood episode recurrence in patients with rapid-cycling bipolar disorder (RCBD) and comorbid substance abuse and/or dependence. Method A 6-month, double-blind, parallel group comparison was carried out in recently manic/hypomanic/mixed patients who had demonstrated a persistent bimodal response to combined treatment with lithium and divalproex. Subjects were randomly assigned to remain on combination treatment or to discontinue divalproex and remain on lithium monotherapy. Results Of 149 patients enrolled into the open-label acute stabilization phase, 79% discontinued prematurely (poor adherence: 42%; nonresponse: 25%; intolerable side effects: 10%). Of 31 patients (21%) randomly assigned to double-blind maintenance treatment, 55% relapsed (24% into depression and 76% into a manic/hypomanic/mixed episode), 26% completed the study, and 19% were poorly adherent or exited prematurely. The median time to recurrence of a new mood episode was 15.9 weeks for patients receiving lithium monotherapy and 17.8 weeks for patients receiving the combination of lithium and divalproex (p=NS). The rate of relapse into a mood episode for those receiving lithium monotherapy or the combination of lithium and divalproex was 56% and 53%, respectively. The rate of depressive relapse in both arms was 13%, while the rate of relapse into a manic, hypomanic, or mixed episode was 44% for lithium monotherapy and 40% for the combination of lithium and divalproex. Conclusion A small subgroup of patients in this study stabilized after six months of treatment with lithium plus divalproex. Of those who did, the addition of divalproex to lithium conferred no additional prophylactic benefit over lithium alone. Although depression is regarded as the hallmark of RCBD in general, these data suggest that recurrent episodes of mania tend to be more common in

Randomized, Double-Blinded, Phase 2 Trial of WR 279,396 (Paromomycin and Gentamicin) for Cutaneous Leishmaniasis in Panama

PubMed Central

Sosa, Néstor; Capitán, Zeuz; Nieto, Javier; Nieto, Melissa; Calzada, José; Paz, Hector; Spadafora, Carmenza; Kreishman-Deitrick, Mara; Kopydlowski, Karen; Ullman, Diane; McCarthy, William F.; Ransom, Janet; Berman, Jonathan; Scott, Charles; Grogl, Max

2013-01-01

In this randomized, double-blinded Phase 2 trial, 30 patients with Leishmania panamensis cutaneous leishmaniasis were randomly allocated (1:1) to receive once daily topical treatment with WR 279,396 (15% paromomycin + 0.5% gentamicin) or Paromomycin Alone (15% paromomycin) for 20 days. The index lesion cure rate after 6 months follow-up was 13 of 15 (87%) for WR 279,396 and 9 of 15 (60%) for Paromomycin Alone (P = 0.099). When all treated lesions were included, the final cure rate for WR 279,398-treated patients was again 87%, but the final cure rate for Paromomycin Alone-treated patients was 8 of 15 (53.3%; P = 0.046). Both creams were well tolerated with mild application site reactions being the most frequent adverse event. The increased final cure rate in the WR 279,396 group in this small Phase 2 study suggests that the combination product may provide greater clinical benefit than paromomycin monotherapy against L. panamensis cutaneous leishmaniasis. PMID:23857024

A randomized, double blinded, placebo-controlled clinical trial of silymarin in ulcerative colitis.

PubMed

Rastegarpanah, Mansoor; Malekzadeh, Reza; Vahedi, Homayoun; Mohammadi, Maryam; Elahi, Elham; Chaharmahali, Meghedi; Safarnavadeh, Tahereh; Abdollahi, Mohammad

2015-12-01

To evaluate the clinical efficacy of silymarin in ulcerative colitis (UC) patients. A randomized double blinded placebo-controlled clinical trial was conducted in 80 UC patients whose disease had been documented and were in remission state between September 2009 and October 2010. Patients were assigned to silymarin group (42 cases) and placebo group (38 cases) using a random number table. Either silymarin (140 mg) or placebo (lactose mono-hydrate, corn starch magnesium stearate) tablets were given once daily for 6 months along with their standard therapy. The efficacies were assessed by disease activity index (DAI), frequency difference of the disease flare-up, and paraclinical data. Ten patients (4 in the silymarin group due to nausea and 6 in the placebo group due to disease flare-up and abdominal pain) discontinued the study. An improvement in hemoglobin level (11.8±1.6 g/dL vs. 13.4±1.2 g/dL,P<0.05) and erythrocyte sedimentation rate (23.7±11.5 mm/h vs.10.8±3.2 mm/h,P<0.05) was observed in the silymarin group but not in the placebo group. DAI significantly decreased in the silymarin group and reached from 11.3±3.5 to 10.7±2.8 (P<0.05). Thirty-five out of 38 patients in the silymarin group were in complete remission with no flare-up after 6 months as compared to 21 out of 32 patients in the placebo group (P=0.5000). Silymarin as a natural supplement may be used in UC patients to maintain remission.

N-Acetylcysteine in the Treatment of Pediatric Trichotillomania: A Randomized, Double-Blind, Placebo-Controlled Add-On Trial

ERIC Educational Resources Information Center

Bloch, Michael H.; Panza, Kaitlyn E.; Grant, Jon E.; Pittenger, Christopher; Leckman, James F.

2013-01-01

Objective: To examine the efficacy of N-acetylcysteine (NAC) for the treatment of pediatric trichotillomania (TTM) in a double-blind, placebo-controlled, add-on study. Method: A total of 39 children and adolescents aged 8 to 17 years with pediatric trichotillomania were randomly assigned to receive NAC or matching placebo for 12 weeks. Our primary…

Six months of daily treatment with vardenafil improves parameters of endothelial inflammation and of hypogonadism in male patients with type 2 diabetes and erectile dysfunction: a randomized, double-blind, prospective trial.

PubMed

Santi, Daniele; Granata, Antonio R M; Guidi, Alessandro; Pignatti, Elisa; Trenti, Tommaso; Roli, Laura; Bozic, Roberto; Zaza, Stefano; Pacchioni, Chiara; Romano, Stefania; Nofer, Jerzy Roch; Rochira, Vincenzo; Carani, Cesare; Simoni, Manuela

2016-04-01

Type 2 diabetes mellitus (T2DM) is associated with endothelial dysfunction, characterized by a reduction of nitric oxide (NO)-mediated relaxation. Phosphodiesterase type 5 inhibitors (PDE5i) improve NO levels. The aim of the study was to investigate whether long-term, chronic treatment with the PDE5i vardenafil improves systemic endothelial function in diabetic men. A prospective, investigator-initiated, randomized, placebo-controlled, double-blind, clinical trial was conducted. In total, 54 male patients affected by T2DM, diagnosed within the last 5 years, and erectile dysfunction were enrolled, regardless of testosterone levels. In all, 26 and 28 patients were assigned to verum and placebo groups respectively. The study consisted of an enrollment phase, a treatment phase (24 weeks) (vardenafil/placebo 10  mg twice in a day) and a follow-up phase (24 weeks). Parameters evaluated were as follows: International Index of Erectile Function 15 (IIEF-15), flow-mediated dilation (FMD), serum interleukin 6 (IL6), endothelin 1 (ET-1), gonadotropins and testosterone (measured by liquid chromatography/tandem mass spectrometry). IIEF-15 erectile function improved during the treatment (P<0.001). At the end of the treatment both FMD (P=0.040) and IL6 (P=0.019) significantly improved. FMD correlated with serum testosterone levels (R(2)=0.299; P<0.001). Testosterone increased significantly under vardenafil treatment and returned in the eugonadal range only in hypogonadal men (n=13), without changes in gonadotropins. Chronic vardenafil treatment did not result in relevant side effects. This is the first double-blind, placebo-controlled clinical trial designed to evaluate the effects of chronic treatment of vardenafil on endothelial health-related parameters and sexual hormones in patients affected by a chronic disease. Chronically administered vardenafil is effective and improves endothelial parameters in T2DM patient. Moreover, chronic vardenafil therapy improves hypogonadism

The 12-month analysis from Basal Cell Carcinoma Outcomes with LDE225 Treatment (BOLT): A phase II, randomized, double-blind study of sonidegib in patients with advanced basal cell carcinoma.

PubMed

Dummer, Reinhard; Guminski, Alexander; Gutzmer, Ralf; Dirix, Luc; Lewis, Karl D; Combemale, Patrick; Herd, Robert M; Kaatz, Martin; Loquai, Carmen; Stratigos, Alexander J; Schulze, Hans-Joachim; Plummer, Ruth; Gogov, Sven; Pallaud, Celine; Yi, Tingting; Mone, Manisha; Chang, Anne Lynn S; Cornélis, Frank; Kudchadkar, Ragini; Trefzer, Uwe; Lear, John T; Sellami, Dalila; Migden, Michael R

2016-07-01

The hedgehog pathway inhibitor sonidegib demonstrated meaningful tumor shrinkage in more than 90% of patients with locally advanced basal cell carcinoma (BCC) or metastatic BCC in the BCC Outcomes with LDE225 Treatment study. This report provides long-term follow-up data collected up to 12 months after the last patient was randomized. In this multicenter, randomized, double-blind phase II study, patients were randomized 1:2 to sonidegib 200 or 800 mg. The primary end point was objective response rate assessed by central review. Objective response rates in the 200- and 800-mg arms were 57.6% and 43.8% in locally advanced BCC and 7.7% and 17.4% in metastatic BCC, respectively. Among the 94 patients with locally advanced BCC who responded, only 18 progressed or died and more than 50% had responses lasting longer than 6 months. In addition, 4 of 5 responders with metastatic BCC maintained an objective response. Grade 3/4 adverse events and those leading to discontinuation were less frequent with sonidegib 200 versus 800 mg (38.0% vs 59.3%; 27.8% vs 37.3%, respectively). No placebo or comparator arms were used because sonidegib demonstrated efficacy in advanced BCC in a phase I study, and the hedgehog pathway inhibitor vismodegib was not yet approved. With longer follow-up, sonidegib demonstrated sustained tumor responses in patients with advanced BCC. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

A randomized, double-blind, placebo-controlled trial of simvastatin to treat Alzheimer disease

PubMed Central

Bell, K.L.; Galasko, D.; Galvin, J.E.; Thomas, R.G.; van Dyck, C.H.; Aisen, P.S.

2011-01-01

Background: Lowering cholesterol is associated with reduced CNS amyloid deposition and increased dietary cholesterol increases amyloid accumulation in animal studies. Epidemiologic data suggest that use of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) may decrease the risk of Alzheimer disease (AD) and a single-site trial suggested possible benefit in cognition with statin treatment in AD, supporting the hypothesis that statin therapy is useful in the treatment of AD. Objective: To determine if the lipid-lowering agent simvastatin slows the progression of symptoms in AD. Methods: This randomized, double-blind, placebo-controlled trial of simvastatin was conducted in individuals with mild to moderate AD and normal lipid levels. Participants were randomly assigned to receive simvastatin, 20 mg/day, for 6 weeks then 40 mg per day for the remainder of 18 months or identical placebo. The primary outcome was the rate of change in the Alzheimer's Disease Assessment Scale–cognitive portion (ADAS-Cog). Secondary outcomes measured clinical global change, cognition, function, and behavior. Results: A total of 406 individuals were randomized: 204 to simvastatin and 202 to placebo. Simvastatin lowered lipid levels but had no effect on change in ADAS-Cog score or the secondary outcome measures. There was no evidence of increased adverse events with simvastatin treatment. Conclusion: Simvastatin had no benefit on the progression of symptoms in individuals with mild to moderate AD despite significant lowering of cholesterol. Classification of evidence: This study provides Class I evidence that simvastatin 40 mg/day does not slow decline on the ADAS-Cog. PMID:21795660

Electrical stimulation for chronic non-specific low back pain in a working-age population: a 12-week double blinded randomized controlled trial.

PubMed

Thiese, Matthew S; Hughes, Matthew; Biggs, Jeremy

2013-03-28

Non-invasive electrotherapy is commonly used for treatment of chronic low back pain. Evidence for efficacy of most electrotherapy modalities is weak or lacking. This study aims to execute a high-quality, double-blinded randomized controlled clinical trial comparing 1) H-Wave(®) Device stimulation plus usual care with 2) transcutaneous electrical nerve stimulation (TENS) plus usual care, and 3) Sham electrotherapy plus usual care to determine comparative efficacy for treatment of chronic non-specific low back pain patients. Chronic non-specific low back pain patients between ages of 18-65 years, with pain of at least 3 months duration and minimal current 5/10 VAS pain. Patients will have no significant signs or symptoms of lumbosacral nerve impingement, malignancy, spinal stenosis, or mood disorders. Double blind RCT with 3 arms and 38 subjects per arm. Randomization by permuted blocks of random length, stratified by Workers Compensation claim (yes vs. no), and use of opioids. The null hypothesis of this study is that there are no statistically significant differences in functional improvement between treatment types during and at the end of a 12-week week treatment period. Subjective data will be collected using Filemaker Pro™ database management collection tools. Objective data will be obtained through functional assessments. Data will be collected at enrollment and at 1, 4, 8, and 12 weeks for each participant by a blinded assessor. H-Wave(®) device stimulation (Intervention A) plus usual care, transcutaneous electrical nerve stimulation (TENS) (Intervention B) plus usual care, and sham electrotherapy plus usual care (control). Each treatment arm will have identical numbers of visits (4) and researcher contact time (approximately 15 hours). Oswestry Disability Index. Secondary measures include: Rowland Morris Instrument, VAS pain score, functional evaluation including strength when pushing and pulling, pain free range of motion in flexion and extension

Interferential and horizontal therapies in chronic low back pain: a randomized, double blind, clinical study.

PubMed

Zambito, A; Bianchini, D; Gatti, D; Viapiana, O; Rossini, M; Adami, S

2006-01-01

Chronic Low Back Pain (CLBP) is one of the most frequent medical problems. Electrical nerve stimulation is frequently used but its efficacy remains controversial. Twenty-six men and 94 women with CLBP associated with either degenerative disk disease or previous multiple vertebral osteoporotic fractures were randomly assigned to either interferential currents (IFT), horizontal therapy (HT) or sham HT administered for 10, 40 and 40 minutes, respectively, daily for 5 days per week for two weeks together with a standard flexion-extension stretching exercise program, Blind efficacy assessment were obtained at baseline and at week 2, 6 and 14 and included a functional questionnaire (Backill), the standard visual analog scale (VAS) and the mean analgesic consumption. At week 2 a significant and similar improvement in both the VAS and Backill score was observed in all three groups. The Backill score continued to improve only in the two active groups with changes significantly greater than those observed in control patients at week 14. The pain VAS score returned to baseline values at week 6 and 14 in the control group while in the IFT and HT groups it continued to improve (p< 0.01 vs controls). The use of analgesic medications significantly improved at week 14 versus pretreatment assessment and over control patients only in the HT group. This randomized double-blind controlled study provides the first evidence that IFT and HT therapy are significantly effective in alleviating both pain and disability in patients with CLBP. The placebo effect is remarkable at the beginning of the treatment but it tends to vanish within a couple of weeks.

Randomized, Double-Blind, Placebo-Controlled Study on Decolonization Procedures for Methicillin-Resistant Staphylococcus aureus (MRSA) among HIV-Infected Adults

PubMed Central

Weintrob, Amy; Bebu, Ionut; Agan, Brian; Diem, Alona; Johnson, Erica; Lalani, Tahaniyat; Wang, Xun; Bavaro, Mary; Ellis, Michael; Mende, Katrin; Crum-Cianflone, Nancy

2015-01-01

Background HIV-infected persons have increased risk of MRSA colonization and skin and soft-tissue infections (SSTI). However, no large clinical trial has examined the utility of decolonization procedures in reducing MRSA colonization or infection among community-dwelling HIV-infected persons. Methods 550 HIV-infected adults at four geographically diverse US military HIV clinics were prospectively screened for MRSA colonization at five body locations every 6 months during a 2-year period. Those colonized were randomized in a double-blind fashion to nasal mupirocin (Bactroban) twice daily and hexachlorophene (pHisoHex) soaps daily for 7 days compared to placeboes similar in appearance but without specific antibacterial activity. The primary endpoint was MRSA colonization at 6-months post-randomization; secondary endpoints were time to MRSA clearance, subsequent MRSA infections/SSTI, and predictors for MRSA clearance at the 6-month time point. Results Forty-nine (9%) HIV-infected persons were MRSA colonized and randomized. Among those with 6-month colonization data (80% of those randomized), 67% were negative for MRSA colonization in both groups (p = 1.0). Analyses accounting for missing 6-month data showed no significant differences could have been achieved. In the multivariate adjusted models, randomization group was not associated with 6-month MRSA clearance. The median time to MRSA clearance was similar in the treatment vs. placebo groups (1.4 vs. 1.8 months, p = 0.35). There was no difference on subsequent development of MRSA infections/SSTI (p = 0.89). In a multivariable model, treatment group, demographics, and HIV-specific factors were not predictive of MRSA clearance at the 6-month time point. Conclusion A one-week decolonization procedure had no effect on MRSA colonization at the 6-month time point or subsequent infection rates among community-dwelling HIV-infected persons. More aggressive or novel interventions may be needed to reduce the burden of MRSA in

Effect of Transcutaneous Electrical Nerve Stimulation on Pain, Function, and Quality of Life in Fibromyalgia: A Double-Blind Randomized Clinical Trial

PubMed Central

Noehren, Brian; Dailey, Dana L.; Rakel, Barbara A.; Vance, Carol G.T.; Zimmerman, Miriam B.; Crofford, Leslie J.

2015-01-01

Background Fibromyalgia is a common chronic pain condition that has a significant impact on quality of life and often leads to disability. To date, there have been few well-controlled trials assessing the utility of nonpharmacological treatment modalities such as transcutaneous electrical nerve stimulation (TENS) in the management of pain and improvement in function in individuals with fibromyalgia. Objectives The purpose of this study will be to complete a long-term, multicenter study to assess the effects of TENS in women with fibromyalgia. Design This will be a phase II randomized, double-blind, placebo-controlled, multicenter clinical trial. Participants Three hundred forty-three participants with fibromyalgia will be recruited for this study. Intervention Participants will be randomly assigned to 1 of 3 groups: the intervention (TENS), placebo, or no treatment. After completing the randomized period, all participants will receive the intervention for 1 month. The participants will be asked to use TENS at the highest tolerable level for at least 2 hours daily during physical activity. Measurements The primary outcome will be pain with movement, with secondary outcomes assessing functional abilities, patient-reported outcomes, and quantitative sensory testing. Limitations Because having participants refrain from their typical medications is not practical, their usage and any change in medication use will be recorded. Conclusions The results of this study will provide some of the first evidence from a large-scale, double-blind, placebo-controlled trial on the effectiveness of TENS on pain control and quality-of-life changes in patients with fibromyalgia. PMID:25212518

Effect of transcutaneous electrical nerve stimulation on pain, function, and quality of life in fibromyalgia: a double-blind randomized clinical trial.

PubMed

Noehren, Brian; Dailey, Dana L; Rakel, Barbara A; Vance, Carol G T; Zimmerman, Miriam B; Crofford, Leslie J; Sluka, Kathleen A

2015-01-01

Fibromyalgia is a common chronic pain condition that has a significant impact on quality of life and often leads to disability. To date, there have been few well-controlled trials assessing the utility of nonpharmacological treatment modalities such as transcutaneous electrical nerve stimulation (TENS) in the management of pain and improvement in function in individuals with fibromyalgia. The purpose of this study will be to complete a long-term, multicenter study to assess the effects of TENS in women with fibromyalgia. This will be a phase II randomized, double-blind, placebo-controlled, multicenter clinical trial. Three hundred forty-three participants with fibromyalgia will be recruited for this study. Participants will be randomly assigned to 1 of 3 groups: the intervention (TENS), placebo, or no treatment. After completing the randomized period, all participants will receive the intervention for 1 month. The participants will be asked to use TENS at the highest tolerable level for at least 2 hours daily during physical activity. The primary outcome will be pain with movement, with secondary outcomes assessing functional abilities, patient-reported outcomes, and quantitative sensory testing. Because having participants refrain from their typical medications is not practical, their usage and any change in medication use will be recorded. The results of this study will provide some of the first evidence from a large-scale, double-blind, placebo-controlled trial on the effectiveness of TENS on pain control and quality-of-life changes in patients with fibromyalgia. © 2015 American Physical Therapy Association.

Commentary on Reconstituting Fibrinogen Concentrate to Maintain Blinding in a Double-blind, Randomized Trial in an Emergency Setting.

PubMed

Bruynseels, Daniel; Solomon, Cristina; Hallam, Angela; Collins, Peter W; Collis, Rachel E; Hamlyn, Vincent; Hall, Judith E

2016-01-01

The gold standard of trial design is the double-blind, placebo-controlled, randomized trial. Intravenous medication, which needs reconstitution by the attending clinician in an emergency situation, can be challenging to incorporate into a suitably blinded study. We have developed a method of blindly reconstituting and administering fibrinogen concentrate (presented as a lyophilized powder), where the placebo is normal saline. Fibrinogen concentrate is increasingly being used early in the treatment of major hemorrhage. Our methodology was designed for a multicenter study investigating the role of fibrinogen concentrate in the treatment of the coagulopathy associated with major obstetric hemorrhage. The method has been verified by a stand-alone pharmaceutical manufacturing unit with an investigational medicinal products license, and to date has successfully been applied 45 times in four study centers. There have been no difficulties in reconstitution and no related adverse events reported. We feel our method is simple to perform and maintains blinding throughout, making it potentially suitable for use in other trials conducted in psychologically high-pressure environments. Although fibrinogen concentrate was the focus of our study, it is likely that the method is applicable to other lyophilized medication with limited shelf life (e.g., antibiotics). Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Randomized, double-blind, placebo-controlled trial of saw palmetto in men with lower urinary tract symptoms.

PubMed

Gerber, G S; Kuznetsov, D; Johnson, B C; Burstein, J D

2001-12-01

To assess the effects of saw palmetto on urinary symptoms, sexual function, and urinary flow rate in men with lower urinary tract symptoms using a double-blind, randomized, placebo-controlled trial. The eligible patients were 45 years of age or older and had an International Prostate Symptom Score of 8 or greater. After a 1-month placebo run-in period, 85 men were randomized to receive saw palmetto or placebo for 6 months. Patients were evaluated using the International Prostate Symptom Score, a sexual function questionnaire, and by measurement of the urinary flow rate. The mean symptom score decreased from 16.7 to 12.3 in the saw palmetto group compared with 15.8 to 13.6 in the placebo group (P = 0.038). The quality-of-life score improved to a greater degree in the saw palmetto group, but this difference was not statistically significant. No change occurred in the sexual function questionnaire results in either group. The peak flow rate increased by 1.0 mL/s and 1.4 mL/s in the saw palmetto and placebo groups, respectively (P = 0.73). Saw palmetto led to a statistically significant improvement in urinary symptoms in men with lower urinary tract symptoms compared with placebo. Saw palmetto had no measurable effect on the urinary flow rates. The mechanism by which saw palmetto improves urinary symptoms remains unknown.

Topical tocopherol for treatment of reticular oral lichen planus: a randomized, double-blind, crossover study.

PubMed

Bacci, C; Vanzo, V; Frigo, A C; Stellini, E; Sbricoli, L; Valente, M

2017-01-01

This randomized, double-blind, placebo-controlled crossover study assessed the efficacy of topical tocopherol acetate compared with placebo in easing oral discomfort in patients with reticular oral lichen planus (ROLP). Thirty-four patients with clinically diagnosed and histologically confirmed ROLP were randomly assigned to two groups, which received first one of two treatments (treatment 1 or 2) for a month, then the other (treatment 2 or 1) for another month, with a two-week washout between them. One treatment contained tocopherol acetate and the other only liquid paraffin. The primary outcome was less discomfort, measured on a visual analog scale (VAS). Secondary outcomes were as follows: length of striae measured and photographed at each follow-up; surface area of lesions; and a modified Thongprasom score. No statistically significant differences emerged between the two treatments (1 vs 2) in terms of VAS scores (P > 0.05; 0.8624) or length of striae (P = 0.0883). Significant differences were seen for surface area of lesions (P < 0.05, P = 0.0045) and modified Thongprasom scores (P = 0.0052). The two treatments differed only in terms of the surface area of the lesions and Thongprasom scores, not in VAS scores for discomfort or the length of patients' striae. Topical tocopherol proved effective in the treatment of ROLP. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effect of whole soy and purified daidzein on ambulatory blood pressure and endothelial function--a 6-month double-blind, randomized controlled trial among Chinese postmenopausal women with prehypertension.

PubMed

Liu, Z-M; Ho, S C; Chen, Y-M; Tomlinson, B; Ho, S; To, K; Woo, J

2015-10-01

Although observational studies suggest that soy foods or isoflavones are cardio-protective, clinical trials on whole soy or isoflavone daidzein (one major isoflavone and the precursor of equol) on blood pressure (BP) and endothelial function (EF) are few and have not been specifically conducted among equol producers, a population most likely to benefit from soy treatment. We performed a 6-month double-blind, randomized, placebo-controlled trial to examine the effect of whole soy (soy flour) or purified daidzein on BP and EF in prehypertensive or untreated hypertensive postmenopausal women verified to be equol producers. A total of 270 eligible women were recruited and randomized to either one of the three treatment groups, 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 (active control group) daily, each given as a solid beverage powder for 6 months. The primary outcome measures were 24 h ambulatory BP (ABP) and EF assessed by flow-mediated dilation using brachial artery ultrasound. A total of 253 subjects completed the study according to protocol. Urinary isoflavones indicated good compliance with the interventions. Intention to treat and per-protocol analysis indicated that there was no significant difference in the 6-month changes or % changes in parameters of ABP and brachial flow-mediated dilation among the three treatment groups. A further subgroup analysis among hypertensive women (n=138) did not alter the conclusions. Whole soy and purified daidzein had no significant effect on BP and vascular function among equol-producing postmenopausal women with prehypertension or untreated hypertension.

Buspirone versus methylphenidate in the treatment of children with attention- deficit/ hyperactivity disorder: randomized double-blind study.

PubMed

Mohammadi, Mohammad-Reza; Hafezi, Poopak; Galeiha, Ali; Hajiaghaee, Reza; Akhondzadeh, Shahin

2012-01-01

A recent randomized clinical trial showed buspirone efficacy in the treatment of attention-deficit/hyperactivity disorder (ADHD) in children. However, results from a recent multi-site controlled clinical trial of transdermal buspirone failed to separate it from placebo in a large sample of children with ADHD. Therefore, due to these inconsistent findings, this study was designed to assess the efficacy of buspirone in the treatment of children with ADHD compared to methylphenidate in a double blind randomized clinical trial. Forty outpatients with a DSM-IV-TR diagnosis of ADHD were study population of this trial. Subjects were recruited from an outpatient child and adolescent clinic for a 6 week double blind, randomized clinical trial. All study subjects were randomly assigned to receive treatment using tablet of buspirone at a dose of 20-30 mg/day depending on weight (20 mg/day for < 30kg and 30 mg/day for > 30kg) (group 1) or methylphenidate at a dose of 20-30 mg/day depending on weight (20 mg/day for < 30kg and 30 mg/day for > 30kg (group 2) for a 6 week double blind, randomized clinical trial. The principal measure of outcome was the Teacher and Parent ADHD Rating Scale IV. Patients were assessed at baseline and at 21 and 42 days after the medication started. Significant differences were observed between the two groups on the Parent and Teacher Rating Scale scores. The changes at the endpoint compared to baseline were: -8.95±8.73 (mean±SD) and -15.60±7.81 (mean±SD) for buspirone and methyphenidate, for Parent ADHD Rating Scale. The changes at the endpoint compared to baseline were: -9.80 ±7.06 (mean±SD) and -22.40±9.90 (mean±SD) for buspirone and methyphenidate, respectively for Teacher ADHD Rating Scale. The difference between the buspirone and methylphenidate groups in the frequency of side effects was not significant except for decreased appetite, headache and insomnia that were observed more frequently in the methylphenidate group. The results of

Novel Once-Daily Extended-Release Tacrolimus Versus Twice-Daily Tacrolimus in De Novo Kidney Transplant Recipients: Two-Year Results of Phase 3, Double-Blind, Randomized Trial.

PubMed

Rostaing, Lionel; Bunnapradist, Suphamai; Grinyó, Josep M; Ciechanowski, Kazimierz; Denny, Jason E; Silva, Helio Tedesco; Budde, Klemens

2016-04-01

1-year data from this trial showed the noninferiority of a novel once-daily extended-release tacrolimus (LCPT; Envarsus XR) to immediate-release tacrolimus (IR-Tac) twice daily after kidney transplantation. Final 24-month analysis of a 2-armed, parallel-group, randomized, double-blind, double-dummy, multicenter, phase 3 trial. 543 de novo kidney recipients randomly assigned to LCPT (n=268) or IR-Tac (n=275); 507 (93.4%) completed the 24-month study. LCPT tablets once daily at 0.17 mg/kg/d or IR-Tac twice daily at 0.1 mg/kg/d; subsequent doses were adjusted to maintain target trough ranges (first 30 days, 6-11 ng/mL; thereafter, 4-11 ng/mL). The intervention was 24 months; the study was double blinded for the entirety. Treatment failure (death, transplant failure, biopsy-proven acute rejection, or loss to follow up) within 24 months. Safety end points included adverse events, serious adverse events, new-onset diabetes, kidney function, opportunistic infections, and malignancies. Pharmacokinetic measures included total daily dose (TDD) of study drugs and tacrolimus trough levels. 24-month treatment failure was LCPT, 23.1%; IR-Tac, 27.3% (treatment difference, -4.14% [95% CI, -11.38% to +3.17%], well below the +10% noninferiority criterion defined for the primary 12-month end point). Subgroup analyses showed fewer treatment failures for LCPT versus IR-Tac among black, older, and female recipients. Safety was similar between groups. From month 1, TDD was lower for LCPT; the difference increased over time. At month 24, mean TDD for LCPT was 24% lower than for the IR-Tac group (P<0.001), but troughs were similar (means at 24 months: LCPT, 5.47 ± 0.17 ng/mL; IR-Tac, 5.8 ± 0.30 ng/mL; P=0.4). Trial participant eligibility criteria may limit the generalizability of results to the global population of de novo kidney transplant recipients. Results suggest that once-daily LCPT in de novo kidney transplantation has comparable efficacy and safety profile to that of IR

The effect of vitamin D on primary dysmenorrhea with vitamin D deficiency: a randomized double-blind controlled clinical trial.

PubMed

Moini, Ashraf; Ebrahimi, Tabandeh; Shirzad, Nooshin; Hosseini, Reihaneh; Radfar, Mania; Bandarian, Fatemeh; Jafari-Adli, Shahrzad; Qorbani, Mostafa; Hemmatabadi, Mahboobeh

2016-06-01

Dysmenorrhea is common among women of reproductive age. This study aim was to investigate the effect of vitamin D (vit D) supplementation in treatment of primary dysmenorrhea with vit D deficiency. A randomized double-blind placebo-controlled clinical trial was conducted on 60 women with primary dysmenorrhea and vit D deficiency referred to our clinic at Arash Women's Hospital from September 2013 to December 2014. Eligible women were randomly assigned into treatment and control groups (30 in each group). Individuals in the treatment group received 50 000 IU oral vit D and the control group received placebo weekly for eight weeks. After two months of treatment, there was a significant difference in serum vit D concentration between the two groups (p < 0.001). Pain severity decreased significantly in treatment group after eight weeks of treatment. There was a significant difference in pain intensity between the two groups after eight weeks of treatment and one month after the end of treatment (p < 0.001 for both). A weekly high dose (50 000 IU) oral vit D supplementation for eight weeks in patients with primary dysmenorrhea and vit D deficiency could improve pain intensity.

A randomized, placebo-controlled, double-blind study to evaluate the efficacy of a citrus bioflavanoid blend in the treatment of senile purpura.

PubMed

Berlin, Joshua M; Eisenberg, David P; Berlin, Mindy B; Sarro, Robert A; Leeman, Douglas R; Fein, Howard

2011-07-01

Senile purpura is a common, chronic skin condition affecting more than 10 percent of individuals over the age of 50. Despite being a benign condition, the continual development of purpura lesions in afflicted patients is frequently a source of significant visual and social concern. To date, there are no known effective treatments for this condition. To evaluate the efficacy of a novel nutraceutical citrus bioflavonoid blend in improving the skin's appearance in patients with senile purpura. A six-week, randomized, multicenter, placebo-controlled, double-blind study was conducted to determine whether a uniquely formulated, oral citrus bioflavonoid supplement could treat active lesions of senile purpura while preventing new lesions from arising. Seventy patients with senile purpura were enrolled and 67 completed the study. Subjects were randomized into two groups receiving either a citrus bioflavonoid blend or placebo medication, which was taken orally twice daily for six weeks. Clinical evaluations were performed by blinded investigators at two locations. A statistically significant reduction in the number of new purpura lesions in the skin area undergoing clinical study was documented. At the end of six weeks, the citrus bioflavonoid blend treated group showed a 50 percent reduction in purpura lesions from baseline. Patient self-assessment of the effectiveness of the medication echoed the results of an investigator global assessment with a statistically significant improvement in the skin's appearance noted by the patients receiving the active medication. No adverse effects were noted by either the patients or investigators. This new treatment appears to both safely and effectively diminish skin bruising in patients with senile purpura.

Changes in biomarkers during a six-month oral immunotherapy intervention for cow's milk allergy.

PubMed

Salmivesi, Susanna; Paassilta, Marita; Huhtala, Heini; Nieminen, Riina; Moilanen, Eeva; Korppi, Matti

2016-11-01

Oral immunotherapy (OIT) is a promising but still experimental method to treat children with cow's milk (CM) allergy (CMA). We evaluated changes in allergic, immunological and inflammatory parameters, which happened during the six-month OIT for CMA. We treated 28 school-aged children with CMA using OIT with a double-blind placebo-controlled design. After the controlled study finished, the placebo group was treated with the same but open-label OIT protocol. Sixteen immune variables were tested before and after the six-month OIT. Before OIT, the median serum CM-specific immunoglobulin (Ig) E was 18.0kIU/L in the intervention group and 9.4kIU/L in the placebo group (p = 0.46). At six months, interleukin (IL)-6 and IL-10 were significantly higher in the intervention group. When the changes during the blinded and open OIT were analysed together for both groups, blood eosinophils and serum total IgE decreased and milk-specific IgG and IgG4, serum IL-4 and IL-6, and serum leptin and resistin increased significantly. Preliminary evidence was found that markers of allergy such as blood eosinophils and serum IgE decreased and milk-specific IgG and IgG4 increased during OIT. Adipokines, leptin and resistin, which functionally are cytokines linked to Th1-type response, increased during OIT. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Reiki therapy for postoperative oral pain in pediatric patients: pilot data from a double-blind, randomized clinical trial.

PubMed

Kundu, Anjana; Lin, Yuting; Oron, Assaf P; Doorenbos, Ardith Z

2014-02-01

To examine the effects of Reiki as an adjuvant therapy to opioid therapy for postoperative pain control in pediatric patients. This was a double-blind, randomized controlled study of children undergoing dental procedures. Participants were randomly assigned to receive either Reiki therapy or the control therapy (sham Reiki) preoperatively. Postoperative pain scores, opioid requirements, and side effects were assessed. Family members were also asked about perioperative care satisfaction. Multiple linear regressions were used for analysis. Thirty-eight children participated. The blinding procedure was successful. No statistically significant difference was observed between groups on all outcome measures. Our study provides a successful example of a blinding procedure for Reiki therapy among children in the perioperative period. This study does not support the effectiveness of Reiki as an adjuvant therapy to opioid therapy for postoperative pain control in pediatric patients. Copyright © 2013 Elsevier Ltd. All rights reserved.

Reiki therapy for postoperative oral pain in pediatric patients: Pilot data from a double-blind, randomized clinical trial

PubMed Central

Kundu, Anjana; Lin, Yuting; Oron, Assaf P.; Doorenbos, Ardith Z.

2014-01-01

Purpose To examine the effects of Reiki as an adjuvant therapy to opioid therapy for postoperative pain control in pediatric patients. Methods This was a double-blind, randomized controlled study of children undergoing dental procedures. Participants were randomly assigned to receive either Reiki therapy or the control therapy (sham Reiki) preoperatively. Postoperative pain scores, opioid requirements, and side effects were assessed. Family members were also asked about perioperative care satisfaction. Multiple linear regressions were used for analysis. Results Thirty-eight children participated. The blinding procedure was successful. No statistically significant difference was observed between groups on all outcome measures. Implications Our study provides a successful example of a blinding procedure for Reiki therapy among children in the perioperative period. This study does not support the effectiveness of Reiki as an adjuvant therapy to opioid therapy for postoperative pain control in pediatric patients. PMID:24439640

A Double-Blind, Randomized Pilot Trial of Chromium Picolinate for Overweight Individuals with Binge-Eating Disorder: Effects on Glucose Regulation.

PubMed

Sala, Margarita; Breithaupt, Lauren; Bulik, Cynthia M; Hamer, Robert M; La Via, Maria C; Brownley, Kimberly A

2017-03-04

Chromium treatment has been shown to improve glucose regulation in some populations. The purpose of this study was to evaluate whether chromium picolinate (CrPic) supplementation improves glucose regulation in overweight individuals with binge-eating disorder (BED). In this double-blinded randomized pilot trial, participants (N = 24) were randomized to high (HIGH, 1000 mcg/day, n = 8) or moderate (MOD, 600 mcg/day, n = 9) dose of CrPic or placebo (PL, n = 7) for 6 months. Participants completed an oral glucose tolerance test (OGTT) at baseline, 3 months, and 6 months. Fixed effects models were used to estimate mean change in glucose area under the curve (AUC), insulin AUC , and insulin sensitivity index (ISI). Results revealed a significant group and time interaction (p < 0.04) for glucose AUC , with glucose AUC increasing significantly in the PL group (p < 0.02) but decreasing significantly in the MOD group (p < 0.03) at 6 months. Insulin AUC increased significantly over time (main effect, p < 0.02), whereas ISI decreased significantly over time (main effect, p < 0.03). As anticipated, a moderate dose of CrPic was associated with improved glycemic control, whereas PL was associated with decreased glycemic control. It was unexpected that the improved glycemic control seen in the MOD dose group was not seen in the HIGH dose group. However, although participants randomized to the HIGH dose group did not have improved glycemic control, they had better glycemic control than participants randomized to the PL group. These findings support the need for larger trials.

Mifepristone versus placebo to treat uterine myoma: a double-blind, randomized clinical trial

PubMed Central

Esteve, Josep Lluis Carbonell; Acosta, Rita; Pérez, Yasmirian; Rodriguez, Barbara; Seigler, Isabel; Sanchez, Carlos; Tomasi, Giuseppe

2013-01-01

Objective To evaluate the efficacy, safety, and quality of life of 5 mg mifepristone per day compared with a placebo in treating uterine fibroids. Design Randomized, double-blind clinical study. Location Eusebio Hernández Gynecology and Obstetrics Teaching Hospital, Havana, Cuba. Subjects One hundred twenty-four subjects with symptomatic uterine fibroids. Treatment One daily capsule of 5 mg mifepristone or a mifepristone placebo over 3 months. Variables in evaluating safety Changes in fibroid and uterine volumes, changes in symptom prevalence and intensity, and changes in quality of life. Results Three months into treatment, fibroid volume was reduced by 28.5% in the mifepristone group with an increase of 1.8% in the placebo group (P = 0.031). There were significant differences between the groups with respect to pelvic pain prevalence (P = 0.006), pelvic pressure (P = 0.027), rectal pain (P = 0.013), hypermenorrhea (P < 0.001), and metrorrhagia (P = 0.002) at the end of treatment. Amenorrhea was 93.1% and 4.3% in the mifepristone and placebo groups, respectively (P < 0.001). Treatment side effects were significantly greater in the mifepristone group. Estradiol levels did not differ significantly between the placebo and mifepristone groups at the end of treatment. Improvement in quality of life was significantly greater in the categories of “symptoms” (P = 0.004) and “activity” (P = 0.045) in the mifepristone group. Conclusion The 5 mg dosage of mifepristone presented significantly superior efficacy compared to the placebo. PMID:23843709

A Randomized, Double-Blind, Crossover Comparison of MK-0929 and Placebo in the Treatment of Adults with ADHD

ERIC Educational Resources Information Center

Rivkin, Anna; Alexander, Robert C.; Knighton, Jennifer; Hutson, Pete H.; Wang, Xiaojing J.; Snavely, Duane B.; Rosah, Thomas; Watt, Alan P.; Reimherr, Fred W.; Adler, Lenard A.

2012-01-01

Objective: Preclinical models, receptor localization, and genetic linkage data support the role of D4 receptors in the etiology of ADHD. This proof-of-concept study was designed to evaluate MK-0929, a selective D4 receptor antagonist as treatment for adult ADHD. Method: A randomized, double-blind, placebo-controlled, crossover study was conducted…

Non-Celiac Gluten Sensitivity Has Narrowed the Spectrum of Irritable Bowel Syndrome: A Double-Blind Randomized Placebo-Controlled Trial.

PubMed

Shahbazkhani, Bijan; Sadeghi, Amirsaeid; Malekzadeh, Reza; Khatavi, Fatima; Etemadi, Mehrnoosh; Kalantri, Ebrahim; Rostami-Nejad, Mohammad; Rostami, Kamran

2015-06-05

Several studies have shown that a large number of patients who are fulfilling the criteria for irritable bowel syndrome (IBS) are sensitive to gluten. The aim of this study was to evaluate the effect of a gluten-free diet on gastrointestinal symptoms in patients with IBS. In this double-blind randomized, placebo-controlled trial, 148 IBS patients fulfilling the Rome III criteria were enrolled between 2011 and 2013. However, only 72 out of the 148 commenced on a gluten-free diet for up to six weeks and completed the study; clinical symptoms were recorded biweekly using a standard visual analogue scale (VAS). In the second stage after six weeks, patients whose symptoms improved to an acceptable level were randomly divided into two groups; patients either received packages containing powdered gluten (35 cases) or patients received placebo (gluten free powder) (37 cases). Overall, the symptomatic improvement was statistically different in the gluten-containing group compared with placebo group in 9 (25.7%), and 31 (83.8%) patients respectively (p < 0.001). A large number of patients labelled as irritable bowel syndrome are sensitive to gluten. Using the term of IBS can therefore be misleading and may deviate and postpone the application of an effective and well-targeted treatment strategy in gluten sensitive patients.

A randomized, double-blind, clinical trial comparing the efficacy and safety of Crocus sativus L. with fluoxetine for improving mild to moderate depression in post percutaneous coronary intervention patients.

PubMed

Shahmansouri, Nazila; Farokhnia, Mehdi; Abbasi, Seyed-Hesammeddin; Kassaian, Seyed Ebrahim; Noorbala Tafti, Ahmad-Ali; Gougol, Amirhossein; Yekehtaz, Habibeh; Forghani, Saeedeh; Mahmoodian, Mehran; Saroukhani, Sepideh; Arjmandi-Beglar, Akram; Akhondzadeh, Shahin

2014-02-01

A significant correlation exists between coronary artery diseases and depression. The aim of this trial was to compare the efficacy and safety of saffron versus fluoxetine in improving depressive symptoms of patients who were suffering from depression after performing percutaneous coronary intervention (PCI). In this randomized double-blind parallel-group study, 40 patients with a diagnosis of mild to moderate depression who had undergone PCI in the last six months were randomized to receive either fluoexetine (40mg/day) or saffron (30mg/day) capsule for six weeks. Participants were evaluated by Hamilton depression rating scale (HDRS) at weeks 3 and 6 and the adverse events were systemically recorded. By the study endpoint, no significant difference was detected between two groups in reduction of HDRS scores (P=0.62). Remission and response rates were not significantly different as well (P=1.00 and P=0.67; respectively). There was no significant difference between two groups in the frequency of adverse events during this trial. Relatively small sample size and short observational period were the major limitations of this study. Short-term therapy with saffron capsules showed the same antidepressant efficacy compared with fluoxetine in patients with a prior history of PCI who were suffering from depression. © 2013 Published by Elsevier B.V.

A randomized, double-blind, placebo-controlled noninferiority trial of amoxicillin for clinically diagnosed acute otitis media in children 6 months to 5 years of age

PubMed Central

Le Saux, Nicole; Gaboury, Isabelle; Baird, Marian; Klassen, Terry P.; MacCormick, Johnna; Blanchard, Colline; Pitters, Carrol; Sampson, Margaret; Moher, David

2005-01-01

Objectives Debate continues with respect to a “watch and wait” approach versus immediate antibiotic treatment for the initial treatment of acute otitis media. In this double-blind noninferiority trial, we compared clinical improvement rates at 14 days for children (6 months to 5 years of age) with acute otitis media who were randomly assigned to receive amoxicillin or placebo. Methods We enrolled healthy children who presented to clinics or the emergency department with a new episode of acute otitis media during the fall and winter months in Ottawa (from December 1999 to the end of March 2002). The children were randomly assigned to receive amoxicillin (60 mg/kg daily) or placebo for 10 days. Telephone follow-up was performed on each of days 1, 2 and 3 and once between day 10 and day 14. The primary outcome was clinical resolution of symptoms, defined as absence of receipt of an antimicrobial (other than the amoxicillin in the treatment group) at any time during the 14-day period. Secondary outcomes were the presence of pain and fever and the activity level in the first 3 days, recurrence rates, and the presence of middle ear effusion at 1 and 3 months. Results According to clinical scoring, 415 of the 512 children who could be evaluated had moderate disease. At 14 days 84.2% of the children receiving placebo and 92.8% of those receiving amoxicillin had clinical resolution of symptoms (absolute difference –8.6%, 95% confidence interval –14.4% to –3.0%). Children who received placebo had more pain and fever in the first 2 days. There were no statistical differences in adverse events between the 2 groups, nor were there any significant differences in recurrence rates or middle ear effusion at 1 and 3 months. Interpretation Our results did not support the hypothesis that placebo was noninferior to amoxicillin (i.e., that the 14-day cure rates among children with clinically diagnosed acute otitis media would not be substantially worse in the placebo group

A randomized double-blind, placebo-controlled trial of minocycline in children and adolescents with fragile x syndrome.

PubMed

Leigh, Mary Jacena S; Nguyen, Danh V; Mu, Yi; Winarni, Tri I; Schneider, Andrea; Chechi, Tasleem; Polussa, Jonathan; Doucet, Paul; Tassone, Flora; Rivera, Susan M; Hessl, David; Hagerman, Randi J

2013-04-01

Minocycline rescued synaptic abnormalities and improved behavior in the fragile X mouse model. Previous open-label human studies demonstrated benefits in individuals with fragile X syndrome (FXS); however, its efficacy in patients with FXS has not been assessed in a controlled trial. Randomized, double-blind, placebo-controlled, crossover trial in individuals with FXS, aged 3.5 years to 16 years (n = 55, mean age 9.2 [SD, 3.6] years). Participants were randomized to minocycline or placebo for 3 months and then switched to the other treatment. Sixty-nine subjects were screened and 66 were randomized. Fifty-five subjects (83.3%) completed at least the first period and 48 (72.7%) completed the full trial. Intention-to-treat analysis demonstrated significantly greater improvements in one primary outcome, Clinical Global Impression Scale-Improvement after minocycline compared with placebo (2.49 ± 0.13 and 2.97 ± 0.13, respectively, p = .0173) and greater improvement in ad hoc analysis of anxiety and mood-related behaviors on the Visual Analog Scale (minocycline: 5.26 cm ± 0.46 cm, placebo: 4.05 cm ± 0.46 cm; p = .0488). Side effects were not significantly different during the minocycline and placebo treatments. No serious adverse events occurred on minocycline. Results may be potentially biased by study design weaknesses, including unblinding of subjects when they completed the study, drug-related side effects unblinding, and preliminary efficacy analysis results known to investigators. Minocycline treatment for 3 months in children with FXS resulted in greater global improvement than placebo. Treatment for 3 months appears safe; however, longer trials are indicated to further assess benefits, side effects, and factors associated with a clinical response to minocycline.

Effects of Febuxostat in Early Gout: A Randomized, Double-Blind, Placebo-Controlled Study.

PubMed

Dalbeth, Nicola; Saag, Kenneth G; Palmer, William E; Choi, Hyon K; Hunt, Barbara; MacDonald, Patricia A; Thienel, Ulrich; Gunawardhana, Lhanoo

2017-12-01

To assess the effect of treatment with febuxostat versus placebo on joint damage in hyperuricemic subjects with early gout (1 or 2 gout flares). In this double-blind, placebo-controlled study, 314 subjects with hyperuricemia (serum uric acid [UA] level of ≥7.0 mg/dl) and early gout were randomized 1:1 to receive once-daily febuxostat 40 mg (increased to 80 mg if the serum UA level was ≥6.0 mg/dl on day 14) or placebo. The primary efficacy end point was the mean change from baseline to month 24 in the modified Sharp/van der Heijde erosion score for the single affected joint. Additional efficacy end points included change from baseline to month 24 in the Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) scores for synovitis, erosion, and edema in the single affected joint, the incidence of gout flares, and serum UA levels. Safety was assessed throughout the study. Treatment with febuxostat did not lead to any notable changes in joint erosion over 2 years. In both treatment groups, the mean change from baseline to month 24 in the modified Sharp/van der Heijde erosion score for the single affected joint was minimal, with no between-group differences. However, treatment with febuxostat significantly improved the RAMRIS synovitis score at month 24 compared with placebo treatment (change from baseline -0.43 versus -0.07; P <0.001), decreased the overall incidence of gout flares (29.3% versus 41.4%; P < 0.05), and improved serum UA control (62.8% versus 5.7%; P < 0.001). No major safety concerns were reported. Urate-lowering therapy with febuxostat improved magnetic resonance imaging-determined synovitis and reduced the incidence of gout flares in subjects with early gout. © 2017 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.

[Tolerance and adequacy of a 100% lactose infant formula. A controlled randomized double-blind study].

PubMed

Girardet, J-P; Fournier, V; Bakhache, P; Beck, L; Kempf, C; Lachambre, E

2012-07-01

Lactose has beneficial nutritional effects in infancy, particularly on calcium retention and on Bifidobacterium colon microflora development. The objective of this controlled, prospective, randomized double-blind study was to assess the adequacy and safety of an infant formula containing only lactose as carbohydrate, as compared to a usual formula. Healthy non-breast-fed infants aged under 7 days were randomized to be fed exclusively with a conventional formula containing lactose (9.6 g/100 kcal) and maltodextrin (1.6 g/100 kcal) or the isocaloric-isoprotein study formula containing 100% lactose (11.2 g/100 kcal) for 120 days. Primary outcome was daily weight gain at D0 and D120. Weight, length, body mass index, formula consumption, tolerance, and safety were assessed monthly. The non-inferiority of the study formula was rejected if the difference in weight gain was higher than 2.5 g/day in the control group. One hundred and seventy-eight infants were enrolled. Mean daily weight gain in the study group differed by 0.71 g/day (95% CI: -2.23; 0.82) indicating the non-inferiority of the study formula. Growth was normal and similar in the two groups, but formula intake was decreased in the study group, leading to a decrease in energy and protein intakes. Tolerance was good and adverse events did not differ between the two groups. The 100% lactose study infant formula was safe and non-inferior to a conventional formula in ensuring normal growth during the first 4 months of life. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Effect of genistein on endothelial function in postmenopausal women: a randomized, double-blind, controlled study.

PubMed

Squadrito, Francesco; Altavilla, Domenica; Crisafulli, Alessandra; Saitta, Antonino; Cucinotta, Domenico; Morabito, Nunziata; D'Anna, Rosario; Corrado, Francesco; Ruggeri, Pietro; Frisina, Nicola; Squadrito, Giovanni

2003-04-15

Genistein, a phytoestrogen found in soybeans, corrects endothelial dysfunction induced by oophorectomy in animals. Using a double-blind, controlled, randomized design, we evaluated its effects on endothelial function in women. We enrolled 79 healthy postmenopausal women (mean [+/- SD] age, 56 +/- 4 years) and randomly assigned them to receive continuous estrogen/progestin therapy (n = 26; 17beta-estradiol [1 mg/d] combined with norethisterone acetate [0.5 mg/d]), genistein (n = 27; 54 mg/d), or placebo (n = 26). Brachial artery flow-mediated, endothelium-dependent vasodilation and plasma levels of nitrites/nitrates (a marker of nitric oxide metabolism) and endothelin-1 were measured at baseline and after 1 year of therapy. Treatment with genistein increased levels of nitrites/nitrates (mean increase, 21 micromol/L; 95% confidence interval [CI]: 15 to 26 micromol/L; P <0.001 vs. placebo); estrogen/progestin therapy caused similar changes (P <0.001 vs. placebo). Plasma endothelin-1 levels decreased following 12 months of genistein (mean decrease, 7 pg/mL; 95% CI: 3 to 10 pg/mL; P <0.001 vs. placebo) and after 12 months of estrogen/progestin (P <0.001 vs. placebo). When compared with placebo, brachial artery flow-mediated dilation was improved by genistein (mean increase, 5.5%; 95% CI: 3.9% to 7.0%; P <0.001) and by estrogen/progestin (P <0.001). There were no significant differences between estrogen and genistein for any of these parameters (all P >0.4). One year of genistein therapy improves endothelium function in postmenopausal women to a similar extent as does an estrogen/progestin regimen.

A double-blind, randomized trial of 0.05% betamethasone vs. topical catalase/dismutase superoxide in vitiligo.

PubMed

Sanclemente, G; Garcia, J J; Zuleta, J J; Diehl, C; Correa, C; Falabella, R

2008-11-01

Among all the topical immunomodulators, vitiligo's mainstay therapy includes topical corticosteroids. Many other non-immune theories have also been suggested for vitiligo's pathogenesis, but the role of oxidative stress has gained more importance in recent years. To compare the effect of topical 0.05% betamethasone vs. catalase/dismutase superoxide (C/DSO). Randomized, matched-paired, double-blind trial. Dermatology Section, University of Antioquia, Medellín, Colombia. Patients (aged > 18 years or between 12 and 18 years) with parent's informed consent, with stable or active bilateral vitiligo. Topical 0.05% betamethasone or C/DSO. Two lesions similar to each other in size were chosen. All assessments were made by two blinded investigators, and photographs were subjected to morphometry analysis. Skin repigmentation by digital morphometry. Twenty-five patients were enrolled in the study (21 women and 4 men). Mean age of participants was 40 years (range: 12-74 years). One patient on C/DSO experienced a mild local erythematous papular rash that self-resolved. At 4 months of therapy, there was no statistical difference on the percentage of repigmentation between betamethasone and C/DSO (5.63% +/- 27.9 vs. 3.22% +/- 25.8, respectively, P = 0.758). After 10 months of therapy, the percentage of skin repigmentation increased to 18.5 +/- 93.14% with betamethasone and to 12.4 +/- 59% with C/DSO, but again, we found no statistical differences (P = 0.79). Few studies have described objective methods to evaluate repigmentation among vitiligo patients. Digital morphometry provides an objective assessment of repigmentation in vitiligo. Objective vitiligo repigmentation with topical C/DSO at 10 months is similar to topical 0.05% betamethasone. Although a mild adverse effect was related to the use of C/DSO, such finding was not severe enough to discontinue treatment.

Effect of short-term estrogen therapy on endothelial function: a double-blinded, randomized, controlled trial.

PubMed

Hurtado, R; Celani, M; Geber, S

2016-10-01

To evaluate the effect of short-term hormone replacement therapy with 0.625 mg conjugated estrogens daily on endothelial function of healthy postmenopausal women, using flow-mediated dilation (FMD) of the brachial artery. We performed a double-blinded, randomized, controlled trial over 3 years. Randomization was performed using computer-generated sorting. All participants were blinded to the use of conjugated equine estrogens (CEE) or placebo and FMD was assessed by a blinded examiner, before and after 28 days of medication. A total of 64 healthy postmenopausal women were selected and randomly assigned into two groups of treatment: 0.625 mg of CEE or placebo. FMD values were statistically different between the groups (p = 0.025): the group receiving CEE showed a FMD value of 0.011 compared to the placebo group (FMD = -0.082). The two groups were additionally evaluated for homogeneity through the Shapiro-Wilk test in respect to variables that could interfere with endothelial function such as age (p = 0.729), body mass index (p = 0.891), and time since menopause (p = 0.724). Other variables were excluded during selection of the participants such as chronic vascular conditions, smoking, and sedentary lifestyle. Our results demonstrate that the administration of 0.625 mg CEE for 28 days is effective in improving vascular nitric oxide-dependent dilation assessed by FMD of the brachial artery in postmenopausal women. NCT01482416.

Magnetic resonance therapy for knee osteoarthritis: a randomized, double blind placebo controlled trial.

PubMed

Gökşen, Nurgül; Çaliş, Mustafa; Doğan, Serap; Çaliş, Havva T; Özgöçmen, Salih

2016-08-01

Therapeutic nuclear magnetic resonance therapy (MRT) works based on the electromagnetic fields. To investigate efficacy of MRT in knee osteoarthritis (OA). Prospective, randomized, double-blind, placebo controlled trial. Outpatient clinic, university hospital. Patients who had mild to moderate knee OA at a single knee joint and between 30-75-years-old were randomized by blinded chip cards (1:1). The treatment group received ten sessions of one hour daily MRT, controls received placebo MRT. All patients underwent clinical examination at baseline, after 2 weeks, and 12 weeks. Imaging included blindly assessed ultrasonography and magnetic resonance (MR) of the knee. Ninety-seven patients completed the study. Both groups improved significantly but the average change from baseline in outcome parameters was similar in MRT group (on VAS-pain,-2.6; WOMAC-pain, -2.09; WOMAC-stiffness, -1.81; WOMAC-physical, -1.96) compared to placebo after two weeks (VAS-pain,-1.6; WOMAC-pain, -1.91; WOMAC-stiffness, -1.27; WOMAC-physical, -1.54). Also changes were quite similar at the 12th week after the treatment. SF-36 components at 12th week improved but changes were not significant. Imaging arm also failed to show significant differences between groups in terms of cartilage thickness on US and MR scores. No adverse events were recorded. MRT is safe, but not superior to placebo in terms of improvement in clinical or imaging parameters after a 10-day course of treatment in mild to moderate knee OA. The present study does not promote use of a 10-day course of MRT in mild to moderate knee OA.

The role of mineral elements and other chemical compounds used in balneology: data from double-blind randomized clinical trials

NASA Astrophysics Data System (ADS)

Morer, Carla; Roques, Christian-François; Françon, Alain; Forestier, Romain; Maraver, Francisco

2017-12-01

The aims of this study were to conduct a systematic literature review on balneotherapy about the specific therapeutic role of mineral elements and other chemical compounds of mineral waters and derivate peloids/muds and to discuss the study methods used to evaluate it (in musculoskeletal conditions). We searched Medline by PubMed using the following key words: "spa therapy" "balneotherapy" "mud" "peloid" "mud pack Therapy" in combination with "randomized controlled trial" "double blind trial." We also reviewed the reference list of articles retrieved by the Medline search. We selected the double-blind randomized clinical trials that assessed the effects of mineral water or mud treatments compared to tap water, attenuated peloid/mud therapy or similar treatments without the specific minerals or chemical compounds of the treatment group ("non-mineral"). We evaluated the internal validity and the quality of the statistical analysis of these trials. The final selection comprised 27 double-blind randomized clinical trials, 20 related to rheumatology. A total of 1118 patients with rheumatological and other musculoskeletal diseases were evaluated in these studies: 552 of knee osteoarthritis, 47 of hand osteoarthritis, 147 chronic low back pain, 308 of reumathoid arthritis, and 64 of osteoporosis; 293 of these participants were assigned to the experimental groups of knee osteoarthritis, 24 in hand osteoarthritis, 82 of low back pain, 152 with reumathoid arthritis, and 32 with osteoporosis. They were treated with mineral water baths and/or mud/peloid (with or without other forms of treatment, like physical therapy, exercise…). The rest were allocated to the control groups; they received mainly tap water and/or "non-mineral" mud/peloid treatments. Mineral water or mud treatments had better and longer improvements in pain, function, quality of life, clinical parameters, and others in some rheumatologic diseases (knee and hand osteoarthritis, chronic low back pain

The role of mineral elements and other chemical compounds used in balneology: data from double-blind randomized clinical trials.

PubMed

Morer, Carla; Roques, Christian-François; Françon, Alain; Forestier, Romain; Maraver, Francisco

2017-12-01

The aims of this study were to conduct a systematic literature review on balneotherapy about the specific therapeutic role of mineral elements and other chemical compounds of mineral waters and derivate peloids/muds and to discuss the study methods used to evaluate it (in musculoskeletal conditions). We searched Medline by PubMed using the following key words: "spa therapy" "balneotherapy" "mud" "peloid" "mud pack Therapy" in combination with "randomized controlled trial" "double blind trial." We also reviewed the reference list of articles retrieved by the Medline search. We selected the double-blind randomized clinical trials that assessed the effects of mineral water or mud treatments compared to tap water, attenuated peloid/mud therapy or similar treatments without the specific minerals or chemical compounds of the treatment group ("non-mineral"). We evaluated the internal validity and the quality of the statistical analysis of these trials. The final selection comprised 27 double-blind randomized clinical trials, 20 related to rheumatology. A total of 1118 patients with rheumatological and other musculoskeletal diseases were evaluated in these studies: 552 of knee osteoarthritis, 47 of hand osteoarthritis, 147 chronic low back pain, 308 of reumathoid arthritis, and 64 of osteoporosis; 293 of these participants were assigned to the experimental groups of knee osteoarthritis, 24 in hand osteoarthritis, 82 of low back pain, 152 with reumathoid arthritis, and 32 with osteoporosis. They were treated with mineral water baths and/or mud/peloid (with or without other forms of treatment, like physical therapy, exercise…). The rest were allocated to the control groups; they received mainly tap water and/or "non-mineral" mud/peloid treatments. Mineral water or mud treatments had better and longer improvements in pain, function, quality of life, clinical parameters, and others in some rheumatologic diseases (knee and hand osteoarthritis, chronic low back pain

Vitamin D as supplementary treatment for tuberculosis: a double-blind, randomized, placebo-controlled trial.

PubMed

Wejse, Christian; Gomes, Victor F; Rabna, Paulo; Gustafson, Per; Aaby, Peter; Lisse, Ida M; Andersen, Paul L; Glerup, Henning; Sodemann, Morten

2009-05-01

Vitamin D has been shown to be involved in the host immune response toward Mycobacterium tuberculosis. To test whether vitamin D supplementation of patients with tuberculosis (TB) improved clinical outcome and reduced mortality. We conducted a randomized, double-blind, placebo-controlled trial in TB clinics at a demographic surveillance site in Guinea-Bissau. We included 365 adult patients with TB starting antituberculosis treatment; 281 completed the 12-month follow-up. The intervention was 100,000 IU of cholecalciferol or placebo at inclusion and again 5 and 8 months after the start of treatment. The primary outcome was reduction in a clinical severity score (TBscore) for all patients with pulmonary TB. The secondary outcome was 12-month mortality. No serious adverse effects were reported; mild hypercalcemia was rare and present in both arms. Reduction in TBscore and sputum smear conversion rates did not differ among patients treated with vitamin D or placebo. Overall mortality was 15% (54 of 365) at 1 year of follow-up and similar in both arms (30 of 187 for vitamin D treated and 24 of 178 for placebo; relative risk, 1.19 [0.58-1.95]). HIV infection was seen in 36% (131 of 359): 21% (76 of 359) HIV-1, 10% (36 of 359) HIV-2, and 5% (19 of 357) HIV-1+2. Vitamin D does not improve clinical outcome among patients with TB and the trial showed no overall effect on mortality in patients with TB; it is possible that the dose used was insufficient. Clinical trial registered with www.controlled-trials.com/isrctn (ISRCTN35212132).

Effect of transcranial direct-current stimulation combined with treadmill training on balance and functional performance in children with cerebral palsy: a double-blind randomized controlled trial.

PubMed

Duarte, Natália de Almeida Carvalho; Grecco, Luanda André Collange; Galli, Manuela; Fregni, Felipe; Oliveira, Cláudia Santos

2014-01-01

Cerebral palsy refers to permanent, mutable motor development disorders stemming from a primary brain lesion, causing secondary musculoskeletal problems and limitations in activities of daily living. The aim of the present study was to determine the effects of gait training combined with transcranial direct-current stimulation over the primary motor cortex on balance and functional performance in children with cerebral palsy. A double-blind randomized controlled study was carried out with 24 children aged five to 12 years with cerebral palsy randomly allocated to two intervention groups (blocks of six and stratified based on GMFCS level (levels I-II or level III).The experimental group (12 children) was submitted to treadmill training and anodal stimulation of the primary motor cortex. The control group (12 children) was submitted to treadmill training and placebo transcranial direct-current stimulation. Training was performed in five weekly sessions for 2 weeks. Evaluations consisted of stabilometric analysis as well as the administration of the Pediatric Balance Scale and Pediatric Evaluation of Disability Inventory one week before the intervention, one week after the completion of the intervention and one month after the completion of the intervention. All patients and two examiners were blinded to the allocation of the children to the different groups. The experimental group exhibited better results in comparison to the control group with regard to anteroposterior sway (eyes open and closed; p<0.05), mediolateral sway (eyes closed; p<0.05) and the Pediatric Balance Scale both one week and one month after the completion of the protocol. Gait training on a treadmill combined with anodal stimulation of the primary motor cortex led to improvements in static balance and functional performance in children with cerebral palsy. Ensaiosclinicos.gov.br/RBR-9B5DH7.

Six months versus nine months anti-tuberculous therapy for female genital tuberculosis: a randomized controlled trial.

PubMed

Sharma, Jai B; Singh, Neeta; Dharmendra, Sona; Singh, Urvashi B; P, Vanamail; Kumar, Sunesh; Roy, K K; Hari, Smriti; Iyer, V; Sharma, S K

2016-08-01

To compare six months versus nine months anti-tuberculous therapy in patients of female genital tuberculosis. It was a randomized controlled trial in a tertiary referral center teaching institute on 175 women presenting with infertility and found to have female genital tuberculosis on clinical examination and investigations. Group I women (86 women) were given 9 months of intermitted anti-tuberculous therapy under directly observed treatment short course (DOTS) strategy while Group II (89 women) were given 6 months of anti-tuberculous therapy under DOTS. Patients were evaluated for primary end points (complete cure, partial response, no response) and secondary end points (recurrence rate, pregnancy rate) during treatment. All patients were followed up further for one year after completion of therapy to assess recurrence of disease and further pregnancies. Baseline characteristics were similar between two randomized groups. There was no difference in the complete clinical response rate (95.3% vs 97.7%, p=0.441) between 9-months and 6-months groups. Four patients in 9-months group and two patients in 6-months group had recurrence of disease and required category II anti tuberculous therapy (p=0.441). Pregnancy rate during treatment and up to one year follow up was also similar in the two groups (23.2% vs 21.3%, p=0.762). Side effects occurred in 27(31.4%) and 29(32.6%) in 9-months and 6-months of therapy and were similar (p=0.866). There was no difference in complete cure rate, recurrent rate and pregnancy rate for either 6-months or 9-months of intermittent directly observed treatment short course anti-tuberculous therapy in female genital tuberculosis. The trial was registered in clinicaltrials.gov with registration no: CTRI/2009/091/001088. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Skin adhesive low-level light therapy for dysmenorrhoea: a randomized, double-blind, placebo-controlled, pilot trial.

PubMed

Shin, Yong-Il; Kim, Nam-Gyun; Park, Kyoung-Jun; Kim, Dong-Wook; Hong, Gi-Youn; Shin, Byung-Cheul

2012-10-01

The cause of dysmenorrhoea is an abnormal function of smooth muscles in the uterus due to long-term deficient blood supply into smooth muscle tissue. The purpose of this study was to evaluate the effectiveness of skin adhesive low-level light therapy (LLLT) in participants with dysmenorrhoea. Thirty-one women were included in this randomized, double-blind, placebo-controlled, pilot trial. Twenty-one women were treated with active LLLT and ten women were treated with placebo one. The therapy was performed in a laboratory room for 20 min a day over a period of 5 days prior to the expected onset of menstruation. The outcome was measured using a visual analog scale (VAS) for each participant's dysmenorrhoeal pain severity. VAS of each subject was measured every month for 6 months. In the active LLLT group, 16 women reported successful results during their first menstrual cycle just after active LLLT and 5 women had successful results from the second menstrual cycle after active LLLT. The pain reduction rate was 83 % in the active LLLT group, whereas there was only a slight and temporary reduction in pain in the placebo LLLT group. Changes of VAS within 6 months of LLLT showed statistical significance (p = 0.001) over placebo control. Our study suggests that skin adhesive LLLT on acupuncture points might be an effective, simple and safe non-pharmacological treatment for dysmenorrhoea.

Maintenance N-acetyl cysteine treatment for bipolar disorder: a double-blind randomized placebo controlled trial.

PubMed

Berk, Michael; Dean, Olivia M; Cotton, Sue M; Gama, Clarissa S; Kapczinski, Flavio; Fernandes, Brisa; Kohlmann, Kristy; Jeavons, Susan; Hewitt, Karen; Moss, Kirsteen; Allwang, Christine; Schapkaitz, Ian; Cobb, Heidi; Bush, Ashley I; Dodd, Seetal; Malhi, Gin S

2012-08-14

N-acetyl cysteine (NAC) is a glutathione precursor that has been shown to have antidepressant efficacy in a placebo-controlled trial. The current study aimed to investigate the maintenance effects of NAC following eight weeks of open-label treatment for bipolar disorder. The efficacy of a double blind randomized placebo controlled trial of 2 g/day NAC as adjunct maintenance treatment for bipolar disorder was examined. Participants (n = 149) had a Montgomery Asberg Depression Rating Score of ≥12 at trial entry and, after eight weeks of open-label NAC treatment, were randomized to adjunctive NAC or placebo, in addition to treatment as usual. Participants (primarily outpatients) were recruited through public and private services and through newspaper advertisements. Time to intervention for a mood episode was the primary endpoint of the study, and changes in mood symptoms, functionality and quality of life measures were secondary outcomes. There was a substantial decrease in symptoms during the eight-week open-label NAC treatment phase. During the subsequent double-blind phase, there was minimal further change in outcome measures with scores remaining low. Consequently, from this low plateau, between-group differences did not emerge on recurrence, clinical functioning or quality of life measures. There were no significant between-group differences in recurrence or symptomatic outcomes during the maintenance phase of the trial; however, these findings may be confounded by limitations. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12607000074493).

The effect of Neuragen PN® on Neuropathic pain: A randomized, double blind, placebo controlled clinical trial

PubMed Central

2010-01-01

Background A double blind, randomized, placebo controlled study to evaluate the safety and efficacy of the naturally derived topical oil, "Neuragen PN®" for the treatment of neuropathic pain. Methods Sixty participants with plantar cutaneous (foot sole) pain due to all cause peripheral neuropathy were recruited from the community. Each subject was randomly assigned to receive one of two treatments (Neuragen PN® or placebo) per week in a crossover design. The primary outcome measure was acute spontaneous pain level as reported on a visual analog scale. Results There was an overall pain reduction for both treatments from pre to post application. As compared to the placebo, Neuragen PN® led to significantly (p < .05) greater pain reduction. Fifty six of sixty subjects (93.3%) receiving Neuragen PN® reported pain reduction within 30 minutes. This reduction within 30 minutes occurred in only twenty one of sixty (35.0%) subjects receiving the placebo. In a break out analysis of the diabetic only subgroup, 94% of subjects in the Neuragen PN® group achieved pain reduction within 30 minutes vs 11.0% of the placebo group. No adverse events were observed. Conclusions This randomized, placebo controlled, clinical trial with crossover design revealed that the naturally derived oil, Neuragen PN®, provided significant relief from neuropathic pain in an all cause neuropathy group. Participants with diabetes within this group experienced similar pain relief. Trial registration ISRCTN registered: ISRCTN13226601 PMID:20487567

OnabotulinumtoxinA Improves Pain in Patients With Post-Stroke Spasticity: Findings From a Randomized, Double-Blind, Placebo-Controlled Trial.

PubMed

Wissel, Jörg; Ganapathy, Vaidyanathan; Ward, Anthony B; Borg, Jörgen; Ertzgaard, Per; Herrmann, Christoph; Haggstrom, Anders; Sakel, Mohamed; Ma, Julia; Dimitrova, Rozalina; Fulford-Smith, Antony; Gillard, Patrick

2016-07-01

Patients with post-stroke spasticity (PSS) commonly experience pain in affected limbs, which may impact quality of life. To assess onabotulinumtoxinA for pain in patients with PSS from the BOTOX(®) Economic Spasticity Trial, a multicenter, randomized, double-blind, placebo-controlled trial. Patients with PSS (N = 273) were randomized to 22- to 34-week double-blind treatment with onabotulinumtoxinA + standard care (SC) or placebo injection + SC and were eligible to receive open-label onabotulinumtoxinA up to 52 weeks. Assessments included change from baseline on the 11-point pain numeric rating scale, proportion of patients with baseline pain ≥4 achieving ≥30% and ≥50% improvement in pain, and pain interference with work at Week 12, end of double-blind treatment, and Week 52. At baseline, most patients (74.3%) experienced pain and 47.4% had pain ≥4 (pain subgroup). Mean pain reduction from baseline at Week 12 was significantly greater with onabotulinumtoxinA + SC (-0.77, 95% CI -1.14 to -0.40) than placebo + SC (-0.13, 95% CI -0.51 to 0.24; P < 0.05). Higher proportions of patients in the pain subgroup achieved ≥30% and ≥50% reductions in pain at Week 12 with onabotulinumtoxinA + SC (53.7% and 37.0%, respectively) compared with placebo (28.8% and 18.6%, respectively; P < 0.05). Reductions in pain were sustained through Week 52. Compared with placebo + SC, onabotulinumtoxinA consistently reduced pain interference with work. This is the first randomized, placebo-controlled trial demonstrating statistically significant and clinically meaningful reductions in pain and pain interference with work with onabotulinumtoxinA in patients with PSS. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

The Study of Mental and Resistance Training (SMART) study—resistance training and/or cognitive training in mild cognitive impairment: a randomized, double-blind, double-sham controlled trial.

