Rupatadine does not potentiate the CNS depressant effects of lorazepam: randomized, double-blind, crossover, repeated dose, placebo-controlled study

PubMed Central

García-Gea, Consuelo; Ballester, Maria Rosa; Martínez, Juan; Antonijoan, Rosa Maria; Donado, Esther; Izquierdo, Iñaki; Barbanoj, Manuel-José

2010-01-01

AIM The main objective was to assess whether benzodiazepine intake when rupatadine plasma concentrations were at steady-state would increase the CNS depressant effects. Rupatadine is a new H1-antihistamine which also inhibits platelet activating factor (PAF) release and has been shown to be clinically effective at doses of 10 mg. METHODS Sixteen healthy young volunteers took part in a crossover, randomized, double-blind, placebo controlled trial comprising two experimental periods (repeated administration for 7 days of rupatadine 10 mg or placebo as single oral daily doses, separated by a washout of 14 days). On days 5 and 7, according to a fully balanced design, a single oral dose of lorazepam 2 mg or placebo was added. CNS effects were evaluated on these days by seven objective tests of psychomotor performance and eight subjective visual analogue scales (VAS) at pre-dose and several times after drug intake. Four treatment conditions were evaluated: placebo, rupatadine 10 mg, lorazepam 2 mg and rupatadine 10 mg + lorazepam 2 mg. RESULTS Significant CNS effects, either impairment of psychomotor performance or subjective sedation, were observed when lorazepam was administered, either alone or in combination with steady state concentrations of rupatadine. No significant differences were found between these two conditions. In addition, rupatadine was not different from placebo. All treatments were well tolerated. CONCLUSION Repeated doses of rupatadine (10 mg orally) did not enhance the CNS depressant effects of lorazepam (2 mg orally, single dose) either in objective psychomotor tasks or in subjective evaluations. PMID:20565458

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

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.

High and low negative pressure suction techniques in EUS-guided fine-needle tissue acquisition by using 25-gauge needles: a multicenter, prospective, randomized, controlled trial.

PubMed

Kudo, Taiki; Kawakami, Hiroshi; Hayashi, Tsuyoshi; Yasuda, Ichiro; Mukai, Tsuyoshi; Inoue, Hiroyuki; Katanuma, Akio; Kawakubo, Kazumichi; Ishiwatari, Hirotoshi; Doi, Shinpei; Yamada, Reiko; Maguchi, Hiroyuki; Isayama, Hiroyuki; Mitsuhashi, Tomoko; Sakamoto, Naoya

2014-12-01

EUS-guided FNA (EUS-FNA) has a high diagnostic accuracy for pancreatic diseases. However, although most reports have typically focused on cytology, histological tissue quality has rarely been investigated. The effectiveness of EUS-FNA combined with high negative pressure (HNP) suction was recently indicated for tissue acquisition, but has not thus far been tested in a prospective, randomized clinical trial. To evaluate the adequacy of EUS-FNA with HNP for the histological diagnosis of pancreatic lesions by using 25-gauge needles. Prospective, single-blind, randomized, controlled crossover trial. Seven tertiary referral centers. Patients referred for EUS-FNA of pancreatic solid lesions. From July 2011 to April 2012, 90 patients underwent EUS-FNA of pancreatic solid masses by using normal negative pressure (NNP) and HNP with 2 respective passes. The order of the passes was randomized, and the sample adequacy, quality, and histology were evaluated by a single expert pathologist. EUS-FNA by using NNP and HNP. The adequacy of tissue acquisition and the accuracy of histological diagnoses made by using the EUS-FNA technique with HNP. We found that 72.2% (65/90) and 90% (81/90) of the specimens obtained using NNP and HNP, respectively, were adequate for histological diagnosis (P = .0003, McNemar test). For 73.3% (66/90) and 82.2% (74/90) of the specimens obtained by using NNP and HNP, respectively, an accurate diagnosis was achieved (P = .06, McNemar test). Pancreatitis developed in 1 patient after this procedure, which subsided with conservative therapy. This was a single-blinded, crossover study. Biopsy procedures that combine the EUS-FNA with HNP techniques are superior to EUS-FNA with NNP procedures for tissue acquisition. ( UMIN000005939.). Copyright © 2014 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

A randomized, controlled cross-over trial of dermally-applied lavender (Lavandula angustifolia) oil as a treatment of agitated behaviour in dementia.

PubMed

O'Connor, Daniel W; Eppingstall, Barbara; Taffe, John; van der Ploeg, Eva S

2013-11-13

Lavender essential oil shows evidence of sedative properties in neurophysiological and animal studies but clinical trials of its effectiveness as a treatment of agitation in people with dementia have shown mixed results. Study methods have varied widely, however, making comparisons hazardous. To help remedy previous methodological shortcomings, we delivered high grade lavender oil in specified amounts to nursing home residents whose agitated behaviours were recorded objectively. 64 nursing home residents with frequent physically agitated behaviours were entered into a randomized, single-blind cross-over trial of dermally-applied, neurophysiologically active, high purity 30% lavender oil versus an inactive control oil. A blinded observer counted the presence or absence of target behaviours and rated participants' predominant affect during each minute for 30 minutes prior to exposure and for 60 minutes afterwards. Lavender oil did not prove superior to the control oil in reducing the frequency of physically agitated behaviours or in improving participants' affect. Studies of essential oils are constrained by their variable formulations and uncertain pharmacokinetics and so optimal dosing and delivery regimens remain speculative. Notwithstanding this, topically delivered, high strength, pure lavender oil had no discernible effect on affect and behaviour in a well-defined clinical sample. Australian and New Zealand Clinical Trials Registry (ACTRN 12609000569202).

A randomized single blind crossover trial comparing leather and commercial wrist splints for treating chronic wrist pain in adults

PubMed Central

Thiele, Jill; Nimmo, Rachel; Rowell, Wendy; Quinn, Stephen; Jones, Graeme

2009-01-01

Background To compare the effectiveness of a custom-made leather wrist splint (LS) with a commercially available fabric splint (FS) in adults with chronic wrist pain. Methods Participants (N = 25, mean age = 54) were randomly assigned to treatment order in a 2-phase crossover trial. Splints were worn for 2 weeks, separated by a one-week washout period. Outcomes were assessed at baseline and after each splint phase using the Australian/Canadian Osteoarthritis Hand Index (AUSCAN), the Canadian Occupational Performance Measure (COPM) and Jamar dynamometer by an observer blinded to treatment allocation. Results Both styles of wrist splint significantly reduced pain (effect size LS 0.79, FS 0.43), improved hand function and increased grip strength compared to baseline (all p < 0.05) with no increase in wrist stiffness. There was a consistent trend for the LS to be superior to the FS but this was statistically significant only for patient perceived occupational performance (p = 0.008) and satisfaction (p = 0.015). Lastly, 72% of patients preferred the custom-made leather splint compared to the commercially available splint. Conclusion Leather wrist splints were superior to a commercially available fabric splint for the short-term relief of pain and dysfunction. PMID:19843345

Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial.

PubMed

Ross, Stephen; Bossis, Anthony; Guss, Jeffrey; Agin-Liebes, Gabrielle; Malone, Tara; Cohen, Barry; Mennenga, Sarah E; Belser, Alexander; Kalliontzi, Krystallia; Babb, James; Su, Zhe; Corby, Patricia; Schmidt, Brian L

2016-12-01

Clinically significant anxiety and depression are common in patients with cancer, and are associated with poor psychiatric and medical outcomes. Historical and recent research suggests a role for psilocybin to treat cancer-related anxiety and depression. In this double-blind, placebo-controlled, crossover trial, 29 patients with cancer-related anxiety and depression were randomly assigned and received treatment with single-dose psilocybin (0.3 mg/kg) or niacin, both in conjunction with psychotherapy. The primary outcomes were anxiety and depression assessed between groups prior to the crossover at 7 weeks. Prior to the crossover, psilocybin produced immediate, substantial, and sustained improvements in anxiety and depression and led to decreases in cancer-related demoralization and hopelessness, improved spiritual wellbeing, and increased quality of life. At the 6.5-month follow-up, psilocybin was associated with enduring anxiolytic and anti-depressant effects (approximately 60-80% of participants continued with clinically significant reductions in depression or anxiety), sustained benefits in existential distress and quality of life, as well as improved attitudes towards death. The psilocybin-induced mystical experience mediated the therapeutic effect of psilocybin on anxiety and depression. In conjunction with psychotherapy, single moderate-dose psilocybin produced rapid, robust and enduring anxiolytic and anti-depressant effects in patients with cancer-related psychological distress. ClinicalTrials.gov Identifier: NCT00957359. © The Author(s) 2016.

Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial

PubMed Central

Ross, Stephen; Bossis, Anthony; Guss, Jeffrey; Agin-Liebes, Gabrielle; Malone, Tara; Cohen, Barry; Mennenga, Sarah E; Belser, Alexander; Kalliontzi, Krystallia; Babb, James; Su, Zhe; Corby, Patricia; Schmidt, Brian L

2016-01-01

Background: Clinically significant anxiety and depression are common in patients with cancer, and are associated with poor psychiatric and medical outcomes. Historical and recent research suggests a role for psilocybin to treat cancer-related anxiety and depression. Methods: In this double-blind, placebo-controlled, crossover trial, 29 patients with cancer-related anxiety and depression were randomly assigned and received treatment with single-dose psilocybin (0.3 mg/kg) or niacin, both in conjunction with psychotherapy. The primary outcomes were anxiety and depression assessed between groups prior to the crossover at 7 weeks. Results: Prior to the crossover, psilocybin produced immediate, substantial, and sustained improvements in anxiety and depression and led to decreases in cancer-related demoralization and hopelessness, improved spiritual wellbeing, and increased quality of life. At the 6.5-month follow-up, psilocybin was associated with enduring anxiolytic and anti-depressant effects (approximately 60–80% of participants continued with clinically significant reductions in depression or anxiety), sustained benefits in existential distress and quality of life, as well as improved attitudes towards death. The psilocybin-induced mystical experience mediated the therapeutic effect of psilocybin on anxiety and depression. Conclusions: In conjunction with psychotherapy, single moderate-dose psilocybin produced rapid, robust and enduring anxiolytic and anti-depressant effects in patients with cancer-related psychological distress. Trial Registration: ClinicalTrials.gov Identifier: NCT00957359 PMID:27909164

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

PubMed

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

2016-01-01

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

Single-case experimental design yielded an effect estimate corresponding to a randomized controlled trial.

PubMed

Shadish, William R; Rindskopf, David M; Boyajian, Jonathan G

2016-08-01

We reanalyzed data from a previous randomized crossover design that administered high or low doses of intravenous immunoglobulin (IgG) to 12 patients with hypogammaglobulinaemia over 12 time points, with crossover after time 6. The objective was to see if results corresponded when analyzed as a set of single-case experimental designs vs. as a usual randomized controlled trial (RCT). Two blinded statisticians independently analyzed results. One analyzed the RCT comparing mean outcomes of group A (high dose IgG) to group B (low dose IgG) at the usual trial end point (time 6 in this case). The other analyzed all 12 time points for the group B patients as six single-case experimental designs analyzed together in a Bayesian nonlinear framework. In the randomized trial, group A [M = 794.93; standard deviation (SD) = 90.48] had significantly higher serum IgG levels at time six than group B (M = 283.89; SD = 71.10) (t = 10.88; df = 10; P < 0.001), yielding a mean difference of MD = 511.05 [standard error (SE) = 46.98]. For the single-case experimental designs, the effect from an intrinsically nonlinear regression was also significant and comparable in size with overlapping confidence intervals: MD = 495.00, SE = 54.41, and t = 495.00/54.41 = 9.10. Subsequent exploratory analyses indicated that how trend was modeled made a difference to these conclusions. The results of single-case experimental designs accurately approximated results from an RCT, although more work is needed to understand the conditions under which this holds. Copyright © 2016 Elsevier Inc. All rights reserved.

Evaluation of 5 Hour Energy Drink on the Blood Pressure and Electrocardiograph Parameters on Young Healthy Volunteers: A Randomized, Double Blind, Crossover, Placebo-Controlled Trial

DTIC Science & Technology

2014-02-11

Travis AFB CA INSTITUTIONAL REVIEW BOARD (IRB) ()~\\) Non-Exempt Study Final Report p3YVJ (Please 1J!J!£ all information. Use additional pages if...QTc interval after acute and chronic consumption. METHODS: This was a randomized, placebo controlled, crossover study enrolling young healthy volunteers...not on any medications. Subjects received the study drink (5 Hour Energy shot or placebo) twice daily separated by approximately 7 hours for the

Ass's milk in children with atopic dermatitis and cow's milk allergy: crossover comparison with goat's milk.

PubMed

Vita, Daniela; Passalacqua, Giovanni; Di Pasquale, Giuseppe; Caminiti, Lucia; Crisafulli, Giuseppe; Rulli, Imma; Pajno, Giovanni B

2007-11-01

Cow milk allergy is a common disease of infancy, often associated with atopic dermatitis (AD). Avoidance of cow milk (CM) implies the use of alternative dietary supports such as mammalian milks. In this study, we assessed the tolerability and clinical effect of ass's milk (AM), when compared with the largely used goat's milk (GM) in a single-blind, controlled, randomized crossover. Twenty-eight children with AD and ascertained allergy to CM were enrolled. The children were randomized to AM or GM for 6 months, then switched to the other milk for further 3 months. The SCORAD index (SI) and a visual analog scale (VAS) were evaluated blindly. After termination of the study, food challenges with GM and AM were performed. An SDS-PAGE analysis of different milks was performed. Two children from the GM group dropped out after randomization and 26 completed the study. Ass milk invariantly led to a significant improvement of SI and VAS of symptoms (p < 0.03 vs. baseline and inter-group), whereas GM had no measurable clinical effect. At the end of the study 23 of 26 children had a positive food challenge with GM and one of 26 with AM. Ass's milk had a protein profile closer to human milk than GM. Ass milk is better tolerated and more effective than GM in reducing symptoms of AD. It may represent a better substitute of CM than the currently used GM.

Ulcerative colitis patients with an inflammatory response upon mesalazine cannot be desensitized: a randomized study.

PubMed

Buurman, Dorien J; De Monchy, Jan G R; Schellekens, Reinout C A; van der Waaij, Laurens A; Kleibeuker, Jan H; Dijkstra, Gerard

2015-04-01

Mesalazine is a key drug in the treatment of ulcerative colitis (UC). Intolerance to mesalazine has been described, including fever and gastrointestinal symptoms. Several case reports reported successful desensitization of patients with mesalazine intolerance. The aim was to assess the number of UC patients who are persistently intolerant to mesalazine after single-blinded rechallenge and to test the effectiveness of a rapid desensitization protocol in UC patients demonstrated mesalazine intolerance. This is a prospective, single-blind randomized study in UC patients who discontinued mesalazine because of intolerance. Patients with severe reactions were excluded. Eligible patients underwent a skin patch test with mesalazine followed by a single-blinded randomized crossover rechallenge with 500 mg mesalazine or placebo. Patients with symptoms upon rechallenge were admitted to the hospital for 3 days oral desensitization. Nine of the 37 identified UC patients who discontinued mesalazine because of intolerance were included. All nine patients had negative patch tests, seven patients had symptoms (fever, nausea, vomiting and diarrhea) within 2 h upon rechallenge. Four of these seven patients participated in the desensitization protocol and in none a successful desensitization could be performed. All four had an inflammatory intolerance reaction with rise in C-reactive protein. There were no elevations in serum tryptase or urinary-methylhistamine levels observed and no signs of immediate type allergic reactions, like urticaria, bronchial obstruction or anaphylaxis. We recommend not to rechallenge UC patients with an inflammatory response upon mesalazine and these patients will not benefit from a rapid desensitization protocol.

Comparison of the inhibitory effects of cilostazol, acetylsalicylic acid and ticlopidine on platelet functions ex vivo. Randomized, double-blind cross-over study.

PubMed

Ikeda, Y; Kikuchi, M; Murakami, H; Satoh, K; Murata, M; Watanabe, K; Ando, Y

1987-05-01

A randomized double-blind cross-over study was conducted to determine the inhibitory effects of acetylsalicylic acid (ASA), ticlopidine (TP) and cilostazol (OPC-13013; in the following briefly called CS), a new antithrombotic agent on platelet functions ex vivo. Nine patients with cerebral thrombosis were enrolled in this study. Patients were given each of the three drugs for one week in a complete cross-over design according to a randomization schedule, followed by a wash-out period with a placebo for one week. It was found that CS and TP significantly inhibited platelet aggregation induced by ADP. Collagen- and arachidonic acid-induced platelet aggregation was all inhibited by CS, TP and ASA. Duncan's multiple range test to compare the anti-platelet effects of the three drugs revealed that: CS greater than ASA and TP greater than ASA in inhibiting ADP-induced platelet aggregation and CS greater than TP and ASA greater than TP in inhibiting arachidonic acid-induced platelet aggregation. These results may suggest that CS is superior to ASA and TP in inhibiting platelet aggregation ex vivo.

A randomized, controlled cross-over trial of dermally-applied lavender (Lavandula angustifolia) oil as a treatment of agitated behaviour in dementia

PubMed Central

2013-01-01

Background Lavender essential oil shows evidence of sedative properties in neurophysiological and animal studies but clinical trials of its effectiveness as a treatment of agitation in people with dementia have shown mixed results. Study methods have varied widely, however, making comparisons hazardous. To help remedy previous methodological shortcomings, we delivered high grade lavender oil in specified amounts to nursing home residents whose agitated behaviours were recorded objectively. Methods 64 nursing home residents with frequent physically agitated behaviours were entered into a randomized, single-blind cross-over trial of dermally-applied, neurophysiologically active, high purity 30% lavender oil versus an inactive control oil. A blinded observer counted the presence or absence of target behaviours and rated participants’ predominant affect during each minute for 30 minutes prior to exposure and for 60 minutes afterwards. Results Lavender oil did not prove superior to the control oil in reducing the frequency of physically agitated behaviours or in improving participants’ affect. Conclusions Studies of essential oils are constrained by their variable formulations and uncertain pharmacokinetics and so optimal dosing and delivery regimens remain speculative. Notwithstanding this, topically delivered, high strength, pure lavender oil had no discernible effect on affect and behaviour in a well-defined clinical sample. Trial registration Australian and New Zealand Clinical Trials Registry (ACTRN 12609000569202) PMID:24219098

A systematic review identifies shortcomings in the reporting of crossover trials in chronic painful conditions.