PubMed

Fiatarone Singh, Maria A; Gates, Nicola; Saigal, Nidhi; Wilson, Guy C; Meiklejohn, Jacinda; Brodaty, Henry; Wen, Wei; Singh, Nalin; Baune, Bernhard T; Suo, Chao; Baker, Michael K; Foroughi, Nasim; Wang, Yi; Sachdev, Perminder S; Valenzuela, Michael

2014-12-01

Mild cognitive impairment (MCI) increases dementia risk with no pharmacologic treatment available. The Study of Mental and Resistance Training was a randomized, double-blind, double-sham controlled trial of adults with MCI. Participants were randomized to 2 supervised interventions: active or sham physical training (high intensity progressive resistance training vs seated calisthenics) plus active or sham cognitive training (computerized, multidomain cognitive training vs watching videos/quizzes), 2-3 days/week for 6 months with 18-month follow-up. Primary outcomes were global cognitive function (Alzheimer's Disease Assessment Scale-cognitive subscale; ADAS-Cog) and functional independence (Bayer Activities of Daily Living). Secondary outcomes included executive function, memory, and speed/attention tests, and cognitive domain scores. One hundred adults with MCI [70.1 (6.7) years; 68% women] were enrolled and analyzed. Resistance training significantly improved the primary outcome ADAS-Cog; [relative effect size (95% confidence interval) -0.33 (-0.73, 0.06); P < .05] at 6 months and executive function (Wechsler Adult Intelligence Scale Matrices; P = .016) across 18 months. Normal ADAS-Cog scores occurred in 48% (24/49) after resistance training vs 27% (14/51) without resistance training [P < .03; odds ratio (95% confidence interval) 3.50 (1.18, 10.48)]. Cognitive training only attenuated decline in Memory Domain at 6 months (P < .02). Resistance training 18-month benefit was 74% higher (P = .02) for Executive Domain compared with combined training [z-score change = 0.42 (0.22, 0.63) resistance training vs 0.11 (-0.60, 0.28) combined] and 48% higher (P < .04) for Global Domain [z-score change = .0.45 (0.29, 0.61) resistance training vs 0.23 (0.10, 0.36) combined]. Resistance training significantly improved global cognitive function, with maintenance of executive and global benefits over 18 months. Copyright © 2014 AMDA – The Society for Post-Acute and Long

Trimethoprim as Adjuvant Treatment in Schizophrenia: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial

PubMed Central

Shibre, Teshome; Alem, Atalay; Abdulahi, Abdulreshid; Araya, Mesfin; Beyero, Teferra; Medhin, Girmay; Deyassa, Negusse; Negash, Alemayehu; Nigatu, Alemayehu; Kebede, Derege

2010-01-01

Various infectious agents, such as Toxoplasma gondii, have been hypothesized to be potentially relevant etiological factors in the onset of some cases of schizophrenia. We conducted a randomized, double-blind, placebo-controlled treatment trial in an attempt to explore the hypothesis that the symptoms of schizophrenia may be related to infection of the central nervous system with toxoplasma gondii. Systematically selected patients with ongoing and at least moderately severe schizophrenia from Butajira, in rural Ethiopia, were randomly allocated to trimethoprim or placebo, which were added on to participants' regular antipsychotic treatments. Trial treatments were given for 6 months. The Positive and Negative Syndrome Scale (PANSS) was used to assess outcome. Ninety-one patients were included in the study, with 80 cases (87.9%) positive for T. gondii immunoglobulin G antibody. Seventy-nine subjects (87.0%) completed the trial. The mean age of subjects was 35.3 (SD = 8.0) years, with a mean duration of illness of 13.2 (SD = 6.7) years. Both treatment groups showed significant reduction in the overall PANSS score with no significant between-group difference. In this sample of patients with chronic schizophrenia, trimethoprim used as adjuvant treatment is not superior to placebo. However, it is not possible to draw firm conclusion regarding the etiological role of toxoplasmosis on schizophrenia based on this study because the timing and the postulated mechanisms through which toxoplasmosis produces schizophrenia are variable. PMID:19193743

Extended Safety, Immunogenicity and Efficacy of a Blood-Stage Malaria Vaccine in Malian Children: 24-Month Follow-Up of a Randomized, Double-Blinded Phase 2 Trial

PubMed Central

Laurens, Matthew B.; Thera, Mahamadou A.; Coulibaly, Drissa; Ouattara, Amed; Kone, Abdoulaye K.; Guindo, Ando B.; Traore, Karim; Traore, Idrissa; Kouriba, Bourema; Diallo, Dapa A.; Diarra, Issa; Daou, Modibo; Dolo, Amagana; Tolo, Youssouf; Sissoko, Mahamadou S.; Niangaly, Amadou; Sissoko, Mady; Takala-Harrison, Shannon; Lyke, Kirsten E.; Wu, Yukun; Blackwelder, William C.; Godeaux, Olivier; Vekemans, Johan; Dubois, Marie-Claude; Ballou, W. Ripley; Cohen, Joe; Dube, Tina; Soisson, Lorraine; Diggs, Carter L.; House, Brent; Bennett, Jason W.; Lanar, David E.; Dutta, Sheetij; Heppner, D. Gray; Plowe, Christopher V.; Doumbo, Ogobara K.

2013-01-01

Background The FMP2.1/AS02A candidate malaria vaccine was tested in a Phase 2 study in Mali. Based on results from the first eight months of follow-up, the vaccine appeared well-tolerated and immunogenic. It had no significant efficacy based on the primary endpoint, clinical malaria, but marginal efficacy against clinical malaria in secondary analyses, and high allele-specific efficacy. Extended follow-up was conducted to evaluate extended safety, immunogenicity and efficacy. Methods A randomized, double-blinded trial of safety, immunogenicity and efficacy of the candidate Plasmodium falciparum apical membrane antigen 1 (AMA1) vaccine FMP2.1/AS02A was conducted in Bandiagara, Mali. Children aged 1–6 years were randomized in a 1∶1 ratio to receive FMP2.1/AS02A or control rabies vaccine on days 0, 30 and 60. Using active and passive surveillance, clinical malaria and adverse events as well as antibodies against P. falciparum AMA1 were monitored for 24 months after the first vaccination, spanning two malaria seasons. Findings 400 children were enrolled. Serious adverse events occurred in nine participants in the FMP2.1/AS02A group and three in the control group; none was considered related to study vaccination. After two years, anti-AMA1 immune responses remained significantly higher in the FMP2.1/AS02A group than in the control group. For the entire 24-month follow-up period, vaccine efficacy was 7.6% (p = 0.51) against first clinical malaria episodes and 9.9% (p = 0.19) against all malaria episodes. For the final 16-month follow-up period, vaccine efficacy was 0.9% (p = 0.98) against all malaria episodes. Allele-specific efficacy seen in the first malaria season did not extend into the second season of follow-up. Interpretation Allele-specific vaccine efficacy was not sustained in the second malaria season, despite continued high levels of anti-AMA1 antibodies. This study presents an opportunity to evaluate correlates of partial protection against

Randomized, double-blind, comparative-effectiveness study comparing pulsed radiofrequency to steroid injections for occipital neuralgia or migraine with occipital nerve tenderness.

PubMed

Cohen, Steven P; Peterlin, B Lee; Fulton, Larry; Neely, Edward T; Kurihara, Connie; Gupta, Anita; Mali, Jimmy; Fu, Diana C; Jacobs, Michael B; Plunkett, Anthony R; Verdun, Aubrey J; Stojanovic, Milan P; Hanling, Steven; Constantinescu, Octav; White, Ronald L; McLean, Brian C; Pasquina, Paul F; Zhao, Zirong

2015-12-01

Occipital neuralgia (ON) is characterized by lancinating pain and tenderness overlying the occipital nerves. Both steroid injections and pulsed radiofrequency (PRF) are used to treat ON, but few clinical trials have evaluated efficacy, and no study has compared treatments. We performed a multicenter, randomized, double-blind, comparative-effectiveness study in 81 participants with ON or migraine with occipital nerve tenderness whose aim was to determine which treatment is superior. Forty-two participants were randomized to receive local anesthetic and saline, and three 120 second cycles of PRF per targeted nerve, and 39 were randomized to receive local anesthetic mixed with deposteroid and 3 rounds of sham PRF. Patients, treating physicians, and evaluators were blinded to interventions. The PRF group experienced a greater reduction in the primary outcome measure, average occipital pain at 6 weeks (mean change from baseline -2.743 ± 2.487 vs -1.377 ± 1.970; P < 0.001), than the steroid group, which persisted through the 6-month follow-up. Comparable benefits favoring PRF were obtained for worst occipital pain through 3 months (mean change from baseline -1.925 ± 3.204 vs -0.541 ± 2.644; P = 0.043), and average overall headache pain through 6 weeks (mean change from baseline -2.738 ± 2.753 vs -1.120 ± 2.1; P = 0.037). Adverse events were similar between groups, and few significant differences were noted for nonpain outcomes. We conclude that although PRF can provide greater pain relief for ON and migraine with occipital nerve tenderness than steroid injections, the superior analgesia may not be accompanied by comparable improvement on other outcome measures.

Randomized, double-blind, comparative-effectiveness study comparing pulsed radiofrequency to steroid injections for occipital neuralgia or migraine with occipital nerve tenderness

PubMed Central

Cohen, Steven P.; Peterlin, B. Lee; Fulton, Larry; Neely, Edward T.; Kurihara, Connie; Gupta, Anita; Mali, Jimmy; Fu, Diana C.; Jacobs, Michael B.; Plunkett, Anthony R.; Verdun, Aubrey J.; Stojanovic, Milan P.; Hanling, Steven; Constantinescu, Octav; White, Ronald L.; McLean, Brian C.; Pasquina, Paul F.; Zhao, Zirong

2015-01-01

Occipital neuralgia (ON) is characterized by lancinating pain and tenderness overlying the occipital nerves. Both steroid injections and pulsed radiofrequency (PRF) are used to treat ON, but few clinical trials have evaluated efficacy, and no study has compared treatments. We performed a multicenter, randomized, double-blind, comparative-effectiveness study in 81 participants with ON or migraine with occipital nerve tenderness whose aim was to determine which treatment is superior. Forty-two participants were randomized to receive local anesthetic and saline, and three 120 second cycles of PRF per targeted nerve, and 39 were randomized to receive local anesthetic mixed with deposteroid and 3 rounds of sham PRF. Patients, treating physicians, and evaluators were blinded to interventions. The PRF group experienced a greater reduction in the primary outcome measure, average occipital pain at 6 weeks (mean change from baseline −2.743 ± 2.487 vs −1.377 ± 1.970; P <0.001), than the steroid group, which persisted through the 6-month follow-up. Comparable benefits favoring PRF were obtained for worst occipital pain through 3 months (mean change from baseline−1.925 ± 3.204 vs−0.541 ± 2.644; P = 0.043), and average overall headache pain through 6 weeks (mean change from baseline −2.738 ± 2.753 vs −1.120 ± 2.1; P = 0.037). Adverse events were similar between groups, and few significant differences were noted for nonpain outcomes. We conclude that although PRF can provide greater pain relief for ON and migraine with occipital nerve tenderness than steroid injections, the superior analgesia may not be accompanied by comparable improvement on other outcome measures. PMID:26447705

A Randomized Double-Blind, Placebo-Controlled Trial of Minocycline in Children and Adolescents with Fragile X Syndrome

PubMed Central

Leigh, Mary Jacena S.; Nguyen, Danh V.; Mu, Yi; Winarni, Tri I.; Schneider, Andrea; Chechi, Tasleem; Polussa, Jonathan; Doucet, Paul; Tassone, Flora; Rivera, Susan M.; Hessl, David; Hagerman, Randi J.

2013-01-01

Objective Minocycline rescued synaptic abnormalities and improved behavior in the fragile X mouse model. Prior open-label human studies demonstrated benefits in individuals with fragile X syndrome (FXS); however, its efficacy in patients with FXS has not been assessed in a controlled trial. Method Randomized, double-blind, placebo-controlled, crossover trial in individuals with FXS, ages 3.5-16 years (n=55, mean age 9.2 (SD 3.6 years)). Participants were randomized to minocycline or placebo for three months, then switched to the other treatment. Results Sixty-nine subjects were screened and 66 were randomized. Fifty-five subjects (83.3%) completed at least the first period and 48 (72.7%) completed the full trial. Intention-to-treat analysis demonstrated significantly greater improvements in one primary outcome, Clinical Global Impression Scale-Improvement after minocycline compared to placebo (2.49 ±0.13, 2.97 ±0.13, respectively, p 0.0173) and greater improvement in ad hoc analysis of anxiety and mood-related behaviors on the Visual Analoge Scale (minocycline 5.26 cm ±0.46 cm, placebo 4.05 cm±0.46cm; p 0.0488). Side effects were not significantly different during the minocycline and placebo treatments. No serious adverse events occurred on minocycline. Results may be potentially biased by study design weaknesses, including unblinding of subjects when they completed the study, drug-related side effects unblinding and preliminary efficacy analysis results known to investigators. Conclusion Minocycline treatment for three months in children with FXS resulted in greater global improvement than placebo. Treatment for three months appears safe; however, longer trials are indicated to further assess benefits, side effects, and factors associated with a clinical response to minocycline. PMID:23572165

Effect of sugar-sweetened beverages on body weight in children: design and baseline characteristics of the Double-blind, Randomized INtervention study in Kids.

PubMed

de Ruyter, Janne Catharine; Olthof, Margreet Renate; Kuijper, Lothar David Jan; Katan, Martijn Bernard

2012-01-01

Intake of sugar-sweetened beverages is associated with overweight in observational studies. A possible explanation is that liquid sugars do not satiate and that their intake is not compensated by reduced caloric intake from other foods. However, evidence from intervention studies for this hypothesis is inconclusive because previous studies were not blinded. Hence results may have been influenced by expectations and behavioral cues rather than by physiological mechanisms. We designed the Double-blind, Randomized INtervention study in Kids (DRINK) to examine the effect on body weight of covertly replacing sugar-sweetened by sugar-free beverages. Children were only eligible if they habitually drank sugar-sweetened beverages. We recruited 642 healthy children (mean age 8.2, range 4.8-11.9). We designed, tested and produced custom-made beverages containing 10% sugar and sugar-free beverages with the same sweet taste and look. Children receive one 250 mL can of study beverage daily for 18 months. We perform body measurements at 0, 6, 12 and 18 months. The primary outcome is the z-score of BMI for age. The maximum predicted difference in this score between groups is 0.72, which corresponds with a difference in body weight of 2.3 kg. The double-blind design eliminates behavioral factors that affect body weight. If children gain less body fat when drinking sugar-free than when drinking sugar-sweetened beverages that would show that liquid sugar indeed bypasses biological satiation mechanisms. It would also suggest that a reduction in liquid sugars could decrease body fat more effectively than reduction of other calorie sources. Copyright © 2011 Elsevier Inc. All rights reserved.

Efficacy and tolerability of Hairgain in individuals with hair loss: a placebo-controlled, double-blind study.

PubMed

Thom, E

2001-01-01

This randomized, placebo-controlled, double-blind study was designed to investigate the efficacy and tolerability of a new agent for the treatment of hair loss, based on a marine protein, minerals and vitamins. Sixty subjects with hair loss of different aetiologies participated in the 6-month blinded phase of the study. Objective assessments indicated that the treatment was effective and subjective assessments showed a statistically significant positive effect of treatment. Exposure to the active preparation for a further 6 months in an open phase indicated a further improvement in hair growth. Exposure of the patients previously treated with placebo to the active preparation for 12 months gave similar results. Tolerability was good and no side-effects were reported. The product investigated may provide an alternative to pharmacotherapy for the treatment of hair-loss problems in individuals with androgenic alopecia.

Amantadine versus methylphenidate in children and adolescents with attention deficit/hyperactivity disorder: a randomized, double-blind trial.

PubMed

Mohammadi, Mohammad-Reza; Kazemi, Mohammad-Reza; Zia, Ebtehal; Rezazadeh, Shams-Ali; Tabrizi, Mina; Akhondzadeh, Shahin

2010-11-01

The aim of the present study was to further evaluate, under double blind and controlled conditions, the efficacy of amantadine for attention-deficit/hyperactivity disorder (ADHD) in children and adolescents as compared to methylphenidate. This was a 6-week randomized clinical trial. Forty patients (28 boys and 12 girls) with a DSM-IV-TR diagnosis of ADHD were the study population of this trial. All study subjects were randomly assigned to receive the treatment using capsule of amantadine at a dose of 100-150 mg/day depending on weight (100 mg/day for <30 kg and 150 mg/day for >30 kg) or methylphenidate at a dose of 20-30 mg/day for a 6-week double blind, randomized clinical trial. The principal measure of outcome was the Teacher and Parent Attention deficit/hyperactivity disorder Rating Scale-IV. No significant differences were observed between the two groups on the Parent and Teacher Rating Scale scores (df = 1; F = 0.02; p = 0.86 and df = 1; F = 0.01; p = 0.89, respectively). Side effects of decreased appetite and restlessness were observed more frequently in the methylphenidate group. The results of this study indicate that amantadine significantly improved symptoms of ADHD and was well tolerated and it may be beneficial in the treatment of children with ADHD. Nevertheless, the present results do not constitute proof of efficacy. Copyright © 2010 John Wiley & Sons, Ltd.

Melatonin improves sleep in children with epilepsy: randomized, double-blind cross-over study

PubMed Central

Jain, Sejal V; Horn, Paul S; Simakajornboon, Narong; Beebe, Dean W; Holland, Katherine; Byars, Anna W; Glauser, Tracy A

2015-01-01

Objective Insomnia, especially maintenance insomnia is widely prevalent in epilepsy. Although melatonin is commonly used, limited data address its efficacy. We performed a randomized, double-blind, placebo-controlled, cross-over study to identify the effects of melatonin on sleep and seizure control in children with epilepsy. Methods Eleven pre-pubertal, developmentally normal children aged 6–11 years with epilepsy were randomized by software algorithm to receive placebo or 9 mg sustained release melatonin for 4 weeks, followed by a 1-week washout and 4-week crossover condition. The pharmacy performed blinding; patients, parents and study staff other than a statistician were blinded. Primary outcomes were sleep onset latency and wakefulness after sleep onset (WASO) measured on polysomnography. Secondary outcomes included seizure frequency, epileptiform spike density per hour of sleep on EEG and reaction time measures on psychomotor vigilance task. Statistical tests appropriate for cross-over designs were used for analysis. Results Data were analyzed from ten subjects who completed the study. Melatonin decreased sleep latency (Mean difference (MD): 11.4 min, p= 0.02) and WASO (MD 22 min, p=0.04) as compared to placebo. No worsening of spike density or seizure frequency was seen. Additionally, Slow-wave sleep duration and REM latency were increased with melatonin and REM sleep duration was decreased. These changes were statistically significant. Worsening of headache was noted in one subject with migraine on melatonin. Conclusion Sustained-release melatonin resulted in statistically significant decreases in sleep latency and WASO. No clear effects on seizures were observed but the study was too small to allow any conclusions to be drawn in this regard. PMID:25862116

Dronabinol and lofexidine for cannabis use disorder: A randomized, double-blind, placebo-controlled trial.

PubMed

Levin, Frances R; Mariani, John J; Pavlicova, Martina; Brooks, Daniel; Glass, Andrew; Mahony, Amy; Nunes, Edward V; Bisaga, Adam; Dakwar, Elias; Carpenter, Kenneth M; Sullivan, Maria A; Choi, Jean C

2016-02-01

Cannabis use disorder is associated with substantial morbidity and, after alcohol, is the most common drug bringing adolescents and adults into treatment. At present, there are no FDA-approved medications for cannabis use disorder. Combined pharmacologic interventions might be particularly useful in mitigating withdrawal symptoms and promoting abstinence. The purpose of this study was to evaluate the safety and efficacy of dronabinol, a synthetic form of delta-9-tetrahydrocannabinol, a naturally occurring pharmacologically active component of marijuana, and lofexidine, an alpha-2 agonist, in treating cannabis dependence. One hundred fifty six cannabis-dependent adults were enrolled and following a 1-week placebo lead-in phase 122 were randomized in a double-blind, placebo-controlled, 11-week trial. Participants were randomized to receive dronabinol 20mg three times a day and lofexidine 0.6 mg three times a day or placebo. Medications were maintained until the end of week eight, were then tapered over two weeks and patients were monitored off medications during the last study week. All participants received weekly motivational enhancement and relapse prevention therapy. Marijuana use was assessed using the timeline follow-back method. There was no significant difference between treatment groups in the proportion of participants who achieved 3 weeks of abstinence during the maintenance phase of the trial (27.9% for the medication group and 29.5% for the placebo group), although both groups showed a reduction over time. Based on this treatment study, the combined intervention did not show promise as a treatment for cannabis use disorder. Published by Elsevier Ireland Ltd.

Dronabinol and Lofexidine for Cannabis Use Disorder: A Randomized, Double-Blind, Placebo-Controlled Trial*

PubMed Central

Levin, Frances R.; Mariani, John J.; Pavlicova, Martina; Brooks, Daniel; Glass, Andrew; Mahony, Amy; Nunes, Edward V.; Bisaga, Adam; Dakwar, Elias; Carpenter, Kenneth M.; Sullivan, Maria A.; Choi, Jean C.

2016-01-01

Background Cannabis use disorder is associated with substantial morbidity and, after alcohol, is the most common drug bringing adolescents and adults into treatment. At present, there are no FDA-approved medications for cannabis use disorder. Combined pharmacologic interventions might be particularly useful in mitigating withdrawal symptoms and promoting abstinence. Objective The purpose of this study was to evaluate the safety and efficacy of dronabinol, a synthetic form of delta-9-tetrahydrocannabinol, a naturally occurring pharmacologically active component of marijuana, and lofexidine, an alpha-2 agonist, in treating cannabis dependence. Methods One hundred fifty six cannabis-dependent adults were enrolled and following a 1-week placebo lead-in phase 122 were randomized in a double-blind, placebo-controlled, 11-week trial. Participants were randomized to receive dronabinol 20 mg three times a day and lofexidine 0.6 mg three times a day or placebo. Medications were maintained until the end of week eight, were then tapered over two weeks and patients were monitored off medications during the last study week. All participants received weekly motivational enhancement and relapse prevention therapy. Marijuana use was assessed using the timeline follow-back method. Results There was no significant difference between treatment groups in the proportion of participants who achieved 3 weeks of abstinence during the maintenance phase of the trial (27.9 % for the medication group and 29.5% for the placebo group), although both groups showed a reduction over time. Conclusions Based on this treatment study, the combined intervention did not show promise as a treatment for cannabis use disorder. PMID:26711160

Reductions of intimate partner violence resulting from supplementing children with omega-3 fatty acids: A randomized, double-blind, placebo-controlled, stratified, parallel-group trial.

PubMed

Portnoy, Jill; Raine, Adrian; Liu, Jianghong; Hibbeln, Joseph R

2018-05-20

Omega-3 supplementation has been found to reduce externalizing behavior in children. Reciprocal models of parent-child behavior suggest that improving child behavior could lead to improvements in parent behavior, however no study has examined whether omega-3 supplementation in children could reduce intimate partner violence or child maltreatment by their adult caregivers. In this randomized, double-blind, placebo-controlled, stratified, parallel group trial, a community sample of children were randomized to receive either a fruit drink containing 1 gm of omega-3 fats (Smartfish Recharge; Omega-3 group, n = 100) or the same fruit drink without omega-3's (Placebo group, n = 100). Child participants, adult caregivers, and research staff were blinded to group assignment. Adult caregivers reported inter-partner and child-directed physical assault and psychological aggression at baseline, 6 months (end of treatment) and 12 months (6 months post-treatment) using the Conflicts Tactics Scale. Caregivers of children in the omega-3 group reported long-term reductions in psychological aggression in a group × time interaction. Improvements in adult psychological aggression were correlated with improvements in child externalizing behavior scores. No differences were reported for child maltreatment. This study is the first to show that omega-3 supplementation in children can reduce inter-partner psychological aggression among adult caregivers not receiving supplements. Findings suggest that improving child behavior through omega-3 supplementation could have long-term benefits to the family system as a whole. © 2018 Wiley Periodicals, Inc.

Homeopathy for Depression: A Randomized, Partially Double-Blind, Placebo-Controlled, Four-Armed Study (DEP-HOM)

PubMed Central

Adler, Ubiratan C.; Krüger, Stephanie; Teut, Michael; Lüdtke, Rainer; Schützler, Lena; Martins, Friederike; Willich, Stefan N.; Linde, Klaus; Witt, Claudia M.

2013-01-01

Background The specific clinical benefit of the homeopathic consultation and of homeopathic remedies in patients with depression has not yet been investigated. Aims To investigate the 1) specific effect of individualized homeopathic Q-potencies compared to placebo and 2) the effect of an extensive homeopathic case taking (case history I) compared to a shorter, rather conventional one (case history II) in the treatment of acute major depression (moderate episode) after six weeks. Methods A randomized, partially double-blind, placebo-controlled, four-armed trial using a 2×2 factorial design with a six-week study duration per patient was performed. Results A total of 44 from 228 planned patients were randomized (2∶1∶2∶1 randomization: 16 homeopathic Q-potencies/case history I, 7 placebo/case history I, 14 homeopathic Q-potencies/case history II, 7 placebo/case history II). Because of recruitment problems, the study was terminated prior to full recruitment, and was underpowered for the preplanned confirmatory hypothesis testing. Exploratory data analyses showed heterogeneous and inconclusive results with large variance in the sample. The mean difference for the Hamilton-D after 6 weeks was 2.0 (95%CI −1.2;5.2) for Q-potencies vs. placebo and −3.1 (−5.9;−0.2) for case history I vs. case history II. Overall, no consistent or clinically relevant results across all outcomes between homeopathic Q-potencies versus placebo and homeopathic versus conventional case taking were observed. The frequency of adverse events was comparable for all groups. Conclusions Although our results are inconclusive, given that recruitment into this trial was very difficult and we had to terminate early, we cannot recommend undertaking a further trial addressing this question in a similar setting. Prof. Dr. Claudia Witt had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Trial registration

Safety and efficacy of pregabalin in adolescents with fibromyalgia: a randomized, double-blind, placebo-controlled trial and a 6-month open-label extension study.

PubMed

Arnold, Lesley M; Schikler, Kenneth N; Bateman, Lucinda; Khan, Tahira; Pauer, Lynne; Bhadra-Brown, Pritha; Clair, Andrew; Chew, Marci L; Scavone, Joseph

2016-07-30

Fibromyalgia (FM) is a common pain condition characterized by widespread musculoskeletal pain and tenderness. Pregabalin is an approved treatment for adults in the United States, but there are no approved treatments for adolescents with FM. This was a 15-week, randomized, double-blind, placebo-controlled study and 6-month open-label safety trial of flexible-dose pregabalin (75-450 mg/day) for the treatment of adolescents (12-17 years) with FM. Primary outcome was change in mean pain score at endpoint (scored from 0-10, with 24-h recall). Secondary outcomes included global assessments and measures of pain, sleep, and FM impact. A total of 107 subjects were randomized to treatment (54 pregabalin, 53 placebo) and 80 completed the study (44 pregabalin, 36 placebo). Improvement in mean pain score at endpoint with pregabalin versus placebo was not statistically significant, treatment difference (95 % CI), -0.66 (-1.51, 0.18), P = 0.121. There were significant improvements with pregabalin versus placebo in secondary outcomes of change in pain score by week (P < 0.05 for 10 of 15 weeks); change in pain score at week 15 (1-week recall), treatment difference (95 % CI), -0.87 (-1.68, -0.05), P = 0.037; and patient global impression of change, 53.1 % versus 29.5 % very much or much improved (P = 0.013). Trends toward improvement with pregabalin in other secondary outcomes measuring pain, sleep, and FM impact were not significant. Safety was consistent with the known profile of pregabalin in adults with FM. Pregabalin did not significantly improve the mean pain score in adolescents with FM. There were significant improvements in secondary outcomes measuring pain and impression of change. NCT01020474 ; NCT01020526 .

Efficacy of chlorophyll c2 for seasonal allergic rhinitis: single-center double-blind randomized control trial.

PubMed

Fujiwara, Takashi; Nishida, Naoya; Nota, Jumpei; Kitani, Takashi; Aoishi, Kunihide; Takahashi, Hirotaka; Sugahara, Takuya; Hato, Naohito

2016-12-01

Chlorophyll c2 extracted from Sargassum horneri improved allergic symptoms in an animal model of allergic rhinitis. In the present study, we explored the efficacy of chlorophyll c2 in patients with seasonal allergic rhinitis. This was a single-center, randomized, double-blind placebo-controlled trial. Sixty-six patients aged 20-43 years, each with a 2-year history of seasonal allergic rhinitis, were randomly assigned to receive either a single daily dose (0.7 mg) of chlorophyll c2 or placebo for 12 weeks. The use of medications including H1-antihistamines and topical nasal steroids was recorded by rescue medication scores (RMSs) noted after 4, 8, and 12 weeks of treatment. Disease-specific quality of life was measured using the Japan Rhinitis Quality of Life Questionnaire (JRQLQ) both before and after 4, 8, and 12 weeks of treatment. The RMS at 8 weeks was significantly better in the chlorophyll c2 than the placebo group (mean RMS difference = -3.09; 95 % confidence interval = -5.96 to -0.22); the mean RMS at 4 weeks was only slightly better in the chlorophyll c2 group. The JRQLQ scores did not differ significantly between the two groups. Chlorophyll c2 would have a potential to be an alternative treatment for allergic rhinitis.

Efficacy of Levofloxacin in the Treatment of BK Viremia: A Multicenter, Double-Blinded, Randomized, Placebo-Controlled Trial

PubMed Central

Lee, Belinda T.; Gabardi, Steven; Grafals, Monica; Hofmann, R. Michael; Akalin, Enver; Aljanabi, Aws; Mandelbrot, Didier A.; Adey, Deborah B.; Heher, Eliot; Fan, Pang-Yen; Conte, Sarah; Dyer-Ward, Christine

2014-01-01

Background and objectives BK virus reactivation in kidney transplant recipients can lead to progressive allograft injury. Reduction of immunosuppression remains the cornerstone of treatment for active BK infection. Fluoroquinolone antibiotics are known to have in vitro antiviral properties, but the evidence for their use in patients with BK viremia is inconclusive. The objective of the study was to determine the efficacy of levofloxacin in the treatment of BK viremia. Design, setting, participants, & measurements Enrollment in this prospective, multicenter, double-blinded, placebo-controlled trial occurred from July 2009 to March 2012. Thirty-nine kidney transplant recipients with BK viremia were randomly assigned to receive levofloxacin, 500 mg daily, or placebo for 30 days. Immunosuppression in all patients was adjusted on the basis of standard clinical practices at each institution. Plasma BK viral load and serum creatinine were measured monthly for 3 months and at 6 months. Results At the 3-month follow-up, the percentage reductions in BK viral load were 70.3% and 69.1% in the levofloxacin group and the placebo group, respectively (P=0.93). The percentage reductions in BK viral load were also equivalent at 1 month (58% versus and 67.1%; P=0.47) and 6 months (82.1% versus 90.5%; P=0.38). Linear regression analysis of serum creatinine versus time showed no difference in allograft function between the two study groups during the follow-up period. Conclusions A 30-day course of levofloxacin does not significantly improve BK viral load reduction or allograft function when used in addition to overall reduction of immunosuppression. PMID:24482066

Efficacy of levofloxacin in the treatment of BK viremia: a multicenter, double-blinded, randomized, placebo-controlled trial.

PubMed

Lee, Belinda T; Gabardi, Steven; Grafals, Monica; Hofmann, R Michael; Akalin, Enver; Aljanabi, Aws; Mandelbrot, Didier A; Adey, Deborah B; Heher, Eliot; Fan, Pang-Yen; Conte, Sarah; Dyer-Ward, Christine; Chandraker, Anil

2014-03-01

BK virus reactivation in kidney transplant recipients can lead to progressive allograft injury. Reduction of immunosuppression remains the cornerstone of treatment for active BK infection. Fluoroquinolone antibiotics are known to have in vitro antiviral properties, but the evidence for their use in patients with BK viremia is inconclusive. The objective of the study was to determine the efficacy of levofloxacin in the treatment of BK viremia. Enrollment in this prospective, multicenter, double-blinded, placebo-controlled trial occurred from July 2009 to March 2012. Thirty-nine kidney transplant recipients with BK viremia were randomly assigned to receive levofloxacin, 500 mg daily, or placebo for 30 days. Immunosuppression in all patients was adjusted on the basis of standard clinical practices at each institution. Plasma BK viral load and serum creatinine were measured monthly for 3 months and at 6 months. At the 3-month follow-up, the percentage reductions in BK viral load were 70.3% and 69.1% in the levofloxacin group and the placebo group, respectively (P=0.93). The percentage reductions in BK viral load were also equivalent at 1 month (58% versus and 67.1%; P=0.47) and 6 months (82.1% versus 90.5%; P=0.38). Linear regression analysis of serum creatinine versus time showed no difference in allograft function between the two study groups during the follow-up period. A 30-day course of levofloxacin does not significantly improve BK viral load reduction or allograft function when used in addition to overall reduction of immunosuppression.

Maintenance N-acetyl cysteine treatment for bipolar disorder: A double-blind randomized placebo controlled trial

PubMed Central

2012-01-01

Background N-acetyl cysteine (NAC) is a glutathione precursor that has been shown to have antidepressant efficacy in a placebo-controlled trial. The current study aimed to investigate the maintenance effects of NAC following eight weeks of open-label treatment for bipolar disorder. Method The efficacy of a double blind randomized placebo controlled trial of 2 g/day NAC as adjunct maintenance treatment for bipolar disorder was examined. Participants (n = 149) had a Montgomery Asberg Depression Rating Score of ≥12 at trial entry and, after eight weeks of open-label NAC treatment, were randomized to adjunctive NAC or placebo, in addition to treatment as usual. Participants (primarily outpatients) were recruited through public and private services and through newspaper advertisements. Time to intervention for a mood episode was the primary endpoint of the study, and changes in mood symptoms, functionality and quality of life measures were secondary outcomes. Results There was a substantial decrease in symptoms during the eight-week open-label NAC treatment phase. During the subsequent double-blind phase, there was minimal further change in outcome measures with scores remaining low. Consequently, from this low plateau, between-group differences did not emerge on recurrence, clinical functioning or quality of life measures. Conclusions There were no significant between-group differences in recurrence or symptomatic outcomes during the maintenance phase of the trial; however, these findings may be confounded by limitations. Trial Registration The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12607000074493). PMID:22891797

Steroid injection for osteoarthritis of the hip: a randomized, double-blind, placebo-controlled trial.

PubMed

Lambert, Robert G W; Hutchings, Edna J; Grace, Michael G A; Jhangri, Gian S; Conner-Spady, Barbara; Maksymowych, Walter P

2007-07-01

To determine the efficacy of fluoroscopically guided corticosteroid injection for hip osteoarthritis (OA) in a randomized, double-blind, placebo-controlled trial. Fifty-two patients with symptomatic hip OA were randomly allocated to receive placebo (10 mg bipuvicaine, 2 ml saline) (n = 21) or corticosteroid treatment (10 mg bipuvicaine, 40 mg triamcinolone hexacetonide) (n = 31). Patients were followed up for 1, 2, 3, and 6 months. The primary outcome measure was the pain improvement response, defined as a 20% decrease in the Western Ontario and McMaster Universities OA Index (WOMAC) pain score (on 5 100-mm visual analog scales [VAS]) (WOMAC20) from baseline to 2 months postinjection. Secondary outcomes were a 50% decrease in the WOMAC pain score (WOMAC50), changes in other WOMAC subscale scores, patient's global assessment of health (on a 100-mm VAS), and Short Form 36 (SF-36) quality of life indices. Analyses were based on the intent-to-treat principle. The mean WOMAC pain score fell 49.2% (decreasing from 310.1 mm to 157.4 mm) at 2 months postinjection in patients receiving corticosteroid, compared with a decrease of 2.5% (from 314.3 mm to 306.5 mm) in the placebo group (P < 0.0001). The proportion of WOMAC20 responders at 2 months' followup was significantly higher in the corticosteroid group (67.7%) compared with the placebo group (23.8%) (P = 0.004); similar proportions of WOMAC50 responders were observed between groups (61.3% in the corticosteroid group versus 14.3% in the placebo group; P = 0.001). Response differences were maintained at 3 months' followup (58.1% responders in the corticosteroid group versus 9.5% responders in the placebo group; P = 0.004). Significant differences in the WOMAC stiffness and physical function scores (P < 0.0001), patient's global health scores (P = 0.005), and SF-36 physical component scores (P = 0.04) were observed, with patients in the corticosteroid group showing greater improvements. There were no differences in the

SSRIs and ejaculation: a double-blind, randomized, fixed-dose study with paroxetine and citalopram.

PubMed

Waldinger, M D; Zwinderman, A H; Olivier, B

2001-12-01

Selective serotonin reuptake inhibitors (SSRIs) are known to induce delayed orgasm and ejaculation. However, different SSRIs may differentially delay ejaculation. A double-blind, fixed-dose study in healthy men with lifelong rapid ejaculation was performed to evaluate potential differences between clinically relevant doses of two selective serotonin reuptake inhibitors, paroxetine and citalopram, in their effects on ejaculation. Thirty men with an intravaginal ejaculation latency time (IELT) less than 1 minute were randomly assigned to receive paroxetine (20 mg/day) and citalopram (20 mg/day) for 5 weeks, after taking half the dosage in the first week. During the 1-month baseline and 6-week treatment period, IELTs were measured at home by using a stopwatch procedure. The trial was completed by 23 men. Analysis of variance revealed a between-group difference in the evolution of IELT delay over time (p = 0.0004); the IELT after paroxetine and citalopram gradually increased from 18 and 21 seconds to approximately 170 and 44 seconds, respectively. Paroxetine 20 mg/day exerted a strong delay (8.9-fold increase), whereas citalopram 20 mg/day mildly delayed ejaculation (1.8-fold increase). These results indicate that paroxetine leads to a significant delay in orgasm and ejaculation, whereas citalopram seems to have less of an effect on it.

Effect of royal jelly ingestion for six months on healthy volunteers.

PubMed

Morita, Hiroyuki; Ikeda, Takahide; Kajita, Kazuo; Fujioka, Kei; Mori, Ichiro; Okada, Hideyuki; Uno, Yoshihiro; Ishizuka, Tatsuo

2012-09-21

Royal jelly is a widely ingested supplement for health, but its effects on humans are not well known. The objective was to evaluate the effects of long-term royal jelly ingestion on humans. We conducted a randomized placebo-controlled, double-blind trial. A total of 61 healthy volunteers aged 42-83 years were enrolled and were randomly divided into a royal jelly group (n = 31) and a control group (n = 30). Three thousand mg of royal jelly (RJ) or a placebo in 100 ml liquid/day were ingested for 6 months. The primary outcomes were changes in anthropometric measurements and biochemical indexes from baseline to 6 months after intervention. Thirty subjects in the RJ group and 26 in the control group were included in the analysis of endpoints. In an adjusted mean change of the variables from the baseline, significant differences between the two groups could be found in red blood cell counts (+0.16x10⁶/μL for the RJ group vs. -0.01x10⁶/μL for the control group, P = 0.0134), hematocrit (+0.9% vs. -0.8%, P = 0.0251), log (fasting plasma glucose) (+0.01 ± 0.01 log mg/dL vs. +0.05 ± 0.01 log mg/dL, P = 0.0297), log (insulinogenic index) (+0.25 vs. -0.13, P = 0.0319), log dehydroepiandrosterone sulfate (DHEA-S) (+0.08 log μg/dL vs. +0.20 log μg/dL, P = 0.0483), log testosterone (T) (+0.12 ± 0.04 log ng/mL vs. -0.02 ± 0.05 log ng/mL, P = 0.0416), log T/DHEA-S ratio (+0.05 ± 0.05 vs. -0.23 ± 0.59, P = 0.0015), and in one of the SF-36 subscale scores, mental health (MH) (+4 vs. -7, P = 0.0276). Six-month ingestion of RJ in humans improved erythropoiesis, glucose tolerance and mental health. Acceleration of conversion from DHEA-S to T by RJ may have been observed among these favorable effects.

Cranberry fruit powder (Flowens™) improves lower urinary tract symptoms in men: a double-blind, randomized, placebo-controlled study.

PubMed

Vidlar, Ales; Student, Vladimir; Vostalova, Jitka; Fromentin, Emilie; Roller, Marc; Simanek, Vilím; Student, Vladimir

2016-03-01

Lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia increase with age. To date, several medications are available to treat LUTS, including herbal remedies which offer less side effects but lack robust efficacy studies. This 6-month, randomized, double-blind, placebo-controlled study aimed at evaluating the dose effect of 250 or 500 mg cranberry powder (Flowens™) on LUTS and uroflowmetry in men over the age of 45. A total of 124 volunteers with PSA levels <2.5 ng/mL and an international prostate symptoms score (IPSS) score ≥8 were recruited and randomized. The primary outcome measure was the IPSS, evaluated at 3 and 6 months. Secondary outcome measures included quality of life, bladder volume (Vol), maximum urinary flow rate (Q max), average urinary flow rate (Q ave), ultrasound-estimated post-void residual urine volume (PVR), serum prostate-specific antigen, selenium, interleukin 6, and C-reactive protein at 6 months. After 6 months, subjects in both Flowens™ groups had a lower IPSS (-3.1 and -4.1 in the 250- and 500-mg groups, p = 0.05 and p < 0.001, respectively) versus the placebo group (-1.5), and a dose-response effect was observed. There were significant differences in Q max, Q ave, PVR, and Vol in the Flowens™ 500-mg group versus baseline (p < 0.05). A dose-dependent effect on Vol was observed, as well as on PVR, for participants with a nonzero PVR. There was no effect on clinical chemistry or hematology markers. Flowens™ showed a clinically relevant, dose-dependent, and significant reduction in LUTS in men over 45.

A randomized, double-blind, placebo-controlled, crossover trial of mifepristone in Gulf War veterans with chronic multisymptom illness.

PubMed

Golier, Julia A; Caramanica, Kimberly; Michaelides, Andreas C; Makotkine, Iouri; Schmeidler, James; Harvey, Philip D; Yehuda, Rachel

2016-02-01

No pharmacological treatments have been demonstrated to effectively treat chronic multisymptom illness (CMI) in Gulf War veterans (GWV). This study assessed the effect of the glucocorticoid receptor antagonist mifepristone in GWV with CMI. A randomized, double-blind, cross-over trial of mifepristone, with two six-week treatment phases separated by a one-month washout period, was conducted at a Veterans Affairs (VA) hospital between 2008 and 2011. Participants were randomized to receive either 200mg of mifepristone per day or matched placebo first. The primary clinical outcome measure was change in self-reported physical health. Neurocognitive functioning and self-reported measures of depression, PTSD, and fatigue were secondary outcomes. Sixty-five participants enrolled, of whom 36 were randomized and 32 (mean age, 49.1 (7.2) years) completed the study. Physical and mental health status and neurocognitive functioning were poor at baseline. Mifepristone treatment was not associated with improvement in self-reported physical health (p=0.838) or in other self-reported measures of mental health. Mifepristone treatment was significantly associated with improvements in verbal learning (p=0.008, d=0.508), in the absence of improvement in other cognitive measures (working memory (p=0.914), visual learning (p=0.643) and a global composite measure (p=0.937). Baseline morning cortisol levels and lysozyme IC50-DEX, a measure of peripheral glucocorticoid sensitivity, displayed a significant relationship with endpoint verbal learning scores (p=0.012 and p=0.007, respectively). The magnitude of cortisol change during treatment mediated the improvement in verbal learning. This study was negative for the primary and secondary clinical outcomes. However, the data suggest a moderate dose of mifepristone may have circumscribed cognitive-enhancing effects in CMI. Further study is warranted to determine whether and through which mechanisms mifepristone treatment can yield clinically

The Role of Thoracic Medial Branch Blocks in Managing Chronic Mid and Upper Back Pain: A Randomized, Double-Blind, Active-Control Trial with a 2-Year Followup

PubMed Central

Manchikanti, Laxmaiah; Singh, Vijay; Falco, Frank J. E.; Cash, Kimberly A.; Pampati, Vidyasagar; Fellows, Bert

2012-01-01

Study Design. A randomized, double-blind, active-control trial. Objective. To determine the clinical effectiveness of therapeutic thoracic facet joint nerve blocks with or without steroids in managing chronic mid back and upper back pain. Summary of Background Data. The prevalence of thoracic facet joint pain has been established as 34% to 42%. Multiple therapeutic techniques utilized in managing chronic thoracic pain of facet joint origin include medial branch blocks, radiofrequency neurotomy, and intraarticular injections. Methods. This randomized double-blind active controlled trial was performed in 100 patients with 50 patients in each group who received medial branch blocks with local anesthetic alone or local anesthetic and steroids. Outcome measures included the numeric rating scale (NRS), Oswestry Disability Index (ODI), opioid intake, and work status, at baseline, 3, 6, 12, 18, and 24 months. Results. Significant improvement with significant pain relief and functional status improvement of 50% or more were observed in 80% of the patients in Group I and 84% of the patients in Group II at 2-year followup. Conclusions. Therapeutic medial branch blocks of thoracic facets with or without steroids may provide a management option for chronic function-limiting thoracic pain of facet joint origin. PMID:22851967

Nadolol reduces insulin sensitivity in liver cirrhosis: a randomized double-blind crossover trial.

PubMed

Lee, Wai Gin; Murphy, Rinki; McCall, John L; Gane, Edward J; Soop, Mattias; Tura, Andrea; Plank, Lindsay D

2017-03-01

Liver cirrhosis is frequently complicated by portal hypertension leading to increased mortality from variceal bleeding and hepatic decompensation. Noncardioselective β-blockers not only reduce portal hypertension and prevent variceal bleeding in cirrhosis but also impair glucose tolerance and insulin sensitivity in other settings. This study aimed to determine whether nonselective β-blockade with nadolol impairs glucose metabolism in liver cirrhosis. A randomized, double-blind, placebo-controlled crossover trial of nadolol in cirrhotic patients examined insulin sensitivity, disposition index, and glucose tolerance. Stable cirrhotic patients of mixed etiology underwent an intravenous glucose tolerance test and hyperinsulinemic-euglycemic clamp for the measurement of insulin secretion and insulin sensitivity (n = 16) and a 75-g oral glucose tolerance test (n = 17). These measurements were conducted twice (after 3 months of treatment with nadolol or placebo and, after a 1-month washout period, after 3 months on the alternative treatment). Total body fat and plasma catecholamines were measured at the end of each 3-month treatment. Compared with placebo, nadolol treatment reduced insulin sensitivity (79.7 ± 10.1 vs 99.6 ± 10.3 μL/kg fat-free mass·min -1 ·(mU/L) -1 , P = .005). Insulin secretion was unchanged (P = .24), yielding a lower disposition index with nadolol (6083 ± 2007 vs 8692 ± 2036, P = .050). There was no change in total body fat or plasma catecholamines. A 2-hour plasma glucose concentration from the oral glucose tolerance test was higher on nadolol than placebo (10.8 ± 0.9 vs 9.9 ± 0.9 mmol/L, P = .035). Nadolol significantly worsened insulin sensitivity, glycemia, and disposition index in patients with liver cirrhosis. These findings may have significant clinical implications because cirrhosis is already associated with an increased prevalence of diabetes. Copyright © 2016 John Wiley & Sons, Ltd.

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.

24-month intervention with a specific multinutrient in people with prodromal Alzheimer's disease (LipiDiDiet): a randomised, double-blind, controlled trial.

PubMed

Soininen, Hilkka; Solomon, Alina; Visser, Pieter Jelle; Hendrix, Suzanne B; Blennow, Kaj; Kivipelto, Miia; Hartmann, Tobias

2017-12-01

Nutrition is an important modifiable risk factor in Alzheimer's disease. Previous trials of the multinutrient Fortasyn Connect showed benefits in mild Alzheimer's disease dementia. LipiDiDiet investigated the effects of Fortasyn Connect on cognition and related measures in prodromal Alzheimer's disease. Here, we report the 24-month results of the trial. LipiDiDiet was a 24-month randomised, controlled, double-blind, parallel-group, multicentre trial (11 sites in Finland, Germany, the Netherlands, and Sweden), with optional 12-month double-blind extensions. The trial enrolled individuals with prodromal Alzheimer's disease, defined according to the International Working Group (IWG)-1 criteria. Participants were randomly assigned (1:1) to active product (125 mL once-a-day drink containing Fortasyn Connect) or control product. Randomisation was computer-generated centrally in blocks of four, stratified by site. All study personnel and participants were masked to treatment assignment. The primary endpoint was change in a neuropsychological test battery (NTB) score. Analysis was by modified intention to treat. Safety analyses included all participants who consumed at least one study product dose. This trial is registered with the Dutch Trial Register, number NTR1705. Between April 20, 2009, and July 3, 2013, 311 of 382 participants screened were randomly assigned to the active group (n=153) or control group (n=158). Mean change in NTB primary endpoint was -0·028 (SD 0·453) in the active group and -0·108 (0·528) in the control group; estimated mean treatment difference was 0·098 (95% CI -0·041 to 0·237; p=0·166). The decline in the control group was less than the prestudy estimate of -0·4 during 24 months. 66 (21%) participants dropped out of the study. Serious adverse events occurred in 34 (22%) participants in the active group and 30 (19%) in control group (p=0·487), none of which were regarded as related to the study intervention. The intervention had no

A Randomized, Double-Blind, Double-Dummy Study to Evaluate the Intranasal Human Abuse Potential and Pharmacokinetics of a Novel Extended-Release Abuse-Deterrent Formulation of Oxycodone

PubMed Central

Kopecky, Ernest A.; Smith, Michael D.; Fleming, Alison B.

2016-01-01

Objective. Evaluate the human abuse potential (HAP) of an experimental, microsphere-in-capsule formulation of extended-release oxycodone (oxycodone DETERx®) (herein “DETERx”). Design. Randomized, double-blind, double-dummy, positive- and placebo-controlled, single-dose, four-phase, four-treatment, crossover study. Setting. Clinical research site. Subjects. There were 39 qualifying subjects (72% male, 85% white, mean age of 27 years) with 36 completing all four Double-blind Treatment Periods. Methods. The four phases encompassed: 1) Screening; 2) Drug Discrimination; 3) Double-blind Treatment; and 4) Follow-up. Drug Discrimination tests ensured that subjects could distinguish placebo from opioid. The four Double-blind Treatments compared DETERx—administered as either a crushed intranasal (IN) or an intact oral (PO) preparation—with immediate-release oxycodone IN (OXY-IR IN) and with an intact IN and PO placebo DETERx control. Results. For primary pharmacokinetic (PK) assessments, abuse quotient (Cmax/Tmax) was lower with DETERx IN than DETERx PO; both treatments were substantially lower than OXY-IR IN (6.24, 8.60, and 69.6 ng/mL/h, respectively). For drug liking, the primary subjective pharmacodynamic (PD) endpoint, both DETERx IN and DETERx PO produced significantly lower scores than OXY-IR IN (P ≤ 0.0001 for each); DETERx IN was less liked than DETERx PO (P ≤ 0.05), mirroring the PK relationships. Objectively assessed pupillometry corroborated the more rapid and significantly greater effect of OXY-IR IN than either DETERx IN or DETERx PO (P ≤ 0.007 for each). Overall safety profiles of DETERx and OXY-IR were comparable and both were well tolerated. Conclusions. Pharmacokinetic and pharmacodynamic outcomes suggest that DETERx IN has relatively low HAP; continued research in larger populations is suggested. PMID:26814256

Implant decontamination during surgical peri-implantitis treatment: a randomized, double-blind, placebo-controlled trial.

PubMed

de Waal, Yvonne C M; Raghoebar, Gerry M; Huddleston Slater, James J R; Meijer, Henny J A; Winkel, Edwin G; van Winkelhoff, Arie Jan

2013-02-01

The objective of this randomized, double-blind, placebo-controlled trial was to study the effect of implant surface decontamination with chlorhexidine (CHX)/cetylpyridinium chloride (CPC) on microbiological and clinical parameters. Thirty patients (79 implants) with peri-implantitis were treated with resective surgical treatment consisting of apically re-positioned flap, bone re-contouring and surface debridement and decontamination. Patients were randomly allocated to decontamination with 0.12% CHX + 0.05% CPC (test-group) or a placebo-solution (without CHX/CPC, placebo-group). Microbiological parameters were recorded during surgery; clinical and radiographical parameters were recorded before (pre-) treatment (baseline), and at 3, 6 and 12 months after treatment. Nine implants in two patients in the placebo-group were lost due to severe persisting peri-implantitis. Both decontamination procedures resulted in significant reductions of bacterial load on the implant surface, but the test-group showed a significantly greater reduction than the placebo-group (log 4.21 ± 1.89 versus log 2.77 ± 2.12, p = 0.006). Multilevel analysis showed no differences between both groups in the effect of the intervention on bleeding, suppuration, probing pocket depth and radiographical bone loss over time. Implant surface decontamination with 0.12% CHX + 0.05% CPC in resective surgical treatment of peri-implantitis leads to a greater immediate suppression of anaerobic bacteria on the implant surface than a placebo-solution, but does not lead to superior clinical results. The long-term microbiological effect remains unknown. © 2012 John Wiley & Sons A/S.

Lymphoid irradiation in intractable rheumatoid arthritis. A double-blind, randomized study comparing 750-rad treatment with 2,000-rad treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hanly, J.G.; Hassan, J.; Moriarty, M.

1986-01-01

Twenty patients with intractable rheumatoid arthritis were treated with 750-rad or 2,000-rad lymphoid irradiation in a randomized double-blind comparative study. Over a 12-month followup period, there was a significant improvement in 4 of 7 and 6 of 7 standard parameters of disease activity following treatment with 750 rads and 2,000 rads, respectively. Transient, short-term toxicity was less frequent with the lower dose. In both groups, there was a sustained peripheral blood lymphopenia, a selective depletion of T helper (Leu-3a+) lymphocytes, and reduced in vitro mitogen responses. These changes did not occur, however, in synovial fluid. These results suggest that 750-radmore » lymphoid irradiation is as effective as, but less toxic than, that with 2,000 rads in the management of patients with intractable rheumatoid arthritis.« less

A Randomized, Double-Blind, Placebo-Controlled Study of Modafinil Film-Coated Tablets in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder

ERIC Educational Resources Information Center

Greenhill, Laurence L.; Biederman, Joseph; Boellner, Samuel W.; Rugino, Thomas A.; Sangal, R. Bart; Earl, Craig Q.; Jiang, John G.; Swanson, James M.

2006-01-01

Objective: To evaluate the efficacy and tolerability of modafinil in children and adolescents, ages 7 to 17, with attention-deficit/hyperactivity disorder (ADHD). Method: In this 9-week, double-blind, flexible-dose study, patients were randomized to once-daily modafinil (170-425 mg) or placebo. Assessments included ADHD Rating Scale-IV…

A 1-year randomized, double-blind, placebo-controlled study of intravenous ibandronate on bone loss following renal transplantation.

PubMed

Smerud, K T; Dolgos, S; Olsen, I C; Åsberg, A; Sagedal, S; Reisæter, A V; Midtvedt, K; Pfeffer, P; Ueland, T; Godang, K; Bollerslev, J; Hartmann, A

2012-12-01

The clinical profile of ibandronate as add-on to calcitriol and calcium was studied in this double-blind, placebo-controlled trial of 129 renal transplant recipients with early stable renal function (≤ 28 days posttransplantation, GFR ≥ 30 mL/min). Patients were randomized to receive i.v. ibandronate 3 mg or i.v. placebo every 3 months for 12 months on top of oral calcitriol 0.25 mcg/day and calcium 500 mg b.i.d. At baseline, 10 weeks and 12 months bone mineral density (BMD) and biochemical markers of bone turnover were measured. The primary endpoint, relative change in BMD for the lumbar spine from baseline to 12 months was not different, +1.5% for ibandronate versus +0.5% for placebo (p = 0.28). Ibandronate demonstrated a significant improvement of BMD in total femur, +1.3% versus -0.5% (p = 0.01) and in the ultradistal radius, +0.6% versus -1.9% (p = 0.039). Bone formation markers were reduced by ibandronate, whereas the bone resorption marker, NTX, was reduced in both groups. Calcium and calcitriol supplementation alone showed an excellent efficacy and safety profile, virtually maintaining BMD without any loss over 12 months after renal transplantation, whereas adding ibandronate significantly improved BMD in total femur and ultradistal radius, and also suppressed biomarkers of bone turnover. Ibandronate was also well tolerated. © Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.

Combined Oral Contraceptives and Sexual Function in Women-a Double-Blind, Randomized, Placebo-Controlled Trial.

PubMed

Zethraeus, Niklas; Dreber, Anna; Ranehill, Eva; Blomberg, Liselott; Labrie, Fernand; von Schoultz, Bo; Johannesson, Magnus; Hirschberg, Angelica Lindén

2016-11-01

There is a lack of knowledge about how oral contraceptives may affect sexual function. To determine whether there is a causal effect of oral contraceptives on sexuality. We hypothesized that a widely used pill impairs sexuality. A double-blind, randomized, placebo-controlled trial. Enrollment began in February 2012 and was completed in August 2015. Karolinska University Hospital, Stockholm, Sweden. A total of 340 healthy women, aged 18-35 years, were randomized to treatment, and 332 completed the study. A combined oral contraceptive (150 μg levonorgestrel and 30 μg ethinylestradiol) or placebo for 3 months of treatment. The primary outcome was the aggregate score on the Profile of Female Sexual Function (PFSF). Secondary outcomes were the seven domains of the PFSF, the Sexual Activity Log, and the Personal Distress Scale. Overall sexual function was similar in women in the oral contraceptive and placebo groups. The PFSF domains desire (-4.4; 95% confidence interval [CI], -8.49 to -0.38; P = .032), arousal (-5.1; 95% CI, -9.63 to -0.48; P = .030), and pleasure (-5.1; 95% CI, -9.97 to -0.32; P = .036) were significantly reduced in comparison to placebo, whereas orgasm, concern, responsiveness, and self-image were similar between groups. The mean frequency of satisfying sexual episodes and personal distress were also similar between groups. This study shows no negative impact of a levonorgestrel-containing oral contraceptive on overall sexual function, although three of seven sexual function domains were adversely affected.

Effect of vitamin D supplementation on anthropometric indices among overweight and obese women: A double blind randomized controlled clinical trial.

PubMed

Roosta, Sajjad; Kharadmand, Mina; Teymoori, Farshad; Birjandi, Mehdi; Adine, Ahmad; Falahi, Ebrahim

2018-03-27

The aim of this study was to investigate effect of vitamin D supplementation on anthropometric indices among women with overweight and obesity. This double blind randomize clinical trial was conducted on 66 overweight and obese women. Those in intervention group received oral supplement of vitamin D 50,000 IU (1250 mcg) per 25 day and in control group participants received placebo for 3 months. Anthropometric indices were measured before and after 3 months intervention. Before the intervention a 24-h dietary recall (3 days) were used to assess dietary intake of individuals. Independent t test and multivariate repeated measure were used to data analysis. The mean difference of anthropometric indices, serum calcium, 25 (OH) D 3 and serum PTH between the intervention and control groups were significant (P < 0/05). However, no significant differences in serum phosphorus between the intervention and control groups were seen. Supplementation with vitamin D 50 μg for each day for 3 months resulted in a significant reduction in anthropometric indices in women with obesity and overweight with normal primary 25(OH) D 3 serum levels. Copyright © 2018. Published by Elsevier Ltd.

Pulsed Electromagnetic Fields in the treatment of fresh scaphoid fractures. A multicenter, prospective, double blind, placebo controlled, randomized trial

PubMed Central

2011-01-01

Background The scaphoid bone is the most commonly fractured of the carpal bones. In the Netherlands 90% of all carpal fractures is a fracture of the scaphoid bone. The scaphoid has an essential role in functionality of the wrist, acting as a pivot. Complications in healing can result in poor functional outcome. The scaphoid fracture is a troublesome fracture and failure of treatment can result in avascular necrosis (up to 40%), non-union (5-21%) and early osteo-arthritis (up to 32%) which may seriously impair wrist function. Impaired consolidation of scaphoid fractures results in longer immobilization and more days lost at work with significant psychosocial and financial consequences. Initially Pulsed Electromagnetic Fields was used in the treatment of tibial pseudoarthrosis and non-union. More recently there is evidence that physical forces can also be used in the treatment of fresh fractures, showing accelerated healing by 30% and 71% reduction in nonunion within 12 weeks after initiation of therapy. Until now no double blind randomized, placebo controlled trial has been conducted to investigate the effect of this treatment on the healing of fresh fractures of the scaphoid. Methods/Design This is a multi center, prospective, double blind, placebo controlled, randomized trial. Study population consists of all patients with unilateral acute scaphoid fracture. Pregnant women, patients having a life supporting implanted electronic device, patients with additional fractures of wrist, carpal or metacarpal bones and pre-existing impairment in wrist function are excluded. The scaphoid fracture is diagnosed by a combination of physical and radiographic examination (CT-scanning). Proven scaphoid fractures are treated with cast immobilization and a small Pulsed Electromagnetic Fields bone growth stimulating device placed on the cast. Half of the devices will be disabled at random in the factory. Study parameters are clinical consolidation, radiological consolidation

POTASSIUM CITRATE DECREASES BONE RESORPTION IN POSTMENOPAUSAL WOMEN WITH OSTEOPENIA: A RANDOMIZED, DOUBLE-BLIND CLINICAL TRIAL.

PubMed

Gregory, Naina Sinha; Kumar, Rekha; Stein, Emily M; Alexander, Ellen; Christos, Paul; Bockman, Richard S; Rodman, John S

2015-12-01

Diets rich in animal protein, such as the typical American diet, are thought to create a high acid load. An association between acid load and bone loss has led to the idea that providing positive alkaline salt therapy could have beneficial effects on bone metabolism. The objective of this study was to investigate the effects of potassium citrate (K-citrate), 40 mEq daily, over 1 year on bone resorption and formation. A randomized, double-blind, placebo-controlled trial of 83 women with postmenopausal osteopenia. Levels of bone turnover markers, specifically urinary N-telopeptide of collagen type 1 (u-NTX), amino-terminal propeptide of type 1 procollagen (P1NP), bone-specific alkaline phosphatase (BSAP), and osteocalcin (OC) were compared. Changes in bone mineral density (BMD) were also examined. K-citrate decreased both u-NTX (P = .005) and serum P1NP (P<.001) starting at month 1 and continuing through month 12. No significant change was seen in BSAP or OC. No significant change was seen in lumbar or hip BMD between the 2 groups. In women with postmenopausal osteopenia, treatment with K-citrate for 1 year resulted in a significant decrease in markers of turnover. The effect on markers of bone formation was not consistent. K-citrate may serve as a potential treatment for bone loss that is well tolerated and without any significant known long-term consequences.

Evaluation of homeopathic Arnica montana for ecchymosis after upper blepharoplasty: a placebo-controlled, randomized, double-blind study.

PubMed

Kotlus, Brett S; Heringer, Dustin M; Dryden, Robert M

2010-01-01

Ecchymosis is commonly encountered after upper eyelid blepharoplasty. The use of homeopathic preparations of Arnica montana, a flowering herb, has been advocated by physicians, patients, and manufacturers for reduction of postsurgical ecchymosis. The authors evaluate its efficacy after upper eyelid blepharoplasty. A prospective, placebo-controlled, double-blind study was performed in which patients were randomly assigned to the administration of homeopathic A. montana or placebo concurrent with unilateral upper eyelid blepharoplasty followed by contralateral treatment at least 1 month later. Ecchymosis was evaluated at days 3 and 7 by rank order of severity and measurement of surface area of observable ecchymosis. There was no statistically significant difference in area of ecchymosis or rank order of ecchymosis severity for days 3 and 7 after treatment with A. montana versus placebo. Additionally, there was no difference in ease of recovery per patient report, and there was no difference in the rate of ecchymosis resolution. The authors find no evidence that homeopathic A. montana, as used in this study, is beneficial in the reduction or the resolution of ecchymosis after upper eyelid blepharoplasty.

Efficacy and safety of Amla (Phyllanthus emblica L.) in non-erosive reflux disease: a double-blind, randomized, placebo-controlled clinical trial.

PubMed

Karkon Varnosfaderani, Shahnaz; Hashem-Dabaghian, Fataneh; Amin, Gholamreza; Bozorgi, Mahbubeh; Heydarirad, Ghazaleh; Nazem, Esmaeil; Nasiri Toosi, Mohsen; Mosavat, Seyed Hamdollah

2018-03-01

Gastroesophageal reflux disease (GERD) is one of the most common gastrointestinal complaints. GERD, caused by the reflux of stomach contents into the esophagus, leads to troublesome symptoms such as heartburn and regurgitation. It is classified into two types: erosive esophagitis, characterized by visible esophageal mucosa erosion in endoscopy, and non-erosive reflux disease (NERD). GERD is a chronic and recurrent disease that impairs the quality of life and imposes socioeconomic and therapeutic burdens to both patients and society. Due to the failure of the conventional treatments for GERD and to the traditional use of Amla (Phyllanthus emblica L.), in addition to beneficial effects shown in recent studies, we evaluated the safety and efficacy of Amla tablet for improvement of symptoms of patients with NERD. We designed a double-arm, randomized, double-blind, placebo-controlled clinical trial. Sixty-eight patients who had classic symptoms of GERD (heartburn, regurgitation and epigastralgia) for at least three months before the start of the trial were randomized in two parallel groups. Patients in the Amla group received two 500 mg Amla tablets twice a day, after meals, for 4 weeks. In the control group, patients received placebo tablets similar to the Amla prescription. The patients were visited at baseline, and at the end of the 2nd and 4th weeks of intervention; their symptoms were measured on a frequency and severity scale for the symptoms of NERD, according to the quality of life in reflux-associated disease questionnaire. Frequencies of heartburn and regurgitation in both groups of the study were significantly reduced after intervention (P < 0.001). Repeated measures logistic regression analysis showed that, in the Amla group, there was a more significant reduction in regurgitation frequency, heartburn frequency, regurgitation severity and heartburn severity during the study period, compared with the placebo group (P < 0.001). This randomized

A randomized, double-blind, placebo-controlled trial of a traditional herbal formula, Yukmijihwang-tang in elderly subjects with xerostomia.

PubMed

Han, Gajin; Ko, Seok-Jae; Kim, Juyeon; Oh, Ja-Young; Park, Jae-Woo; Kim, Jinsung

2016-04-22

Yukmijihwang-tang (YMJ) is a typical herbal formula to treat Yin-deficiency (YD) syndrome by enriching the fluid-humor of the body. YMJ has been used to treat dry mouth symptoms for hundreds of years in traditional East Asian medicine. Xerostomia, a subjective oral dryness, is common in the elderly and results in impaired quality of life. Many conventional treatments for xerostomia provide only temporary symptom relief, and have side effects. The aim of this study is to investigate the efficacy and safety of YMJ for the treatment of xerostomia in the elderly. This study was designed as a randomized, placebo-controlled, double-blinded, two center trial. Ninety-six subjects aged 60-80 years who had experienced xerostomia for at least 3 months and presented with score>40 on the visual analog scale (VAS) for subjective oral dryness were recruited and randomly allocated to YMJ and placebo groups. YMJ or placebo was administered to each group for 8 weeks (3g of YMJ or placebo, three times per day). The primary outcome was change of VAS for xerostomia from 0 to 8 weeks. VAS for xerostomia was decreased by 22.04±22.76 in the YMJ group and 23.58±23.04 in the placebo group. YMJ had no effect on xerostomia. However, participants with BMIs lower than 29.37kg/m(2) showed improvement of xerostomia after 8 weeks of treatment with YMJ compared to placebo. In addition, YMJ improved oral moisture, which is associated with subjective oral dryness in the YMJ group, and the relationship between VAS for xerostomia and YD was significant. A trend was observed in which YMJ improved oral moisture status and subjective oral dryness in elderly subjects with lower BMI and greater tendency toward YD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Once daily controlled-release pregabalin in the treatment of patients with fibromyalgia: a phase III, double-blind, randomized withdrawal, placebo-controlled study.

PubMed

Arnold, Lesley M; Arsenault, Pierre; Huffman, Cynthia; Patrick, Jeffrey L; Messig, Michael; Chew, Marci L; Sanin, Luis; Scavone, Joseph M; Pauer, Lynne; Clair, Andrew G

2014-10-01

Safety and efficacy of a once daily controlled-released (CR) formulation of pregabalin was evaluated in patients with fibromyalgia using a placebo-controlled, randomized withdrawal design. This multicenter study included 6 week single-blind pregabalin CR treatment followed by 13 week double-blind treatment with placebo or pregabalin CR. The starting dose of 165 mg/day was escalated during the first 3 weeks, up to 495 mg/day based on efficacy and tolerability. Patients with ≥50% reduction in average daily pain score at the end of the single-blind phase were randomized to continue pregabalin CR at the optimized dose (330-495 mg/day) or to placebo. The primary endpoint was time to loss of therapeutic response (LTR), defined as <30% pain reduction relative to single-blind baseline or discontinuation owing to lack of efficacy or adverse event (AE). Secondary endpoints included measures of pain severity, global assessment, functional status, tiredness/fatigue, and sleep. ClinicalTrials.gov NCT01271933. A total of 441 patients entered the single-blind phase, and 63 were randomized to pregabalin CR and 58 to placebo. The median time to LTR (Kaplan-Meier analysis) was significantly longer in the pregabalin CR group than placebo (58 vs. 22 days, p = 0.02). By trial end, 34/63 (54.0%) pregabalin CR and 41/58 (70.7%) placebo patients experienced LTR. Significantly more patients reported 'benefit from treatment' (Benefit, Satisfaction, and Willingness to Continue Scale) in the pregabalin CR group; no other secondary endpoints were statistically significant. Most AEs were mild to moderate in severity (most frequent: dizziness, somnolence). The percentage of pregabalin CR patients discontinuing because of AEs was 12.2% and 4.8% in the single-blind and double-blind phases, respectively (placebo, 0%). Time to LTR was significantly longer with pregabalin CR versus placebo in fibromyalgia patients who initially showed improvement with pregabalin CR, indicating maintenance

Vaccine for Cocaine Dependence: A Randomized Double-Blind Placebo-Controlled Efficacy Trial

PubMed Central

Kosten, Thomas R.; Domingo, Coreen B.; Shorter, Daryl; Orson, Frank; Green, Charles; Somoza, Eugene; Sekerka, Rachelle; Levin, Frances R.; Mariani, John J.; Stitzer, Maxine; Tompkins, D. Andrew; Rotrosen, John; Thakkar, Vatsal; Smoak, Benjamin; Kampman, Kyle

2014-01-01

Aims We evaluated the immunogenicity, efficacy, and safety of succinylnorcocaine conjugated to cholera toxin B protein as a vaccine for cocaine dependence. Methods This 6-site, 24 week Phase III randomized double-blind placebo-controlled trial assessed efficacy during weeks 8 to 16. We measured urine cocaine metabolites thrice weekly as the main outcome. Results The 300 subjects (76% male, 72% African-American, mean age 46 years) had smoked cocaine on average for 13 days monthly at baseline. We hypothesized that retention might be better and positive urines lower for subjects with anti-cocaine IgG levels of ≥ 42 μg/mL (high IgG), which was attained by 67% of the 130 vaccine subjects receiving five vaccinations. Almost 3-times fewer high than low IgG subjects dropped out (7% vs 20%). Although for the full 16 weeks cocaine positive urine rates showed no significant difference between the three groups (placebo, high, low IgG), after week 8, more vaccinated than placebo subjects attained abstinence for at least two weeks of the trial (24% vs 18%), and the high IgG group had the most cocaine-free urines for the last 2 weeks of treatment (OR=3.02), but neither were significant. Injection site reactions of induration and tenderness differed between placebo and active vaccine, and the 29 serious adverse events did not lead to treatment related withdrawals, or deaths. Conclusions The vaccine was safe, but it only partially replicated the efficacy found in the previous study based on retention and attaining abstinence. PMID:24793366

Primaquine prophylaxis against malaria in nonimmune Colombian soldiers: efficacy and toxicity. A randomized, double-blind, placebo-controlled trial.

PubMed

Soto, J; Toledo, J; Rodriquez, M; Sanchez, J; Herrera, R; Padilla, J; Berman, J

1998-08-01

Primaquine had a prophylactic efficacy of 90% to 95% against infection with Plasmodium falciparum and P. vivax in Indonesian settlers. To evaluate the efficacy of primaquine prophylaxis for protecting nonimmune persons from malaria. Randomized, double-blind, placebo-controlled field study. A malaria-endemic area in Colombia. 176 healthy, young, nonimmune adult male soldiers. Primaquine, 30 mg/d, or matching placebo during 15 weeks of patrol in the endemic area and 1 week afterward. Symptomatic parasitemia was determined over the 16-week intervention period and for 3 weeks in base camp. Protective efficacy in the primaquine group (122 participants) was 89% (95% CI, 75% to 96%) against all types of malaria, 94% (CI, 78% to 99%) against P. falciparum malaria, and 85% (CI, 57% to 95%) against P. vivax malaria. Six primaquine recipients had mild to moderate gastrointestinal distress, and three had severe distress. For prophylaxis against P. falciparum malaria, primaquine has an efficacy and toxicity competitive with those of standard agents. A potential advantage of primaquine is that prophylaxis may be discontinued 1 week after the recipient has left the endemic area.