PubMed

Straube, Sebastian; Werny, Benedikt; Friede, Tim

2015-12-01

To investigate the reporting of study features of interest in abstracts and full texts of journal publications of crossover trials in chronic painful conditions. Systematic review based on a MEDLINE (PubMed) search (January 1990-August 2014). Ninety-eight publications on crossover studies with 3,513 study participants were eligible for inclusion. Double-blind status and randomized allocation to treatment groups are commonly reported in both abstracts and full texts (90 of 98 publications and 82 of 98 publications, respectively). Adverse events are reported in both abstract and full text in 49 of 98 publications and in the full text only in 44 of 98. A breakdown of results by treatment period is provided only in 23 of 98 publications, and if so, is reported only in the full text, never in the abstract. There is a time trend for the reporting of randomization in abstracts; it is more likely to be reported in recent studies (P = 0.0094). No time trends are detected in the reporting of double-blind status (P = 0.1087) and adverse events (P = 0.6084). The reporting of adverse events in the abstract and the reporting of results specified by crossover period in the full texts of journal publications on crossover pain trials should be improved. Copyright © 2015 Elsevier Inc. All rights reserved.

Efficacy of the Ubiquitous Spaced Retrieval-based Memory Advancement and Rehabilitation Training (USMART) program among patients with mild cognitive impairment: a randomized controlled crossover trial.

PubMed

Han, Ji Won; Son, Kyung Lak; Byun, Hye Jin; Ko, Ji Won; Kim, Kayoung; Hong, Jong Woo; Kim, Tae Hyun; Kim, Ki Woong

2017-06-06

Spaced retrieval training (SRT) is a nonpharmacological intervention for mild cognitive impairment (MCI) and dementia that trains the learning and retention of target information by recalling it over increasingly long intervals. We recently developed the Ubiquitous Spaced Retrieval-based Memory Advancement and Rehabilitation Training (USMART) program as a convenient, self-administered tablet-based SRT program. We also demonstrated the utility of USMART for improving memory in individuals with MCI through an open-label uncontrolled trial. This study had an open-label, single-blind, randomized, controlled, two-period crossover design. Fifty patients with MCI were randomized into USMART-usual care and usual care-USMART treatment sequences. USMART was completed or usual care was provided biweekly over a 4-week treatment period with a 2-week washout period between treatment periods. Primary outcome measures included the Word List Memory Test, Word List Recall Test (WLRT), and Word List Recognition Test. Outcomes were measured at baseline, week 5, and week 11 by raters who were blinded to intervention type. An intention-to-treat analysis and linear mixed modeling were used. Of 50 randomized participants, 41 completed the study (18% dropout rate). The USMART group had larger improvements in WLRT score (effect size = 0.49, p = 0.031) than the usual care group. There were no significant differences in other primary or secondary measures between the USMART and usual care groups. Moreover, no USMART-related adverse events were reported. The 4-week USMART modestly improved information retrieval in older people with MCI, and was well accepted with minimal technical support. ClinicalTrials.gov NCT01688128 . Registered 12 September 2012.

Effect of knee joint icing on knee extension strength and knee pain early after total knee arthroplasty: a randomized cross-over study.

PubMed

Holm, Bente; Husted, Henrik; Kehlet, Henrik; Bandholm, Thomas

2012-08-01

To investigate the acute effect of knee joint icing on knee extension strength and knee pain in patients shortly after total knee arthroplasty. A prospective, single-blinded, randomized, cross-over study. A fast-track orthopaedic arthroplasty unit at a university hospital. Twenty patients (mean age 66 years; 10 women) scheduled for primary unilateral total knee arthroplasty. The patients were treated on two days (day 7 and day 10) postoperatively. On one day they received 30 minutes of knee icing (active treatment) and on the other day they received 30 minutes of elbow icing (control treatment). The order of treatments was randomized. Maximal knee extension strength (primary outcome), knee pain at rest and knee pain during the maximal knee extensions were measured 2-5 minutes before and 2-5 minutes after both treatments by an assessor blinded for active or control treatment. The change in knee extension strength associated with knee icing was not significantly different from that of elbow icing (knee icing change (mean (1 SD)) -0.01 (0.07) Nm/kg, elbow icing change -0.02 (0.07) Nm/kg, P = 0.493). Likewise, the changes in knee pain at rest (P = 0.475), or knee pain during the knee extension strength measurements (P = 0.422) were not different between treatments. In contrast to observations in experimental knee effusion models and inflamed knee joints, knee joint icing for 30 minutes shortly after total knee arthroplasty had no acute effect on knee extension strength or knee pain.

Native whey induces higher and faster leucinemia than other whey protein supplements and milk: A randomized controlled trial

USDA-ARS?s Scientific Manuscript database

Resistance exercise and protein intake are both strong stimuli for muscle protein synthesis. The potential for a protein to acutely increase muscle protein synthesis seems partly dependent on absorption kinetics and the amino acid composition. The aim of this double-blinded randomized cross-over stu...

The Sonoma Water Evaluation Trial (SWET): A randomized drinking water intervention trial to reduce gastrointestinal illness in older adults

EPA Science Inventory

Objectives. We estimate the risk of highly credible gastrointestinal illness (HCGI) among adults 55 and older in a community drinking tap water meeting current U.S. standards. Methods. We conducted a randomized, triple-blinded, crossover trial in 714 households (988 indiv...

Effects of Ayurvedic Oil-Dripping Treatment with Sesame Oil vs. with Warm Water on Sleep: A Randomized Single-Blinded Crossover Pilot Study.

PubMed

Tokinobu, Akiko; Yorifuji, Takashi; Tsuda, Toshihide; Doi, Hiroyuki

2016-01-01

Ayurvedic oil-dripping treatment (Shirodhara) is often used for treating sleep problems. However, few properly designed studies have been conducted, and the quantitative effect of Shirodhara is unclear. This study sought to quantitatively evaluate the effect of sesame oil Shirodhara (SOS) against warm water Shirodhara (WWS) on improving sleep quality and quality of life (QOL) among persons reporting sleep problems. This randomized, single-blinded, crossover study recruited 20 participants. Each participant received seven 30-minute sessions within 2 weeks with either liquid. The washout period was at least 2 months. The Shirodhara procedure was conducted by a robotic oil-drip system. The outcomes were assessed by the Pittsburgh Sleep Quality Index (PSQI) for sleep quality, Epworth Sleepiness Scale (ESS) for daytime sleepiness, World Health Organization Quality of Life 26 (WHO-QOL26) for QOL, and a sleep monitor instrument for objective sleep measures. Changes between baseline and follow-up periods were compared between the two types of Shirodhara. Analysis was performed with generalized estimating equations. Of 20 participants, 15 completed the study. SOS improved sleep quality, as measured by PSQI. The SOS score was 1.83 points lower (95% confidence interval [CI], -3.37 to -0.30) at 2-week follow-up and 1.73 points lower (95% CI, -3.84 to 0.38) than WWS at 6-week follow-up. Although marginally significant, SOS also improved QOL by 0.22 points at 2-week follow-up and 0.19 points at 6-week follow-up compared with WWS. After SOS, no beneficial effects were observed on daytime sleepiness or objective sleep measures. This pilot study demonstrated that SOS may be a safe potential treatment to improve sleep quality and QOL in persons with sleep problems.

Double blind study of the effects of zinc sulfate on taste and smell dysfunction

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

Henkin, R.I.; Schecter, P.J.; Friedewald, W.T.

1976-01-01

A randomized, double blind crossover study of the effects of zinc sulfate and placebo was carried out in 106 patients with taste and smell dysfunction secondary to a variety of etiological factors. In the patient group prior to treatment, mean serum zinc concentration and leukocyte alkaline phosphatase activity were significantly lower than normal. Results indicate that zinc sulfate was effectively equivalent to placebo in the treatment of these disorders. Although these results demonstrate abnormalities of zinc metabolism in some patients with taste and smell dysfunction they fail to provide evidence for a single, therapeutic approach to the many disorders whichmore » are associated with abnormalities of taste and smell. However, the methods and procedures developed in this study demonstrate that taste and smell dysfunction can be studied in a quantitative, systematic manner.« less

Tolerance of beta blocked hypertensives during orthostatic and altitude stress.

DOT National Transportation Integrated Search

1992-04-01

To evaluate the effects of orthostatic, altitude, and pharmacologic stresses upon civil aviation-specific performance, a double-blind, randomized, crossover trial of atenolol, 100mg, was designed and executed. Hypertensive males are females qualifyin...

Explicit Bias Toward High-Income-Country Research: A Randomized, Blinded, Crossover Experiment Of English Clinicians.

PubMed

Harris, Matthew; Marti, Joachim; Watt, Hillary; Bhatti, Yasser; Macinko, James; Darzi, Ara W

2017-11-01

Unconscious bias may interfere with the interpretation of research from some settings, particularly from lower-income countries. Most studies of this phenomenon have relied on indirect outcomes such as article citation counts and publication rates; few have addressed or proven the effect of unconscious bias in evidence interpretation. In this randomized, blinded crossover experiment in a sample of 347 English clinicians, we demonstrate that changing the source of a research abstract from a low- to a high-income country significantly improves how it is viewed, all else being equal. Using fixed-effects models, we measured differences in ratings for strength of evidence, relevance, and likelihood of referral to a peer. Having a high-income-country source had a significant overall impact on respondents' ratings of relevance and recommendation to a peer. Unconscious bias can have far-reaching implications for the diffusion of knowledge and innovations from low-income countries.

The Gluten-Free, Casein-Free Diet in Autism: Results of a Preliminary Double Blind Clinical Trial

ERIC Educational Resources Information Center

Elder, Jennifer Harrison; Shankar, Meena; Shuster, Jonathan; Theriaque, Douglas; Burns, Sylvia; Sherrill, Lindsay

2006-01-01

This study tested the efficacy of a gluten-free and casein-free (GFCF) diet in treating autism using a randomized, double blind repeated measures crossover design. The sample included 15 children aged 2-16 years with autism spectrum disorder. Data on autistic symptoms and urinary peptide levels were collected in the subjects' homes over the 12…

Antihyperalgesic efficacy of 5% lidocaine medicated plaster in capsaicin and sunburn pain models--two randomized, double-blinded, placebo-controlled crossover trials in healthy volunteers.

PubMed

Gustorff, Burkhard; Hauer, David; Thaler, Johannes; Seis, Astrid; Draxler, Julia

2011-12-01

The aim of this research is to analyze analgesic efficacy of the 5% lidocaine medicated plaster in two randomized, double-blinded, placebo-controlled, crossover studies in 16 healthy volunteers using capsaicin and sunburn pain models. Lidocaine and placebo plasters were simultaneously applied to forearms and thighs at contralateral body sites for three alternating 12-h plaster-on/plaster-off periods. Between the second and third plaster-on period, 4.2-cm circular spots on both pretreated thighs were irradiated with three times the individual minimal erythema dose of UVB light. After the last plaster-on period, 20 μl of 0.1% capsaicin was injected intradermally into both forearms. The study was repeated using a single 12-h plaster application. The area of pinprick hyperalgesia was diminished by 53% (p < 0.003) in the capsaicin model and by 84% (p < 0.0001) in the sunburn model; the intensity of mechanical hyperalgesia to rigid filaments (8 - 512 mN) was reduced in both models. Cold pain perception threshold was reduced (19.7°C ± 8.0 vs 21.8°C ± 6.8 for placebo, p < 0.05, sunburn). Similar effects were observed in the 12-h exposure study. No effect was seen on capsaicin-induced spontaneous pain and flare size, or blood flow in the sunburn area, and heat hyperalgesia in either study. Lidocaine plaster effectively treats mechanical hyperalgesia and cold pain.

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

USDA-ARS?s Scientific Manuscript database

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

Myofascial Induction Effects on Neck-Shoulder Pain in Breast Cancer Survivors: Randomized, Single-Blind, Placebo-Controlled Crossover Design.

PubMed

Castro-Martín, Eduardo; Ortiz-Comino, Lucía; Gallart-Aragón, Tania; Esteban-Moreno, Bernabé; Arroyo-Morales, Manuel; Galiano-Castillo, Noelia

2017-05-01

To (1) investigate the immediate effects of myofascial induction (MI), with placebo electrotherapy as a control, on perceived pain, cervical/shoulder range of motion (ROM), and mood state in breast cancer survivors (BCSs) with shoulder/arm morbidity; and (2) examine the relationships between pain modifications and cervical/shoulder ROM on the side affected by breast cancer. Randomized, single-blind, placebo-controlled crossover study. Physical therapy laboratory. BCSs (N=21) who had a diagnosis of stage I-IIIA breast cancer and had completed adjuvant therapy (except hormonal treatment). During each session, the BCSs received either an MI (fascial unwinding) intervention focused on the upper limb area following the Pilat approach or placebo pulsed shortwave therapy (control group). Each session lasted 30 minutes, and an adequate washout period of 4 weeks between sessions was established. The visual analog scale (VAS) for pain and anxiety, shoulder-cervical goniometry for ROM, the Profile of Mood States for psychological distress, and the Attitudes Towards Massage Scale were used. An analysis of covariance (ANCOVA) revealed significant time × group interactions for VAS affected arm (P=.031) but not for VAS cervical (P=.332), VAS nonaffected arm (P=.698), or VAS anxiety (P=.266). The ANCOVA also revealed significant interactions for affected shoulder flexion (P<.001), abduction (P<.001), external rotation (P=.004), and internal rotation (P=.001). Significant interactions for affected cervical rotation (P=.022) and affected cervical lateral flexion (P=.038) were also found. A significant negative correlation was found between changes in VAS affected arm and shoulder/arm internal rotation ROM (r=-.46; P=.03). A single MI session decreases pain intensity and improves neck-shoulder ROM to a greater degree than placebo electrotherapy for BCSs experiencing pain. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Immediate effects of kinesiotaping on quadriceps muscle strength: a single-blind, placebo-controlled crossover trial.

PubMed

Vercelli, Stefano; Sartorio, Francesco; Foti, Calogero; Colletto, Lorenzo; Virton, Domenico; Ronconi, Gianpaolo; Ferriero, Giorgio

2012-07-01

To investigate the immediate effects on maximal muscle strength of kinesiotaping (KT) applied to the dominant quadriceps of healthy subjects. Single-blind, placebo-controlled crossover trial. "Salvatore Maugeri" Foundation. With ethical approval and informed consent, a convenience sample of 36 healthy volunteers were recruited. Two subjects did not complete the sessions and were excluded from the analysis. Subjects were tested across 3 different sessions, randomly receiving 2 experimental KT conditions applied with the aim of enhancing and inhibiting muscle strength and a sham KT application. Quadriceps muscle strength was measured by means of an isokinetic maximal test performed at 60 and 180 degrees per second. Two secondary outcome measures were performed: the single-leg triple hop for distance to measure limb performance and the Global Rating of Change Scale (GRCS) to calculate agreement between KT application and subjective perception of strength. Compared with baseline, none of the 3 taping conditions showed a significant change in muscle strength and performance (all P > 0.05). Effect size was very low under all conditions (≤0.08). Very few subjects showed an individual change greater than the minimal detectable change. Global Rating of Change Scale scores demonstrated low to moderate agreement with the type of KT applied, but some placebo effects were reported independently of condition. Our findings indicated no significant effect in the maximal quadriceps strength immediately after the application of inhibition, facilitation, or sham KT. These results do not support the use of KT applied in this way to change maximal muscle strength in healthy people.

Intervention for phantom limb pain: A randomized single crossover study of mirror therapy.

PubMed

Ramadugu, Shashikumar; Nagabushnam, Satish C; Katuwal, Nagendra; Chatterjee, Kaushik

2017-01-01

Mirror therapy suggested to help relieve phantom limb pain (PLP) by resolving the visual- proprioceptive dissociation in the brain, but studies so far either had shorter follow-up or smaller sample size. In this randomized single crossover trial, 64 amputees with PLP in the age group of 15-75 years of age were distributed into test and control groups by simple randomization method. Of these 28 in control and 32 in test groups, respectively, completed the 4 weeks of mirror therapy and 12 weeks of follow-up assessments. A standardized set of exercises for 15 min/day for 4 and 8 weeks in test and control groups (in the first 4 weeks, the mirror was covered), respectively, was administered under supervision of one of the authors. All were assessed using the visual analog scale and Short-Form McGill Pain Questionnaire on day 0 and at 4, 8, and 12 weeks after therapy. In control group for the initial 4 weeks, the mirror was covered. The assessing author was blinded to the group to which the participants belonged. Significant reduction in PLP was noted in the test group at 4 weeks compared to the control group ( P < 0.0001). Significant reduction was seen in control group also after the switchover and sustained for 12 weeks in both. No harm was reported. Mirror therapy is effective in relieving the intensity, duration, frequency, and overall PLP, and improvement is maintained up to 12 weeks' posttherapy.

A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles.

PubMed

Kurosawa, Yuko; Nirengi, Shinsuke; Homma, Toshiyuki; Esaki, Kazuki; Ohta, Mitsuhiro; Clark, Joseph F; Hamaoka, Takafumi

2015-06-25

Our aim was to determine the quantitative effects of a single-dose of Nattokinase (NK) administration on coagulation/fibrinolysis parameters comprehensively in healthy male subjects. A double-blind, placebo-controlled cross-over NK intervention study was carried out in 12 healthy young males. Following the baseline blood draw, each subject was randomized to receive either a single-dose of 2,000 FU NK (NSK-SD, Japan Bio Science Laboratory Co., Ltd) or placebo with subsequent cross-over of the groups. Subjects donated blood samples at 2, 4, 6 and 8 hours following administration for analysis of coagulation/fibrinolysis parameters. As a result, D-dimer concentrations at 6, and 8 hours, and blood fibrin/fibrinogen degradation products at 4 hours after NK administration elevated significantly (p < 0.05, respectively). Factor VIII activity declined at 4 and 6 hours (p < 0.05, respectively), blood antithrombin concentration was higher at 2 and 4 hours (p < 0.05, respectively), and the activated partial thromboplastin time prolonged significantly at 2 and 4 hours following NK administration (p < 0.05 and p < 0.01, respectively). All the changes, however, were within the normal range. In conclusion, thus, a single-dose of NK administration appears enhancing fibrinolysis and anti-coagulation via several different pathways simultaneously.

Upper airway stabilization by osteopathic manipulation of the sphenopalatine ganglion versus sham manipulation in OSAS patients: a proof-of-concept, randomized, crossover, double-blind, controlled study.