Comparative Efficacy and Durability of Continuation Phase Cognitive Therapy for Preventing Recurrent Depression: Design of a Double-Blinded, Fluoxetine- and Pill-Placebo–Controlled, Randomized Trial with 2-Year Follow-up

PubMed Central

Thase, Michael E.

2010-01-01

Background Major depressive disorder (MDD) is highly prevalent and associated with disability and chronicity. Although cognitive therapy (CT) is an effective short-term treatment for MDD, a significant proportion of responders subsequently suffer relapses or recurrences. Purpose This design prospectively evaluates: 1) a method to discriminate CT-treated responders at lower versus higher risk for relapse; and 2) the subsequent durability of 8-month continuation phase therapies in randomized higher risk responders followed for an additional 24-months. The primary prediction is: after protocol treatments are stopped, higher risk patients randomly assigned to continuation phase CT (C-CT) will have a lower risk of relapse/recurrence than those randomized to fluoxetine (FLX). Methods Outpatients, aged 18 to 70 years, with recurrent MDD received 12–14 weeks of CT provided by 15 experienced therapists from two sites. Responders (i.e., no MDD and 17-item Hamilton Rating Scale for Depression ≤ 12) were stratified into higher and lower risk groups based on stability of remission during the last 6 weeks of CT. The lower risk group entered follow-up for 32 months; the higher risk group was randomized to 8 months of continuation phase therapy with either C-CT or clinical management plus either double-blinded FLX or pill placebo. Following the continuation phase, higher risk patients were followed by blinded evaluators for 24 months. Results The trial began in 2000. Enrollment is complete (N=523). The follow-up continues. Conclusions The trial evaluates the preventive effects and durability of acute and continuation phase treatments in the largest known sample of CT responders collected worldwide. PMID:20451668

Multicenter, Double-Blind, Placebo-Controlled, Randomized Phase II Trial of Gemcitabine/Cisplatin Plus Bevacizumab or Placebo in Patients With Malignant Mesothelioma

PubMed Central

Kindler, Hedy L.; Karrison, Theodore G.; Gandara, David R.; Lu, Charles; Krug, Lee M.; Stevenson, James P.; Jänne, Pasi A.; Quinn, David I.; Koczywas, Marianna N.; Brahmer, Julie R.; Albain, Kathy S.; Taber, David A.; Armato, Samuel G.; Vogelzang, Nicholas J.; Chen, Helen X.; Stadler, Walter M.; Vokes, Everett E.

2012-01-01

Purpose Gemcitabine plus cisplatin is active in malignant mesothelioma (MM), although single-arm phase II trials have reported variable outcomes. Vascular endothelial growth factor (VEGF) inhibitors have activity against MM in preclinical models. We added the anti-VEGF antibody bevacizumab to gemcitabine/cisplatin in a multicenter, double-blind, placebo-controlled randomized phase II trial in patients with previously untreated, unresectable MM. Patients and Methods Eligible patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 and no thrombosis, bleeding, or major blood vessel invasion. The primary end point was progression-free survival (PFS). Patients were stratified by ECOG performance status (0 v 1) and histologic subtype (epithelial v other). Patients received gemcitabine 1,250 mg/m2 on days 1 and 8 every 21 days, cisplatin 75 mg/m2 every 21 days, and bevacizumab 15 mg/kg or placebo every 21 days for six cycles, and then bevacizumab or placebo every 21 days until progression. Results One hundred fifteen patients were enrolled at 11 sites; 108 patients were evaluable. Median PFS time was 6.9 months for the bevacizumab arm and 6.0 months for the placebo arm (P = .88). Median overall survival (OS) times were 15.6 and 14.7 months in the bevacizumab and placebo arms, respectively (P = .91). Partial response rates were similar (24.5% for bevacizumab v 21.8% for placebo; P = .74). A higher pretreatment plasma VEGF concentration (n = 56) was associated with shorter PFS (P = .02) and OS (P = .0066), independent of treatment arm. There were no statistically significant differences in toxicity of grade 3 or greater. Conclusion The addition of bevacizumab to gemcitabine/cisplatin in this trial did not significantly improve PFS or OS in patients with advanced MM. PMID:22665541

[Randomized double-blind comparative study of minaprine (200mg/j) and of placebo on memory loss].

PubMed

Allain, H; Belliard, S; Lieury, A; Menard, G; Patat, A; Le Coz, F; Gandon, J M

1996-01-01

Thirty five subjects (age: 45-69 years) with subjective memory loss, without any other neuropsychiatric or somatic disease, were recruited in a phase II study. This double blind randomized versus placebo controlled study compared the effects of minaprine (200 mg/d) with placebo, in two parallel groups, during 2 months, on memory, attention and vigilance. Three psychometric tests were the main criteria of assessment: a standardized battery of memory tests (SM 5), the dual-coding test, the analysis of choice reaction times (CRT) and the critical flicker fusion point (CFF). A positive effect of minaprine was detected on words delayed recall (p = 0.028) and immediate recognition of words (p = 0.049). The global clinical tests (CGI, MacNair scale) were not statistically modified. Tolerability of minaprine and placebo were comparable. A positive pharmacodynamic activity on mnemonic performance is thus demonstrated in favour of minaprine (200 mg/d) in this specific population characterized by a memory complaint. These results would lead to a phase III study in which the main criteria would be global scales in order to confirm the clinical reliability of the present results.

A double-blind comparison of clebopride and placebo in dyspepsia secondary to delayed gastric emptying.

PubMed

Bavestrello, L; Caimi, L; Barbera, A

1985-01-01

Seventy-six patients suffering from dyspeptic symptoms secondary to roentgenologically demonstrated delayed gastric emptying were treated with clebopride (0.5 mg TID) or with placebo during a three-month double-blind trial. Clebopride was more effective (P less than or equal to 0.001) than placebo in reducing or relieving symptoms and roentgenological findings associated with delayed gastric emptying. No interactions of clebopride with concomitant drugs or coexisting disorders were observed, and the incidence of side effects was low. We conclude that clebopride will be beneficial in the management of patients with delayed gastric emptying.

Treatment of hypothyroidism with levothyroxine plus liothyronine: a randomized, double-blind, crossover study.

PubMed

Kaminski, Juliana; Miasaki, Fabíola Yukiko; Paz-Filho, Gilberto; Graf, Hans; Carvalho, Gisah Amaral de

2016-01-01

To compare the effects of a unique fixed combination levothyroxine/liothyronine (LT4/LT3) therapy in patients with primary hypothyroidism. This is a randomized, double-blind, crossover study. Adults with primary hypothyroidism (n = 32, age 42.6 ± 13.3, 30 females) on stable doses of LT4 for ≥ 6 months (125 or 150 μg/day) were randomized to continue LT4 treatment (G1) or to start LT4/LT3 therapy (75/15 μg/day; G2). After 8 weeks, participants switched treatments for 8 more weeks. Thyroid function, lipid profile, plasma glucose, body weight, electrocardiogram, vital signs, and quality of life (QoL) were evaluated at weeks 0, 8 and 16. Free T4 levels were significantly lower while on LT4/LT3 (G1: 1.07 ± 0.29 vs. 1.65 ± 0.46; G2: 0.97 ± 0.26 vs. 1.63 ± 0.43 ng/dL; P < 0.001). TSH and T3 levels were not affected by type of therapy. More patients on LT4/LT3 had T3 levels above the upper limit (15% vs. 3%). The combination therapy led to an increase in heart rate, with no significant changes in electrocardiogram or arterial blood pressure. Lipid profile, body weight and QoL remained unchanged. The combination therapy yielded significantly lower free T4 levels, with no changes in TSH or T3 levels. More patients on LT4/T3 had elevated T3 levels, with no significant alterations in the evaluated outcomes. No clear clinical benefit of the studied formulation could be observed. Future trials need to evaluate different formulations and the impact of the combined therapy in select populations with genetic polymorphisms.

Xylitol pediatric topical oral syrup to prevent dental caries: a double blind, randomized clinical trial of efficacy

PubMed Central

Milgrom, Peter; Ly, Kiet A.; Tut, Ohnmar K.; Mancl, Lloyd; Roberts, Marilyn C.; Briand, Kennar; Gancio, Mary Jane

2009-01-01

Objective To evaluate the effectiveness of a xylitol pediatric topical oral syrup to reduce the incidence of dental caries of very young children. Design Randomized, double-blinded, controlled trial. Setting Communities in the Republic of the Marshall Islands. Participants 108 children aged 9 to 15 months were screened and 100 were enrolled. Intervention Children were randomized and parents administered topical oral xylitol syrup two times (Xyl-2X, two xylitol 4.00 g/dose + one sorbitol dose) or three times (Xyl-3X, three xylitol 2.67 g/dose) per day (total 8 g) or control (one xylitol 2.67 g/dose + two sorbitol dose). Outcome Measures The outcome end-point of the study was the number of decayed primary teeth. Results Ninety-four of 100 children (mean±SD age, 15.0±2.7 months at randomization) with at least one follow-up exam were included in the intent-to-treat analysis. The mean±SD follow-up period was 10.5±2.2 months. Nearly 52% of children in the control condition had tooth decay compared to 40.6% among Xyl-3X and 24.2% among Xyl-2X conditions. The mean±SD number of decayed teeth was 1.9±2.4 for control, 1.0±1.4 for Xyl-3X, and 0.6±1.1 for Xyl-2X condition. Compared to controls, there was significantly fewer decayed teeth in the Xyl-2X (relative risk [RR], 0.30; 95% confidence interval [CI] 0.13, 0.66; P=.003) and Xyl-3X (RR, 0.50; 95% CI 0.26, 0.96; P=0.037) conditions. There was no statistical difference between the two xylitol treatment conditions (P=0.22). Conclusion Oral xylitol syrup administered topically two or three times each day at a total dose of 8 g was effective in preventing Early Childhood Caries. PMID:19581542

Immediate effects of blood donation on physical and cognitive performance-A randomized controlled double-blinded trial.

PubMed

Eliassen, Håkon S; Hervig, Tor; Backlund, Sebastian; Sivertsen, Joar; Iversen, Vegard Vereide; Kristoffersen, Morten; Wengaard, Eivind; Gramstad, Arne; Fosse, Theodor; Bjerkvig, Christopher K; Apelseth, Torunn; Doughty, Heidi; Strandenes, Geir

2018-06-01

The success of implementing damage control resuscitation principles pre-hospital has been at the expense of several logistic burdens including the requirements for resupply, and the question of donor safety during the development of whole blood programs. Previous studies have reported effects on physical performance after blood donation; however, none have investigated the effects of blood donation on cognitive performance. We describe a prospective double-blinded, randomized, controlled study comprised of a battery of tests: three cognitive tests, and VO2max testing on a cycle ergometer. Testing was performed 7 days before blinded donation (baseline day), immediately after donation (Day 0), and 7 days (Day 7) after donation. The inclusion criteria included being active blood donors at the Haukeland University Hospital blood bank, where eligibility requirements were met on the testing days, and providing informed consent. Participants were randomized to either the experimental (n = 26) or control group (n = 31). Control group participants underwent a 'mock donation" in which a phlebotomy needle was placed but blood was not withdrawn. In the experimental group, mean ± SEM VO2max declined 6% from 41.35 ± 1.7 mLO2/(min·kg) at baseline to 39.0 ± 1.6 mLO2/(min·kg) on Day 0 and increased to 40.51 ± 1.5 mLO2/(min·kg) on Day 7. Comparable values in the control group were 42.1 ± 1.8 mLO2/(min·kg) at baseline, 41.6 ± 1.8 mLO2/(min·kg)) on Day 1 (1% decline from baseline), and 41.8 ± 1.8 mLO2/(min·kg) on Day 7.Comparing scores of all three cognitive tests on Day 0 and Day 7 showed no significant differences (p > 0.05). Our main findings are that executive cognitive and physical performances were well maintained after whole blood donation in healthy blood donors. The findings inform postdonation guidance on when donors may be required to return to duty. Randomized, controlled, double-blinded prospective trial study, level 1.

Comparison of Murraya koenigii- and Tribulus terrestris-based oral formulation versus tamsulosin in the treatment of benign prostatic hyperplasia in men aged >50 years: a double-blind, double-dummy, randomized controlled trial.

PubMed

Sengupta, Gairik; Hazra, Avijit; Kundu, Anup; Ghosh, Anirban

2011-12-01

Drug treatment can defer surgical intervention in benign prostatic hyperplasia (BPH), a common disorder in elderly men, and is widely practiced. Various herbal formulations have been used for the treatment of BPH, but few have been compared with established modern medicines in head-to-head clinical trials. We compared the effectiveness and tolerability of an oral formulation, comprising standardized extracts of Murraya koenigii and Tribulus terrestris leaves being marketed in India under Ayurvedic license, versus tamsulosin in the treatment of symptomatic BPH. A double-blind, double-dummy, parallel-group, randomized controlled trial was conducted with treatment-naive ambulatory patients with BPH aged >50 years. Patients received either the plant drug in a dose of 2 capsules BID or tamsulosin 400 μg once daily for 12 weeks with 2 interim follow-up visits at the end of 4 and 8 weeks. The double-dummy technique was used to ensure double-blinding. The primary effectiveness measure was reduction in the International Prostate Symptom Score (IPSS). Proportion of patients becoming completely or relatively symptom free (IPSS <8), change in prostate volume (assessed by using ultrasonography conducted by a radiologist blinded to the nature or duration of treatment), and peak urinary flow rate (assessed by using uroflowmetry) were secondary measures. Treatment-emergent adverse events, changes in weight, vital signs, and routine laboratory safety parameters were recorded. Forty-six patients were randomized (23 per group); 19 completed all study visits in the plant drug group and 21 in the tamsulosin group. However, applying modified intention-to-treat criterion, 23 and 21 patients, respectively, were considered for effectiveness analysis. Mean (SD) age and baseline weight were 58.5 (14.0) years and 57.5 (10.5) kg in the plant drug arm, and 62.9 (6.3) years and 59.8 (9.9) kg in the tamsulosin arm, respectively. Median (interquartile range) symptom duration was 12.0 (12

A pilot randomized double-blind placebo-controlled trial on topical chamomile (Matricaria chamomilla L.) oil for severe carpal tunnel syndrome.

PubMed

Hashempur, Mohammad Hashem; Lari, Zeinab Nasiri; Ghoreishi, Parissa Sadat; Daneshfard, Babak; Ghasemi, Mohammad Sadegh; Homayouni, Kaynoosh; Zargaran, Arman

2015-11-01

To assess the effectiveness of standardized topical Chamomile (Matricaria chamomilla L.) oil in patients with severe carpal tunnel syndrome, as a complementary treatment. A pilot randomized double-blind placebo-controlled trial was conducted. Twenty six patients with documented severe carpal tunnel syndrome were treated in two parallel groups with a night splint plus topical chamomile oil or placebo. They were instructed to use their prescribed oil for 4 weeks, twice daily. Symptomatic and functional status of the patients and their electrodiagnostic parameters were evaluated when enrolled and after the trial period, as our outcome measures. A significant improvement of symptomatic and functional status of patients in the chamomile oil group was observed (p = 0.019 and 0.016, respectively) compared with those in the placebo group. However, electrodiagnostic parameters showed no significant changes between the two groups. Chamomile oil improved symptomatic and functional status of patients with severe carpal tunnel syndrome. Copyright © 2015 Elsevier Ltd. All rights reserved.

Efficacy of topical chamomile oil for mild and moderate carpal tunnel syndrome: A randomized double-blind placebo-controlled clinical trial.

PubMed

Hashempur, Mohammad Hashem; Ghasemi, Mohammad Sadegh; Daneshfard, Babak; Ghoreishi, Parissa Sadat; Lari, Zeinab Nasiri; Homayouni, Kaynoosh; Zargaran, Arman

2017-02-01

To evaluate the efficacy of topical chamomile oil in patients with mild and moderate carpal tunnel syndrome (CTS). Eighty six patients with electrodiagnostic criteria of mild and moderate CTS were enrolled in this randomized double-blind placebo-controlled clinical trial and received wrist splint plus topical chamomile oil or placebo for 4 weeks. They were evaluated at the baseline and end of the study regarding functional and symptomatic scores, dynamometry, and electrodiagnostic indexes. Dynamometry, functionality, and symptom severity scores of the patients were significantly improved in the chamomile oil group compared with the placebo group (P = 0.040, P = 0.0001, P = 0.017, respectively). Additionally, compound latency of the median nerve in the chamomile oil group significantly decreased (P = 0.035) compared to the placebo group. Other electerodiagnostic measurements did not change significantly. Complementary treatment with topical chamomile oil may have some benefits for patients with mild and moderate CTS, both subjectively and objectively. Copyright © 2016 Elsevier Ltd. All rights reserved.

Metformin effects on ovarian ultrasound appearance and steroidogenic function in normal-weight normoinsulinemic women with polycystic ovary syndrome: a randomized double-blind placebo-controlled clinical trial.

PubMed

Romualdi, Daniela; Giuliani, Maddalena; Cristello, Francesca; Fulghesu, Anna Maria; Selvaggi, Luigi; Lanzone, Antonio; Guido, Maurizio

2010-05-01

To investigate metformin effects on the endocrine-metabolic parameters and ovarian morphology in normoinsulinemic women with polycystic ovary syndrome (PCOS). Randomized double-blind study. Operative Division of Endocrinological Gynecology, Università Cattolica del Sacro Cuore. Twenty-eight normal-weight normoinsulinemic PCOS women. Patients were randomized to receive metformin 500 mg twice a day (group A, 15 subjects) or placebo (group B, 13 subjects) for 6 months. Ultrasonographic pelvic exams, hormonal and lipid features, and oral glucose tolerance test were performed at baseline and after 3 and 6 months of treatment. Hormonal and glycoinsulinemic assessment, ovarian ultrasound appearance. Glycoinsulinemic assessment remained unvaried in both groups. About 70% of patients in group A experienced a restoration of menstrual cyclicity. Metformin significantly decreased testosterone levels at 3 and 6 months) and 17-hydroxyprogesterone levels at 6 months, and improved hirsutism score at 6 months. No clinical or hormonal modifications occurred in group B. Metformin, but not placebo, reduced ovarian volume and stromal/total area ratio at 3 and 6 months. Metformin seems to improve the menstrual pattern and ultrasonographic ovarian features in normoinsulinemic PCOS women. These effects seem to be, at least in part, independent of the insulin-lowering properties of the drug. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Lumbar Intradiskal Platelet-Rich Plasma (PRP) Injections: A Prospective, Double-Blind, Randomized Controlled Study.

PubMed

Tuakli-Wosornu, Yetsa A; Terry, Alon; Boachie-Adjei, Kwadwo; Harrison, Julian R; Gribbin, Caitlin K; LaSalle, Elizabeth E; Nguyen, Joseph T; Solomon, Jennifer L; Lutz, Gregory E

2016-01-01

To determine whether single injections of autologous platelet-rich plasma (PRP) into symptomatic degenerative intervertebral disks will improve participant-reported pain and function. Prospective, double-blind, randomized controlled study. Outpatient physiatric spine practice. Adults with chronic (≥6 months), moderate-to-severe lumbar diskogenic pain that was unresponsive to conservative treatment. Participants were randomized to receive intradiskal PRP or contrast agent after provocative diskography. Data on pain, physical function, and participant satisfaction were collected at 1 week, 4 weeks, 8 weeks, 6 months, and 1 year. Participants in the control group who did not improve at 8 weeks were offered the option to receive PRP and subsequently followed. Functional Rating Index (FRI), Numeric Rating Scale (NRS) for pain, the pain and physical function domains of the 36-item Short Form Health Survey, and the modified North American Spine Society (NASS) Outcome Questionnaire were used. Forty-seven participants (29 in the treatment group, 18 in the control group) were analyzed by an independent observer with a 92% follow-up rate. Over 8 weeks of follow-up, there were statistically significant improvements in participants who received intradiskal PRP with regards to pain (NRS Best Pain) (P = .02), function (FRI) (P = .03), and patient satisfaction (NASS Outcome Questionnaire) (P = .01) compared with controls. No adverse events of disk space infection, neurologic injury, or progressive herniation were reported following the injection of PRP. Participants who received intradiskal PRP showed significant improvements in FRI, NRS Best Pain, and NASS patient satisfaction scores over 8 weeks compared with controls. Those who received PRP maintained significant improvements in FRI scores through at least 1 year of follow-up. Although these results are promising, further studies are needed to define the subset of participants most likely to respond to biologic intradiskal

Transcutaneous pulsed radiofrequency treatment for patients with shoulder pain booked for surgery: a double-blind, randomized controlled trial.

PubMed

Taverner, Murray; Loughnan, Terence

2014-02-01

Shoulder pain is the third most common musculoskeletal problem and accounts for 5% of general practitioner consultations. Although many treatments are described, there is no consensus on optimal treatment and up to 40% of patients still have pain 12 months after initially seeking help for pain. Previously, the effect of transcutaneous pulsed radiofrequency treatment (TCPRFT) was evaluated in a retrospective audit that showed good pain relief for a mean 395 days and justified this randomized sham controlled trial. In this study, 51 patients entered into a randomized double-blinded, placebo controlled study of TCPRFT. Patients were assessed at 4 and 12 weeks by a blinded observer and compared with baseline. We observed sustained reductions in pain at night, pain with activity, and functional improvement at 4 and 12 weeks with active but not sham TCPRFT. The 25 subjects who received active treatment showed statistically significant reductions of 24/100 in pain at night and 20/100 of pain with activity at 4 weeks and 18/100 and 19/100, respectively, at 12 weeks from baseline. Statistically significant lower Brief Pain Inventory pain and function scores (4 and 12 weeks), improved pain self-efficacy (4 weeks), Oxford Shoulder scores (12 weeks), and internal rotation (12 weeks) were seen. Pain at both rest and shoulder elevation were not improved by active treatment. No complications were seen. This study of a simple, low risk, outpatient treatment confirms the findings of our earlier study of TCPRFT for knee pain and shoulder pain audit that transcutaneous pulsed radiofrequency treatment may help some people with painful shoulders. © 2013 The Authors Pain Practice © 2013 World Institute of Pain.

A Randomized Double-Blind Study of Atomoxetine versus Placebo for Attention-Deficit/Hyperactivity Disorder Symptoms in Children with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Harfterkamp, Myriam; van de Loo-Neus, Gigi; Minderaa, Ruud B.; van der Gaag, Rutger-Jan; Escobar, Rodrigo; Schacht, Alexander; Pamulapati, Sireesha; Buitelaar, Jan K.; Hoekstra, Pieter J.

2012-01-01

Objective: The efficacy of atomoxetine as treatment of symptoms of attention-deficit/hyperactivity disorder (ADHD) in patients with autism spectrum disorder (ASD) has not been established. Method: In this study, 97 patients aged 6 to 17 years with ADHD and ASD were randomly assigned to double-blind treatment with 1.2 mg/kg/day atomoxetine or…

Garlic extract favorably modifies markers of endothelial function in obese patients -randomized double blind placebo-controlled nutritional intervention.

PubMed

Szulińska, Monika; Kręgielska-Narożna, Matylda; Świątek, Joanna; Styś, Paulina; Kuźnar-Kamińska, Barbara; Jakubowski, Hieronim; Walkowiak, Jarosław; Bogdański, Paweł

2018-06-01

Garlic exerts a range of effects relevant to human health. However, its influence on the endothelium in obese individuals remains unknown. We aimed to determine the effects of garlic extract (GE) on arterial stiffness and markers of endothelial function. Ninety-two subjects were enrolled in this study. The participants were randomly assigned to receive 400 mg of GE or placebo daily for 3 months. The arterial stiffness index (SI) and markers of endothelial function such as high-sensitivity C-reactive protein (hsCRP), cholesterol (total, LDL, HDL), triglycerides, and plasminogen activator inhibitor 1 (PAI-1), as well as total antioxidant status (TAS) were quantified at baseline and the end of study. At the end of study SI (p = 0.01), hsCRP (p < 0.001, PAI-1 (p < 0.001), LDL cholesterol (p < 0.001), and TAS (p < 0.01) were reduced in the GE-supplemented group, but not in the placebo group. This randomized, double-blind, placebo-controlled trial demonstrates that supplementation with GE favorably modifies endothelial biomarkers associated with cardiovascular risk and suggests that GE can be used to suppress chronic inflammation in obese individuals. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

A double-blind, randomized, placebo-controlled trial of the effect of testosterone cream on the sexual motivation of menopausal hysterectomized women with hypoactive sexual desire disorder.

PubMed

El-Hage, G; Eden, J A; Manga, R Zoa

2007-08-01

To assess the safety and efficacy of 10 mg topical testosterone therapy daily (2 cm Andro-Feme cream) as a treatment for low sexual desire in postmenopausal hysterectomized women who were already on transdermal estrogen. A double-blind, randomized, placebo-controlled, cross-over study (each period being of 3 months' duration) was performed in the research center of a tertiary referral women's hospital. Thirty-six menopausal healthy women were recruited who had undergone a hysterectomy, who were not depressed, were in a stable relationship and who fulfilled diagnostic criteria for low sexual desire, as measured by the Brief Index of Sexual Function for Women (BISF-W). The primary outcome measure was improvement in the sexuality score as measured by a validated tool (BISF-W); secondary measures were sub-scores of the BISF-W, effect on mood and energy, lipids and testosterone levels. Testosterone cream significantly improved sexual desire, frequency of sex, receptivity and initiation as measured by the BISF-W score. It did not change mood, energy, lipids, blood pressure or weight over the study period. Testosterone cream significantly improved sexual scores in menopausal women with low sexual desire. It was effective, easy to use and had no side-effects over the 3-month period of active treatment. It offers a novel and acceptable method of administering testosterone to menopausal women.

Melatonin for sedative withdrawal in older patients with primary insomnia: a randomized double-blind placebo-controlled trial

PubMed Central

Lähteenmäki, Ritva; Puustinen, Juha; Vahlberg, Tero; Lyles, Alan; Neuvonen, Pertti J; Partinen, Markku; Räihä, Ismo; Kivelä, Sirkka-Liisa

2014-01-01

Aim We compared the efficacy of melatonin and placebo as adjuvants in the withdrawal of patients from long term temazepam, zopiclone or zolpidem (here ‘BZD’) use. Methods A double-blind, placebo-controlled, randomized trial was conducted in a primary health care outpatient clinic. Ninety-two men or women (≥55 years) with primary insomnia and chronic BZD use received controlled release melatonin 2 mg (CRM) (n = 46) or placebo (n = 46) during the 1 month withdrawal from BZDs. Psychosocial support was provided. Follow-up continued for up to 6 months. Successful BZD withdrawal by the end of 1 month was confirmed by BZD plasma determinations, while reduction in BZD use and abstinence continuing for 6 months were noted. Results There were two drop-outs on CRM and one on placebo. After a 1 month withdrawal, 31 participants (67%; 95% CI 54, 81) on CRM and 39 (85%; 74, 95) on placebo had withdrawn completely (intention-to-treat analysis between groups, P = 0.051; per protocol P = 0.043). Reduction in BZD use was similar or even more rare in the CRM than in the placebo group (P = 0.052 per protocol). After 6 months, 14 participants in the CRM group and 20 in the placebo group remained non-users of BZD (NS between groups). BZD doses were higher in the CRM than in the placebo group at the end of the 6 month follow-up (P = 0.025). Withdrawal symptoms did not differ between the groups. Conclusions Gradual dose reduction of BZDs combined with CRM or placebo, and psychosocial support produced high short term and moderate long term BZD abstinence. CRM showed no withdrawal benefit compared with placebo. PMID:24286360

Effect of Agaricus sylvaticus supplementation on nutritional status and adverse events of chemotherapy of breast cancer: a randomized, placebo-controlled, double-blind clinical trial.

PubMed

Valadares, Fabiana; Garbi Novaes, Maria Rita Carvalho; Cañete, Roberto

2013-01-01

Breast cancer (BC) represents the highest incidence of malignancy in women throughout the world. Medicinal fungi can stimulate the body, reduce side-effects associated with chemotherapy and improve the quality of life in patients with cancer. To evaluate the effects of dietary supplementation of Agaricus sylvaticus on clinical and nutritional parameters in BC patients undergoing chemotherapy. A randomized, placebo-controlled, double-blind, clinical trial was carried out at the Oncology Clinic, Hospital of the Federal District-Brazil from September 2007 to July 2009. Forty six patients with BC, Stage II and III, were randomly assigned to receive either nutritional supplement with A. sylvaticus (2.1 g/day) or placebo. Patients were evaluated during treatment period. Patient supplemented with A. sylvaticus improved in clinical parameters and gastrointestinal functions. Poor appetite decreased by 20% with no changes in bowel functions (92.8%), nausea and vomiting (80%). Dietary supplementation with A. sylvaticus improved nutritional status and reduced abnormal bowel functions, nausea, vomiting, and anorexia in patients with BC receiving chemotherapy.

Randomized, double-blind, controlled study of glycerol phenylbutyrate in hepatic encephalopathy

PubMed Central

Rockey, Don C; Vierling, John M; Mantry, Parvez; Ghabril, Marwan; Brown, Robert S; Alexeeva, Olga; Zupanets, Igor A; Grinevich, Vladimir; Baranovsky, Andrey; Dudar, Larysa; Fadieienko, Galyna; Kharchenko, Nataliya; Klaryts'ka, Iryna; Morozov, Vyacheslav; Grewal, Priya; McCashland, Timothy; Reddy, K Gautham; Reddy, K Rajender; Syplyviy, Vasyl; Bass, Nathan M; Dickinson, Klara; Norris, Catherine; Coakley, Dion; Mokhtarani, Masoud; Scharschmidt, Bruce F

2014-01-01

Glycerol phenylbutyrate (GPB) lowers ammonia by providing an alternate pathway to urea for waste nitrogen excretion in the form of phenylacetyl glutamine, which is excreted in urine. This randomized, double-blind, placebo-controlled phase II trial enrolled 178 patients with cirrhosis, including 59 already taking rifaximin, who had experienced two or more hepatic encephalopathy (HE) events in the previous 6 months. The primary endpoint was the proportion of patients with HE events. Other endpoints included the time to first event, total number of events, HE hospitalizations, symptomatic days, and safety. GPB, at 6 mL orally twice-daily, significantly reduced the proportion of patients who experienced an HE event (21% versus 36%; P = 0.02), time to first event (hazard ratio [HR] = 0.56; P < 0.05), as well as total events (35 versus 57; P = 0.04), and was associated with fewer HE hospitalizations (13 versus 25; P = 0.06). Among patients not on rifaximin at enrollment, GPB reduced the proportion of patients with an HE event (10% versus 32%; P < 0.01), time to first event (HR = 0.29; P < 0.01), and total events (7 versus 31; P < 0.01). Plasma ammonia was significantly lower in patients on GPB and correlated with HE events when measured either at baseline or during the study. A similar proportion of patients in the GPB (79%) and placebo groups (76%) experienced adverse events. Conclusion: GPB reduced HE events as well as ammonia in patients with cirrhosis and HE and its safety profile was similar to placebo. The findings implicate ammonia in the pathogenesis of HE and suggest that GPB has therapeutic potential in this population. (Clinicaltrials.gov, NCT00999167). (Hepatology 2014;59:1073-1083) PMID:23847109

The Effect of Trimethoprim on Serum Folate Levels in Humans: A Randomized, Double-Blind, Placebo-Controlled Trial.

PubMed

Meidahl Petersen, Kasper; Eplov, Kasper; Kjær Nielsen, Torben; Jimenez-Solem, Espen; Petersen, Morten; Broedbaek, Kasper; Daugaard Popik, Sara; Kallehave Hansen, Lina; Enghusen Poulsen, Henrik; Trærup Andersen, Jon

2016-01-01

Trimethoprim antagonize the actions of folate by inhibition of dihydrofolate reductase. This could diminish serum folate levels in humans and causes folate deficiency in some patients. We conducted a randomized, double-blind, placebo-controlled trial, to investigate the effect of trimethoprim on serum folate levels in healthy participants after a 7-day trial period. Thirty young, healthy males were randomly allocated to receive trimethoprim, 200 mg twice daily, and 30 were randomly allocated to placebo. Before trial initiation, participant numbers were given randomly generated treatment allocations within sealed opaque envelopes. Participants and all staff were kept blinded to treatment allocations during the trial. Serum folate was measured at baseline and at end of trial. In the 58 participants analyzed (30 in the trimethoprim group and 28 in the placebo group), 8 had folate deficiency at baseline. Within the trimethoprim group, serum folate was significantly decreased (P = 0.018) after the trial. We found a mean decrease in serum folate among trimethoprim exposed of 1.95 nmol/L, compared with a 0.21 nmol/L mean increase in the placebo group (P = 0.040). The proportion of folate-deficient participants increased significantly within the trimethoprim group (P = 0.034). No serious adverse events were observed. In conclusion, we found that a daily dose of 400 mg trimethoprim for 7 days significantly lowered serum folate levels in healthy study participants.

Clinical Outcomes of Knee Osteoarthritis Treated With an Autologous Protein Solution Injection: A 1-Year Pilot Double-Blinded Randomized Controlled Trial.

PubMed

Kon, Elizaveta; Engebretsen, Lars; Verdonk, Peter; Nehrer, Stefan; Filardo, Giuseppe

2018-01-01

Osteoarthritis (OA) is a debilitating disease resulting in substantial pain and functional limitations. A novel blood derivative has been developed to concentrate both growth factors and antagonists of inflammatory cytokines, with promising preliminary findings in terms of safety profile and clinical improvement. To investigate if one intra-articular injection of autologous protein solution (APS) can reduce pain and improve function in patients affected by knee OA in a multicenter, randomized, double-blind, saline-controlled study. Randomized controlled trial; Level of evidence, 2. Forty-six patients with unilateral knee OA (Kellgren-Lawrence 2 or 3) were randomized into the APS group (n = 31), which received a single ultrasound-guided injection of APS, and the saline (control) group (n = 15), which received a single saline injection. Patient-reported outcomes and adverse events were collected at 2 weeks and at 1, 3, 6, and 12 months through visual analog scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Knee injury and Osteoarthritis Outcome Score (KOOS), Short Form-36 (SF-36), Clinical Global Impression of Severity/Change (CGI-S/C), Patient Global Impression of Severity/Change (PGI-S/C), and Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) responder rate. Imaging evaluation was also performed with radiograph and magnetic resonance imaging (MRI) before and after treatment (12 months and 3 and 12 months, respectively). The safety profile was positive, with no significant differences in frequency and severity of adverse events between groups. The improvement from baseline to 2 weeks and to 1, 3, and 6 months was similar between treatments. At 12 months, improvement in WOMAC pain score was 65% in the APS group and 41% in the saline group ( P = .02). There were no significant differences in VAS pain improvement between groups. At 12 months, APS group showed improved SF-36 Bodily Pain

[Stimulation of wound healing by tetrachlordecaoxide. Results of a randomized double-blind study].

PubMed

Hinz, J; Hautzinger, H; Helling, J; Schirren, G; Sell, G; Stahl, K W; Kühne, F W

1984-05-10

In 38 patients with chronic therapeutically resistant wounds, which, in 25 cases, had been existing for more than one year, Tetrachlorodecaoxide ( TCDO ) in a water solution containing glycerin was analyzed for its capacity to induce wound healing and compared in this respect to the standard in moist wound treatment, physiological sodium chloride. The results of the clinical trial demonstrate that the TCDO solution is significantly superior to physiological saline in local wound treatment regarding the degree of wound smear reduction, the formation of wound granulation tissue, the stimulation of epithelisation on the wound borders and the shrinking of the wound surface. The differences in therapeutic efficiency are so large that, in spite of the relatively small patient samples (21 + 17) it was possible to verify the superiority of a method for wound treatment in a randomized double blind clinical trial.

Effect of SSRI antidepressants on ejaculation: a double-blind, randomized, placebo-controlled study with fluoxetine, fluvoxamine, paroxetine, and sertraline.

PubMed

Waldinger, M D; Hengeveld, M W; Zwinderman, A H; Olivier, B

1998-08-01

Depression is a common cause of sexual dysfunction, but also antidepressant medication is often associated with sexual side effects. This article includes two related studies. The first double-blind, placebo-controlled study was conducted in men with lifelong rapid ejaculation and aimed to assess putative differences between the major selective serotonin reuptake inhibitors (SSRIs) (fluoxetine, fluvoxamine, paroxetine, and sertraline) with regard to their ejaculation-delaying effect. Sixty men with an intravaginal ejaculation latency time (IELT) of 1 minute or less were randomly assigned to receive fluoxetine 20 mg/day, fluvoxamine 100 mg/day, paroxetine 20 mg/day, sertraline 50 mg/day, or placebo for 6 weeks. During the 1-month baseline and 6-week treatment periods, the men measured their IELT at home using a stopwatch. The trial was completed by 51 men. During the 6-week treatment period, the geometric mean IELT in the placebo group was constant at approximately 20 seconds. Analysis of variance revealed a between-groups difference in the evolution of IELT delay (p = 0.0004); in the paroxetine, fluoxetine, and sertraline groups there was a gradual increase to about 110 seconds, whereas in the fluvoxamine group, IELT was increased to only approximately 40 seconds. The paroxetine, fluoxetine, and sertraline groups differed significantly (p < 0.001, p < 0.001, p = 0.017, respectively) from placebo but the fluvoxamine group did not (p = 0.38). Compared with baseline, paroxetine exerted the strongest delay in ejaculation, followed by fluoxetine and sertraline. There was no clinically relevant delay in ejaculation with fluvoxamine. In men with lifelong rapid ejaculation, paroxetine delayed ejaculation most strongly, whereas fluvoxamine delayed ejaculation the least. The second double-blind, placebo-controlled study was carried out in men with lifelong rapid ejaculation (IELT < or = 1 minute) and in men with lifelong less-rapid ejaculation (IELT > 1 minute) to

Human lactobacilli as supplementation of clindamycin to patients with bacterial vaginosis reduce the recurrence rate; a 6-month, double-blind, randomized, placebo-controlled study

PubMed Central

2008-01-01

Background The primary objective of this study was to investigate if supplementary lactobacilli treatment could improve the initial cure rate after vaginal clindamycin therapy, and secondly, if lactobacilli as repeated adjunct treatment during 3 menstrual cycles could lengthen the time to relapse after initial cure. Methods Women (n = 100) with bacterial vaginosis diagnosed by Amsel criteria were after informed consent offered vaginal clindamycin therapy followed by vaginal gelatine capsules containing either 109 freeze-dried lactobacilli or identical placebo capsules for 10 days during 3 menstrual cycles in a double-blind, randomized, placebo-controlled trial. Results The initial intent to treat (ITT) analysis for the one-month cure rate was 64% in the lactobacilli group and 78% in the placebo group (p > 0.05). However, any patient with missing or unclassified smears at the initial visit who continued the study and whose next smear indicated a cure was included in the cured group; the study also excluded two of the patients in the lactobacilli group who reported that they did not take any vaginal capsules. With consideration to these population changes, the initial cure rate would be 77% in the lactobacilli group. The 76 cured women were followed for 6 menstrual cycles or until relapse within that time span. At the end of the study, 64.9% (24/37) of the lactobacilli treated women were still BV-free compared to 46.2% (18/39) of the placebo treated women. Comparison of the two groups regarding "Time from cure to relapse" was statistically significant (p = 0.027) in favour of the lactobacilli treatment. Adjuvant therapy with lactobacilli contributed significantly to avoidance of relapse with a proportional Hazard Risk ratio (HR) of 0.73 (0.54–0.98) (p < 0.05) Conclusion The study shows that supplementary treatment combining two different strains of probiotic lactobacilli does not improve the efficacy of BV therapy during the first month of treatment, but for women

Effects of evening vs morning levothyroxine intake: a randomized double-blind crossover trial.

PubMed

Bolk, Nienke; Visser, Theo J; Nijman, Judy; Jongste, Ineke J; Tijssen, Jan G P; Berghout, Arie

2010-12-13

Levothyroxine sodium is widely prescribed to treat primary hypothyroidism. There is consensus that levothyroxine should be taken in the morning on an empty stomach. A pilot study showed that levothyroxine intake at bedtime significantly decreased thyrotropin levels and increased free thyroxine and total triiodothyronine levels. To date, no large randomized trial investigating the best time of levothyroxine intake, including quality-of-life evaluation, has been performed. To ascertain if levothyroxine intake at bedtime instead of in the morning improves thyroid hormone levels, a randomized double-blind crossover trial was performed between April 1, 2007, and November 30, 2008, among 105 consecutive patients with primary hypothyroidism at Maasstad Hospital Rotterdam in the Netherlands. Patients were instructed during 6 months to take 1 capsule in the morning and 1 capsule at bedtime (one containing levothyroxine and the other a placebo), with a switch after 3 months. Primary outcome measures were thyroid hormone levels; secondary outcome measures were creatinine and lipid levels, body mass index, heart rate, and quality of life. Ninety patients completed the trial and were available for analysis. Compared with morning intake, direct treatment effects when levothyroxine was taken at bedtime were a decrease in thyrotropin level of 1.25 mIU/L (95% confidence interval [CI], 0.60-1.89 mIU/L; P < .001), an increase in free thyroxine level of 0.07 ng/dL (0.02-0.13 ng/dL; P = .01), and an increase in total triiodothyronine level of 6.5 ng/dL (0.9-12.1 ng/dL; P = .02) (to convert thyrotropin level to micrograms per liter, multiply by 1.0; free thyroxine level to picomoles per liter, multiply by 12.871; and total triiodothyronine level to nanomoles per liter, multiply by 0.0154). Secondary outcomes, including quality-of-life questionnaires (36-Item Short Form Health Survey, Hospital Anxiety and Depression Scale, 20-Item Multidimensional Fatigue Inventory, and a symptoms

Effect of atorvastatin on progression of sensorineural hearing loss and tinnitus in the elderly: results of a prospective, randomized, double-blind clinical trial.

PubMed

Olzowy, Bernhard; Canis, Martin; Hempel, John-Martin; Mazurek, Birgit; Suckfüll, Markus

2007-06-01

To test whether the 3-hydroxy-3-methylglutaryl- coenzyme A reductase inhibitor atorvastatin can slow down the progression of presbycusis. Fifty patients 60- to 75-years-old with presbycusis and moderately elevated serum cholesterol. In a double-blind design, patients were randomly assigned to treatment with either atorvastatin (40 mg/d orally) or placebo. Pure-tone audiometry and tinnitus evaluation at enrolment and after 7 and 13 months. Development of hearing thresholds after 7 and 13 months showed no significant differences between the groups. Tinnitus score continuously improved in the atorvastatin group (34.8 at 7 and 27.6 at 13 mo), whereas it slightly deteriorated in the placebo group (24.8 at 7 and 26.8 at 13 mo). The effect on tinnitus was a tendency without statistic significance (p = 0.0833). Atorvastatin had no effect on the development of hearing thresholds, but resulted in a trend toward a relief of tinnitus.

Six-month treatment with low-dose dexamethasone further reduces androgen levels in PCOS women treated with diet and lifestyle advice, and metformin.

PubMed

Vanky, E; Salvesen, K A; Carlsen, S M

2004-03-01

The purpose of this study was to investigate the effect of low-dose dexamethasone on androgen levels in women with polycystic ovary syndrome (PCOS) treated with diet and lifestyle counselling, and metformin. A prospective, randomized, double blind, placebo-controlled study was carried out. Thirty-eight women with PCOS were randomized to either dexamethasone 0.25 mg daily or placebo for 26 weeks. All received diet and lifestyle counselling at inclusion and metformin 850 mg three times daily during the whole study. Main outcome measures were: androgen levels, body mass index (BMI), insulin c-peptide, fasting glucose and serum lipids. Two-tailed t-tests and Pearson's statistics were used. Compared with the placebo, dexamethasone reduced testosterone by 27%, androstenedione by 21%, dehydroepiandrosterone sulphate by 46% and free testosterone index by 50% in women with PCOS treated with diet and lifestyle advice, and metformin. BMI, fasting glucose, insulin c-peptide and serum lipid levels were unaffected. Six-month, low-dose dexamethasone treatment further reduces androgen levels in metformin-treated PCOS women.

Comparison of growth and nutritional status in infants receiving goat milk-based formula and cow milk-based formula: a randomized, double-blind study.

PubMed

Xu, Meihong; Wang, Yibin; Dai, Zhiyong; Zhang, Yanchun; Li, Yong; Wang, Junbo

2015-01-01

To compare the growth and nutritional status of infants fed goat milk-based formula (GMF) and cow milk-based formula (CMF). The study was conducted in Beijing, China. It was a double-blind randomized controlled trial. A total of 79 infants aged 0-3 months old were recruited and randomized in GMF or CMF group. The infants were fed the allocated formula to 6 months. The weight, length, and head circumference were measured at the enrolment, 3 and 6 months. The start time and types of solid food were recorded. Blood elements, urinal, and fecal parameters were also tested. The average weight of infants in the GMF group (mean±SD) was 4.67±0.99 kg and in the CMF group 4.73±1.10 kg at enrolment, and 8.75±0.98 kg (GMF) and 8.92±0.88 kg (CMF) at 6 months. There were no differences in the adjusted intention-to-treat analyses of weight, length, head circumference, and BMI z-scores between the two formula-fed groups over the 6-month study. Similarly, there were no remarkable differences in the timing and types of solid food, blood elements, urinal, and feces parameters, between the GMF and CMF group. No group differences have been shown in bowel motion consistency, duration of crying, ease of settling, or frequency of adverse events. GMF-provided growth and nutritional outcomes did not differ from those provided by CMF.

Implant decontamination with 2% chlorhexidine during surgical peri-implantitis treatment: a randomized, double-blind, controlled trial.

PubMed

de Waal, Y C M; Raghoebar, G M; Meijer, H J A; Winkel, E G; van Winkelhoff, A J

2015-09-01

The objective of this randomized, double-blind, controlled trial was to evaluate the clinical, radiographic, and microbiological effects of implant surface decontamination with a 2% chlorhexidine (CHX) solution in comparison with a 0.12% chlorhexidine + 0.05% cetylpyridinium chloride (CPC) solution during resective surgical peri-implantitis treatment. Forty-four patients (108 implants) with peri-implantitis were treated with resective surgical treatment consisting of bone re-contouring, surface debridement and chemical decontamination, and apically repositioned flap. Patients were randomly allocated to decontamination with a 2% CHX solution (test group) or 0.12% CHX + 0.05% CPC (control group). Clinical and radiographic parameters were recorded before treatment (baseline), and at 3, 6, and 12 months after treatment. Microbiological parameters were recorded during surgery. Multilevel analysis showed no significant differences in bleeding, suppuration, probing pocket depth, and radiographic bone loss between control and test group over three follow-up measurements (3, 6, and 12 months) from baseline. Both decontamination procedures resulted in significant reductions in anaerobic bacterial counts on the implant surface, but no significant difference was noted between control and test group (mean log 3.37 ± 2.34 vs. 3.65 ± 2.87, P = 0.99). The use of a 2% CHX solution for implant surface decontamination during resective peri-implantitis therapy does not lead to improved clinical, radiographic, or microbiological results compared with a 0.12% CHX + 0.05% CPC solution. Overall, the additional use of CHX reduces anaerobic bacterial load on the implant surface better than mechanical debridement alone, but does not seem to enhance clinical treatment outcomes (ClinicalTrials.gov number NCT01852253). © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A randomized double-blind, placebo-controlled efficacy and safety study of ALO-02 (extended-release oxycodone surrounding sequestered naltrexone) for moderate-to-severe chronic low back pain treatment.

PubMed

Rauck, Richard L; Hale, Martin E; Bass, Almasa; Bramson, Candace; Pixton, Glenn; Wilson, Jacquelyn G; Setnik, Beatrice; Meisner, Paul; Sommerville, Kenneth W; Malhotra, Bimal K; Wolfram, Gernot

2015-09-01

The objective of this multicenter, double-blind, placebo-controlled, randomized withdrawal study was to evaluate the efficacy and safety of ALO-02, an abuse-deterrent formulation containing pellets of extended-release oxycodone hydrochloride (HCl) surrounding sequestered naltrexone HCl, compared with placebo in the treatment of moderate-to-severe chronic low back pain. An open-label titration period in which all patients received ALO-02 was followed by a double-blind treatment period where patients meeting treatment response criteria were randomized to either a fixed dose of ALO-02 or placebo. Daily average low back pain was assessed using an 11-point numeric rating scale (NRS)-Pain. Of the 663 patients screened, 410 received ALO-02 during the open-label conversion and titration period and 281 patients were randomized to the double-blind treatment period (n = 134, placebo; n = 147, ALO-02). Change in the mean NRS-Pain score from randomization baseline to the final 2 weeks of the treatment period was significantly different favoring ALO-02 compared with placebo (P = 0.0114). Forty-four percent of patients treated with placebo and 57.5% of patients treated with ALO-02 reported ≥30% improvement in weekly average NRS-Pain scores from screening to the final 2 weeks of the treatment period (P = 0.0248). In the double-blind treatment period, 56.8% of patients in the ALO-02 group and 56.0% of patients in the placebo group experienced a treatment-emergent adverse event (TEAE). The most common treatment-related TEAEs for ALO-02 during the treatment period were nausea, vomiting, and constipation, consistent with opioid therapy. ALO-02 has been demonstrated to provide significant reduction of pain in patients with chronic low back pain and has a safety profile similar to other opioids.

White spot lesion remineralization by sugar-free chewing gum containing bio-available calcium and fluoride: A double-blind randomized controlled trial.

PubMed

Sugiura, Miho; Kitasako, Yuichi; Sadr, Alireza; Shimada, Yasushi; Sumi, Yasunori; Tagami, Junji

2016-11-01

To assess the effect of chewing gum containing phosphoryl oligosaccharides of calcium (POs-Ca) and fluoride on white spot lesion (WSL) remineralization in comparison with POs-Ca or placebo (control) chewing gums, in double- blind, randomized, controlled trial. Thirty-seven healthy subjects, who had at least one WSL, with an ICDAS score of 2 or 1, were recruited for this study. The subjects were randomly divided into three groups (control, POs-Ca, POs-Ca+F) and chewed two slabs of each gum three times every day for 3 months. WSLs were assessed using ICDAS criteria and optical boundary depth (BD) by optical coherence tomography (OCT) system at a monthly recall. Data were analyzed by Wilcoxon rank-sum test and Wilcoxon signed rank test with Bonferroni corrections at 0.05 significance level. Visual score changes from ICDAS score 2 to score 1 over the course of the study were observed; control (30%), POs-Ca (48%) and POs-Ca+F (45%). Unlike the control gum, chewing POs-Ca and POs-Ca+F gums resulted in significant changes in the mean value of BD over the 3 months course of the study (p<0.05). There was a significant difference in mean value of BD after first month between POs-Ca+F and control groups (p<0.05). This study highlighted the importance of calcium and fluoride ion bioavailability in the reinforcement of demineralized enamel lesions by chewing gums. Furthermore, adding fluoride to POs-Ca might speed up the remineralization progress on natural WSL. Copyright © 2016 Elsevier Ltd. All rights reserved.

Lactobacillus GG (LGG) and smectite versus LGG alone for acute gastroenteritis: a double-blind, randomized controlled trial.

PubMed

Pieścik-Lech, Małgorzata; Urbańska, Magdalena; Szajewska, Hania

2013-02-01

Diarrhea treatment with either Lactobacillus GG (LGG) or smectite as an adjuvant to standard rehydration therapy has proven efficacy. In countries where both LGG and smectite are available, concomitant use is frequently practiced. We investigated whether LGG plus smectite is superior to LGG alone in the management of children with acute gastroenteritis (AGE). A double-blind, placebo-controlled, randomized trial was performed. Children aged 4 to 60 months with AGE received LGG 6 × 10(9) colony forming units/day plus randomly either smectite (3 g) or placebo as an adjuvant to the standard rehydration therapy. Of the 88 children randomized, 81 (92 %) were available for intention-to-treat analysis. The duration of diarrhea in the LGG/smectite group (n = 44) compared with the LGG/placebo group (n = 37) was similar (P = 0.43). There were no significant differences between the study groups for the secondary outcomes, with three exceptions. On day 4, in the LGG/placebo group compared to the LGG/smectite group, there was significantly reduced stool frequency (P = 0.03). While there was a significant (P = 0.05) difference in stool consistency on the Bristol Stool Form Scale on day 4, it was not of clinical relevance. Finally, in the LGG/smectite group compared to the LGG/placebo group, there was a significantly shorter duration of intravenous therapy after randomization (P = 0.02). No adverse events were observed in the study groups. LGG plus smectite and LGG alone are equally effective for treating young children with AGE. Combined use of the two interventions is not justified.

Transdermal buprenorphine in the treatment of chronic pain: results of a phase III, multicenter, randomized, double-blind, placebo-controlled study.

PubMed

Sorge, Jürgen; Sittl, Reinhard

2004-11-01

Buprenorphine, a potent opioid analgesic, has been available in parenteral and oral or sublingual(SL) formulations for >25 years. In 2001, the buprenorphine transdermal delivery system (TES) was introduced at 3 release rates (35, 52.5, and 70 microg/h) for the treatment of chronic cancer and noncancer pain. This study compared the analgesic efficacy and tolerability of buprenorphine TES at a release rate of 35 microg/h with those of buprenorphine SL and placebo in patients with severe or very severe chronic cancer or noncancer pain. This multicenter, double-blind, placebo-controlled, parallel-group trial was 1 of 3 Phase III studies involved in the clinical development of buprenorphine TDS. It comprised a 6-day open-label run-in phase in which patients received buprenorphine SL 0.8 to 1.6 mg/d as needed and a double-blind phase in which patients were randomized to receive 3 sequential patches containing buprenorphine TES 35 microg/h or placebo, each lasting 72 hours. Rescue analgesia consisting of buprenorphine SL 02-mg tablets was available as needed throughout the double-blind phase. The main outcome measures were (1) the number of buprenorphine SL tablets required in addition to buprenorphine TES during the double-blind phase compared with the placebo group and compared with the buprenorphine SL requirement during the run-in phase, and (2) patients' assessments of pain intensity, pain relief, and duration of sleep uninterrupted by pain in the double-blind phase compared with the run-in phase. Adverse events were documented throughout the study. One hundred thirty-seven patients were included in the double-blind phase (90 buprenorphine TES, 47 placebo). The buprenorphine TES group included 47 men and 43 women (mean [SD] age, 56.0 [12.1] years), and the placebo group included 23 men and 24 women (mean age, 55.7 [12.9] years). Forty-five patients had cancer-related pain and 92 had noncancer-related pain. The 2 treatment groups were comparable with respect to sex

Topiramate for the management of methamphetamine dependence: a pilot randomized, double-blind, placebo-controlled trial.

PubMed

Rezaei, Farzin; Ghaderi, Ebrahim; Mardani, Roya; Hamidi, Seiran; Hassanzadeh, Kambiz

2016-06-01

To date, no medication has been approved as an effective treatment for methamphetamine dependence. Topiramate has attracted considerable attention as a treatment for the dependence on alcohol and stimulants. Therefore, this study aimed to evaluate the effect of topiramate for methamphetamine dependence. This study was a double-blind, randomized, placebo-controlled trial. In the present investigation, 62 methamphetamine-dependent adults were enrolled and randomized into two groups, and received topiramate or a placebo for 10 weeks in escalating doses from 50 mg/day to the target maintenance dose of 200 mg/day. Addiction severity index (ASI) and craving scores were registered every week. The Beck questionnaire was also given to each participant at baseline and every 2 weeks during the treatment. Urine samples were collected at baseline and every 2 weeks during the treatment. Fifty-seven patients completed 10 weeks of the trial. There was no significant difference between both groups in the mean percentage of prescribed capsules taken by the participants. At week six, the topiramate group showed a significantly lower proportion of methamphetamine-positive urine tests in comparison with the placebo group (P = 0.01). In addition, there were significantly lower scores in the topiramate group in comparison with the placebo group in two domains of ASI: drug use severity (P < 0.001) and drug need (P < 0.001). Furthermore, the craving score (duration) significantly declined in the topiramate patients compared to those receiving the placebo. In conclusion, the results of this trial suggest that topiramate may be beneficial for the treatment of methamphetamine dependence. © 2016 Société Française de Pharmacologie et de Thérapeutique.

The effect of oscillating-energy manual therapy on lateral epicondylitis: a randomized, placebo-control, double-blinded study.

PubMed

Nourbakhsh, Mohammad Reza; Fearon, Frank J

2008-01-01

Symptoms of lateral epicondylitis (LE) are attributed to degenerative changes and inflammatory reactions in the common extensor tendon induced by microscopic tears in the tissue after repetitive or overload functions of the wrist and hand extensor muscles. Conventional treatments, provided on the premise of inflammatory basis of LE, have shown 39-80% failure rate. An alternative approach suggests that symptoms of LE could be due to active tender points developed in the origin of hand and wrist extensor muscles after overuse or repetitive movements. Oscillating-energy Manual Therapy (OEMT), also known as V-spread, is a craniosacral manual technique that has been clinically used for treating tender points over the suture lines in the skull. Considering symptoms of LE may result from active tender points, the purpose of this study was to investigate the effect of OEMT on pain, grip strength, and functional abilities of subjects with chronic LE. Twenty-three subjects with chronic LE (>3mo) between ages of 24 and 72 years participated in this study. Before their participation, all subjects were screened to rule out cervical and other pathologies that could possibly contribute to their lateral elbow pain. Subjects who met the inclusion criteria were randomized into treatment and placebo treatment groups by a second (treating) therapist. Subjects were blinded to their group assignment. Subjects in the treatment group received OEMT for six sessions. During each treatment session, first a tender point was located through palpation. After proper hand placement, the therapist focused the direction of the oscillating energy on the localized tender point. Subjects in the placebo group underwent the same procedure, but the direction of the oscillating energy was directed to an area above or below the tender points, not covering the affected area. Jamar Dynamometer, Patient Specific Functional Scale (PSFS), and Numeric Rating Scale (NRS) were used to measure grip strength

Memantine as an Adjuvant Treatment for Obsessive Compulsive Symptoms in Manic Phase of Bipolar Disorder: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

PubMed

Sahraian, Ali; Jahromi, Leila Razeghian; Ghanizadeh, Ahmad; Mowla, Arash

2017-04-01

The aim of this study is to examine the effects of memantine as an adjuvant treatment for obsessive compulsive (OC) symptoms in patients with bipolar disorder (BD) type I, manic phase. In this 16-week double-blind placebo-controlled randomized clinical trial, 58 patients in the manic phase of BD who had OC symptoms were randomly allocated to receive memantine or placebo plus their routine medications (lithium + olanzapine + clonazepam). The Yale Brown Obsessive Compulsive Behavior Scale was used to assess the outcomes. Adverse effects were also recorded. Thirty-eight patients (19 in the memantine group and 19 in the placebo group) completed the trial. Throughout the trial, the mean score decreased from 20.26 ± 5.91 to 9.73 ± 5.44 in the memantine group (P < 0.000) and from 22.89 ± 5.70 to 16.63 ± 4.00 in the placebo group (P < 0.000). At the end of the study, 15 (78.94%) patients in the memantine group and 7 (36.84%) patients in the placebo group demonstrated more than 34% decline in the Yale Brown Obsessive Compulsive Behavior Scale score (P < 0.01). No serious adverse effects were reported. Our double-blind controlled clinical trial showed that memantine is an effective adjuvant agent for reducing OC symptoms in patients with BD. However, it needs to be noted that our study is preliminary, and larger double-blind controlled studies are needed to confirm the results.

Bacteriophages for treating urinary tract infections in patients undergoing transurethral resection of the prostate: a randomized, placebo-controlled, double-blind clinical trial.

PubMed

Leitner, Lorenz; Sybesma, Wilbert; Chanishvili, Nina; Goderdzishvili, Marina; Chkhotua, Archil; Ujmajuridze, Aleksandre; Schneider, Marc P; Sartori, Andrea; Mehnert, Ulrich; Bachmann, Lucas M; Kessler, Thomas M

2017-09-26

Urinary tract infections (UTI) are among the most prevalent microbial diseases and their financial burden on society is substantial. The continuing increase of antibiotic resistance worldwide is alarming. Thus, well-tolerated, highly effective therapeutic alternatives are urgently needed. Although there is evidence indicating that bacteriophage therapy may be effective and safe for treating UTIs, the number of investigated patients is low and there is a lack of randomized controlled trials. This study is the first randomized, placebo-controlled, double-blind trial investigating bacteriophages in UTI treatment. Patients planned for transurethral resection of the prostate are screened for UTIs and enrolled if in urine culture eligible microorganisms ≥10 4 colony forming units/mL are found. Patients are randomized in a double-blind fashion to the 3 study treatment arms in a 1:1:1 ratio to receive either: a) bacteriophage (i.e. commercially available Pyo bacteriophage) solution, b) placebo solution, or c) antibiotic treatment according to the antibiotic sensitivity pattern. All treatments are intended for 7 days. No antibiotic prophylaxes will be given to the double-blinded treatment arms a) and b). As common practice, the Pyo bacteriophage cocktail is subjected to periodic adaptation cycles during the study. Urinalysis, urine culture, bladder and pain diary, and IPSS questionnaire will be completed prior to and at the end of treatment (i.e. after 7 days) or at withdrawal/drop out from the study. Patients with persistent UTIs will undergo antibiotic treatment according to antibiotic sensitivity pattern. Based on the high lytic activity and the potential of resistance optimization by direct adaptation of bacteriophages, and considering the continuing increase of antibiotic resistance worldwide, bacteriophage therapy is a very promising treatment option for UTIs. Thus, our randomized controlled trial investigating bacteriophages for treating UTIs will provide

Essential fatty acids for premenstrual syndrome and their effect on prolactin and total cholesterol levels: a randomized, double blind, placebo-controlled study

PubMed Central

2011-01-01

Objective To evaluate the effectiveness and safety of polyunsaturated fatty acids for the treatment of the premenstrual syndrome (PMS) using a graded symptom scale and to assess the effect of this treatment on basal plasma levels of prolactin and total cholesterol. Methods A randomized, double-blind, placebo-controlled study was conducted with 120 women with PMS divided into three groups and treated with 1 or 2 grams of the medication or placebo. Symptoms were recorded over a 6-month period using the Prospective Record of the Impact and Severity of Menstruation (PRISM) calendar. Total cholesterol and prolactin levels were measured. Analysis of variance (ANOVA), Pearson's chi-square test, Wilcoxon's nonparametric signed-rank test for paired samples and the Mann-Whitney nonparametric test for independent samples were used in the statistical analysis. Results There were no differences in age, marital status, schooling or ethnicity between the groups. In the group treated with 1 gram of the medication, a significant reduction was found when the median PRISM score recorded in the luteal phase at baseline (99) was compared with the median score recorded in the 3rd month (58) and in the 6th month of evaluation (35). In the 2-gram group, these differences were even more significant (baseline score: 98; 3rd month: 48; 6th month: 28). In the placebo group, there was a significant reduction at the 3rd but not at the 6th month (baseline: 96.5; 3rd month: 63.5; 6th month: 62). The difference between the phases of the menstrual cycle was greater in the 2-gram group compared to the group treated with 1 gram of the medication. There were no statistically significant differences in prolactin or total cholesterol levels between baseline values and those recorded after six months of treatment. Conclusion The difference between the groups using the medication and the placebo group with respect to the improvement in symptomatology appears to indicate the effectiveness of the drug

Placebo effect of medication cost in Parkinson disease: a randomized double-blind study.

PubMed

Espay, Alberto J; Norris, Matthew M; Eliassen, James C; Dwivedi, Alok; Smith, Matthew S; Banks, Christi; Allendorfer, Jane B; Lang, Anthony E; Fleck, David E; Linke, Michael J; Szaflarski, Jerzy P

2015-02-24

To examine the effect of cost, a traditionally "inactive" trait of intervention, as contributor to the response to therapeutic interventions. We conducted a prospective double-blind study in 12 patients with moderate to severe Parkinson disease and motor fluctuations (mean age 62.4 ± 7.9 years; mean disease duration 11 ± 6 years) who were randomized to a "cheap" or "expensive" subcutaneous "novel injectable dopamine agonist" placebo (normal saline). Patients were crossed over to the alternate arm approximately 4 hours later. Blinded motor assessments in the "practically defined off" state, before and after each intervention, included the Unified Parkinson's Disease Rating Scale motor subscale, the Purdue Pegboard Test, and a tapping task. Measurements of brain activity were performed using a feedback-based visual-motor associative learning functional MRI task. Order effect was examined using stratified analysis. Although both placebos improved motor function, benefit was greater when patients were randomized first to expensive placebo, with a magnitude halfway between that of cheap placebo and levodopa. Brain activation was greater upon first-given cheap but not upon first-given expensive placebo or by levodopa. Regardless of order of administration, only cheap placebo increased activation in the left lateral sensorimotor cortex and other regions. Expensive placebo significantly improved motor function and decreased brain activation in a direction and magnitude comparable to, albeit less than, levodopa. Perceptions of cost are capable of altering the placebo response in clinical studies. This study provides Class III evidence that perception of cost is capable of influencing motor function and brain activation in Parkinson disease. © 2015 American Academy of Neurology.

Pulsed Electromagnetic Fields in the treatment of fresh scaphoid fractures. A multicenter, prospective, double blind, placebo controlled, randomized trial.

PubMed

Hannemann, Pascal; Göttgens, Kevin W A; van Wely, Bob J; Kolkman, Karel A; Werre, Andries J; Poeze, Martijn; Brink, Peter R G

2011-05-06

The scaphoid bone is the most commonly fractured of the carpal bones. In the Netherlands 90% of all carpal fractures is a fracture of the scaphoid bone. The scaphoid has an essential role in functionality of the wrist, acting as a pivot. Complications in healing can result in poor functional outcome. The scaphoid fracture is a troublesome fracture and failure of treatment can result in avascular necrosis (up to 40%), non-union (5-21%) and early osteo-arthritis (up to 32%) which may seriously impair wrist function. Impaired consolidation of scaphoid fractures results in longer immobilization and more days lost at work with significant psychosocial and financial consequences.Initially Pulsed Electromagnetic Fields was used in the treatment of tibial pseudoarthrosis and non-union. More recently there is evidence that physical forces can also be used in the treatment of fresh fractures, showing accelerated healing by 30% and 71% reduction in nonunion within 12 weeks after initiation of therapy. Until now no double blind randomized, placebo controlled trial has been conducted to investigate the effect of this treatment on the healing of fresh fractures of the scaphoid. This is a multi center, prospective, double blind, placebo controlled, randomized trial. Study population consists of all patients with unilateral acute scaphoid fracture. Pregnant women, patients having a life supporting implanted electronic device, patients with additional fractures of wrist, carpal or metacarpal bones and pre-existing impairment in wrist function are excluded. The scaphoid fracture is diagnosed by a combination of physical and radiographic examination (CT-scanning).Proven scaphoid fractures are treated with cast immobilization and a small Pulsed Electromagnetic Fields bone growth stimulating device placed on the cast. Half of the devices will be disabled at random in the factory.Study parameters are clinical consolidation, radiological consolidation evaluated by CT-scanning, functional

Double-blind randomized controlled trial of rolls fortified with microencapsulated iron.

PubMed

Barbosa, Teresa Negreira Navarro; Taddei, José Augusto de Aguiar Carrazedo; Palma, Domingos; Ancona-Lopez, Fábio; Braga, Josefina Aparecida Pellegrini

2012-01-01

To evaluate the impact of the fortification of rolls with microencapsulated iron sulfate with sodium alginate on the hemoglobin levels in preschoolers as compared to controls. Double-blind randomized controlled trial comprised of children aged 2 to 6 years with initial hemoglobin exceeding 9 g/dL from four not-for-profit daycares randomly selected in the city of São Paulo - Brazil. Children of 2 daycares (n = 88) received rolls with fortified wheat flour as the exposed group (EC) and children of 2 daycares (n = 85) received rolls without fortification as the control group (CG) over a 24-week period. Rolls with 4 mg iron each were offered once a day, five days a week. Hemoglobin concentrations were determined in capillary blood by HemoCue® at three moments of trial: baseline (Ml), after 12 and 24 weeks of intervention (M2, M3). Hemoglobin concentration presented significant increase up to M3 in EG (11.7-12.5-12.6 g/dL) and in CG (11.1-12.4-12.3 g/dL) with higher elevations in children initially with anemia. There was significant reduction in the occurrence of anemia from 22% to 9% in EG and from 47% to 8.2% in CG at M3. Rolls fortified with microencapsulated iron sulfate were well tolerated, increased hemoglobin levels and reduced the occurrence of anemia, but with no difference compared to the control group.

Pharmacotherapy Relapse Prevention in Body Dysmorphic Disorder: A Double-Blind Placebo-Controlled Trial

PubMed Central

Phillips, Katharine A.; Keshaviah, Aparna; Dougherty, Darin; Stout, Robert L.; Menard, William; Wilhelm, Sabine

2016-01-01

Objective Body dysmorphic disorder (BDD) is common, distressing, and often severely impairing. Serotonin-reuptake inhibitors (SRIs) appear efficacious for BDD, but the few existing pharmacotherapy studies were short-term (≤4 months), and no relapse prevention studies or continuation phase studies have been conducted. We report results from the first BDD relapse prevention study. Method Adults (N=100) with DSM-IV BDD received open-label escitalopram for 14 weeks (Phase 1); 58 responders were then randomized to double-blind continuation treatment with escitalopram versus switch to placebo for six months (Phase 2). Reliable and valid outcome measures were utilized. Results Phase 1: Overall, 67.0% of treated subjects and 81.1% of completers were escitalopram responders (p’s<0.0001). BDD severity, BDD-related insight, depressive symptoms, psychosocial functioning, and quality of life significantly improved from baseline to end of Phase 1 (all p's<0.0001). Phase 2: Time to relapse was significantly longer for subjects receiving escitalopram than those receiving placebo (hazard ratio=2.72, 95% CI [1.01, 8.57], p=0.049). Phase 2 relapse proportions were 18% for escitalopram versus 40% for placebo. In escitalopram-treated subjects, BDD severity significantly decreased over time during the continuation treatment phase (p=0.036); further improvement occurred in 35.7% of the escitalopram group. There were no significant group differences in BDD severity, insight, depressive symptoms, psychosocial functioning, or quality of life. Conclusions Continuation-phase escitalopram delayed time to relapse, and fewer escitalopram-treated subjects relapsed compared with placebo-treated subjects. BDD severity significantly further improved during six additional months of escitalopram treatment following acute response; more than one-third of escitalopram-treated subjects had further improvement during continuation phase treatment. PMID:27056606

Topical Botulinum Toxin Type A Liposomal Cream for Primary Axillary Hyperhidrosis: A Double-Blind, Randomized, Split-Site, Vehicle-Controlled Study.

PubMed

Lueangarun, Suparuj; Sermsilp, Chairat; Tempark, Therdpong

2018-04-13

Despite its effectiveness in treating primary axillary hyperhidrosis (PAH), topical botulinum toxin type A (BTX-A) is highly resistant to transdermal absorption. Topical BTX-A liposomal cream is recommended as a novel, noninvasive modality to enhance skin penetration. To evaluate the efficacy and safety of topical BTX-A liposomal cream in comparison with liposomal vehicle cream alone in the treatment of PAH. A prospective, randomized, double-blinded, split-site study was conducted in 20 subjects, aged 18 to 50 years, all of whom had symmetrical axillary sweating with Hyperhidrosis Disease Severity Scale scores between 2 to 4. All subjects were double-blinded to treatment regimens and randomly given 2 bottles, one containing topical BTX-A liposomal cream and one containing the vehicle cream without BTX-A, to be applied consistently to the same axilla nightly for 7 consecutive days. Clinical improvement and adverse reactions were evaluated at every follow-up visit. Axillary skin treated with topical BTX-A demonstrated superior sweat reduction and patient satisfaction to vehicle cream-treated axillary skin, with clinical and statistical significance, at baseline, weeks 2, 4, 6, and 8 of follow-up, without adverse effects. Topical BTX-A liposomal cream pharmaceutically enhances drug delivery, is painless, cost-effective, and overall an innovative treatment of PAH.

Blind or ultrasound-guided corticosteroid injections and short-term response in subacromial impingement syndrome: a randomized, double-blind, prospective study.

PubMed

Dogu, Beril; Yucel, Serap Dalgic; Sag, Sinem Yamac; Bankaoglu, Mujdat; Kuran, Banu

2012-08-01

The aim of this study was to compare the accuracy of blind vs. ultrasonography-guided corticosteroid injections in subacromial impingement syndrome and determine the correlation between accuracy of the injection location and clinical outcome. Forty-six patients with subacromial impingement syndrome were randomized for ultrasonography-guided (group 1, n = 23) and blind corticosteroid injections (group 2, n = 23). Magnetic resonance imaging analysis was performed immediately after the injection. Changes in shoulder range of motion, pain, and shoulder function were recorded. All patients were assessed before the injection and 6 wks after the injection. Accurate injections were performed in 15 (65%) group 1 patients and in 16 (70%) group 2 patients. There was no statistically significant difference in the injection location accuracy between the two groups (P > 0.05). At the end of the sixth week, regardless of whether the injected mixture was found in the subacromial region or not, all of the patients showed improvements in all of the parameters evaluated (P < 0.05). Blind injections performed in the subacromial region by experienced individuals were reliably accurate and could therefore be given in daily routines. Corticosteroid injections in the subacromial region were very effective in improving the pain and functional status of patients with subacromial impingement syndrome during the short-term follow-up.

Efficacy and safety of pimecrolimus cream 1% in mild-to-moderate chronic hand dermatitis: a randomized, double-blind trial.