PubMed

Jacq, Olivier; Arnulf, Isabelle; Similowski, Thomas; Attali, Valérie

2017-12-20

Osteopathic manipulative treatment (OMT) of the sphenopalatine ganglion (SPG) is used empirically for the treatment of rhinitis and snoring and is thought to increase pharyngeal stability. This trial was designed to study the effects of this treatment on pharyngeal stability evaluated by critical closing pressure in obstructive sleep apnoea syndrome. This single-centre, randomized, crossover, double-blind study compared active manipulation and sham manipulation of the SPG. Randomization was computer-generated. Patients each received one active manipulation and one sham manipulation at an interval of 21 days and were evaluated 30 min and 48 h after each session administered by a qualified osteopath. Neither the patients, nor the investigator performing the evaluations were informed about the order of the two techniques (double-blind). The primary endpoint was the percentage of responding patients presenting increased pharyngeal stability defined by a variation of critical closing pressure (Pcrit) of at least -4 cmH 2 O at 30 min. Secondary endpoints were the variation of Pcrit in absolute values, sleepiness and snoring. Others endpoints were lacrimation (Schirmer's test), induced pain, sensations experienced during OMT. Ten patients were included and nine (57 [50; 58] years, comprising 7 men, with an apnoea-hypopnoea index of 31.0 [25.5; 33.2]/h; (values are median [quartiles])) were analysed. Seven patients were analysed for the primary endpoint and nine patients were analysed for secondary endpoints. Five patients responded after active manipulation versus no patients after sham manipulation (p = 0.0209). Active manipulation induced more intense pain (p = 0.0089), increased lacrimation (ns) and more tactile, nociceptive and gustatory sensations (13 versus 1) compared to sham manipulation. No significant difference was observed for the other endpoints. Osteopathic manipulative treatment of the SPG may improve pharyngeal stability in obstructive sleep apnoea syndrome. This trial validates the feasibility of the randomized, controlled, double-blind methodology for evaluation of this osteopathic treatment. Studies on a larger sample size must specify the efficacy on the apnoea-hypopnoea index. The study was retrospectively registered in the clinicaltrial.gov registry under reference NCT01193738 on 1st September 2010 (first inclusion May 19, 2010).

Efficacy of low-frequency low-intensity electrotherapy in the treatment of breast cancer-related lymphoedema: a cross-over randomized trial.

PubMed

Belmonte, Roser; Tejero, Marta; Ferrer, Montse; Muniesa, Josep Maria; Duarte, Esther; Cunillera, Oriol; Escalada, Ferran

2012-07-01

To compare the efficacy of low-frequency low-intensity electrotherapy and manual lymphatic drainage in the treatment of chronic upper limb breast cancer-related lymphoedema. Cross-over single-blind random clinical trial. Rehabilitation service. Thirty-six women with chronic upper limb breast cancer-related lymphoedema. Patients were randomized to undergo 10 sessions of manual lymphatic drainage followed by 10 sessions of low-frequency low-intensity electrotherapy or to undergo first low-frequency low-intensity electrotherapy followed by manual lymphatic drainage. There was a month of washout time between treatments. Each patient was examined just before and after each treatment. Researchers and outcome assessors were blinded for assigned treatment. Outcomes were lymphoedema volume, pain, heaviness and tightness, and health-related quality of life measured with the Functional Assessment of Cancer Therapy Questionnaire for Breast Cancer version 4 (FACT-B+4). Carry-over, period and treatment effects were analysed. Treatment effect was assessed using paired t-test. Thirty patients finalized treatment. Comparing the changes in low-frequency low-intensity electrotherapy with manual lymphatic drainage changes, there were no significant differences. Low-frequency low-intensity electrotherapy did not reduce lymphoedema volume (mean of change = 19.77 mL, P = 0.36), but significant reductions were observed in pain, heaviness and tightness (mean of change = 13.1, 16.2 and 6.4 mm, respectively), and FACT-B+4 summaries improved significantly (Trial Outcome Index mean of change = 5.4, P = 0.015). Manual lymphatic drainage showed no significant changes in any of the outcomes Although there are no significant differences between treatment changes, the observed trend towards a better health-related quality of life is remarkable in low-frequency low-intensity electrotherapy.

Efficacy of low-frequency low-intensity electrotherapy in the treatment of breast cancer-related lymphoedema: a cross-over randomized trial

PubMed Central

Tejero, Marta; Ferrer, Montse; Muniesa, Josep M; Duarte, Esther; Cunillera, Oriol; Escalada, Ferran

2012-01-01

Objective: To compare the efficacy of low-frequency low-intensity electrotherapy and manual lymphatic drainage in the treatment of chronic upper limb breast cancer-related lymphoedema. Design: Cross-over single-blind random clinical trial. Setting: Rehabilitation service. Participants: Thirty-six women with chronic upper limb breast cancer-related lymphoedema. Methods: Patients were randomized to undergo 10 sessions of manual lymphatic drainage followed by 10 sessions of low-frequency low-intensity electrotherapy or to undergo first low-frequency low-intensity electrotherapy followed by manual lymphatic drainage. There was a month of washout time between treatments. Each patient was examined just before and after each treatment. Researchers and outcome assessors were blinded for assigned treatment. Measures: Outcomes were lymphoedema volume, pain, heaviness and tightness, and health-related quality of life measured with the Functional Assessment of Cancer Therapy Questionnaire for Breast Cancer version 4 (FACT-B+4). Carry-over, period and treatment effects were analysed. Treatment effect was assessed using paired t-test. Results: Thirty patients finalized treatment. Comparing the changes in low-frequency low-intensity electrotherapy with manual lymphatic drainage changes, there were no significant differences. Low-frequency low-intensity electrotherapy did not reduce lymphoedema volume (mean of change = 19.77 mL, P = 0.36), but significant reductions were observed in pain, heaviness and tightness (mean of change = 13.1, 16.2 and 6.4 mm, respectively), and FACT-B+4 summaries improved significantly (Trial Outcome Index mean of change = 5.4, P = 0.015). Manual lymphatic drainage showed no significant changes in any of the outcomes Conclusion: Although there are no significant differences between treatment changes, the observed trend towards a better health-related quality of life is remarkable in low-frequency low-intensity electrotherapy. PMID:22172923

Randomized, Double-Blind, Placebo- and Active Comparator-Controlled Crossover Study Evaluating the Abuse Potential of the Antiepileptic Drug Lacosamide in Healthy Recreational Drug Users.

PubMed

Schoedel, Kerri A; Andreas, Jens-Otto; Doty, Pamela; Eckhardt, Klaus; Sellers, Edward M

2017-12-01

This phase 1, randomized, double-blind, placebo- and active comparator-controlled crossover study assessed the abuse potential of the antiepileptic drug, lacosamide. After a qualification phase, 38 healthy, recreational central nervous system-depressant users were randomized to treatment sequences comprising single oral therapeutic (200 mg) and supratherapeutic (800 mg) doses of lacosamide, alprazolam (1.5 and 3 mg), and placebo. Subjective effects were assessed for 24 hours following each dose using a range of scales, with a 5- to 9-day washout between treatments. Mean subjective effects for 200 mg lacosamide were statistically similar to placebo and significantly lower than with alprazolam for most end points. Lacosamide 800 mg elicited transient, statistically significant positive effects compared with placebo, but also persistent Bad Drug Effects including statistically greater maximum effect (Emax) scores for Nausea and Dysphoria compared with other treatments (P < 0.0002). Consistent with this, the 800 mg lacosamide dose showed a significantly lower "at this moment" Drug Liking visual analog scale (VAS) Emax compared with 3 mg alprazolam, but was not different from 1.5 mg alprazolam (73.1/100, 85.4/100, and 78.9/100, respectively, where 50 is neutral). Overall Drug Liking VAS and Take Drug Again VAS Emax for 800 mg lacosamide were not significantly different from placebo and were lower than those for both alprazolam doses (P < 0.0001). These results suggest that in recreational central nervous system-depressant users, lacosamide has detectable abuse-related subjective effects, but a relatively low potential for abuse compared with alprazolam. These findings contributed toward placement of lacosamide into Schedule V of the US Controlled Substances Act.

Enriched Air Nitrox Breathing Reduces Venous Gas Bubbles after Simulated SCUBA Diving: A Double-Blind Cross-Over Randomized Trial.

PubMed

Souday, Vincent; Koning, Nick J; Perez, Bruno; Grelon, Fabien; Mercat, Alain; Boer, Christa; Seegers, Valérie; Radermacher, Peter; Asfar, Pierre

2016-01-01

To test the hypothesis whether enriched air nitrox (EAN) breathing during simulated diving reduces decompression stress when compared to compressed air breathing as assessed by intravascular bubble formation after decompression. Human volunteers underwent a first simulated dive breathing compressed air to include subjects prone to post-decompression venous gas bubbling. Twelve subjects prone to bubbling underwent a double-blind, randomized, cross-over trial including one simulated dive breathing compressed air, and one dive breathing EAN (36% O2) in a hyperbaric chamber, with identical diving profiles (28 msw for 55 minutes). Intravascular bubble formation was assessed after decompression using pulmonary artery pulsed Doppler. Twelve subjects showing high bubble production were included for the cross-over trial, and all completed the experimental protocol. In the randomized protocol, EAN significantly reduced the bubble score at all time points (cumulative bubble scores: 1 [0-3.5] vs. 8 [4.5-10]; P < 0.001). Three decompression incidents, all presenting as cutaneous itching, occurred in the air versus zero in the EAN group (P = 0.217). Weak correlations were observed between bubble scores and age or body mass index, respectively. EAN breathing markedly reduces venous gas bubble emboli after decompression in volunteers selected for susceptibility for intravascular bubble formation. When using similar diving profiles and avoiding oxygen toxicity limits, EAN increases safety of diving as compared to compressed air breathing. ISRCTN 31681480.

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

PubMed

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

2016-12-01

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

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.

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.

Comparison of lorazepam and zopiclone for insomnia in patients with stroke and brain injury: a randomized, crossover, double-blinded trial.

PubMed

Li Pi Shan, Rodney S; Ashworth, Nigel L

2004-06-01

To determine if lorazepam or zopiclone is more effective in providing a restful night of sleep and to assess the effects of these medications on cognition. A randomized, double-blinded, crossover trial was performed at a tertiary care rehabilitation inpatient unit in a teaching hospital. A total of 18 brain-injured and stroke patients, aged 20-78 yrs, were administered lorazepam, 0.5-1.0 mg, orally at bedtime as needed for 7 days and zopiclone, 3.75-7.5 mg, orally at bedtime as needed for 7 days. Total sleep time and characteristics of sleep were measured. Effects on cognition were also measured using the Folstein Mini Mental Status Exam. There was no difference in average sleep duration or in subjective measures of sleep. Cognition as assessed by the Mini Mental Status Exam revealed no difference in the zopiclone arm compared with the lorazepam arm. Zopiclone is equally effective as lorazepam in the treatment of insomnia in stroke and brain-injured patients.

Lactobacillus salivarius WB21--containing tablets for the treatment of oral malodor: a double-blind, randomized, placebo-controlled crossover trial.

PubMed

Suzuki, Nao; Yoneda, Masahiro; Tanabe, Kazunari; Fujimoto, Akie; Iha, Kosaku; Seno, Kei; Yamada, Kazuhiko; Iwamoto, Tomoyuki; Masuo, Yosuke; Hirofuji, Takao

2014-04-01

This study evaluated the effect of probiotic intervention using lactobacilli on oral malodor. We conducted a 14-day, double-blind, placebo-controlled, randomized crossover trial of tablets containing Lactobacillus salivarius WB21 (2.0 × 10(9) colony-forming units per day) or placebo taken orally by patients with oral malodor. Organoleptic test scores significantly decreased in both the probiotic and placebo periods compared with the respective baseline scores (P < .001 and P = .002), and no difference was detected between periods. In contrast, the concentration of volatile sulfur compounds (VSCs) (P = .019) and the average probing pocket depth (P = .001) decreased significantly in the probiotic period compared with the placebo period. Bacterial quantitative analysis found significantly lower levels of ubiquitous bacteria (P = .003) and Fusobacterium nucleatum (P = .020) in the probiotic period. These results indicated that daily oral consumption of tablets containing probiotic lactobacilli could help to control oral malodor and malodor-related factors. Copyright © 2014 Elsevier Inc. All rights reserved.

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 2014;37(3):483-487. PMID:24587570

Effects of sitagliptin on counter-regulatory and incretin hormones during acute hypoglycaemia in patients with type 1 diabetes: a randomized double-blind placebo-controlled crossover study.

PubMed

Schopman, J E; Hoekstra, J B L; Frier, B M; Ackermans, M T; de Sonnaville, J J J; Stades, A M; Zwertbroek, R; Hartmann, B; Holst, J J; Knop, F K; Holleman, F

2015-06-01

To assess whether the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin affects glucagon and other counter-regulatory hormone responses to hypoglycaemia in patients with type 1 diabetes. We conducted a single-centre, randomized, double-blind, placebo-controlled, three-period crossover study. We studied 16 male patients with type 1 diabetes aged 18-52 years, with a diabetes duration of 5-20 years and intact hypoglycaemia awareness. Participants received sitagliptin (100 mg/day) or placebo for 6 weeks and attended the hospital for three acute hypoglycaemia studies (at baseline, after sitagliptin treatment and after placebo). The primary outcome was differences between the three hypoglycaemia study days with respect to plasma glucagon responses from the initialization phase of the hypoglycaemia intervention to 40 min after onset of the autonomic reaction. Sitagliptin treatment significantly increased active levels of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1. No significant differences were observed for glucagon or adrenergic counter-regulatory responses during the three hypoglycaemia studies. Growth hormone concentration at 40 min after occurrence of autonomic reaction was significantly lower after sitagliptin treatment [median (IQR) 23 (0.2-211.0) mEq/l] compared with placebo [median (IQR) 90 (8.8-180) mEq/l; p = 0.008]. Sitagliptin does not affect glucagon or adrenergic counter-regulatory responses in patients with type 1 diabetes, but attenuates the growth hormone response during late hypoglycaemia. © 2015 John Wiley & Sons Ltd.

Assessment of abuse liability of Tramadol among experienced drug users: Double-blind crossover randomized controlled trial.

PubMed

Das, Mrinmay; Jain, Raka; Dhawan, Anju; Kaur, Amandeep

Tramadol is a widely used opioid analgesic. Different preclinical, clinical, and postmarketing surveillance studies show conflicting results regarding abuse potential of this drug. A randomized double-blind complete crossover study was conducted at National Drug Dependence Treatment Centre, All India Institute of Medical Sciences, New Delhi. Total subjects were 10, comprising total 120 observations (each subject assessed at baseline, 5, 45, and 240 minutes). Subjects with history of substance abuse were included after detoxification and informed consent. Assessment was done using modified single dose opiate questionnaire, morphine benzedrine group (MBG), pentobarbital chlorpromazine alcohol group (PCAG), and two bipolar visual analogue scales (VAS) after administration of three drugs-Tramadol (100 mg), Buprenorphine (0.6 mg), and Placebo (Normal Saline) intramuscularly, at 5-day interval. In intra-group analysis, there was statistically significant increase in scores of all four scales from baseline to all three time points after Tramadol and Buprenorphine administration. In inter-group analysis, statistically higher scores were seen for Buprenorphine in comparison to Tramadol at 5, 45, and 240 minutes for MBG scale; the score was significantly higher for Buprenorphine in VAS for pleasurable effect at 45 and 240 minutes, but not at baseline and 5 minutes. There was no significant difference in score at any point of time between Tramadol and Buprenorphine in PCAG scale and VAS for sedative/alertness effect. The scores were statistically insignificant in case of Placebo. All the subjects liked Buprenorphine most and then Tramadol followed by Placebo. Tramadol has abuse potential (even in therapeutic doses) more than Placebo but less than or comparable to Buprenorphine.

Intervention for phantom limb pain: A randomized single crossover study of mirror therapy

PubMed Central

Ramadugu, Shashikumar; Nagabushnam, Satish C.; Katuwal, Nagendra; Chatterjee, Kaushik

2017-01-01

Introduction: Mirror therapy suggested to help relieve phantom limb pain (PLP) by resolving the visual- proprioceptive dissociation in the brain, but studies so far either had shorter follow-up or smaller sample size. Materials and Methods: In this randomized single crossover trial, 64 amputees with PLP in the age group of 15–75 years of age were distributed into test and control groups by simple randomization method. Of these 28 in control and 32 in test groups, respectively, completed the 4 weeks of mirror therapy and 12 weeks of follow-up assessments. A standardized set of exercises for 15 min/day for 4 and 8 weeks in test and control groups (in the first 4 weeks, the mirror was covered), respectively, was administered under supervision of one of the authors. All were assessed using the visual analog scale and Short-Form McGill Pain Questionnaire on day 0 and at 4, 8, and 12 weeks after therapy. In control group for the initial 4 weeks, the mirror was covered. The assessing author was blinded to the group to which the participants belonged. Results: Significant reduction in PLP was noted in the test group at 4 weeks compared to the control group (P < 0.0001). Significant reduction was seen in control group also after the switchover and sustained for 12 weeks in both. No harm was reported. Conclusion: Mirror therapy is effective in relieving the intensity, duration, frequency, and overall PLP, and improvement is maintained up to 12 weeks’ posttherapy. PMID:29497188

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.

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.

A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles

PubMed Central

Kurosawa, Yuko; Nirengi, Shinsuke; Homma, Toshiyuki; Esaki, Kazuki; Ohta, Mitsuhiro; Clark, Joseph F.; Hamaoka, Takafumi

2015-01-01

Our aim was to determine the quantitative effects of a single-dose of Nattokinase (NK) administration on coagulation/fibrinolysis parameters comprehensively in healthy male subjects. A double-blind, placebo-controlled cross-over NK intervention study was carried out in 12 healthy young males. Following the baseline blood draw, each subject was randomized to receive either a single-dose of 2,000 FU NK (NSK-SD, Japan Bio Science Laboratory Co., Ltd) or placebo with subsequent cross-over of the groups. Subjects donated blood samples at 2, 4, 6 and 8 hours following administration for analysis of coagulation/fibrinolysis parameters. As a result, D-dimer concentrations at 6, and 8 hours, and blood fibrin/fibrinogen degradation products at 4 hours after NK administration elevated significantly (p < 0.05, respectively). Factor VIII activity declined at 4 and 6 hours (p < 0.05, respectively), blood antithrombin concentration was higher at 2 and 4 hours (p < 0.05, respectively), and the activated partial thromboplastin time prolonged significantly at 2 and 4 hours following NK administration (p < 0.05 and p < 0.01, respectively). All the changes, however, were within the normal range. In conclusion, thus, a single-dose of NK administration appears enhancing fibrinolysis and anti-coagulation via several different pathways simultaneously. PMID:26109079

Extra virgin olive oil phenols and markers of oxidation in Greek smokers: a randomized cross-over study.

PubMed

Moschandreas, J; Vissers, M N; Wiseman, S; van Putte, K P; Kafatos, A

2002-10-01

To examine the effect of a low phenol olive oil and high phenol olive oil on markers of oxidation and plasma susceptibility to oxidation in normolipaemic smokers. Randomized single-blind cross-over trial with two intervention periods. The Medical School and University Hospital of the University of Crete, Heraklion, Crete, Greece. Twenty-five healthy males and females completed the study. Each intervention was of three weeks duration and intervention periods were separated by a two week washout. Seventy grams of extra virgin olive oil was supplied to each subject per day in the intervention periods. The olive oils supplied differed in their phenol content by 18.6 mg/day. Two fasting venous blood samples were taken at the end of each intervention period. The markers of antioxidant capacity measured in fasting plasma samples (total plasma resistance to oxidation, concentrations of protein carbonyl as a marker of protein oxidation, malondialdehyde and lipid hydroperoxides as markers of lipid oxidation and the ferric reducing ability of plasma) did not differ significantly between the low and high phenol olive oil diets. No effect of olive oil phenols on markers of oxidation in smokers was detected. It may be that the natural concentrations of phenols in olive oil are too low to produce an effect in the post-absorptive phase. Possible reasons for period effects and interactions between diet and administration period need attention to aid further cross-over trials of this kind. Unilever Research Vlaardingen, The Netherlands.