PubMed

Hordinsky, Maria; Fleischer, Alan; Rivers, Jason K; Poulin, Yves; Belsito, Donald; Hultsch, Thomas

2010-08-01

Chronic hand dermatitis is common and difficult to treat. Our aim was to assess the efficacy of pimecrolimus cream 1% in mild-to-moderate chronic hand dermatitis. Adult patients (n = 652) were randomized to pimecrolimus 1% or vehicle cream twice daily with overnight occlusion for 6 weeks, followed by a 6-week open-label pimecrolimus treatment. Primary efficacy was 5-point Investigators' Global Assessment of prospectively selected 'target hand' as treatment success (Investigators' Global Assessment 0 or 1) and treatment failure. Pruritus relief was also assessed. Following double-blind phase treatment, target hand treatment success was achieved in 29.8 and 23.2% of the patients in the pimecrolimus and vehicle groups, respectively (p = 0.057). The proportion of patients experiencing pruritus relief was significantly higher in the pimecrolimus group compared to the vehicle group at all time points throughout the double-blind phase. The groups were comparable with respect to treating disease signs. Pruritus relief, however, was significantly greater in the pimecrolimus group. Copyright 2010 S. Karger AG, Basel.

Intravenous dextrose for children with gastroenteritis and dehydration: a double-blind randomized controlled trial.

PubMed

Levy, Jason A; Bachur, Richard G; Monuteaux, Michael C; Waltzman, Mark

2013-03-01

We seek to determine whether an initial intravenous bolus of 5% dextrose in normal saline solution compared with normal saline solution will lead to a lower proportion of hospitalized patients and a greater reduction in serum ketone levels in children with gastroenteritis and dehydration. We enrolled children aged 6 months to 6 years in a double-blind, randomized controlled trial of patients presenting to a pediatric emergency department. Subjects were randomized to receive a 20 mL/kg infusion of either 5% dextrose in normal saline solution or normal saline solution. Serum ketone levels were measured before and at 1- and 2-hour intervals after the initial study fluid bolus administration. Primary outcome was the proportion of children hospitalized. Secondary outcome was change in serum ketone levels over time. One hundred eighty-eight children were enrolled. The proportion of children hospitalized did not differ between groups (35% in the 5% dextrose in normal saline solution group versus 44% in the normal saline solution group; risk difference 9%; 95% confidence interval [CI] -5% to 22%). Compared with children who received normal saline solution, those who received 5% dextrose in normal saline solution had a greater reduction in mean serum ketone levels at both 1 hour (mean Δ 1.2 versus 0.1 mmol/L; mean difference 1.1 mmol/L; 95% CI 0.4 to 1.9 mmol/L) and 2 hours (mean Δ 1.9 versus 0.3 mmol/L; mean difference 1.6 mmol/L; 95% CI 0.9 to 2.3 mmol/L). Administration of a dextrose-containing bolus compared with normal saline did not lead to a lower rate of hospitalization for children with gastroenteritis and dehydration. There was, however, a greater reduction in serum ketone levels in patients who received 5% dextrose in normal saline solution. Copyright © 2012. Published by Mosby, Inc.

The efficacy of cetirizine hydrochloride on the pruritus of cats with atopic dermatitis: a randomized, double-blind, placebo-controlled, crossover study.

PubMed

Wildermuth, Kerstin; Zabel, Sonja; Rosychuk, Rod A W

2013-12-01

Various antihistamines have been used in the management of feline atopic dermatitis, with variable reported benefit. To date, there have been no randomized, double-blind, placebo-controlled, crossover clinical trials on the use of this drug class in cats. To evaluate the clinical efficacy of cetirizine hydrochloride for the control of pruritus and dermatitis in cats diagnosed with atopic dermatitis. In this randomized, double-blind, placebo-controlled crossover clinical trial, 21 client-owned cats diagnosed with mild to moderate nonseasonal atopic dermatitis were randomly assigned to two groups. Cats in each group received either 1 mg/kg cetirizine hydrochloride or placebo once daily per os for 28 days followed by a 14 day wash-out period. Treatments were then crossed over, and cats received placebo or cetirizine hydrochloride for another 28 days. Owners marked a pruritus severity scale before inclusion in the study and weekly throughout the entire study period. Lesions were scored by the clinician using a Canine Atopic Dermatitis Extent and Severity Index (CADESI)-03 modified for the cat before enrolment and at day 28 of each treatment. Nineteen cats completed the study. There were no statistically significant differences between treatment with cetirizine hydrochloride and placebo for modified CADESI-03 or pruritus scores. This study suggests that cetirizine hydrochloride cannot be recommended for the management of feline atopic dermatitis. © 2013 ESVD and ACVD.

Randomized double-blind placebo-controlled trial of buccal misoprostol to reduce the need for additional uterotonic drugs during cesarean delivery.

PubMed

Hernández-Castro, Flavio; López-Serna, Norberto; Treviño-Salinas, Emilio M; Soria-López, Juan A; Sordia-Hernández, Luis H; Cárdenas-Estrada, Eloy

2016-02-01

To determine whether buccal misoprostol during cesarean delivery in conjunction with active management of the third stage of labor reduces the need for additional uterotonic drugs. A double-blind, randomized, placebo-controlled trial was performed in Monterrey, Mexico, between February 2008 and December 2013. Eligible women had risk factors for uterine atony and were to undergo cesarean delivery under epidural block. Using a computer-generated sequence and blocks of six, patients were randomly assigned to receive 400μg misoprostol or 800μg placebo buccally after cord clamping. Both groups received an intravenous oxytocin infusion. The primary outcome was the need for additional uterotonic drugs. Analyses were performed per protocol. Patients, investigators, and data analysts were masked to group assignment. A total of 120 women were included in analyses (60 in each group). At least one additional uterotonic drug was required in 24 (40%) women in the placebo group versus 6 (10%) women in the misoprostol group (relative risk 0.16; 95% confidence interval 0.06-0.44). No adverse effects due to misoprostol were recorded. Buccal misoprostol during cesarean delivery reduced the need for additional uterotonic drugs to treat uterine atony. ClinicalTrials.gov:NCT01733329. Copyright © 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Effects of 6 months of resveratrol versus placebo on pentraxin 3 in patients with type 2 diabetes mellitus: a double-blind randomized controlled trial.

PubMed

Bo, S; Ponzo, V; Evangelista, A; Ciccone, G; Goitre, I; Saba, F; Procopio, M; Cassader, M; Gambino, R

2017-05-01

The anti-inflammatory effects of the polyphenol resveratrol in patients with type 2 diabetes mellitus (T2DM) are controversial. Its role on pentraxin 3 (PTX3) concentrations, a human acute phase protein, has never been evaluated. Our aim was to determine whether a two-dosage resveratrol supplementation (500 and 40 mg/day) has an impact on PTX3 values in T2DM patients from a double-blind randomized placebo-controlled trial. Variations in total antioxidant status (TAS) were evaluated too. A total of 192 T2DM patients were randomized to receive resveratrol 500 mg/day (Resv 500 arm), resveratrol 40 mg/day (Resv 40 arm) or placebo for 6 months. At baseline and at the trial end, PTX3 and TAS values were determined. A dose-dependent increase in PTX3 concentrations of 4.7% (Resv 40 arm) and 26.3% (Resv 500 arm), and 8.0% reduction after placebo were found. Adjusted mean differences of change versus placebo were 0.16 (95% CI 0.01-0.32) and 0.25 (0.09-0.42) in the Resv 40 and Resv 500 arms, respectively. At subgroup analyses, lower diabetes duration, aspirin, alcohol use, younger age, female gender, smoking (Resv 500 arm) and female gender and aspirin use (Resv 40 arm) were associated with higher PTX3 increments. A dose-dependent increment in TAS values in the resveratrol arms (1.4 and 6.4% for Resv 40 and Resv 500, respectively), and a reduction in placebo arm (-8.9%) were observed. Adjusted mean differences of change were 28.5 (95% CI 10.1-46.8) and 44.8 (25.4-64.1) in the Resv 40 and Resv 500 arms, respectively. Resveratrol supplementation increased PTX3 and TAS levels in a dose-dependent manner in T2DM patients. At present, potential clinical implications of these results remain unclear. CLINICALTRIALS. NCT02244879.

Lansoprazole 15 mg once daily for 14 days is effective for treatment of frequent heartburn: results of 2 randomized, placebo-controlled, double-blind studies.

PubMed

Kushner, Pamela R; Snoddy, Andrew M; Gilderman, Larry; Peura, David A

2009-07-01

To investigate the efficacy and safety of a 14-day treatment period with lansoprazole 15 mg for frequent heartburn in patients who are likely to select a nonprescription medication before consulting a prescriber. Adults with untreated frequent heartburn > or = 2 days a week over the past month were recruited for 2 identical multicenter, double-blind studies conducted with a 1-week screening and heartburn medication washout, a 1-week placebo run-in, a 2-week placebo-controlled treatment, and a 1-week placebo follow-up. After the washout and placebo run-in, subjects were randomly assigned to receive lansoprazole 15 mg or placebo once daily for 14 days in a double-blind fashion. Antacid tablets were permitted as rescue medication. Endpoints included percentage of 24-hour days without heartburn (primary), percentage of night-times without heartburn, and percentage of subjects without heartburn during day 1 of treatment (secondary endpoints). Data were collected daily via an interactive voice response system. In studies 1 and 2, 282 and 288 subjects, respectively, were randomly assigned to lansoprazole, and 282 in each study received placebo. The mean percentage of days without heartburn was greater among lansoprazole recipients compared with placebo recipients (P < 0.0001). Significantly more subjects treated with lansoprazole also reported no night-time heartburn and no heartburn during day 1 of the 14-day treatment. Adverse events were infrequent and were similar for lansoprazole and placebo groups. During the 14-day treatment period in a population with frequent heartburn who were likely to select a medication without consulting a prescriber, lansoprazole 15 mg once daily showed rapid and sustained effectiveness throughout a 24-hour period and was well tolerated.

Botulinum toxin, a new treatment modality for chronic idiopathic constipation in children: long-term follow-up of a double-blind randomized trial.

PubMed

Keshtgar, Alireza S; Ward, Harry C; Sanei, Ahmad; Clayden, Graham S

2007-04-01

Myectomy of the internal anal sphincter (IAS) has been performed on some children after failure of medical treatment to treat idiopathic constipation. The aim of this study was to compare botulinum toxin injection with myectomy of the IAS in the treatment of chronic idiopathic constipation and soiling in children. This was a double-blind randomized trial. Patients between 4 and 16 years old were included in the study if they had failed to respond to laxative treatment and anal dilatation for chronic idiopathic constipation. All study patients had anorectal manometry and anal endosonography under ketamine anesthesia. Outcome was measured using a validated symptom severity (SS) scoring system, with scores ranging from 0 to 65. Of 42 children, 21 were randomized to the botulinum group and 21 were randomized to the myectomy group. At the 3-month follow-up, the median preoperative SS score improved from 34 (range = 19-47) to 20 (range = 2-43) in the botulinum group (P < .001) and from 31 (range = 18-49) to 19 (range = 3-47) in the myectomy group (P < .002). At the 12-month follow-up, the scores were 19 (range = 0-45) and 14.5 (range = 0-41) for the botulinum group and the myectomy group, respectively (P < .0001). There was no complication in both groups. Botulinum toxin is equally effective as and less invasive than myectomy of the IAS for chronic idiopathic constipation and fecal incontinence in children.

Effect of Uric Acid-Lowering Agents on Endothelial Function: A Randomized, Double-Blind, Placebo-Controlled Trial.

PubMed

Borgi, Lea; McMullan, Ciaran; Wohlhueter, Ann; Curhan, Gary C; Fisher, Naomi D; Forman, John P

2017-02-01

Higher levels of serum uric acid are independently associated with endothelial dysfunction, a mechanism for incident hypertension. Overweight/obese individuals are more prone to endothelial dysfunction than their lean counterparts. However, the effect of lowering serum uric acid on endothelial dysfunction in these individuals has not been examined thoroughly. In this randomized, double-blind, placebo-controlled trial of nonhypertensive, overweight, or obese individuals with higher serum uric acid (body mass index ≥25 kg/m 2 and serum uric acid ≥5.0 mg/dL), we assigned subjects to probenecid (500-1000 mg/d), allopurinol (300-600 mg/d), or matching placebo. The primary outcome was endothelium-dependent vasodilation measured by brachial artery ultrasound at baseline and 8 weeks. By the end of the trial, 47, 49, and 53 participants had been allocated to receive probenecid, allopurinol, and placebo, respectively. Mean serum uric acid levels significantly decreased in the probenecid (from 6.1 to 3.5 mg/dL) and allopurinol groups (from 6.1 to 2.9 mg/dL) but not in the placebo group (6.1 to 5.6 mg/dL). None of the interventions produced any significant change in endothelium-dependent vasodilation (probenecid, 7.4±5.1% at baseline and 8.3±5.1% at 8 weeks; allopurinol, 7.6±6.0% at baseline and 6.2±4.8% at 8 weeks; and placebo, 6.5±3.8% at baseline and 7.1±4.9% at 8 weeks). In this randomized, double-blind, placebo-controlled trial, uric acid lowering did not affect endothelial function in overweight or obese nonhypertensive individuals. These data do not support the hypothesis that uric acid is causally related to endothelial dysfunction, a potential mechanism for development of hypertension. © 2016 American Heart Association, Inc.

Xylitol pediatric topical oral syrup to prevent dental caries: a double-blind randomized clinical trial of efficacy.

PubMed

Milgrom, Peter; Ly, Kiet A; Tut, Ohnmar K; Mancl, Lloyd; Roberts, Marilyn C; Briand, Kennar; Gancio, Mary Jane

2009-07-01

To evaluate the effectiveness of a xylitol pediatric topical oral syrup to reduce the incidence of dental caries among very young children and to evaluate the effect of xylitol in reducing acute otitis media in a subsequent study. Double-blind randomized controlled trial. Communities in the Republic of the Marshall Islands. One hundred eight children aged 9 to 15 months were screened, and 100 were enrolled. Intervention Children were randomized to receive xylitol topical oral syrup (administered by their parents) twice a day (2 xylitol [4.00-g] doses and 1 sorbitol dose) (Xyl-2 x group) or thrice per day (3 xylitol [2.67-g] doses) (Xyl-3x group) vs a control syrup (1 xylitol [2.67-g] dose and 2 sorbitol doses) (control group). The primary outcome end point of the study was the number of decayed primary teeth. A secondary outcome end point was the incidence of acute otitis media for reporting in a subsequent report. Ninety-four children (mean [SD] age, 15.0 [2.7] months at randomization) with at least 1 follow-up examination were included in the intent-to-treat analysis. The mean (SD) follow-up period was 10.5 (2.2) months. Fifteen of 29 of the children in the control group (51.7%) had tooth decay compared with 13 of 32 children in the Xyl-3x group (40.6%) and eight of 33 children in the Xyl-2x group (24.2%). The mean (SD) numbers of decayed teeth were 1.9 (2.4) in the control group, 1.0 (1.4) in the Xyl-3x group, and 0.6 (1.1) in the Xyl-2x group. Compared with the control group, there were significantly fewer decayed teeth in the Xyl-2x group (relative risk, 0.30; 95% confidence interval, 0.13-0.66; P = .003) and in the Xyl-3x group (0.50; 0.26-0.96; P = .04). No statistical difference was noted between the 2 xylitol treatment groups (P = .22). Xylitol oral syrup administered topically 2 or 3 times daily at a total daily dose of 8 g was effective in preventing early childhood caries.

Neurofeedback to improve neurocognitive functioning of children treated for a brain tumor: design of a randomized controlled double-blind trial.

PubMed

de Ruiter, Marieke A; Schouten-Van Meeteren, Antoinette Y N; van Mourik, Rosa; Janssen, Tieme W P; Greidanus, Juliette E M; Oosterlaan, Jaap; Grootenhuis, Martha A

2012-12-06

Neurotoxicity caused by treatment for a brain tumor is a major cause of neurocognitive decline in survivors. Studies have shown that neurofeedback may enhance neurocognitive functioning. This paper describes the protocol of the PRISMA study, a randomized controlled trial to investigate the efficacy of neurofeedback to improve neurocognitive functioning in children treated for a brain tumor. Efficacy of neurofeedback will be compared to placebo training in a randomized controlled double-blind trial. A total of 70 brain tumor survivors in the age range of 8 to 18 years will be recruited. Inclusion also requires caregiver-reported neurocognitive problems and being off treatment for more than two years. A group of 35 healthy siblings will be included as the control group. On the basis of a qEEG patients will be assigned to one of three treatment protocols. Thereafter patients will be randomized to receive either neurofeedback training (n=35) or placebo training (n=35). Neurocognitive tests, and questionnaires administered to the patient, caregivers, and teacher, will be used to evaluate pre- and post-intervention functioning, as well as at 6-month follow-up. Siblings will be administered the same tests and questionnaires once. If neurofeedback proves to be effective for pediatric brain tumor survivors, this can be a valuable addition to the scarce interventions available to improve neurocognitive and psychosocial functioning. ClinicalTrials.gov NCT00961922.

Effect of methylphenidate and/or levodopa coupled with physiotherapy on functional and motor recovery after stroke--a randomized, double-blind, placebo-controlled trial.

PubMed

Lokk, J; Salman Roghani, R; Delbari, A

2011-04-01

Amphetamine-like drugs are reported to enhance motor recovery and activities of daily living (ADL) in stroke rehabilitation, but results from trials with humans are inconclusive. This study is aimed at investigating whether levodopa (LD) and/or methylphenidate (MPH) in combination with physiotherapy could improve functional motor recovery and ADL in patients with stroke. A randomized, double-blind, placebo-controlled trial with ischemic stroke patients randomly allocated to one of four treatment groups of either MPH, LD or MPH+LD or placebo combined with physiotherapy was performed. Motor function, ADL, and stroke severity were assessed by Fugl-Meyer (FM), Barthel index (BI), and National Institute of Health Stroke Scale (NIHSS) at baseline, 15, 90, and 180 days respectively. All participants showed recovery of motor function and ADL during treatment and at 6-month follow-up. There were slightly but significant differences in BI and NIHSS compared to placebo at the 6-month follow-up. Ischemic chronic stroke patients having MPH and/or LD in combination with physiotherapy showed a slight ADL and stroke severity improvement over time. Future studies should address the issue of the optimal therapeutic window and dosage of medications to identify those patients who would benefit most. © 2010 John Wiley & Sons A/S.

A double-blind randomized placebo-controlled trial with short-term beta-glucuronidase therapy in children with chronic rhinoconjunctivitis and/or asthma due to dust mite allergy.

PubMed

Galli, E; Bassi, M S; Mora, E; Martelli, M; Gianni, S; Auricchio, G; Arabito, E; Rossi, P

2006-01-01

Enzyme potentiated desensitization, in which beta-glucuronidase (BG) is administered with low doses of mixed allergens, was proposed in the 1970s for specific immunotherapy. The BG currently commercially available in a purified and standardized preparation devoid of any allergen has been suggested as a regulator in the allergic immune response, acting on the cytokine-network of type 2 helper T cells. A double-blind trial with a single-dose of BG proved effective in preventing symptoms in adult patients with rhinoconjunctivitis due to grass pollens. The aim of this randomized double-blind placebo-controlled trial was to confirm the safety and effectiveness of double-dose intradermal BG immunotherapy in preventing symptoms in children suffering from chronic rhinoconjunctivitis and/or asthma due to dust mite. We randomized 125 children with dust-mite related chronic rhinoconjunctivitis and/or asthma to the BG treated group (67) or the placebo group (58). All patients were screened before treatment (TO), at BG or placebo administration (T1 and T3), and at 3 and 9 months after T1 (T2 and T4). Drug intake and bronchial, nasal and ocular symptoms were recorded in a diary. Patients in both groups completed the study and BG treatment was well tolerated without side effects. Significant differences in symptoms were observed, in particular for conjunctivitis (P= .008). The total drug intake for allergic symptoms was significantly lower in the treated group than in the placebo group (P<. 01). BG immunotherapy is efficacious, safe, and well tolerated in allergic children. Moreover, good compliance with the administration of 2 doses per year and the lack of significant side effects makes the benefit/risk ratio of this treatment particularly favorable.

Solifenacin in the treatment of urgency and other symptoms of overactive bladder: results from a randomized, double-blind, placebo-controlled, rising-dose trial.

PubMed

Cardozo, Linda; Hessdörfer, Elke; Milani, Rodolfo; Arañó, Pedro; Dewilde, Luc; Slack, Mark; Drogendijk, Ted; Wright, Mark; Bolodeoku, John

2008-11-01

To examine the effects of the antimuscarinic agent solifenacin on urinary urgency, using a range of novel and established outcome measures, as urgency is the principal symptom of the overactive bladder syndrome (OAB). The study (SUNRISE, solifenacin in the treatment of urgency symptoms of OAB in a rising dose, randomized, placebo-controlled, double-blind, efficacy trial) was a randomized, double-blind, 16-week, placebo-controlled, multicentre study of solifenacin 5/10 mg in 863 patients with symptoms of OAB for > or = 3 months. The primary efficacy variable was the change from baseline to endpoint in the number of episodes of severe urgency with or without urgency incontinence per 24 h, as measured using the Patient Perception of Intensity of Urgency Scale, grade 3 + 4. Secondary efficacy variables included patient-reported outcomes for bladder condition, urgency bother and treatment satisfaction. A 3-day voiding diary was used to record micturition frequency and episodes of urgency and incontinence. A 7-day diary was used to assess speed of onset of effect. Solifenacin 5/10 mg was significantly more effective than placebo in reducing the mean number of episodes of severe urgency with or without incontinence per 24 h from baseline to endpoint (-2.6 vs -1.8, P < 0.001). There were also statistically significant differences in favour of solifenacin 5/10 mg over placebo for all secondary variables measured at endpoint, including patient-reported outcomes. There was a significant improvement in urgency as early as day 3 of treatment. Treatmente-mergent adverse events with solifenacin 5/10 mg were mainly mild or moderate in severity, and only led to discontinuation in 3.6% of patients. Solifenacin significantly reduced the number of urgency episodes and the extent of urgency bother, and was well tolerated; it was effective as early as day 3 of treatment.

Protection of Salivary Function by Concomitant Pilocarpine During Radiotherapy: A Double-Blind, Randomized, Placebo-Controlled Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burlage, Fred R.; Roesink, Judith M.; Kampinga, Harm H.

2008-01-01

Purpose: To investigate the effect of concomitant administration of pilocarpine during radiotherapy for head-and-neck squamous cell carcinoma (HNSCC) on postradiotherapy xerostomia. Methods and Materials: A prospective, double blind, placebo-controlled randomized trial including 170 patients with HNSCC was executed to study the protective effect of pilocarpine on radiotherapy-induced parotid gland dysfunction. The primary objective endpoint was parotid flow rate complication probability (PFCP) scored 6 weeks, 6 months, and 12 months after radiotherapy. Secondary endpoints included Late Effects of Normal Tissue/Somatic Objective Management Analytic scale (LENT SOMA) and patient-rated xerostomia scores. For all parotid glands, dose-volume histograms were assessed because the dosemore » distribution in the parotid glands is considered the most important prognostic factor with regard to radiation-induced salivary dysfunction. Results: Although no significant differences in PFCP were found for the two treatments arms, a significant (p = 0.03) reduced loss of parotid flow 1 year after radiotherapy was observed in those patients who received pilocarpine and a mean parotid dose above 40 Gy. The LENT SOMA and patient-rated xerostomia scores showed similar trends toward less dryness-related complaints for the pilocarpine group. Conclusions: Concomitant administration of pilocarpine during radiotherapy did not improve the PFCP or LENT SOMA and patient-rated xerostomia scores. In a subgroup of patients with a mean dose above 40 Gy, pilocarpine administration resulted in sparing of parotid gland function. Therefore, pilocarpine could be provided to patients in whom sufficient sparing of the parotid is not achievable.« less

Six-Month Evaluation of a Sodium Bicarbonate-Containing Toothpaste for Reduction of Established Gingivitis: A Randomized USA-Based Clinical Trial.

PubMed

Jose, Anto; Pratten, Jonathan; Bosma, Mary-Lynn; Milleman, Kimberly R; Milleman, Jeffery L; Wang, Nan

2018-03-01

Short-term use of sodium bicarbonate (NaHCO3)-containing toothpaste reduces plaque and improves clinical measures of gingivitis. To examine this over a longer period, we compared efficacy and tolerability of twice-daily brushing for 24 weeks with 67% or 0% NaHCO3-containing toothpastes in USA-based participants with moderate gingivitis (Clinicaltrials.gov:NCT02207400). This was a six-month, randomized, examiner-blind, parallel-group, clinical trial. Investigators randomized adults with blood in expectorate after brushing and ≥ 20 gingival bleeding sites to 67% NaHCO3 (n = 123; n = 107 completed study) or 0% NaHCO3 (n = 123; n = 109 completed study) toothpastes. Primary efficacy variables included between-treatment differences in number of bleeding sites and Modified Gingival Index (MGI) score at 24 weeks. Secondary efficacy variables included Bleeding Index and Turesky modification of the Quigley-Hein Plaque Index (overall and interproximal sites) at six, 12, and 24 weeks. A subset of 50 participants underwent sampling to assess plaque microbiology over the course of treatment. Compared with the 0% NaHCO3 toothpaste, the 67% NaHCO3 toothpaste produced statistically significant improvements at Week 24 in number of bleeding sites (46.7% difference) and MGI (33.9% difference), and for all other endpoints (all p < 0.0001). There was no significant between-treatment difference in the proportion of participants harboring opportunistic pathogens. Products were generally well tolerated, with two and five treatment-related adverse events reported in the 67% and 0% NaHCO3 toothpaste groups, respectively. Gingival bleeding, gingivitis, and plaque indices were significantly improved at six, 12, and 24 weeks with twice-daily brushing with 67% NaHCO3-containing toothpaste in participants with moderate gingivitis. Copyright© by the YES Group, Inc.

Ringers lactate vs Normal saline for children with acute diarrhea and severe dehydration- a double blind randomized controlled trial.

PubMed

Mahajan, Vidushi; Sajan, Shiv Saini; Sharma, Amit; Kaur, Jasbinder

2012-12-01

WHO recommends Ringers lactate (RL) and Normal Saline (NS) for rapid intravenous rehydration in childhood diarrhea and severe dehydration. We compared these two fluids for improvement in pH over baseline during rapid intravenous rehydration in children with acute diarrhea. Double-blind randomized controlled trial Pediatric emergency facilities at a tertiary-care referral hospital. Children with acute diarrhea and severe dehydration received either RL (RL-group) or NS (NS-group), 100 mL/kg over three or six hours. Children were reassessed after three or six hours. Rapid rehydration was repeated if severe dehydration persisted. Blood gas was done at baseline and repeated after signs of severe dehydration disappeared. Primary outcome was change in pH from baseline. Secondary outcomes included changes in serum electrolytes, bicarbonate levels, and base-deficit from baseline; mortality, duration of hospital stay, and fluids requirement. Twenty two children, 11 each were randomized to the two study groups. At primary end point (disappearance of signs of severe dehydration), the improvement in pH from baseline was not significant in RL-group [from 7.17 (0.11) to 7.28 (0.09)] as compared to NS-group [7.09 (0.11) to 7.21 (0.09)], P=0.17 (after adjusting for baseline serum Na/ Cl). Among this limited sample size, children in RL group required less fluids [median 310 vs 530 mL/kg, P=0.01] and had shorter median hospital stay [38 vs 51 hours, P=0.03]. There was no difference in improvement in pH over baseline between RL and NS among children with acute diarrhea and severe dehydration.

Do TETRA (Airwave) base station signals have a short-term impact on health and well-being? A randomized double-blind provocation study.

PubMed

Wallace, Denise; Eltiti, Stacy; Ridgewell, Anna; Garner, Kelly; Russo, Riccardo; Sepulveda, Francisco; Walker, Stuart; Quinlan, Terence; Dudley, Sandra; Maung, Sithu; Deeble, Roger; Fox, Elaine

2010-06-01

"Airwave" is the new communication system currently being rolled out across the United Kingdom for the police and emergency services, based on the Terrestrial Trunked Radio Telecommunications System (TETRA). Some police officers have complained about skin rashes, nausea, headaches, and depression as a consequence of using their Airwave handsets. In addition, a small subgroup in the population self-report being sensitive to electromagnetic fields (EMFs) in general. We conducted a randomized double-blind provocation study to establish whether short-term exposure to a TETRA base station signal has an impact on the health and well-being of individuals with self-reported "electrosensitivity" and of participants who served as controls. Fifty-one individuals with self-reported electrosensitivity and 132 age- and sex-matched controls participated in an open provocation test; 48 sensitive and 132 control participants went on to complete double-blind tests in a fully screened semianechoic chamber. Heart rate, skin conductance, and blood pressure readings provided objective indices of short-term physiological response. Visual analog scales and symptom scales provided subjective indices of well-being. We found no differences on any measure between TETRA and sham (no signal) under double-blind conditions for either controls or electrosensitive participants, and neither group could detect the presence of a TETRA signal at rates greater than chance (50%). When conditions were not double blind, however, the self-reported electrosensitive individuals did report feeling worse and experienced more severe symptoms during TETRA compared with sham. Our findings suggest that the adverse symptoms experienced by electrosensitive individuals are due to the belief of harm from TETRA base stations rather than to the low-level EMF exposure itself.

MIDAS (Modafinil in Debilitating Fatigue After Stroke): A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Trial.

PubMed

Bivard, Andrew; Lillicrap, Thomas; Krishnamurthy, Venkatesh; Holliday, Elizabeth; Attia, John; Pagram, Heather; Nilsson, Michael; Parsons, Mark; Levi, Christopher R

2017-05-01

This study aimed to assess the efficacy of modafinil, a wakefulness-promoting agent in alleviating post-stroke fatigue ≥3 months after stroke. We hypothesized that 200 mg of modafinil daily for 6 weeks would result in reduced symptoms of fatigue compared with placebo. This single-center phase 2 trial used a randomized, double-blind, placebo-controlled, crossover design. The key inclusion criterion was a multidimensional fatigue inventory score of ≥60. Patients were randomized to either modafinil or placebo for 6 weeks of therapy, then after a 1 week washout period swapped treatment arms for a second 6 weeks of therapy. The primary outcome was the multidimensional fatigue inventory; secondary outcomes included the Montreal cognitive assessment, the Depression, Anxiety, and Stress Scale (DASS), and the Stroke-Specific Quality of Life (SSQoL) scale. The multidimensional fatigue inventory is a self-administered questionnaire with a range of 0 to 100. Treatment efficacy was assessed using linear regression by estimating within-person, baseline-adjusted differences in mean outcomes after therapy. This trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12615000350527). A total of 232 stroke survivors were screened and 36 were randomized. Participants receiving modafinil reported a significant decrease in fatigue (multidimensional fatigue inventory, -7.38; 95% CI, -21.76 to -2.99; P <0.001) and improved quality of life (SSQoL, 11.81; 95% CI, 2.31 to 21.31; P =0.0148) compared with placebo. Montreal cognitive assessment and DASS were not significantly improved with modafinil therapy during the study period ( P >0.05). Stroke survivors with nonresolving fatigue reported reduced fatigue and improved quality of life after taking 200 mg daily treatment with modafinil. URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368268. Unique identifier: ACTRN12615000350527. © 2017 The Authors.

Treatment of tension-type headache with articulatory and suboccipital soft tissue therapy: A double-blind, randomized, placebo-controlled clinical trial.

PubMed

Espí-López, Gemma V; Gómez-Conesa, Antonia; Gómez, Anna Arnal; Martínez, Josep Benítez; Pascual-Vaca, Angel Oliva; Blanco, Cleofás Rodríguez

2014-10-01

This study researches the effectiveness of two manual therapy treatments focused on the suboccipital region for tension-type headache. A randomized double-blind clinical trial was conducted over a period of four weeks with a follow-up at one month. Eighty-four patients with a mean age of 39.7 years (SD 11.4) with tension-type headache were assigned to 4 groups which included the following manual therapy treatment: suboccipital soft tissue inhibition; occiput-atlas-axis global manipulation; combination of both techniques; and a control group. The primary assessment consisted of collecting socio-demographic data and headache characteristics in a one-month base period, data such as age, gender, severity of pain, intensity and frequency of headache, among other. Outcome secondary assessment were: impact of headache, disability, ranges of motion of the craniocervical junction, frequency and intensity of headache, and pericranial tenderness. In the month prior to the study, average pain intensity, was rated at 6.49 (SD 1.69), and 66.7% subjects suffered headaches of moderate intensity. After 8 weeks, statistically significant improvements were noted. OAA manipulative treatment and combined therapy treatments proved to be more effective than suboccipital soft tissue inhibition for tension-type headache. The treatment with suboccipital soft tissue inhibition, despite producing less significant results, also has positive effects on different aspects of headache. Copyright © 2014 Elsevier Ltd. All rights reserved.

Sono-electro-magnetic therapy for treating chronic pelvic pain syndrome in men: a randomized, placebo-controlled, double-blind trial.

PubMed

Kessler, Thomas M; Mordasini, Livio; Weisstanner, Christian; Jüni, Peter; da Costa, Bruno R; Wiest, Roland; Thalmann, George N

2014-01-01

To assess the efficacy and safety of sono-electro-magnetic therapy compared to placebo in men with refractory CPPS. In a randomized, placebo-controlled, double-blind single center trial, we assessed the effect of sono-electro-magnetic therapy in men with treatment refractory CPPS. Sixty male patients were randomly assigned to treatment with either sono-electro-magnetic (n = 30) or placebo therapy (n = 30) for 12 weeks. The primary outcome was a change in the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) from baseline to 12 weeks. The 12-week difference between sono-electro-magnetic and placebo therapy in changes of the NIH-CPSI total score was -3.1 points (95% CI -6.8 to 0.6, p = 0.11). In secondary comparisons of NIH-CPSI sub-scores, we found differences between groups most pronounced for the quality-of-life sub-score (difference at 12 weeks -1.6, 95% CI -2.8 to -0.4, p = 0.015). In stratified analyses, the benefit of sono-electro-magnetic therapy appeared more pronounced among patients who had a symptom duration of 12 months or less (difference in NIH-CPSI total score -8.3, 95% CI -14.5 to 2.6) than in patients with a longer symptom duration (-0.8, 95% CI -4.6 to 3.1; p for interaction = 0.023). Sono-electro-magnetic therapy did not result in a significant improvement of symptoms in the overall cohort of treatment refractory CPPS patients compared to placebo treatment. Subgroup analysis indicates, however, that patients with a symptom-duration of 12 months or less may benefit from sono-electro-magnetic therapy, warranting larger randomized controlled trials in this subpopulation. ClinicalTrials.gov NCT00688506.

Palmitoylethanolamide as adjunctive therapy in major depressive disorder: A double-blind, randomized and placebo-controlled trial.

PubMed

Ghazizadeh-Hashemi, Maryam; Ghajar, Alireza; Shalbafan, Mohammad-Reza; Ghazizadeh-Hashemi, Fatemeh; Afarideh, Mohsen; Malekpour, Farzaneh; Ghaleiha, Ali; Ardebili, Mehrdad Eftekhar; Akhondzadeh, Shahin

2018-05-01

Experimental studies provide evidence for antidepressant effects of Palmitoylethanolamide (PEA) in animal models of depression. We aimed to evaluate the efficacy and tolerability of PEA add-on therapy in treatment of patients with major depressive disorder (MDD). In a randomized double-blind, and placebo-controlled study, 58 patients with MDD (DSM-5) and Hamilton Depression Rating Scale (HAM-D) score ≥ 19 were randomized to receive either 600 mg twice daily Palmitoylethanolamide or placebo in addition to citalopram for six weeks. Patients were assessed using the HAM-D scale at baseline and weeks 2, 4, and 6. Fifty-four individuals completed the trial. At week 2, patients in the PEA group demonstrated significantly greater reduction in HAM-D scores compared to the placebo group (8.30 ± 2.41 vs. 5.81 ± 3.57, P = .004). The PEA group also demonstrated significantly greater improvement in depressive symptoms [F (3, 156) = 3.35, P = .021] compared to the placebo group throughout the trial period. The patients in the PEA group experienced more response rate (≥ 50% reduction in the HAM-D score) than the placebo group (100% vs. 74% respectively, P = .01) at the end of the trial. Baseline parameters and frequency of side effects were not significantly different between the two groups. The population size in this study was small and the follow-up period was relatively short. Palmitoylethanolamide adjunctive therapy to citalopram can effectively improve symptoms of patients (predominantly male gender) with major depressive disorder. PEA showed rapid-onset antidepressant effects which need further investigation. Copyright © 2018 Elsevier B.V. All rights reserved.

Homeopathic Individualized Q-Potencies versus Fluoxetine for Moderate to Severe Depression: Double-Blind, Randomized Non-Inferiority Trial

PubMed Central

Adler, U. C.; Paiva, N. M. P.; Cesar, A. T.; Adler, M. S.; Molina, A.; Padula, A. E.; Calil, H. M.

2011-01-01

Homeopathy is a complementary and integrative medicine used in depression, The aim of this study is to investigate the non-inferiority and tolerability of individualized homeopathic medicines [Quinquagintamillesmial (Q-potencies)] in acute depression, using fluoxetine as active control. Ninety-one outpatients with moderate to severe depression were assigned to receive an individualized homeopathic medicine or fluoxetine 20 mg day−1 (up to 40 mg day−1) in a prospective, randomized, double-blind double-dummy 8-week, single-center trial. Primary efficacy measure was the analysis of the mean change in the Montgomery & Åsberg Depression Rating Scale (MADRS) depression scores, using a non-inferiority test with margin of 1.45. Secondary efficacy outcomes were response and remission rates. Tolerability was assessed with the side effect rating scale of the Scandinavian Society of Psychopharmacology. Mean MADRS scores differences were not significant at the 4th (P = .654) and 8th weeks (P = .965) of treatment. Non-inferiority of homeopathy was indicated because the upper limit of the confidence interval (CI) for mean difference in MADRS change was less than the non-inferiority margin: mean differences (homeopathy-fluoxetine) were −3.04 (95% CI −6.95, 0.86) and −2.4 (95% CI −6.05, 0.77) at 4th and 8th week, respectively. There were no significant differences between the percentages of response or remission rates in both groups. Tolerability: there were no significant differences between the side effects rates, although a higher percentage of patients treated with fluoxetine reported troublesome side effects and there was a trend toward greater treatment interruption for adverse effects in the fluoxetine group. This study illustrates the feasibility of randomized controlled double-blind trials of homeopathy in depression and indicates the non-inferiority of individualized homeopathic Q-potencies as compared to fluoxetine in acute treatment of outpatients

Early cessation of triptorelin in in vitro fertilization: a double-blind, randomized study.

PubMed

Simons, Arnold H M; Roelofs, Henny J M; Schmoutziguer, Alex P E; Roozenburg, Brigitte J; van't Hof-van den Brink, Eefje P; Schoonderwoerd, Simon A

2005-04-01

To compare the efficacy of two early cessation protocols of triptorelin treatment in controlled ovarian hyperstimulation with the conventional long protocol in in vitro fertilization/intracytoplasmic sperm injection. A double-blind, randomized, multicenter study. Three Dutch hospitals. One hundred seventy-eight women randomized to one of three treatment groups at the start of stimulation. Midluteally started triptorelin administration was continued until the first day of hMG treatment (group S), or up to and including the fourth day of hMG treatment (group M) or the day of hCG injection (group L). Occurrence of a premature LH surge. One premature LH surge was observed in group M but not in groups S and L. Both early cessation protocols (S and M) are at least as effective as the long protocol (L) with regard to the number of oocytes (11.1 and 10.3 vs. 9.3), number of embryos (7.3 and 6.5 vs. 5.5), and ongoing pregnancy rate (28% and 24% vs. 21%). Early cessation of triptorelin on day 1 of hMG treatment in a midluteally started IVF protocol is as effective as the traditional long protocol in preventing a premature LH surge and results in similar fertility effects.

Phenobarbital for acute alcohol withdrawal: a prospective randomized double-blind placebo-controlled study.

PubMed

Rosenson, Jonathan; Clements, Carter; Simon, Barry; Vieaux, Jules; Graffman, Sarah; Vahidnia, Farnaz; Cisse, Bitou; Lam, Joseph; Alter, Harrison

2013-03-01

Acute alcohol withdrawal syndrome (AAWS) is encountered in patients presenting acutely to the Emergency Department (ED) and often requires pharmacologic management. We investigated whether a single dose of intravenous (i.v.) phenobarbital combined with a standardized lorazepam-based alcohol withdrawal protocol decreases intensive care unit (ICU) admission in ED patients with acute alcohol withdrawal. This was a prospective, randomized, double-blind, placebo-controlled study. Patients were randomized to receive either a single dose of i.v. phenobarbital (10 mg/kg in 100 mL normal saline) or placebo (100 mL normal saline). All patients were placed on the institutional symptom-guided lorazepam-based alcohol withdrawal protocol. The primary outcome was initial level of hospital admission (ICU vs. telemetry vs. floor ward). There were 198 patients enrolled in the study, and 102 met inclusion criteria for analysis. Fifty-one patients received phenobarbital and 51 received placebo. Baseline characteristics and severity were similar in both groups. Patients that received phenobarbital had fewer ICU admissions (8% vs. 25%, 95% confidence interval 4-32). There were no differences in adverse events. A single dose of i.v. phenobarbital combined with a symptom-guided lorazepam-based alcohol withdrawal protocol resulted in decreased ICU admission and did not cause increased adverse outcomes. Copyright © 2013 Elsevier Inc. All rights reserved.

Attentional bias modification training for insomnia: A double-blind placebo controlled randomized trial

PubMed Central

Lancee, Jaap; Yasiney, Samya L.; Brendel, Ruben S.; Boffo, Marilisa; Clarke, Patrick J. F.; Salemink, Elske

2017-01-01

Background Attentional bias toward sleep-related information is believed to play a key role in insomnia. If attentional bias is indeed of importance, changing this bias should then in turn have effects on insomnia complaints. In this double-blind placebo controlled randomized trial we investigated the efficacy of attentional bias modification training in the treatment of insomnia. Method We administered baseline, post-test, and one-week follow-up measurements of insomnia severity, sleep-related worry, depression, and anxiety. Participants meeting DSM-5 criteria for insomnia were randomized into an attentional bias training group (n = 67) or a placebo training group (n = 70). Both groups received eight training sessions over the course of two weeks. All participants kept a sleep diary for four consecutive weeks (one week before until one week after the training sessions). Results There was no additional benefit for the attentional bias training over the placebo training on sleep-related indices/outcome measures. Conclusions The absence of the effect may be explained by the fact that there was neither attentional bias at baseline nor any reduction in the bias after the training. Either way, this study gives no support for attentional bias modification training as a stand-alone intervention for ameliorating insomnia complaints. PMID:28423038

Organic brain syndrome treated with oxiracetam. A double-blind randomized controlled trial.

PubMed

Hjorther, A; Browne, E; Jakobsen, K; Viskum, P; Gyntelberg, F

1987-04-01

In a 12-week double-blind study, oxiracetam (CGP 21690 E), a new nootropic drug, at a dose of 2.4 mg per day, was compared to placebo in the treatment of 106 middle-aged patients suffering from mild to moderate organic brain syndrome due to prolonged exposure to organic solvents. At the beginning of the study and after 12 weeks treatment, the patients underwent a battery of neuropsychological tests to determine their mental and memory functioning. A symptom questionnaire consisting of 21 items was rated pre-treatment, and improvement or worsening of any of the symptoms recorded monthly. At the end of the study a global evaluation was performed by the patients themselves, their relatives, the psychologist and the doctor. The code was not broken until the final writing of this paper. No statistically significant differences were observed between the treatment groups in any of the above-mentioned evaluations; neither were any differences in the neuropsychological tests performance observed. Thus, oxiracetam seems to have no effect in the treatment of organic brain syndrome.

Six-month exercise training program to treat post-thrombotic syndrome: a randomized controlled two-centre trial

PubMed Central

Kahn, Susan R.; Shrier, Ian; Shapiro, Stan; Houweling, Adrielle H.; Hirsch, Andrew M.; Reid, Robert D.; Kearon, Clive; Rabhi, Khalil; Rodger, Marc A.; Kovacs, Michael J.; Anderson, David R.; Wells, Philip S.

2011-01-01

Background Exercise training may have the potential to improve post-thrombotic syndrome, a frequent, chronic complication of deep venous thrombosis. We conducted a randomized controlled two-centre pilot trial to assess the feasibility of a multicentre-based evaluation of a six-month exercise training program to treat post-thrombotic syndrome and to obtain preliminary data on the effectiveness of such a program. Methods Patients were randomized to receive exercise training (a six-month trainer-supervised program) or control treatment (an education session with monthly phone follow-ups). Levels of eligibility, consent, adherence and retention were used as indicators of study feasibility. Primary outcomes were change from baseline to six months in venous disease-specific quality of life (as measured using the Venous Insufficiency Epidemiological and Economic Study Quality of Life [VEINES-QOL] questionnaire) and severity of post-thrombotic syndrome (as measured by scores on the Villalta scale) in the exercise training group versus the control group, assessed by t tests. Secondary outcomes were change in generic quality of life (as measured using the Short-Form Health Survey-36 [SF-36] questionnaire), category of severity of post-thrombotic syndrome, leg strength, leg flexibility and time on treadmill. Results Of 95 patients with post-thrombotic syndrome, 69 were eligible, 43 consented and were randomized, and 39 completed the study. Exercise training was associated with improvement in VEINES-QOL scores (exercise training mean change 6.0, standard deviation [SD] 5.1 v. control mean change 1.4, SD 7.2; difference 4.6, 95% CI 0.54 to 8.7; p = 0.027) and improvement in scores on the Villalta scale (exercise training mean change −3.6, SD 3.7 v. control mean change −1.6, SD 4.3; difference −2.0, 95% CI −4.6 to 0.6; p = 0.14). Most secondary outcomes also showed greater improvement in the exercise training group. Interpretation Exercise training may improve post

A 6-month, randomized, double-blind, placebo-controlled study evaluating the ability of a marine complex supplement to promote hair growth in men with thinning hair.

PubMed

Ablon, Glynis

2016-12-01

Male pattern baldness, or androgenetic alopecia, affects approximately 50% of the adult population and can cause poor self-image, low self-esteem and have a significant negative impact on the quality of life. An oral nutraceutical supplement based on a marine complex formulation has previously been reported to significantly increase the number of terminal hairs in women with thinning hair. The objective of this double-blind, placebo-controlled study was to confirm the beneficial effects of a similar marine complex supplement in adult male subjects with thinning hair (Viviscal ® Man; Lifes2good, Inc., Chicago, IL, USA). Healthy adult male subjects with thinning hair associated with clinically diagnosed male pattern hair loss were enrolled and randomized to receive study drug or placebo twice daily. At Day 90, subjects indicated a significant improvement in three of six quality of life measures as well as a significant overall improvement in quality of life. After 180 days, significant increases were observed for total hair count, total hair density, and terminal hair density (for each, P = 0.001). The investigator assessments revealed significant improvements in terminal and vellus hair count and terminal hair density. Hair pull test results were significantly lower (fewer hairs removed) for study drug vs. placebo at Days 90 (P < 0.05) and 180 (P < 0.01). There were no reports of treatment-emergent adverse events. The results of this study showed for the first time that a dietary supplement containing a marine complex and other ingredients can decrease hair shedding and promote hair growth in men with thinning hair. © 2016 Wiley Periodicals, Inc.

Efficacy and safety of sacubitril/valsartan (LCZ696) in Japanese patients with chronic heart failure and reduced ejection fraction: Rationale for and design of the randomized, double-blind PARALLEL-HF study.

PubMed

Tsutsui, Hiroyuki; Momomura, Shinichi; Saito, Yoshihiko; Ito, Hiroshi; Yamamoto, Kazuhiro; Ohishi, Tomomi; Okino, Naoko; Guo, Weinong

2017-09-01

The prognosis of heart failure patients with reduced ejection fraction (HFrEF) in Japan remains poor, although there is growing evidence for increasing use of evidence-based pharmacotherapies in Japanese real-world HF registries. Sacubitril/valsartan (LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor shown to reduce mortality and morbidity in the recently completed largest outcome trial in patients with HFrEF (PARADIGM-HF trial). The prospectively designed phase III PARALLEL-HF (Prospective comparison of ARNI with ACE inhibitor to determine the noveL beneficiaL trEatment vaLue in Japanese Heart Failure patients) study aims to assess the clinical efficacy and safety of LCZ696 in Japanese HFrEF patients, and show similar improvements in clinical outcomes as the PARADIGM-HF study enabling the registration of LCZ696 in Japan. This is a multicenter, randomized, double-blind, parallel-group, active controlled study of 220 Japanese HFrEF patients. Eligibility criteria include a diagnosis of chronic HF (New York Heart Association Class II-IV) and reduced ejection fraction (left ventricular ejection fraction ≤35%) and increased plasma concentrations of natriuretic peptides [N-terminal pro B-type natriuretic peptide (NT-proBNP) ≥600pg/mL, or NT-proBNP ≥400pg/mL for those who had a hospitalization for HF within the last 12 months] at the screening visit. The study consists of three phases: (i) screening, (ii) single-blind active LCZ696 run-in, and (iii) double-blind randomized treatment. Patients tolerating LCZ696 50mg bid during the treatment run-in are randomized (1:1) to receive LCZ696 100mg bid or enalapril 5mg bid for 4 weeks followed by up-titration to target doses of LCZ696 200mg bid or enalapril 10mg bid in a double-blind manner. The primary outcome is the composite of cardiovascular death or HF hospitalization and the study is an event-driven trial. The design of the PARALLEL-HF study is aligned with the PARADIGM-HF study and aims to assess

Ease of intubation: A randomized, double-blind study to compare two doses of rocuronium bromide for endotracheal intubation.

PubMed

Shukla, Aparna; Misra, Shilpi

2016-01-01

Clinical need for a nondepolarizing agent with a rapid onset time and a brief duration of action has led to the development of rocuronium bromide. The aim of this study was to evaluate optimal dose of rocuronium bromide for intubation and to compare the onset time, duration of action, intubating conditions, and hemodynamic effects of two doses of rocuronium bromide. A prospective, randomized, double-blind study. All the patients were divided in a randomized, double-blind fashion into two groups of twenty patients each. Group I patients received rocuronium bromide 0.6 mg/kg intravenously and intubated at 60 s, Group II patients received rocuronium bromide 0.9 mg/kg and intubated at 60 s. The neuromuscular block was assessed using single twitch stimulation of 0.1 Hz at adductor pollicis muscle of hand at every 10 s. The results were compiled and analyzed statistically using Chi-square test for qualitative data and Student's t -test for quantitative data. Time of onset was significantly shorter ( P < 0.01) and duration of action was prolonged ( P < 0.001) for Group II as compared to Group I. The intubating conditions were (excellent + good) in 100% patients of Group II and (excellent + good) in 80% of Group I. There was no significant change in pulse rate and mean arterial pressure from the baseline value after the administration of muscle relaxants in either of the two groups. Rocuronium bromide 0.9 mg/kg is a safer alternative to rocuronium bromide 0.6 mg/kg for endotracheal intubation with shorter time of onset and better intubating conditions.

A randomized, double-blind, placebo-controlled trial of oral Matricaria recutita (chamomile) extract therapy for generalized anxiety disorder.

PubMed

Amsterdam, Jay D; Li, Yimei; Soeller, Irene; Rockwell, Kenneth; Mao, Jun James; Shults, Justine

2009-08-01

We conducted a randomized, double-blind, placebo-controlled efficacy and tolerability trial of Matricaria recutita (chamomile) extract therapy in patients with mild to moderate generalized anxiety disorder (GAD). We hypothesized that chamomile would be superior to placebo in reducing GAD symptoms with a comparable tolerability profile. Sixty-one outpatients with mild to moderate GAD were enrolled, and 57 were randomized to either double-blind chamomile extract (n = 28) or placebo therapy (n = 29) for 8 weeks. The study was powered to detect a statistically significant and clinically meaningful group difference in change over time in total Hamilton Anxiety Rating (HAM-A) scores. Secondary outcomes included change in the Beck Anxiety Inventory, Psychological Well Being, and Clinical Global Impression Severity scores and the proportion of patients with 50% reduction or more in baseline HAM-A score. We observed a significantly greater reduction in mean total HAM-A score during chamomile versus placebo therapy (P = 0.047). Although the study was not powered to identify small to moderate differences in secondary outcomes, we observed a positive change in all secondary outcomes in the same direction as the primary outcome measure. One patient in each treatment group discontinued therapy for adverse events. The proportion of patients experiencing 0, 1, 2, or 3 adverse events or more was not significantly different between groups (P = 0.417). This is the first controlled clinical trial of chamomile extract for GAD. The results suggest that chamomile may have modest anxiolytic activity in patients with mild to moderate GAD. Future studies are needed to replicate these observations.

Evaluation of intralesional injection of hyaluronic acid compared with verapamil in Peyronie's disease: preliminary results from a prospective, double-blinded, randomized study.

PubMed

Favilla, V; Russo, G I; Zucchi, A; Siracusa, G; Privitera, S; Cimino, S; Madonia, M; Cai, T; Cavallini, G; Liguori, G; D'Achille, G; Silvani, M; Franco, G; Verze, P; Palmieri, A; Torrisi, B; Mirone, V; Morgia, G

2017-07-01

Several intralesional therapeutic protocols have been proposed for the treatment of Peyronie's disease. Among all, hyaluronic acid (HA) and verapamil have been differently tested. We aimed to evaluate the efficacy of intralesional verapamil (ILVI) compared with intralesional HA in patients with early onset of Peyronie's disease (PD). This is a multi-centre prospective double-arm, randomized, double-blinded study comparing ILVI vs. intralesional HA after 12-weeks. Sexually active men, older than 18 years and affected by the acute phase of PD were eligible for this study. Patients have been double-blinded randomly divided into two groups (1 : 1 ratio): Group A received intralesional treatment with Verapamil (10 mg in 5 mL of normal saline water) weekly for 12 weeks, while group B received intralesional treatment with HA (0.8% highly purified sodium salt HA 16 mg/2 mL) weekly for 12 weeks. The primary efficacy outcome was the change from the baseline to the endpoint (12 weeks after therapy) for the penile curvature (degree). The secondary outcome was the change in the plaque size and in the International Index of erectile Function (IIEF-5) score. The difference between post- and pre-treatment plaque size was -1.36 mm (SD ± 1.27) for Group A and -1.80 mm (SD ± 2.47) for Group B (p-value = NS). IIEF-5 increased of 1.46 points (SD ± 2.18) in Group A and 1.78 (SD ± 2.48) in Group B (p-value ± NS). No difference in penile curvature was observed in Group A, while in Group B the penile curvature decreased of 4.60° (SD ± 5.63) from the baseline (p < 0.001) and vs. Group A. According to PGI-I results, we found significant difference as concerning patient global impression of improvement (PGI-I) (4.0 vs. 2.0; p < 0.05). This prospective, double-arm, randomized, double-blinded study comparing ILVI vs. HA as intralesional therapy showed greater efficacy of HA in terms of penile curvature and PGI-I. © 2017 American Society of Andrology and

Pentoxifylline for the treatment of nonalcoholic fatty liver disease: a meta-analysis of randomized double-blind, placebo-controlled studies.

PubMed

Zeng, Tao; Zhang, Cui-Li; Zhao, Xiu-Lan; Xie, Ke-Qin

2014-06-01

Pentoxifylline has been used to treat nonalcoholic fatty liver diseases (NAFLDs) due to its anti-tumor necrosis factor-α effects. We conducted a meta-analysis of randomized, double-blinded, placebo-controlled trials to investigate the effect of pentoxifylline on the biochemical and histological parameters of NAFLD patients. A comprehensive literature search was conducted in the database including PubMed, Embase, ISI web of knowledge, the Cochrane Library, and Google Scholar to identify randomized, double-blind, placebo-controlled clinical trials about the effects of pentoxifylline on NAFLD. The pooled weighted mean difference (WMD) with 95% confidence interval (CI) was calculated to compare the effects of pentoxifylline and placebo. Five well-designed studies were retrieved. Pooled results showed that pentoxifylline significantly reduced the serum alanine transaminase activity (WMD=-27.97; 95% CI: -42.59, -13.34) and aspartate transaminase activity (WMD=-13.97; 95% CI: -23.31, -4.63) in NAFLD patients compared with placebo. In addition, pentoxifylline significantly improved steatosis (WMD=-0.68; 95% CI: -1.01, -0.34), lobular inflammation (WMD=-0.49; 95% CI: -0.86, -0.12), and fibrosis (WMD=-0.60; 95% CI: -0.99, -0.21). Furthermore, pentoxifylline also led to significant reduction in BMI (WMD=-0.51; 95% CI: -0.96, -0.06) and fasting glucose (WMD=-8.97; 95% CI: -14.52, -3.42), but did not significantly affect the serum tumor necrosis factor α and adiponectin levels when compared with placebo. Pentoxifylline could reduce the aminotransferase activities and improve the histological parameters in NAFLD patients. Large well-designed, randomized, placebo-controlled studies are needed to confirm these results.

Secure entanglement distillation for double-server blind quantum computation.

PubMed

Morimae, Tomoyuki; Fujii, Keisuke

2013-07-12

Blind quantum computation is a new secure quantum computing protocol where a client, who does not have enough quantum technologies at her disposal, can delegate her quantum computation to a server, who has a fully fledged quantum computer, in such a way that the server cannot learn anything about the client's input, output, and program. If the client interacts with only a single server, the client has to have some minimum quantum power, such as the ability of emitting randomly rotated single-qubit states or the ability of measuring states. If the client interacts with two servers who share Bell pairs but cannot communicate with each other, the client can be completely classical. For such a double-server scheme, two servers have to share clean Bell pairs, and therefore the entanglement distillation is necessary in a realistic noisy environment. In this Letter, we show that it is possible to perform entanglement distillation in the double-server scheme without degrading the security of blind quantum computing.

Linagliptin as add-on to empagliflozin and metformin in patients with type 2 diabetes: Two 24-week randomized, double-blind, double-dummy, parallel-group trials.

PubMed

Tinahones, Francisco J; Gallwitz, Baptist; Nordaby, Matias; Götz, Sophia; Maldonado-Lutomirsky, Mario; Woerle, Hans J; Broedl, Uli C

2017-02-01

To evaluate the efficacy and safety of linagliptin vs placebo as add-on to empagliflozin and metformin in patients with type 2 diabetes. Patients with inadequate glycaemic control despite stable-dose metformin received open-label empagliflozin 10 mg (study 1) or 25 mg (study 2) as add-on therapy for 16 weeks. Subsequently, those with HbA1c ≥7.0 and ≤10.5% (>53 and ≤91 mmol/mol) (N = 482) were randomized to 24 weeks' double-blind, double-dummy treatment with linagliptin 5 mg or placebo in study 1, or to linagliptin 5 mg or placebo in study 2; all patients continued treatment with metformin and empagliflozin 10 mg (study 1) or metformin and empagliflozin 25 mg (study 2). The primary endpoint was change from baseline (defined as the last value before first intake of randomized, double-blind treatment) in HbA1c at week 24. At week 24, HbA1c (mean baseline 7.82-8.04 [62-64 mmol/mol]) was significantly reduced with linagliptin vs placebo; adjusted mean (SE) differences in change from baseline in HbA1c with linagliptin vs placebo were -.32% (.10) (-3.59 [1.08] mmol/mol) ( P = .001) for patients on empagliflozin 10 mg and metformin, and -0.47% (0.10) (-5.15 [1.04] mmol/mol) ( P < 0.001) for patients on empagliflozin 25 mg and metformin. Adverse events were reported in more patients receiving placebo than in those receiving linagliptin: 55.5% vs 48.4% in study 1 and 58.9% vs 52.7% in study 2. Linagliptin as add-on to empagliflozin and metformin for 24 weeks improved glycaemic control vs placebo, and was well tolerated. © 2016 John Wiley & Sons Ltd.

Racemic versus l-epinephrine aerosol in the treatment of postextubation laryngeal edema: results from a prospective, randomized, double-blind study.

PubMed

Nutman, J; Brooks, L J; Deakins, K M; Baldesare, K K; Witte, M K; Reed, M D

1994-10-01

To determine whether any advantage exists using racemic epinephrine instead of the more potent and less expensive levo(1)-epinephrine in the treatment of postextubation laryngeal edema. Prospective, double-blind, randomized study. Pediatric intensive care unit in a university teaching hospital. Twenty-eight patients with stridor during the immediate postextubation period. After extubation, patients demonstrating clinically important stridor were randomized in a double-blind fashion to receive an aerosol containing either 2.25% racemic or 1% l-epinephrine. Heart rate, respiratory rate, blood pressure, and stridor score were determined at 20, 40, and 60 mins and 4 and 8 hrs after the initial aerosol administration. Patients in both groups demonstrated significant (p < .01) reductions in stridor score after aerosol administration. No significant differences were observed between treatment groups in improvement in stridor score or the number of subsequent aerosols required. Respiratory rate decreased significantly 40 and 60 mins after l-epinephrine but not after racemic epinephrine. No significant change in heart rate or blood pressure occurred after aerosol administration in either group. These data suggest that aerosolized l-epinephrine is as effective as aerosolized racemic epinephrine in the treatment of postextubation laryngeal edema without additional adverse side effects. When dosed appropriately, l-epinephrine is a less expensive and more widely available alternative to racemic epinephrine for the treatment of postextubation laryngeal edema.

Obsessive-compulsive symptoms in a randomized, double-blind study with olanzapine or risperidone in young patients with early psychosis.

PubMed

van Nimwegen, Lonneke; de Haan, Lieuwe; van Beveren, Nico; Laan, Winfried; van den Brink, Wim; Linszen, Don

2008-04-01

The prevalence of obsessive-compulsive symptoms (OCS) in patients with schizophrenia is relatively high. Antipsychotics have been found to influence OCS. To determine whether induction or severity of OCS differs during treatment with olanzapine or risperidone in young patients with early psychosis. One hundred twenty-two patients with a Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition diagnosis of schizophrenia, schizoaffective disorder, or schizophreniform disorder were randomized in a double-blind design to groups of 6 weeks' treatment with olanzapine (n = 59) or risperidone (n = 63), with a mean dose of 11.3 mg olanzapine and 3.0 mg risperidone at 6 weeks. Primary outcome measures were the mean baseline-to-endpoint change in total score on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Treatment with olanzapine was associated with greater decreases in Y-BOCS total score than treatment with risperidone in total group (N = 122: -2.2 vs -0.3, z = -2.651, P < 0.01), in patients with baseline Y-BOCS total score greater than 0 (n = 58: -5.1 vs -0.4, z = -2.717, P < 0.01), and in patients with baseline Y-BOCS total score greater than 10 (n = 29: -7.1 vs -0.6, z = -2.138, P = 0.032). In this randomized, 6-week, double-blind trial, we found a significant and clinically relevant difference in decrease in Y-BOCS scores favoring olanzapine compared with risperidone.

Prevention of upper gastrointestinal bleeding in critically ill Chinese patients: a randomized, double-blind study evaluating esomeprazole and cimetidine.

PubMed

Lou, Wenhui; Xia, Ying; Xiang, Peng; Zhang, Liangqing; Yu, Xiangyou; Lim, Sam; Xu, Mo; Zhao, Lina; Rydholm, Hans; Traxler, Barry; Qin, Xinyu

2018-04-20

To assess the efficacy and safety of esomeprazole in preventing upper gastrointestinal (GI) bleeding in critically ill Chinese patients, using cimetidine as an active comparator. A pre-specified non-inferiority limit (5%) was used to compare rates of significant upper GI bleeding in this randomized, double-blind, parallel-group, phase 3 study across 27 intensive care units in China. Secondary endpoints included safety and tolerability measures. Patients required mechanical ventilation and had at least one additional risk factor for stress ulcer bleeding. Patients were randomized to receive either active esomeprazole 40 mg, as a 30-min intravenous (IV) infusion twice daily, and an IV placebo cimetidine infusion or active cimetidine 50 mg/h, as a continuous infusion following an initial bolus of 300 mg, and placebo esomeprazole injections, given up to 14 days. Patients were blinded using this double-dummy technique. Of 274 patients, 2.7% with esomeprazole and 4.6% with cimetidine had significant upper GI bleeding (bright red blood in the gastric tube not clearing after lavage or persistent Gastroccult-positive "coffee grounds" material). Non-inferiority of esomeprazole to cimetidine was demonstrated. The safety profiles of both drugs were similar and as expected in critically ill patients. Esomeprazole is effective in preventing upper GI bleeding in critically ill Chinese patients, as demonstrated by the non-inferiority analysis using cimetidine as an active control. ClinicalTrials.gov identifier NCT02157376.

Intralesional immunotherapy with tuberculin purified protein derivative (PPD) in recalcitrant wart: A randomized, placebo-controlled, double-blind clinical trial including an extra group of candidates for cryotherapy.

PubMed

Amirnia, Mehdi; Khodaeiani, Effat; Fouladi, Daniel F; Masoudnia, Sima

2016-01-01

Due to paucity of randomized clinical trials, intralesional immunotherapy has not been yet accepted as a standard therapeutic method. To examine the efficacy and safety of intralesional immunotherapy with tuberculin purified protein derivative (PPD) for treating recalcitrant wart. In this randomized, placebo-controlled, double-blind clinical trial, a total of 69 patients with recalcitrant warts received either intralesional PPD antigen (n = 35) or intralesional saline (n = 34) for six times at 2-week intervals. A third group of candidates for cryotherapy (n = 33) was also included. The decrease in lesion size (good: complete response, intermediate: 50-99% improvement, poor: <50% improvement), adverse effects and recurrence within 6-month follow-up were documented. At the final session, good, intermediate and poor responses were observed in 77.1%, 22.9% and 0% of the PPD patients; 0%, 14.7% and 85.3% of the placebo patients and 18.2%, 33.3% and 48.5% of the cryotherapy patients, respectively (PPD versus placebo: p < 0.001; PPD versus cryotherapy: p < 0.001). No significant complication was seen in the PPD group. The recurrence rate was 8.6%, 5.9% and 24.2% in the PPD, placebo and cryotherapy groups, respectively (p > 0.05). Intralesional immunotherapy with PPD antigen is highly effective and safe for treating recalcitrant warts. IRCT201407089844N3 in the Iranian Registry of Clinical Trials (IRCT).

Effect of transcranial direct current stimulation combined with gait and mobility training on functionality in children with cerebral palsy: study protocol for a double-blind randomized controlled clinical trial

PubMed Central

2013-01-01

Background The project proposes three innovative intervention techniques (treadmill training, mobility training with virtual reality and transcranial direct current stimulation that can be safely administered to children with cerebral palsy. The combination of transcranial stimulation and physical therapy resources will provide the training of a specific task with multiple rhythmic repetitions of the phases of the gait cycle, providing rich sensory stimuli with a modified excitability threshold of the primary motor cortex to enhance local synaptic efficacy and potentiate motor learning. Methods/design A prospective, double-blind, randomized, controlled, analytical, clinical trial will be carried out.Eligible participants will be children with cerebral palsy classified on levels I, II and III of the Gross Motor Function Classification System between four and ten years of age. The participants will be randomly allocated to four groups: 1) gait training on a treadmill with placebo transcranial stimulation; 2) gait training on a treadmill with active transcranial stimulation; 3) mobility training with virtual reality and placebo transcranial stimulation; 4) mobility training with virtual reality and active transcranial stimulation. Transcranial direct current stimulation will be applied with the anodal electrode positioned in the region of the dominant hemisphere over C3, corresponding to the primary motor cortex, and the cathode positioned in the supraorbital region contralateral to the anode. A 1 mA current will be applied for 20 minutes. Treadmill training and mobility training with virtual reality will be performed in 30-minute sessions five times a week for two weeks (total of 10 sessions). Evaluations will be performed on four occasions: one week prior to the intervention; one week following the intervention; one month after the end of the intervention;and 3 months after the end of the intervention. The evaluations will involve three-dimensional gait analysis

Oral Glucosamine Hydrochloride Combined With Hyaluronate Sodium Intra-Articular Injection for Temporomandibular Joint Osteoarthritis: A Double-Blind Randomized Controlled Trial.

PubMed

Yang, Wenbin; Liu, Wei; Miao, Cheng; Sun, Haibin; Li, Longjiang; Li, Chunjie

2018-06-02

Temporomandibular joint (TMJ) disorders occur in many people and osteoarthritis (OA) is a severe form of this disease. Glucosamine has been used to treat OA of the large joints for many years and has been proved effective. A double-blinded randomized controlled trial was designed to investigate the effectiveness and safety of oral glucosamine hydrochloride pills combined with hyaluronate sodium intra-articular injection in TMJ OA. One hundred forty-four participants with TMJ OA were randomized to 4 hyaluronate sodium injections and oral glucosamine hydrochloride (1.44 g/day) for 3 months (group A) or 4 hyaluronate sodium injections and oral placebo for 3 months (group B). All participants were followed for 1 year. Eighteen participants were lost to follow-up. The intention-to-treat analysis showed that group A had similar maximal interincisal mouth opening and pain intensity during TMJ function at months 1 and 6 (P > .05). However, during long-term follow-up, group A had significantly greater maximal interincisal mouth opening compared with group B at month 12 (41.5 vs 37.9 mm; P < .001). For pain intensity, group A showed obviously lower visual analog scale scores than group B at month 6 (20.6 vs 29.2 mm; P = .007) and month 12 (17.4 vs 28.6 mm; P = .001). Twenty-four participants had gastrointestinal tract side effects, fatigue, and rash. Of these, 23 had slight side effects that were not correlated with glucosamine. There was no significant difference between the 2 groups (P > .05). The results of this study suggest that, compared with hyaluronate sodium injection alone, glucosamine hydrochloride pills added to hyaluronate sodium injection had no meaningful effect on TMJ OA in the short-term but did relieve the pain caused by TMJ OA and improved TMJ functions in the long-term. Copyright © 2018 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Efficacy of Intravenous Acetaminophen in Periimplantation Pain of Cardiac Electronic Devices: A Randomized Double-Blinded Study.

PubMed

Mollazadeh, Reza; Eftekhari, Mohammad Reza; Eslami, Masoud

2017-06-01

Although intravenous acetaminophen has been administered to reduce postoperative pain, it has not been used during cardiac implantable electronic devices (CIEDs) implantation. This was a randomized double-blinded interventional study. Thirty-two patients who were referred for new CIED implantation during July 2012 until April 2013 randomly received placebo or 1 g of intravenous acetaminophen. All patients were treated with local anesthesia. Pain score during incision, pocket creation, and in the recovery room, and the patients' need for analgesics during the 6 hours after the procedure were recorded in both groups. Seventeen and 15 patients received acetaminophen and placebo, respectively. Pain scores in patients treated with acetaminophen were significantly lower (4.4 vs 2.9, P = .004), and they received less analgesics (17% vs 60%, P = .014). Intravenous administration of acetaminophen is effective for pain relief in patients undergoing CIED implantation and decreases the need for postoperative analgesics. Copyright © 2016 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.

Effect of Transcranial Direct Current Stimulation on Neurorehabilitation of Task-Specific Dystonia: A Double-Blind, Randomized Clinical Trial.

PubMed

Rosset-Llobet, Jaume; Fàbregas-Molas, Sílvia; Pascual-Leone, Álvaro

2015-09-01

Task-specific focal hand dystonia can disable affected individuals. Although neurorehabilitation techniques such as sensory motor retuning can result in complete recovery in some patients, it requires many months of treatment. Combining transcranial direct current stimulation (tDCS) with neurorehabilitation is a new and promising approach that can help these patients. However, the results in different studies are contradictory. Analyze whether delivering tDCS (cathode over left and anode over right parietal region) during the neurorehabilitation process for musicians with dystonia can increase the effectiveness of therapy. A parallel double-blind randomized design was used to study 30 musicians with right-hand primary focal dystonia. All patients underwent a 2-week course of neurorehabilitation based on sensory motor retuning therapy coupled with either real or sham tDCS for the first 30 minutes of each daily 1-hour therapy session (total 10 sessions). The therapist and patient were blind to the tDCS condition. A dystonia severity score was obtained before and after the 2-week protocol. The therapist also rated the evolution of each patient. Both groups significantly improved their dystonia severity score during the 2 weeks. Score differences were 88.23 (±40.51) and 63.36 (±30.57) for the active and sham groups, respectively. The active group showed a statistically significant greater improvement. Biparietal tDCS with left-sided cathode is a safe technique that does not interfere with the neurorehabilitation procedure and can increase therapy effectiveness in rehabilitation patients with right-hand task-specific focal dystonia.

The Effects of Oscillatory Biofield Therapy on Pain and Functional Limitations Associated with Carpal Tunnel Syndrome: Randomized, Placebo-Controlled, Double-Blind Study.

PubMed

Nourbakhsh, Mohammad Reza; Bell, Thomas J; Martin, Jason Benson; Arab, Amir Massoud

2016-11-01

Biofield treatments have been used for pain control in patients with cancer and chronic pain. However, research on the effect of biofield treatment on specific somatic disorders is lacking. This study intends to investigate the effect of oscillating biofield therapy (OBFT) on symptoms of carpal tunnel syndrome. Randomized, placebo-controlled, double-blind study. Thirty patients with chronic carpal tunnel syndrome participated in the study. Patients were randomly assigned to active or placebo treatment groups. Those in the treatment group received six sessions of OBFT with intention to treat during a period of 2 weeks. Patients in the placebo group had the same number of treatment sessions with mock OBFT treatment. The Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire; Symptom Severity Scale (SSS); and Functional Status Scale (FSS) were used for outcome assessment. Both clinically and statistically significant changes in intensity of pain with activity (95% confidence interval [CI], 2.5-4.2; p = 0.000), night pain (p = 0.000, 95% CI, 3.2-5.7), DASH questionnaire (95% CI, 12.0-21.9; p = 0.000), SSS (95% CI, 0.64-1.15; p = 0.003), and FSS (95% CI, 0.41-0.97; p = 0.029) were found between the treatment and placebo groups. Statistically significant reduction in number of patients with positive results on the Phalen test (87%; p = 0.000), Tinel sign (73%; p = 0.000), and hand paresthesia (80%; p = 0.000) was noted in the treatment group. During 6-month follow-up, 86% of patients in the treatment group remained pain free and had no functional limitations. OBFT can be a viable and effective treatment for improving symptoms and functional limitations associated with chronic carpal tunnel syndrome.

The Effects of Oscillatory Biofield Therapy on Pain and Functional Limitations Associated with Carpal Tunnel Syndrome: Randomized, Placebo-Controlled, Double-Blind Study

PubMed Central

Bell, Thomas J.; Martin, Jason Benson; Arab, Amir Massoud

2016-01-01

Abstract Objectives: Biofield treatments have been used for pain control in patients with cancer and chronic pain. However, research on the effect of biofield treatment on specific somatic disorders is lacking. This study intends to investigate the effect of oscillating biofield therapy (OBFT) on symptoms of carpal tunnel syndrome. Design: Randomized, placebo-controlled, double-blind study. Participants: Thirty patients with chronic carpal tunnel syndrome participated in the study. Intervention: Patients were randomly assigned to active or placebo treatment groups. Those in the treatment group received six sessions of OBFT with intention to treat during a period of 2 weeks. Patients in the placebo group had the same number of treatment sessions with mock OBFT treatment. Outcome measure: The Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire; Symptom Severity Scale (SSS); and Functional Status Scale (FSS) were used for outcome assessment. Results: Both clinically and statistically significant changes in intensity of pain with activity (95% confidence interval [CI], 2.5–4.2; p = 0.000), night pain (p = 0.000, 95% CI, 3.2–5.7), DASH questionnaire (95% CI, 12.0–21.9; p = 0.000), SSS (95% CI, 0.64–1.15; p = 0.003), and FSS (95% CI, 0.41–0.97; p = 0.029) were found between the treatment and placebo groups. Statistically significant reduction in number of patients with positive results on the Phalen test (87%; p = 0.000), Tinel sign (73%; p = 0.000), and hand paresthesia (80%; p = 0.000) was noted in the treatment group. During 6-month follow-up, 86% of patients in the treatment group remained pain free and had no functional limitations. Conclusion: OBFT can be a viable and effective treatment for improving symptoms and functional limitations associated with chronic carpal tunnel syndrome. PMID:27487406

How "Blind" Are Double-Blind Studies?

ERIC Educational Resources Information Center

Margraf, Jurgen; And Others

1991-01-01

Compared alprazolam, imipramine, and placebo in the treatment of panic disorder patients (n=59) to investigate concerns about the internal validity of the double-blind design. Found that the great majority of patients and physicians were able to rate accurately whether active drug or placebo had been given and physicians could distinguish between…

Impact of Vitamin D Replacement on Markers of Glucose Metabolism and Cardio-Metabolic Risk in Women with Former Gestational Diabetes--A Double-Blind, Randomized Controlled Trial.

PubMed

Yeow, Toh Peng; Lim, Shueh Lin; Hor, Chee Peng; Khir, Amir S; Wan Mohamud, Wan Nazaimoon; Pacini, Giovanni

2015-01-01

Gestational Diabetes Mellitus (GDM) and vitamin D deficiency are related to insulin resistance and impaired beta cell function, with heightened risk for future development of diabetes. We evaluated the impact of vitamin D supplementation on markers of glucose metabolism and cardio metabolic risk in Asian women with former GDM and hypovitaminosis D. In this double blind, randomized controlled trial, 26 participants were randomized to receive either daily 4000 IU vitamin D3 or placebo capsules. 75 g Oral Glucose Tolerance Test (OGTT) and biochemistry profiles were performed at baseline and 6 month visits. Mathematical models, using serial glucose, insulin and C peptide measurements from OGTT, were employed to calculate insulin sensitivity and beta cell function. Thirty three (76%) women with former GDM screened had vitamin D level of <50 nmol/L at baseline. Supplementation, when compared with placebo, resulted in increased vitamin D level (+51.1 nmol/L vs 0.2 nmol/L, p<0.001) and increased fasting insulin (+20% vs 18%, p = 0.034). The vitamin D group also demonstrated a 30% improvement in disposition index and an absolute 0.2% (2 mmol/mol) reduction in HbA1c. There was no clear change in insulin sensitivity or markers of cardio metabolic risk. This study highlighted high prevalence of vitamin D deficiency among Asian women with former GDM. Six months supplementation with 4000 IU of vitamin D3 safely restored the vitamin D level, improved basal pancreatic beta-cell function and ameliorated the metabolic state. There was no effect on markers of cardio metabolic risk. Further mechanistic studies exploring the role of vitamin D supplementation on glucose homeostasis among different ethnicities may be needed to better inform future recommendations for these women with former GDM at high risk of both hypovitaminosis D and future diabetes.

The effectiveness and safety of topical PhotoActif phosphatidylcholine-based anti-cellulite gel and LED (red and near-infrared) light on Grade II-III thigh cellulite: a randomized, double-blinded study.

PubMed

Sasaki, Gordon H; Oberg, Kerby; Tucker, Barbara; Gaston, Margaret

2007-06-01

Cellulite of the upper lateral and posterior thighs and lower buttocks represents a common, physiological and unwanted condition whose etiologies and effective management are subjects of continued debate. The purpose of this controlled, double-blinded study is to evaluate the efficacy and safety of a novel phosphatidylcholine-based, cosmeceutical anti-cellulite gel combined with a light-emitting diode (LED) array at the wavelengths of red (660 nm) and near-infrared (950 nm), designed to counter the possible mechanisms that purportedly accentuate the presence of thigh cellulite. Nine healthy female volunteers with Grade II-III thigh cellulite were randomly treated twice daily with an active gel on one thigh and a placebo gel on the control thigh for 3 months. Twice weekly, each thigh was exposed for a 15-minute treatment with LED light for a total of 24 treatments. At 0, 6, and 12 weeks of the study the following clinical determinants were obtained: standardized digital photography, height and weight measurements, standardized thigh circumference tape measurements, pinch testing, body mass index (kg/m2), body fat analysis (Futrex-5500/XL near-infrared analyzer), and digital high-resolution ultrasound imaging of the dermal-adiposal border. In selected patients, full-thickness biopsies of the placebo and active-treated sites were obtained. At 18 months, repeat standardized digital photography, height and weight measurements, and body mass index measurements were obtained. At the end of 3 months, eight of nine thighs treated with the phosphatidylcholine-based, anti-cellulite gel and LED treatments were downgraded to a lower cellulite grade by clinical examination, digital photography, and pinch test assessment. Digital ultrasound at the dermal-adiposal interface demonstrated not only a statistically significant reduction of immediate hypodermal depth, but also less echo-like intrusions into the dermal layer. Three of six biopsies from thighs treated for 3 months with

Randomized, double-blind trial of fluconazole versus voriconazole for prevention of invasive fungal infection after allogeneic hematopoietic cell transplantation

PubMed Central

Carter, Shelly L.; Walsh, Thomas J.; Kurtzberg, Joanne; Small, Trudy N.; Baden, Lindsey R.; Gersten, Iris D.; Mendizabal, Adam M.; Leather, Helen L.; Confer, Dennis L.; Maziarz, Richard T.; Stadtmauer, Edward A.; Bolaños-Meade, Javier; Brown, Janice; DiPersio, John F.; Boeckh, Michael; Marr, Kieren A.

2010-01-01

Invasive fungal infection (IFI) is a serious threat after allogeneic hematopoietic cell transplant (HCT). This multicenter, randomized, double-blind trial compared fluconazole (N = 295) versus voriconazole (N = 305) for the prevention of IFI in the context of a structured fungal screening program. Patients undergoing myeloablative allogeneic HCT were randomized before HCT to receive study drugs for 100 days, or for 180 days in higher-risk patients. Serum galactomannan was assayed twice weekly for 60 days, then at least weekly until day 100. Positive galactomannan or suggestive signs triggered mandatory evaluation for IFI. The primary endpoint was freedom from IFI or death (fungal-free survival; FFS) at 180 days. Despite trends to fewer IFIs (7.3% vs 11.2%; P = .12), Aspergillus infections (9 vs 17; P = .09), and less frequent empiric antifungal therapy (24.1% vs 30.2%, P = .11) with voriconazole, FFS rates (75% vs 78%; P = .49) at 180 days were similar with fluconazole and voriconazole, respectively. Relapse-free and overall survival and the incidence of severe adverse events were also similar. This study demonstrates that in the context of intensive monitoring and structured empiric antifungal therapy, 6-month FFS and overall survival did not differ in allogeneic HCT recipients given prophylactic fluconazole or voriconazole. This trial was registered at www.clinicaltrials.gov as NCT00075803. PMID:20826719

One year double blind study of high vs low frequency subcallosal cingulate stimulation for depression.

PubMed

Eitan, Renana; Fontaine, Denys; Benoît, Michel; Giordana, Caroline; Darmon, Nelly; Israel, Zvi; Linesky, Eduard; Arkadir, David; Ben-Naim, Shiri; Iserlles, Moshe; Bergman, Hagai; Hulse, Natasha; Abdelghani, Mohamed; McGuffin, Peter; Farmer, Anne; DeLea, Peichel; Ashkan, Keyoumars; Lerer, Bernard

2018-01-01

Subcallosal Brodmann's Area 25 (Cg25) Deep Brain Stimulation (DBS) is a new promising therapy for treatment resistant major depressive disorder (TR-MDD). While different DBS stimulating parameters may have an impact on the efficacy and safety of the therapy, there is no data to support a protocol for optimal stimulation parameters for depression. Here we present a prospective multi-center double-blind randomized crossed-over 13-month study that evaluated the effects of High (130 Hz) vs Low (20 Hz) frequency Cg25 stimulation for nine patients with TR-MDD. Four out of nine patients achieved response criteria (≥40% reduction of symptom score) compared to mean baseline values at the end of the study. The mean percent change of MADRS score showed a similar improvement in the high and low frequency stimulation groups after 6 months of stimulation (-15.4 ± 21.1 and -14.7 ± 21.1 respectively). The mean effect at the end of the second period (6 months after cross-over) was higher than the first period (first 6 months of stimulation) in all patients (-23.4 ± 19.9 (n = 6 periods) and -13.0 ± 22 (n = 9 periods) respectively). At the end of the second period, the mean percent change of the MADRS scores improved more in the high than low frequency groups (-31.3 ± 19.3 (n = 4 patients) and -7.7 ± 10.9 (n = 2 patients) respectively). Given the small numbers, detailed statistical analysis is challenging. Nonetheless the results of this study suggest that long term high frequency stimulation might confer the best results. Larger scale, randomized double blind trials are needed in order to evaluate the most effective stimulation parameters. Copyright © 2017 Elsevier Ltd. All rights reserved.

Randomized double-blind trial comparing the cosmetic outcome of cutting diathermy versus scalpel for skin incisions.

PubMed

Aird, L N F; Bristol, S G; Phang, P T; Raval, M J; Brown, C J

2015-04-01

Controversy exists about whether cutting diathermy for skin incisions leads to a cosmetically inferior scar. Cosmetic outcomes were compared between skin incisions created with cutting diathermy versus scalpel. Wound infection rates and postoperative incisional pain were also compared. This was a randomized double-blind trial comparing cutting diathermy and scalpel in patients undergoing bowel resection. Scar cosmesis was assessed at 6 months after surgery by a plastic surgeon and a research associate using the Vancouver Scar Scale (VSS) and the Patient and Observer Scar Assessment Scale (POSAS). Patients also used POSAS to self-evaluate their scars. Wound infections within 30 days were recorded, and incision pain scores were measured on the first 5 days after operation. A total of 66 patients were randomized to cutting diathermy (31) or scalpel (35). At 6 months, there was no significant difference between the diathermy and scalpel groups in mean(s.d.) VSS scores (4·9(2·6) versus 5·0(1·9); P = 0·837), mean POSAS total scores (19·2(8·0) versus 20·0(7·4); P = 0·684) or subjective POSAS total scores (20·2(12·1) versus 21·3(10·4); P = 0·725). Neither were there significant differences in wound infection rates between the groups (5 of 30 versus 5 of 32; P = 1·000). Pain scores on day 1 after operation were significantly lower in the diathermy group (mean 1·68 versus 3·13; P = 0·018), but were not significantly different on days 2-5. Cutting diathermy is a cosmetically acceptable technique for abdominal skin incisions. There is no increased risk of wound infection, and diathermy may convey benefit in terms of early postoperative wound pain. NCT01496404 ( http://www.clinicaltrials.gov). © 2015 BJS Society Ltd Published by John Wiley & Sons Ltd.

Do TETRA (Airwave) Base Station Signals Have a Short-Term Impact on Health and Well-Being? A Randomized Double-Blind Provocation Study

PubMed Central

Wallace, Denise; Eltiti, Stacy; Ridgewell, Anna; Garner, Kelly; Russo, Riccardo; Sepulveda, Francisco; Walker, Stuart; Quinlan, Terence; Dudley, Sandra; Maung, Sithu; Deeble, Roger; Fox, Elaine

2010-01-01

Background “Airwave” is the new communication system currently being rolled out across the United Kingdom for the police and emergency services, based on the Terrestrial Trunked Radio Telecommunications System (TETRA). Some police officers have complained about skin rashes, nausea, headaches, and depression as a consequence of using their Airwave handsets. In addition, a small subgroup in the population self-report being sensitive to electromagnetic fields (EMFs) in general. Objectives We conducted a randomized double-blind provocation study to establish whether short-term exposure to a TETRA base station signal has an impact on the health and well-being of individuals with self-reported “electrosensitivity” and of participants who served as controls. Methods Fifty-one individuals with self-reported electrosensitivity and 132 age- and sex-matched controls participated in an open provocation test; 48 sensitive and 132 control participants went on to complete double-blind tests in a fully screened semianechoic chamber. Heart rate, skin conductance, and blood pressure readings provided objective indices of short-term physiological response. Visual analog scales and symptom scales provided subjective indices of well-being. Results We found no differences on any measure between TETRA and sham (no signal) under double-blind conditions for either controls or electrosensitive participants, and neither group could detect the presence of a TETRA signal at rates greater than chance (50%). When conditions were not double blind, however, the self-reported electrosensitive individuals did report feeling worse and experienced more severe symptoms during TETRA compared with sham. Conclusions Our findings suggest that the adverse symptoms experienced by electrosensitive individuals are due to the belief of harm from TETRA base stations rather than to the low-level EMF exposure itself. PMID:20075020

Immunogenicity and safety of a high-dose hepatitis B vaccine among patients receiving methadone maintenance treatment: A randomized, double-blinded, parallel-controlled trial.

PubMed

Shi, Jing; Feng, Yongliang; Gao, Linying; Feng, Dan; Yao, Tian; Shi, Shan; Zhang, Yawei; Liang, Xiaofeng; Wang, Suping

2017-04-25

To explore whether the immunization with high-dose (60μg) hepatitis B vaccines in patients receiving methadone maintenance treatment (MMT) could yield a superior protection against hepatitis B infection than did the standard dose (20μg). We conducted a randomized, double-blinded, parallel-controlled trial in MMT patients. Patients with serologically negative hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs) were randomized in a ratio of 1:1 to receive three intramuscular injections of 20μg or 60μg recombinant hepatitis B vaccine at months 0, 1, and 6. Serum HBsAg and anti-HBs were measured at months 7 and 12 post-vaccination to assess the immunogenicity. A total of 196 MMT patients were randomized and 195 received at least one injection (98 and 97 in 20 and 60μg vaccine groups, respectively). The 60μg vaccine group showed a seroconversion of anti-HBs of 87.3%, high-level response rate of 56.3%, and GMC of 742.9mIU/mL at month 7. While these results were numerically higher than the 20μg group, a statistical difference was not found. HIV infection and concomitant drug abuse were negatively associated with the robust immune responses. 7.7% of MMT patients receiving at least one dose of vaccine reported solicited adverse reactions within 7days after vaccination, 2.6% reported unsolicited adverse reactions within 28days after vaccination. None of the MMT patients reported serious adverse events or became HBsAg positive during the follow-up. The three-dose regimen of 60μg recombinant hepatitis B vaccine at months 0, 1, and 6 can yield a similar immunogenicity among MMT patients as compared to the 20μg vaccine. ClinicalTrials.gov identifier: NCT02991599. Copyright © 2017. Published by Elsevier Ltd.

Comparison of oral amoxicillin with placebo for the treatment of world health organization-defined nonsevere pneumonia in children aged 2-59 months: a multicenter, double-blind, randomized, placebo-controlled trial in pakistan.

PubMed

Hazir, Tabish; Nisar, Yasir Bin; Abbasi, Saleem; Ashraf, Yusra Pervaiz; Khurshid, Joza; Tariq, Perveen; Asghar, Rai; Murtaza, Asifa; Masood, Tahir; Maqbool, Sajid

2011-02-01

world Health Organization (WHO) acute respiratory illness case management guidelines classify children with fast breathing as having pneumonia and recommend treatment with an antibiotic. There is concern that many of these children may not have pneumonia and are receiving antibiotics unnecessarily. This could increase antibiotic resistance in the community. The aim was to compare the clinical outcome at 72 h in children with WHO-defined nonsevere pneumonia when treated with amoxicillin, compared with placebo. we performed a double-blind, randomized, equivalence trial in 4 tertiary hospitals in Pakistan. Nine hundred children aged 2-59 months with WHO defined nonsevere pneumonia were randomized to receive either 3 days of oral amoxicillin (45mg/kg/day) or placebo; 873 children completed the study. All children were followed up on days 3, 5, and 14. The primary outcome was therapy failure defined a priori at 72 h. in per-protocol analysis at day 3, 31 (7.2%) of the 431 children in the amoxicillin arm and 37 (8.3%) of the 442 in placebo group had therapy failure. This difference was not statistically significant (odds ratio [OR], .85; 95%CI, .50-1.43; P = .60). The multivariate analysis identified history of difficult breathing (OR, 2.86; 95% CI, 1.29-7.23; P = .027) and temperature >37.5°C 100°F at presentation (OR, 1.99; 95% CI, 1.37-2.90; P = .0001) as risk factors for treatment failure by day 5. clinical outcome in children aged 2-59 months with WHO-defined nonsevere pneumonia is not different when treated with an antibiotic or placebo. Similar trials are needed in countries with a high burden of pneumonia to rationalize the use of antibiotics in these communities.

Evaluation of pulsing magnetic field effects on paresthesia in multiple sclerosis patients, a randomized, double-blind, parallel-group clinical trial.

PubMed

Afshari, Daryoush; Moradian, Nasrin; Khalili, Majid; Razazian, Nazanin; Bostani, Arash; Hoseini, Jamal; Moradian, Mohamad; Ghiasian, Masoud

2016-10-01

Evidence is mounting that magnet therapy could alleviate the symptoms of multiple sclerosis (MS). This study was performed to test the effects of the pulsing magnetic fields on the paresthesia in MS patients. This study has been conducted as a randomized, double-blind, parallel-group clinical trial during the April 2012 to October 2013. The subjects were selected among patients referred to MS clinic of Imam Reza Hospital; affiliated to Kermanshah University of Medical Sciences, Iran. Sixty three patients with MS were included in the study and randomly were divided into two groups, 35 patients were exposed to a magnetic pulsing field of 4mT intensity and 15-Hz frequency sinusoidal wave for 20min per session 2 times per week over a period of 2 months involving 16 sessions and 28 patients was exposed to a magnetically inactive field (placebo) for 20min per session 2 times per week over a period of 2 months involving 16 sessions. The severity of paresthesia was measured by the numerical rating scale (NRS) at 30, 60days. The study primary end point was NRS change between baseline and 60days. The secondary outcome was NRS change between baseline and 30days. Patients exposing to magnetic field showed significant paresthesia improvement compared with the group of patients exposing to placebo. According to our results pulsed magnetic therapy could alleviate paresthesia in MS patients .But trials with more patients and longer duration are mandatory to describe long-term effects. Copyright © 2016 Elsevier B.V. All rights reserved.

Inorganic Nitrate in Angina Study: A Randomized Double-Blind Placebo-Controlled Trial.

PubMed

Schwarz, Konstantin; Singh, Satnam; Parasuraman, Satish K; Rudd, Amelia; Shepstone, Lee; Feelisch, Martin; Minnion, Magdalena; Ahmad, Shakil; Madhani, Melanie; Horowitz, John; Dawson, Dana K; Frenneaux, Michael P

2017-09-08

In this double-blind randomized placebo-controlled crossover trial, we investigated whether oral sodium nitrate, when added to existing background medication, reduces exertional ischemia in patients with angina. Seventy patients with stable angina, positive electrocardiogram treadmill test, and either angiographic or functional test evidence of significant ischemic heart disease were randomized to receive oral treatment with either placebo or sodium nitrate (600 mg; 7 mmol) for 7 to 10 days, followed by a 2-week washout period before crossing over to the other treatment (n=34 placebo-nitrate, n=36 nitrate-placebo). At baseline and at the end of each treatment, patients underwent modified Bruce electrocardiogram treadmill test, modified Seattle Questionnaire, and subgroups were investigated with dobutamine stress, echocardiogram, and blood tests. The primary outcome was time to 1 mm ST depression on electrocardiogram treadmill test. Compared with placebo, inorganic nitrate treatment tended to increase the primary outcome exercise time to 1 mm ST segment depression (645.6 [603.1, 688.0] seconds versus 661.2 [6183, 704.0] seconds, P =0.10) and significantly increased total exercise time (744.4 [702.4, 786.4] seconds versus 760.9 [719.5, 802.2] seconds, P =0.04; mean [95% confidence interval]). Nitrate treatment robustly increased plasma nitrate (18.3 [15.2, 21.5] versus 297.6 [218.4, 376.8] μmol/L, P <0.0001) and almost doubled circulating nitrite concentrations (346 [285, 405] versus 552 [398, 706] nmol/L, P =0.003; placebo versus nitrate treatment). Other secondary outcomes were not significantly altered by the intervention. Patients on antacid medication appeared to benefit less from nitrate supplementation. Sodium nitrate treatment may confer a modest exercise capacity benefit in patients with chronic angina who are taking other background medication. URL: https://www.clinicaltrials.gov/. Unique identifier: NCT02078921. EudraCT number: 2012-000196-17. �

Effects of raloxifene on cognition in postmenopausal women with schizophrenia: a double-blind, randomized, placebo-controlled trial.

PubMed

Huerta-Ramos, Elena; Iniesta, Raquel; Ochoa, Susana; Cobo, Jesús; Miquel, Eva; Roca, Mercedes; Serrano-Blanco, Antoni; Teba, Fernando; Usall, Judith

2014-02-01

Studies of estrogen therapy in postmenopausal women provide evidence of an effect of sex hormones on cognitive function. Estrogen has demonstrated some utility in the prevention of normal, age-related decline in cognitive functions, especially in memory. The potential therapeutic utility of estrogens in schizophrenia is increasingly being recognized. Raloxifene, a selective estrogen receptor modulator (SERM), appears to act similarly to conjugated estrogens on dopamine and serotonin brain systems, and may be a better option since it lacks the possible negative effects of estrogen on breast and uterine tissue. We assessed the utility of raloxifene as an adjuvant treatment for cognitive symptoms in postmenopausal women with schizophrenia in a 12-week, double-blind, randomized, placebo-controlled study. Patients were recruited from both the inpatient and outpatient departments. Thirty-three postmenopausal women with schizophrenia (DSM-IV) were randomized to receive either adjuvant raloxifene (16 women) or adjuvant placebo (17 women) for three months. The main outcome measures were: Memory, attention and executive functions. Assessment was conducted at baseline and week 12. The total sample is homogenous with respect to: age, years of schooling, illness duration, baseline symptomatology and pharmacological treatment. The addition of raloxifene (60 mg) to regular antipsychotic treatment showed: we found significant differences in some aspects of memory and executive function in patients treated with raloxifene. This improvement does not correlate with clinical improvement. The use of raloxifene as an adjuvant treatment in postmenopausal women with schizophrenia seems to be useful in improving cognitive symptoms. © 2013 Published by Elsevier B.V. and ECNP.

The EMPOWER study: randomized, prospective, double-blind, multicenter trial of vagal blockade to induce weight loss in morbid obesity.

PubMed

Sarr, Michael G; Billington, Charles J; Brancatisano, Roy; Brancatisano, Anthony; Toouli, James; Kow, Lilian; Nguyen, Ninh T; Blackstone, Robin; Maher, James W; Shikora, Scott; Reeds, Dominic N; Eagon, J Christopher; Wolfe, Bruce M; O'Rourke, Robert W; Fujioka, Ken; Takata, Mark; Swain, James M; Morton, John M; Ikramuddin, Sayeed; Schweitzer, Michael; Chand, Bipan; Rosenthal, Raul

2012-11-01

Intermittent, reversible intraabdominal vagal blockade (VBLOC® Therapy) demonstrated clinically important weight loss in feasibility trials. EMPOWER, a randomized, double-blind, prospective, controlled trial was conducted in USA and Australia. Five hundred three subjects were enrolled at 15 centers. After informed consent, 294 subjects were implanted with the vagal blocking system and randomized to the treated (n = 192) or control (n = 102) group. Main outcome measures were percent excess weight loss (percent EWL) at 12 months and serious adverse events. Subjects controlled duration of therapy using an external power source; therapy involved a programmed algorithm of electrical energy delivered to the subdiaphragmatic vagal nerves to inhibit afferent/efferent vagal transmission. Devices in both groups performed regular, low-energy safety checks. Data are mean ± SEM. Study subjects consisted of 90 % females, body mass index of 41 ± 1 kg/m(2), and age of 46 ± 1 years. Device-related complications occurred in 3 % of subjects. There was no mortality. 12-month percent EWL was 17 ± 2 % for the treated and 16 ± 2 % for the control group. Weight loss was related linearly to hours of device use; treated and controls with ≥ 12 h/day use achieved 30 ± 4 and 22 ± 8 % EWL, respectively. VBLOC® therapy to treat morbid obesity was safe, but weight loss was not greater in treated compared to controls; clinically important weight loss, however, was related to hours of device use. Post-study analysis suggested that the system electrical safety checks (low charge delivered via the system for electrical impedance, safety, and diagnostic checks) may have contributed to weight loss in the control group.

The influence of ginger (Zingiber officinale) on human sperm quality and DNA fragmentation: A double-blind randomized clinical trial

PubMed Central

Hosseini, Jalil; Mardi Mamaghani, Azar; Hosseinifar, Hani; Sadighi Gilani, Mohammad Ali; Dadkhah, Farid; Sepidarkish, Mahdi

2016-01-01

Background: Although the effectiveness of ginger as an antioxidant agent has been exploited, little human research has been conducted on its activity on male reproductive functions. Objective: This study was designed to investigate the effects of ginger (Zingiber officinale) on sperm DNA fragmentation (SDF) in infertile men. Materials and Methods: This randomized double-blind, placebo-controlled trial with a 1:1 allocation was performed on 100 infertility treatment candidates who were admitted to Royan Institute for Reproductive Biomedicine, Tehran, Iran. Patients were randomly assigned to receive one of two treatments: ginger and placebo. Patients were given a 3-month oral treatment (members received capsules containing 250 mg of ginger powder twice a day in ginger and a placebo in other group). Before and after treatment, standardized semen samples were obtained to determine sperm concentration, motility, and SDF according to World Health Organization. Results: There was no significant difference between two groups regarding SDF at baseline (53.48. 95%CI: 37.95-69.02) in cases and (56.75, 95%CI: 40.01-73.5) in controls. The average positive percentage of SDF in patients receiving ginger (17.77, 95%CI: 6.16-29.39) was lower compared with placebo (40.54, 95%CI: 23.94-57.13) after three month of treatment (p=0.02). In multivariate analysis, SDF was significantly lower in patients receiving ginger compared with placebo (mean difference: 3.21, 95%CI: 0.78-5.63, p=0.009). There were no significant differences between two groups regarding to semen parameters. Conclusion: The present study has demonstrated that ginger in a controlled study of efficacy was effective in decreasing SDF in infertile men. PMID:27679829

A Randomized, Double-Blind Study Assessing Changes in Cognitive Function in Indian School Children Receiving a Combination of Bacopa monnieri and Micronutrient Supplementation vs. Placebo

PubMed Central

Mitra-Ganguli, Tora; Kalita, Soumik; Bhushan, Sakshi; Stough, Con; Kean, James; Wang, Nan; Sethi, Vidhu; Khadilkar, Anuradha

2017-01-01

Several studies have indicated a chronic cognitive enhancing effect of Bacopa monnieri across different ages and cognitive impairment associated with vitamin and mineral deficiencies in children. Therefore, we investigated the effects of 4-month supplementation with a combination of B. monnieri extract and multiple micronutrients on cognitive functions in Indian school children aged 7–12 years. This was a randomized, double-blind, parallel design, single-center study in which 300 children were randomized to receive a beverage either fortified with B. monnieri and multiple micronutrients (“fortified”) or a non-fortified isocaloric equivalent (“control”) twice-daily for 4 months. Cognitive function was assessed by the Cambridge Neuropsychological Automated Test Battery (CANTAB) administered at baseline, Day 60 and Day 121. The primary endpoint was change in short-term memory (working memory) from baseline in subjects receiving “fortified” vs. “control” beverages after 4 months. Secondary endpoints included sustained attention, episodic memory, and executive function. The “fortified” beverage did not significantly improve short-term memory or any of the secondary outcomes tested relative to the “control” beverage. However, the spatial working memory “strategy” score showed significant improvement on Day 60 (difference between groups in change from baseline: −0.55; p < 0.05), but not on Day 121 due to the active intervention. Study products were well-tolerated. Reasons for these unexpected findings are discussed. PMID:29204115

Does selenium supplementation affect thyroid function? Results from a randomized, controlled, double-blinded trial in a Danish population.

PubMed

Winther, Kristian Hillert; Bonnema, Steen Joop; Cold, Frederik; Debrabant, Birgit; Nybo, Mads; Cold, Søren; Hegedüs, Laszlo

2015-06-01

Selenium is present in the active site of proteins important for thyroid hormone synthesis and metabolism. The objective of this study is to investigate the effect of selenium supplementation in different doses on thyroid function, under conditions of suboptimal dietary selenium intake. The Danish PREvention of Cancer by Intervention with SElenium pilot study (DK-PRECISE) is a randomized, double-blinded, placebo-controlled trial. A total of 491 males and females aged 60-74 years were randomized to 100 μg (n=124), 200 μg (n=122), or 300 μg (n=119) selenium-enriched yeast or matching yeast-based placebo tablets (n=126). A total of 361 participants, equally distributed across treatment groups, completed the 5-year intervention period. Plasma samples were analyzed for selenium and serum samples for TSH, free triiodothyronine (FT3), and free thyroxine (FT4) at baseline, and after 6 months, and 5 years of supplementation. Plasma selenium concentrations increased significantly and dose-dependently in treatment groups receiving selenium (P<0.001). Serum TSH and FT4 concentrations decreased significantly and dose-dependently by 0.066 mIU/l (P=0.010) and 0.11 pmol/l (P=0.015), respectively, per 100 μg/day increase, with insignificant differences between 6 months and 5 years. No significant effects were found for FT3 and FT3:FT4 ratio. In euthyroid subjects, selenium supplementation minutely and dose-dependently affects thyroid function, when compared with placebo, by decreasing serum TSH and FT4 concentrations. Based on these findings, selenium supplementation is not warranted under conditions of marginal selenium deficiency. However, a role for selenium supplementation in the treatment of autoimmune thyroid diseases is still unresolved. © 2015 European Society of Endocrinology.

Lack of efficacy of moclobemide or imipramine in the treatment of recurrent brief depression: results from an exploratory randomized, double-blind, placebo-controlled treatment study.

PubMed

Baldwin, David S; Green, Mary; Montgomery, Stuart A

2014-11-01

'Recurrent brief depression' (RBD) is a common, distressing and impairing depressive disorder for which there is no current proven pharmacological or psychological treatment. This multicentre, randomized, fixed-dose, parallel-group, placebo-controlled study of the reversible inhibitor of monoamine oxidase moclobemide (450 mg/day) and the tricyclic antidepressant imipramine (150 mg/day) evaluated the potential efficacy of active medication, when compared with placebo, in patients with recurrent brief depression, recruited in the mid-1990s. After a 2-4-week single-blind placebo run-in period, a total of 35 patients were randomized to receive double-blind medication for 4 months, but only 16 completed the active treatment period. An intention-to-treat analysis of the 34 evaluable patients found no evidence for the efficacy of moclobemide or imipramine, when compared with placebo, in significantly reducing the severity, duration or frequency of depressive episodes. A total of 28 patients experienced at least one adverse event, and four patients engaged in nonfatal self-harm. Limitations of the study include the small sample size and the high rate of participant withdrawal. The lack of efficacy of these antidepressant drugs and the previous finding of the lack of efficacy of the selective serotonin reuptake inhibitor fluoxetine together indicate that medications other than antidepressant drugs should be investigated as potential treatments for what remains a common, distressing and potentially hazardous condition.

The Impact of Preoperative Enteral Nutrition Enriched with Eicosapentaenoic Acid on Postoperative Hypercytokinemia after Pancreatoduodenectomy: The Results of a Double-Blinded Randomized Controlled Trial.

PubMed

Ashida, Ryo; Okamura, Yukiyasu; Wakabayashi-Nakao, Kanako; Mizuno, Takashi; Aoki, Shuichi; Uesaka, Katsuhiko

2018-06-08

To investigate whether preoperative enteral diets -enriched in eicosapentaenoic acid (EPA) supplements could reduce the incidence of hypercytokinemia after pancreatoduodenectomy (PD) in a double-blinded randomized -controlled trial. Patients with resectable periampullary cancer were randomized into either the control group or the treatment group. Patients in the treatment group received oral supplementation (600 kcal/day) containing EPA for 7 days before surgery. Patients in the control group received isocaloric isonitrogenous standard nutrition (600 kcal/day) without EPA for 7 days before surgery. The primary endpoint was postoperative serum concentrations of interleukin-6 (IL-6). The secondary endpoints were the postoperative nutritional status and the incidence of postoperative infectious complications. Twenty-four patients were enrolled in the present study. After exclusion, 20 patients (control group, n = 9; treatment group, n = 11) were analyzed. There were no significant differences in the curves for the serum concentration of IL-6 (p = 0.68) or the incidence of infectious complications between the 2 groups (control group: 78%, treatment group: 55%, p = 0.37). The results of a double-blinded randomized controlled trial indicated that preoperative immunonutrition had no marked impact on the rates of postoperative hypercytokinemia or infectious complications after PD. © 2018 S. Karger AG, Basel.

Gastrografin in Prolonged Postoperative Ileus: A Double-blinded Randomized Controlled Trial.

PubMed

Vather, Ryash; Josephson, Rachel; Jaung, Rebekah; Kahokehr, Arman; Sammour, Tarik; Bissett, Ian

2015-07-01

To investigate the therapeutic value of Gastrografin in shortening duration of prolonged postoperative ileus (PPOI) after elective colorectal surgery. Gut wall edema is central to the pathogenesis of PPOI. Hyperosmotic, orally administered, water-soluble contrast media such as Gastrografin are theoretically capable of mitigating this edema. A double-blinded, placebo-controlled, randomized trial was conducted. Participants were allocated to receive 100 mL of Gastrografin (Exposure Group) or flavored distilled water (Control Group) administered enterally. Other aspects of management were standardized. Resolution of PPOI was assessed 12-hourly. Eighty patients were randomized equally, with 5 in the Exposure Group and 4 in the Control Group excluded from analysis. Participants were evenly matched at baseline. Mean duration of PPOI did not differ between Exposure and Control Groups (83.7 vs 101.3 hours; P = 0.191). When considering individual markers of PPOI resolution, Gastrografin did not affect time to resolution of nausea and vomiting (64.5 vs 74.3 hours; P = 0.404) or consumption of oral diet (75.8 vs 90.0 hours; P = 0.297). However, it accelerated time to flatus or stool (18.9 vs 32.7 hours; P = 0.047) and time to resolution of abdominal distension (52.8 vs 77.7 hours; P = 0.013). There were no significant differences between groups in nasogastric output; analgesia, antiemetic, or fluid requirement; complications; or length of stay. Gastrografin is not clinically useful in shortening an episode of PPOI characterized by upper and lower gastrointestinal symptoms. It may however be of therapeutic benefit in the subset of PPOI patients who display lower gastrointestinal symptoms exclusively after surgery.

Double-blind, placebo-controlled, randomized study of chlorhexidine prophylaxis for 5-fluorouracil-based chemotherapy-induced oral mucositis with nonblinded randomized comparison to oral cooling (cryotherapy) in gastrointestinal malignancies.

PubMed

Sorensen, Jens Benn; Skovsgaard, Torben; Bork, Ellen; Damstrup, Lars; Ingeberg, Sten

2008-04-01

The purpose was to evaluate prevention of oral mucositis (OM) using chlorhexidine compared with placebo and with oral cooling (cryotherapy) during fluorouracil (5-FU)-based chemotherapy in gastrointestinal (GI) cancer. Patients with previously untreated GI cancer receiving bolus 5-FU/leucovorin chemotherapy were randomized to chlorhexidine mouthrinse 3 times a day for 3 weeks (Arm A), double-blind placebo (normal saline) with the same dose and frequency (Arm B), or cryotherapy with crushed ice 45 minutes during chemotherapy (Arm C). Patients self-reported on severity (CTC-grading) and duration of OM. Among 225 patients randomized, 206 answered the questionnaire (70, 64, and 63 patients in Arms A, B, and C, respectively) and were well balanced with respect to diagnoses, stage, age, sex, smoking habits, and performance status. Mucositis grade 3-4 occurred more frequently in Arm B (33%) than in A (13%, P< .01) and C (11%, P< .005). Duration was significantly longer in B than in both A (P= .035) and C (P= .003). The frequency and duration of OM are significantly improved by prophylactic chlorhexidine and by cryotherapy. The latter is easy and inexpensive but has limited use, as it is drug- and schedule-dependent. The current study is the first double-blind randomized evaluation of prophylactic chlorhexidine in a large adult patient population with solid tumors receiving highly OM-inducing chemotherapy. A role for chlorhexidine in the prevention of OM is suggested, which should be evaluated further.

Aniracetam tested in chronic psychosyndrome after long-term exposure to organic solvents. A randomized, double-blind, placebo-controlled cross-over study with neuropsychological tests.

PubMed

Somnier, F E; Ostergaard, M S; Boysen, G; Bruhn, P; Mikkelsen, B O

1990-01-01

In order to examine if the nootropic drug, aniracetam, was capable of improving cognitive performance, 44 subjects suffering from chronic psychosyndrome after long-term exposure to organic solvents were included in a randomized, double-blind, placebo-controlled, cross-over study. The treatment periods were 3 months with aniracetam 1 g daily and 3 months with placebo. Neuropsychological tests as well as a physical and neurological examination were performed at entry into the study and after each treatment period, together with an evaluation of the subjects' overall condition. Neither the doctors' nor the subjects' own assessment of the overall condition indicated that the trial medication had had any effect. No significant changes in neuropsychological symptoms were observed. A statistically significant difference in favour of antiracetam was found in only 1 of the 19 neuropsychological test measures, namely a test for constructional ability. However, in another test on visuo-spatial function, a statistically significant result was found in favour of placebo. Thus, aniracetam was found to be ineffective in the treatment of subjects suffering from chronic psychosyndrome after long-term exposure to organic solvents.

Randomized sham-controlled, double-blind, multicenter clinical trial on the effect of percutaneous radiofrequency at the ramus communicans for lumbar disc pain.

PubMed

van Tilburg, C W J; Stronks, D L; Groeneweg, J G; Huygen, F J P M

2017-03-01

Investigate the effect of percutaneous radiofrequency compared to a sham procedure, applied to the ramus communicans for treatment of lumbar disc pain. Randomized sham-controlled, double-blind, crossover, multicenter clinical trial. Multidisciplinary pain centres of two general hospitals. Sixty patients aged 18 or more with medical history and physical examination suggestive for lumbar disc pain and a reduction of two or more on a numerical rating scale (0-10) after a diagnostic ramus communicans test block. Treatment group: percutaneous radiofrequency treatment applied to the ramus communicans; sham: same procedure except radiofrequency treatment. pain reduction. Secondary outcome measure: Global Perceived Effect. No statistically significant difference in pain level over time between the groups, as well as in the group was found; however, the factor period yielded a statistically significant result. In the crossover group, 11 out of 16 patients experienced a reduction in NRS of 2 or more at 1 month (no significant deviation from chance). No statistically significant difference in satisfaction over time between the groups was found. The independent factors group and period also showed no statistically significant effects. The same applies to recovery: no statistically significant effects were found. The null hypothesis of no difference in pain reduction and in Global Perceived Effect between the treatment and sham group cannot be rejected. Post hoc analysis revealed that none of the investigated parameters contributed to the prediction of a significant pain reduction. Interrupting signalling through the ramus communicans may interfere with the transition of painful information from the discs to the central nervous system. Methodological differences exist in studies evaluating the efficacy of radiofrequency treatment for lumbar disc pain. A randomized, sham-controlled, double-blind, multicenter clinical trial on the effect of radiofrequency at the ramus

Effect of melatonin on depressive symptoms and anxiety in patients undergoing breast cancer surgery: a randomized, double-blind, placebo-controlled trial.

PubMed

Hansen, Melissa V; Andersen, Lærke T; Madsen, Michael T; Hageman, Ida; Rasmussen, Lars S; Bokmand, Susanne; Rosenberg, Jacob; Gögenur, Ismail

2014-06-01

Depression, anxiety and sleep disturbances are known problems in patients with breast cancer. The effect of melatonin as an antidepressant in humans with cancer has not been investigated. We investigated whether melatonin could lower the risk of depressive symptoms in women with breast cancer in a three-month period after surgery and assessed the effect of melatonin on subjective parameters: anxiety, sleep, general well-being, fatigue, pain and sleepiness. Randomized, double-blind, placebo-controlled trial undertaken from July 2011 to December 2012 at a department of breast surgery in Copenhagen, Denmark. Women, 30-75 years, undergoing surgery for breast cancer and without signs of depression on Major Depression Inventory (MDI) were included 1 week before surgery and received 6 mg oral melatonin or placebo for 3 months. The primary outcome was the incidence of depressive symptoms measured by MDI. The secondary outcomes were area under the curve (AUC) for the subjective parameters. 54 patients were randomized to melatonin (n = 28) or placebo (n = 26) and 11 withdrew from the study (10 placebo group and 1 melatonin group, P = 0.002). The risk of developing depressive symptoms was significantly lower with melatonin than with placebo (3 [11 %] of 27 vs. 9 [45 %] of 20; relative risk 0.25 [95 % CI 0.077-0.80]), giving a NNT of 3.0 [95 % CI 1.7-11.0]. No significant differences were found between AUC for the subjective parameters. No differences in side effects were found (P = 0.78). Melatonin significantly reduced the risk of depressive symptoms in women with breast cancer during a three-month period after surgery.

Calcium Hydroxylapatite Dermal Filler for Treatment of Dorsal Hand Volume Loss: Results From a 12-Month, Multicenter, Randomized, Blinded Trial.

PubMed

Goldman, Mitchel P; Moradi, Amir; Gold, Michael H; Friedmann, Daniel P; Alizadeh, Kaveh; Adelglass, Jeffrey M; Katz, Bruce E

2018-01-01

Calcium hydroxylapatite (CaHA) microspheres suspended in a carrier gel is an opaque dermal filler that has been used to provide immediate volume correction in the dorsal hands. To assess the safety and effectiveness of CaHA for the correction of volume loss in the hands up to 12 months. This multicenter, controlled, single-blind study (NCT01832090) included 114 subjects randomized 3:1 to CaHA treatment and untreated control groups. Effectiveness was assessed by blinded investigators using the validated Merz Hand Grading Scale (MHGS). Subject-reported improvement was assessed using the Global Aesthetic Improvement Scale. Effects of treatment on hand function were also assessed. A total of 75% of subjects achieved ≥1-point improvement on the MHGS (p < .0001) at 3 months (primary end point); this response was generally maintained through 12 months. Proportions of subjects reporting improvement ranged from 98% (3 months) to 86% (12 months). There were no clinically significant differences between control and CaHA-treated subjects in any hand function measure. Adverse events were generally expected, minor, short-lived, injection-related, and similar to those observed in previous CaHA clinical studies. Treatment with CaHA results in significant improvement in the appearance of the dorsal hand and is well tolerated.

Long-Term Chamomile Therapy of Generalized Anxiety Disorder: A Study Protocol for a Randomized, Double-Blind, Placebo- Controlled Trial.

PubMed

Mao, Jun J; Li, Qing S; Soeller, Irene; Rockwell, Kenneth; Xie, Sharon X; Amsterdam, Jay D

2014-11-01

Anxiety symptoms are among the most common reasons for consumers to use Complementary and Alternative Medicine (CAM) therapy. Although many botanicals have been proposed as putative remedies for anxiety symptoms, there has been a paucity of controlled trials of these remedies. A preliminary study of the anxiolytic effect of Chamomile ( Matricaria recutita ) in humans suggests that chamomile may have anxiolytic and antidepressant activity. We now seek to conduct a 5-year randomized, double-blind, placebo-substitution study to examine the short and long-term safety and efficacy of chamomile extract in Generalized Anxiety Disorder (GAD). 180 subjects with moderate to severe GAD will receive initial open-label pharmaceutical-grade chamomile extract 500-1,500 mg daily for 8 weeks. Responders to treatment who remain well for an additional 4 weeks of consolidation therapy, will be randomized to double-blind continuation therapy with either chamomile extract 500-1,500 mg daily or placebo for an additional 26 weeks. The primary outcome will be the time to relapse during study continuation therapy in each treatment condition. Secondary outcomes will include the proportion of subjects in each treatment condition who relapse, as well as the proportion of subjects with treatment-emergent adverse events. Quality of life ratings will also be compared between treatment conditions during short and long-term therapy. Many individuals with mental disorders decline conventional therapy and seek CAM therapies for their symptoms. Thus, the identification of effective CAM therapy is of relevance to reducing the burden of mental illness. This study builds upon our prior findings of significant superiority of chamomile versus placebo in reducing GAD symptoms. We now extend these preliminary findings by conducting a randomized long-term safety and efficacy study of chamomile in GAD.

Long-Term Chamomile Therapy of Generalized Anxiety Disorder: A Study Protocol for a Randomized, Double-Blind, Placebo- Controlled Trial

PubMed Central

Mao, Jun J; Li, Qing S.; Soeller, Irene; Rockwell, Kenneth; Xie, Sharon X; Amsterdam, Jay D.

2017-01-01

Background Anxiety symptoms are among the most common reasons for consumers to use Complementary and Alternative Medicine (CAM) therapy. Although many botanicals have been proposed as putative remedies for anxiety symptoms, there has been a paucity of controlled trials of these remedies. A preliminary study of the anxiolytic effect of Chamomile (Matricaria recutita) in humans suggests that chamomile may have anxiolytic and antidepressant activity. We now seek to conduct a 5-year randomized, double-blind, placebo-substitution study to examine the short and long-term safety and efficacy of chamomile extract in Generalized Anxiety Disorder (GAD). Methods/Design 180 subjects with moderate to severe GAD will receive initial open-label pharmaceutical-grade chamomile extract 500–1,500 mg daily for 8 weeks. Responders to treatment who remain well for an additional 4 weeks of consolidation therapy, will be randomized to double-blind continuation therapy with either chamomile extract 500–1,500 mg daily or placebo for an additional 26 weeks. The primary outcome will be the time to relapse during study continuation therapy in each treatment condition. Secondary outcomes will include the proportion of subjects in each treatment condition who relapse, as well as the proportion of subjects with treatment-emergent adverse events. Quality of life ratings will also be compared between treatment conditions during short and long-term therapy. Discussion Many individuals with mental disorders decline conventional therapy and seek CAM therapies for their symptoms. Thus, the identification of effective CAM therapy is of relevance to reducing the burden of mental illness. This study builds upon our prior findings of significant superiority of chamomile versus placebo in reducing GAD symptoms. We now extend these preliminary findings by conducting a randomized long-term safety and efficacy study of chamomile in GAD. PMID:29057164

A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL OF ORAL MATRICARIA RECUTITA (CHAMOMILE) EXTRACT THERAPY OF GENERALIZED ANXIETY DISORDER

PubMed Central

Amsterdam, Jay D.; Li, Yimei; Soeller, Irene; Rockwell, Kenneth; Mao, Jun James; Shults, Justine

2013-01-01

Objective We conducted a randomized, double-blind, placebo-controlled efficacy and tolerability trial of Matricaria recutita (chamomile) extract therapy in patients with mild to moderate Generalized Anxiety Disorder (GAD). We hypothesized that chamomile would be superior to placebo in reducing GAD symptoms with a comparable tolerability profile. Materials & Methods 61 outpatients with mild to moderate GAD were enrolled and 57 were randomized to either double blind chamomile extract (n=28) or placebo (n=29) therapy for 8 weeks. The study was powered to detect a statistically significant and clinically meaningful group difference in change over time in total Hamilton Anxiety Rating (HAM-A) scores. Secondary outcomes included change in the Beck Anxiety Inventory score, Psychological Well Being score, Clinical Global Impression Severity score, and the proportion of patients with ≥50% reduction in baseline HAM-A score. Results We observed a significantly greater reduction in mean total HAM-A score during chamomile versus placebo therapy (p=0.047). Although the study was not powered to identify small to moderate differences in secondary outcomes, we observed a positive change in all secondary outcomes in the same direction as the primary outcome measure. One patient in each treatment group discontinued therapy for adverse events. The proportion of patients experiencing 0, 1, 2, or ≥3 adverse events was not significantly different between groups (p=0.417). Conclusion This is the first, controlled clinical trial of chamomile extract for GAD. The results suggest that chamomile may have modest anxiolytic activity in patients with mild to moderate GAD. Future studies are needed to replicate these observations. PMID:19593179

Double-blind, placebo-controlled pilot study of adjunctive quetiapine SR in the treatment of PMS/PMDD.

PubMed

Jackson, Christine; Pearson, Brenda; Girdler, Susan; Johnson, Jacqueline; Hamer, Robert M; Killenberg, Susan; Meltzer-Brody, Samantha

2015-11-01

Premenstrual dysphoric disorder (PMDD), a more severe form of premenstrual syndrome (PMS), afflicts 5-8% of reproductive age women and results in significant functional impairment. We conducted a double-blind, placebo-controlled trial of adjunctive quetiapine in patients with PMS/PMDD who had inadequate response to selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor therapy for their symptoms. A PMS/PMDD diagnosis was confirmed by 2-month prospective diagnostic assessment of PMS/PMDD using the Prospective Record of the Impact and Severity of Premenstrual Symptoms (PRISM) calendar. Women were randomized equally to receive quetiapine sustained-release (SR) or placebo (25-mg starting dose) during the luteal phase for 3 months. Outcome variables included the Hamilton Depression and Anxiety Scales, Clinical Global Impression Scale, and PRISM. Twenty women were enrolled in the treatment phase. Although the study was underpowered, greater reductions in luteal phase mood ratings were observed in the quetiapine group on the 17-item Hamilton Depression Rating Scale, Clinical Global Impression improvement rating, and PRISM daily score. The quetiapine group showed most improvement in symptoms of mood lability, anxiety, and irritability. This small double-blind study suggests that adjunctive treatment with quetiapine SR may be a useful addition to selective serotonin reuptake inhibitor therapy in women with PMS/PMDD by reducing symptoms and improving quality of life. Copyright © 2015 John Wiley & Sons, Ltd.

Memantine for Prophylactic Treatment of Migraine Without Aura: A Randomized Double-Blind Placebo-Controlled Study.

PubMed

Noruzzadeh, Rezvan; Modabbernia, Amirhossein; Aghamollaii, Vajiheh; Ghaffarpour, Majid; Harirchian, Mohammad Hossein; Salahi, Sarvenaz; Nikbakht, Nikta; Noruzi, Nahid; Tafakhori, Abbas

2016-01-01

Uncontrolled studies in human have suggested that memantine might be a suitable option for migraine prophylaxis. To assess the efficacy and tolerability of memantine for migraine prophylaxis. This was a 12-week randomized double-blind placebo-controlled parallel-group study. Sixty patients with migraine without aura were randomized using a computer-generated list to receive memantine (10 mg/day) or placebo for 12 weeks. The primary outcome was the difference in change from baseline in the monthly attack frequency at week 12 between the two groups (using migraine diary). Secondary efficacy measures were assessed using several clinical, functional, and psychological instruments. We performed both complete case (CC) and intention-to-treat analyses (ITT). Twenty-five patients in the memantine group and 27 patients in the placebo group completed the study. Patients in the memantine group showed significantly greater reduction (mean change; 3.4; 95%CI, 2.3-4.4) in the monthly attack frequency than the placebo group (mean change, 1.0; 95%CI, 0.3-1.7) (mean difference [MD], 2.3; 95%CI, 1.1-3.5, P < .001). Both CC (MD, 4.9; 95%CI, 2.6-7.2 days), and ITT analyses (MD, 5.2; 95%CI, 2.0-8.5) showed significantly higher reduction in the mean number of migraine days in the memantine group than the placebo group (P < .01). Patients in the memantine group experienced greater reduction in the number of work absence days, severity, and disability score than the patients in the placebo group in both ITT and CC analyses. Changes in quality of life, sleep, depression, and anxiety did not differ between the two groups. Three patients in the memantine group complained of sedation, mild vertigo and nausea, and drowsiness. In the placebo group, one patient complained of nausea and another patient discontinued treatment after 2 weeks due to vertigo. Memantine might be a tolerable and efficacious option for prophylaxis in patients with migraine without aura. Tolerability, short

Effect of sibutramine on weight reduction in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial.

PubMed

Lindholm, Asa; Bixo, Marie; Björn, Inger; Wölner-Hanssen, Pål; Eliasson, Mats; Larsson, Anders; Johnson, Owe; Poromaa, Inger Sundström

2008-05-01

To examine the efficacy of sibutramine together with brief lifestyle modification for weight reduction in obese women with polycystic ovary syndrome (PCOS). Investigator-initiated, multicenter, double-blind, randomized, parallel-group clinical trial. Departments of Obstetrics and Gynecology in primary care, referral centers, and private practice. Forty-two patients with confirmed PCOS were included in the study, and 34 patients completed the study. Sibutramine 15 mg once daily together with brief lifestyle modification was compare with placebo together with brief lifestyle modification. The primary endpoint was to assess weight loss. Secondary endpoints included the efficacy of sibutramine for treatment of menstrual pattern and cardiovascular risk factors. After 6 months the sibutramine group had lost 7.8 +/- 5.1 kg compared with a weight loss of 2.8 +/- 6.2 kg in the placebo group. Sibutramine treatment resulted in significant decreases in apolipoprotein B, apolipoprotein B/apolipoprotein A ratio, triglycerides, and cystatin C levels. Sibutramine in combination with lifestyle intervention results in significant weight reduction in obese patients with PCOS. In addition to the weight loss, sibutramine seems to have beneficial effects on metabolic and cardiovascular risk factors.

Equimolar mixture of nitroux oxyde and oxygen during post-operative physiotherapy in patients with cerebral palsy: A randomized, double-blind, placebo-controlled study.

PubMed

Delafontaine, A; Presedo, A; Mohamed, D; Lopes, D; Wood, C; Alberti, C

2017-11-01

The administration of an equimolar mixture of nitrous oxide and oxygen (N2O) is recommended during painful procedures. However, the evaluation of its use during physiotherapy after surgery has not been reported, although pain may hamper physiotherapy efficiency. This study investigated whether the use of N2O improves the efficacy of post-operative physiotherapy after multilevel surgery in patients with cerebral palsy. It was a randomized 1:1, double-blind, placebo-controlled study. All patients had post-operative physiotherapy starting the day after surgery. Patients received either N2O or placebo gas during the rehabilitation sessions. All patients had post-operative pain management protocol, including pain medication as needed for acute pain. The primary objective was to reach angles of knee flexion of 110° combined with hip extension of 10°, with the patient lying prone, within six or less physiotherapy sessions. Secondary evaluation criteria were the number of sessions required to reach the targeted angles, the session-related pain intensity and the analgesics consumption for managing post-operative pain. Sixty-four patients were enrolled. Targeted angles were achieved more often in the N2O group (23 of 32, 72%, vs. Placebo: 13/ of 32, 41%; p = 0.01). The administration of N2O during post-operative physiotherapy can help to achieve more quickly an improved range of motion, and, although not significant in our study, to alleviate the need for pain medication. Further studies evaluating the administration of N2O in various settings are warranted. During this randomized placebo-controlled double-blind study, children receiving nitrous oxide and oxygen (N2O) achieved more often the targeted range of motion during physiotherapy sessions after multilevel surgery. Compared to placebo, nitrous oxide and oxygen (N2O) enabled a better management of acute pain related to physiotherapy procedures. © 2017 European Pain Federation - EFIC®.

Effects of nebivolol and atenolol on central aortic pressure in hypertensive patients: a multicenter, randomized, double-blind study.

PubMed

Redón, Josep; Pascual-Izuel, Jose M; Rodilla, Enrique; Vicente, Antonio; Oliván, Josefina; Bonet, Josep; Torguet, Josep Pere; Calaforra, Oscar; Almirall, Jaume

2014-06-01

The main objective was to compare the mean change in augmentation index of hypertensive patients treated with nebivolol or atenolol. Multicenter, double-blind randomized study conducted in six Spanish centers. We enrolled outpatients between the ages of 40 and 65 years with mild or moderate essential hypertension (systolic blood pressure, SBP ≥ 140 mmHg to ≤ 179 mmHg and diastolic blood pressure, DBP ≥ 90 mmHg to ≤ 109 mmHg after a 2-week run-in placebo period). Patients received nebivolol 5 mg or atenolol 50 mg once daily. At week 3, atenolol could be titrated up to 100 mg qd for non-responders. Additionally, patients not achieving normal blood pressure after 6 weeks could be treated with 25 mg hydrochlorothiazide. Follow-up visits were at 3, 6 and 10 weeks. The final study population of 138 patients (58% men; median age 52.6 years, range 40-67 years) was randomized into two groups of 69 patients each. Baseline characteristics of the two groups were similar. At the screening visit, 69% presented with mild hypertension. Nebivolol modified the mean augmentation index to a lesser extent than atenolol after 10 weeks (mean difference 3.1%, 95% CI 0.55-5.69; p = 0.027). A higher proportion of patients in the atenolol group required a diuretic. Reductions in central aortic pressure and peripheral arterial pressure were similar for both treatment groups. The study confirms that nebivolol produces a less pronounced impact on augmentation index than atenolol.

A randomized, double-blind, 24-week study of escitalopram (10 mg/day) versus citalopram (20 mg/day) in primary care patients with major depressive disorder.

PubMed

Colonna, Lucien; Andersen, Henning Friis; Reines, Elin Heldbo

2005-10-01

A randomized, double-blind, 24-week-fixed-dose study comparing the efficacy and safety of escitalopram to that of citalopram was safety was conducted in primary care patients with moderate to severe major depressive disorder (MDD). This was a randomized, double-blind, 24-week fixeddose study. Patients were randomly assigned to treatment with escitalopram 10 mg/day (n = 175) or citalopram 20 mg/day (n = 182). Clinical response was evaluated using the Montgomery-Asberg Depression Rating Scale (MADRS) and Clinical Global Impression-Severity (CGI-S) scale. The prospectively defined primary parameter of antidepressant efficacy was the change from baseline in the mean MADRS total score during the 24 weeks of double-blind treatment, using a repeated measures analysis of variance to compare the treatment groups over all assessment points simultaneously. Based on the primary parameter, escitalopram was at least as efficacious as citalopram. Based on the prospectively defined secondary parameter, mean change from baseline in the CGI-S score, escitalopram was statistically significantly superior to citalopram at Week 24. The importance of long-term treatment could be demonstrated, in that more than half (55% and 51%) of the patients who had not responded by Week 8 achieved remission by Week 24. Both escitalopram and citalopram were safe and well tolerated in acute and long-term treatment, and the overall adverse event profiles for the two drugs were similar. For the intent-to-treat population, there were statistically significantly fewer withdrawals in the escitalopram group than in the citalopram group, particularly after Week 8. Patients with MDD responded well to long-term treatment with either escitalopram or citalopram. This study demonstrated the importance of extending treatment of depression beyond 8 weeks.

Infliximab for chronic cutaneous sarcoidosis: a subset analysis from a double-blind randomized clinical trial.

PubMed

Baughman, Robert P; Judson, Marc A; Lower, Elyse E; Drent, Marjolein; Costabel, Ulrich; Flavin, Susan; Lo, Kim Hung; Barnathan, Elliot S

2016-01-15

Limited evidence exists demonstrating an effective treatment for chronic cutaneous sarcoidosis. To determine infliximab's effectiveness in sarcoidosis. We conducted a subset analysis from a randomized, double-blind, placebo-controlled trial for chronic pulmonary sarcoidosis to determine infliximab's effectiveness. Patients with chronic cutaneous sarcoidosis received infliximab (3 or 5 mg/kg) or placebo over 24 weeks. Of 138 patients, the subset analysis evaluated 17 patients with chronic facial and another 9 patients with nonfacial skin involvement. The SASI evaluated lesions for degree of erythema, desquamation, induration, and percentage of area involved. Facial and nonfacial lesions were scored in a blinded manner. Among 5 placebo-treated and 12 infliximab-treated patients, an improvement was observed with infliximab versus placebo in change from baseline to weeks 12 and 24 in desquamation (P<0.005) and induration (P<0.01) at week 24. Erythema, percentage of area involved and the evaluation of paired photographs did not reveal significant differences. Sample size; more extensive disease in placebo patients; chronic therapy upon enrollment; lung as primary organ of sarcoidosis involvement; limited investigator experience with SASI. Infliximab appears to be a beneficial treatment for chronic cutaneous sarcoidosis. The SASI scoring system demonstrated significant improvement versus placebo in lesion desquamation and induration.

Extract of valerian root (Valeriana officinalis L.) vs. placebo in treatment of obsessive-compulsive disorder: a randomized double-blind study.

PubMed

Pakseresht, Siroos; Boostani, Hatam; Sayyah, Mehdi

2011-10-11

Obsessive-Compulsive Disorder (OCD) is a common neuropsychiatric condition. Many herbs with psychotropic effects exist which can have fewer side effects compared to more conventional medications. Valeriana Officinalis L. is a well-known medicinal plant with a long history of usage in the world with an effect on GABA. This plant is reported to be safe on humans. Our objective in this study was to compare the efficacy of the extract of Valeriana Officinalis L. with placebo in the treatment of OCD. The study was an 8-week pilot double-blind randomized trial. Thirty-one adult outpatients who met the DSM-IV-TR criteria for OCD based on the structured clinical interview participated in the trial. In this double-blind and randomized trial, patients were randomly assigned to receive either capsule of the extract (765 mg/day) or placebo (30 mg/day) for 8 weeks. The results showed significant difference between the extract and placebo in the end of treatment (P=0.000). Somnolence was the only significant difference between the two groups in terms of observed side effects (P=0.02). The results suggest that Valeriana Officinalis L. has some antiobsessive and compulsive effects. However, further studies are needed to confirm these findings. Psychiatrists often find that many patients cannot tolerate the side effects of psychiatry medicine Valeriana Officinalis L. is a well-known medicinal plant with a long history of usage in world with effect on GABA.The results showed significant difference between the extract and placebo in the treatment of OCD. There was also no significant difference between the two groups in terms of observed side effects.

Efficacy and safety of extended- versus immediate-release pramipexole in Japanese patients with advanced and L-dopa-undertreated Parkinson disease: a double-blind, randomized trial.

PubMed

Mizuno, Yoshikuni; Yamamoto, Mitsutoshi; Kuno, Sadako; Hasegawa, Kazuko; Hattori, Nobutaka; Kagimura, Tatsuro; Sarashina, Akiko; Rascol, Olivier; Schapira, Anthony H V; Barone, Paolo; Hauser, Robert A; Poewe, Werner

2012-01-01

To compare the efficacy, safety, tolerability, and trough plasma levels of pramipexole extended-release (ER) and pramipexole immediate-release (IR), and to assess the effects of overnight switching from an IR to an ER formulation, in L-dopa-treated patients with Parkinson disease (PD). After a 1- to 4-week screening/enrollment, 112 patients who had exhibited L-dopa-related problems or were receiving suboptimal L-dopa dosage were randomized in double-blind, double-dummy, 1:1 fashion to pramipexole ER once daily or pramipexole IR 2 to 3 times daily for 12 weeks, both titrated to a maximum daily dose of 4.5 mg. Successful completers of double-blind treatment were switched to open-label pramipexole ER, beginning with a 4-week dose-adjustment phase. Among the double-blind treatment patients (n = 56 in each group), Unified Parkinson's Disease Rating Scale Parts II+III total scores decreased significantly from baseline and to a similar degree with pramipexole ER and IR formulations. In each group, 47 double-blind patients (83.9%) reported adverse events (AEs), requiring withdrawal of 3 ER patients (5.4%) and 2 IR patients (3.6%). Trough plasma levels at steady state (at the same doses and dose-normalized concentrations) were also similar with both formulations. Among open-label treatment patients (n = 53 from IR to ER), 83% were successfully switched (no worsening of PD symptoms) to pramipexole ER. In L-dopa-treated patients, pramipexole ER and pramipexole IR demonstrated similar efficacy, safety, tolerability, and trough plasma levels. Patients can be safely switched overnight from pramipexole IR to pramipexole ER with no impact on efficacy.

Allogeneic Mesenchymal Stem Cells Ameliorate Aging Frailty: A Phase II Randomized, Double-Blind, Placebo-Controlled Clinical Trial

PubMed Central

Tompkins, Bryon A; DiFede, Darcy L; Khan, Aisha; Landin, Ana Marie; Schulman, Ivonne Hernandez; Pujol, Marietsy V; Heldman, Alan W; Miki, Roberto; Goldschmidt-Clermont, Pascal J; Goldstein, Bradley J; Mushtaq, Muzammil; Levis-Dusseau, Silvina; Byrnes, John J; Lowery, Maureen; Natsumeda, Makoto; Delgado, Cindy; Saltzman, Russell; Vidro-Casiano, Mayra; Da Fonseca, Moisaniel; Golpanian, Samuel; Premer, Courtney; Medina, Audrey; Valasaki, Krystalenia; Florea, Victoria; Anderson, Erica; El-Khorazaty, Jill; Mendizabal, Adam; Green, Geoff; Oliva, Anthony A; Hare, Joshua M

2017-01-01

Abstract Background Aging frailty, characterized by decreased physical and immunological functioning, is associated with stem cell depletion. Human allogeneic mesenchymal stem cells (allo-hMSCs) exert immunomodulatory effects and promote tissue repair. Methods This is a randomized, double-blinded, dose-finding study of intravenous allo-hMSCs (100 or 200-million [M]) vs placebo delivered to patients (n = 30, mean age 75.5 ± 7.3) with frailty. The primary endpoint was incidence of treatment-emergent serious adverse events (TE-SAEs) at 1-month postinfusion. Secondary endpoints included physical performance, patient-reported outcomes, and immune markers of frailty measured at 6 months postinfusion. Results No therapy-related TE-SAEs occurred at 1 month. Physical performance improved preferentially in the 100M-group; immunologic improvement occurred in both the 100M- and 200M-groups. The 6-minute walk test, short physical performance exam, and forced expiratory volume in 1 second improved in the 100M-group (p = .01), not in the 200M- or placebo groups. The female sexual quality of life questionnaire improved in the 100M-group (p = .03). Serum TNF-α levels decreased in the 100M-group (p = .03). B cell intracellular TNF-α improved in both the 100M- (p < .0001) and 200M-groups (p = .002) as well as between groups compared to placebo (p = .003 and p = .039, respectively). Early and late activated T-cells were also reduced by MSC therapy. Conclusion Intravenous allo-hMSCs were safe in individuals with aging frailty. Treated groups had remarkable improvements in physical performance measures and inflammatory biomarkers, both of which characterize the frailty syndrome. Given the excellent safety and efficacy profiles demonstrated in this study, larger clinical trials are warranted to establish the efficacy of hMSCs in this multisystem disorder. Clinical Trial Registration www.clinicaltrials.gov: CRATUS (#NCT02065245). PMID:28977399

A double-blind, randomized trial of deep repetitive transcranial magnetic stimulation (rTMS) for autism spectrum disorder.

PubMed

Enticott, Peter G; Fitzgibbon, Bernadette M; Kennedy, Hayley A; Arnold, Sara L; Elliot, David; Peachey, Amy; Zangen, Abraham; Fitzgerald, Paul B

2014-01-01

Biomedical treatment options for autism spectrum disorder (ASD) are extremely limited. Repetitive transcranial magnetic stimulation (rTMS) is a safe and efficacious technique when targeting specific areas of cortical dysfunction in major depressive disorder, and a similar approach could yield therapeutic benefits in ASD, if applied to relevant cortical regions. The aim of this study was to examine whether deep rTMS to bilateral dorsomedial prefrontal cortex improves social relating in ASD. 28 adults diagnosed with either autistic disorder (high-functioning) or Asperger's disorder completed a prospective, double-blind, randomized, placebo-controlled design with 2 weeks of daily weekday treatment. This involved deep rTMS to bilateral dorsomedial prefrontal cortex (5 Hz, 10-s train duration, 20-s inter-train interval) for 15 min (1500 pulses per session) using a HAUT-Coil. The sham rTMS coil was encased in the same helmet of the active deep rTMS coil, but no effective field was delivered into the brain. Assessments were conducted before, after, and one month following treatment. Participants in the active condition showed a near significant reduction in self-reported social relating symptoms from pre-treatment to one month follow-up, and a significant reduction in social relating symptoms (relative to sham participants) for both post-treatment assessments. Those in the active condition also showed a reduction in self-oriented anxiety during difficult and emotional social situations from pre-treatment to one month follow-up. There were no changes for those in the sham condition. Deep rTMS to bilateral dorsomedial prefrontal cortex yielded a reduction in social relating impairment and socially-related anxiety. Further research in this area should employ extended rTMS protocols that approximate those used in depression in an attempt to replicate and amplify the clinical response. Copyright © 2014 Elsevier Inc. All rights reserved.

Six months therapy for tuberculous meningitis

PubMed Central

Jullien, Sophie; Ryan, Hannah; Modi, Manish; Bhatia, Rohit

2016-01-01

Background Tuberculous meningitis (TBM) is the main form of tuberculosis that affects the central nervous system and is associated with high rates of death and disability. Most international guidelines recommend longer antituberculous treatment (ATT) regimens for TBM than for pulmonary tuberculosis disease to prevent relapse. However, longer regimens are associated with poor adherence, which could contribute to increased relapse, development of drug resistance, and increased costs to patients and healthcare systems. Objectives To compare the effects of short-course (six months) regimens versus prolonged-course regimens for people with tuberculous meningitis (TBM). Search methods We searched the following databases up to 31 March 2016: the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE; EMBASE; LILACS; INDMED; and the South Asian Database of Controlled Clinical Trials. We searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov for ongoing trials. We also checked article reference lists and contacted researchers in the field. Selection criteria We included randomized controlled trials (RCTs) and prospective cohort studies of adults and children with TBM treated with antituberculous regimens that included rifampicin for six months or longer than six months. The primary outcome was relapse, and included studies required a minimum of six months follow-up after completion of treatment. Data collection and analysis Two review authors (SJ and HR) independently assessed the literature search results for eligibility, and performed data extraction and 'Risk of bias' assessments of the included studies. We contacted study authors for additional information when necessary. Most data came from single arm cohort studies without a direct comparison so we pooled the findings for each group of cohorts and

Chorionic gonadotropin in weight control. A double-blind crossover study.

PubMed

Young, R L; Fuchs, R J; Woltjen, M J

1976-11-29

Two hundred two patients participated in a double-blind random cross-over study of the effectiveness of human chorionic gonadotropin (HCG) vs placebo in a wieght reduction program. Serial measurements were made of weight, skin-fold thickness, dropout rates, reasons for dropping out, and patient subjective response. There was no statistically significant difference between those receiving HCG vs placebo during any phase of this study (P greater than .1).

Aprepitant as an add-on therapy in children receiving highly emetogenic chemotherapy: a randomized, double-blind, placebo-controlled trial.

PubMed

Bakhshi, Sameer; Batra, Atul; Biswas, Bivas; Dhawan, Deepa; Paul, Reeja; Sreenivas, Vishnubhatla

2015-11-01

Aprepitant, a neurokinin-1 receptor antagonist, in combination with 5 HT-3 antagonist and dexamethasone is recommended in adults receiving moderately and highly emetogenic chemotherapy to reduce chemotherapy-induced vomiting (CIV). Data for use of aprepitant in children is limited and hence aprepitant is not recommended by Pediatric Oncology Group of Ontario guidelines for prevention of CIV in children <12 years. A randomized, double-blind, placebo-controlled trial was conducted at a single center in chemotherapy naïve children (5-18 years) receiving highly emetogenic chemotherapy. All patients received intravenous ondansetron (0.15 mg/kg) and dexamethasone (0.15 mg/kg) prior to chemotherapy followed by oral ondansetron and dexamethasone. Patients randomly assigned to aprepitant arm received oral aprepitant (15-40 kg = days 1-3, 80 mg; 41-65 kg = day 1, 125 mg and days 2-3, 80 mg) 1 h before chemotherapy. Control group received placebo as add-on therapy. Primary outcome measure was the incidence of acute moderate to severe vomiting, which was defined as more than two vomiting episodes within 24 h after the administration of the first chemotherapy dose until 24 h after the last chemotherapy dose in the block. Complete response (CR) was defined as absence of vomiting and retching during the specified phase. Of the 96 randomized patients, three were excluded from analysis; 93 patients were analyzed (50 in aprepitant arm and 43 in placebo arm). Acute moderate and severe vomiting was reported in 72 % patients receiving placebo and 38 % patients receiving aprepitant (p = 0.001). Complete response rates during acute phase were significantly higher in aprepitant arm (48 vs. 12 %, p < 0.001). No major adverse effects were reported by patients/guardians. This double-blind, randomized, placebo-controlled trial shows that aprepitant significantly decreases the incidence of CIV during acute phase when used as an add-on drug with ondansetron and dexamethasone in children

Statin therapy worsens insulin sensitivity in women with polycystic ovary syndrome (PCOS): a prospective, randomized, double-blind, placebo-controlled study.