Differential effects of estrogen and progestin on apolipoprotein B100 and B48 kinetics in postmenopausal women

USDA-ARS?s Scientific Manuscript database

The distinct effects of the estrogen and progestin components of hormonal therapy on the metabolism of apolipoprotein (apo) B-containing lipoproteins have not been studied. We enrolled eight healthy postmenopausal women in a placebo-controlled, randomized, double-blind, crossover study. Each subject...

Digestive and physiological effects of a wheat bran extract, arabino-xylan-oligosaccharide, in breakfast cereal

USDA-ARS?s Scientific Manuscript database

We assessed whether a wheat bran extract containing arabino-xylan-oligosaccharide (AXOS) elicited a prebiotic effect and influenced other physiologic parameters when consumed in ready-to-eat cereal at two dose levels. This double-blind, randomized, controlled, crossover trial evaluated the effects o...

Two Formulations of Venlafaxine are Bioequivalent when Administered as Open Capsule Mixed with Applesauce to Healthy Subjects.

PubMed

Jain, Renu T; Panda, J; Srivastava, A

2011-09-01

Venlafaxine is a unique antidepressant approved for treatment of various depressive disorders. A single dose, cross-over bioequivalence study was performed with two different formulations of venlafaxine 150 mg extended-release capsules in which the contents of capsule were mixed with applesauce and administered to healthy subjects under fed condition. A total of 24 healthy adult male subjects participated in this randomized, single-dose, non-blinded, two-way crossover study conducted at a single centre and 23 subjects completed the study as per the study protocol. After an overnight fast of 10 h, a high-fat and high-calorie breakfast was served 30 min before dosing. The subjects then received a single dose of either formulation administered with apple sauce followed by 240 ml of water as per randomized schedule in each period separated by a washout period of 7 days. A series of blood samples were collected upto 72 h for estimation of venlafaxine and its active metabolite, O-desmethylvenlafaxine. The quantification of venlafaxine and O-desmethylvenlafaxine was done by LC-MS/MS method and pharmacokinetic and statistical analysis by WinNonlin(®) 5.2 and SAS(®) 9.1.3. The results of the study demonstrated bioequivalence of two formulations as the 90% confidence interval for the intra-individual mean ratio of log-transformed C(max), AUC(0-t) and AUC(0-inf) of the test to the reference formulation were found within the defined bioequivalence range of 80.00%-125.00%. Both the formulations were well tolerated. This alternative mode of administration may provide benefits to patients who have difficulty in swallowing the capsule as a whole.

Two Formulations of Venlafaxine are Bioequivalent when Administered as Open Capsule Mixed with Applesauce to Healthy Subjects

PubMed Central

Jain, Renu T.; Panda, J.; Srivastava, A.

2011-01-01

Venlafaxine is a unique antidepressant approved for treatment of various depressive disorders. A single dose, cross-over bioequivalence study was performed with two different formulations of venlafaxine 150 mg extended-release capsules in which the contents of capsule were mixed with applesauce and administered to healthy subjects under fed condition. A total of 24 healthy adult male subjects participated in this randomized, single-dose, non-blinded, two-way crossover study conducted at a single centre and 23 subjects completed the study as per the study protocol. After an overnight fast of 10 h, a high-fat and high-calorie breakfast was served 30 min before dosing. The subjects then received a single dose of either formulation administered with apple sauce followed by 240 ml of water as per randomized schedule in each period separated by a washout period of 7 days. A series of blood samples were collected upto 72 h for estimation of venlafaxine and its active metabolite, O-desmethylvenlafaxine. The quantification of venlafaxine and O-desmethylvenlafaxine was done by LC-MS/MS method and pharmacokinetic and statistical analysis by WinNonlin® 5.2 and SAS® 9.1.3. The results of the study demonstrated bioequivalence of two formulations as the 90% confidence interval for the intra-individual mean ratio of log-transformed Cmax, AUC0-t and AUC0-inf of the test to the reference formulation were found within the defined bioequivalence range of 80.00%-125.00%. Both the formulations were well tolerated. This alternative mode of administration may provide benefits to patients who have difficulty in swallowing the capsule as a whole. PMID:22923863

Effects of Ayurvedic Oil-Dripping Treatment with Sesame Oil vs. with Warm Water on Sleep: A Randomized Single-Blinded Crossover Pilot Study

PubMed Central

Yorifuji, Takashi; Tsuda, Toshihide; Doi, Hiroyuki

2016-01-01

Abstract Objectives: Ayurvedic oil-dripping treatment (Shirodhara) is often used for treating sleep problems. However, few properly designed studies have been conducted, and the quantitative effect of Shirodhara is unclear. This study sought to quantitatively evaluate the effect of sesame oil Shirodhara (SOS) against warm water Shirodhara (WWS) on improving sleep quality and quality of life (QOL) among persons reporting sleep problems. Methods: This randomized, single-blinded, crossover study recruited 20 participants. Each participant received seven 30-minute sessions within 2 weeks with either liquid. The washout period was at least 2 months. The Shirodhara procedure was conducted by a robotic oil-drip system. The outcomes were assessed by the Pittsburgh Sleep Quality Index (PSQI) for sleep quality, Epworth Sleepiness Scale (ESS) for daytime sleepiness, World Health Organization Quality of Life 26 (WHO-QOL26) for QOL, and a sleep monitor instrument for objective sleep measures. Changes between baseline and follow-up periods were compared between the two types of Shirodhara. Analysis was performed with generalized estimating equations. Results: Of 20 participants, 15 completed the study. SOS improved sleep quality, as measured by PSQI. The SOS score was 1.83 points lower (95% confidence interval [CI], −3.37 to −0.30) at 2-week follow-up and 1.73 points lower (95% CI, −3.84 to 0.38) than WWS at 6-week follow-up. Although marginally significant, SOS also improved QOL by 0.22 points at 2-week follow-up and 0.19 points at 6-week follow-up compared with WWS. After SOS, no beneficial effects were observed on daytime sleepiness or objective sleep measures. Conclusions: This pilot study demonstrated that SOS may be a safe potential treatment to improve sleep quality and QOL in persons with sleep problems. PMID:26669255

Comparison of a robotic-assisted gait training program with a program of functional gait training for children with cerebral palsy: design and methods of a two group randomized controlled cross-over trial.

PubMed

Hilderley, Alicia J; Fehlings, Darcy; Lee, Gloria W; Wright, F Virginia

2016-01-01

Enhancement of functional ambulation is a key goal of rehabilitation for children with cerebral palsy (CP) who experience gross motor impairment. Physiotherapy (PT) approaches often involve overground and treadmill-based gait training to promote motor learning, typically as free walking or with body-weight support. Robotic-assisted gait training (RAGT), using a device such as the Lokomat ® Pro, may permit longer training duration, faster and more variable gait speeds, and support walking pattern guidance more than overground/treadmill training to further capitalize on motor learning principles. Single group pre-/post-test studies have demonstrated an association between RAGT and moderate to large improvements in gross motor skills, gait velocity and endurance. A single published randomized controlled trial (RCT) comparing RAGT to a PT-only intervention showed no difference in gait kinematics. However, gross motor function and walking endurance were not evaluated and conclusions were limited by a large PT group drop-out rate. In this two-group cross-over RCT, children are randomly allocated to the RAGT or PT arm (each with twice weekly sessions for eight weeks), with cross-over to the other intervention arm following a six-week break. Both interventions are grounded in motor learning principles with incorporation of individualized mobility-based goals. Sessions are fully operationalized through manualized, menu-based protocols and post-session documentation to enhance internal and external validity. Assessments occur pre/post each intervention arm (four time points total) by an independent assessor. The co-primary outcomes are gross motor functional ability (Gross Motor Function Measure (GMFM-66) and 6-minute walk test), with secondary outcome measures assessing: (a) individualized goals; (b) gait variables and daily walking amounts; and (c) functional abilities, participation and quality of life. Investigators and statisticians are blinded to study group allocation in the analyses, and assessors are blinded to treatment group. The primary analysis will be the pre- to post-test differences (change scores) of the GMFM-66 and 6MWT between RAGT and PT groups. This study is the first RCT comparing RAGT to an active gait-related PT intervention in paediatric CP that addresses gait-related gross motor, participation and individualized outcomes, and as such, is expected to provide comprehensive information as to the potential role of RAGT in clinical practice. Trial registration ClinicalTrials.gov NCT02196298.

Dark chocolate and vascular function in patients with peripheral artery disease: a randomized, controlled cross-over trial.

PubMed

Hammer, Alexandra; Koppensteiner, Renate; Steiner, Sabine; Niessner, Alexander; Goliasch, Georg; Gschwandtner, Michael; Hoke, Matthias

2015-01-01

Flavonoid-rich dark chocolate has positive effects on vascular function in healthy subjects and in patients at risk of atherosclerosis. The impact of dark chocolate on endothelial and microvascular function in patients with symptomatic peripheral artery disease (PAD) has not been investigated so far. In an investigator blinded, randomized, controlled, cross-over trial we assessed the effect of flavonoid-rich dark chocolate and cocoa-free control chocolate on flow-mediated dilatation (FMD) of the brachial artery and on microvascular function (assessed by Laser Doppler fluxmetry) in 21 patients with symptomatic (Fontaine stage II) PAD. Measurements were done in each patient on 2 single days, with an interval of 7 days, at baseline and at 2 hours after ingestion of 50 g dark chocolate or 50 g white chocolate, respectively. FMD remained unchanged after intake of dark chocolate (baseline and 2 hours after ingestion, %: 5.1 [IQR 4.4 to 7.3] and 5.5 [IQR 3.9 to 10.4]; p = 0.57, and after intake of white chocolate (baseline and 2 hours after ingestion, %: 6.4 [IQR 4.5 to 11.4] and 4.4 [IQR 2.6 to 8.7]; p = 0.14. Similarly, microcirculatory parameters were not significantly altered after intake of any chocolate compared with the respective baseline values. In conclusion, a single consumption of 50 g dark chocolate has no effect on endothelial and microvascular function in patients with symptomatic PAD.

Comparison of chocolate to cacao-free white chocolate in Parkinson's disease: a single-dose, investigator-blinded, placebo-controlled, crossover trial.

PubMed

Wolz, Martin; Schleiffer, Christine; Klingelhöfer, Lisa; Schneider, Christine; Proft, Florian; Schwanebeck, Uta; Reichmann, Heinz; Riederer, Peter; Storch, Alexander

2012-11-01

A previous questionnaire study suggests an increased chocolate consumption in Parkinson's disease (PD). The cacao ingredient contains caffeine analogues and biogenic amines, such as β-phenylethylamine, with assumed antiparkinsonian effects. We thus tested the effects of 200 g of chocolate containing 80 % of cacao on UPDRS motor score after 1 and 3 h in 26 subjects with moderate non-fluctuating PD in a mono-center, single-dose, investigator-blinded crossover study using cacao-free white chocolate as placebo comparator. At 1 h after chocolate intake, mean UPDRS motor scores were mildly decreased compared to baseline in both treatments with significant results only for dark chocolate [-1.3 (95 % CI 0.18-2.52, RMANOVA F = 4.783, p = 0.013¸ Bonferroni p = 0.021 for 1 h values)]. A 2 × 2-cross-over analysis revealed no significant differences between both treatments [-0.54 ± 0.47 (95 % CI -1.50 to 0.42), p = 0.258]. Similar results were obtained at 3 h after intake. β-phenylethylamine blood levels were unaltered. Together, chocolate did not show significant improvement over white cacao-free chocolate in PD motor function.

Laboratory- and community-based health outcomes in people with transtibial amputation using crossover and energy-storing prosthetic feet: A randomized crossover trial

PubMed Central

Morgan, Sara J.; McDonald, Cody L.; Halsne, Elizabeth G.; Cheever, Sarah M.; Salem, Rana; Kramer, Patricia A.

2018-01-01

Contemporary prosthetic feet are generally optimized for either daily or high-level activities. Prosthesis users, therefore, often require multiple prostheses to participate in activities that span a range of mobility. Crossover feet (XF) are designed to increase the range of activities that can be performed with a single prosthesis. However, little evidence exists to guide clinical prescription of XF relative to traditional energy storing feet (ESF). The objective of this study was to assess the effects of XF and ESF on health outcomes in people with transtibial amputation. A randomized crossover study was conducted to assess changes in laboratory-based (endurance, perceived exertion, walking performance) and community-based (step activity and self-reported mobility, fatigue, balance confidence, activity restrictions, and satisfaction) outcomes. Twenty-seven participants were fit with XF and ESF prostheses with standardized sockets, interfaces, and suspensions. Participants were not blinded to the intervention, and wore each prosthesis for one month while their steps were counted with an activity monitor. After each accommodation period, participants returned for data collection. Endurance and perceived exertion were measured with the Six-Minute Walk Test and Borg-CR100, respectively. Walking performance was measured using an electronic walkway. Self-reported mobility, fatigue, balance confidence, activity restrictions, and satisfaction were measured with survey instruments. Participants also reported foot preferences upon conclusion of the study. Differences between feet were assessed with a crossover analysis. While using XF, users experienced improvements in most community-based outcomes, including mobility (p = .001), fatigue (p = .001), balance confidence (p = .005), activity restrictions (p = .002), and functional satisfaction (p < .001). Participants also exhibited longer sound side steps in XF compared to ESF (p < .001). Most participants (89%) reported an overall preference for XF; others (11%) reported no preference. Results indicate that XF may be a promising alternative to ESF for people with transtibial amputation who engage in a range of mobility activities. Trial registration: ClinicalTrials.gov NCT02440711 PMID:29414988

Differential Effects of Methylphenidate on Attentional Functions in Children with Attention-Deficit-Hyperactivity Disorder

ERIC Educational Resources Information Center

Konrad, Kerstin; Gunther, Thomas; Hanisch, Charlotte; Herpertz-Dahlmann, Beate

2004-01-01

Objective: To examine the effects of methylphenidate on different attentional functions and behavior in children with attention-deficit-hyperactivity disorder (ADHD). Method: A total of 60 ADHD children aged between 8 and 12 years completed a randomized, double-blind, placebo-controlled, within-subject crossover trial with two doses of…

Simulated Driving Changes in Young Adults with ADHD Receiving Mixed Amphetamine Salts Extended Release and Atomoxetine

ERIC Educational Resources Information Center

Kay, Gary G.; Michaels, M. Alex; Pakull, Barton

2009-01-01

Background: Psychostimulant treatment may improve simulated driving performance in young adults with attention-deficit/hyperactivity disorder (ADHD). Method: This was a randomized, double-blind, placebo-controlled, crossover study of simulated driving performance with mixed amphetamine salts--extended release (MAS XR) 50 mg/day (Cohort 1) and…

A randomized, placebo-controlled, crossover study of an herbal preparation containing Vernonia cinerea in the treatment of type 2 diabetes.

PubMed

Bin Sayeed, Muhammad Shahdaat; Mostofa, A G M; Ferdous, F M Touhidul Islam; Islam, Md Siddiqul

2013-09-01

A randomized, single-center, double-blind, crossover clinical trial investigated the effects of an herbal preparation containing Vernonia cinerea in patients with type 2 diabetes mellitus. 48 patients with type 2 diabetes mellitus for longer than 6 months were divided into two groups matched for demographic and paraclinical variables. One group received a standard preparation of V. cinerea for 3 months, followed by placebo for another 3 months, and the other group received treatment in the reverse order. All patients received detailed advice on diet, exercise, and lifestyle modification. Glucose level was documented every 2 weeks, and hemoglobin A1c, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein cholesterol, triglycerides, aspartate aminotransferase, alanine aminotransferase, and creatinine levels were determined at recruitment, 3 months, and study completion at 6 months. Glucose, hemoglobin A1c, cholesterol, LDL cholesterol, and triglyceride levels decreased significantly in both groups. No significant differences were seen in aspartate aminotransferase, alanine aminotransferase, or creatinine levels, indicating that use of the herbal preparation had no adverse effect on liver or renal function. Herbal treatment with V. cinerea has a beneficial effect on reducing the glycemic state in patients with type 2 diabetes.

The acute effect of pleasurable music on craving for alcohol: A pilot crossover study.

PubMed

Mathis, Walter S; Han, Xiaotong

2017-07-01

Chronic administration of drugs of abuse leads to a dopamine deficient state in the mesolimbic system, causing dysphoria in abstinence and contributing to craving and return to use. Recent functional imaging studies have shown that listening to personally pleasing music activates the mesolimbic reward system in a fashion similar to drugs of abuse. It has been proposed that such activation could ameliorate the dysphoria and craving of the hypodopaminergic state. The present study sought to evaluate the efficacy of listening to personally pleasing or moving music on reducing craving in abstinent alcoholics using a single-blind, within-subject randomized block design, with three randomly determined presentations of each condition. Twelve participants with Alcohol Use Disorder on a residential substance rehabilitation unit reported their level of craving with a Visual Analog Scale before and after listening to either the participant-selected song or white noise. Using a mixed model to analyze the crossover design, the music intervention was found to have a statistically significant advantage in craving reduction compared to the noise control. Our results indicate that personally pleasing music might have a role in augmenting substance use disorder treatment via craving reduction. Further study is warranted to elucidate factors which predict the most robust response from this intervention. Copyright © 2017 Elsevier Ltd. All rights reserved.

Efficacy and safety of creatine supplementation in juvenile dermatomyositis: A randomized, double-blind, placebo-controlled crossover trial.

PubMed

Solis, Marina Yazigi; Hayashi, Ana Paula; Artioli, Guilherme Giannini; Roschel, Hamilton; Sapienza, Marcelo Tatit; Otaduy, Maria Concepción; De Sã Pinto, Ana Lucia; Silva, Clovis Artur; Sallum, Adriana Maluf Elias; Pereira, Rosa Maria R; Gualano, Bruno

2016-01-01

It has been suggested that creatine supplementation is safe and effective for treating idiopathic inflammatory myopathies, but no pediatric study has been conducted to date. The objective of this study was to examine the efficacy and safety of creatine supplementation in juvenile dermatomyositis (JDM) patients. In this study, JDM patients received placebo or creatine supplementation (0.1 g/kg/day) in a randomized, crossover, double-blind design. Subjects were assessed at baseline and after 12 weeks. The primary outcome was muscle function. Secondary outcomes included body composition, aerobic conditioning, health-related quality of life, and muscle phosphocreatine (PCr) content. Safety was assessed by laboratory parameters and kidney function measurements. Creatine supplementation did not affect muscle function, intramuscular PCr content, or any other secondary outcome. Kidney function was not affected, and no side effects were reported. Twelve weeks of creatine supplementation in JDM patients were well-tolerated and free of adverse effects, but treatment did not affect muscle function, intramuscular PCr, or any other parameter. © 2015 Wiley Periodicals, Inc.