PubMed

Puurunen, Johanna; Piltonen, Terhi; Puukka, Katri; Ruokonen, Aimo; Savolainen, Markku J; Bloigu, Risto; Morin-Papunen, Laure; Tapanainen, Juha S

2013-12-01

Statins have been shown to improve hyperandrogenism in women with polycystic ovary syndrome (PCOS). However, their use has also been associated with impairment of glucose metabolism and an increased risk of type 2 diabetes mellitus. Because women with PCOS are prone to disturbances in glucose metabolism, statin therapy could also have negative effects. Our objective was to explore the effects of atorvastatin therapy on hormonal and metabolic parameters in women with PCOS. We conducted a randomized, double-blind, placebo-controlled 6-month follow-up study conducted at Oulu University Hospital, Finland. Women with PCOS (Rotterdam criteria) were treated with atorvastatin (20 mg/d, n = 15) or placebo (n = 13) for 6 months. Fasting serum samples were collected at baseline and at 3 and 6 months. Oral and iv glucose tolerance tests were performed at 0 and 6 months. Androgen secretion and glucose metabolism were measured. Fasting levels and area under the curve of insulin increased significantly and insulin sensitivity (insulinogenic and Matsuda indexes) decreased during 6 months of atorvastatin therapy. Serum levels of dehydroepiandrosterone sulfate decreased in the atorvastatin group, whereas no change was observed in serum testosterone levels. Levels of C-reactive protein, total and low-density lipoprotein-cholesterol, and triglycerides decreased significantly during statin therapy. Atorvastatin therapy improves chronic inflammation and lipid profile, but it impairs insulin sensitivity in women with PCOS. Because women with PCOS have an increased risk of developing type 2 diabetes mellitus, the results suggest that statin therapy should be initiated on the basis of generally accepted criteria and individual risk assessment of cardiovascular disease, and not only because of PCOS.

Blueberries improve endothelial function, but not blood pressure, in adults with metabolic syndrome: a randomized, double-blind, placebo-controlled clinical trial.

PubMed

Stull, April J; Cash, Katherine C; Champagne, Catherine M; Gupta, Alok K; Boston, Raymond; Beyl, Robbie A; Johnson, William D; Cefalu, William T

2015-05-27

Blueberry consumption has been shown to have various health benefits in humans. However, little is known about the effect of blueberry consumption on blood pressure, endothelial function and insulin sensitivity in humans. The present study investigated the role of blueberry consumption on modifying blood pressure in subjects with metabolic syndrome. In addition, endothelial function and insulin sensitivity (secondary measurements) were also assessed. A double-blind and placebo-controlled study was conducted in 44 adults (blueberry, n = 23; and placebo, n = 21). They were randomized to receive a blueberry or placebo smoothie twice daily for six weeks. Twenty-four-hour ambulatory blood pressure, endothelial function and insulin sensitivity were assessed pre- and post-intervention. The blood pressure and insulin sensitivity did not differ between the blueberry and placebo groups. However, the mean change in resting endothelial function, expressed as reactive hyperemia index (RHI), was improved significantly more in the group consuming the blueberries versus the placebo group (p = 0.024). Even after adjusting for confounding factors, i.e., the percent body fat and gender, the blueberry group still had a greater improvement in endothelial function when compared to their counterpart (RHI; 0.32 ± 0.13 versus -0.33 ± 0.14; p = 0.0023). In conclusion, daily dietary consumption of blueberries did not improve blood pressure, but improved (i.e., increased) endothelial function over six weeks in subjects with metabolic syndrome.

A double-blind randomized controlled pilot trial examining the safety and efficacy of therapeutic touch in premature infants.

PubMed

Whitley, Julie Anne; Rich, Bonnie L

2008-12-01

To explore the hypothesis that nontouch therapy such as therapeutic touch (TT) reduces stress to a clinically important degree and is safe to use in preterm infants. A pilot randomized, double-blind, controlled trial. Two groups of 10 infants were enrolled and randomly assigned to treatment or nontreatment groups. Gestational age was less than 29 weeks. Demographic descriptions of the 2 groups were statistically similar. The observer and staff were blinded to assignment; the TT practitioner was blinded to observed measurements. Each infant received either TT or no therapeutic touch (NTT) for 5 minutes on 3 consecutive days at the same time of day, behind a curtain. Heart period variability (HPV) was measured 5 minutes before, during, and after the treatment phase. Examination of the parameters of oxygen saturation and episodes of apnea demonstrated no increase in adverse events in TT group compared with NTT group. Repeated-measures multivariate analysis of variance on HPV revealed differences in the interaction of group assignment with low-frequency, high-frequency, and low-to-high- frequency ratio interaction (F2,143 = 8.076, P = .000) and for group, day, and low-frequency, high-frequency, and low-to-high-frequency ratio (F2,288 = 3.146, P = .015), and in the posttreatment time period (F1,16 = 6.259, P = .024), reflective of greater parasympathetic activity in TT group. In this pilot trial, HPV showed an increase for the TT group compared with the NTT group. The study reveals no adverse effects of TT in preterm infants.

Efficacy and safety of teneligliptin add-on to insulin monotherapy in Japanese patients with type 2 diabetes mellitus: a 16-week, randomized, double-blind, placebo-controlled trial with an open-label period.

PubMed

Kadowaki, Takashi; Kondo, Kazuoki; Sasaki, Noriyuki; Miyayama, Kyoko; Yokota, Shoko; Terata, Ryuji; Gouda, Maki

2017-09-01

To assess the efficacy and safety of teneligliptin as add-on to insulin monotherapy in patients with type 2 diabetes mellitus (T2DM). In a 16-week, double-blind period, 148 Japanese T2DM patients with inadequate glycemic control with insulin and diet/exercise therapies were randomized to placebo or teneligliptin 20 mg. In a subsequent 36-week, open-label period, all patients received teneligliptin once daily. The primary outcome measure was change in HbA1c at the end of the double-blind period. The difference between placebo and teneligliptin in change in HbA1c in the double-blind period (least squares mean ± SE) was -0.80% ± 0.11%; teneligliptin was superior (ANCOVA, P < 0.001). The HbA1c-lowering effect of teneligliptin was maintained throughout the open-label period. The incidence of adverse events was 53.5% with placebo and 44.2% with teneligliptin in the double-blind period, 66.7% in the placebo/teneligliptin group in the open-label period, and 77.9% in the teneligliptin/teneligliptin group over both double-blind/open-label periods. The incidence of hypoglycemic symptoms was 11.1% in the placebo/teneligliptin group in the open-label period and 27.3% in the teneligliptin/teneligliptin group over both double-blind/open-label periods. Teneligliptin was effective and well tolerated in Japanese T2DM patients with inadequate glycemic control. NCT02081599.

Randomized double-blind trial of darbepoetin alfa in patients with symptomatic heart failure and anemia.

PubMed

Ghali, Jalal K; Anand, Inder S; Abraham, William T; Fonarow, Gregg C; Greenberg, Barry; Krum, Henry; Massie, Barry M; Wasserman, Scott M; Trotman, Marie-Louise; Sun, Yan; Knusel, Beat; Armstrong, Paul

2008-01-29

Substantial evidence suggests that anemia is an independent risk factor for worse outcomes in patients with heart failure (HF). The Study of Anemia in Heart Failure Trial (STAMINA-HeFT) is the largest multicenter, randomized, double-blind, placebo-controlled trial to date evaluating the effect of treating anemia in HF. Patients (N=319) with symptomatic HF, left ventricular ejection fraction < or = 40%, and hemoglobin > or = 9.0 g/dL and < or = 12.5 g/dL were randomized (double-blind) to placebo (N=157) or darbepoetin alfa (N=162) subcutaneously every 2 weeks for 1 year (target hemoglobin, 14.0+/-1.0 g/dL). The primary end point was change from baseline to week 27 in treadmill exercise time. Secondary end points were change from baseline in New York Heart Association class and quality of life at week 27. An additional prespecified efficacy analysis included the time to death by any cause or first HF-related hospitalization by 1 year. At baseline, the median (interquartile range) hemoglobin was 11.4 (10.9, 12.0) g/dL. At week 27, darbepoetin alfa treatment increased median (interquartile range) hemoglobin by 1.8 (1.1, 2.5) g/dL (placebo, 0.3 [-0.2, 1.0] g/dL; P<0.001). Of the patients treated with darbepoetin alfa, 85% achieved 2 consecutive hemoglobin levels of 14.0+/-1.0 g/dL during the study and experienced a hemoglobin increase of > or = 1.0 g/dL from baseline. By intent-to-treat analysis, darbepoetin alfa treatment did not significantly improve exercise duration, New York Heart Association class, or quality of life score compared with placebo. A nonsignificant trend was observed toward a lower risk of all-cause mortality or first HF hospitalization in darbepoetin alfa-treated patients compared with placebo (hazard ratio, 0.68; 95% CI, 0.43, 1.08; P=0.10). Occurrences of adverse events were similar in both treatment groups. In this study of patients with symptomatic HF and anemia, treatment with darbepoetin alfa was not associated with significant clinical

Escitalopram in the treatment of adolescent depression: a randomized, double-blind, placebo-controlled extension trial.

PubMed

Findling, Robert L; Robb, Adelaide; Bose, Anjana

2013-09-01

The purpose of this study was to evaluate the extended efficacy, safety, and tolerability of escitalopram relative to placebo in adolescents with major depressive disorder (MDD). Adolescents (12-17 years) who completed an 8-week randomized, double-blind, flexible-dose, placebo-controlled, lead-in study of escitalopram 10-20 mg versus placebo could enroll in a 16-24-week, multisite extension trial; patients maintained the same lead-in randomization (escitalopram or placebo) and dosage (escitalopram 10 or 20 mg/day, or placebo) during the extension. The primary efficacy was Children's Depression Rating Scale-Revised (CDRS-R) change from the lead-in study baseline to treatment week 24 (8-week lead-in study plus 16-week extension); the secondary efficacy was Clinical Global Impressions-Improvement (CGI-I) score at week 24. All efficacy analyses used the last observation carried forward (LOCF) approach; sensitivity analyses used observed cases (OC) and mixed-effects model for repeated measures (MMRM). Safety was evaluated via adverse event (AE) reports and the clinician-rated Columbia-Suicide Severity Rating Scale (C-SSRS). Following lead-in, 165 patients enrolled in the double-blind extension (82 placebo; 83 escitalopram); 40 (48.8%) placebo and 37 (44.6%) escitalopram patients completed treatment. CDRS-R total score improvement was significantly greater for escitalopram than for placebo (p=0.005, LOCF; p=0.014; MMRM). Response rates (CDRS-R ≥ 40% reduction from baseline [adjusted and unadjusted] and CGI-I ≤ 2) were significantly higher for escitalopram than for placebo (LOCF); remission rates (CDRS-R ≤ 28) were 50.6% for escitalopram and 35.7% for placebo (p=0.002). OC analyses were not significantly different between groups. The most frequent escitalopram AEs (≥ 5% and more frequent than placebo) were headache, nausea, insomnia, vomiting, influenza-like symptoms, diarrhea, and urinary tract infection. Most AEs were mild/moderate and not related to the study

A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease.

PubMed

Turner, R Scott; Thomas, Ronald G; Craft, Suzanne; van Dyck, Christopher H; Mintzer, Jacobo; Reynolds, Brigid A; Brewer, James B; Rissman, Robert A; Raman, Rema; Aisen, Paul S

2015-10-20

A randomized, placebo-controlled, double-blind, multicenter 52-week phase 2 trial of resveratrol in individuals with mild to moderate Alzheimer disease (AD) examined its safety and tolerability and effects on biomarker (plasma Aβ40 and Aβ42, CSF Aβ40, Aβ42, tau, and phospho-tau 181) and volumetric MRI outcomes (primary outcomes) and clinical outcomes (secondary outcomes). Participants (n = 119) were randomized to placebo or resveratrol 500 mg orally once daily (with dose escalation by 500-mg increments every 13 weeks, ending with 1,000 mg twice daily). Brain MRI and CSF collection were performed at baseline and after completion of treatment. Detailed pharmacokinetics were performed on a subset (n = 15) at baseline and weeks 13, 26, 39, and 52. Resveratrol and its major metabolites were measurable in plasma and CSF. The most common adverse events were nausea, diarrhea, and weight loss. CSF Aβ40 and plasma Aβ40 levels declined more in the placebo group than the resveratrol-treated group, resulting in a significant difference at week 52. Brain volume loss was increased by resveratrol treatment compared to placebo. Resveratrol was safe and well-tolerated. Resveratrol and its major metabolites penetrated the blood-brain barrier to have CNS effects. Further studies are required to interpret the biomarker changes associated with resveratrol treatment. This study provides Class II evidence that for patients with AD resveratrol is safe, well-tolerated, and alters some AD biomarker trajectories. The study is rated Class II because more than 2 primary outcomes were designated. © 2015 American Academy of Neurology.

Oral preoperative antioxidants in pancreatic surgery: a double-blind, randomized, clinical trial.

PubMed

Braga, Marco; Bissolati, Massimiliano; Rocchetti, Simona; Beneduce, Aldo; Pecorelli, Nicolò; Di Carlo, Valerio

2012-02-01

Oxidative stress due to ischemia/reperfusion injury increases systemic inflammation and impairs immune defenses. Much interest has developed for the administration of antioxidant substrates in surgical patients. The purpose of this study was to perform a pilot evaluation of the impact of a carbohydrate- containing preconditioning oral nutritional supplement (pONS) enriched with glutamine, antioxidants, and green tea extract on postoperative oxidative stress. We performed a double-blind placebo-controlled randomized clinical trial, involving 36 cancer patients undergoing pancreaticoduodenectomy. Patients were randomized to receive either pONS or placebo twice the day before surgery and once 3 hours before surgery. Total endogenous antioxidant capacity (TEAC), plasma levels of vitamin C, vitamin E, selenium, zinc, F2-isoprostanes, and C-reactive protein were measured at baseline and on postoperative day (POD) 1, 3, and 7. At surgery, the mean gastric residual volume (mL) was 54.2 in the pONS group versus 51.3 in the placebo group (P = NS). On POD 1 plasma levels of vitamin C (P = 0.001), selenium (P = 0.07), and zinc (P = 0.06) were higher in the pONS group compared to placebo. TEAC was improved on POD 1, 3, and 7 in the pONS group compared to placebo (P = 0.01). No difference was found in plasma C-reactive protein levels after surgery in both groups. Perioperative pONS administration positively affected plasma vitamin C levels and improved TEAC shortly after surgery, but did not reduce oxidative stress and systemic inflammation markers. Copyright © 2012 Elsevier Inc. All rights reserved.

Probiotic Supplementation in Chronic Kidney Disease: A Double-blind, Randomized, Placebo-controlled Trial.

PubMed

Borges, Natália A; Carmo, Flávia L; Stockler-Pinto, Milena B; de Brito, Jessyca S; Dolenga, Carla J; Ferreira, Dennis C; Nakao, Lia S; Rosado, Alexandre; Fouque, Denis; Mafra, Denise

2018-01-01

The objective of the study was to evaluate the effects of probiotic supplementation on the gut microbiota profile and inflammatory markers in chronic kidney disease patients undergoing maintenance hemodialysis (HD). This was a randomized, double-blind, placebo-controlled study. Forty-six HD patients were assigned to receive 1 of 2 treatments: probiotic (n = 23; Streptococcus thermophilus, Lactobacillus acidophilus e Bifidobacterialongum, 90 billion colony-forming units per day) or placebo (n = 23) daily for 3 months. Blood and feces were collected at baseline and after intervention. The inflammatory markers (C-reactive protein and interleukin-6) were analyzed by immunoenzymatic assay (enzyme-linked immunosorbent assay). Uremic toxins plasma levels (indoxyl sulfate, p-cresyl sulfate, and indole-3-acetic acid) were obtained by Reversed-Phase High-Performance Liquid Chromatography. Routine laboratory parameters were measured by standard techniques. Fecal pH was measured by the colorimetric method, and the gut microbiota profile was assessed by Denaturing Gradient Gel Electrophoresis analysis. Sixteen patients remained in the probiotic group (11 men, 53.6 ± 11.0 year old, 25.3 ± 4.6 kg/m 2 ) and 17 in the placebo group (10 men, 50.3 ± 8.5 year old, 25.2 ± 5.7 kg/m 2 ). After probiotic supplementation there was a significant increase in serum urea (from 149.6 ± 34.2 mg/dL to 172.6 ± 45.0 mg/dL, P = .02), potassium (from 4.4 ± 0.4 mmol/L to 4.8 ± 0.4 mmol/L, P = .02), and indoxyl sulfate (from 31.2 ± 15.9 to 36.5 ± 15.0 mg/dL, P = .02). The fecal pH was reduced from 7.2 ± 0.8 to 6.5 ± 0.5 (P = .01). These parameters did not change significantly in placebo group. Changes in the percentage delta (Δ) between groups were exhibited with no statistical differences observed. The inflammatory markers and gut profile were not altered by supplementation. Aprobiotic supplementation failed to reduce uremic toxins and

Albendazole versus metronidazole in the treatment of adult giardiasis: a randomized, double-blind, clinical trial.

PubMed

Cañete, Roberto; Rodríguez, Pablo; Mesa, Lumey; Brito, Katia; Prior, Ada; Guilhem, Dirce; Novaes, M R C G

2012-01-01

Albendazole (ABZ) is a benzimidazole carbamate compound currently in use for human medical practice against enterobiasis and soil-transmitted helminthiasis (STH); However, its spectrum of activity is broad and goes beyond these infections. This study compares the efficacy and safety of ABZ versus metronidazole (MTZ) in human giardiasis. A randomized, double-blind, clinical trial was carried out at the Centre of Hygiene, Epidemiology and Microbiology in Matanzas City, Cuba. Adult patients with confirmed symptomatic G. duodenalis mono-infection were randomly assigned to receive either ABZ [400 mg daily (n = 75)] or MTZ [250 mg t.i.d. (n = 75)], both for 5 days. Follow-up fecal samples were obtained at 3, 5, 7 days after treatment end. The efficacy was similar for both treatment groups: ABZ (82.6%) and MTZ (85.3%); p > 0.05. Side-effects including bitter taste, headache, vomiting and dizziness were significantly higher in the MTZ group. Abdominal pain was significantly higher in ABZ group. ABZ was found as effective as MTZ in the treatment of G. duodenalis infections in adult patients from Cuba and could be a useful drug in areas where co-infection with STH infections is common.

Modafinil Improves Real Driving Performance in Patients with Hypersomnia: A Randomized Double-Blind Placebo-Controlled Crossover Clinical Trial

PubMed Central

Philip, Pierre; Chaufton, Cyril; Taillard, Jacques; Capelli, Aurore; Coste, Olivier; Léger, Damien; Moore, Nicholas; Sagaspe, Patricia

2014-01-01

Study Objective: Patients with excessive daytime sleepiness (EDS) are at high risk for driving accidents, and physicians are concerned by the effect of alerting drugs on driving skills of sleepy patients. No study has up to now investigated the effect of modafinil (a reference drug to treat EDS in patients with hypersomnia) on on-road driving performance of patients suffering from central hypersomnia. The objective is to evaluate in patients with central hypersomnia the effect of a wake-promoting drug on real driving performance and to assess the relationship between objective sleepiness and driving performance. Design and Participants: Randomized, crossover, double-blind placebo-controlled trial conducted among 13 patients with narcolepsy and 14 patients with idiopathic hypersomnia. Patients were randomly assigned to receive modafinil (400 mg) or placebo for 5 days prior to the driving test. Each condition was separated by at least 3 weeks of washout. Measurements: Mean number of Inappropriate Line Crossings, Standard Deviation of Lateral Position of the vehicle and mean sleep latency in the Maintenance of Wakefulness Test were assessed. Results: Modafinil reduced the mean number of Inappropriate Line Crossings and Standard Deviation of Lateral Position of the vehicle compared to placebo (F(1,25) = 4.88, P < 0.05 and F(1,25) = 3.87, P = 0.06 tendency). Mean sleep latency at the Maintenance of Wakefulness Test significantly correlated with the mean number of Inappropriate Line Crossings (r = -0.41, P < 0.001). Conclusions: Modafinil improves driving performance in patients with narcolepsy and idiopathic hypersomnia. The Maintenance of Wakefulness Test is a suitable clinical tool to assess fitness to drive in this population. Citation: Philip P; Chaufton C; Taillard J; Capelli A; Coste O; Léger D; Moore N; Sagaspe P. Modafinil improves real driving performance in patients with hypersomnia: a randomized double-blind placebo-controlled crossover clinical trial. SLEEP

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 effect of combined somatosensory stimulation and task-specific training on upper limb function in chronic stroke: a double-blind randomized controlled trial.

PubMed

Fleming, Melanie K; Sorinola, Isaac O; Roberts-Lewis, Sarah F; Wolfe, Charles D; Wellwood, Ian; Newham, Di J

2015-02-01

Somatosensory stimulation (SS) is a potential adjuvant to stroke rehabilitation, but the effect on function needs further investigation. To explore the effect of combining SS with task-specific training (TST) on upper limb function and arm use in chronic stroke survivors and determine underlying mechanisms. In this double-blinded randomized controlled trial (ISRCTN 05542931), 33 patients (mean 37.7 months poststroke) were block randomized to 2 groups: active or sham SS. They received 12 sessions of 2 hours of SS (active or sham) to all 3 upper limb nerves immediately before 30 minutes of TST. The primary outcome was the Action Research Arm Test (ARAT) score. Secondary outcomes were time to perform the ARAT, Fugl-Meyer Assessment score (FM), Motor Activity Log (MAL), and Goal Attainment Scale (GAS). Underlying mechanisms were explored using transcranial magnetic stimulation stimulus-response curves and intracortical inhibition. Outcomes were assessed at baseline, immediately following the intervention (mean 2 days), and 3 and 6 months (mean 96 and 190 days) after the intervention. The active group (n = 16) demonstrated greater improvement in ARAT score and time immediately postintervention (between-group difference; P < .05), but not at 3- or 6-month follow-ups (P > .2). Within-group improvements were seen for both groups for ARAT and GAS, but for the active group only for FM and MAL (P < .05). Corticospinal excitability did not change. Long-lasting improvements in upper limb function were observed following TST. Additional benefit of SS was seen immediately post treatment, but did not persist and the underlying mechanisms remain unclear. © The Author(s) 2014.

Treatment of Multiple-Resistant and/or Recurrent Cutaneous Warts With Squaric Acid Dibutylester: A Randomized, Double-blind, Vehicle-controlled Clinical Trial.

PubMed

DallʼOglio, Federica; Luca, Maria; Barresi, Sebastiano; Micali, Giuseppe

Contact immunotherapy with squaric acid dibutylester (SADBE) for cutaneous warts has been reported to be effective, although no controlled studies are available so far. The aim of this study was to evaluate the efficacy of SADBE on cutaneous warts by a randomized, double-blind, vehicle-controlled, clinical trial. Thirty-six patients were randomly assigned to SADBE (18 cases) or vehicle (18 cases) group. At 8 weeks, subjects were clinically evaluated for number/size reduction rate and for Investigator Global Assessment. Those who showed improvement extended therapy up to 40 weeks, whereas those who showed unresponsiveness were either switched to SADBE application for up to 48 weeks (if in the vehicle group) or withdrawn from the study (if under SADBE). At 8 weeks, a significant reduction in wart number (P = 0.020) and size (P = 0.010) in the SADBE group, with clearing rates of 41.2% versus 12.5% in the SADBE and vehicle groups, respectively, was observed. Nine remaining SADBE responders who underwent treatment extension up to 40 weeks achieved clearing versus 2 patients of the vehicle group who remained unresponsive. Clearing was obtained in 81.8% of patients who underwent previous ineffective vehicle treatment and had been switched to SADBE. Squaric acid dibutylester is an effective therapeutic option and is significantly more effective than vehicle.

[The efficacy of the complex medication Phyto-Hypophyson L in female, hormone-related sterility. A randomized, placebo-controlled clinical double-blind study].

PubMed

Bergmann, J; Luft, B; Boehmann, S; Runnebaum, B; Gerhard, I

2000-08-01

In a prospective, randomized, placebo-controlled, double-blind study, the effects of Phyto Hypophyson L (Steierl-Pharma GmbH, Herrsching, Germany), an Agnus castus-containing homeopathic preparation, were investigated in 67 women with fertility disorders. 37 women with oligomenorrhea and 30 women with amenorrhea received 50 drops of Phyto Hypophyson L or placebo 3 times a day over 3 months or 3 cycles. OUTCOME MEASURE AND RESULTS: The outcome measure being spontaneous menstruation, improved concentration of progesterone in the luteal phase, shortening of the cycle, earlier ovulation, and pregnancy was achieved in 38 out of 67 women. It was achieved more often from women with oligomenorrhea in the Phyto Hypophyson L group compared to the placebo group (82 versus 45%, p = 0.021). However, there was no significant effect when viewing the whole group. The baby take-home rate during the therapy and 6 months after the end of the therapy showed a ratio of 6 : 2 (18.7 : 6.4%). This result was not significant. Furthermore, in the oligomenorrhea verum group we observed a significant increase of progesterone during the luteal phase compared to the oligomenorrhea placebo group. Only very few undesirable drug effects were observed. In women with sterility and oligomenorrhea, a treatment with Phyto Hypophyson L can be recommended over a period of 3-6 months. Copyright 2000 S. Karger GmbH, Freiburg

Yukmijihwang-tang for the treatment of xerostomia in the elderly: study protocol for a randomized, double-blind, placebo-controlled, two-center trial.

PubMed

Han, Gajin; Park, Jae-Woo; Ko, Seok-Jae; Son, Jihee; Seon, Jongki; Kim, Juyeon; Kim, Seulki; Yeo, Inkwon; Ryu, Bongha; Kim, Jinsung

2013-09-03

Xerostomia, a subjective sense of dry mouth, is not generally regarded a disease despite its high prevalence among the elderly, and therefore continues to impair affected patients' quality of life. In traditional Korean medicine, 'Yin-Deficiency' has been implicated in the pathogenesis of xerostomia among the elderly. Yukmijihwang-tang is a famous herbal prescription used to relieve 'Yin-Deficiency', and reportedly has antioxidant effects; therefore, it is postulated that Yukmijihwang-tang can be used to treat xerostomia in the elderly. However, to our knowledge, no clinical trial has been conducted on the effects of Yukmijihwang-tang on xerostomia. Thus, we designed a randomized clinical trial to investigate the effects and safety of Yukmijihwang-tang on xerostomia in the elderly. In addition, we will clarify the aforementioned assumption that 'Yin-Deficiency' is the major cause of xerostomia in the elderly by identifying a correlation between xerostomia and 'Yin-Deficiency'. This randomized, double-blind, placebo-controlled trial will be carried out at two centers: Kyung Hee University Korean Medicine Hospital and Kyung Hee University Hospital at Gangdong. We will recruit 96 subjects aged 60-80 years who have experienced xerostomia for 3 months prior to participation. Subjects who present with score >40 on the visual analogue scale for xerostomia and unstimulated salivary flow rate under 0.3mL/min will be included and the randomization will be carried out by an independent statistician by using a random number creation program. The subjects and all researchers except the statistician will be blinded to the group assignment. Yukmijihwang-tang or placebo will be administered to each group for 8 weeks. The primary outcome is change in the scores for the visual analogue scale for xerostomia and the dry mouth symptom questionnaire from 0 to 8 weeks. It will be assessed whether Yukmijihwang-tang can be used as a new herbal treatment for xerostomia in the elderly by

Yukmijihwang-tang for the treatment of xerostomia in the elderly: study protocol for a randomized, double-blind, placebo-controlled, two-center trial

PubMed Central

2013-01-01

Background Xerostomia, a subjective sense of dry mouth, is not generally regarded a disease despite its high prevalence among the elderly, and therefore continues to impair affected patients’ quality of life. In traditional Korean medicine, ‘Yin-Deficiency’ has been implicated in the pathogenesis of xerostomia among the elderly. Yukmijihwang-tang is a famous herbal prescription used to relieve ‘Yin-Deficiency’, and reportedly has antioxidant effects; therefore, it is postulated that Yukmijihwang-tang can be used to treat xerostomia in the elderly. However, to our knowledge, no clinical trial has been conducted on the effects of Yukmijihwang-tang on xerostomia. Thus, we designed a randomized clinical trial to investigate the effects and safety of Yukmijihwang-tang on xerostomia in the elderly. In addition, we will clarify the aforementioned assumption that ‘Yin-Deficiency’ is the major cause of xerostomia in the elderly by identifying a correlation between xerostomia and ‘Yin-Deficiency’. Methods/Design This randomized, double-blind, placebo-controlled trial will be carried out at two centers: Kyung Hee University Korean Medicine Hospital and Kyung Hee University Hospital at Gangdong. We will recruit 96 subjects aged 60-80 years who have experienced xerostomia for 3 months prior to participation. Subjects who present with score >40 on the visual analogue scale for xerostomia and unstimulated salivary flow rate under 0.3mL/min will be included and the randomization will be carried out by an independent statistician by using a random number creation program. The subjects and all researchers except the statistician will be blinded to the group assignment. Yukmijihwang-tang or placebo will be administered to each group for 8 weeks. The primary outcome is change in the scores for the visual analogue scale for xerostomia and the dry mouth symptom questionnaire from 0 to 8 weeks. Discussion It will be assessed whether Yukmijihwang-tang can be used as a

Effects of preoperative aspirin in coronary artery bypass grafting: a double-blind, placebo-controlled, randomized trial.

PubMed

Deja, Marek A; Kargul, Tomasz; Domaradzki, Wojciech; Stącel, Tomasz; Mazur, Witold; Wojakowski, Wojciech; Gocoł, Radosław; Gaszewska-Żurek, Ewa; Żurek, Paweł; Pytel, Agata; Woś, Stanisław

2012-07-01

This trial was undertaken to determine the safety and efficacy of preoperative aspirin administration in a contemporary cardiac surgical practice setting. This randomized, double-blind, parallel-group, single-center trial involved patients with stable coronary artery disease who were assigned to receive either 300 mg of aspirin or placebo the night before coronary bypass surgery. Using a random digit table, patients were allocated to receive the tablet from 1 of the 40 coded bottles containing either aspirin or placebo. Patients, surgeons, anesthetists, and investigators were all masked to treatment allocation. The primary safety end points were as follows: more than 750 mL of bleeding during the first postoperative 12 hours and more than 1000 mL of total discharge from the chest drains. The secondary efficacy end point was a composite of cardiovascular death, myocardial infarction, or repeat revascularization. A total of 390 patients were allocated to aspirin (387 analyzed) and 399 to placebo (396 analyzed). The follow-up median was 53 months. Fifty-four placebo recipients and 86 aspirin recipients bled more than 750 mL in the first 12 hours (odds ratio [OR], 1.81; 95% confidence interval [CI], 1.25-2.63), while total chest drain discharge was above 1000 mL in 96 placebo and 131 aspirin recipients (OR, 1.60; 95% CI, 1.17-2.18). Preoperative aspirin decreased the long-term hazard of nonfatal coronary event (infarction or repeat revascularization)-hazard ratio (HR), 0.58 (95% CI, 0.33-0.99)--and tended to decrease the hazard of a major cardiac event (cardiovascular death, infarction, or repeat revascularization--HR, 0.65 [95% CI, 0.41-1.03]). Performing coronary grafts on aspirin is associated with increased postoperative bleeding but may decrease the long-term hazard of coronary events. Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

A double-blind, randomized, placebo-controlled comparison of botulinum toxin type a injection sites and doses in the prevention of episodic migraine.

PubMed

Saper, Joel R; Mathew, Ninan T; Loder, Elizabeth W; DeGryse, Ronald; VanDenburgh, Amanda M

2007-09-01

Several randomized, controlled studies have reported benefits of botulinum toxin type A (BoNTA; Allergan Inc., Irvine, CA, USA) over placebo in the treatment of migraine. Some studies reported significant benefits at dosages as low as 16 U, while other studies reported safety, tolerability, and efficacy at dosages up to 260 U. However, the optimal treatment paradigm and patient population have yet to be defined. To compare different injection sites and doses of BoNTA in the prevention of episodic migraine. This was a randomized, double-blind, placebo-controlled study of 232 patients with a history of four to eight moderate to severe migraines per month, with or without aura. Patients were randomized to placebo or one of four BoNTA groups that received injections into different muscle regions: frontal (10 U), temporal (6 U), glabellar (9 U), or all three areas (total dose 25 U). For 3 months following a single treatment, patients recorded migraine-related variables in a daily diary. BoNTA and placebo produced comparable decreases from baseline in the frequency of migraines (P > or = 0.411). In general, no statistically significant differences were observed for any efficacy variable. The overall rates of adverse events (any type) or treatment-related adverse events were similar among the groups. In this exploratory study of episodic migraine patients, low-dose injections of BoNTA into the frontal, temporal, and/or glabellar muscle regions were not more effective than placebo. BoNTA was safe and well tolerated. Future studies may examine higher BoNTA doses, flexible injection sites, multiple treatments, and disallow concomitant prophylactic medications.

Effects of fixed orthodontic treatment using conventional (two-piece) versus metal injection moulding brackets on hair nickel and chromium levels: a double-blind randomized clinical trial.

PubMed

Khaneh Masjedi, Mashallah; Haghighat Jahromi, Nima; Niknam, Ozra; Hormozi, Elham; Rakhshan, Vahid

2017-02-01

Although nickel and chromium are known as allergen and cytotoxic orthodontic metals, very few and controversial studies have assessed the effect of orthodontic treatment on their systemic levels especially those reflected by their best biomarker of exposure, hair. Additionally, metal injection moulding (MIM) brackets are not studied, and there is no study on systemic ion changes following their usage. In this double-blind randomized clinical trial, scalp hair samples of 24 female and 22 male fixed orthodontic patients [as two groups of conventional (two-piece) versus MIM brackets, n = 23×2] were collected before treatment and 6 months later. Randomization was carried out using a computer-generated random number table. The patients, laboratory expert, and author responsible for analyses were blinded of the bracket allocations. Hair nickel and chromium levels were measured using atomic absorption spectrophotometry. The effects of treatment, bracket types, gender, and age on hair ions were analysed statistically (α = 0.05, β ≤ 0.02). In both groups combined (n = 46), nickel increased from 0.1600±0.0890 µg/g dry hair mass (pre-treatment) to 0.3199±0.1706 (6th month). Chromium increased from 0.1657±0.0884 to 0.3066±0.1362 µg/g. Both of these increases were significant (paired t-test, P = 0.0000). Bracket types, age, and gender had no significant influence on ion levels (P > 0.05). ANCOVA indicated different patterns of chromium increases in different genders (P = 0.033) and ages (P = 0.056). Sample size determination should have accounted for the grouping as well. Hair nickel and chromium levels might increase about 185-200% after 6 months. They might not be affected by bracket types. Gender and age might not influence the baseline or 6th-month levels of both metals. Gender might however interact with orthodontic treatment, only in the case of chromium. The research is registered offline (thesis) and online (IR.AJUMS.REC.1394.516). The protocol was pre

Metformin extended release treatment of adolescent obesity: a 48-week randomized, double-blind, placebo-controlled trial with 48-week follow-up.

PubMed

Wilson, Darrell M; Abrams, Stephanie H; Aye, Tandy; Lee, Phillip D K; Lenders, Carine; Lustig, Robert H; Osganian, Stavroula V; Feldman, Henry A

2010-02-01

Metformin has been proffered as a therapy for adolescent obesity, although long-term controlled studies have not been reported. To test the hypothesis that 48 weeks of daily metformin hydrochloride extended release (XR) therapy will reduce body mass index (BMI) in obese adolescents, as compared with placebo. Multicenter, randomized, double-blind, placebo-controlled clinical trial. The 6 centers of the Glaser Pediatric Research Network from October 2003 to August 2007. Obese (BMI > or = 95th percentile) adolescents (aged 13-18 years) were randomly assigned to the intervention (n = 39) or placebo groups. Intervention Following a 1-month run-in period, subjects following a lifestyle intervention program were randomized 1:1 to 48 weeks' treatment with metformin hydrochloride XR, 2000 mg once daily, or an identical placebo. Subjects were monitored for an additional 48 weeks. Main Outcome Measure Change in BMI, adjusted for site, sex, race, ethnicity, and age and metformin vs placebo. After 48 weeks, mean (SE) adjusted BMI increased 0.2 (0.5) in the placebo group and decreased 0.9 (0.5) in the metformin XR group (P = .03). This difference persisted for 12 to 24 weeks after cessation of treatment. No significant effects of metformin on body composition, abdominal fat, or insulin indices were observed. Metformin XR caused a small but statistically significant decrease in BMI when added to a lifestyle intervention program. clinicaltrials.gov Identifiers: NCT00209482 and NCT00120146.

Add-on treatment of benzoate for schizophrenia: a randomized, double-blind, placebo-controlled trial of D-amino acid oxidase inhibitor.

PubMed

Lane, Hsien-Yuan; Lin, Ching-Hua; Green, Michael F; Hellemann, Gerhard; Huang, Chih-Chia; Chen, Po-Wei; Tun, Rene; Chang, Yue-Cung; Tsai, Guochuan E

2013-12-01

In addition to dopaminergic hyperactivity, hypofunction of the N-methyl-d-aspartate receptor (NMDAR) has an important role in the pathophysiology of schizophrenia. Enhancing NMDAR-mediated neurotransmission is considered a novel treatment approach. To date, several trials on adjuvant NMDA-enhancing agents have revealed beneficial, but limited, efficacy for positive and negative symptoms and cognition. Another method to enhance NMDA function is to raise the levels of d-amino acids by blocking their metabolism. Sodium benzoate is a d-amino acid oxidase inhibitor. To examine the clinical and cognitive efficacy and safety of add-on treatment of sodium benzoate for schizophrenia. A randomized, double-blind, placebo-controlled trial in 2 major medical centers in Taiwan composed of 52 patients with chronic schizophrenia who had been stabilized with antipsychotic medications for 3 months or longer. Six weeks of add-on treatment of 1 g/d of sodium benzoate or placebo. The primary outcome measure was the Positive and Negative Syndrome Scale (PANSS) total score. Clinical efficacy and adverse effects were assessed biweekly. Cognitive functions were measured before and after the add-on treatment. Benzoate produced a 21% improvement in PANSS total score and large effect sizes (range, 1.16-1.69) in the PANSS total and subscales, Scales for the Assessment of Negative Symptoms-20 items, Global Assessment of Function, Quality of Life Scale and Clinical Global Impression and improvement in the neurocognition subtests as recommended by the National Institute of Mental Health's Measurement and Treatment Research to Improve Cognition in Schizophrenia initiative, including the domains of processing speed and visual learning. Benzoate was well tolerated without significant adverse effects. Benzoate adjunctive therapy significantly improved a variety of symptom domains and neurocognition in patients with chronic schizophrenia. The preliminary results show promise for d-amino acid oxidase

Management of Neuropathic Chronic Pain with Methadone Combined with Ketamine: A Randomized, Double Blind, Active-Controlled Clinical Trial.

PubMed

Rigo, Flavia Karine; Trevisan, Gabriela; Godoy, Maria C; Rossato, Mateus Fortes; Dalmolin, Gerusa D; Silva, Mariane A; Menezes, Mirian S; Caumo, Wolnei; Ferreira, Juliano

2017-03-01

Methadone and ketamine are used in neuropathic pain management. However, the benefits of both drugs association are uncertain in the treatment of neuropathic pain. Our primary objective was test the hypothesis that oral methadone combined with oral ketamine is more effective than oral methadone or ketamine alone in reducing neuropathic pain. We conducted a randomized, double blind, active-controlled parallel-group clinical trial. Forty-two patients with neuropathic pain refractory to conventional therapy were randomly assigned to receive oral methadone (n = 14), ketamine (n = 14), or methadone plus ketamine (n = 14) over a 3-month period. During these 90 days, we observed pain scores using a visual analogical scale (VAS), allodynia, burning/shooting pain, and some side effects. All treatments were effective in reducing pain scores by at least 40%. However, a significant improvement in pain was observed only in the ketamine alone group compared with both the methadone or methadone/ketamine groups. No significant differences were observed among the treatment groups for the reduction of burning or shooting pain, while ketamine alone was more effective than methadone or methadone/ketamine for the reduction of allodynia. Formal assessment for awareness of the allocation was not performed, some co-intervention bias may have occurred, our results could be only relevant to the patient population investigated and the use of VAS as the primary outcome detect changes in pain intensity but not to assess neuropathic pain symptoms. This study indicates that ketamine was better than methadone or methadone/ketamine for treating neuropathic pain.Key words: Multimodal analgesia, refractory pain, NMDA receptor, opioid.

Targeted nalmefene with simple medical management in the treatment of heavy drinkers: a randomized double-blind placebo-controlled multicenter study.

PubMed

Karhuvaara, Sakari; Simojoki, Kaarlo; Virta, Antti; Rosberg, Markus; Löyttyniemi, Eliisa; Nurminen, Tommi; Kallio, Antero; Mäkelä, Rauno

2007-07-01

Clinical studies with opioid antagonists for treatment of problem drinking have mainly been conducted in specialized alcohol treatment centers, included structured psychosocial treatment, and have focused on maintaining abstinence after a period of abstinence from alcohol. This multisite, randomized double-blind study investigated targeted nalmefene in reducing heavy drinking. Specialized alcohol treatment centers and private general practices enrolled 403 subjects (328 men, 75 women). Subjects were instructed to take nalmefene 10 to 40 mg (n=242) or placebo (n=161) when they believed drinking to be imminent. After 28 weeks, 57 subjects from the nalmefene group continued into a 24-week randomized withdrawal extension. Concomitant psychosocial intervention was minimal and no treatment goals were imposed. Alcohol consumption was recorded using the time-line follow-back method. Biochemical indicators of alcohol use were also measured. The mean monthly number of heavy drinking days (HDDs) during the 12-week period before inclusion was 15.5 (SD 6.9) in the nalmefene group and 16.2 (SD 6.9) in the placebo group. During treatment, the mean numbers of HDDs were 8.6 to 9.3 in the nalmefene group and 10.6 to 12.0 in the placebo group (p=0.0065). The levels of serum alanine aminotransferase and gamma-glutamyl transferase decreased in the nalmefene group compared with the placebo group (p=0.0088 and 0.0023). During the randomized withdrawal period, subjects randomized to placebo apparently returned to heavier drinking. Subjects receiving nalmefene reported more nausea, insomnia, fatigue, dizziness, and malaise than subjects on placebo. Nalmefene appears to be effective and safe in reducing heavy drinking, even when accompanied by minimal psychosocial support.

Randomized Double-Blinded Dose Escalation Trial of Triptorelin for Ovary Protection in Childhood-Onset Systemic Lupus Erythematosus

PubMed Central

Brunner, Hermine I.; Silva, Clovis A; Reiff, Andreas; Higgins, Gloria C.; Imundo, Lisa; Williams, Calvin B.; Wallace, Carol A; Aikawa, Nadia E.; Nelson, Shannen; Klein-Gitelman, Marisa S.; Rose, Susan R.

2015-01-01

Objectives To determine for females with childhood-onset systemic lupus erythematosus (cSLE) who require cyclophosphamide the dose of triptorelin that suffices to maintain complete ovarian suppression (COS); measure the time needed to achieve ovarian suppression after triptorelin initiation, and explore the safety of triptorelin. Methods In this randomized double-blind placebo-controlled dose-escalation study females (< 21 years) were randomized 4:1 to receive triptorelin or placebo (25 triptorelin, 6 placebo). Starting doses of triptorelin between 25 and 100 microgram/kg/dose were used. Triptorelin dosage was escalated until COS was maintained. The primary outcome was the weight-adjusted dose of triptorelin that for at least 90% of the patients provides COS based on Gonadotropin-releasing-hormone Agonist Stimulation Testing. Secondary outcomes were time to ovarian suppression measured by unstimulated FSH and LH levels after study drug initiation. Results Triptorelin dosed at 120 microgram/kg bodyweight led to sustained COS in 90% of the patients. After the initial dose of triptorelin 22 days were needed for achieve COS. Rates of adverse events (AE) and serious adverse events (SAE) per 100 patient-month of follow-up were not higher in the triptorelin group as compared to the placebo group (triptorelin vs. placebo; AE: 189 vs. 362; SAE: 2.05 vs. 8.48). Conclusions For achieving and maintaining COS high doses of triptorelin are needed but appear to be well tolerated in adolescent females with cSLE. Our data suggest that a lag time of 22 days after triptorelin initiation is required before starting or continuing cyclophosphamide-therapy. Trial Registration Number clinicaltrials.gov identifier: NCT00124514 PMID:25676588

Effect of Febuxostat on the Endothelial Dysfunction in Hemodialysis Patients: A Randomized, Placebo-Controlled, Double-Blinded Study.

PubMed

Alshahawey, Mona; Shahin, Sara Mahmoud; Elsaid, Tamer Wahid; Sabri, Nagwa Ali

2017-01-01

Endothelial dysfunction is an important risk factor for cardiovascular diseases to occur in end-stage renal disease patients. Febuxostat, being a novel xanthine oxidase inhibitor, is apparently having a beneficial role in improving the endothelial dysfunction; however, data among hemodialysis patients are still limited. A prospective, placebo-controlled, block-randomized, double-blinded study was carried out to evaluate the effect of oral febuxostat on the endothelial dysfunction in hemodialysis patients. Fifty-seven eligible hemodialysis patients were randomly assigned to either the drug group (40 mg thrice weekly) or the placebo group. Serum Asymmetric dimethylarginine (ADMA), Serum uric acid (UA), and serum high sensitivity C-reactive protein (hsCRP) were measured at baseline and at the end of a 2-month study. Serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), and the occurrence of pancytopenia were tested as safety parameters at baseline and at the end of study. Serum UA significantly decreased from 7.5 ± 0.8 to 5.1 ± 1.2 mg/dL in the febuxostat group, while it did not change significantly in the placebo group. Treatment with febuxostat resulted in a significant decrease in the serum ADMA level from 1.027 ± 0.116 to 0.944 ± 0.104 µmol/L and the serum hsCRP level from 12.5 ± 1.65 to 12.1 ± 1.70 mg/L. Testing of serum ALT, serum AST, and pancytopenia revealed no significant difference in both groups. Febuxostat appears to improve hyperuricemia and endothelial dysfunction and ameliorate inflammation in hemodialysis patients with no safety concerns. © 2017 S. Karger AG, Basel.

Desiccated thyroid extract compared with levothyroxine in the treatment of hypothyroidism: a randomized, double-blind, crossover study.

PubMed

Hoang, Thanh D; Olsen, Cara H; Mai, Vinh Q; Clyde, Patrick W; Shakir, Mohamed K M

2013-05-01

Patients previously treated with desiccated thyroid extract (DTE), when being switched to levothyroxine (L-T₄), occasionally did not feel as well despite adequate dosing based on serum TSH levels. Our objective was to investigate the effectiveness of DTE compared with L-T₄ in hypothyroid patients. We conducted a randomized, double-blind, crossover study at a tertiary care center. Patients (n = 70, age 18-65 years) diagnosed with primary hypothyroidism on a stable dose of L-T₄ for 6 months were included in the study. Patients were randomized to either DTE or L-T₄ for 16 weeks and then crossed over for the same duration. Biochemical and neurocognitive tests at baseline and at the end of each treatment period were evaluated. There were no differences in symptoms and neurocognitive measurements between the 2 therapies. Patients lost 3 lb on DTE treatment (172.9 ± 36.4 lb vs 175.7 ± 37.7 lb, P < .001). At the end of the study, 34 patients (48.6%) preferred DTE, 13 (18.6%) preferred L-T₄, and 23 (32.9%) had no preference. In the subgroup analyses, those patients who preferred DTE lost 4 lb during the DTE treatment, and their subjective symptoms were significantly better while taking DTE as measured by the general health questionnaire-12 and thyroid symptom questionnaire (P < .001 for both). Five variables were predictors of preference for DTE. DTE therapy did not result in a significant improvement in quality of life; however, DTE caused modest weight loss and nearly half (48.6%) of the study patients expressed preference for DTE over L-T₄. DTE therapy may be relevant for some hypothyroid patients.

Topical corticosteroids in the treatment of acute sunburn: a randomized, double-blind clinical trial.

PubMed

Faurschou, Annesofie; Wulf, Hans C

2008-05-01

To examine the effect of topical corticosteroid treatment on acute sunburn. Randomized, double-blind clinical trial. University dermatology department. Twenty healthy volunteers with Fitzpatrick skin types I (highly sensitive, always burns easily, tans minimally) through III (sun-sensitive skin, sometimes burns, slowly tans to light brown). Seven 34-cm(2) areas were marked on the upper aspect of the back of each participant. An untreated area was tested to determine UV sensitivity. Two areas were treated with excess amounts (2 mg/cm(2)) of either a moderate-potency corticosteroid or a high-potency corticosteroid 30 minutes before UV-B exposure as controls. Six or 23 hours after exposure to radiation, the remaining areas were treated with the 2 corticosteroid preparations. The sunburn improvement factor (SIF) was determined by the following equation: SIF = MED (minimal erythema dose) on treated skin/MED on nontreated skin. An SIF greater than 1 indicated an effect of topical corticosteroids in sunburn relief. The SIFs in the areas treated with either topical corticosteroid 30 minutes before UV-B exposure or high-potency corticosteroid 6 hours after UV-B exposure were significantly different from SIFs in areas that received no treatment (SIF 1.1-1.7; P < .05). Only the median SIF of 1.7 in the areas treated with high-potency corticosteroid 30 minutes before UV-B exposure was clinically relevant. The areas treated 23 hours after UV-B exposure and the areas treated with a moderate-potency corticosteroid 6 hours after UV-B exposure showed no significant reduction in redness. Treatment with topical moderate-potency or high-potency corticosteroids does not provide a clinically useful decrease in the acute sunburn reaction when applied 6 or 23 hours after UV exposure.

Alleviation of mandibular anterior crowding with copper-nickel-titanium vs nickel-titanium wires: a double-blind randomized control trial.

PubMed

Pandis, Nikolaos; Polychronopoulou, Argy; Eliades, Theodore

2009-08-01

The purpose of this study was to investigate the efficiency of copper-nickel-titanium (CuNiTi) vs nickel-titanium (NiTi) archwires in resolving crowding of the anterior mandibular dentition. Sixty patients were included in this single-center, single-operator, double-blind randomized trial. All patients were bonded with the In Ovation-R self-ligating bracket (GAC, Central Islip, NY) with a 0.022-in slot, and the amount of crowding of the mandibular anterior dentition was assessed by using the irregularity index. The patients were randomly allocated into 2 groups of 30 patients, each receiving a 0.016-in CuNiTi 35 degrees C (Ormco, Glendora, Calif) or a 0.016-in NiTi (ModernArch, Wyomissing, Pa) wire. The type of wire selected for each patient was not disclosed to the provider or the patient. The date that each patient received a wire was recorded, and all patients were followed monthly for a maximum of 6 months. Demographic and clinical characteristics between the 2 wire groups were compared with the t test or the chi-square test and the Fisher exact test. Time to resolve crowding was explored with statistical methods for survival analysis, and alignment rate ratios for wire type and crowding level were calculated with Cox proportional hazards multivariate modeling. The type of wire (CuNiTi vs NiTi) had no significant effect on crowding alleviation (129.4 vs 121.4 days; hazard ratio, 1.3; P >0.05). Severe crowding (>5 on the irregularity index) showed a significantly higher probability of crowding alleviation duration relative to dental arches with a score of <5 (138.5 vs 113.1 days; hazard ratio, 2.2; P=0.02). The difference of the loading pattern of wires in laboratory and clinical conditions might effectively eliminate the laboratory-derived advantage of CuNiTi wires.

Estrogen for Alzheimer's disease in women: randomized, double-blind, placebo-controlled trial.

PubMed

Henderson, V W; Paganini-Hill, A; Miller, B L; Elble, R J; Reyes, P F; Shoupe, D; McCleary, C A; Klein, R A; Hake, A M; Farlow, M R

2000-01-25

AD, the most prevalent cause of dementia, affects twice as many women as men. Therapeutic options are limited, but results of prior studies support the hypothesis that estrogen treatment may improve symptoms of women with this disorder. Forty-two women with mild-to-moderate dementia due to AD were enrolled into a randomized, double-blind, placebo-controlled, parallel-group trial of unopposed conjugated equine estrogens (1.25 mg/day) for 16 weeks. Outcome data were available for 40 women at 4 weeks and 36 women at 16 weeks. At both 4 and 16 weeks, there were no significant differences or statistical trends between treatment groups on the primary outcome measure (the cognitive subscale of the Alzheimer's Disease Assessment Scale), clinician-rated global impression of change, or caregiver-rated functional status. Exploratory analyses of mood and specific aspects of cognitive performance also failed to demonstrate substantial group differences. Although conclusions are limited by small sample size and the possibility of a type II error, results suggest that short-term estrogen therapy does not improve symptoms of most women with AD. These findings do not address possible long-term effects of estrogen in AD, possible interactions between estrogen and other treatment modalities, or putative effects of estrogen in preventing or delaying onset of this disorder.

Randomized, Double-Blind, Phase III Trial of Ipilimumab Versus Placebo in Asymptomatic or Minimally Symptomatic Patients With Metastatic Chemotherapy-Naive Castration-Resistant Prostate Cancer.

PubMed

Beer, Tomasz M; Kwon, Eugene D; Drake, Charles G; Fizazi, Karim; Logothetis, Christopher; Gravis, Gwenaelle; Ganju, Vinod; Polikoff, Jonathan; Saad, Fred; Humanski, Piotr; Piulats, Josep M; Gonzalez Mella, Pablo; Ng, Siobhan S; Jaeger, Dirk; Parnis, Francis X; Franke, Fabio A; Puente, Javier; Carvajal, Roman; Sengeløv, Lisa; McHenry, M Brent; Varma, Arvind; van den Eertwegh, Alfonsus J; Gerritsen, Winald

2017-01-01

Purpose Ipilimumab increases antitumor T-cell responses by binding to cytotoxic T-lymphocyte antigen 4. We evaluated treatment with ipilimumab in asymptomatic or minimally symptomatic patients with chemotherapy-naive metastatic castration-resistant prostate cancer without visceral metastases. Patients and Methods In this multicenter, double-blind, phase III trial, patients were randomly assigned (2:1) to ipilimumab 10 mg/kg or placebo every 3 weeks for up to four doses. Ipilimumab 10 mg/kg or placebo maintenance therapy was administered to nonprogressing patients every 3 months. The primary end point was overall survival (OS). Results Four hundred patients were randomly assigned to ipilimumab and 202 to placebo; 399 were treated with ipilimumab and 199 with placebo. Median OS was 28.7 months (95% CI, 24.5 to 32.5 months) in the ipilimumab arm versus 29.7 months (95% CI, 26.1 to 34.2 months) in the placebo arm (hazard ratio, 1.11; 95.87% CI, 0.88 to 1.39; P = .3667). Median progression-free survival was 5.6 months in the ipilimumab arm versus 3.8 with placebo arm (hazard ratio, 0.67; 95.87% CI, 0.55 to 0.81). Exploratory analyses showed a higher prostate-specific antigen response rate with ipilimumab (23%) than with placebo (8%). Diarrhea (15%) was the only grade 3 to 4 treatment-related adverse event (AE) reported in ≥ 10% of ipilimumab-treated patients. Nine (2%) deaths occurred in the ipilimumab arm due to treatment-related AEs; no deaths occurred in the placebo arm. Immune-related grade 3 to 4 AEs occurred in 31% and 2% of patients, respectively. Conclusion Ipilimumab did not improve OS in patients with metastatic castration-resistant prostate cancer. The observed increases in progression-free survival and prostate-specific antigen response rates suggest antitumor activity in a patient subset.

Omega-3 (ω-3) and social skills interventions for reactive aggression and childhood externalizing behavior problems: a randomized, stratified, double-blind, placebo-controlled, factorial trial.

PubMed

Raine, Adrian; Ang, Rebecca P; Choy, Olivia; Hibbeln, Joseph R; Ho, Ringo M-H; Lim, Choon Guan; Lim-Ashworth, Nikki S J; Ling, Shichun; Liu, Jean C J; Ooi, Yoon Phaik; Tan, Yi Ren; Fung, Daniel S S

2018-05-10

While studies suggest that nutritional supplementation may reduce aggressive behavior in children, few have examined their effects on specific forms of aggression. This study tests the primary hypothesis that omega-3 (ω-3), both alone and in conjunction with social skills training, will have particular post-treatment efficacy for reducing childhood reactive aggression relative to baseline. In this randomized, double-blind, stratified, placebo-controlled, factorial trial, a clinical sample of 282 children with externalizing behavior aged 7-16 years was randomized into ω-3 only, social skills only, ω-3 + social skills, and placebo control groups. Treatment duration was 6 months. The primary outcome measure was reactive aggression collected at 0, 3, 6, 9, and 12 months, with antisocial behavior as a secondary outcome. Children in the ω-3-only group showed a short-term reduction (at 3 and 6 months) in self-report reactive aggression, and also a short-term reduction in overall antisocial behavior. Sensitivity analyses and a robustness check replicated significant interaction effects. Effect sizes (d) were small, ranging from 0.17 to 0.31. Findings provide some initial support for the efficacy of ω-3 in reducing reactive aggression over and above standard care (medication and parent training), but yield only preliminary and limited support for the efficacy of ω-3 in reducing overall externalizing behavior in children. Future studies could test further whether ω-3 shows promise in reducing more reactive, impulsive forms of aggression.

Transdermal rotigotine in advanced Parkinson's disease: a randomized, double-blind, placebo-controlled trial.

PubMed

Nomoto, Masahiro; Mizuno, Yoshikuni; Kondo, Tomoyoshi; Hasegawa, Kazuko; Murata, Miho; Takeuchi, Masahiro; Ikeda, Junji; Tomida, Takayuki; Hattori, Nobutaka

2014-10-01

Rotigotine, a non-ergot dopamine receptor agonist, offers potential for continuous dopaminergic stimulation that could avoid the fluctuations observed with traditional treatments. We conducted a randomized, double-blind, placebo-controlled trial in Japanese patients with advanced Parkinson's disease (PD) to investigate the efficacy and safety of rotigotine. Inclusion criteria included the presence of motor complications, such as wearing off, on-off, delayed-on/no-on, any circumstances that could interfere with levodopa dose escalation because of side effects, or declining levodopa efficacy. The enrolled patients received once-daily applications of rotigotine transdermal patches or matched placebo patches. A total of 174 patients were randomly assigned to rotigotine (87 patients) or placebo (87 patients). The full analysis set included 172 patients (86 for the rotigotine group and 86 for the placebo group). The maximum maintenance dose of rotigotine was set at 16 mg/24 h. The changes in unified PD rating scale Part III scores from baseline to the end of the trial were -10.1 ± 9.0 (mean ± standard deviation) in the rotigotine group and -4.4 ± 7.4 in the placebo group (p < 0.001). There was a significantly greater reduction in the off-time (p = 0.014) in the rotigotine group. Rotigotine was well tolerated, with serious adverse events being reported in only three patients in each group. Rotigotine at doses of up to 16 mg/24 h is efficacious and safe in Japanese patients with advanced PD.

Acute rejection characteristics from a prospective, randomized, double-blind, placebo-controlled multicenter trial of early corticosteroid withdrawal.

PubMed

Gaber, A Osama; Moore, Linda W; Alloway, Rita R; Woodle, E Steve; Pirsch, John; Shihab, Fuad; Henning, Alice; Fitzsimmons, William; Holman, John; Reisfield, Robin; First, M Roy

2013-02-27

This report characterizes acute rejection and rejection outcomes in subjects randomized to continuous corticosteroid therapy (CCS) or early corticosteroid withdrawal (CSWD; 7 days after transplantation) in the Astellas Blinded CSWD Trial. The Astellas Blinded CSWD Trial was a 5-year, prospective, multicenter, randomized, double-blind trial of early CCS withdrawal in 386 kidney transplant recipients (195 CCS and 191 CSWD). Tacrolimus and mycophenolate mofetil were required as well as either rabbit antithymocyte globulin or interleukin-2 receptor antibody induction. Biopsy-confirmed acute rejection (BCAR) was grade 1A or higher by Banff criteria. This report also provides borderline changes (BL) that did not meet Banff grade 1A included with BCAR (BCAR+BL). BCAR+BL was 25 (12.8%) in CCS group and 42 (22.0%) in CSWD group (P=0.022). Early BCAR+BL (first 90 days after transplantation) was less frequent in CCS (n=5 [2.6%]) than in CSWD (n=22 [11.5%]; P<0.001). Among non-African-American subjects, early BCAR+BL occurred more often in CSWD (n=20 [12.7%]) versus CCS (n=2 [1.3%]; P<0.001). Late acute rejection (>2 years) occurred more often in African-American subjects in CCS (n=5 [13.9%]) than in CSWD (n=0; P=0.056). Risk factors were CSWD (hazard ratio [HR], 4.72; P<0.002) and human leukocyte antigen mismatch (HR, 1.48; P<0.005) for early BCAR+BL and CSWD (HR, 1.9; P<0.02), human leukocyte antigen mismatch (HR, 1.2; P<0.01), and age (HR, 0.97; P<0.002) for 5-year rejection. The HR for graft loss associated with BCAR+BL was 8.8. BCAR+BL may occur more frequently during the early period after transplantation under an early CSWD regimen with tacrolimus plus induction compared with CCS, particularly among non-African-Americans.

The Effect of Adjuvant Zinc Therapy on Recovery from Pneumonia in Hospitalized Children: A Double-Blind Randomized Controlled Trial

PubMed Central

Qasemzadeh, Mohammad Javad; Fathi, Mahdi; Tashvighi, Maryam; Gharehbeglou, Mohammad; Yadollah-Damavandi, Soheila; Parsa, Yekta; Rahimi, Ebrahim

2014-01-01

Objectives. Pneumonia is one of the common mortality causes in young children. Some studies have shown beneficial effect of zinc supplements on treatment of pneumonia. The present study aimed to investigate the effects of short courses of zinc administration on recovery from this disease in hospitalized children. Methods. In a parallel Double-Blind Randomized Controlled Trial at Ayatollah Golpaygani Hospital in Qom, 120 children aged 3–60 months with pneumonia were randomly assigned 1 : 1 to receive zinc or placebo (5 mL every 12 hours) along with the common antibiotic treatments until discharge. Primary outcome was recovery from pneumonia which included the incidence and resolving clinical symptoms and duration of hospitalization. Results. The difference between two groups in all clinical symptoms at admittance and the variables affecting the disease such as age and sex were not statistically significant (P < 0.05) at baseline. Compared to the placebo group, the treatment group showed a statistically significant decrease in duration of clinical symptoms (P = 0.044) and hospitalization (P = 0.004). Conclusions. Supplemental administration of zinc can expedite the healing process and results in faster resolution of clinical symptoms in children with pneumonia. In general, zinc administration, along with common antibiotic treatments, is recommended in this group of children. It can also reduce the drug resistance caused by multiple antibiotic therapies. This trial is approved by Medical Ethic Committee of Islamic Azad University in Iran (ID Number: 8579622-Q). This study is also registered in AEARCTR (The American Economic Association's Registry for Randomized Controlled Trials). This trial is registered with RCT ID: AEARCTR-0000187. PMID:24955282

Escitalopram treatment of depression in human immunodeficiency virus/acquired immunodeficiency syndrome: a randomized, double-blind, placebo-controlled study.

PubMed

Hoare, Jacqueline; Carey, Paul; Joska, John A; Carrara, Henri; Sorsdahl, Katherine; Stein, Dan J

2014-02-01

Depression can be a chronic and impairing illness in people with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome. Large randomized studies of newer selective serotonin reuptake inhibitors such as escitalopram in the treatment of depression in HIV, examining comparative treatment efficacy and safety, have yet to be done in HIV-positive patients. This was a fixed-dose, placebo-controlled, randomized, double-blind study to investigate the efficacy of escitalopram in HIV-seropositive subjects with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, major depressive disorder. One hundred two participants were randomly assigned to either 10 mg of escitalopram or placebo for 6 weeks. An analysis of covariance of the completers found that there was no advantage for escitalopram over placebo on the Montgomery-Asberg Depression Rating Scale (p = 0.93). Sixty-two percent responded to escitalopram and 59% responded to placebo on the Clinical Global Impression Scale. Given the relatively high placebo response, future trials in this area need to be selective in participant recruitment and to be adequately powered.

Low-Dose Daily Intake of Vitamin K(2) (Menaquinone-7) Improves Osteocalcin γ-Carboxylation: A Double-Blind, Randomized Controlled Trials.

PubMed

Inaba, Naoko; Sato, Toshiro; Yamashita, Takatoshi

2015-01-01

Vitamin K is essential for bone health, but the effects of low-dose vitamin K intake in Japanese subjects remain unclear. We investigated the effective minimum daily menaquinone-7 dose for improving osteocalcin γ-carboxylation. Study 1 was a double-blind, randomized controlled dose-finding trial; 60 postmenopausal women aged 50-69 y were allocated to one of four dosage group and consumed 0, 50, 100, or 200 μg menaquinone-7 daily for 4 wk, respectively, with a controlled diet in accordance with recommended daily intakes for 2010 in Japan. Study 2 was a double-blind, randomized placebo-controlled trial based on the results of Study 1; 120 subjects aged 20-69 y were allocated to the placebo or MK-7 group and consumed 0 or 100 μg menaquinone-7 daily for 12 wk, respectively. In both studies, circulating carboxylated osteocalcin and undercarboxylated osteocalcin were measured. The carboxylated osteocalcin/undercarboxylated osteocalcin ratio decreased significantly from baseline in the 0 μg menaquinone-7 group, in which subjects consumed the recommended daily intake of vitamin K with vitamin K1 and menaquinone-4 (Study 1). Menaquinone-7 increased the carboxylated osteocalcin/undercarboxylated osteocalcin ratio dose dependently, and significant effects were observed in both the 100 and 200 μg groups compared with the 0 μg group. Undercarboxylated osteocalcin concentrations decreased significantly, and the carboxylated osteocalcin/undercarboxylated osteocalcin ratio increased significantly in the 100 μg menaquinone-7 group compared with the placebo group (Study 2). Daily menaquinone-7 intake ≥100 μg was suggested to improve osteocalcin γ-carboxylation.

Six-month therapy for abdominal tuberculosis

PubMed Central

Jullien, Sophie; Jain, Siddharth; Ryan, Hannah; Ahuja, Vineet

2016-01-01

Background Tuberculosis (TB) of the gastrointestinal tract and any other organ within the abdominal cavity is abdominal TB, and most guidelines recommend the same six-month regimen used for pulmonary TB for people with this diagnosis. However, some physicians are concerned whether a six-month treatment regimen is long enough to prevent relapse of the disease, particularly in people with gastrointestinal TB, which may sometimes cause antituberculous drugs to be poorly absorbed. On the other hand, longer regimens are associated with poor adherence, which could increase relapse, contribute to drug resistance developing, and increase costs to patients and health providers. Objectives To compare six-month versus longer drug regimens to treat people that have abdominal TB. Search methods We searched the following electronic databases up to 2 September 2016: the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase (accessed via OvidSP), LILACS, INDMED, and the South Asian Database of Controlled Clinical Trials. We searched the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov for ongoing trials. We also checked article reference lists. Selection criteria We included randomized controlled trials (RCTs) that compared six-month regimens versus longer regimens that consisted of isoniazid, rifampicin, pyrazinamide, and ethambutol to treat adults and children that had abdominal TB. The primary outcomes were relapse, with a minimum of six-month follow-up after completion of antituberculous treatment (ATT), and clinical cure at the end of ATT. Data collection and analysis Two review authors independently selected trials, extracted data, and assessed the risk of bias in the included trials. For analysis of dichotomous outcomes, we used risk ratios (RR) with 95% confidence intervals (CIs). Where appropriate, we pooled data from the included

Does an L-glutamine-containing, Glucose-free, Oral Rehydration Solution Reduce Stool Output and Time to Rehydrate in Children with Acute Diarrhoea? A Double-blind Randomized Clinical Trial

PubMed Central

Gutiérrez, Claudia; Villa, Sofía; Mota, Felipe R.; Calva, Juan J.

2007-01-01

This study assessed whether an oral rehydration solution (ORS) in which glucose is replaced by L-glutamine (L-glutamine ORS) is more effective than the standard glucose-based rehydration solution recommended by the World Health Organization (WHO-ORS) in reducing the stool volume and time to rehydrate in acute diarrhoea. In a double-blind, randomized controlled trial in a Mexican hospital, 147 dehydrated children, aged 1–60 month(s), were assigned either to the WHO-ORS (74 children), or to the L-glutamine ORS (73 children) and followed until successful rehydration. There were no significant differences between the groups in stool output during the first four hours, time to successful rehydration, volume of ORS required for rehydration, urinary output, and vomiting. This was independent of rotavirus-associated infection. An L-glutamine-containing glucose-free ORS seems not to offer greater clinical benefit than the standard WHO-ORS in mildly-to-moderately-dehydrated children with acute non-cholera diarrhoea. PMID:18330060

Does Bacopa monnieri improve memory performance in older persons? Results of a randomized, placebo-controlled, double-blind trial.

PubMed

Morgan, Annette; Stevens, John

2010-07-01

The objective of this study was to investigate the effectiveness of Bacopa monnieri Linn. for improvement of memory performance in healthy older persons. This was a randomized, double-blind, placebo-controlled trial. The trial took place in Lismore, NSW, Australia between February and July 2005. Ninety-eight (98) healthy participants over 55 years of age were recruited from the general population. Participants were randomized to receive an extract of Bacopa monnieri called BacoMind(TM) (Natural Remedies Pvt. Ltd.), 300 mg/day, or an identical placebo. Following screening, neuropsychologic and subjective memory assessments were performed at baseline and at 12 weeks. Audioverbal and visual memory performance were measured by the Rey Auditory Verbal Learning Test (AVLT), the Rey-Osterrieth Complex Figure Test (CFT), and the Reitan Trail Making Test (TMT). Subjective memory performance was measured by the Memory Complaint Questionnaire (MAC-Q). One hundred and thirty-six (136) subjects volunteered; 103 met entry criteria, 98 commenced, and 81 completed the trial. Bacopa significantly improved verbal learning, memory acquisition, and delayed recall as measured by the AVLT: trial a4 (p = 0.000), trial a5 (p = 0.016); trial a6 (p = 0.000); trial a7 (delayed recall) (p = 0.001); total learning (p = 0.011); and retroactive interference (p = 0.048). CFT, MAC-Q, and TMT scores improved but group differences were not significant. Bacopa versus placebo caused gastrointestinal tract (GIT) side-effects. Bacopa significantly improved memory acquisition and retention in healthy older Australians. This concurs with previous findings and traditional use. Bacopa caused GIT side-effects of increased stool frequency, abdominal cramps, and nausea.

Efficacy and safety of pioglitazone added to alogliptin in Japanese patients with type 2 diabetes mellitus: a multicentre, randomized, double-blind, parallel-group, comparative study.

PubMed

Kaku, K; Katou, M; Igeta, M; Ohira, T; Sano, H

2015-12-01

A phase IV, multicentre, randomized, double-blind, parallel-group, comparative study was conducted in Japanese subjects with type 2 diabetes mellitus (T2DM) who had inadequate glycaemic control, despite treatment with alogliptin in addition to diet and/or exercise therapy. Subjects with glycated haemoglobin (HbA1c) concentrations of 6.9-10.5% were randomized to receive 16 weeks' double-blind treatment with pioglitazone 15 mg, 30 mg once daily or placebo added to alogliptin 25 mg once daily. The primary endpoint was the change in HbA1c from baseline at the end of treatment period (week 16). Both pioglitazone 15 and 30 mg combination therapy resulted in a significantly greater reduction in HbA1c than alogliptin monotherapy [-0.80 and -0.90% vs 0.00% (the least squares mean using analysis of covariance model); p < 0.0001, respectively]. The overall incidence rates of treatment-emergent adverse events were similar among the treatment groups. Pioglitazone/alogliptin combination therapy was effective and generally well tolerated in Japanese subjects with T2DM and is considered to be useful in clinical settings. © 2015 John Wiley & Sons Ltd.

Efficacy of kinesio taping on isokinetic quadriceps torque in knee osteoarthritis: a double blinded randomized controlled study.