Aged Garlic Extract Improves Adiponectin Levels in Subjects with Metabolic Syndrome: A Double-Blind, Placebo-Controlled, Randomized, Crossover Study

PubMed Central

Gómez-Arbeláez, Diego; Lahera, Vicente; Oubiña, Pilar; Valero-Muñoz, Maria; de las Heras, Natalia; Rodríguez, Yudy; García, Ronald Gerardo; Camacho, Paul Anthony; López-Jaramillo, Patricio

2013-01-01

Background. Garlic (Allium sativum) has been shown to have important benefits in individuals at high cardiovascular risk. The aim of the present study was to evaluate the effects of the administration of aged garlic extract (AGE) on the risk factors that constitute the cluster of metabolic syndrome (MS). Methods and Design. Double-blind, crossover, randomized, placebo-controlled clinical trial to assess the effect of 1.2 g/day of AGE (Kyolic), for 24 weeks of treatment (12 weeks of AGE and 12 weeks of placebo), on subjects with MS. Results. The administration of AGE increased the plasma levels of adiponectin (P = 0.027). No serious side effects associated with the intervention were reported. Conclusion. The present results have shown for the first time that the administration of AGE for 12 weeks increased plasma adiponectin levels in patients with MS. This suggests that AGE might be a useful, novel, nonpharmacological therapeutic intervention to increase adiponectin and to prevent cardiovascular (CV) complications in individuals with MS. PMID:23533302

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

PubMed

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

2016-02-08

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

Effects of Oral L-Carnitine Administration in Narcolepsy Patients: A Randomized, Double-Blind, Cross-Over and Placebo-Controlled Trial

PubMed Central

Miyagawa, Taku; Kawamura, Hiromi; Obuchi, Mariko; Ikesaki, Asuka; Ozaki, Akiko; Tokunaga, Katsushi; Inoue, Yuichi; Honda, Makoto

2013-01-01

Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness, cataplexy, and rapid eye movement (REM) sleep abnormalities. A genome-wide association study (GWAS) identified a novel narcolepsy-related single nucleotide polymorphism (SNP), which is located adjacent to the carnitine palmitoyltransferase 1B (CPT1B) gene encoding an enzyme involved in β-oxidation of long-chain fatty acids. The mRNA expression levels of CPT1B were associated with this SNP. In addition, we recently reported that acylcarnitine levels were abnormally low in narcolepsy patients. To assess the efficacy of oral l-carnitine for the treatment of narcolepsy, we performed a clinical trial administering l-carnitine (510 mg/day) to patients with the disease. The study design was a randomized, double-blind, cross-over and placebo-controlled trial. Thirty narcolepsy patients were enrolled in our study. Two patients were withdrawn and 28 patients were included in the statistical analysis (15 males and 13 females, all with HLA-DQB1*06:02). l-carnitine treatment significantly improved the total time for dozing off during the daytime, calculated from the sleep logs, compared with that of placebo-treated periods. l-carnitine efficiently increased serum acylcarnitine levels, and reduced serum triglycerides concentration. Differences in the Japanese version of the Epworth Sleepiness Scale (ESS) and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) vitality and mental health subscales did not reach statistical significance between l-carnitine and placebo. This study suggests that oral l-carnitine can be effective in reducing excessive daytime sleepiness in narcolepsy patients. Trial Registration University hospital Medical Information Network (UMIN) UMIN000003760 PMID:23349733

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

PubMed Central

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

2016-01-01

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

Electrically Assisted Movement Therapy in Chronic Stroke Patients With Severe Upper Limb Paresis: A Pilot, Single-Blind, Randomized Crossover Study.

PubMed

Carda, Stefano; Biasiucci, Andrea; Maesani, Andrea; Ionta, Silvio; Moncharmont, Julien; Clarke, Stephanie; Murray, Micah M; Millán, José Del R

2017-08-01

To evaluate the effects of electrically assisted movement therapy (EAMT) in which patients use functional electrical stimulation, modulated by a custom device controlled through the patient's unaffected hand, to produce or assist task-specific upper limb movements, which enables them to engage in intensive goal-oriented training. Randomized, crossover, assessor-blinded, 5-week trial with follow-up at 18 weeks. Rehabilitation university hospital. Patients with chronic, severe stroke (N=11; mean age, 47.9y) more than 6 months poststroke (mean time since event, 46.3mo). Both EAMT and the control intervention (dose-matched, goal-oriented standard care) consisted of 10 sessions of 90 minutes per day, 5 sessions per week, for 2 weeks. After the first 10 sessions, group allocation was crossed over, and patients received a 1-week therapy break before receiving the new treatment. Fugl-Meyer Motor Assessment for the Upper Extremity, Wolf Motor Function Test, spasticity, and 28-item Motor Activity Log. Forty-four individuals were recruited, of whom 11 were eligible and participated. Five patients received the experimental treatment before standard care, and 6 received standard care before the experimental treatment. EAMT produced higher improvements in the Fugl-Meyer scale than standard care (P<.05). Median improvements were 6.5 Fugl-Meyer points and 1 Fugl-Meyer point after the experimental treatment and standard care, respectively. The improvement was also significant in subjective reports of quality of movement and amount of use of the affected limb during activities of daily living (P<.05). EAMT produces a clinically important impairment reduction in stroke patients with chronic, severe upper limb paresis. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Curcuma decreases serum hepcidin levels in healthy volunteers: a placebo-controlled, randomized, double-blind, cross-over study.

PubMed

Lainé, Fabrice; Laviolle, Bruno; Bardou-Jacquet, Edouard; Fatih, Nadia; Jezequel, Caroline; Collet, Nicolas; Ropert, Martine; Morcet, Jeff; Hamon, Catherine; Reymann, Jean-Michel; Loréal, Olivier

2017-10-01

Hepcidin, secreted by hepatocytes, controls iron metabolism by limiting iron egress in plasma. Hepcidin is upregulated during inflammation through the activation of the signal transducer and activator of transcription 3 (STAT3) transduction pathway, which decreases iron bioavailability and may explain the anemia of chronic inflammatory disease. In vitro, it has been shown that curcumin can decrease hepcidin synthesis by decreasing STAT3 activity. We conducted a proof-of-concept study to assess the effect of curcuma on hepcidin synthesis in human. This was a placebo-controlled, randomized, double-blind, cross-over, two-period study performed in 18 healthy male volunteers. Subjects received a single oral dose of 6 g curcuma containing 2% of curcumin or placebo. Serum hepcidin and iron parameters were assessed repeatedly until 48 h after dosing. When compared with a placebo curcuma decreased hepcidin levels significantly at 6 h (-19%, P = 0.004), 8 h (-17%, P = 0.009), and 12 h (-17%, P = 0.007) and tended to decrease hepcidin at 24 h (-15%, P = 0.076). Curcuma also significantly increased serum ferritin levels at 6 and 8 h (+7% for both times, P = 0.018, 0.030, respectively) and had no effects on serum iron, transferrin, and transferrin saturation. This pilot study showed that curcuma decreases serum hepcidin levels in human and supports the idea that curcuma could be useful in treating hepcidin overproduction during inflammatory processes. Confirmatory studies in patients with chronic inflammation are now required to determine the optimal dose and therapeutic scheme of curcuma. © 2017 Société Française de Pharmacologie et de Thérapeutique.

Pharmacological treatments of cerebellar ataxia.

PubMed

Ogawa, Masafumi

2004-01-01

The confirmed pharmacological treatment of cerebellar ataxia is still lacking. In a recent preliminary trial, we showed that D-cycloserine, a partial NMDA allosteric agonist, may relieve the symptoms. In this paper, major clinical trials to relieve ataxic symptoms are reviewed. Previous studies showed some efficacy of physostigmine in ataxic patients. However, physostigmine did not improve the ataxia in a recent double-blind crossover study. The replacement therapy of the deficient cholinergic system with choline or choline derivatives was tried in patients with Friedreich's ataxia and other ataxic patients, but the result was not definitive. A levorotatory form of hydroxytryptophan (a serotonin precursor), a serotoninergic 5-HT1A agonist, a serotoninergic 5-HT3 antagonist, and a serotonin reuptake inhibitor were also used for the therapy for ataxia. In a double-blind randomized study, buspirone, a 5-HT1A agonist was active in cerebellar ataxia, but the effect is partial and not major. The effects of the studies with the other serotoninergic drugs were not consistent. The effect of sulfamethoxazole-trimethoprim therapy in spinocerebellar ataxia type3/Machado-Joseph disease (MJD) was reported, although the therapy improved spasticity or rigidity, rather than ataxia. In contrast to previous studies, sulfamethoxazole-trimethoprim therapy in MJD had no effect in a 2001 double-blind crossover study. The thyrotropin-releasing hormone, D-cycloserine, and acetazolamide for SCA6 may have some efficacy. However, a well-designed double-blind crossover trial is needed to confirm the effect.

The Effect of Beta Adrenergic Blockade on Ratings of Perceived Exertion.

DTIC Science & Technology

1984-01-01

exrcis is uvo Hughson, et al. (47) investigated the effect of beta blockade using a single, 100-mg oral dose of metoprolol or matched placebo on 12...administered either placebo, propranolol (80 mug) or metoprolol (100 mug) in a double- blind, randomised manner. Before the muscle-strength tests were...The non-selective BABA propranolol and the selective agent metoprolol were compared with a placebo in a double blind cross-over design. Measurements

Evaluation of the gastrointestinal tolerability of corn starch fiber, a novel dietary fiber, in two independent randomized, double-blind, crossover studies in healthy men and women.

PubMed

Crincoli, Christine M; Garcia-Campayo, Vicenta; Rihner, Marisa O; Nikiforov, Andrey I; Liska, DeAnn; van de Ligt, Jennifer L G

2016-11-01

Two independent clinical studies were conducted to compare the gastrointestinal (GI) tolerability of corn starch fiber, a novel dietary fiber, at up to 50 g/day (single-dose study) or 90 g/day (multiple-serving study) with a negative control (no fiber) and a positive control (50 or 90 g polydextrose, for single- and multiple-serving studies, respectively) in generally healthy study volunteers. Flatulence and borborygmus were the primary symptoms reported at the higher doses of corn starch fiber and for the positive control interventions. Bowel movements were increased over 48 h with corn starch fiber at 90 g. Thresholds for mild GI effects were established at 30 g as a single dose and 60 g as multiple servings spread over the day. Other than moderate abdominal pain and mild increased appetite in one subject at 90-g corn starch fiber, no test article-related adverse events were reported.

Single-center, single-dose, open-label, randomized, two-period crossover study on the bioavailability of methotrexate administered using a novel prefilled, needle-free delivery system.

PubMed

Bienvenu, Boris; Aouba, Achille; Gottenberg, Jacques-Eric; Verstuyft, Celine

2017-04-01

Zeneo 1 is a needle-free injection device. We performed a pharmacokinetic study to investigate the bioequivalence of methotrexate administered subcutaneously using either the needle-free injection device or a conventional needle and syringe. This was a single-dose, open-label, laboratory-blind, randomized crossover study performed in adult healthy volunteers. Each participant received two methotrexate injections (each 25 mg), one via needle-free injection device and one via conventional injection, with a 21-28 day wash-out interval between dosing. For each participant, the administration site for both injections was either the abdomen or the thigh. The primary pharmacokinetic outcome parameters were AUC (0- t ) and C max . Bioequivalence was assessed by standard criteria: whether 90% confidence intervals of geometric mean ratios for the two administration methods were within 80-125%. Fifty-two individuals completed the study. Bioequivalence criteria were met for AUC (0- t ) , for the overall analysis (both injection sites: 90% confidence interval: 99.4-103.1%), and for each injection site separately. Bioequivalence was similarly demonstrated with AUC (0-∞) . Bioequivalence criteria for C max were fulfilled for abdominal administration but not for the overall analysis. Injection via the needle-free injection device was well tolerated. Limitations include conducting the study in healthy volunteers and the relatively small subject number (albeit satisfactory for bioequivalence). This study shows that methotrexate injection via needle-free injection device is bioequivalent to a conventional needle and syringe in relation to AUC (0- t ) and AUC (0-∞) . Studies of needle-free injection device use in patients requiring methotrexate therapy are planned.

Increased calcium absorption from synthetic stable amorphous calcium carbonate: double-blind randomized crossover clinical trial in postmenopausal women.

PubMed

Vaisman, Nachum; Shaltiel, Galit; Daniely, Michal; Meiron, Oren E; Shechter, Assaf; Abrams, Steven A; Niv, Eva; Shapira, Yami; Sagi, Amir

2014-10-01

Calcium supplementation is a widely recognized strategy for achieving adequate calcium intake. We designed this blinded, randomized, crossover interventional trial to compare the bioavailability of a new stable synthetic amorphous calcium carbonate (ACC) with that of crystalline calcium carbonate (CCC) using the dual stable isotope technique. The study was conducted in the Unit of Clinical Nutrition, Tel Aviv Sourasky Medical Center, Israel. The study population included 15 early postmenopausal women aged 54.9 ± 2.8 (mean ± SD) years with no history of major medical illness or metabolic bone disorder, excess calcium intake, or vitamin D deficiency. Standardized breakfast was followed by randomly provided CCC or ACC capsules containing 192 mg elemental calcium labeled with 44Ca at intervals of at least 3 weeks. After swallowing the capsules, intravenous CaCl2 labeled with 42Ca on was administered on each occasion. Fractional calcium absorption (FCA) of ACC and CCC was calculated from the 24-hour urine collection following calcium administration. The results indicated that FCA of ACC was doubled (± 0.96 SD) on average compared to that of CCC (p < 0.02). The higher absorption of the synthetic stable ACC may serve as a more efficacious way of calcium supplementation. © 2014 American Society for Bone and Mineral Research.

Time Course of Treatment Effect of OROS[R] Methylphenidate in Children with ADHD

ERIC Educational Resources Information Center

Armstrong, Robert B.; Damaraju, C. V.; Ascher, Steve; Schwarzman, Lesley; O'Neill, James; Starr, H. Lynn

2012-01-01

Objective: The authors evaluated the time course of the treatment effect of Osmotic-Release Oral System methylphenidate (OROS[R] MPH) HCl (Concerta[R], Raritan, NJ) CII in children with ADHD. Method: Data were combined from two double-blind, randomized, placebo-controlled, cross-over, analog classroom studies in children (9-12 years) with ADHD.…

Increased cytokine production by monocytes from human subjects who consumed grape powder was not mediated by differences in dietary intake patterns

USDA-ARS?s Scientific Manuscript database

Recently, in a randomized, double-blind cross-over study, we reported that consumption of grape powder by obese human subjects increased the production of the pro-inflammatory cytokines interleukin-1' and interleukin-6 by ex vivo-derived peripheral blood monocytes after exposure to bacterial lipopol...

Evaluation of 5 Hour Energy Drink on the Blood Pressure and Electrocardiograph Parameters on Young Healthy Volunteers: A Randomized, Double Blind, Crossover, Placebo-Controlled Trial (Presentation)

DTIC Science & Technology

2014-02-11

other substances. • There have been reports of atrial fibrillation , Takotsubo cardiomyopathy and sudden cardiac deaths in healthy individuals...baseline cardiac rhythm, history of atrial or ventricular arrhythmia, baseline corrected QT (QTc) interval greater than 440 milliseconds (msec

Cap Assisted Upper Endoscopy for Examination of the Major Duodenal Papilla: A Randomized, Blinded, Controlled Crossover Study (CAPPA Study).

PubMed

Abdelhafez, Mohamed; Phillip, Veit; Hapfelmeier, Alexander; Elnegouly, Mayada; Poszler, Alexander; Strobel, Kilian; Born, Peter; Dollhopf, Markus; Kassem, Abdel Meguid; Calavrezos, Lenika; Klare, Peter; Schlag, Christoph; Bajbouj, Monther; Schmid, Roland M; von Delius, Stefan

2017-05-01

Examination of major duodenal papilla (MDP) by standard forward-viewing esophagogastroduodenoscopy (S-EGD) is limited. Cap assisted esophagogastroduodenoscopy (CA-EGD) utilizes a cap fitted to the tip of the endoscope that can depress the mucosal folds and thus might improve visualization of MDP. The aim of this study was to compare CA-EGD to S-EGD for complete examination of the MDP. Prospective, randomized, blinded, controlled crossover study. Subjects scheduled for elective EGD were randomized to undergo S-EGD (group A) or CA-EGD (group B) before undergoing a second examination by the alternate method. Images of the MDP were evaluated by three blinded multicenter-experts. Our primary outcome measure was complete examination of the papilla. Secondary outcome measures were duration and overall diagnostic yield. A total of 101 patients were randomized and completed the study. Complete examination of MDP was achieved in 98 patients using CA-EGD compared to 24 patients using S-EGD (97 vs. 24%, P<0.001). Median duration from intubation of the esophagus until localization of the MDP was shorter with CA-EGD (46. vs. 96 s., P<0.001). In group A, 11 extra lesions and 12 additional incidental findings were detected by secondary CA-EGD, whereas neither were detected by secondary S-EGD in group B (22 vs. 0% and 24 vs. 0%, P<0.001 and P<0.001). CA-EGD enabled complete examination of MDP in almost all cases compared to a low success rate of S-EGD. CA-EGD detected a significant amount of lesions and incidental findings when added to S-EGD. CA-EGD is a safe and effective method for examination of MDP.

Right ventricular function during one-lung ventilation: effects of pressure-controlled and volume-controlled ventilation.

PubMed

Al Shehri, Abdullah M; El-Tahan, Mohamed R; Al Metwally, Roshdi; Qutub, Hatem; El Ghoneimy, Yasser F; Regal, Mohamed A; Zien, Haytham

2014-08-01

To test the effects of pressure-controlled (PCV) and volume-controlled (VCV) ventilation during one-lung ventilation (OLV) for thoracic surgery on right ventricular (RV) function. A prospective, randomized, double-blind, controlled, crossover study. A single university hospital. Fourteen pairs of consecutive patients scheduled for elective thoracotomy. Patients were assigned randomly to ventilate the dependent lung with PCV or VCV mode, each in a randomized crossover order using tidal volume of 6 mL/kg, I: E ratio 1: 2.5, positive end-expiratory pressure (PEEP) of 5 cm H2O and respiratory rate adjusted to maintain normocapnia. Intraoperative changes in RV function (systolic and early diastolic tricuspid annular velocity (TAV), end-systolic volume (ESV), end-diastolic volume (EDV) and fractional area changes (FAC)), airway pressures, compliance and oxygenation index were recorded. The use of PCV during OLV resulted in faster systolic (10.1±2.39 vs. 5.8±1.67 cm/s, respectively), diastolic TAV (9.2±1.99 vs. 4.6±1.42 cm/s, respectively) (p<0.001) and compliance and lower ESV, EDV and airway pressures (p<0.05) than during the use of VCV. Oxygenation indices were similar during the use of VCV and PCV. The use of PCV offers more improved RV function than the use of VCV during OLV for open thoracotomy. These results apply specifically to younger patients with good ventricular and pulmonary functions. © 2014 Elsevier Inc. All rights reserved.

Overview of registered studies in orthodontics: Evaluation of the ClinicalTrials.gov registry.

PubMed

Allareddy, Veerasathpurush; Rampa, Sankeerth; Masoud, Mohamed I; Lee, Min Kyeong; Nalliah, Romesh; Allareddy, Veerajalandhar

2014-11-01

The Food and Drug Administration Modernization Act of 1997 made it mandatory for all phase II through IV trials regulated by this Act to be registered. After this, the National Institutes of Health created ClinicalTrials.gov, which is a registry of publicly and privately supported clinical studies of human participants. The objective of this study was to examine the characteristics of registered studies in orthodontics. The ClinicalTrials.gov Web site was used to query all registered orthodontic studies. The search term used was "orthodontics." No limitations were placed for the time period. All registered studies regardless of their recruitment status, study results, and study type were selected for analysis. A total of 64 orthodontic studies were registered as of January 1, 2014. Of these, 52 were interventional, and 12 were observational. Close to 60% of the interventional studies and 66.7% of the observational studies had sample sizes of 50 or fewer subjects. About 21.2% of the interventional studies and 16.7% of the observational studies had sample sizes greater than 100. Only 1 study was funded by the National Institutes of Health, and the rest were funded by "other" or "industry" sources. Close to 87.7% of the interventional studies were randomized. Interventional model assignments included factorial assignment (3.9%), parallel assignments (74.5%), crossover assignment (7.8%), and single-group assignment (13.7%). Most studies were treatment oriented (80.4%). The types of masking used by the interventional studies included open label (28.9%), single blind (44.2%), and double blind (26.9%). Outcome assessors were blinded in only 6 studies. Orthodontic studies registered in ClinicalTrials.gov are dominated by small single-center studies. There are wide variations with regard to treatment allocation approaches and randomization methods in the studies. These results also indicate the need for multicenter clinical studies in orthodontics. Copyright © 2014 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

Dapoxetine has no pharmacokinetic or cognitive interactions with ethanol in healthy male volunteers.

PubMed

Modi, Nishit B; Dresser, Mark; Desai, Dhaval; Edgar, Christopher; Wesnes, Keith

2007-03-01

Dapoxetine is being investigated for the treatment of premature ejaculation. This study evaluated the potential pharmacokinetic and cognitive interactions of dapoxetine 60 mg with ethanol 0.5 g/kg in a single-center, double-blind, randomized, placebo-controlled crossover study in healthy adult male participants (n = 24). Dapoxetine was rapidly absorbed and eliminated; peak concentrations were noted 1.47 hours after administration and decreased with an alpha half-life of 1.33 hours and a terminal half-life of 15.6 hours. Pharmacokinetic parameters (C(max), AUC(infinity), t((1/2)), and t(max)) of dapoxetine were not altered with concurrent ethanol consumption. Furthermore, coadministration of dapoxetine did not affect the pharmacokinetics of ethanol or potentiate the cognitive and subjective effects of ethanol.

An investigation of the safety and pharmacokinetics of the novel TRPV1 antagonist XEN-D0501 in healthy subjects

PubMed Central

Round, Patrick; Priestley, Anthony; Robinson, Jan

2011-01-01

AIMS XEN-D0501, a novel TRPV1 antagonist, is being developed to treat overactive bladder. This study investigated the safety and pharmacokinetics of repeat-dose XEN-D0501 in healthy subjects. METHODS The study was conducted in two parts. Part 1 was a double-blind, randomized, placebo-controlled, two-way crossover study in three cohorts of 12 young male subjects. Each subject received XEN-D0501 and placebo (in random order) twice daily for 13 days, with a final single dose on day 14. Doses of 1, 2.5 and 5 mg XEN-D0501 were investigated. Part 2 was an open-label, randomized, two-way crossover study in male and female subjects (45 to 65 years). Subjects received single doses of 5 mg XEN-D0501 under fasted and fed conditions in random order. Blood sampling and safety assessments were conducted throughout the study. RESULTS XEN-D0501 was rapidly absorbed (tmax generally 0.5–4 h post dose). XEN-D0501 exposure increased less than proportionally to dose over the range studied and exhibited minimal accumulation with twice daily dosing. Food had no clinically relevant effects on the pharmacokinetics of XEN-D0501. There were no severe or serious adverse events and all doses were well tolerated. A dose-related increase in body temperature was seen with XEN-D0501 which attenuated over time. Differences from placebo in mean maximum core body temperatures were 0.22°C, 0.5°C and 0.74°C following 1 mg, 2.5 mg and 5 mg twice daily XEN-D0501. The observed increase in body temperature was not considered to be of clinical concern. CONCLUSIONS XEN-D0501 appeared safe and well tolerated at doses up to 5 mg twice daily for 14 days in healthy subjects. PMID:21676011

A randomized multi-institutional crossover comparison of the GlideScope® Cobalt Video laryngoscope to the flexible fiberoptic bronchoscope in a Pierre Robin manikin.

PubMed

Fiadjoe, John E; Hirschfeld, Matthew; Wu, Stephan; Markley, James; Gurnaney, Harshad; Jawad, Abbas F; Stricker, Paul; Kilbaugh, Todd; Ross, Patrick; Kovatsis, Pete

2015-08-01

The GlideScope Cobalt Video laryngoscope is being used more often in children with challenging laryngoscopy. There are, however, no pediatric trials comparing it to flexible fiberoptic bronchoscopy, the current accepted gold standard. This preliminary manikin study compares the first-attempt intubation success of the GlideScope Cobalt video laryngoscope to the flexible fiberoptic bronchoscope when performed by attending pediatric anesthesiologists at two major pediatric centers. This prospective randomized, crossover study evaluated 120 attempts (60 with each study device) to intubate the AirSim Pierre Robin manikin (PRM) with fiberoptic bronchoscopy and video laryngoscopy (VL). Attending pediatric anesthesiologists from two quaternary pediatric centers were eligible to participate. Each attending anesthesiologist randomly performed a single tracheal intubation attempt with one of the study devices followed by the alternate method. The primary outcome was the first-attempt success rate of tracheal intubation. Blinding was not feasible. We hypothesized that first-attempt success would be higher with fiberoptic bronchoscopy. Thirty anesthesiologists from each center were randomized to use one of the study devices followed by the alternate method. We analyzed all participants' data. There was no overall difference in first-attempt success between VL and fiberoptic bronchoscopy (88.3% vs 85% respectively, P = 0.59). There were significant institutional differences in first-attempt success using VL (76.7% vs 100%). There was no difference in first-attempt success of tracheal intubation using VL vs fiberoptic bronchoscopy when performed by attending anesthesiologists at two large pediatric centers. However, institutional differences exist in success rates with VL across the two centers. Results from single-center device evaluations should be verified by multi-center evaluations. A significant proportion of attending anesthesiologists lack experience with advanced airway devices; targeted education may enhance intubation success and patient safety. © 2015 John Wiley & Sons Ltd.

Orodispersible sublingual piribedil to abort OFF episodes: a single dose placebo-controlled, randomized, double-blind, cross-over study.

PubMed

Rascol, Olivier; Azulay, Jean-Philippe; Blin, Olivier; Bonnet, Anne-Marie; Brefel-Courbon, Christine; Césaro, Pierre; Damier, Philippe; Debilly, Bérengère; Durif, Frank; Galitzky, Monique; Grouin, Jean-Marie; Pennaforte, Sylvie; Villafane, Gabriel; Yaici, Sadek; Agid, Yves

2010-02-15

S90049, a novel sublingual formulation of the non-ergoline D(2)-D(3) agonist piribedil, has a pharmacokinetic profile promising to provide rapid relief on motor signs in Parkinson's disease (PD). We assessed the efficacy and safety of S90049 in aborting OFF episodes responding to subcutaneous apomorphine in PD patients with motor fluctuations. This was a single-dose double-blind double-placebo 3 x 3 cross-over study. Optimal tested doses were determined during a previous open-label titration phase (S90049 median dose: 60 mg, apomorphine: 5 mg). Primary endpoint was the maximal change versus baseline in UPDRS motor score (Delta UPDRS III) assessed after drug administration following an overnight withdrawal of antiparkinsonian medications. Thirty patients (age: 60 +/- 8 years, PD duration: 12 +/- 6 years, UPDRS III OFF: 37 +/- 15) participated. S90049 was superior to placebo on Delta UPDRS III (-13 +/- 12 versus -7 +/- 9 respectively; estimated difference -5.2, 95% Confidence Interval (CI)[-10.4;0.05], P = 0.05). This was also true for secondary outcomes: number of patients switching from OFF to ON (17 on S90049 vs. 8 on placebo, P = 0.03), time to turn ON (P = 0.013) and duration of the ON phase (P = 0.03). In the 17 patients who switched ON on S90049, Delta UPDRS III was similar on S90049 (-21.2 +/- 10.1) and apomorphine (-23.6 +/- 14.1) (estimated difference: 4.0 95% CI [-2.9;10.9]). S90049 was well tolerated: no serious or unexpected adverse event occurred. A single dose of up to 60 mg of S90049 given sublingually was superior to placebo in improving UPDRS III and aborting a practical OFF in patients with advanced PD. Testing greater doses might improve response rate. (c) 2009 Movement Disorder Society.

The effects of St. John's wort extract and amitriptyline on autonomic responses of blood vessels and sweat glands in healthy volunteers.

PubMed

Siepmann, Martin; Kirch, Wilhelm; Krause, Stephanie; Joraschky, Peter; Mueck-Weymann, Michael

2004-02-01

St. John's wort extract is widely used and advertised as a "natural antidepressant" lacking autonomic side effects. This randomized, double-blind, placebo-controlled study compared the effects of St. John's wort extract on autonomic responses of blood vessels and sweat glands with those of amitriptyline and placebo. A randomized, double-blind, crossover study was performed in healthy male volunteers aged 22 to 31 years (25 +/- 3 years; mean +/- SD) years. Subjects orally received capsules with 255 to 285 mg St. John's wort extract (900 microg hypericin content), 25 mg amitriptyline, and placebo 3 times daily for periods of 14 days each with at least 14 days between. Vasoconstrictory response of cutaneous blood flow (VR) and skin conductance response (SR) following a single deep inspiration were employed as parameters of autonomic function. St. John's wort extract had no effect on VR and SR. In contrast, SR was diminished and the dilation phase of VR was prolonged following multiple dosing with amitriptyline (P < 0.05). Decreased electrodermal reactivity observed with amitriptyline reflects inhibition of acetylcholine at peripheral m3-cholinoreceptors, whereas prolongation of VR induced by the tricyclic drug may be due to sustained activation of central and/or peripheral sympathetic neurons.

Dietary supplementation with purified citrus limonin glucoside does not alter ex vivo functions of circulating T lymphocytes or monocytes in overweight/obese human adults

USDA-ARS?s Scientific Manuscript database

Overweight/obesity is associated with chronic inflammation and impairs both innate and adaptive immune responses. Limonoids found in citrus fruits have shown health benefits in human and animal studies. In a double-blind, randomized, crossover study, 10 overweight/obese human subjects were fed pur...

Influence of Caffeine Ingestion on Perceived Mood States, Concentration, and Arousal Levels during a 75-Min University Lecture

ERIC Educational Resources Information Center

Peeling, Peter; Dawson, Brian

2007-01-01

This investigation aimed to assess the effect of a caffeine supplement on perceived mood state, concentration, and arousal during a 75-min university lecture. Methods. This randomized, blind, cross-over design investigation ran over a course of 2 consecutive weeks. During "week" 1, 10 third-year Human Movement and Exercise Science…

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.

Effects of SuperUlam on Supporting Concentration and Mood: A Randomized, Double-Blind, Placebo-Controlled Crossover Study.

PubMed

Udani, Jay K

2013-01-01

Background. SuperUlam is a proprietary blend of natural ingredients aimed at supporting brain health. We aimed to evaluate the effect of SuperUlam on attention and mood in healthy adults. Methods. Twenty healthy individuals aged 35-65 were enrolled in this randomized, double-blind, placebo-controlled, crossover study. Study duration was 3 weeks and consisted of 3 visits. Measurement of cognitive function included computer-based testing of reaction time, complex attention, working memory, sustained attention, and executive functioning. Mood testing was performed via the profile of mood states (POMS) survey and the Chalder fatigue scale. Results. Cognitive function testing demonstrated a significant improvement from baseline in executive functioning, cognitive flexibility, reaction time, and working memory in the product group only (P < 0.05). When comparing the study product to placebo, the data demonstrated a significant decrease in tension, depression, and anger (P < 0.05). There was no significant difference between the product and placebo in the other measures of mood, including vigor, fatigue, confusion, and total mood disturbance. No adverse events were reported. Conclusions. Supplementation with SuperUlam is safe to consume with potential benefits to cognitive function and mood.

Effects of SuperUlam on Supporting Concentration and Mood: A Randomized, Double-Blind, Placebo-Controlled Crossover Study

PubMed Central

Udani, Jay K

2013-01-01

Background. SuperUlam is a proprietary blend of natural ingredients aimed at supporting brain health. We aimed to evaluate the effect of SuperUlam on attention and mood in healthy adults. Methods. Twenty healthy individuals aged 35–65 were enrolled in this randomized, double-blind, placebo-controlled, crossover study. Study duration was 3 weeks and consisted of 3 visits. Measurement of cognitive function included computer-based testing of reaction time, complex attention, working memory, sustained attention, and executive functioning. Mood testing was performed via the profile of mood states (POMS) survey and the Chalder fatigue scale. Results. Cognitive function testing demonstrated a significant improvement from baseline in executive functioning, cognitive flexibility, reaction time, and working memory in the product group only (P < 0.05). When comparing the study product to placebo, the data demonstrated a significant decrease in tension, depression, and anger (P < 0.05). There was no significant difference between the product and placebo in the other measures of mood, including vigor, fatigue, confusion, and total mood disturbance. No adverse events were reported. Conclusions. Supplementation with SuperUlam is safe to consume with potential benefits to cognitive function and mood. PMID:24371452

Synbiotic Lactobacillus acidophilus NCFM and cellobiose does not affect human gut bacterial diversity but increases abundance of lactobacilli, bifidobacteria and branched-chain fatty acids: a randomized, double-blinded cross-over trial.

PubMed

van Zanten, Gabriella C; Krych, Lukasz; Röytiö, Henna; Forssten, Sofia; Lahtinen, Sampo J; Abu Al-Soud, Waleed; Sørensen, Søren; Svensson, Birte; Jespersen, Lene; Jakobsen, Mogens

2014-10-01

Probiotics, prebiotics, and combinations thereof, that is synbiotics, have been reported to modulate gut microbiota of humans. In this study, effects of a novel synbiotic on the composition and metabolic activity of human gut microbiota were investigated. Healthy volunteers (n = 18) were enrolled in a double-blinded, randomized, and placebo-controlled cross-over study and received synbiotic [Lactobacillus acidophilus NCFM (10(9) CFU) and cellobiose (5 g)] or placebo daily for 3 weeks. Fecal samples were collected and lactobacilli numbers were quantified by qPCR. Furthermore, 454 tag-encoded amplicon pyrosequencing was used to monitor the effect of synbiotic on the composition of the microbiota. The synbiotic increased levels of Lactobacillus spp. and relative abundances of the genera Bifidobacterium, Collinsella, and Eubacterium while the genus Dialister was decreased (P < 0.05). No other effects were found on microbiota composition. Remarkably, however, the synbiotic increased concentrations of branched-chain fatty acids, measured by gas chromatography, while short-chain fatty acids were not affected. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

No evidence for differential dose effects of hydrocortisone on intrusive memories in female patients with complex post-traumatic stress disorder--a randomized, double-blind, placebo-controlled, crossover study.

PubMed

Ludäscher, Petra; Schmahl, Christian; Feldmann, Robert E; Kleindienst, Nikolaus; Schneider, Miriam; Bohus, Martin

2015-10-01

Post-traumatic stress disorder is characterized by intrusive traumatic memories. Presently, a controversial debate is ongoing regarding whether reduced cortisol secretion in post-traumatic stress disorder promotes an automatic retrieval of trauma-associated memories. Hence, a pharmacological elevation of cortisol was proposed to decrease post-traumatic stress disorder symptoms, particularly intrusions. The present study investigated the impact of two different doses of hydrocortisone on automatic memory retrieval using a randomized, double-blind, placebo-controlled, crossover study in 30 inpatients with post-traumatic stress disorder. All participants were female and received various psychotropic medications. They were randomly assigned to one of two groups within a crossover design: they received either 1 week placebo followed by 1 week hydrocortisone 10/d, followed by 1 week placebo, followed by hydrocortisone 30 mg/d (15 participants) or 1 week hydrocortisone 30 mg/d, followed by 1 week placebo, followed by 1 week hydrocortisone 10 mg/d, followed by 1 week placebo (15 participants). The outcome measures were the frequency and the intensity of intrusions, the overall symptomatology of post-traumatic stress disorder and the general psychopathology. We did not find any differences in the frequency and the intensity of post-traumatic stress disorder-related intrusions between the 10 mg hydrocortisone, the 30 mg hydrocortisone and the placebo condition. All effect sizes for the hydrocortisone condition vs. placebo were very small. Additionally, the overall symptomatology of post-traumatic stress disorder and the general psychopathology did not differ between the hydrocortisone therapies and placebo. Our results do not show any effect of the hydrocortisone administration on intrusions in complex post-traumatic stress disorder. © The Author(s) 2015.

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

PubMed

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

2015-09-01

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

Comparison of the Effects of Intermittent Boluses to Simple Continuous Infusion on Patients' Global Perceived Effect in Intrathecal Therapy for Pain: A Randomized Double-Blind Crossover Study.