PubMed

Anandkumar, Sudarshan; Sudarshan, Shobhalakshmi; Nagpal, Pratima

2014-08-01

Double blind pre-test post-test control group design. To compare the isokinetic quadriceps torque, standardized stair-climbing task (SSCT) and pain during SSCT between subjects diagnosed with knee osteoarthritis pre and post kinesio tape (KT) application with and without tension. Strength of the quadriceps and torque producing capability is frequently found to be compromised in knee osteoarthritis. The efficacy of KT in improving isokinetic quadriceps torque in knee osteoarthritis is unknown, forming the basis for this study. Forty subjects were randomly allocated to either the experimental (therapeutic KT with tension) or control group (sham KT without tension) with the allocation being concealed. Pre and post test measurements of isokinetic quadriceps torque, SSCT and pain during SSCT were carried out by a blinded assessor. A large effect size with significant improvements in the peak quadriceps torque (concentric and eccentric at angular velocities of 90° per second and 120° per second), SSCT and pain were obtained in the experimental group when compared to the control group. Application of therapeutic KT is effective in improving isokinetic quadriceps torque, SSCT and reducing pain in knee osteoarthritis.

Oral or vaginal misoprostol administration for induction of labor: a randomized, double-blind trial.

PubMed

Adair, C D; Weeks, J W; Barrilleaux, S; Edwards, M; Burlison, K; Lewis, D F

1998-11-01

To compare the efficacy and vaginal birth intervals after intravaginal or oral misoprostol for labor induction. One hundred seventy-eight women were randomized to one of two double-blind groups: 1) oral misoprostol 200 microg and one-half tablet placebo intravaginal or 2) oral placebo tablet and one-half tablet of a 100-microg misoprostol intravaginal (dose 50 microg). Doses were repeated every 6 hours until labor was established (maximum of three doses). Ninety-three subjects were assigned to oral misoprostol and 85 to intravaginal administration. Oral administration was accompanied by significantly shorter intervals to the onset of uterine contractility (133+/-78 minutes versus 168+/-93, P < .01) but a higher incidence of abnormal uterine contractile activity (tachysystole 38.7% versus 20.0%, P < .01; hyperstimulation syndrome 44.1% versus 21.2%, P < .01). No adverse maternal or neonatal outcomes were noted, nor were there differences in cesarean delivery rates or total lengths of labor. Oral administration of 200 microg misoprostol has similar efficacy to intravaginal administration of 50 microg but is associated with more frequent abnormal uterine contractility.

Treatment of snorers with a volatile oil: a randomized, double-blind placebo-controlled trial.

PubMed

Ulfberg, J; Nyström, B

2001-01-01

Snoring is a significant problem both for the patient and for the bed partner. Seventy-two male and female heavy snorers and their bed partners participated in a double-blinded, placebo-controlled study on the effects of a volatile oil administered by gargling. The patients were diagnosed as heavy snorers after they underwent overnight polysomnography showing that their apnea indexes were below 5, thus sleep apnea patients were not included in the study. The participants and their partners filled out evaluations concerning snoring intensity, mouth dryness, nasal stuffiness and the Epworth Sleepiness Scale prior to and after using the volatile oil or placebo for 14 consecutive nights. There were no statistically significant decreases in snoring as graded by the bed partner or in mouth dryness, nasal stuffiness, or the Epworth Sleepiness Scale scores graded by the patients who were randomized to use the volatile oil. The results of this study indicate that this volatile oil is not an effective treatment in patients presenting with symptoms of snoring. Copyright 2001 S. Karger AG, Basel

High Voltage Pulsed Radiofrequency for the Treatment of Refractory Neuralgia of the Infraorbital Nerve: A Prospective Double-Blinded Randomized Controlled Study.

PubMed

Luo, Fang; Wang, Tao; Shen, Ying; Meng, Lan; Lu, Jingjing; Ji, Nan

2017-05-01

A recent study showed that 50% of patients who suffered from refractory neuralgia of the infraorbital nerve obtained satisfactory efficacy after pulsed radiofrequency (PRF) treatment. A pilot study showed that increasing the output voltage of PRF significantly improved the efficacy for trigeminal neuralgia; however, whether increasing the output voltage of PRF can improve the treatment outcomes for neuralgia of the infraorbital nerve is unknown. To evaluate the efficacy and safety of high voltage PRF treatment in comparison with standard voltage PRF for neuralgia of the infraorbital nerve. Prospective, single-center, double-blinded, randomized, controlled trial. Beijing Tiantan Hospital, Capital Medical University. A total of 60 patients with refractory neuralgia of the infraorbital nerve were randomly divided into the high voltage PRF group and the standard voltage PRF group to treat their infraorbital nerves. Neither the patients, pain physicians, nor the follow-up evaluators knew the patient group assignments. The primary outcome measure was the one-year response rate. The secondary outcome measures included the time to take effect after PRF, the one-month, 3-month, and 6-month response rates, the relapse rate, and adverse reactions. The intent-to-treat analysis showed that the one-month, 3-month, 6-month, and one-year response rates were all 90% in the high voltage group, which were significantly higher than the rates in the standard voltage group (67% [P < 0.05], 67% [P < 0.05], 63% [P < 0.05], and 60% [P <0.01], respectively). Furthermore, 27% of the patients in the high-voltage group and 13% of the patients in the standard voltage group experienced minor transient (10 - 30 days) numbness in the innervation area after PRF; no other serious adverse reactions were observed in the 2 groups (P > 0.05). We did not investigate the dose-effect relationship between the output voltage and efficacy or the effect of a higher pulse dose on efficacy. This study was a

Long-Term Safety and Efficacy of Fulranumab in Patients With Moderate-to-Severe Osteoarthritis Pain: A Phase II Randomized, Double-Blind, Placebo-Controlled Extension Study.

PubMed

Sanga, Panna; Katz, Nathaniel; Polverejan, Elena; Wang, Steven; Kelly, Kathleen M; Haeussler, Juergen; Thipphawong, John

2017-04-01

To evaluate the long-term safety and efficacy of fulranumab in patients with knee or hip pain caused by moderate-to-severe chronic osteoarthritis (OA). In this phase II double-blind, placebo-controlled extension study, patients who were randomized in equal proportions to receive subcutaneous doses of either placebo or fulranumab (1 mg every 4 weeks, 3 mg every 8 weeks, 3 mg every 4 weeks, 6 mg every 8 weeks, or 10 mg every 8 weeks) in the 12-week double-blind efficacy phase and who completed this double-blind efficacy phase were eligible to continue the dosage throughout a 92-week double-blind extension phase, followed by a 24-week posttreatment follow-up period. Safety assessments included evaluation of treatment-emergent adverse events (TEAEs), pre-identified AEs of interest, and joint replacements. Efficacy assessments included changes from baseline to the end of the double-blind extension phase in scores on the patient's global assessment and the pain and physical function subscales of the Western Ontario and McMaster Universities Osteoarthritis Index. Overall, 401 of the 423 patients who completed the 12-week double-blind efficacy phase entered the extension study. Long-term sustained improvements were observed in all efficacy parameters following fulranumab treatment (1 mg every 4 weeks, 3 mg every 4 weeks, and 10 mg every 8 weeks) as compared with placebo. Similar percentages of patients in both groups experienced TEAEs (88% taking placebo and 91% taking fulranumab; all phases). Across all fulranumab groups, arthralgia (21%) and OA (18%) (e.g., exacerbation of OA pain) were the most common TEAEs. The most common serious TEAEs were the requirement for knee (10%) and hip (7%) arthroplasty, with 80% occurring during the posttreatment follow-up period. Neurologic-related TEAEs (28%; all phases) were generally mild-to-moderate. Overall, 81 joint replacements were performed in 71 patients (8 [11%] receiving placebo and 63 [89%] receiving fulranumab); 15 patients

A randomized, double-blind evaluation of D-cycloserine or alprazolam combined with virtual reality exposure therapy for posttraumatic stress disorder in Iraq and Afghanistan War veterans.

PubMed

Rothbaum, Barbara Olasov; Price, Matthew; Jovanovic, Tanja; Norrholm, Seth D; Gerardi, Maryrose; Dunlop, Boadie; Davis, Michael; Bradley, Bekh; Duncan, Erica J; Rizzo, Albert; Ressler, Kerry J

2014-06-01

The authors examined the effectiveness of virtual reality exposure augmented with D-cycloserine or alprazolam, compared with placebo, in reducing posttraumatic stress disorder (PTSD) due to military trauma. After an introductory session, five sessions of virtual reality exposure were augmented with D-cycloserine (50 mg) or alprazolam (0.25 mg) in a double-blind, placebo-controlled randomized clinical trial for 156 Iraq and Afghanistan war veterans with PTSD. PTSD symptoms significantly improved from pre- to posttreatment across all conditions and were maintained at 3, 6, and 12 months. There were no overall differences in symptoms between D-cycloserine and placebo at any time. Alprazolam and placebo differed significantly on the Clinician-Administered PTSD Scale score at posttreatment and PTSD diagnosis at 3 months posttreatment; the alprazolam group showed a higher rate of PTSD (82.8%) than the placebo group (47.8%). Between-session extinction learning was a treatment-specific enhancer of outcome for the D-cycloserine group only. At posttreatment, the D-cycloserine group had the lowest cortisol reactivity and smallest startle response during virtual reality scenes. A six-session virtual reality treatment was associated with reduction in PTSD diagnoses and symptoms in Iraq and Afghanistan veterans, although there was no control condition for the virtual reality exposure. There was no advantage of D-cycloserine for PTSD symptoms in primary analyses. In secondary analyses, alprazolam impaired recovery and D-cycloserine enhanced virtual reality outcome in patients who demonstrated within-session learning. D-cycloserine augmentation reduced cortisol and startle reactivity more than did alprazolam or placebo, findings that are consistent with those in the animal literature.

A preliminary double-blind, placebo-controlled randomized study of baclofen effects in alcoholic smokers

PubMed Central

Zywiak, William H.; Edwards, Steven M.; Tidey, Jennifer W.; Swift, Robert M.; Kenna, George A.

2014-01-01

Rationale There is presently no approved single treatment for dual alcohol and nicotine dependencies. Objective This pilot study investigated baclofen effects in alcoholic smokers. Methods This was a preliminary double-blind placebo-controlled randomized clinical study with 30 alcoholic smokers randomized to baclofen at 80 mg/day or placebo. A subgroup (n=18) participated in an alcohol cue-reactivity experiment. Results Baclofen, compared with placebo, significantly decreased the percent days of abstinence from alcohol-tobacco co-use (p=0.004). Alcohol dependence severity moderated baclofen effects, with the higher severity group having the greater baclofen response (p<0.001). Although the percent days of alcohol-tobacco co-use declined in both groups, this decline was greater after placebo than baclofen (p<0.001). Secondary analyses on alcohol or tobacco use alone suggested that the increase in percent days of co-abstinence was driven by the medication differences on heavy drinking days and on percent days smoking. In the cue-reactivity substudy, baclofen slightly decreased alcohol urge (p=0.058) and significantly reduced salivation (p=0.001), but these effects were not related to cue type. Conclusions This study provides preliminary evidence suggesting a possible role of baclofen in the treatment of alcoholic smokers. However, the mixed results and the small sample require larger confirmatory studies. PMID:24973894

Dietary nitrate supplementation in COPD: an acute, double-blind, randomized, placebo-controlled, crossover trial.

PubMed

Kerley, Conor P; Cahill, Kathleen; Bolger, Kenneth; McGowan, Aisling; Burke, Conor; Faul, John; Cormican, Liam

2015-01-30

The acute consumption of dietary nitrate has been shown to improve exercise capacity in athletes, healthy adults and subjects with peripheral vascular disease. Many COPD patients have reduced exercise capacity. We hypothesized that acute nitrate consumption might increase incremental shuttle walk test (ISWT) distance in COPD subjects. Eleven COPD subjects were randomly assigned to consume either a high nitrate or a matched, low nitrate beverage in a double-blind, randomized, placebo-controlled, crossover design. ISWT distance was measured both before and 3 h after the beverage and change was recorded. After a 7-day washout, ISWT distances were re-measured before and 3 h after the alternate beverage and changes were recorded. We observed an increase in ISWT distance after consuming the high nitrate juice (25 m) compared with a reduction after the low nitrate juice (14 m) (p < 0.01). This improvement in exercise capacity was associated with significant increases in serum nitrate (p < 0.000005) and nitrite (p < 0.01) levels and a significant lowering of resting blood pressure (<0.05). In patients with stable COPD, the acute consumption of dietary nitrate increased serum nitrate/nitrite levels and exercise capacity and was associated with a decrease in resting blood pressure. Nitrate consumption might alter exercise capacity in COPD patients. Copyright © 2014 Elsevier Inc. All rights reserved.

Double-Blind Randomized Trial of Pirfenidone in Chinese Idiopathic Pulmonary Fibrosis Patients.

PubMed

Huang, Hui; Dai, Hua Ping; Kang, Jian; Chen, Bao Yuan; Sun, Tie Ying; Xu, Zuo Jun

2015-10-01

Idiopathic pulmonary fibrosis (IPF) lacks effective treatment. Pirfenidone has been used to treat IPF patients. N-acetylcysteine (NAC) exerts antioxidant and antifibrotic effects on IPF cases.This study is a double-blind, modified placebo-controlled, randomized phase II trial of pirfenidone in Chinese IPF patients. We randomly assigned the enrolled Chinese IPF patients with mild to moderate impairment of pulmonary function to receive either oral pirfenidone (1800 mg per day) and NAC (1800 mg per day) or placebo and NAC (1800 mg per day) for 48 weeks. The primary endpoints were the changes in forced vital capacity (FVC) and walking distance and the lowest SPO2 during the 6-minute walk test (6MWT) at week 48. The key secondary endpoint was the progression-free survival time. This study is registered in ClinicalTrials.gov as number NCT01504334.Eighty-six patients were screened, and 76 cases were enrolled (pirfenidone + NAC: 38; placebo + NAC: 38). The effect of pirfenidone treatment was significant at the 24th week, but this effect did not persist to the 48th week. At the 24th week, the mean decline in both FVC and ΔSPO2 (%) during the 6MWT in the pirfenidone group was lower than that in the control group (-0.08 ± 0.20 L vs -0.22 ± 0.29 L, P = 0.02 and -3.44% ± 4.51% vs -6.29% ± 6.06%, P = 0.03, respectively). However, there was no significant difference between these 2 groups at the 48th week (-0.15 ± 0.25 L vs -0.25 ± 0.28 L, P = 0.11 and -4.25% ± 7.27% vs -5.31% ± 5.49%, P = 0.51, respectively). The pirfenidone treatment group did not achieve the maximal distance difference on the 6MWT at either the 24th or the 48th week. But pirfenidone treatment prolonged the progression-free survival time in the IPF patients (hazard ratio = 1.88, 95% confidence interval: 1.092-3.242, P = 0.02). In the pirfenidone group, the adverse event (AE) rate (52.63%) was higher than that in the control group (26.3%, P = 0.03). Rash was more common in the pirfenidone group (39

Curcuma longa extract reduces inflammatory and oxidative stress biomarkers in osteoarthritis of knee: a four-month, double-blind, randomized, placebo-controlled trial.

PubMed

Srivastava, Shobhit; Saksena, Anil K; Khattri, Sanjay; Kumar, Santosh; Dagur, Raghubendra Singh

2016-12-01

Curcuma longa L. (CL), an Indian herb, has been used to treat many disorders because of its wide spectrum of pharmacological activities. It has been shown to exhibit anti-oxidant and anti-inflammatory properties, and is being used as herbal remedy since ancient times. Osteoarthritis of knee (KOA) is a chronic painful disorder in which prolong use of non-steroidal anti-inflammatory drugs (NSAIDs) or steroids may result into many serious side effects; hence, there is a need to develop herbal drugs, having good analgesia without side effects. Therefore, we planned to evaluate the efficacy of CL in KOA. The study was designed as a randomized, double-blind, placebo-controlled trial in patients of KOA. After obtaining ethical clearance and written informed consent, a total of 160 patients of KOA were randomly enrolled into two groups to receive either CL extract or placebo along with the standard drug regimen. The patients were assessed on day 0, day 60, and day 120. On the days of their visit, the clinical prognosis was assessed by visual analog scale (VAS) and Western Ontario and McMaster Universities (WOMAC) Osteoarthritis index. On these days, the radiographs were also taken for Kellgren and Lawrence grading and blood samples were collected for assessing the changes in levels of IL-1β and biomarkers of oxidative stress, such as reactive oxygen species and malondialdehyde (MDA). Over all significant improvement was observed in the patients of CL extract group as compared to placebo group. Clinically, the VAS and WOMAC scores became better, and simultaneously, the levels of biomarkers, viz., IL-1β, ROS, and MDA, were also significantly (p < 0.05) improved. It may be concluded that on chronic administration, CL suppresses inflammation and brings clinical improvement in patients of KOA, which may be observed by decreased level of IL-1β and VAS/WOMAC scores, respectively. At the same time, CL decreases the oxidative stress also.

Randomized, double-blind trial of CO2 versus air insufflation in children undergoing colonoscopy.

PubMed

Homan, Matjaž; Mahkovic, Dora; Orel, Rok; Mamula, Petar

2016-05-01

Studies in adults have shown that postprocedural abdominal pain is reduced with the use of carbon dioxide (CO(2)) instead of air for insufflation during colonoscopy. The aim of our study was to compare postprocedural abdominal pain and girth in children undergoing colonoscopy using CO(2) or air for insufflation. This was a prospective, randomized, double-blind study that included 76 consecutive pediatric patients undergoing colonoscopy for various indications. Patients were randomly assigned to either CO(2) or air insufflation. At 2, 4, and 24 hours after the examination, the patients' pain was assessed by using the 11-point numerical rating scale. The waist circumference was measured 10 minutes and 2 and 4 hours after colonoscopy. A significantly higher proportion of patients had no pain after colonoscopy in the CO(2) group compared with the air group (82 vs 37% at 2 hours and 95% vs. 63% at 4 hours, P < .001). Mean abdominal pain scores 2 and 4 hours after the procedure were statistically significantly lower in the CO(2) group compared with the control air group (0.5 vs 2.6 at 2 hours and 0.1 vs 1.2 at 4 hours, P < .001). There was no difference in waist circumference between the 2 groups at all time intervals. The results of this randomized trial show clear benefits of CO(2) insufflation for colonoscopy in reducing postprocedural discomfort. ( NCT02407639.). Copyright © 2016 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

A randomized, double-blind, placebo-controlled study of the effects of pomegranate extract on rising PSA levels in men following primary therapy for prostate cancer.

PubMed

Pantuck, A J; Pettaway, C A; Dreicer, R; Corman, J; Katz, A; Ho, A; Aronson, W; Clark, W; Simmons, G; Heber, D

2015-09-01

The primary objective of this study was to compare the effects of pomegranate juice on PSA doubling times (PSADT) in subjects with rising PSA levels after primary therapy for prostate cancer. Double-blind, placebo-controlled multi-institutional study, evaluated the effects of pomegranate liquid extract on serum PSA levels. The primary end point of this study was change in serum PSADT. Additional secondary and exploratory objectives were to evaluate the safety of pomegranate juice and to determine the interaction of manganese superoxide dismutase (MnSOD) AA genotype and pomegranate treatment on PSADT. One-hundred eighty-three eligible subjects were randomly assigned to the active and placebo groups with a ratio of 2:1 (extract N=102; placebo N=64; juice N=17). The majority of adverse events were of moderate or mild grade. Median PSADT increased from 11.1 months at baseline to 15.6 months in the placebo group (P<0.001) compared with an increase from 12.9 months at baseline to 14.5 months in the extract group (P=0.13) and an increase from 12.7 at baseline to 20.3 in the juice group (P=0.004). However, none of these changes were statistically significant between the three groups (P>0.05). Placebo AA patients experienced a 1.8 month change in median PSADT from 10.9 months at baseline to 12.7 months (P=0.22), while extract patients experienced a 12 month change in median PSADT from 13.6 at baseline to 25.6 months (P=0.03). Compared with placebo, pomegranate extract did not significantly prolong PSADT in prostate cancer patients with rising PSA after primary therapy. A significant prolongation in PSADT was observed in both the treatment and placebo arms. Men with the MnSOD AA genotype may represent a group that is more sensitive to the antiproliferative effects of pomegranate on PSADT; however, this finding requires prospective hypothesis testing and validation.

Transcutaneous electrical nerve stimulation for postoperative pain relief after arthroscopic rotator cuff repair: a prospective double-blinded randomized trial.

PubMed

Mahure, Siddharth A; Rokito, Andrew S; Kwon, Young W

2017-09-01

Arthroscopic rotator cuff repair (ARCR) can be associated with significant postoperative pain. Concern for opioid abuse has led surgeons to identify alternative, efficacious methods of postoperative analgesia. To determine whether transcutaneous electrical nerve stimulation (TENS) can have a similarly beneficial effect after shoulder procedures, we conducted a prospective double-blinded randomized trial in patients undergoing outpatient ARCR. All patients undergoing ARCR of a full-thickness rotator cuff tear by the senior authors were identified. Patients with a history of recent narcotic use or prior narcotic abuse and those under management of a pain control specialist were excluded. Patients were randomized into 2 groups, active or placebo TENS, and used the device for 4 sessions/day for 45 minutes/session for the first postoperative week. All patients received Percocet 5/325 mg (oxycodone/acetaminophen) for use as rescue pain pills. One-week narcotic consumption and visual analog scale pain scores were compared between groups. The final analysis included 37 patients (21 active,16 placebo). Baseline and procedural differences were not different between groups. At 1 week postoperatively, patients in the active group had significantly lower pain scores (3.6 ± 2.1 vs. 5.8 ± 1.2; P= .008). Postoperative Percocet consumption during the initial 48 hours (12.8 ± 4.7 vs. 17.2 ± 6.3; P = .020) and during the first week (25.2 ± 9.9 vs. 33.8 ± 14.3; P = .037) was also significantly lower in the active group. Results from this prospective double-blinded randomized trial demonstrate that compared with placebo TENS, active TENS can result in significantly less pain and reduced opioid use in the immediate postoperative period after ARCR, suggesting that TENS may be potentially useful in a multimodal approach to managing postoperative pain. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier

A novel submucosal injection solution for endoscopic resection of large colorectal lesions: a randomized, double-blind trial.

PubMed

Repici, Alessandro; Wallace, Michael; Sharma, Prateek; Bhandari, Pradeep; Lollo, Gianluca; Maselli, Roberta; Hassan, Cesare; Rex, Douglas K

2018-05-08

SIC-8000 (Eleview) is a new FDA-approved solution for submucosal injection developed to provide long-lasting cushion to facilitate endoscopic resection maneuvers. Our aim was to compare the efficacy and safety of SIC-8000 with those of saline solution, when performing endoscopic mucosal resection (EMR) of large colorectal lesions. In a randomized double-blind trial, patients undergoing EMR for ≥20 mm colorectal non-pedunculated lesions were randomized in a 1:1 ratio between SIC-8000 and saline solution as control solution in 5 tertiary centers. Endoscopists and patients were blinded to the type of submucosal solution used. Total volume to complete EMR and per lesion size and time of resection were primary end-points, whereas the Sydney Resection Quotient (SRQ), as well as other EMR outcomes, and the rate of adverse events were secondary. A 30-day telephone follow up was performed. An alpha level <0.05 was considered as statistically significant (NCT 02654418). Of the 327 patients screened, 226 (mean age: 66±10; males: 56%) were enrolled in the study and randomized between the 2 submucosal agents. Of these, 211 patients (mean size of the lesions 33±13 mm; I-s: 36%; proximal colon: 74%) entered in the final analysis (SIC-8000: 102; saline solution: 109). EMR was complete in all cases. The total volume needed for EMR was significantly less in the SIC-8000 arm compared with saline solution (16.1±9.8 mL vs 31.6±32.0 mL; p<0.001). This corresponded to an average volume per lesion size of 0.5±0.3 mL/mm and 0.9±0.6 mL/mm with SIC-8000 and saline solution, respectively, (p<0.001). The mean time to completely resect the lesion tended to be lower with SIC-8000 as compared with saline solution (19.1±16.8 minutes vs 29.7±68.9 minutes; p=0.1). The SRQ was significantly higher with SIC-8000 as compared with saline solution (10.3±8.1 vs 8.0±5.7; p=0.04) with a trend for a lower number of resected pieces (5.7±6.0 vs 6.5±5.04; p=0.052) and a higher rate of en bloc

SA19. N-Acetyl-Cysteine in a Double-Blind Randomized Placebo-Controlled Trial: Toward Biomarker-Guided Treatment in Early Psychosis

PubMed Central

Do, Kim; Seidman, Larry J.; Fournier, Margot; Xin, Lijing; Cleusix, Martine; Baumann, Philipp S.; Ferrari, Carina; Cousins, Ann; Alameda, Luis; Gholam-Rezaee, Mehdi; Golay, Philippe; Jenni, Raoul; Woo, T-U Wilson; Keshavan, Matcheri S.; Eap, Chin B.; Wojcik, Joanne; Cuenod, Michel; Buclin, Thierry; Gruetter, Rolf; Conus, Philippe

2017-01-01

Abstract Background: Biomarker-guided treatments are needed in psychiatry and previous data suggest redox dysregulation / oxidative stress may be a target in schizophrenia (1,2). A previous add-on trial with the antioxidant N-Acetyl-Cysteine (NAC) led to negative symptoms reductions in chronic patients (3). We aim to study NAC impact on symptoms and neurocognition in early psychosis (EP) and to explore whether glutathione (GSH)/redox markers could represent valid biomarkers to guide treatment. Methods: In a double-blind, randomized, placebo-controlled trial in 63 EP patients, we assessed the effect of NAC supplementation (2700 mg/day, 6 months) on PANSS, neurocognition (MATRICS Consensus Cognitive Battery [MCCB]), and redox markers (brain GSH [GSH-mPFC], blood cells GSH [GSH-BC] levels, and GSH peroxidase activity [GPx-BC]). Results: No changes in negative, positive symptoms, or functional outcome were observed with NAC, but significant improvements were found in favor of NAC on the MCCB Processing Speed factor and two of its components: Trail Making and Verbal Fluency. NAC leads to increases in GSH-mPFC by 23% (P = .005) and GSH-BC by 19% (P = .05). In patients with high-baseline GPx-BC (>22.3U/gHb), subgroup explorations revealed an improvement with NAC of positive symptoms when compared to patients with low-baseline GPx (P = .02), with an improvement of positive symptoms in parallel with that of the redox status. Conclusion: In conclusion, NAC supplementation in a limited sample of EP patients did not improve negative symptoms, which were at modest levels at baseline. However, NAC leads to neurocognition improvement as well as to brain GSH levels increases, pointing to good target engagement. Blood GPx activity, a redox peripheral index associated with brain GSH levels, could help to identify a subgroup of patients who improve their positive symptoms with NAC. Future trials with antioxidant in EP should consider biomarker-guided treatment. References 1

A double-blind, randomized clinical trial of dietary supplementation on cognitive and immune functioning in healthy older adults.

PubMed

Lewis, John E; Melillo, Angelica B; Tiozzo, Eduard; Chen, Lawrence; Leonard, Susanna; Howell, Mark; Diaz, Janelle; Gonzalez, Kathy; Woolger, Judi M; Konefal, Janet; Paterson, Elaine; Barnes, David

2014-02-04

Declining cognitive function is relatively common and increasingly prevalent. Studies have shown that different nutrients (e.g., Ginkgo biloba and vitamin E) appear to be effective at improving memory and concentration, while less is known about their effect on immunity. This study investigated the effect of Ginkgo Synergy(®) plus Choline (n = 33) and OPC Synergy(®) plus Catalyn(®) (n = 31) versus placebo (n = 33) in a 6-month, randomized, double-blind trial on cognitive and immune functioning among English-speaking, non-smoking, healthy older adults. The Stroop Color and Word Test, Trail Making Test A and B, Controlled Oral Word Association, Hopkins Verbal Learning, Mini-Mental State Exam, and Digit Symbol were administered at baseline and 3 and 6 months follow-up to assess cognitive functioning. Cytokines and growth factors were measured at baseline and 6 months to assess inflammation and immune functioning. Data were analyzed with linear mixed modeling. No serious adverse events were noted in this study. According to time on the Trail Making Test-B, the Ginkgo Synergy(®) plus Choline arm showed improvement from baseline to 3 months follow-up (mean difference = 24.2; SE = 6.4; 95% CI: 8.6, 39.7; p = 0.01). On the Controlled Oral Word Association Trial-S, the scores significantly increased for the Ginkgo Synergy(®) plus Choline arm from baseline to 6 months follow-up (mean difference = 2.1; SE = 0.8; 95% CI: 0.2, 3.9; p < 0.05) and for the OPC Synergy(®) plus Catalyn(®) arm from baseline to 3 months follow-up (mean difference = 2.1; SE = 0.8; 95% CI: 0.2, 4.0; p < 0.05). Epidermal growth factor significantly decreased from baseline to 6 months follow-up for the Ginkgo Synergy(®) plus Choline arm (mean difference = 120.7; SE = 28.4; 95% CI: 62.6, 178.8; p < 0.001). Our study showed isolated and modest effects of a Ginkgo biloba plus choline-based formula on cognitive and immune functioning among healthy older adults with no history of significant cognitive

Efficacy of a Carrageenan gel Against Transmission of Cervical HPV (CATCH): Interim analysis of a randomized, double-blind, placebo-controlled, phase 2B trial.

PubMed

Magnan, Sindy; Tota, Joseph E; El-Zein, Mariam; Burchell, Ann N; Schiller, John T; Ferenczy, Alex; Tellier, Pierre-Paul; Coutlée, François; Franco, Eduardo L

2018-04-20

We evaluated the efficacy of a carrageenan-based lubricant gel in reducing the risk of genital human papillomavirus (HPV) infections in women. We conducted a planned interim analysis of a randomized, double-blind, placebo-controlled, phase 2B trial. Women aged 18 years and older were randomly assigned (1:1) to a carrageenan-based or a placebo gel to be self-applied every other day for the first month and prior to and following each intercourse during follow-up. Assessments were done at 0·5, 1, 3, 6, 9, and 12 months. The primary outcome was incidence of a new infection by an HPV type that was not present at baseline. Analyses were performed by intention-to-treat. Between January 2013 and June 2017, 280 participants were randomly assigned to the carrageenan (n=141) or the placebo (n=139) arm. All participants were included in safety analyses, but 3 (1%) were excluded from efficacy analyses (HPV results unavailable: carrageenan=2, placebo=1). The median follow-up time was 9·2 months (inter-quartile range: 1·9-13·2). 59 (42%) of 139 participants in the carrageenan arm and 78 (57%) of 138 participants in the placebo arm got infected by at least one new HPV type (hazard ratio=0·64, 95% confidence interval=0·45-0·89, p=0·009). 62 (44%) of 141 participants in the carrageenan arm versus 43 (31%) of 139 participants in the placebo arm reported an adverse event (p=0.02); none of which were deemed related to the gels. Our trial's interim analysis suggests that using a carrageenan-based lubricant gel can reduce the risk of genital HPV infections in women. Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. All rights reserved.

Clinical Efficacy of Intravenous Lidocaine for Thyroidectomy: A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial.

PubMed

Choi, Geun Joo; Kang, Hyun; Ahn, Eun Jin; Oh, Jong In; Baek, Chong Wha; Jung, Yong Hun; Kim, Jin Yun

2016-12-01

Systemic lidocaine has analgesic and anti-inflammatory effects. The purpose of this prospective, randomized, double-blind study was to evaluate the effects of intravenous lidocaine on pain following thyroidectomy. Fifty-eight adult patients scheduled for total thyroidectomy were randomly allocated to receive a 1.5 mg/kg lidocaine bolus followed by a 2 mg/kg/h infusion during surgery, or the same volume of normal saline (control). After thyroidectomy, we evaluated postoperative pain, nausea, fentanyl consumption, frequency of pushing the button (FPB) for patient-controlled analgesia (PCA), High-sensitivity C-reactive protein (hs-CRP) in serum, and patient satisfaction scores regarding the recovery process. Postoperative pain and nausea scores were significantly lower in the lidocaine group for the first 4 h following thyroidectomy, compared to the control group. Fentanyl consumption and FPB for the PCA were also significantly reduced in the lidocaine group for 4 h following thyroidectomy, and hs-CRP was significantly less in the lidocaine group at postoperative days 1 and 3. Furthermore, satisfaction scores were significantly higher in the lidocaine group compared to the control group. Intravenous lidocaine effectively reduced postoperative pain and nausea following thyroidectomy as well as improved the quality of recovery. Clinicaltrials.gov NCT01608360.

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.

Intracorporeal pneumatic shock application for the treatment of chronic plantar fasciitis: a randomized, double blind prospective clinical trial.

PubMed

Dogramaci, Yunus; Kalaci, Aydiner; Emir, Anil; Yanat, Ahmet Nedim; Gökçe, Ahmet

2010-04-01

Plantar fasciitis (PF) is a common clinical condition that usually resolves with non-operative treatments. Extracorporeal shock wave therapy (ESWT) has been used in the treatment of chronic PF not responding to other conservative measures; however, ESWT devices are expensive and available for daily practice in only few centers (In developing countries). A pneumatic lithotripter is a cheap and readily available device which uses pneumatic shock application for the intracorporeal lithotripsy. The aim of this study was to investigate the clinical efficacy of intracorporeal pneumatic shock therapy (IPST) application for the treatment of chronic PF using a cheap and readily available pneumatic lithotripter. A randomized, double-blind, placebo-controlled study was conducted. A total of 50 patients with clinically and radiologically confirmed PF were randomly allocated to either an active- (treatment) (n = 25) or inactive (placebo) (n = 25) group. Under local anesthesia and posterior tibial nerve block, a rigid probe was directly introduced into the calcaneal spur under fluoroscopic control; a standard protocol of 1,000 shock was applied during a single session into the calcaneal spur. The main outcome measure was the patients' subjective assessment of pain by means of a Visual Analog Scale (VAS) and the Roles and Maudsley Score before the treatment and 6 months later. At the 6 months, the rate of successful outcomes (excellent + good results) in the treatment group (92%) were significantly higher comparing to the control group (24%) (P < 0.001). Heel pain measured 6 months after using the VAS were 2.04 +/- 1.67 in treatment group and 7.16 +/- 1.57 in control group as compared to 8.92 +/- 1.22 and 9.12 +/- 1.23 before the commencement of the treatment. No complications attributable to the procedure such as rupture of the planter fascia, hematoma, or infection were observed during the study. This pilot study showed that IPST is an effective and safe method of treatment of

Urtica dioica for treatment of benign prostatic hyperplasia: a prospective, randomized, double-blind, placebo-controlled, crossover study.

PubMed

Safarinejad, Mohammad Reza

2005-01-01

To determine the effects of therapy with Urtica dioica for symptomatic relief of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). A 6-month, double-blind, placebo-controlled, randomized, partial crossover, comparative trial of Urtica dioica with placebo in 620 patients was conducted. Patients were evaluated using the International Prostate Symptom Score (IPSS), the maximum urinary flow rate (Qmax), postvoid residual urine volume (PVR), Serum Prostatic- Specific Antigen (PSA), testosterone levels, and prostate size. At the end of 6-month trial, unblinding revealed that patients who initially received the placebo were switched to Urtica dioica. Both groups continued the medication up to 18 months. 558 patients (90%) completed the study (287/305, 91% in the Urtica dioica group, and 271/315, 86% in the placebo group). By intention- to-treat analysis, at the end of 6-month trial, 232 (81%) of 287 patients in the Urtica dioica group reported improved LUTS compared with 43 (16%) of 271 patients in the placebo group (P < 0.001). Both IPSS and Qmax showed greater improvement with drug than with placebo. The IPSS went from 19.8 down to 11.8 with Urtica dioica and from 19.2 to 17.7 with placebo (P = 0.002). Peak flow rates improved by 3.4 mL/s for placebo recipients and by 8.2 mL/s for treated patients (P < 0.05). In Urtica dioica group, PVR decreased from an initial value of 73 to 36 mL (P < 0.05). No appreciable change was seen in the placebo group. Serum PSA and testosterone levels were unchanged in both groups. A modest decrease in prostate size as measured by transrectal ultrasonography (TRUS) was seen in Urtica dioica group (from 40.1 cc initially to 36.3 cc; P < 0.001). There was no change in the prostate volume at the end of study with placebo. At 18-month follow-up, only patients who continued therapy, had a favorable treatment variables value. No side effects were identified in either group. In the present study, Urtica dioica

Serenoa repens, lycopene and selenium versus tamsulosin for the treatment of LUTS/BPH. An Italian multicenter double-blinded randomized study between single or combination therapy (PROCOMB trial).

PubMed

Morgia, Giuseppe; Russo, Giorgio I; Voce, Salvatore; Palmieri, Fabiano; Gentile, Marcello; Giannantoni, Antonella; Blefari, Franco; Carini, Marco; Minervini, Andrea; Ginepri, Andrea; Salvia, Giuseppe; Vespasiani, Giuseppe; Santelli, Giorgio; Cimino, Sebastiano; Allegro, Rosalinda; Collura, Zaira; Fragalà, Eugenia; Arnone, Salvatore; Pareo, Rosaria M

2014-11-01

Phytotherapy has been used to treat patients with lower urinary tract symptoms (LUTS). We evaluated the efficacy and tolerability of combination therapy between Serenoa Repens (SeR), Lycopene (Ly), and Selenium (Se) + tamsulosin versus single therapies. PROCOMB trial (ISRCTN78639965) was a randomized double-blinded, double-dummy multicenter study of 225 patients between 55 and 80 years old, PSA ≤ 4 ng/ml, IPSS ≥12, prostate volume ≤60 cc, Qmax ≤15 ml/sec, postvoid residual urine (PVR) <150 ml. Participants were randomized group A (SeR-Se-Ly), group B (tamsulosin 0.4 mg), group C (SeR-Se-Ly + tamsulosin 0.4 mg). The primary endpoints of the study were the reduction of IPSS, PVR, and increase of Qmax in group C versus monotherapy groups. The decrease for combination therapy was significantly greater versus group A (P < 0.05) and group B (P < 0.01) for IPSS and versus group A (P < 0.01) for PVR from baseline to 6 months. A greater decrease in IPSS was observed for Group C versus group A (P < 0.01) and increase in Qmax versus group B (P < 0.01), from 6 months to 12 months. At one year, the changes of IPSS and Qmax were greater for Group C versus monotherapies (each comparison <0.05). The proportions of men with a decrease of at least three points (each comparison P < 0.05) and decrease of 25% for IPSS (each comparison P < 0.01) were greater for Group C. SeR-Se-Ly + tamsulosin therapy is more effective than single therapies in improving IPSS and increasing Qmax in patients with LUTS. © 2014 Wiley Periodicals, Inc.

Atomoxetine Increased Effect over Time in Adults with Attention-Deficit/Hyperactivity Disorder Treated for up to 6 Months: Pooled Analysis of Two Double-Blind, Placebo-Controlled, Randomized Trials.

PubMed

Wietecha, Linda A; Clemow, David B; Buchanan, Andrew S; Young, Joel L; Sarkis, Elias H; Findling, Robert L

2016-07-01

Changes in the magnitude of efficacy throughout 26 weeks of atomoxetine treatment, along with impact of dosing, were evaluated in adults with ADHD from two randomized, double-blind, placebo-controlled studies. Pooled placebo (n = 485) and atomoxetine (n = 518) patients, dosed 25, 40, 60, 80 (target dose), or 100 mg daily, were assessed. Change from baseline in Conners' Adult ADHD Rating Scale-Investigator Rated Scale: Screening Version (CAARS) total ADHD symptoms score and Adult ADHD Investigator Symptom Rating Scale (AISRS) total score were analyzed using mixed-model repeated measures, with least squares mean change, effect size, and response rate calculated at 1, 2, 4, 8, 12, 16, 22, and 26 weeks. Decreases on CAARS for atomoxetine- versus placebo-treated patients were consistently statistically significantly greater at every time point beginning at one week (P ≤ 0.006, 0.28 effect size). By 4 weeks, comparison was -13.19 compared with -8.84 (P < 0.0001, 0.45 effect size). By 26 weeks, mean change was -15.42 versus -9.71 (0.52 effect size); increase in effect size over time was most pronounced in the 80 mg group (0.82 effect size). AISRS demonstrated similar results. Atomoxetine response rate (CAARS 50% decrease) continued to increase throughout 26 weeks. Atomoxetine treatment in adults with ADHD was associated with small effect sizes after 4 weeks and moderate effect sizes by 6 months of treatment. The data support increased effect size and response rate over time during longer-term treatment at target dose. © 2016 Eli Lilly and Company. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.

Does Prolonged Enteral Feeding With Supplemental Omega-3 Fatty Acids Impact on Recovery Post-esophagectomy: Results of a Randomized Double-Blind Trial.

PubMed

Healy, Laura A; Ryan, Aoife; Doyle, Suzanne L; Ní Bhuachalla, Éadaoin Bríd; Cushen, Samantha; Segurado, Ricardo; Murphy, Thomas; Ravi, Narayanasamy; Donohoe, Claire L; Reynolds, John V

2017-11-01

This randomized controlled trial (RCT) hypothesized that prolonged enteral nutrition (EN) with supplemental eicosapentanoic acid (EPA), an omega-3 fatty acid with immune and anabolic properties, may impact on clinical and nutritional outcomes. Esophagectomy is associated with significant weight loss and catabolism, and negatively impacts quality of life (QL). Strategies to counter sustained catabolism have therapeutic rationale. This multicenter, double-blind, placebo-controlled RCT was powered on a 5% difference in lean body mass (LBM) at 1 month. Patients were randomly assigned to receive either EN-EPA (2.2 g EPA/day) (n = 97) or isocaloric isonitrogenous standard EN (EN-S) (n = 94), preoperatively (5 days orally), and postoperatively via a jejunostomy until 1 month postdischarge. Assessments perioperatively, and at 1, 3, and 6 months included weight, body mass index (BMI), body composition, muscle strength, cytokines, complications, and QL. The median (range) nutrition support was for 51 (36 to 78) days, and overall compliance was 96%. For the entire cohort, a significant (P < 0.005) decrease in weight (-7.4 ± 6.6 kg), BMI (-2.6 ± 2.2 kg/m), LBM (-2.5 ± 8.7 kg), and fat mass (-3.4 ± 5.8 kg) was evident from preoperatively to 6 months. The mean (±SD) loss of LBM (kg) at 1 month was -3.7 ± 8.7 in the EN-S group, compared with -5.6 ± 12.1 in the EN-EPA group (P = 0.355). Per-protocol analysis revealed no difference between the EN-EPA and EN-S in any clinical, nutritional, functional, QL or immune parameter at any time point. The thesis that EPA impacts on anabolism, immune function, and clinical outcomes post-esophagectomy was not supported. Compliance with home EN was excellent, but weight, muscle, and fat loss was significant in 30% of patients, highlighting the complexity of postoperative weight loss.

Chocolate flavanols and skin photoprotection: a parallel, double-blind, randomized clinical trial.

PubMed

Mogollon, Jaime Andres; Boivin, Catherine; Lemieux, Simone; Blanchet, Claudine; Claveau, Joël; Dodin, Sylvie

2014-06-27

Solar ultraviolet (UV) radiation has deleterious effects on the skin, including sunburn, photoaging and cancer. Chocolate flavanols are naturally-occurring antioxidant and anti-inflammatory molecules that could play a role in preventing cutaneous UV damage. We investigated the influence of 12-week high-flavanol chocolate (HFC) consumption on skin sensitivity to UV radiation, measured by minimal erythema dose (MED). We also evaluated skin elasticity and hydration. In this 2-group, parallel, double-blind, randomized controlled trial, 74 women aged 20-65 years and Fitzpatrick skin phototypes I or II were recruited from the general community in Quebec City, for randomization to either HFC (n = 33) or low-flavanol chocolate (LFC) (n = 41). A blocked randomisation (4), considering date of entry, skin type and age as factors, generated a sequentially-numbered allocation list. Study participants and research assistants were blinded. Totally, 30 g of chocolate were consumed daily for 12 weeks, followed by a 3-week washout period. MED was assessed at baseline and at 6, 9, 12 and 15 weeks. Main outcome was changes in MED at week 12. 33 participants in the HFC group and 41 in the LFC group were analyzed with 15 weeks of follow-up. Both groups showed similarly-increased MED at 12 weeks (HFC: 0.0252 ± 0.1099 J/cm2 [mean ± standard deviation (SD)]; LFC: 0.0151 ± 0.1118; mean difference (MD): 0.0100 J/cm2; 95% confidence interval (CI): -0.0417 to 0.0618). However, after 3-week washout, the HFC group presented decreased MED (-0.0248 ± 0.1145) whereas no effect was seen in the LFC group (0.0168 ± 0.1698) (MD: -0.0417; 95% CI: -0.1106 to 0.0272). Net temple elasticity increased slightly but significantly by 0.09 ± 0.12 mm in the HFC group at 12 weeks compared to 0.02 ± 0.12 mm in the LFC group (MD: 0.06; 95% CI: 0.01 to 0.12 ). No significant adverse events were reported. Our study failed to demonstrate a statistically

Chocolate flavanols and skin photoprotection: a parallel, double-blind, randomized clinical trial

PubMed Central

2014-01-01

Background Solar ultraviolet (UV) radiation has deleterious effects on the skin, including sunburn, photoaging and cancer. Chocolate flavanols are naturally-occurring antioxidant and anti-inflammatory molecules that could play a role in preventing cutaneous UV damage. We investigated the influence of 12-week high-flavanol chocolate (HFC) consumption on skin sensitivity to UV radiation, measured by minimal erythema dose (MED). We also evaluated skin elasticity and hydration. Methods In this 2-group, parallel, double-blind, randomized controlled trial, 74 women aged 20–65 years and Fitzpatrick skin phototypes I or II were recruited from the general community in Quebec City, for randomization to either HFC (n = 33) or low-flavanol chocolate (LFC) (n = 41). A blocked randomisation (4), considering date of entry, skin type and age as factors, generated a sequentially-numbered allocation list. Study participants and research assistants were blinded. Totally, 30 g of chocolate were consumed daily for 12 weeks, followed by a 3-week washout period. MED was assessed at baseline and at 6, 9, 12 and 15 weeks. Main outcome was changes in MED at week 12. Results 33 participants in the HFC group and 41 in the LFC group were analyzed with 15 weeks of follow-up. Both groups showed similarly-increased MED at 12 weeks (HFC: 0.0252 ± 0.1099 J/cm2 [mean ± standard deviation (SD)]; LFC: 0.0151 ± 0.1118; mean difference (MD): 0.0100 J/cm2; 95% confidence interval (CI): -0.0417 to 0.0618). However, after 3-week washout, the HFC group presented decreased MED (-0.0248 ± 0.1145) whereas no effect was seen in the LFC group (0.0168 ± 0.1698) (MD: -0.0417; 95% CI: -0.1106 to 0.0272). Net temple elasticity increased slightly but significantly by 0.09 ± 0.12 mm in the HFC group at 12 weeks compared to 0.02 ± 0.12 mm in the LFC group (MD: 0.06; 95% CI: 0.01 to 0.12 ). No significant adverse events were reported. Conclusion Our study failed to

Blueberries Improve Endothelial Function, but Not Blood Pressure, in Adults with Metabolic Syndrome: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

PubMed Central

Stull, April J.; Cash, Katherine C.; Champagne, Catherine M.; Gupta, Alok K.; Boston, Raymond; Beyl, Robbie A.; Johnson, William D.; Cefalu, William T.

2015-01-01

Blueberry consumption has been shown to have various health benefits in humans. However, little is known about the effect of blueberry consumption on blood pressure, endothelial function and insulin sensitivity in humans. The present study investigated the role of blueberry consumption on modifying blood pressure in subjects with metabolic syndrome. In addition, endothelial function and insulin sensitivity (secondary measurements) were also assessed. A double-blind and placebo-controlled study was conducted in 44 adults (blueberry, n = 23; and placebo, n = 21). They were randomized to receive a blueberry or placebo smoothie twice daily for six weeks. Twenty-four-hour ambulatory blood pressure, endothelial function and insulin sensitivity were assessed pre- and post-intervention. The blood pressure and insulin sensitivity did not differ between the blueberry and placebo groups. However, the mean change in resting endothelial function, expressed as reactive hyperemia index (RHI), was improved significantly more in the group consuming the blueberries versus the placebo group (p = 0.024). Even after adjusting for confounding factors, i.e., the percent body fat and gender, the blueberry group still had a greater improvement in endothelial function when compared to their counterpart (RHI; 0.32 ± 0.13 versus −0.33 ± 0.14; p = 0.0023). In conclusion, daily dietary consumption of blueberries did not improve blood pressure, but improved (i.e., increased) endothelial function over six weeks in subjects with metabolic syndrome. PMID:26024297

Effect of Dill (Anethum graveolens) on the severity of primary dysmenorrhea in compared with mefenamic acid: A randomized, double-blind trial

PubMed Central

Heidarifar, Reza; Mehran, Nahid; Heidari, Akram; Tehran, Hoda Ahmari; Koohbor, Mohammad; Mansourabad, Mostafa Kazemian

2014-01-01

Background: Dysmenorrhea has negative effects on women's life. Due to side-effects of chemical drugs, there is growing trend toward herbal medicine. The aim of this study was to assess the effect of Dill compared to mefenamic acid on primary dysmenorrhea. Materials and Methods: This double-blind, randomized, clinical trial study was conducted on 75 single female students between 18 and 28 years old educating in Nursing and Midwifery School and Paramedical Faculty of Qom University of Medical Sciences of Iran in 2011. They were allocated randomly into one of the three groups: In Dill group, they took 1000 mg of Dill powder q12h for 5 days from 2 days before the beginning of menstruation for two cycles. Other groups received 250 mg mefenamic acid or 500 mg starch capsule as placebo, respectively. Dysmenorrhea severity was determined by a verbal multidimensional scoring system and a visual analog scale (VAS). Students with mild dysmenorrhea were excluded. Data were analyzed by SPSS using the descriptive statistic, paired-samples t-test, Wilcoxon signed-rank test, Mann-Whitney test, and Kruskal-Wallis test. Results: There were no significant differences between three groups for demographic or descriptive variables. Comprising the VAS showed that the participants of Dill and mefenamic acid groups had lower significant pain in the 1st and the 2nd months after treatment, whereas in the placebo group this was only significant in the 2nd month (P < 0.05). Conclusion: Dill was as effective as mefenamic acid in reducing the pain severity in primary dysmenorrhea. Further studies regarding side-effects of Dill and its interactivity are recommended. PMID:25097605

A double-blind vehicle-controlled study of a preparation containing undecylenoyl phenylalanine 2% in the treatment of melasma in females.

PubMed

Katoulis, Alexander; Alevizou, Antigoni; Soura, Efthymia; Mantas, Nikolaos; Bozi, Evangelia; Gregoriou, Stamatis; Makris, Michalis; Rigopoulos, Dimitris

2014-06-01

Undecylenoyl phenylalanine is a novel skin-lightening agent, probably acting as α-melanocyte-stimulating hormone (α-MSH) and beta-adrenergic receptor (β-ADR) antagonist. The objective of this double-blind randomized comparative study was to evaluate the efficacy and safety of a preparation containing undecylenoyl phenylalanine 2% in the topical treatment of melasma in females. Forty female patients with melasma were randomly assigned to apply either the active preparation or the vehicle alone, twice daily for 12 weeks. Patients were evaluated monthly for efficacy and safety. In all, 37 patients completed the study. Of the 20 patients on active treatment, no one responded completely, but 17 (85%) had partial response. Of them, 11 had moderate improvement and six had marked improvement. Lightening of the lesions was evident from the first follow-up visit at 4 weeks. A statistically significant difference (P < 0.001) in efficacy between the active preparation and the vehicle was documented. Using patient assessment ratings, 80% were extremely satisfied or satisfied with the result. The reported side effects were minor and included erythema and itching or burning at the site of application. Undecylenoyl phenylalanine 2% achieved a significant lightening of melasma lesions with minimal side effects. © 2014 Wiley Periodicals, Inc.

A randomized, double-blind, placebo-controlled trial of selective digestive decontamination in a medical-surgical intensive care unit.

PubMed

Wiener, J; Itokazu, G; Nathan, C; Kabins, S A; Weinstein, R A

1995-04-01

A randomized, double-blind, placebo-controlled trial of selective decontamination of the oropharynx and gastrointestinal tract was conducted on 61 intubated patients in a medical-surgical intensive care unit (ICU) to determine the impact on nosocomial pneumonia, other infections, and emergence of colonization or infection with antibiotic-resistant bacteria. Over 8 months, 30 patients received an oral paste and solution containing polymyxin, gentamicin, and nystatin; 31 patients received a placebo paste and solution. At study entry, patients in both groups were seriously ill (mean acute physiologic score, 27.2), frequently had pulmonary infiltrates (73.8%), and were likely to be receiving systemic antibiotics (86.9%). There were no differences between study patients and control patients in these characteristics or in frequency of any nosocomial infection (50% vs. 55%), nosocomial pneumonia (27% vs. 26%), febrile days (2.3 vs. 2.0), duration of antibiotic therapy (14.0 vs. 13.4), or mortality rates (37% vs. 48%). There was no difference in infections caused by antibiotic-resistant gram-negative bacilli, although a trend towards more frequent infection with gentamicin-resistant enterococci was found for study patients. Selective decontamination did not appear to be effective in our very ill medical-surgical ICU patients, although the number of patients in our trial was sufficient to detect only a 50% or greater reduction in pneumonia rates.

Effect of testosterone supplementation on sexual functioning in aging men: a 6-month randomized controlled trial.

PubMed

Emmelot-Vonk, M H; Verhaar, H J J; Nakhai-Pour, H R; Grobbee, D E; van der Schouw, Y T

2009-01-01

Serum testosterone levels decline significantly with aging and this has been associated with reduced sexual function. We have conducted a double-blind, randomized, placebo-controlled trial to investigate the effect of testosterone supplementation on sexual function in 237 elderly men with a testosterone level <13.7 nmol l(-1). Participants were randomly assigned to receive oral testosterone undecanoate or a placebo for 6 months. A total of 207 men completed the study. After treatment, there were no differences in scores on sexual function between the groups. Subanalysis showed that although a baseline testosterone level in the lowest tertile was associated with significantly lower scores for sexual fantasies, desire of sexual contact and frequency of sexual contact, supplementation of testosterone did not result in improvement on any of these items in this group. In conclusion, the findings do not support the view that testosterone undecanoate supplementation for 6 months to elderly men with low-normal testosterone concentrations favorably affects sexual function.

Hawthorn Extract Randomized Blinded Chronic Heart Failure (HERB CHF) Trial

PubMed Central

Zick, Suzanna M.; Vautaw, Bonnie Motyka; Gillespie, Brenda; Aaronson, Keith D.

2009-01-01

Aims Hawthorn's efficacy when added to contemporary evidence-based heart failure therapy is unknown. We aimed to determine whether hawthorn increases submaximal exercise capacity when added to standard medical therapy. Methods and results We performed a randomized, double-blind, placebo-controlled trial in 120 ambulatory patients aged ≥18 years with New York Heart Association (NYHA) class II-III chronic heart failure. All patients received conventional medical therapy, as tolerated, and were randomized to either hawthorn 450 mg twice daily or placebo for 6 months. The primary outcome was change in 6 min walk distance at 6 months. Secondary outcomes included quality of life (QOL) measures, peak oxygen consumption, and anaerobic threshold during maximal treadmill exercise testing, NYHA classification, left ventricular ejection fraction (LVEF), neurohormones, and measures of oxidative stress and inflammation. There were no significant differences between groups in the change in 6 min walk distance (P = 0.61), or on measures of QOL, functional capacity, neurohormones, oxidative stress, or inflammation. A modest difference in LVEF favoured hawthorn (P = 0.04). There were significantly more adverse events reported in the hawthorn group (P = 0.02), although most were non-cardiac. Conclusion Hawthorn provides no symptomatic or functional benefit when given with standard medical therapy to patients with heart failure. This trial is registered in ClinicalTrials.gov ID: NCT00343902. PMID:19789403

Hawthorn Extract Randomized Blinded Chronic Heart Failure (HERB CHF) trial.

PubMed

Zick, Suzanna M; Vautaw, Bonnie Motyka; Gillespie, Brenda; Aaronson, Keith D

2009-10-01

Hawthorn's efficacy when added to contemporary evidence-based heart failure therapy is unknown. We aimed to determine whether hawthorn increases submaximal exercise capacity when added to standard medical therapy. We performed a randomized, double-blind, placebo-controlled trial in 120 ambulatory patients aged > or = 18 years with New York Heart Association (NYHA) class II-III chronic heart failure. All patients received conventional medical therapy, as tolerated, and were randomized to either hawthorn 450 mg twice daily or placebo for 6 months. The primary outcome was change in 6 min walk distance at 6 months. Secondary outcomes included quality of life (QOL) measures, peak oxygen consumption, and anaerobic threshold during maximal treadmill exercise testing, NYHA classification, left ventricular ejection fraction (LVEF), neurohormones, and measures of oxidative stress and inflammation. There were no significant differences between groups in the change in 6 min walk distance (P = 0.61), or on measures of QOL, functional capacity, neurohormones, oxidative stress, or inflammation. A modest difference in LVEF favoured hawthorn (P = 0.04). There were significantly more adverse events reported in the hawthorn group (P = 0.02), although most were non-cardiac. Hawthorn provides no symptomatic or functional benefit when given with standard medical therapy to patients with heart failure. This trial is registered in ClinicalTrials.gov ID: NCT00343902.

Randomized, double-blind, placebo-controlled trial of fluoxetine treatment for elderly patients with dysthymic disorder.

PubMed

Devanand, D P; Nobler, Mitchell S; Cheng, Jocelyn; Turret, Nancy; Pelton, Gregory H; Roose, Steven P; Sackeim, Harold A

2005-01-01

The authors compared the efficacy and side effects of fluoxetine and placebo in elderly outpatients with dysthymic disorder. Patients were randomly assigned to fluoxetine (20 mg-60 mg/day) or placebo for 12 weeks in a double-blind trial. Of 90 randomized patients, 71 completed the trial. In the intent-to-treat sample, random regression analyses of the Hamilton Rating Scale for Depression (Ham-D; 24-item) and Cornell Dysthymia Rating Scale (CDRS) scores at each visit produced significant time x treatment group interactions favoring the fluoxetine group. Analysis of percentage change in Ham-D scores yielded no effect for treatment group, but a similar analysis of percentage change in CDRS scores yielded a main effect for treatment group, favoring fluoxetine over placebo. In the intent-to-treat sample, response rates were 27.3% for fluoxetine and 19.6% for placebo. In the completer sample, response rates were 37.5% for fluoxetine and 23.1% for placebo. Fluoxetine had limited efficacy in elderly dysthymic patients. The clinical features of elderly dysthymic patients are typically distinct from those of dysthymic disorder in young adults, and the findings suggest that treatments effective for young adult dysthymic patients may not be as useful in elderly dysthymic patients. Further research is needed to identify efficacious treatments for elderly patients with dysthymic disorder, and investigative tools such as electronic/computerized brain scans and neuropsychological testing may help identify the factors that moderate antidepressant treatment response and resistance.

Feasibility and acceptability of maternal choline supplementation in heavy drinking pregnant women: A randomized, double-blind, placebo-controlled clinical trial.

PubMed

Jacobson, Sandra W; Carter, R Colin; Molteno, Christopher D; Meintjes, Ernesta M; Senekal, Marjanne; Lindinger, Nadine M; Dodge, Neil C; Zeisel, Steven H; Duggan, Christopher P; Jacobson, Joseph L

2018-05-11

Choline, an essential nutrient, serves as a methyl-group donor for DNA methylation and is a constituent of the neurotransmitter acetylcholine and a precursor to major components of cell membranes. Findings from animal studies suggest that choline supplementation during pregnancy may mitigate adverse effects of prenatal alcohol exposure on growth and neurocognitive function. We conducted a randomized, double-blind exploratory trial to examine feasibility and acceptability of a choline supplementation intervention during pregnancy. 70 heavy drinkers, recruited in mid-pregnancy, were randomly assigned to receive a daily oral dose of 2g of choline or a placebo from time of enrollment until delivery. Each dose consisted of an individually wrapped packet of powder that, when mixed with water, produced a sweet tasting grape-flavored drink. Adherence was assessed by collecting used and unused drink packets on a monthly basis and tabulating the number used. Side effects were assessed in monthly interviews. Blood samples obtained at enrollment and at 4 and 12 weeks after randomization were assayed for plasma choline concentration. Adherence was good-to-excellent (median doses taken=74.0%; interquartile range=53.9-88.7%) and was not related to a range of sociodemographic characteristics or to alcohol consumption ascertained using a timeline follow-back interview. By 4 weeks, plasma choline concentrations were significantly higher in the choline supplementation than the placebo arm, and this group difference continued to be evident at 12 weeks. The only side effect was a small increase in nausea/dyspepsia. No effects were seen for diarrhea, vomiting, muscle stiffness, blood pressure, or body odor changes. This study demonstrated that a choline supplementation program with very heavy drinkers during pregnancy is feasible even among highly disadvantaged, poorly educated women. The broad acceptability of this intervention is indicated by our finding that adherence was not related

Randomized Double-Blind Placebo-Controlled Trial of Bevacizumab Therapy for Radiation Necrosis of the Central Nervous System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Levin, Victor A., E-mail: vlevin49@comcast.ne; Bidaut, Luc; Hou, Ping

Purpose: To conduct a controlled trial of bevacizumab for the treatment of symptomatic radiation necrosis of the brain. Methods and Materials: A total of 14 patients were entered into a placebo-controlled randomized double-blind study of bevacizumab for the treatment of central nervous system radiation necrosis. All patients were required to have radiographic or biopsy proof of central nervous system radiation necrosis and progressive neurologic symptoms or signs. Eligible patients had undergone irradiation for head-and-neck carcinoma, meningioma, or low- to mid-grade glioma. Patients were randomized to receive intravenous saline or bevacizumab at 3-week intervals. The magnetic resonance imaging findings 3 weeksmore » after the second treatment and clinical signs and symptoms defined the response or progression. Results: The volumes of necrosis estimated on T{sub 2}-weighted fluid-attenuated inversion recovery and T{sub 1}-weighted gadolinium-enhanced magnetic resonance imaging scans demonstrated that although no patient receiving placebo responded (0 of 7), all bevacizumab-treated patients did so (5 of 5 randomized and 7 of 7 crossover) with decreases in T{sub 2}-weighted fluid-attenuated inversion recovery and T{sub 1}-weighted gadolinium-enhanced volumes and a decrease in endothelial transfer constant. All bevacizumab-treated patients-and none of the placebo-treated patients-showed improvement in neurologic symptoms or signs. At a median of 10 months after the last dose of bevacizumab in patients receiving all four study doses, only 2 patients had experienced a recurrence of magnetic resonance imaging changes consistent with progressive radiation necrosis; one patient received a single additional dose of bevacizumab and the other patient received two doses. Conclusion: The Class I evidence of bevacizumab efficacy from the present study in the treatment of central nervous system radiation necrosis justifies consideration of this treatment option for people with

Escitalopram in the Treatment of Adolescent Depression: A Randomized, Double-Blind, Placebo-Controlled Extension Trial

PubMed Central

Robb, Adelaide; Bose, Anjana

2013-01-01

Abstract Objective The purpose of this study was to evaluate the extended efficacy, safety, and tolerability of escitalopram relative to placebo in adolescents with major depressive disorder (MDD). Methods Adolescents (12–17 years) who completed an 8-week randomized, double-blind, flexible-dose, placebo-controlled, lead-in study of escitalopram 10–20 mg versus placebo could enroll in a 16–24-week, multisite extension trial; patients maintained the same lead-in randomization (escitalopram or placebo) and dosage (escitalopram 10 or 20 mg/day, or placebo) during the extension. The primary efficacy was Children's Depression Rating Scale-Revised (CDRS-R) change from the lead-in study baseline to treatment week 24 (8-week lead-in study plus 16-week extension); the secondary efficacy was Clinical Global Impressions-Improvement (CGI-I) score at week 24. All efficacy analyses used the last observation carried forward (LOCF) approach; sensitivity analyses used observed cases (OC) and mixed-effects model for repeated measures (MMRM). Safety was evaluated via adverse event (AE) reports and the clinician-rated Columbia-Suicide Severity Rating Scale (C-SSRS). Results Following lead-in, 165 patients enrolled in the double-blind extension (82 placebo; 83 escitalopram); 40 (48.8%) placebo and 37 (44.6%) escitalopram patients completed treatment. CDRS-R total score improvement was significantly greater for escitalopram than for placebo (p=0.005, LOCF; p=0.014; MMRM). Response rates (CDRS-R ≥40% reduction from baseline [adjusted and unadjusted] and CGI-I ≤2) were significantly higher for escitalopram than for placebo (LOCF); remission rates (CDRS-R ≤28) were 50.6% for escitalopram and 35.7% for placebo (p=0.002). OC analyses were not significantly different between groups. The most frequent escitalopram AEs (≥5% and more frequent than placebo) were headache, nausea, insomnia, vomiting, influenza-like symptoms, diarrhea, and urinary tract infection. Most AEs were

Randomized, double-blind, dose-escalation trial of triptorelin for ovary protection in childhood-onset systemic lupus erythematosus.

PubMed

Brunner, Hermine I; Silva, Clovis A; Reiff, Andreas; Higgins, Gloria C; Imundo, Lisa; Williams, Calvin B; Wallace, Carol A; Aikawa, Nadia E; Nelson, Shannen; Klein-Gitelman, Marisa S; Rose, Susan R

2015-05-01

To determine the dose of triptorelin that is sufficient to maintain complete ovarian suppression in female patients with childhood-onset systemic lupus erythematosus (SLE) who require cyclophosphamide therapy, to determine the length of time needed to achieve ovarian suppression after initiation of triptorelin treatment, and to investigate the safety of triptorelin. In this randomized, double-blind, placebo-controlled, dose-escalation study, female patients ages <21 years were randomized 4:1 to receive triptorelin (n = 25) or placebo (n = 6). The starting doses of triptorelin were 25, 50, 75, and 100 μg/kg, and the dose was escalated until complete ovarian suppression was maintained. The primary outcome was the weight-adjusted dose of triptorelin that provided complete ovarian suppression in at least 90% of the patients, as determined by gonadotropin-releasing hormone agonist stimulation testing. The secondary outcome was the period of time required to achieve ovarian suppression, as measured by unstimulated follicle-stimulating hormone and luteinizing hormone levels after the initiation of triptorelin treatment. Treatment with triptorelin at a weight-adjusted dose of 120 μg/kg body weight provided sustained complete ovarian suppression in 90% of the patients. After administration of the initial dose of triptorelin, 22 days were required to achieve complete ovarian suppression. The rates of adverse events (AEs) and serious adverse events (SAEs) per 100 patient-months of followup were not higher in the triptorelin group compared with the placebo group (for AEs, 189 versus 362; for SAEs, 2.1 versus 8.5). High doses of triptorelin are needed to achieve and maintain complete ovarian suppression, but such doses appear to be well tolerated in adolescent female patients with childhood-onset SLE. Our data suggest that a lag time of 22 days after initiation of triptorelin treatment is required before cyclophosphamide therapy is started or continued. © 2015

Antidepressants and ejaculation: a double-blind, randomized, placebo-controlled, fixed-dose study with paroxetine, sertraline, and nefazodone.

PubMed

Waldinger, M D; Zwinderman, A H; Olivier, B

2001-06-01

Antidepressant medication is often associated with sexual side effects. A double-blind, placebo-controlled study in men with lifelong rapid ejaculation was performed to assess the effects of two selective serotonin (5-HT) reuptake inhibitors--paroxetine and sertraline--and the 5-HT2 antagonist and 5-HT/noradrenaline reuptake inhibitor nefazodone on the latency to ejaculate. Forty-eight men with an intravaginal ejaculation latency time (IELT) of a maximum of 1 minute were randomly assigned to receive paroxetine (20 mg/day), sertraline (50 mg/day), nefazodone (400 mg/day), or placebo for 6 weeks. During the 1-month baseline and 6-week treatment period, IELTs were measured at home with a stopwatch. The trial was completed by 40 men. During the 6-week treatment period, the geometric mean IELT in the placebo group was stable at approximately 20 seconds. Analysis of variance revealed a between-group difference in the evolution of IELT delay over time (p = 0.002); the IELT after paroxetine and sertraline gradually increased to approximately 146 and 58 seconds, respectively, compared with 28 seconds in the nefazodone group. The paroxetine and sertraline groups differed significantly (p < 0.001 and p = 0.024, respectively) from placebo, but the nefazodone group did not (p = 0.85). Compared with baseline, paroxetine exerted the strongest delay in ejaculation, whereas sertraline delayed it only moderately. There was no clinically relevant delay in ejaculation with nefazodone.

Pain physiology education improves health status and endogenous pain inhibition in fibromyalgia: a double-blind randomized controlled trial.

PubMed

Van Oosterwijck, Jessica; Meeus, Mira; Paul, Lorna; De Schryver, Mieke; Pascal, Aurelie; Lambrecht, Luc; Nijs, Jo

2013-10-01

There is evidence that education on pain physiology can have positive effects on pain, disability, and catastrophization in patients with chronic musculoskeletal pain disorders. A double-blind randomized controlled trial (RCT) was performed to examine whether intensive pain physiology education is also effective in fibromyalgia (FM) patients, and whether it is able to influence the impaired endogenous pain inhibition of these patients. Thirty FM patients were randomly allocated to either the experimental (receiving pain physiology education) or the control group (receiving pacing self-management education). The primary outcome was the efficacy of the pain inhibitory mechanisms, which was evaluated by spatially accumulating thermal nociceptive stimuli. Secondary outcome measures included pressure pain threshold measurements and questionnaires assessing pain cognitions, behavior, and health status. Assessments were performed at baseline, 2 weeks, and 3 months follow-up. Repeated measures ANOVAS were used to reveal possible therapy effects and effect sizes were calculated. After the intervention the experimental group had improved knowledge of pain neurophysiology (P<0.001). Patients from this group worried less about their pain in the short term (P=0.004). Long-term improvements in physical functioning (P=0.046), vitality (P=0.047), mental health (P<0.001), and general health perceptions (P<0.001) were observed. In addition, the intervention group reported lower pain scores and showed improved endogenous pain inhibition (P=0.041) compared with the control group. These results suggest that FM patients are able to understand and remember the complex material about pain physiology. Pain physiology education seems to be a useful component in the treatment of FM patients as it improves health status and endogenous pain inhibition in the long term.

Chinese herbal medicine (Ma Zi Ren Wan) for functional constipation: study protocol for a prospective, double-blinded, double-dummy, randomized controlled trial

PubMed Central

2013-01-01

Background Functional constipation is a common clinical complaint. Although the effectiveness of Ma Zi Ren Wan for alleviating functional constipation symptoms has been proven in a previous randomized placebo-controlled study, further evidence is needed to make clinical recommendations about Chinese herbal medicine. In particular, a comparison with conventional western medicine for functional constipation patients is needed. Methods/Design This is a prospective, double-blinded, double dummy, randomized, controlled trial. After a 2-week run-in period, eligible patients (Rome III) with excessive traditional Chinese medicine syndrome will randomly be assigned to the Chinese medicine arm (Ma Zi Ren Wan and western medicine placebo), western medicine arm (senna and Chinese medicine placebo) or placebo arm (Chinese medicine placebo and western medicine placebo). Patients will undergo an 8-week treatment and an 8-week follow-up. The primary outcome is the responder rate for complete spontaneous bowel movement (CSBM) during treatment. Patients with a mean increase of CSBM ≧1/week in comparison with their baselines are defined as responders. The secondary outcomes include responder rate during follow-up, changes of colonic transit as measured with radio-opaque markers, individual and global symptom assessments, and reported adverse effects. Discussion This study is the first study to compare a Chinese Herbal Medicine (Ma Zi Ren Wan) with a laxative that is commonly used in the clinical practice of western medicine, and with a placebo. This study will complete the investigation of Ma Zi Ren Wan for functional constipation, and should, therefore, suggest recommendations for clinical practice. Furthermore, the process of first conducting a systematic review, then implementing a dose determination study followed by a placebo-control trial, and finally, comparing traditional Chinese medicine with an active conventional medicine in a controlled trial can be a reference to other

Chinese herbal medicine (Ma Zi Ren Wan) for functional constipation: study protocol for a prospective, double-blinded, double-dummy, randomized controlled trial.

PubMed

Zhong, Linda L D; Cheng, Chung Wah; Chan, Yawen; Chan, King Hong; Lam, Ting Wa; Chen, Xiao Rui; Wong, Chi Tak; Wu, Justin C Y; Bian, Zhao Xiang

2013-11-04

Functional constipation is a common clinical complaint. Although the effectiveness of Ma Zi Ren Wan for alleviating functional constipation symptoms has been proven in a previous randomized placebo-controlled study, further evidence is needed to make clinical recommendations about Chinese herbal medicine. In particular, a comparison with conventional western medicine for functional constipation patients is needed. This is a prospective, double-blinded, double dummy, randomized, controlled trial. After a 2-week run-in period, eligible patients (Rome III) with excessive traditional Chinese medicine syndrome will randomly be assigned to the Chinese medicine arm (Ma Zi Ren Wan and western medicine placebo), western medicine arm (senna and Chinese medicine placebo) or placebo arm (Chinese medicine placebo and western medicine placebo). Patients will undergo an 8-week treatment and an 8-week follow-up. The primary outcome is the responder rate for complete spontaneous bowel movement (CSBM) during treatment. Patients with a mean increase of CSBM ≧1/week in comparison with their baselines are defined as responders. The secondary outcomes include responder rate during follow-up, changes of colonic transit as measured with radio-opaque markers, individual and global symptom assessments, and reported adverse effects. This study is the first study to compare a Chinese Herbal Medicine (Ma Zi Ren Wan) with a laxative that is commonly used in the clinical practice of western medicine, and with a placebo. This study will complete the investigation of Ma Zi Ren Wan for functional constipation, and should, therefore, suggest recommendations for clinical practice. Furthermore, the process of first conducting a systematic review, then implementing a dose determination study followed by a placebo-control trial, and finally, comparing traditional Chinese medicine with an active conventional medicine in a controlled trial can be a reference to other researches on Chinese medicine

Etanercept in Alzheimer disease: A randomized, placebo-controlled, double-blind, phase 2 trial.