PubMed

Eldabe, Sam; Duarte, Rui V; Madzinga, Grace; Batterham, Alan M; Brookes, Morag E; Gulve, Ashish P; Perruchoud, Christophe; Raphael, Jon H; Lorenzana, David; Buchser, Eric

2017-05-01

Intrathecal drug delivery (ITDD) is commonly used for intractable pain management. A paucity of good-quality studies in chronic noncancer patients and concerns over increased dosages have focused interest on different modes of administration. The aim of this international multicenter randomized double-blind crossover trial was to compare the efficacy of the same daily dose of drugs administered by intermittent boluses vs simple continuous infusion. Eligible patients implanted with a programmable ITDD device were randomized to receive two weeks of either intermittent boluses or a simple continuous flow in period 1, followed by a crossover to the alternative mode of administration. The primary outcome measure was the Patients' Global Impression of Change (PGIC) scale. The mean proportion of positive responders (at least "minimally improved") was 38.4% in the continuous condition vs 37.3% in the bolus (difference in proportions = 1.1%, 95% confidence interval [CI] = -21.8-24.0%, P  = 0.93). The mean PGIC in the continuous condition was 3.8 vs 3.9 in the bolus (mean difference = -0.1, -0.6-0.4, P  = 0.72). Exploratory analyses revealed a tendency for the mean proportion of positive responders to be higher at low vs high flow rates for both bolus and continuous administrations. Two patients were withdrawn from the study due to adverse events during the bolus phase, both with symptoms of increased pain, and one patient with additional symptoms of numbness and urinary retention. The mean PGIC and proportion of positive responders was not substantially different after intermittent bolus vs continuous administration. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

A randomized placebo-controlled trial of miglustat in cystic fibrosis based on nasal potential difference.

PubMed

Leonard, Anissa; Lebecque, Patrick; Dingemanse, Jasper; Leal, Teresinha

2012-05-01

Preclinical data suggest that miglustat could restore the function of the cystic fibrosis transmembrane conductance regulator gene in cystic fibrosis cells. Single-center, randomized, double-blind, placebo-controlled, crossover Phase II study in 11 patients (mean±SD age, 26.3±7.7 years) homozygous for the F508del mutation received oral miglustat 200 mgt.i.d. or placebo for two 8-day cycles separated by a 14-day washout period. The primary endpoint was the change in total chloride secretion (TCS) assessed by nasal potential difference. No statistically significant changes in TCS, sweat chloride values or FEV(1) were detected. Pharmacokinetic and safety were similar to those observed in patients with other diseases exposed to miglustat. There was no evidence of a treatment effect on any nasal potential difference variable. Further studies with miglustat need to adequately address criteria for assessment of nasal potential difference. Copyright © 2011 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Influence of experimental esophageal acidification on sleep bruxism: a randomized trial.

PubMed

Ohmure, H; Oikawa, K; Kanematsu, K; Saito, Y; Yamamoto, T; Nagahama, H; Tsubouchi, H; Miyawaki, S

2011-05-01

The aim of this cross-over, randomized, single-blinded trial was to examine whether intra-esophageal acidification induces sleep bruxism (SB). Polysomnography with electromyogram (EMG) of masseter muscle, audio-video recording, and esophageal pH monitoring were performed in a sleep laboratory. Twelve healthy adult males without SB participated. Intra-esophageal infusions of 5-mL acidic solution (0.1 N HCl) or saline were administered. The frequencies of EMG bursts, rhythmic masticatory muscle activity (RMMA) episodes, grinding noise, and the RMMA/microarousal ratio were significantly higher in the 20-minute period after acidic infusion than after saline infusion. RMMA episodes including SB were induced by esophageal acidification. This trial is registered with the UMIN Clinical Trials Registry, UMIN000002923. ASDA, American Sleep Disorders Association; EMG, electromyogram; GER, gastroesophageal reflux; LES, lower esophageal sphincter; NREM, non-rapid eye movement; REM, rapid eye movement; RMMA, rhythmic masticatory muscle activity; SB, sleep bruxism; SD, standard deviation; UES, upper esophageal sphincter.

Anesthetic efficacy of a repeated intraosseous injection following a primary intraosseous injection.

PubMed

Jensen, Joanne; Nusstein, John; Drum, Melissa; Reader, Al; Beck, Mike

2008-02-01

The purpose of this prospective, randomized, single-blinded study was to determine the anesthetic efficacy of a repeated intraosseous injection given 30 minutes after a primary intraosseous injection. Using a crossover design, 55 subjects randomly received a primary X-tip intraosseous injection (Dentsply Inc, York, PA) of 1.4 mL of 2% lidocaine with epinephrine (using the Wand; Milestone Scientific, Deerfield, IL) and a repeated intraosseous or mock injection at 30 minutes in two appointments. The first molar and adjacent teeth were pulp tested every 2 minutes for a total of 120 minutes. Success was defined as obtaining two consecutive 80 readings with the electric pulp tester. Success of the initial intraosseous injection was 100% for the first molar. The repeated intraosseous injection mimicked the initial intraosseous injection in terms of pulpal anesthesia and statistically provided another 15 minutes of pulpal anesthesia. In conclusion, using the methodology presented, repeating the intraosseous injection 30 minutes after an initial intraosseous injection will provide an additional 15 minutes of pulpal anesthesia.

Consuming High-Carotenoid Fruit and Vegetables Influences Skin Yellowness and Plasma Carotenoids in Young Women: A Single-Blind Randomized Crossover Trial.

PubMed

Pezdirc, Kristine; Hutchesson, Melinda J; Williams, Rebecca L; Rollo, Megan E; Burrows, Tracy L; Wood, Lisa G; Oldmeadow, Christopher; Collins, Clare E

2016-08-01

Consumption of dietary carotenoids from fruits and vegetables (F/V) leads to accumulations in human skin, altering skin yellowness. The influence of the quantity of F/V consumed on skin yellowness and plasma carotenoid concentrations has not been examined previously. To compare the influence of consuming high-carotenoid-containing F/V (HCFV) (176,425 μg beta carotene/wk) vs low-carotenoid F/V (LCFV) (2,073 μg beta carotene/wk) on skin yellowness and plasma carotenoid concentrations, over 4 weeks. A single-blind randomized controlled crossover trial from October 2013 to March 2014. Thirty women were randomized to receive 7 daily servings of HCFV or LCFV for 4 weeks. Following a 2-week washout period they followed the alternate intervention. Skin color (Commission Internationale de l'Eclairage L*a*b* color space, where L* represents skin lightness and positive values of a* and b* represent degrees of redness and yellowness, respectively) was assessed by reflectance spectroscopy in both sun-exposed and nonexposed skin areas. Fasting plasma carotenoids were determined by high-performance liquid chromatography, before and after each intervention period. Linear mixed models were used to determine the HCFV and LCFV response on skin color and plasma carotenoids, adjusting for intervention order, time, and interaction between baseline differences and time. There were no significant differences in mean daily fruit (P=0.42) and vegetable (P=0.17) intakes between HCFV and LCFV groups. Dietary alpha carotene, beta carotene, lutein, and beta cryptoxanthin intakes were significantly different between the two groups (P<0.01). Following HCFV there was a significantly greater increase in skin yellowness (b*) in both sun-exposed (P<0.001) and unexposed areas, (P<0.001), with no change in skin lightness (L*) or redness (a*). Significantly higher plasma alpha carotene (P=0.004), beta carotene (P=0.001), and lutein (P=0.028) concentrations were found following the HCFV intervention. Skin yellowness correlated with alpha carotene and beta carotene. Skin yellowness (b*) and fasting plasma carotenoid concentrations were significantly higher following HCFV than LCFV over 4 weeks. Copyright © 2016 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

Feasibility of a randomized single-blind crossover trial to assess the effects of the second-generation slow-release dopamine agonists pramipexole and ropinirole on cued recall memory in idiopathic mild or moderate Parkinson's disease without cognitive impairment.

PubMed

Shepherd, Thomas A; Edelstyn, Nicola M J; Longshaw, Laura; Sim, Julius; Watts, Keira; Mayes, Andrew R; Murray, Michael; Ellis, Simon J

2018-01-01

The aim was to assess the feasibility of a single-centre, single-blind, randomized, crossover design to explore the effects of two slow-release dopamine agonists, ropinirole and pramipexole, on cued recall in Parkinson's disease. As the design required a switch from the prescribed agonist (pramipexole-to-ropinirole, or ropinirole-to-pramipexole), the primary objectives were to (a) examine the efficacy of processes and procedures used to manage symptoms during the washout period and (b) to use cued recall estimates to inform a power calculation for a definitive trial. Secondary objectives were to assess consent and missing data rates, acceptability of clinical support for the OFF sessions, experience of the OFF sessions and of agonist switching, barriers-to-participation for patients and informal caregivers. Patients were randomized in a 1:1 ratio to two treatment arms and stabilized on each agonist for 6 weeks. The arms differed only in the sequence in which the agonists were administered. Cued recall was assessed ON medication and, following a washout period resulting in 93.75% agonist elimination, OFF medication. A total of 220 patients were screened: 145 were excluded and 75 invitations to participate were sent to eligible patients. Fifty-three patients declined, 22 consented and 16 completed the study. There were no serious adverse events, and rates of non-serious adverse events were equivalent between the agonists. Using the largest standard deviation (SD) of the ON-OFF difference cued recall score (inflated by ~25% to give a conservative estimate of the SD in a definitive trial) and assuming an effect of at least 10% of the observed range of OFF medication cued recall scores for either agonist to be clinically important, a main trial requires a sample size of just under 150 patients. The consent and missing data rates were 29 and 27% respectively. The washout period and the preparation for the OFF sessions were acceptable, and the sessions were manageable. The experience of switching was also manageable. Barriers to participation included concerns about disease stability, side effects, research process, carer workload and accessibility of the information sheet. This study presented challenges to recruitment both in design and execution, and while it was a major aim of the study to assess this, evaluation of these challenges provided the opportunity to explore how they could be overcome for future studies. EudraCT 2012-000801-64.

The dynamics of the metabolism of acetate and bicarbonate associated with use of hemodialysates in the ABChD trial: a phase IV, prospective, single center, single blind, randomized, cross-over, two week investigation.

PubMed

Smith, William B; Gibson, Sandy; Newman, George E; Hendon, Kendra S; Askelson, Margarita; Zhao, James; Hantash, Jamil; Flanagan, Brigid; Larkin, John W; Usvyat, Len A; Thadhani, Ravi I; Maddux, Franklin W

2017-08-29

In the United States, hemodialysis (HD) is generally performed via a bicarbonate dialysate. It is not known if small amounts of acid used in dialysate to buffer the bicarbonate can meaningfully contribute to overall buffering administered during HD. We aimed to investigate the metabolism of acetate with use of two different acid buffer concentrates and determine if it effects blood bicarbonate concentrations in HD patients. The Acid-Base Composition with use of hemoDialysates (ABChD) trial was a Phase IV, prospective, single blind, randomized, cross-over, 2 week investigation of peridialytic dynamics of acetate and bicarbonate associated with use of acid buffer concentrates. Eleven prevalent HD patients participated from November 2014 to February 2015. Patients received two HD treatments, with NaturaLyte® and GranuFlo® acid concentrates containing 4 and 8 mEq/L of acetate, respectively. Dialysate order was chosen in a random fashion. The endpoint was to characterize the dynamics of acetate received and metabolized during hemodialysis, and how it effects overall bicarbonate concentrations in the blood and dialysate. Acetate and bicarbonate concentrations were assessed before, at 8 time points during, and 6 time points after the completion of HD. Data from 20 HD treatments for 11 patients (10 NaturaLyte® and 10 GranuFlo®) was analyzed. Cumulative trajectories of arterialized acetate were unique between NaturaLyte® and GranuFlo® (p = 0.003), yet individual time points demonstrated overlap without remarkable differences. Arterialized and venous blood bicarbonate concentrations were similar at HD initiation, but by 240 min into dialysis, mean arterialized bicarbonate concentrations were 30.2 (SD ± 4.16) mEq/L in GranuFlo® and 28.8 (SD ± 4.26) mEq/L in NaturaLyte®. Regardless of acid buffer concentrate, arterial blood bicarbonate was primarily dictated by the prescribed bicarbonate level. Subjects tolerated HD with both acid buffer concentrates without experiencing any related adverse events. A small fraction of acetate was delivered to HD patients with use of NaturaLyte® and GranuFlo® acid buffers; the majority of acetate received was observed to be rapidly metabolized and cleared from the circulation. Blood bicarbonate concentrations appear to be determined mainly by the prescribed concentration of bicarbonate. This trial was registered on ClinicalTrials.gov on 11 Dec 2014 ( NCT02334267 ).

Effects of polydextrose with breakfast or with a midmorning preload on food intake and other appetite-related parameters in healthy normal-weight and overweight females: An acute, randomized, double-blind, placebo-controlled, and crossover study.

PubMed

Ibarra, Alvin; Olli, Kaisa; Pasman, Wilrike; Hendriks, Henk; Alhoniemi, Esa; Raza, Ghulam Shere; Herzig, Karl-Heinz; Tiihonen, Kirsti

2017-03-01

Polydextrose (PDX) reduces subsequent energy intake (EI) when administered at midmorning in single-blind trials of primarily normal-weight men. However, it is unclear if this effect also occurs when PDX is given at breakfast time. Furthermore, for ecological validity, it is desirable to study a female population, including those at risk for obesity. We studied the effects of PDX, served as part of a breakfast or midmorning preload, on subsequent EI and other appetite-related parameters in healthy normal-weight and overweight females. Per earlier studies, the primary outcome was defined as the difference in subsequent EI when PDX was consumed at midmorning versus placebo. Thirty-two volunteers were enrolled in this acute, double-blind, placebo-controlled, randomized, and crossover trial to examine the effects of 12.5 g of PDX, administered as part of a breakfast or midmorning preload, on subsequent EI, subjective feelings of appetite, well-being, and mood. Gastric emptying rates and the blood concentrations of glucose, insulin, cholecystokinin, ghrelin, glucagon-like peptide 1 (GLP-1), and peptide tyrosine-tyrosine were measured in the group that received PDX as part of their breakfast. There were no differences in EI between volunteers who were fed PDX and placebo. PDX intake with breakfast tended to elevate blood glucose (P = 0.06) during the postabsorptive phase, significantly lowered insulin by 15.7% (P = 0.04), and increased GLP-1 by 39.9% (P = 0.02); no other effects on blood parameters or gastric emptying rates were observed. PDX intake at midmorning reduced hunger by 31.4% during the satiation period (P = 0.02); all other subjective feelings of appetite were unaffected. Volunteers had a uniform mood profile during the study. PDX was well tolerated, causing one mild adverse event throughout the trial. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Beta-1 vs. beta-2 adrenergic control of coronary blood flow during isometric handgrip exercise in humans.

PubMed

Maman, Stephan R; Vargas, Alvaro F; Ahmad, Tariq Ali; Miller, Amanda J; Gao, Zhaohui; Leuenberger, Urs A; Proctor, David N; Muller, Matthew D

2017-08-01

During exercise, β-adrenergic receptors are activated throughout the body. In healthy humans, the net effect of β-adrenergic stimulation is an increase in coronary blood flow. However, the role of vascular β1 vs. β2 receptors in coronary exercise hyperemia is not clear. In this study, we simultaneously measured noninvasive indexes of myocardial oxygen supply (i.e., blood velocity in the left anterior descending coronary artery; Doppler echocardiography) and demand [i.e., rate pressure product (RPP) = heart rate × systolic blood pressure) and tested the hypothesis that β1 blockade with esmolol improves coronary exercise hyperemia compared with nonselective β-blockade with propranolol. Eight healthy young men received intravenous infusions of esmolol, propranolol, and saline on three separate days in a single-blind, randomized, crossover design. During each infusion, subjects performed isometric handgrip exercise until fatigue. Blood pressure, heart rate, and coronary blood velocity (CBV) were measured continuously, and RPP was calculated. Changes in parameters from baseline were compared with paired t -tests. Esmolol (Δ = 3296 ± 1204) and propranolol (Δ = 2997 ± 699) caused similar reductions in peak RPP compared with saline (Δ = 5384 ± 1865). In support of our hypothesis, ΔCBV with esmolol was significantly greater than with propranolol (7.3 ± 2.4 vs. 4.5 ± 1.6 cm/s; P = 0.002). This effect was also evident when normalizing ΔCBV to ΔRPP. In summary, not only does selective β1 blockade reduce myocardial oxygen demand during exercise, but it also unveils β2-receptor-mediated coronary exercise hyperemia. NEW & NOTEWORTHY In this study, we evaluated the role of vascular β1 vs. β2 receptors in coronary exercise hyperemia in a single-blind, randomized, crossover study in healthy men. In response to isometric handgrip exercise, blood flow velocity in the left anterior descending coronary artery was significantly greater with esmolol compared with propranolol. These findings increase our understanding of the individual and combined roles of coronary β1 and β2 adrenergic receptors in humans. Copyright © 2017 the American Physiological Society.

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

Effect of low oral doses of disopyramide and amiodarone on ventricular and atrial arrhythmias of chagasic patients with advanced myocardial damage.

PubMed

Carrasco, H A; Vicuña, A V; Molina, C; Landaeta, A; Reynosa, J; Vicuña, N; Fuenmayor, A; López, F

1985-12-01

Low-dose (7 mg/kg per day) disopyramide administration to arrhythmic chagasic patients decreased the frequency of ventricular extrasystoles in 4 of 17 patients (24%) and suppressed most complex ventricular arrhythmias in 12 of 15 patients (80%). This assessment was made from 72-h continuous Holter monitoring recorded during the course of this double blind, placebo-controlled randomized crossover study. Seven patients (41%) complained of anticholinergic side effects, but no contractile or conduction system depression was seen. Amiodarone (200 mg) given on a single blind, placebo-controlled basis to 9 of these patients reduced the frequency of ventricular extrasystoles in 6 of 9 patients (67%) and suppressed complex ventricular ectopy in 6 of 7 patients (85%). One patient was unable to tolerate this drug (11%). Both drugs seemed less effective in controlling supraventricular arrhythmias, although disopyramide eliminated paroxysms of supraventricular tachycardia in 9 of 13 (69%) and amiodarone in all 6 patients with this arrhythmia. Amiodarone appears to be a better antiarrhythmic drug for chagasic patients, due to its greater effectiveness and lower incidence of side effects.

A Randomized, Crossover Trial of a Novel Sound-to-Sleep Mattress Technology in Children with Autism and Sleep Difficulties.