PubMed

Butchart, Joseph; Brook, Laura; Hopkins, Vivienne; Teeling, Jessica; Püntener, Ursula; Culliford, David; Sharples, Richard; Sharif, Saif; McFarlane, Brady; Raybould, Rachel; Thomas, Rhodri; Passmore, Peter; Perry, V Hugh; Holmes, Clive

2015-05-26

To determine whether the tumor necrosis factor α inhibitor etanercept is well tolerated and obtain preliminary data on its safety in Alzheimer disease dementia. In a double-blind study, patients with mild to moderate Alzheimer disease dementia were randomized (1:1) to subcutaneous etanercept (50 mg) once weekly or identical placebo over a 24-week period. Tolerability and safety of this medication was recorded including secondary outcomes of cognition, global function, behavior, and systemic cytokine levels at baseline, 12 weeks, 24 weeks, and following a 4-week washout period. This trial is registered with EudraCT (2009-013400-31) and ClinicalTrials.gov (NCT01068353). Forty-one participants (mean age 72.4 years; 61% men) were randomized to etanercept (n = 20) or placebo (n = 21). Etanercept was well tolerated; 90% of participants (18/20) completed the study compared with 71% (15/21) in the placebo group. Although infections were more common in the etanercept group, there were no serious adverse events or new safety concerns. While there were some interesting trends that favored etanercept, there were no statistically significant changes in cognition, behavior, or global function. This study showed that subcutaneous etanercept (50 mg/wk) was well tolerated in this small group of patients with Alzheimer disease dementia, but a larger more heterogeneous group needs to be tested before recommending its use for broader groups of patients. This study shows Class I evidence that weekly subcutaneous etanercept is well tolerated in Alzheimer disease dementia. © 2015 American Academy of Neurology.

Double-blind, randomized, double-dummy clinical trial comparing the efficacy of ketorolac trometamol and naproxen for acute low back pain.

PubMed

Plapler, Pérola Grinberg; Scheinberg, Morton Aaron; Ecclissato, Christina da Cunha; Bocchi de Oliveira, Monalisa Fernanda; Amazonas, Roberto Bleuel

2016-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most common type of medication used in the treatment of acute pain. Ketorolac trometamol (KT) is a nonnarcotic, peripherally acting nonsteroidal anti-inflammatory drug with analgesic effects comparable to certain opioids. The aim of this study was to compare the efficacy of KT and naproxen (NA) in the treatment of acute low back pain (LBP) of moderate-to-severe intensity. In this 10-day, Phase III, randomized, double-blind, double-dummy, noninferiority trial, participants with acute LBP of moderate-to-severe intensity as determined through a visual analog scale (VAS) were randomly assigned in a 1:1 ratio to receive sublingual KT 10 mg three times daily or oral NA 250 mg three times daily. From the second to the fifth day of treatment, if patient had VAS >40 mm, increased dosage to four times per day was allowed. The primary end point was the reduction in LBP as measured by VAS. We also performed a post hoc superiority analysis. KT was not inferior to NA for the reduction in LBP over 5 days of use as measured by VAS scores (P=0.608 for equality of variance; P=0.321 for equality of means) and by the Roland-Morris Disability Questionnaire (P=0.180 for equality of variance test; P=0.446 for equality of means) using 95% confidence intervals. The percentage of participants with improved pain relief 60 minutes after receiving the first dose was higher in the KT group (24.2%) than in the NA group (6.5%; P=0.049). The most common adverse effects were heartburn, nausea, and vomiting. KT is not inferior in efficacy and delivers faster pain relief than NA.

Double-blind, randomized, double-dummy clinical trial comparing the efficacy of ketorolac trometamol and naproxen for acute low back pain

PubMed Central

Plapler, Pérola Grinberg; Scheinberg, Morton Aaron; Ecclissato, Christina da Cunha; Bocchi de Oliveira, Monalisa Fernanda; Amazonas, Roberto Bleuel

2016-01-01

Background Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most common type of medication used in the treatment of acute pain. Ketorolac trometamol (KT) is a nonnarcotic, peripherally acting nonsteroidal anti-inflammatory drug with analgesic effects comparable to certain opioids. Objective The aim of this study was to compare the efficacy of KT and naproxen (NA) in the treatment of acute low back pain (LBP) of moderate-to-severe intensity. Patients and methods In this 10-day, Phase III, randomized, double-blind, double-dummy, noninferiority trial, participants with acute LBP of moderate-to-severe intensity as determined through a visual analog scale (VAS) were randomly assigned in a 1:1 ratio to receive sublingual KT 10 mg three times daily or oral NA 250 mg three times daily. From the second to the fifth day of treatment, if patient had VAS >40 mm, increased dosage to four times per day was allowed. The primary end point was the reduction in LBP as measured by VAS. We also performed a post hoc superiority analysis. Results KT was not inferior to NA for the reduction in LBP over 5 days of use as measured by VAS scores (P=0.608 for equality of variance; P=0.321 for equality of means) and by the Roland–Morris Disability Questionnaire (P=0.180 for equality of variance test; P=0.446 for equality of means) using 95% confidence intervals. The percentage of participants with improved pain relief 60 minutes after receiving the first dose was higher in the KT group (24.2%) than in the NA group (6.5%; P=0.049). The most common adverse effects were heartburn, nausea, and vomiting. Conclusion KT is not inferior in efficacy and delivers faster pain relief than NA. PMID:27382251

Effects of Two Chinese Herbal Formulae for the Treatment of Moderate to Severe Stable Chronic Obstructive Pulmonary Disease: A Multicenter, Double-Blind, Randomized Controlled Trial

PubMed Central

Cao, Yuxue; Du, Yijie; Zhang, Hongying; Luo, Qingli; Li, Bei; Wu, Jinfeng; Lv, Yubao; Sun, Jing; Jin, Hualiang; Wei, Kai; Zhao, Zhengxiao; Kong, Lingwen; Zhou, Xianmei; Miao, Qing; Wang, Gang; Zhou, Qingwei; Dong, Jingcheng

2014-01-01

Objective The study aims to evaluate the efficacy and safety of two Chinese herbal formulae for the treatment of stable COPD. Methods A multicenter, double-blind, double-dummy, and randomized controlled trial (RCT) was conducted. All groups were treated with additional conventional medicines. There were a 6-month treatment and a 12-month follow-up for 5 times. Primary outcomes included lung function test, exacerbation frequency, score of SGRQ. Second outcomes consisted of 6MWD, BODE index, psychological field score, inflammatory factors and cortisol. Results A total of 331 patients were randomly divided into two active treatment groups (Bushen Yiqi (BY) granule group, n = 109; Bushen Fangchuan (BF) tablet group, n = 109) and a placebo group (n = 113). Finally 262 patients completed the study. BY granule & BF tablet increased the values of VC, FEV1 (%) and FEV1/FVC (%), compared with placebo. BY granule improved PEF. Both treatments reduced acute exacerbation frequency (P = 0.067), BODE index and psychological field score, while improved 6MWD. In terms of descent rang of SGRQ score, both treatments increased (P = 0.01). Both treatments decreased inflammatory cytokines, such as IL-8, and IL-17(P = 0.0219). BY granule obviously descended IL-17(P<0.05), IL-1β (P = 0.05), IL-6, compared with placebo. They improved the level of IL-10 and cortisol. BY granule raised cortisol (P = 0.07) and decreased TNF-α. Both treatments slightly descended TGF-β1. In terms of safety, subject compliance and drug combination, there were no differences (P>0.05) among three groups. Conclusions BY granule and BF tablet were positively effective for the treatment of COPD, and the former performed better in general. Trial Registration Chinese Clinical Trial Register center ChiCTR-TRC-09000530 PMID:25118962

Homeopathy for Depression - DEP-HOM: study protocol for a randomized, partially double-blind, placebo controlled, four armed study

PubMed Central

2011-01-01

Background Homeopathy is often sought by patients with depression. In classical homeopathy, the treatment consists of two main elements: the case history and the prescription of an individually selected homeopathic remedy. Previous data suggest that individualized homeopathic Q-potencies were not inferior to the antidepressant fluoxetine in a sample of patients with moderate to severe depression. However, the question remains whether individualized homeopathic Q-potencies and/or the type of the homeopathic case history have a specific therapeutical effect in acute depression as this has not yet been investigated. The study aims to assess the two components of individualized homeopathic treatment for acute depression, i.e., to investigate the specific effect of individualized Q-potencies versus placebo and to investigate the effect of different approaches to the homeopathic case history. Methods/Design A randomized, partially double-blind, placebo-controlled, four-armed trial using a 2 × 2 factorial design with a six-week study duration per patient will be performed. 228 patients diagnosed with major depression (moderate episode) by a psychiatrist will be included. The primary endpoint is the total score on the 17-item Hamilton Depression Rating Scale after six weeks. Secondary end points are: Hamilton Depression Rating Scale total score after two and four weeks; response and remission rates, Beck Depression inventory total score, quality of life and safety at two, four and six weeks. Statistical analyses will be by intention-to-treat. The main endpoint will be analysed by a two-factorial analysis of covariance. Within this model generalized estimation equations will be used to estimate differences between verum and placebo, and between both types of case history. Discussion For the first time this study evaluates both the specific effect of homeopathic medicines and of a homeopathic case taking in patients with depression. It is an attempt to deal with the

Omega-3 fatty acids for major depressive disorder during pregnancy: results from a randomized, double-blind, placebo-controlled trial.

PubMed

Su, Kuan-Pin; Huang, Shih-Yi; Chiu, Tsan-Hung; Huang, Kuo-Cherh; Huang, Chieh-Liang; Chang, Hui-Chih; Pariante, Carmine M

2008-04-01

Perinatal depression is common, and treatment remains challenging. Depression has been reported to be associated with the abnormality of omega-3 polyunsaturated fatty acids (PUFAs). A profound decrease of omega-3 PUFAs in the mother during pregnancy is associated with the higher demand of fetal development and might precipitate the occurrence of depression. In this study, we examined the efficacy of omega-3 PUFA monotherapy for the treatment of depression during pregnancy. From June 2004 to June 2006, we conducted an 8-week, double-blind, placebo-controlled trial comparing omega-3 PUFAs (3.4 g/d) with placebo in pregnant women with major depressive disorder (DSM-IV criteria). No psychotropic agent was given 1 month prior to or during the study period. The Hamilton Rating Scale for Depression (HAM-D) was scored every other week as the primary measurement of efficacy, while the Edinburgh Postnatal Depression Scale (EPDS) and Beck Depression Inventory (BDI) were secondary measures. Thirty-six subjects were randomly assigned to either omega-3 PUFAs or placebo, and 33 among them were evaluated in more than 2 visits. A total of 24 subjects completed the study. As compared to the placebo group, subjects in the omega-3 group had significantly lower HAM-D scores at weeks 6 (p = .001) and 8 (p = .019), a significantly higher response rate (62% vs. 27%, p = .03), and a higher remission rate, although the latter did not reach statistical significance (38% vs. 18%, p = .28). At the study end point, subjects in the omega-3 group also had significantly lower depressive symptom ratings on the EPDS and BDI. The omega-3 PUFAs were well tolerated and there were no adverse effects on the subjects and newborns. Omega-3 PUFAs may have therapeutic benefits in depression during pregnancy. In regard to the safety issue and psychotherapeutic effect, as well as health promotion to mothers and their newborns, it is worthy to conduct replication studies in a larger sample with a broad regimen

'Benifuuki' green tea containing o-methylated catechin reduces symptoms of Japanese cedar pollinosis: a randomized, double-blind, placebo-controlled trial.

PubMed

Masuda, Sawako; Maeda-Yamamoto, Mari; Usui, Satoko; Fujisawa, Takao

2014-06-01

Methylated catechin, one of the active ingredients in green tea, has been reported to ameliorate allergic reactions. We evaluated the efficacy of 'Benifuuki' green tea, which contains O-methylated epigallocatechin-3-O-[3-O-methyl] gallate (O-methylated EGCG), in alleviating Japanese cedar pollinosis (JCP). The study was a double-blind, randomized, placebo-controlled trial. The subjects with JCP were randomly assigned to drink 700ml of 'Benifuuki' green tea containing O-methylated EGCG or 'Yabukita' green tea (not containing O-methylated EGCG) as a placebo every day from December 2007 through March 2008, which includes the pollen season. The primary outcome was the area under the curve (AUC) of symptom scores during the peak pollen season. Fifty-one adults with JCP participated in the study. Twenty-six subjects were assigned to 'Benifuuki' and 25 to 'Yabukita'. The AUC of symptom score during the peak pollen season in the 'Benifuuki' group was significantly smaller than in the 'Yabukita' group for each of runny nose, itchy eyes, tearing, total nasal symptom score, total ocular symptom score, nasal symptom-medication score and ocular symptom-medication score. The total QOL-related questionnaire score for one week in the peak pollen season was significantly better in the 'Benifuuki' group. Increase in the peripheral eosinophil count in response to pollen exposure was suppressed in the 'Benifuuki' group. No adverse events were reported in either group. 'Benifuuki' green tea containing a large amount of O-methylated EGCG reduced the symptoms of JCP and has potential as a complementary/alternative medicine for treating seasonal allergic rhinitis.

6-month versus 36-month isoniazid preventive treatment for tuberculosis in adults with HIV infection in Botswana: a randomised, double-blind, placebo-controlled trial.

PubMed

Samandari, Taraz; Agizew, Tefera B; Nyirenda, Samba; Tedla, Zegabriel; Sibanda, Thabisa; Shang, Nong; Mosimaneotsile, Barudi; Motsamai, Oaitse I; Bozeman, Lorna; Davis, Margarett K; Talbot, Elizabeth A; Moeti, Themba L; Moffat, Howard J; Kilmarx, Peter H; Castro, Kenneth G; Wells, Charles D

2011-05-07

In accordance with WHO guidelines, people with HIV infection in Botswana receive daily isoniazid preventive therapy against tuberculosis without obtaining a tuberculin skin test, but duration of prophylaxis is restricted to 6 months. We aimed to assess effectiveness of extended isoniazid therapy. In our randomised, double-blind, placebo-controlled trial we enrolled adults infected with HIV aged 18 years or older at government HIV-care clinics in Botswana. Exclusion criteria included current illness such as cough and an abnormal chest radiograph without antecedent tuberculosis or pneumonia. Eligible individuals were randomly allocated (1:1) to receive 6 months' open-label isoniazid followed by 30 months' masked placebo (control group) or 6 months' open-label isoniazid followed by 30 months' masked isoniazid (continued isoniazid group) on the basis of a computer-generated randomisation list with permuted blocks of ten at each clinic. Antiretroviral therapy was provided if participants had CD4-positive lymphocyte counts of fewer than 200 cells per μL. We used Cox regression analysis and the log-rank test to compare incident tuberculosis in the groups. Cox regression models were used to estimate the effect of antiretroviral therapy. The trial is registered at ClinicalTrials.gov, number NCT00164281. Between Nov 26, 2004, and July 3, 2009, we recorded 34 (3·4%) cases of incident tuberculosis in 989 participants allocated to the control group and 20 (2·0%) in 1006 allocated to the continued isoniazid group (incidence 1·26% per year vs 0·72%; hazard ratio 0·57, 95% CI 0·33-0·99, p=0·047). Tuberculosis incidence in those individuals receiving placebo escalated approximately 200 days after completion of open-label isoniazid. Participants who were tuberculin skin test positive (ie, ≥5 mm induration) at enrolment received a substantial benefit from continued isoniazid treatment (0·26, 0·09-0·80, p=0·02), whereas participants who were tuberculin skin test

Does a mineral wristband affect balance? A randomized, controlled, double-blind study.

PubMed

Hansson, Eva Ekvall; Beckman, Anders; Persson, Liselott

2015-06-26

Having good balance is a facilitating factor in the performance of everyday activities. Good balance is also essential in various sport activities in order to both get results and prevent injury. A common measure of balance is postural sway, which can be measured both antero-posteriorly and medio-laterally. There are several companies marketing wristbands whose intended function is to improve balance, strength and flexibility. Randomized controlled trials have shown that wristbands with holograms have no effect on balance but studies on wristbands with minerals seem to be lacking. The aim of this study was to investigate if the mineral wristband had any effect on postural sway in a group of healthy individuals. Randomized, controlled, double-blind study. The study group consisted of 40 healthy persons. Postural sway was measured antero-posteriorly and medio-laterally on a force plate, to compare: the mineral wristband, a placebo wristband, and without any wristband. The measurements were performed for 30 s, in four situations: with open eyes and closed eyes, standing on a firm surface and on foam. Analyses were made with multilevel technique. The use of wristband with or without minerals did not alter postural sway. Closed eyes and standing on foam both prolonged the dependent measurement, irrespective if it was medio-lateral or antero-posterior. Wearing any wristband (mineral or placebo) gave a small (0.22-0.36 mm/s) but not statistically significant reduction of postural sway compared to not wearing wristband. This study showed no effect on postural sway by using the mineral wristband, compared with a placebo wristband or no wristband. Wearing any wristband at all (mineral or placebo) gave a small but not statistically significant reduction in postural sway, probably caused by sensory input.

[A prospective, randomized, double-blinded control study on comparison of tramadol, clonidine and dexmedetomidine for post spinal anesthesia shivering].

PubMed

Venkatraman, Rajagopalan; Karthik, Krishnamoorthy; Pushparani, Anand; Mahalakshmi, Annadurai

Shivering, a common intraoperative problem under spinal anesthesia increases the oxygen consumption considerably and is uncomfortable and distressing to the patient, anesthesiologist as well as surgeon. The present study was designed to explore the effectiveness of tramadol, clonidine and dexmedetomidine in the treatment of post spinal anesthesia shivering and to look for their adverse effects. This prospective, randomized, double blinded control study was done on 90 patients who developed shivering under spinal anesthesia. They were randomly allocated into three groups with Group T receiving tramadol 1mg.kg -1 , Group C getting clonidine 1mcg.kg -1 and Group D patients receiving dexmedetomidine 0.5mcg.kg -1 . The time taken to control shivering, recurrence rate, hemodynamic variables, sedation score and adverse effects were observed. Dexmedetomidine was faster in the control of shivering in 5.7±0.79minutes (min) whereas tramadol took 6.76±0.93min and clonidine was slower with 9.43±0.93min. The recurrence rate was much lower in the dexmedetomidine group with 3.3% than for clonidine (10%) and tramadol (23.3%) group. The sedation achieved with dexmedetomidine was better than clonidine and tramadol. The tramadol group had more cases of vomiting (four) and dexmedetomidine group had six cases of hypotension and two cases of bradycardia. Two of the clonidine patients encountered bradycardia and hypotension. Dexmedetomidine is better than tramadol and clonidine in the control of shivering because of its faster onset and less recurrence rate. Though complications are encountered in the dexmedetomidine group, they are treatable. Copyright © 2016 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Traditional Chinese medicine compound ShengJinRunZaoYangXue granules for treatment of primary Sjögren's syndrome: a randomized, double-blind, placebo-controlled clinical trial.

PubMed

Hu, Wei; Qian, Xian; Guo, Feng; Zhang, Miaojia; Lyu, Chengyin; Tao, Juan; Gao, Zhong'en; Zhou, Zhengqiu

2014-01-01

Traditional Chinese medical treatment of primary Sjögren's syndrome has advantages over Western medicine in terms of fewer side effects and improved patient conditions. This study was a multicenter, randomized, double-blind, placebo-controlled clinical trial of the efficacy and safety of ShengJinRunZaoYangXue granules for the treatment of primary Sjögren's syndrome, including the symptoms of dry mouth and dry eye. We undertook a 6-week, double-blind, randomized trial involving 240 patients with primary Sjögren's syndrome at five centers in East China. A computer-generated randomization schedule assigned patients at a 2:1 ratio to receive either ShengJinRunZaoYangXue granules or placebo once daily. Patients and investigators were blinded to treatment allocation. The primary endpoints were the salivary flow rate, Schirmer test results, and sugar test results. Intention-to-treat and per-protocol analyses were performed. All 240 patients were randomly allocated to either the treatment group (n = 160, ShengJinRunZaoYangXue granules) or placebo group (n = 80) and were included in the intention-to-treat analysis. After program violation and loss to follow-up, a total of 199 patients were included in the per-protocol analysis. At six week, intention-to-treat and per-protocol analyses of the left-eye Schirmer I test results showed an improved difference of 1.36 mm/5 min (95% CI: 0.03 to 2.69 mm/5 min) and 1.35 mm/5 min (95% CI: 0.04 to 2.73 mm/5 min), respectively, and those of the right-eye Schirmer I test results showed an improved difference of 1.12 mm/5 min (95% CI: 0.02 to 2.22 mm/5 min) and 1.12 mm/5 min (95% CI: -0.02 to 2.27 mm/5 min), respectively. There was no significant difference between the two groups before treatment. After treatment, the between-group and within-group before-and-after paired comparison results were statistically significant (P < 0.05). Intention-to-treat and per-protocol analyses showed an improved salivary flow rate by 0.04 ml/15 min (95

The use of Lactobacillus GG in irritable bowel syndrome in children: a double-blind randomized control trial.

PubMed

Bauserman, Melissa; Bausserman, Melissa; Michail, Sonia

2005-08-01

To determine whether oral administration of the probiotic Lactobacillus GG under randomized, double-blinded, placebo-controlled conditions would improve symptoms of irritable bowel syndrome (IBS) in children. Fifty children fulfilling the Rome II criteria for IBS were given Lactobacillus GG or placebo for 6 weeks. Response to therapy was recorded and collected on a weekly basis using the Gastrointestinal Symptom Rating Scale (GSRS). Lactobacillus GG was not superior to placebo in relieving abdominal pain (40.0% response rate in the placebo group vs 44.0% in the Lactobacillus GG group; P=.774). There was no difference in the other gastrointestinal symptoms, except for a lower incidence of perceived abdominal distention (P=.02 favoring Lactobacillus GG). Lactobacillus GG was not superior to placebo in the treatment of abdominal pain in children with IBS but may help relieve such symptoms as perceived abdominal distention.

Cryopreserved human amniotic membrane injection for plantar fasciitis: a randomized, controlled, double-blind pilot study.

PubMed

Hanselman, Andrew E; Tidwell, John E; Santrock, Robert D

2015-02-01

Treatment options for plantar fasciitis have resulted in varied patient outcomes. The aim of this study was to compare a novel treatment, cryopreserved human amniotic membrane (c-hAM), to a traditional treatment, corticosteroid. Our hypothesis was that c-hAM would be safe and comparable to corticosteroids for plantar fasciitis in regard to patient outcomes. A randomized, controlled, double-blind, single-center pilot study was completed. Patients were randomized into one of 2 treatment groups: c-hAM or corticosteroid. Patients received an injection at their initial baseline visit with an option for a second injection at their first 6-week follow-up. Total follow-up was obtained for 12 weeks after the most recent injection. The primary outcome measurement was the Foot Health Status Questionnaire (FHSQ). The secondary outcome measurements were the Visual Analog Scale (VAS) and verbally reported percentage improvement. Data were analyzed between groups for the 2 different cohorts (1 injection versus 2 injections). Twenty-three patients had complete follow-up. Fourteen were randomized to receive corticosteroid and 9 were randomized to receive c-hAM. Three patients in each group received second injections. With the numbers available, the majority of outcome measurements showed no statistical difference between groups. The corticosteroid did, however, have greater FHSQ shoe fit improvement (P = .0244) at 6 weeks, FHSQ general health improvement (P = .0132) at 6 weeks, and verbally reported improvement (P = .041) at 12 weeks in the one-injection cohort. Cryopreserved hAM had greater FHSQ foot pain improvement (P = .0113) at 18 weeks in the 2-injection cohort. Cryopreserved hAM injection may be safe and comparable to corticosteroid injection for treatment of plantar fasciitis. This is a pilot study and requires further investigation. Level I, prospective randomized trial. © The Author(s) 2014.

Supplementation with 1000 IU vitamin D/d leads to parathyroid hormone suppression, but not increased fractional calcium absorption, in 4-8-y-old children: A double-blind randomized controlled trial

USDA-ARS?s Scientific Manuscript database

The effects of vitamin D supplementation in healthy prepubertal children on physiologic outcomes have not been investigated. The objective was to evaluate the effects of supplementation with 1000 IU vitamin D(3)/d on calcium absorption. In a double-blind, placebo-controlled trial, we randomly assign...

Empagliflozin as adjunct to insulin in Japanese participants with type 1 diabetes: Results of a 4-week, double-blind, randomized, placebo-controlled phase 2 trial.

PubMed

Shimada, Akira; Hanafusa, Toshiaki; Yasui, Atsutaka; Lee, Ganghyuck; Taneda, Yusuke; Sarashina, Akiko; Shiki, Kosuke; George, Jyothis; Soleymanlou, Nima; Marquard, Jan

2018-05-15

This phase 2, double-blind, randomized, placebo-controlled trial (ClinicalTrials.gov NCT02702011) with 4 sites in Japan investigated the pharmacodynamics (PD), pharmacokinetics (PK) and safety profile of empagliflozin in Japanese participants with type 1 diabetes mellitus (T1DM) as adjunctive therapy to insulin. Participants using multiple daily injections of insulin for ≥12 months, with HbA1c of 7.5%-10.0%, entered a 2-week, open-label, placebo run-in period, followed by a 4-week, double-blind period during which participants were randomized 1:1:1:1 to receive empagliflozin 2.5 mg (n = 13), empagliflozin 10 mg (n = 12), empagliflozin 25 mg (n = 12) or placebo (n = 11). The primary objective was to assess the effect of empagliflozin vs placebo on urinary glucose excretion (UGE) after 7 days of treatment. PD: Empagliflozin resulted in a dose-dependent significant increase in 24-hour UGE compared with placebo (UGE placebo-corrected mean [95% confidence interval] change from baseline: 2.5 mg, 65.10 [43.29, 86.90] g/24 h; 10 mg, 81.19 [58.80, 103.58] g/24 h; 25 mg, 98.11 [75.91, 120.31] g/24 h). After 4 weeks of treatment, UGE increase was associated with improved glycaemic control, reduced body weight and decreased insulin needs. Empagliflozin treatment also resulted in dose-dependent increases in serum ketone bodies and free fatty acids. PK: Plasma empagliflozin levels increased in a dose-dependent manner and peaked at 1.5 hours. In this short study, empagliflozin was well tolerated, with no increase in rate of hypoglycaemia and no diabetic ketoacidosis events reported. Based on this short-duration phase 2 study, the PK/PD profile of empagliflozin in Japanese participants with T1DM is comparable to that of non-Japanese participants. © 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Intraportal Infusion of Bone Marrow Mononuclear or CD133+ Cells in Patients With Decompensated Cirrhosis: A Double-Blind Randomized Controlled Trial

PubMed Central

Mohamadnejad, Mehdi; Vosough, Massoud; Moossavi, Shirin; Nikfam, Sepideh; Mardpour, Soura; Akhlaghpoor, Shahram; Ashrafi, Mandana; Azimian, Vajiheh; Jarughi, Neda; Hosseini, Seyedeh-Esmat; Moeininia, Fatemeh; Bagheri, Mohamad; Sharafkhah, Maryam; Aghdami, Nasser

2016-01-01

The present study assessed the effects of intraportal infusions of autologous bone marrow-derived mononuclear cells (MNCs) and/or CD133+ cells on liver function in patients with decompensated cirrhosis. We randomly assigned 27 eligible patients to a placebo, MNCs, and/or CD133+ cells. Cell infusions were performed at baseline and month 3. We considered the absolute changes in the Model for End-Stage Liver Disease (MELD) scores at months 3 and 6 after infusion as the primary outcome. The participants and those who assessed the outcomes were unaware of the treatment intervention assignments. After 6 months, 9 patients were excluded because of liver transplantation (n = 3), hepatocellular carcinoma (n = 1), loss to follow-up (n = 3), and death (n = 2). The final analysis included 4 patients from the CD133+ group, 8 from the MNC group, and 6 from the placebo group. No improvement was seen in the MELD score at month 6 using either CD133+ cells or MNC infusions compared with placebo. However, at month 3 after infusion, a trend was seen toward a higher mean absolute change in the MELD score in patients who had received CD133+ cells compared with placebo (−2.00 ± 1.87 vs. −0.13 ± 1.46; p = .08). No significant adverse events occurred in the present study. A transient improvement in the MELD score was observed in subjects treated with CD133+ cells but not in the MNC or placebo group. Although the study was not powered to make definitive conclusions, the data justify further study of CD133+ therapy in cirrhotic patients. Significance Cell therapy is a new approach in liver disease. Several clinical experiments have been reported on the safety of bone marrow-derived stem cells to treat liver disorders. However, the effectiveness of these approaches in the long-term follow-ups of patients initiated controversial discussions among the scientific community. A double-blind randomized controlled trial was designed to address this concern scientifically. A transient

Effect of vitamin D on gastrointestinal symptoms and health-related quality of life in irritable bowel syndrome patients: a randomized double-blind clinical trial.

PubMed

Abbasnezhad, A; Amani, R; Hajiani, E; Alavinejad, P; Cheraghian, B; Ghadiri, A

2016-10-01

Low-grade mucosal inflammation and immune activation are involved in the pathogenesis of irritable bowel syndrome (IBS). Furthermore, IBS symptoms are associated with a significantly higher prevalence of psychological distress, which in itself results into an impaired quality of life (QoL). Vitamin D could ameliorate the symptoms of patients suffering from IBS through its beneficial effects on psychological factors and inflammation. A total of 90 IBS patients participated in this double-blind, randomized, placebo-controlled study. Participants were randomly selected to receive either 50 000 IU vitamin D3 or a placebo fortnightly for a period of 6 months. Patients reported their IBS symptoms at the baseline and monthly during intervention periods. The IBS severity score system (IBSSS) and IBS-specific QoL questionnaires were used at the baseline and postintervention. Over the 6-month intervention period, a significantly greater improvement in IBS symptoms such as abdominal pain and distention, flatulence, rumbling, and overall gastrointestinal (GI) symptoms (except dissatisfaction with bowel habits) was observed in the patients receiving vitamin D as compared to the placebo group. The IBSSS and the IBS-QoL scores in the vitamin D group significantly improved compared to the placebo group postintervention (mean IBSSS score change: -53.82 ± 23.3 vs -16.85 ± 25.01, p < 0.001, respectively; mean IBS-QoL score change: 14.26 ± 3 vs 11 ± 2.34, p < 0.001, respectively). Vitamin D seems to be an effective and safe option to improve QoL and symptoms of IBS. ClinicalTrials.gov (NCT02579902). © 2016 John Wiley & Sons Ltd.

Effect of Miracle Fruit (Synsepalum dulcificum) Seed Oil (MFSO®) on the Measurable Improvement of Hair Breakage in Women with Damaged Hair: A Randomized, Double-blind, Placebo-controlled, Eight-month Trial.

PubMed

Del Campo, Roberta; Zhang, Yu; Wakeford, Charles

2017-11-01

Background: Hair breakage is a common unrecognized form of hair loss in women most often the result of hair weathering and traumatic grooming practices. Lipids are major determinants of the physical properties of the hair. Synsepalum dulcificum seed oil (MFSO ® ; Miracle Fruit Oil Co., Miami Beach, Florida), is an exotic fruit oil with physicochemical properties suited to providing a superior ability to reduce hair breakage. Objective: To assess the safety and efficacy of a hair oil containing MFSO and its effects on hair breakage rates. Methods: Healthy, long-haired women (age range: 19-63 years, mean age: 36.7 years, standard deviation: 10.77 years) with excessive hair breakage were randomized in this double-blind, placebo-controlled study to receive MFSO (n=24), vehicle (n=17), or argan oil (n=16). Measurements of hair length, hair diameter, and Hair Mass Index were performed at baseline, Month 4, and Month 8. Hair Breakage Index and the Healthy Hair Index values were calculated from the trichometer measurements, and subject self-assessment questionnaires were conducted. The primary efficacy endpoints were the percent change in Healthy Hair Index 75 and Healthy Hair Index 50 measurements from baseline to the eighth month. Results: The Healthy Hair Index calculations, expressed as percent change from baseline to Month 4 and from baseline to Month 8, revealed that the MFSO ® treatment group improved by 103.6 percent and 215.7 percent for the Healthy Hair Index 75 and 133.7 and 188.3 percent for the Healthy Hair Index 50 values, respectively. When compared with the vehicle and the argan oil brand groups, the Healthy Hair Index levels were significantly higher (p < 0.001) for the MFSO ® treatment group, indicating a much greater ability to increase the levels of unbroken hairs by reducing hair breakage. With respect to the mean percent improvements from baseline to Month 4 and Month 8, the MFSO ® hair oil treatment group was better than each of the other two

Cerebellar transcranial direct current stimulation in patients with ataxia: A double-blind, randomized, sham-controlled study.

PubMed

Benussi, Alberto; Koch, Giacomo; Cotelli, Maria; Padovani, Alessandro; Borroni, Barbara

2015-10-01

Numerous studies have highlighted the possibility of modulating the excitability of cerebellar circuits using transcranial direct current stimulation. The present study investigated whether a single session of cerebellar anodal transcranial direct current stimulation could improve symptoms in patients with ataxia. Nineteen patients with ataxia underwent a clinical and functional evaluation pre- and post-double-blind, randomized, sham, or anodal transcranial direct current stimulation. There was a significant interaction between treatment and time on the Scale for the Assessment and Rating of Ataxia, on the International Cooperative Ataxia Rating Scale, on the 9-Hole Peg Test, and on the 8-Meter Walking Time (P < 0.001). At the end of the sessions, all performance scores were significantly different in the sham trial, compared to the intervention trial. A single session of anodal cerebellar transcranial direct current stimulation can transiently improve symptoms in patients with ataxia and might represent a promising tool for future rehabilitative approaches. © 2015 International Parkinson and Movement Disorder Society.

Cardiovascular benefits from ancient grain bread consumption: findings from a double-blinded randomized crossover intervention trial.

PubMed

Sereni, Alice; Cesari, Francesca; Gori, Anna Maria; Maggini, Niccolò; Marcucci, Rossella; Casini, Alessandro; Sofi, Francesco

2017-02-01

Ancient grain varieties have been shown to have some beneficial effects on health. Forty-five clinically healthy subjects were included in a randomized, double-blinded crossover trial aimed at evaluating the effect of a replacement diet with bread derived from ancient grain varieties versus modern grain variety on cardiovascular risk profile. After 8 weeks of intervention, consumption of bread obtained by the ancient varieties showed a significant amelioration of various cardiovascular parameters. Indeed, the ancient varieties were shown to result in a significant reduction of total cholesterol, low-density lipoprotein (LDL)-cholesterol and blood glucose, whereas no significant differences during the phase with the modern variety were reported. Moreover, a significant increase in circulating endothelial progenitor cells were reported after the consumption of products made from the ancient "Verna" variety. The present results suggest that a dietary consumption of bread obtained from ancient grain varieties was effective in reducing cardiovascular risk factors.

Effects of pioglitazone on bone in postmenopausal women with impaired fasting glucose or impaired glucose tolerance: a randomized, double-blind, placebo-controlled study.

PubMed

Bone, Henry G; Lindsay, Robert; McClung, Michael R; Perez, Alfonso T; Raanan, Marsha G; Spanheimer, Robert G

2013-12-01

Meta-analyses of clinical studies have suggested an increased incidence of peripheral fractures in postmenopausal women with type 2 diabetes mellitus taking pioglitazone. The mechanism behind this apparent increase is unknown. The objective of the study was to examine the effects of pioglitazone on bone mineral density (BMD) and turnover. Twenty-five sites (in the United States) enrolled participants in this randomized, double-blind, placebo-controlled study. Postmenopausal women (n = 156) with impaired fasting glucose or impaired glucose tolerance participated in the study. The intervention consisted of pioglitazone 30 mg/d (n = 78) or placebo (n = 78), increased to 45 mg/d after 1 month, for 12 months of treatment total, followed by 6 months of washout/follow-up. Percentage changes from baseline to month 12 and from month 12 to month18 in BMD in total proximal femur (primary end point), total body, femoral neck, lumbar spine, and radius were measured. Least squares mean changes from baseline to month 12 in total proximal femur BMD were -0.69% for pioglitazone and -0.14% for placebo (P = .170). No statistically significant between-group differences were observed for any BMD or bone remodeling marker end point. We observed improved glycemic control and insulin sensitivity with pioglitazone treatment. In addition, pioglitazone appeared to increase body fat, which may affect bone density measurements, especially in the lumbar spine. One pioglitazone-treated and three placebo-treated women experienced confirmed fractures. Over 18 months, one pioglitazone-treated (1.3%) and eight placebo-treated women (10.3%) developed overt type 2 diabetes mellitus. The pattern and incidence of adverse events with pioglitazone were consistent with clinical experience with thiazolidinediones. Maximal-dose pioglitazone had no effects on BMD or bone turnover, while improving glycemic control as expected, in postmenopausal women with impaired fasting glucose or impaired glucose tolerance.

Chuanhu Anti-Gout Mixture versus Colchicine for Acute Gouty Arthritis: A Randomized, Double-Blind, Double-Dummy, Non-Inferiority Trial

PubMed Central

Wang, YanGang; Wang, Luan; Li, EnZe; Li, Yang; Wang, ZhongChao; Sun, XiaoFang; Yu, XiaoLong; Ma, Lin; Wang, YunLong; Wang, YouXin

2014-01-01

Background The Chuanhu anti-gout mixture has been used for many years in the treatment of gout in Chinese Traditional Medicine, and current methods for treatments for acute gouty arthritis have been either less effective or have had serious side effects. Methods In this 12-week, double-blind, double-dummy, non-inferiority study, outpatient individuals with newly diagnosed acute gouty arthritis were randomly assigned to receive Chuanhu anti-gout mixture or colchicine. Both the study investigators and the participants were masked to the treatment assignments. The primary outcome was the recurrence rate of acute gouty arthritis, and the secondary outcomes were changes in white blood cells (WHC) and C-reactive protein (CRP). This trial is registered at ISRCTN.org as trial ISRCTN65219941. Results A total of 176 patients were randomly assigned to receive either the Chuanhu anti-gout mixture or Colchicine. The overall recurrence rates in the Chuanhu anti-gout mixture group (CH group) and the Colchicine group (Col group) were 12.50% vs 14.77% (difference -2.22%, 95% confidence interval (95% CI): -10.78%~6.23%), meeting the predefined non-inferiority criterion of 15%, as did the data for WHC and CRP. The incidence of adverse events (mainly diarrhea) was less in the Col group than in the CH group (2.27% vs 28.41%, 95% CI 0.01~0.26). In addition, changes in blood uric acid, alanine aminotransferase, aspartate aminotransferase and creatinine in the CH group were significantly larger compared to those in the Col group (P<0.05). Conclusions The Chuanhu anti-gout mixture was non-inferior to colchicine for the treatment of acute gouty arthritis. The study suggested that the Chuanhu anti-gout mixture can be considered an alternative choice for the treatment of acute gouty arthritis because of its lower incidence of adverse events and its protection of kidney and renal function. PMID:25013367

Transdermal rotigotine in early stage Parkinson's disease: a randomized, double-blind, placebo-controlled trial.

PubMed

Mizuno, Yoshikuni; Nomoto, Masahiro; Kondo, Tomoyoshi; Hasegawa, Kazuko; Murata, Miho; Takeuchi, Masahiro; Ikeda, Junji; Tomida, Takayuki; Hattori, Nobutaka

2013-09-01

We conducted a randomized, double-blind, placebo-controlled trial to determine the safety and efficacy of transdermal rotigotine at doses up to 16 mg/24 hours in patients with early stage Parkinson's disease (PD) in Japan. Patients received once-daily rotigotine 2 to 16 mg/24 hours (mean dose, 12.8 mg/24 hours; n = 82) or placebo (n = 90) for 12 weeks. The primary endpoint was the change in Unified Parkinson's Disease Rating Scale (UPDRS) part II (activities of daily living) and part III (motor function) scores from baseline to the end of treatment. The mean (± standard deviation) changes in UPDRS part II and III scores were -8.4 ± 9.7 in the rotigotine group and -4.1 ± 8.2 in the placebo group and were significantly different (P = 0.002). More patients in the rotigotine group than in the placebo group had a ≥ 20% score reduction. No serious drug-related adverse events were reported. Rotigotine at doses up to 16 mg/24 hours was well tolerated and improved function in patients with early stage PD. © 2013 International Parkinson and Movement Disorder Society.

A booster dose of an inactivated enterovirus 71 vaccine in chinese young children: a randomized, double-blind, placebo-controlled clinical trial.

PubMed

Shenyu, Wang; Jingxin, Li; Zhenglun, Liang; Xiuling, Li; Qunying, Mao; Fanyue, Meng; Hua, Wang; Yuntao, Zhang; Fan, Gao; Qinghua, Chen; Yuemei, Hu; Xin, Yao; Huijie, Guo; Fengcai, Zhu

2014-10-01

A significant waning of enterovirus 71 (EV71) antibody titer after priming immunization with an inactivated EV71 vaccine implied the potential need for a booster dose. In this randomized, double-blind, placebo-controlled clinical trial, we recruited participants who had received at least 1 dose of priming EV71 vaccine in an early phase 2 clinical trial that was conducted in healthy infants and children aged 6-35 months. All participants were grouped according to the priming EV71 vaccine formulations (160 U, 320 U, and 640 U with adjuvant and 640 U without adjuvant) and then randomly assigned (ratio, 2:1) to receive a booster dose of vaccine or placebo within each formulation group. The primary end point was the geometric mean titer 28 days after the booster dose. A total of 773 participants were enrolled. Significantly greater immunological responses were induced by the booster shot of all 4 formulations of EV71 vaccine, compared with that induced by placebo (P < .0001). The frequencies of adverse reactions were similar between vaccine and placebo groups within each formulation group. A booster dose of EV71 vaccine 1 year after the priming EV71 immunization shows excellent immunogenicity and good safety profile. Clinical Trials Registration: NCT01734408. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Joint lavage associated with triamcinolone hexacetonide injection in knee osteoarthritis: a randomized double-blind controlled study.

PubMed

Parmigiani, Leandro; Furtado, Rita N V; Lopes, Roberta V; Ribeiro, Luiza H C; Natour, Jamil

2010-11-01

Compare the medium-term effectiveness and tolerance between joint lavage (JL) in combination with triamcinolone hexacetonide (TH) intra-articular injection (IAI) and IAI with TH alone for treatment of primary osteoarthritis (OA) of the knee. A randomized, double-blind, controlled study was carried out on 60 patients with primary OA of the knee, randomized into two intervention groups: JL/TH group, joint lavage in combination with TH intra-articular injection and TH group, TH intra-articular injection. Patients were followed for 12 weeks by a blind observer using the following outcome measurements: visual analogue scale for pain at rest and in movement, goniometry, WOMAC, Lequesne's index, timed 50-ft walk, perception of improvement, Likert scale for improvement assessment, use of nonsteroidal anti-inflammatory drugs and analgesics, and local side effects. There were no statistical differences in the inter-group analysis for any of the variables studied over the 12-week period. Although both groups demonstrated statistical improvement in the intra-group evaluation (except for Likert scale according to patient and the use of anti-inflammatory drugs). In the Kellgren-Lawrence scale (KL) 2 and 3 sub-analysis, there was a statistical difference regarding joint flexion among patients classified as KL 2, favoring the TH group (p=0.03). For the KL 3 patients, there were statistical differences favoring the JL/TH group regarding Lequesne (p=0.021), WOMAC pain score (p=0.01), and Likert scale according to the patient (p=0.028) and the physician (p=0.034). The combination of joint lavage and IAI with TH was not more effective than IAI with TH alone in the treatment of primary OA of the knee. However, KL 3 patients may receive a major benefit from this combination.

KINECT 3: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial of Valbenazine for Tardive Dyskinesia.

PubMed

Hauser, Robert A; Factor, Stewart A; Marder, Stephen R; Knesevich, Mary Ann; Ramirez, Paul M; Jimenez, Roland; Burke, Joshua; Liang, Grace S; O'Brien, Christopher F

2017-05-01

Tardive dyskinesia is a persistent movement disorder induced by dopamine receptor blockers, including antipsychotics. Valbenazine (NBI-98854) is a novel, highly selective vesicular monoamine transporter 2 inhibitor that demonstrated favorable efficacy and tolerability in the treatment of tardive dyskinesia in phase 2 studies. This phase 3 study further evaluated the efficacy, safety, and tolerability of valbenazine as a treatment for tardive dyskinesia. This 6-week, randomized, double-blind, placebo-controlled trial included patients with schizophrenia, schizoaffective disorder, or a mood disorder who had moderate or severe tardive dyskinesia. Participants were randomly assigned in a 1:1:1 ratio to once-daily placebo, valbenazine at 40 mg/day, or valbenazine at 80 mg/day. The primary efficacy endpoint was change from baseline to week 6 in the 80 mg/day group compared with the placebo group on the Abnormal Involuntary Movement Scale (AIMS) dyskinesia score (items 1-7), as assessed by blinded central AIMS video raters. Safety assessments included adverse event monitoring, laboratory tests, ECG, and psychiatric measures. The intent-to-treat population included 225 participants, of whom 205 completed the study. Approximately 65% of participants had schizophrenia or schizoaffective disorder, and 85.5% were receiving concomitant antipsychotics. Least squares mean change from baseline to week 6 in AIMS dyskinesia score was -3.2 for the 80 mg/day group, compared with -0.1 for the placebo group, a significant difference. AIMS dyskinesia score was also reduced in the 40 mg/day group (-1.9 compared with -0.1). The incidence of adverse events was consistent with previous studies. Once-daily valbenazine significantly improved tardive dyskinesia in participants with underlying schizophrenia, schizoaffective disorder, or mood disorder. Valbenazine was generally well tolerated, and psychiatric status remained stable. Longer trials are necessary to understand the long-term effects

Tribulus terrestris for treatment of sexual dysfunction in women: randomized double-blind placebo - controlled study.

PubMed

Akhtari, Elham; Raisi, Firoozeh; Keshavarz, Mansoor; Hosseini, Hamed; Sohrabvand, Farnaz; Bioos, Soodabeh; Kamalinejad, Mohammad; Ghobadi, Ali

2014-04-28

Tribulus terrestris as a herbal remedy has shown beneficial aphrodisiac effects in a number of animal and human experiments. This study was designed as a randomized double-blind placebo-controlled trial to assess the safety and efficacy of Tribulus terrestris in women with hypoactive sexual desire disorder during their fertile years. Sixty seven women with hypoactive sexual desire disorder were randomly assigned to Tribulus terrestris extract (7.5 mg/day) or placebo for 4 weeks. Desire, arousal, lubrication, orgasm, satisfaction, and pain were measured at baseline and after 4 weeks after the end of the treatment by using the Female Sexual Function Index (FSFI). Two groups were compared by repeated measurement ANOVA test. Thirty women in placebo group and thirty women in drug group completed the study. At the end of the fourth week, patients in the Tribulus terrestris group had experienced significant improvement in their total FSFI (p < 0.001), desire (p < 0.001), arousal (p = 0.037), lubrication (p < 0.001), satisfaction (p < 0.001) and pain (p = 0.041) domains of FSFI. Frequency of side effects was similar between the two groups. Tribulus terrestris may safely and effectively improve desire in women with hypoactive sexual desire disorder. Further investigation of Tribulus terrestris in women is warranted.

Tribulus terrestris for treatment of sexual dysfunction in women: randomized double-blind placebo - controlled study

PubMed Central

2014-01-01

Background Tribulus terrestris as a herbal remedy has shown beneficial aphrodisiac effects in a number of animal and human experiments. This study was designed as a randomized double-blind placebo-controlled trial to assess the safety and efficacy of Tribulus terrestris in women with hypoactive sexual desire disorder during their fertile years. Sixty seven women with hypoactive sexual desire disorder were randomly assigned to Tribulus terrestris extract (7.5 mg/day) or placebo for 4 weeks. Desire, arousal, lubrication, orgasm, satisfaction, and pain were measured at baseline and after 4 weeks after the end of the treatment by using the Female Sexual Function Index (FSFI). Two groups were compared by repeated measurement ANOVA test. Results Thirty women in placebo group and thirty women in drug group completed the study. At the end of the fourth week, patients in the Tribulus terrestris group had experienced significant improvement in their total FSFI (p < 0.001), desire (p < 0.001), arousal (p = 0.037), lubrication (p < 0.001), satisfaction (p < 0.001) and pain (p = 0.041) domains of FSFI. Frequency of side effects was similar between the two groups. Conclusions Tribulus terrestris may safely and effectively improve desire in women with hypoactive sexual desire disorder. Further investigation of Tribulus terrestris in women is warranted. PMID:24773615

Static magnetic therapy does not decrease pain or opioid requirements: a randomized double-blind trial.

PubMed

Cepeda, M Soledad; Carr, Daniel B; Sarquis, Tony; Miranda, Nelcy; Garcia, Ricardo J; Zarate, Camilo

2007-02-01

A growing multibillion dollar industry markets magnetic necklaces, bracelets, bands, insoles, back braces, mattresses, etc., for pain relief, although there is little evidence for their efficacy. We sought to evaluate the effect of magnetic therapy on pain intensity and opioid requirements in patients with postoperative pain. We designed a randomized, double-blind, controlled trial. One-hundred-sixty-five patients older than 12 yr of age were randomized to magnetic (n = 81) or sham therapy (n = 84) upon reporting moderate-to-severe pain in the postanesthesia care unit. Devices were placed over the surgical incision and left in place for 2 h. Patients rated their pain intensity on a 0-10 scale every 10 min and received incremental doses of morphine until pain intensity was < or =4 of 10. Pain intensity levels were similar in both groups. The magnet group had on average 0.04 U more pain intensity (95% confidence interval, -0.4 to 0.5) than the sham group. Opioid requirements also were similar in both groups. The active magnet group required 1.5 mg more morphine (95% confidence interval, -1.8 to 4.0) than the sham magnet group. Magnetic therapy lacks efficacy in controlling acute postoperative pain intensity levels or opioid requirements and should not be recommended for pain relief in this setting.

Short-term tibolone does not interfere with endothelial function: a double-blinded, randomized, controlled trial.

PubMed

Celani, M F S; Hurtado, R; Brandão, A H F; Maciel da Fonseca, A M R; Geber, S

2016-06-01

Objective To evaluate the effect of short-term hormone replacement therapy with tibolone 2.5 mg daily on endothelial function of healthy postmenopausal women, using flow-mediated dilation (FMD) of the brachial artery. Methods We performed a randomized, double-blinded, placebo-controlled study. A total of 100 healthy postmenopausal women were randomly allocated to receive tibolone (n = 50) or placebo (n = 50) for 28 days. Measurement of the FMD of the brachial artery was performed before and after the use of tibolone and placebo. Results A total of 31 women completed the study in the tibolone group, and 32 women completed the study in the control group. The results of the FMD measurements obtained from the women in the two groups before treatment were similar (0.018 and 0.091, for tibolone and placebo, p = 0.57). The values of the FMD in women who used tibolone and placebo, before and after the treatment, were similar in both groups. The numbers of women who presented an increase in the values of the FMD in both groups were also similar. Conclusion Our results demonstrate that the administration of 2.5 mg tibolone to healthy postmenopausal women for 28 days does not promote endothelial-dependent vasodilation, measured by FMD of the brachial artery.

Effects of dehydroepiandrosterone supplementation during stressful military training: a randomized, controlled, double-blind field study.

PubMed

Taylor, Marcus K; Padilla, Genieleah A; Stanfill, Katherine E; Markham, Amanda E; Khosravi, Jasmine Y; Ward, Michael D Dial; Koehler, Matthew M

2012-01-01

Dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) are anabolic prehormones involved in the synthesis of testosterone. Both have been shown to exert neuroprotective effects during stress. In this randomized, controlled, double-blind field study, we examined the effects of a 12-day DHEA regimen on stress indices in military men undergoing survival training. Forty-eight men were randomized to either a DHEA treatment group or placebo control group. The treatment group received 50 mg of oral DHEA supplementation daily for 5 days during classroom training followed by 7 days of 75 mg during stressful field operations. Control subjects received identical placebo pills. Salivary assays (DHEA[S], testosterone, and cortisol) were conducted at four time points: distal pre-stress (T1), proximal pre-stress (T2), mock-captivity stress (T3), and 24 h recovery (T4). Subjective distress was also assessed at T1, T3, and T4. As expected, DHEA treatment resulted in higher salivary concentrations of DHEA and DHEAS during daily living, mock-captivity stress, and recovery. Similar patterns were observed for salivary markers of anabolic balance: DHEA/cortisol, DHEAS/cortisol, and testosterone/cortisol concentration ratios. Despite notable time effects, no group differences emerged for subjective distress. A brief, low dose DHEA regimen yielded large increases in salivary DHEA(S) concentrations and enhanced anabolic balance throughout sustained military stress. These physiological changes did not extrapolate to subjective distress.

Tapentadol immediate-release for acute postbunionectomy pain: a phase 3, randomized, double-blind, placebo-controlled, parallel-group study in Taiwan.

PubMed

Chen, Yeung-Jen; Chiang, Chao-Ching; Huang, Peng-Ju; Huang, Jason; Karcher, Keith; Li, Honglan

2015-11-01

To evaluate the efficacy and safety of tapentadol immediate-release (IR) for treating acute pain following orthopedic bunionectomy surgery in a Taiwanese population. This was a phase 3, randomized, double-blind, placebo-controlled, parallel-group bridging study in which Taiwanese patients (N = 60) with moderate-to-severe pain following bunionectomy were randomized (1:1:1) to receive tapentadol IR 50 or 75 mg or placebo orally every 4-6 hours over a 72 hour period. The primary endpoint was the sum of pain intensity difference over 48 hours (SPID48), analyzed using analysis of variance. Out of 60 patients randomized (mainly women [96.7%]; median age 44 years), 41 (68.3%) completed the treatment. Mean SPID48 values were significantly higher for tapentadol IR (p ≤ 0.006: 50 mg, p ≤ 0.004: 75 mg) compared with placebo. Between-group differences in LS means of SPID48 (vs. placebo) were tapentadol IR 50 mg: 105.6 (95% CI: 32.0; 179.2); tapentadol IR 75 mg: 126.6 (95% CI: 49.5; 203.7). Secondary endpoints including SPID at 12, 24, and 72 hours, time to first use of rescue medication, cumulative distribution of responder rates, total pain relief and sum of total pain relief and sum of pain intensity difference at 12, 24, 48, and 72 hours, and patient global impression of change showed numerically better results supporting that tapentadol IR (50 and 75 mg) was more efficacious than placebo in relieving acute pain. The most frequent treatment emergent adverse events reported in ≥ 10% patients in either group were dizziness, nausea, and vomiting. A limitation of this study may possibly include more controlled patient monitoring through 4-6 hour dosing intervals, which reflects optimal conditions and thus may not approximate real-world clinical practice. However, all treatment groups would be equally affected by such bias of frequent monitoring, if any, since it was a randomized and double-blind study. Tapentadol IR treatment significantly relieved acute postoperative

A new universal simplified adhesive: 36-Month randomized double-blind clinical trial.

PubMed

Loguercio, Alessandro D; de Paula, Eloisa Andrade; Hass, Viviane; Luque-Martinez, Issis; Reis, Alessandra; Perdigão, Jorge

2015-09-01

It is still debatable which technique should be used with universal adhesives, either etch-and-rinse (wet or dry) or self-etch strategy (with or without selective enamel etching). To evaluate the 36-month clinical performance of Scotchbond Universal Adhesive (SU, 3M ESPE) in non-carious cervical lesions (NCCLs) using two evaluation criteria. Thirty-nine patients participated in this study. Two-hundred restorations were assigned to four groups: ERm: etch-and-rinse+moist dentin; ERd: etch-and-rinse+dry dentin; Set: selective enamel etching; and SE: self-etch. The same composite resin was inserted for all restorations in up to 3 increments. The restorations were evaluated at baseline and at 6-, 18-, and 36-months using both the FDI and the USPHS criteria. Statistical analyses were performed with Friedman repeated measures ANOVA by rank and McNemar test for significance in each pair (α=0.05). Eight restorations (ERm: 1; ERd: 1; Set: 1 and SE: 5) were lost after 36 months, but only significant for SE when compared with baseline (p=0.02 for either criteria). Marginal staining occurred in 6.8% of the restorations (groups ERm, ERd, and Set) and 17.5% of the restorations (group SE), with significant difference for each group when compared with baseline using the FDI criteria (p<0.04), while statistical significance was reached only for SE when compared with baseline using the USPHS criteria (p<0.03). Twenty-eight and 49 restorations were scored as bravo for marginal adaptation using the USPHS and FDI criteria, respectively, with significant difference for each group when compared with baseline (p<0.05). While there was no statistical difference among bonding strategies when a universal adhesive was used, there were signs of degradation when the universal adhesive was applied in SE mode. The FDI criteria remain more sensitive than the USPHS criteria, especially for the criteria marginal staining and marginal adaptation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Nicergoline in mild to moderate dementia. A multicenter, double-blind, placebo-controlled study.

PubMed

Battaglia, A; Bruni, G; Ardia, A; Sacchetti, G

1989-04-01

In view of some controversies still existing about the real efficacy of ergot derivatives in the management of dementia, a double-blind, randomized, parallel group trial extending up to 6 months was carried out to compare the effects of nicergoline, 60 mg daily, and placebo in 315 patients suffering from mild to moderate dementia. Clinical evaluation was performed by the SCAG scale. The trial, which included a 1-month placebo run-in period, showed that both placebo and nicergoline were associated with some degree of improvement. The effect of nicergoline, however, was significantly greater and more sustained, steadily increasing with time. In particular, the difference between nicergoline and placebo in mean total SCAG score was 5.5 at 3 months (95% confidence interval: 3.6-7.4) and increased to 9.8 at 6 months (95% confidence interval: 7.8-11.8). A comparison of nicergoline versus placebo in the frequencies of changes in each item of the SCAG showed also a significant difference at 6 months, the percent of patients displaying an improvement by at least 2 points ranging from 13.5 (bothersome) to 30.2 (disorientation) in nicergoline group, against 4.1 (self-care) to 14.3 (fatigue) in placebo group. The safety of nicergoline, as judged by hemodynamic changes and drug-related adverse reactions, was quite satisfactory.

Effect of probiotics (Saccharomyces boulardii) on microbial translocation and inflammation in HIV-treated patients: a double-blind, randomized, placebo-controlled trial.

PubMed

Villar-García, Judit; Hernández, Juan J; Güerri-Fernández, Robert; González, Alicia; Lerma, Elisabet; Guelar, Ana; Saenz, David; Sorlí, Lluisa; Montero, Milagro; Horcajada, Juan P; Knobel Freud, Hernando

2015-03-01

Microbial translocation has been associated with an increase in immune activation and inflammation in HIV infection despite effective highly active antiretroviral therapy. It has been shown that some probiotics have a beneficial effect by reducing intestinal permeability and, consequently, microbial translocation. To assess changes in microbial translocation and inflammation after treatment with probiotics (Saccharomyces boulardii) in HIV-1-infected patients with virologic suppression. A double-blind, randomized, placebo-controlled trial was conducted in 44 nonconsecutive HIV-1-infected patients with viral load of <20 copies per milliliter for at least 2 years. Patients were randomized to oral supplementation with probiotics or placebo during 12 weeks. Markers of microbial translocation (lipopolysaccharide-binding protein [LBP] and soluble CD14), inflammation (interleukin 6 [IL-6], tumor necrosis factor alpha, interferon gamma, high-sensitivity C-reactive protein), and immunological and clinical data were determined before and after the intervention and 3 months after treatment discontinuation. Quantitative variables were compared using the Mann-Whitney U test, and categorical variables were compared using the Fisher exact test. After 12 weeks of treatment, differences between the probiotic arm and the placebo arm were observed in LBP values (-0.30 vs +0.70 pg/mL) and IL-6 (-0.60 vs +0.78 pg/mL). These differences were also noted at 3 months after treatment withdrawal. Qualitative analysis was performed, defining a variable as "decreased" or "increased" from baseline LBP. A significant decrease of LBP at 12 weeks of treatment was observed (57.9% patients in the probiotic group vs 6.2% in the placebo group, P = 0.002). Treatment with S. boulardii decreases microbial translocation (LBP) and inflammation parameters (IL-6) in HIV-1-infected patients with long-term virologic suppression.

Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial

PubMed Central

Griffiths, Roland R; Johnson, Matthew W; Carducci, Michael A; Umbricht, Annie; Richards, William A; Richards, Brian D; Cosimano, Mary P; Klinedinst, Margaret A

2016-01-01

Cancer patients often develop chronic, clinically significant symptoms of depression and anxiety. Previous studies suggest that psilocybin may decrease depression and anxiety in cancer patients. The effects of psilocybin were studied in 51 cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety. This randomized, double-blind, cross-over trial investigated the effects of a very low (placebo-like) dose (1 or 3 mg/70 kg) vs. a high dose (22 or 30 mg/70 kg) of psilocybin administered in counterbalanced sequence with 5 weeks between sessions and a 6-month follow-up. Instructions to participants and staff minimized expectancy effects. Participants, staff, and community observers rated participant moods, attitudes, and behaviors throughout the study. High-dose psilocybin produced large decreases in clinician- and self-rated measures of depressed mood and anxiety, along with increases in quality of life, life meaning, and optimism, and decreases in death anxiety. At 6-month follow-up, these changes were sustained, with about 80% of participants continuing to show clinically significant decreases in depressed mood and anxiety. Participants attributed improvements in attitudes about life/self, mood, relationships, and spirituality to the high-dose experience, with >80% endorsing moderately or greater increased well-being/life satisfaction. Community observer ratings showed corresponding changes. Mystical-type psilocybin experience on session day mediated the effect of psilocybin dose on therapeutic outcomes. Trial Registration ClinicalTrials.gov identifier: NCT00465595 PMID:27909165

Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial.

PubMed

Griffiths, Roland R; Johnson, Matthew W; Carducci, Michael A; Umbricht, Annie; Richards, William A; Richards, Brian D; Cosimano, Mary P; Klinedinst, Margaret A

2016-12-01

Cancer patients often develop chronic, clinically significant symptoms of depression and anxiety. Previous studies suggest that psilocybin may decrease depression and anxiety in cancer patients. The effects of psilocybin were studied in 51 cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety. This randomized, double-blind, cross-over trial investigated the effects of a very low (placebo-like) dose (1 or 3 mg/70 kg) vs. a high dose (22 or 30 mg/70 kg) of psilocybin administered in counterbalanced sequence with 5 weeks between sessions and a 6-month follow-up. Instructions to participants and staff minimized expectancy effects. Participants, staff, and community observers rated participant moods, attitudes, and behaviors throughout the study. High-dose psilocybin produced large decreases in clinician- and self-rated measures of depressed mood and anxiety, along with increases in quality of life, life meaning, and optimism, and decreases in death anxiety. At 6-month follow-up, these changes were sustained, with about 80% of participants continuing to show clinically significant decreases in depressed mood and anxiety. Participants attributed improvements in attitudes about life/self, mood, relationships, and spirituality to the high-dose experience, with >80% endorsing moderately or greater increased well-being/life satisfaction. Community observer ratings showed corresponding changes. Mystical-type psilocybin experience on session day mediated the effect of psilocybin dose on therapeutic outcomes. ClinicalTrials.gov identifier: NCT00465595. © The Author(s) 2016.

A randomized double-blind study of testosterone replacement therapy or placebo in testicular cancer survivors with mild Leydig cell insufficiency (Einstein-intervention).

PubMed

Bandak, Mikkel; Jørgensen, Niels; Juul, Anders; Lauritsen, Jakob; Kreiberg, Michael; Oturai, Peter Sandor; Helge, Jørn Wulff; Daugaard, Gedske

2017-07-03

Elevated serum levels of luteinizing hormone and slightly decreased serum levels of testosterone (mild Leydig cell insufficiency) is a common hormonal disturbance in testicular cancer (TC) survivors. A number of studies have shown that low serum levels of testosterone is associated with low grade inflammation and increased risk of metabolic syndrome. However, so far, no studies have evaluated whether testosterone substitution improves metabolic dysfunction in TC survivors with mild Leydig cell insufficiency. This is a single-center, randomized, double-blind, placebo-controlled study, designed to evaluate the effect of testosterone replacement therapy in TC survivors with mild Leydig cell insufficiency. Seventy subjects will be randomized to receive either testosterone replacement therapy or placebo. The subjects will be invited for an information meeting where informed consent will be obtained. Afterwards, a 52-weeks treatment period begins in which study participants will receive a daily dose of transdermal testosterone or placebo. Dose adjustment will be made three times during the initial 8 weeks of the study to a maximal daily dose of 40 mg of testosterone in the intervention arm. Evaluation of primary and secondary endpoints will be performed at baseline, 26 weeks post-randomization, at the end of treatment (52 weeks) and 3 months after completion of treatment (week 64). This study is the first to investigate the effect of testosterone substitution in testicular cancer survivors with mild Leydig cell insufficiency. If positive, it may change the clinical handling of testicular cancer survivors with borderline low levels of testosterone. ClinicalTrials.gov : NCT02991209 (November 25, 2016).

Early botulinum toxin treatment for spastic pes equinovarus--a randomized double-blind placebo-controlled study.

PubMed

Fietzek, U M; Kossmehl, P; Schelosky, L; Ebersbach, G; Wissel, J

2014-08-01

Spastic pes equinovarus is a frequent pathological posture of the lower extremity. Botulinum toxin (BoNT/A) has been successfully applied to treat lower limb spasticity. However, the best time to initiate treatment remains unclear. A beneficial effect of an early treatment has been suggested in previous studies. A single-centre double-blind randomized placebo-controlled trial was performed to investigate the efficacy of BoNT/A to reduce muscle hypertonicity at the ankle. Fifty-two patients with unilateral or bilateral spastic pes equinovarus with a modified Ashworth score (mAS) of at least 1+ after stroke, traumatic brain injury or hypoxic encephalopathy were allocated to receive either BoNT/A or placebo treatment. A second, open injection was optional at week 12. Patients received unilateral or bilateral injections with 230 or 460 U onabotulinumtoxinA, respectively. The course of the mAS was explored during the open study phase. Patients who had received BoNT/A treatment had lower mAS compared with placebo at week 12 (P < 0.01). During the open label phase, patients from the placebo group showed further deterioration of muscle tone despite starting from a similar baseline and receiving BoNT treatment. Spastic feet that had received BoNT/A in the first cycle had comparatively lower mAS scores over all follow-up data and at week 24 (P < 0.01). The study demonstrates a reduction of muscular hypertonicity in spastic pes equines with BoNT/A treatment given during the first 3 months after the lesion. Exploratory analyses of the course of muscular hypertonicity during the open phase favour earlier to later treatment. © 2014 The Author(s) European Journal of Neurology © 2014 EAN.

A double-blind randomized controlled trial of N-acetylcysteine in cannabis-dependent adolescents

PubMed Central

Gray, Kevin M.; Carpenter, Matthew J.; Baker, Nathaniel L.; DeSantis, Stacia M.; Kryway, Elisabeth; Hartwell, Karen J.; McRae-Clark, Aimee L.; Brady, Kathleen T.

2012-01-01

Objective Preclinical findings suggest that the over-the-counter supplement N-acetylcysteine, via glutamate modulation in the nucleus accumbens, holds promise as a pharmacotherapy targeting substance dependence. We sought to investigate N-acetylcysteine as a novel cannabis cessation treatment in adolescents, a vulnerable group for whom existing treatments have limited efficacy. Method In this 8-week double-blind randomized placebo-controlled trial, treatment-seeking cannabis-dependent adolescents (age 15-21, N = 116) received N-acetylcysteine (1200 mg) or placebo twice daily, each added to a contingency management intervention and brief (≤10 minute) weekly cessation counseling. The primary efficacy measure was the odds of negative weekly urine cannabinoid tests during treatment among participants receiving N-acetylcysteine versus placebo, via intent-to-treat analysis. The primary tolerability measure was frequency of adverse events, compared by treatment group. Results N-acetylcysteine was well tolerated with minimal adverse events. N-acetylcysteine participants had more than twice the odds, compared to placebo participants, of submitting negative urine cannabinoid tests during treatment (odds ratio = 2.4, [95% CI: 1.1-5.2], p = 0.029). Exploratory secondary abstinence outcomes numerically favored N-acetylcysteine, but were not statistically significant. Conclusions This is the first randomized trial of pharmacotherapy for cannabis dependence in any age group yielding a positive primary cessation outcome via intent-to-treat analysis. Findings support N-acetylcysteine as a pharmacotherapy to complement psychosocial treatment for cannabis dependence in adolescents. Further research is needed to replicate these findings and explore the efficacy of N-acetylcysteine across a variety of treatment contexts and outcomes. Trial Registration clinicaltrials.gov identifier: NCT 01005810 PMID:22706327

Metabolic and hormonal effects of caffeine: randomized, double-blind, placebo-controlled crossover trial.

PubMed

MacKenzie, Todd; Comi, Richard; Sluss, Patrick; Keisari, Ronit; Manwar, Simone; Kim, Janice; Larson, Robin; Baron, John A

2007-12-01

In short-term studies, caffeine has been shown to increase insulin levels, reduce insulin sensitivity, and increase cortisol levels. However, epidemiological studies have indicated that long-term consumption of beverages containing caffeine such as coffee and green tea is associated with a reduced risk of type 2 diabetes mellitus. There is a paucity of randomized studies addressing the metabolic and hormonal effects of consuming caffeine over periods of more than 1 day. We evaluated the effect of oral intake of 200 mg of caffeine taken twice a day for 7 days on glucose metabolism, as well as on serum cortisol, dehydroepiandrosterone (DHEA), and androstenedione, and on nighttime salivary melatonin. A double-blind, randomized, placebo-controlled crossover study with periods of 7 days and washouts of 5 days comparing caffeine with placebo capsules was conducted. Participants were 16 healthy adults aged 18 to 22 years with a history of caffeine consumption. Blood samples from each subject were assayed for glucose, insulin, serum cortisol, DHEA, and androstenedione on the eighth day of each period after an overnight fast. Nighttime salivary melatonin was also measured. Insulin levels were significantly higher (by 1.80 microU/mL; 95% confidence interval, 0.33-3.28) after caffeine intake than after placebo. The homeostasis model assessment index of insulin sensitivity was reduced by 35% (95% confidence interval, 7%-62%) by caffeine. There were no differences in glucose, DHEA, androstenedione, and melatonin between treatment periods. This study provides evidence that daily caffeine intake reduces insulin sensitivity; the effect persists for at least a week and is evident up to 12 hours after administration.

Differences in taste between three polyethylene glycol preparations: a randomized double-blind study.

PubMed

Lam, Tze J; Mulder, Chris Jj; Felt-Bersma, Richelle Jf

2011-01-01

Patients suffering from chronic constipation require long-term, regular therapy with laxatives. Literature regarding patient preference and acceptance in polyethylene glycol preparations is scarce. Therefore, this research aimed to identify preference between the three polyethylene glycol 3350, namely Molaxole(®), Movicol(®), and Laxtra Orange(®). Furthermore, taste is one of the most important factors leading to patients' adherence, particularly when the treatment lasts for a long time. In this randomized, cross-over double-blind study, 100 volunteers were recruited by advertisement. The volunteers were invited to taste the preparations and grade the taste using a five-point hedonic scale (extremely poor taste [1] to extremely good taste [5]). The volunteers were then asked to choose the most palatable preparation. One hundred volunteers with a mean age of 35 years (range 20-61) were randomized (76 females). Molaxole(®), Movicol(®), and Laxtra Orange(®) had a mean hedonic score of 2.76 (SD: 0.82), 2.81 (SD: 0.76) and 3.12 (SD: 0.82) respectively. The hedonic taste score for Laxtra Orange(®) was significantly better than Molaxole(®) (P = 0.001) and Movicol(®) (P = 0.001). No difference was found between Molaxole(®) and Movicol(®) (P = 0.61). Molaxole(®) was the most preferred preparation for 19 volunteers (19%), Movicol(®) for 24 volunteers (25%) and Laxtra Orange(®) for 55 volunteers (56%). Two volunteers had no preference. The order in which volunteers tested the preparations had no influence on the taste results. No significant differences in age or gender were observed. Laxtra Orange(®) was most palatable preparation. This may have implications for adherence in patients with chronic constipation.

Hyoscine N-Butylbromide for Preventing Propofol Injection Pain: A Randomized, Placebo-Controlled and Double-Blind Study

PubMed Central

Sargın, Mehmet; Uluer, Mehmet Selçuk; Aydoğan, Eyüp

2018-01-01

Objective In this study, the aim was to investigate the effect of hyoscine N-butylbromide (HnBB) pretreatment on pain during propofol injection. Subjects and Methods In this prospective, randomized, placebo-controlled and double-blind trial, 60 patients scheduled to undergo routine outpatient surgery under general anesthesia were randomly allocated to 2 groups, the HnBB (n = 30) and sodium chloride (n = 30) groups. Twenty seconds after the injection of 20 mg HnBB or 0.9 % sodium chloride, a 50-mg dose of propofol was injected in 2–3 s. Ten seconds later, the pain intensity was assessed using a 4-point scale: no pain (0), mild (1), moderate (2), and severe (3) pain. The Student t test was used for the analysis of parametric data and the Pearson χ2 test for categorical data. Results The occurrence of pain in the HnBB group (43.3%) was significantly lower than the control group (73.3%) (p < 0.018). Of the 30 patients in each group, 10 in the control group and 3 in the HnBB group experienced severe pain (p = 0.001). Conclusions Pretreatment with 20 mg HnBB significantly reduced propofol injection pain compared to placebo. PMID:29402789