PubMed

Frazier, Thomas W; Krishna, Jyoti; Klingemier, Eric; Beukemann, Mary; Nawabit, Rawan; Ibrahim, Sally

2017-01-15

This preliminary study investigated the tolerability and efficacy of a novel mattress technology-the Sound-To-Sleep (STS) system-in the treatment of sleep problems in children with autism. After screening, 45 children, ages 2.5 to 12.9 years, were randomized to order of mattress technology use (On-Off vs. Off-On). Treatment conditions (On vs. Off) lasted two weeks with immediate crossover. Tolerability, including study discontinuation and parent-report of mattress tolerance and ease of use, was tracked throughout the study. Efficacy assessments were obtained at baseline, prior to crossover, and end of study and included measures of autism traits, other psychopathology symptoms, sensory abnormalities, communication difficulties, quality of life, sleep diary parameters, and single-blinded actigraphy-derived sleep parameters. Statistical analyses evaluated differences in tolerability and efficacy when the STS system was on versus off. STS system use was well tolerated (n = 2, 4.4% dropout) and resulted in parent-reported sleep quality improvements (STS off mean = 4.3, 95% CI = 4.05-4.54 vs. on mean = 4.9, 95%CI = 4.67-5.14). The technology was described by parents as very easy to use and child tolerance was rated as good. Parent-diary outcomes indicated improvements in falling asleep and reduced daytime challenging behavior. Actigraphy-derived sleep parameters indicated improved sleep duration and sleep efficiency. Improvements in child and family quality of life were identified on parent questionnaires. A future large sample phase 2 trial of the STS system is warranted and would benefit from extended study duration, an objective primary efficacy outcome, and careful attention to methodological issues that promote compliance with the intervention and study procedures. © 2017 American Academy of Sleep Medicine

Acute Garcinia mangostana (mangosteen) supplementation does not alleviate physical fatigue during exercise: a randomized, double-blind, placebo-controlled, crossover trial.

PubMed

Chang, Chih-Wei; Huang, Tzu-Zung; Chang, Wen-Hsin; Tseng, Yi-Chun; Wu, Yu-Tse; Hsu, Mei-Chich

2016-01-01

The purple mangosteen (Garcinia mangostana), known as the "queen of fruit," is widely consumed and unique not only because of its outstanding appearance and flavor but also its remarkable and diverse pharmacological effects. The aim of the present study is to evaluate the effect of acute mangosteen supplementation on physical fatigue during exercise. A randomized, double-blind, placebo-controlled, crossover study was carried out by 12 healthy adults. The participants were randomly assigned to receive acute oral administration of either 250 mL of the mangosteen-based juice (supplementation treatment; 305 mg of α-mangostin and 278 mg of hydroxycitric acid) or a placebo (control treatment) 1 h before cycle ergometer exercise. Time to exhaustion, heart rate, Borg Rating of Perceived Exertion score, blood biochemical markers (namely ammonia, cortisol, creatine kinase, aspartate aminotransferase, alanine aminotransferase, glucose, and lactate), muscle dynamic stiffness, and Profile of Mood States (POMS) were evaluated and recorded. The results showed all parameters we examined were significantly altered by the exercise challenge, which demonstrated they directly reflected the condition of fatigue. However, there were no differences between the two treatments besides a positive impact on the POMS examination. The occurrence of physical fatigue depends on multiple underlying mechanisms. We concluded that acute mangosteen supplementation had no impact on alleviating physical fatigue during exercise.

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.

Multimodal Cognitive Enhancement Therapy for Patients with Mild Cognitive Impairment and Mild Dementia: A Multi- Center, Randomized, Controlled, Double-Blind, Crossover Trial.

PubMed

Han, Ji Won; Lee, Hyeonggon; Hong, Jong Woo; Kim, Kayoung; Kim, Taehyun; Byun, Hye Jin; Ko, Ji Won; Youn, Jong Chul; Ryu, Seung-Ho; Lee, Nam-Jin; Pae, Chi-Un; Kim, Ki Woong

2017-01-01

We developed and evaluated the effect of Multimodal Cognitive Enhancement Therapy (MCET) consisting of cognitive training, cognitive stimulations, reality orientation, physical therapy, reminiscence therapy, and music therapy in combination in older people with mild cognitive impairment (MCI) or mild dementia. This study was a multi-center, double-blind, randomized, placebo-controlled, two-period cross-over study (two 8-week treatment phases separated by a 4-week wash-out period). Sixty-four participants with MCI or dementia whose Clinical Dementia Rating was 0.5 or 1 were randomized to the MCET group or the mock-therapy (placebo) group. Outcomes were measured at baseline, week 9, and week 21. Fifty-five patients completed the study. Mini-Mental State Examination (effect size = 0.47, p = 0.013) and Alzheimer's Disease Assessment Scale-Cognitive Subscale (effect size = 0.35, p = 0.045) scores were significantly improved in the MCET compared with mock-therapy group. Revised Memory and Behavior Problems Checklist frequency (effect size = 0.38, p = 0.046) and self-rated Quality of Life - Alzheimer's Disease (effect size = 0.39, p = 0.047) scores were significantly improved in the MCET compared with mock-therapy. MCET improved cognition, behavior, and quality of life in people with MCI or mild dementia more effectively than conventional cognitive enhancing activities did.

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.

Electrocardiographic effects of hawthorn (Crataegus oxyacantha) in healthy volunteers: A randomized controlled trial.

PubMed

Trexler, Stephanie E; Nguyen, Elaine; Gromek, Samantha M; Balunas, Marcy J; Baker, William L

2018-04-19

The objective of this study was to evaluate the electrocardiographic effects of hawthorn in healthy adult volunteers. It was double-blind cross-over trial randomized 20 healthy adult volunteers to receive either a single oral 160-mg dose of hawthorn or matching placebo. Triplicate 12-lead electrocardiograms were taken before treatment and at 1-, 2-, 4-, and 6-hr post-dose. Following at least a 7-day washout period, participants were crossed over to the opposing treatment arm and had the measurements repeated. The primary endpoint was the change in corrected (Fridericia) QT intervals (QT c I) at 4 and 6 hr. Maximum post-dose QT c I and changes in PR and QRS intervals were measured. No significant differences in 4- or 6-hr QT c I were seen between hawthorn and placebo. Maximum post-dose QT c I in the hawthorn and placebo groups were similar (346 ± 35 vs 346 ± 40 ms; p = .979). No significant adverse events were seen. In conclusion, a single dose of oral hawthorn had no effect on electrocardiographic parameters in healthy volunteers. Copyright © 2018 John Wiley & Sons, Ltd.

A Randomized, Double Crossover Study to Investigate the Influence of Saline Infusion on Sleep Apnea Severity in Men

PubMed Central

Yadollahi, Azadeh; Gabriel, Joseph M.; White, Laura H.; Taranto Montemurro, Luigi; Kasai, Takatoshi; Bradley, T. Douglas

2014-01-01

Study Objectives: Obstructive sleep apnea (OSA) is commoner in patients with fluid-retaining states than in those without fluid retention, in men than in women, and worsens with aging. In men, OSA severity is related to the amount of fluid shifting out of the legs overnight, but a cause-effect relationship is not established. Our objective was to test the hypothesis that mimicking fluid overload during sleep would increase severity of OSA more in older (≥ 40 years) than in younger men (< 40 years). Design: Randomized, single-blind, double crossover study. Setting: Research sleep laboratory. Patients or Participants: Seven older and 10 younger men with non-severe or no sleep apnea, matched for body mass index. Interventions: During the control arm, normal saline was infused to keep the vein open. During intervention, subjects received an intravenous bolus of normal saline (22 mL/kg body weight) after sleep onset while they were wearing compression stockings to prevent fluid accumulation in the legs. Measurements and Results: Compared to younger men, infusion of similar amounts of saline in older men caused a greater increase in neck circumference (P < 0.05) and in the AHI (32.2 ± 22.1 vs. 2.2 ± 7.1, P = 0.002). Conclusions: Older men are more susceptible to the adverse effects of intravenous fluid loading on obstructive sleep apnea severity than younger men. This may be due to age-related differences in the amount of fluid accumulating in the neck or upper airway collapsibility in response to intravenous fluid loading. These possibilities remain to be tested in future studies. Citation: Yadollahi A, Gabriel JM, White LH, Taranto Montemurro L, Kasai T, Bradley TD. A randomized, double crossover study to investigate the influence of saline infusion on sleep apnea severity in men. SLEEP 2014;37(10):1699-1705. PMID:25197812

Advanced Cancer Detection Center

DTIC Science & Technology

2007-10-01

therapy in children: A Phase II randomized double blinded cross-over study (HLMCC 0708) • Risperidone for the Treatment of Cerebellar Mutism Syndrome...each question, the participant selects the answer by using the left and right arrow keys and then pressing the Choose button. The next question is...transformed to a quantitative scale measure for transmission. Numeric responses can be entered directly or can be selected from a list of

High-resolution endoscopy plus chromoendoscopy or narrow-band imaging in Barrett's esophagus: a prospective randomized crossover study.

PubMed

Kara, M A; Peters, F P; Rosmolen, W D; Krishnadath, K K; ten Kate, F J; Fockens, P; Bergman, J J G H

2005-10-01

High-resolution endoscopy (HRE) may improve the detection of early neoplasia in Barrett's esophagus. Indigo carmine chromoendoscopy (ICC) and narrow-band imaging (NBI) may be useful techniques to complement HRE. The aim of this study was to compare HRE-ICC with HRE-NBI for the detection of high-grade dysplasia or early cancer (HGD/EC) in patients with Barrett's esophagus. Twenty-eight patients with Barrett's esophagus underwent HRE-ICC and HRE-NBI (separated by 6 - 8 weeks) in a randomized sequence. The two procedures were performed by two different endoscopists, who were blinded to the findings of the other examination. Targeted biopsies were taken from all detected lesions, followed by four-quadrant biopsies at 2-cm intervals. Biopsy evaluation was supervised by a single expert pathologist, who was blinded to the imaging technique used. Fourteen patients were diagnosed with HGD/EC. The sensitivity for HGD/EC was 93 % and 86 % for HRE-ICC and HRE-NBI, respectively. Targeted biopsies had a sensitivity of 79 % with HRE alone. HGD was diagnosed from random biopsies alone in only one patient. ICC and NBI detected a limited number of additional lesions occult to HRE, but these lesions did not alter the sensitivity for identifying patients with HGD/EC. In most patients with high-grade dysplasia or early cancer in Barrett's esophagus, subtle lesions can be identified with high-resolution endoscopy. Indigo carmine chromoendoscopy and narrow-band imaging are comparable as adjuncts to high-resolution endoscopy.

Nifedipine--a calcium channel blocker--in asthmatic patients. Interaction with terbutaline.

PubMed

Svedmyr, K; Löfdahl, C G; Svedmyr, N

1984-01-01

Seven asthmatic patients were studied in a single-blind randomized, crossover study after oral administration of 20 mg nifedipine or placebo. Four increasing doses of i.v. terbutaline were then given with 30 min interval. The study was concluded with inhalation of five terbutaline puffs. FEV1 measurements 30 min after intake of nifedipine did not show any difference compared to placebo. During the terbutaline treatment, however, there was a more pronounced bronchodilation after nifedipine than after placebo (P less than 0.05). Terbutaline-induced skeletal muscle tremor was similar after nifedipine and placebo pretreatments. After nifedipine intake there was a decrease of diastolic blood pressure and a reflexogenic tachycardia. Thus, this study showed a small potentiation of the beta 2-adrenoceptor mediated bronchodilation, which is of importance when treating patients with simultaneous asthma and hypertension or angina pectoris.

Psychomotor and cognitive effects of piribedil, a dopamine agonist, in young healthy volunteers.

PubMed

Schück, Stéphane; Bentué-Ferrer, Danièle; Kleinermans, Diane; Reymann, Jean-Michel; Polard, Elisabeth; Gandon, Jean-Marc; Allain, Hervé

2002-02-01

Piribedil is a dopamine agonist acting on D2 and D3 central nervous system dopamine receptors. This drug has been administered to 12 young healthy male volunteers (age 22 +/- 2 years) according to a single center randomized, double-blind, two ways cross-over, placebo controlled trial, including a washout period of one week. Placebo and piribedil were administered by a single intravenous infusion over 2 h (3 mg). Psychomotor performance and cognitive functions were assessed through a standardized and computerized psychometric tests battery and a continuous electroencephalogram (EEG) mapping. Piribedil improved simple reaction time (P=0.02), immediate (P=0.045 and 0.004), and delayed free recall (P=0.05), dual coding test (P=0.02) and increased theta and fast beta waves on the EEG (P < 0.05 and 0.001, respectively). No deleterious effect was observed on the tests exploring attention and concentration via the other procedures. It is concluded that a single intravenous perfusion of piribedil 3 mg improves alertness and the information processing speed within the central nervous system, in healthy volunteers.

Does granisetron eliminate the gag reflex? A crossover, double-blind, placebo-controlled pilot study.

PubMed

Barenboim, Silvina Friedlander; Dvoyris, Vladislav; Kaufman, Eliezer

2009-01-01

Although gagging is a frequent problem that, when severe, can jeopardize the dental procedure, no single protocol is used to alleviate this phenomenon. Selective 5-HT3 antagonists, such as granisetron, may attenuate gagging. In this study, granisetron and placebo were administered intravenously, in a crossover, double-blind manner, to 25 healthy volunteers in 2 different sessions. Gagging levels were recorded before and after administration, as were BP, pulse, and O2 saturation. Recorded results were analyzed with the use of tests for nonparametric values (P = .05). A significant increase in the depth of swab insertion was noted after administration of both placebo and drug. The increase in drug effectiveness correlated with decreased body weight. The true efficacy of granisetron in gagger patients with this treatment protocol has yet to be fully established, although it has been theorized that an increased dosage of granisetron may have a better effect.

Does Granisetron Eliminate the Gag Reflex? A Crossover, Double-Blind, Placebo-Controlled Pilot Study

PubMed Central

Friedlander Barenboim, Silvina; Dvoyris, Vladislav; Kaufman, Eliezer

2009-01-01

Although gagging is a frequent problem that, when severe, can jeopardize the dental procedure, no single protocol is used to alleviate this phenomenon. Selective 5-HT3 antagonists, such as granisetron, may attenuate gagging. In this study, granisetron and placebo were administered intravenously, in a crossover, double-blind manner, to 25 healthy volunteers in 2 different sessions. Gagging levels were recorded before and after administration, as were BP, pulse, and O2 saturation. Recorded results were analyzed with the use of tests for nonparametric values (P = .05). A significant increase in the depth of swab insertion was noted after administration of both placebo and drug. The increase in drug effectiveness correlated with decreased body weight. The true efficacy of granisetron in gagger patients with this treatment protocol has yet to be fully established, although it has been theorized that an increased dosage of granisetron may have a better effect. PMID:19562886

Safety, Tolerability, and Pharmacokinetic Properties of Intravenous Delafloxacin After Single and Multiple Doses in Healthy Volunteers.

PubMed

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

2016-01-01

The objective of this report was to determine the pharmacokinetic properties, safety, and tolerability of single and multiple doses of intravenous delafloxacin. In addition, the absolute bioavailability (BA) of the 450-mg tablet formulation of delafloxacin was determined. Three clinical trials are summarized. The first study was a randomized, double-blind, placebo-controlled, single- (300, 450, 600, 750, 900, and 1200 mg) ascending-dose study of IV delafloxacin in 62 (52 active, 10 placebo) healthy volunteers. The second study was a randomized, double-blind, placebo-controlled study of IV delafloxacin (300 mg) given as a single dose on day 1, followed by twice-daily dosing on days 2 through 14; 12 (8 active, 4 placebo) healthy volunteers were enrolled. The third study was an open-label, randomized, 2-period, 2-sequence crossover study in which 56 healthy volunteers were randomly assigned to 1 of 2 sequences of a single oral dose of delafloxacin (450-mg tablet) or IV delafloxacin (300 mg). Serial blood samples were collected, and plasma pharmacokinetic parameters of delafloxacin were calculated. Delafloxacin Cmax values increased proportionally with increasing single IV dose for the dose range of 300 to 1200 mg, whereas the AUC values increased more than proportionally to dose for the same dose range. The mean terminal half-life of delafloxacin was approximately 12 hours (ranging from 8 to 17 hours). The volume of distribution (Vd) at steady state was approximately 35 L, which is similar to the volume of total body water. There was minimal accumulation of delafloxacin after twice-daily IV administration of 300 mg with an accumulation ratio of 1.09. The delafloxacin total exposure after a single 1-hour IV infusion of 300 mg and a single oral dose of a 450-mg tablet were equivalent with geometric least square mean ratio (90% CI) of 0.8768 (0.8356-0.9200) for AUC0-∞ and 0.8445 (0.8090-0.8815) for AUC0-t, respectively. The Cmax values of delafloxacin were not equivalent for the 2 formulations with a ratio (90% CI) of 0.5516 (0.5150-0.5908), respectively. The mean absolute bioavailability of delafloxacin was 58.8%. Delafloxacin was well tolerated in healthy volunteers after single and multiple IV doses. The total systemic exposure to IV (300 mg) and oral (450 mg) delafloxacin is comparable, supporting that a switch between the 2 formulations is appropriate. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

The potential for improvement of outcomes by personalized insulin treatment of type 1 diabetes as assessed by analysis of single-patient data from a randomized controlled cross-over insulin trial.

PubMed

Pedersen-Bjergaard, Ulrik; Kristensen, Peter L; Beck-Nielsen, Henning; Nørgaard, Kirsten; Perrild, Hans; Christiansen, Jens S; Jensen, Tonny; Parving, Hans-Henrik; Thorsteinsson, Birger; Tarnow, Lise

2017-01-01

The evidence for optimal insulin treatment in type 1 diabetes is mainly based on randomised controlled trials applying a parallel-group design. Such trials yield robust general results but crucial individual treatment effects cannot be extracted. We aimed to assess the potential for further improvement of outcomes by personalized insulin therapy by analyzing data from a cross-over trial at individual level. Post hoc analysis of data from a two-year multicentre, prospective, randomised, open, blinded endpoint (PROBE) trial (the HypoAna trial). In a cross-over design 114 patients with type 1 diabetes and recurrent severe hypoglycemia were treated with basal-bolus therapy based on analog (detemir/aspart) or human (NPH/regular) insulin aiming at maintenance of baseline HbA1c levels. For each patient a superior outcome was defined as fewer events of severe hypoglycemia defined by need for third party treatment assistance or a more than 0.4% (4.4mmol/mol) lower HbA1c. Only one quarter had comparable outcome of the two treatments in terms of rate of severe hypoglycemia or HbA1c. Twice as many patients had superior outcome of analog-based as compared to human insulin-based insulin treatment. The rate of severe hypoglycemia with the superior treatment was lower compared to the rates obtained with analog insulin and with human insulin (0.67, 1.09, and 1.57 episode per patient-year, respectively (p<0.0001)). Personalized insulin treatment of type 1 diabetes based on single-patient evidence may improve outcomes significantly compared to a general treatment approach. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Efficacy of the Power Balance Silicone Wristband: a single-blind, randomized, triple placebo-controlled study.

PubMed

Pothier, David D; Thiel, Gundula; Khoo, S G; Dillon, Wanda A; Sulway, Shaleen; Rutka, John A

2012-06-01

The Power Balance Silicone Wristband (Power Balance LLC, Laguna Niguel, CA) (power balance band; PBB) consists of a silicone wristband, incorporating two holograms, which is meant to confer improvements in balance on the wearer. Despite its popularity, the PBB has become somewhat controversial, with a number of articles being published in the news media regarding its efficacy. The PBB has not been formally evaluated but remains popular, largely based on anecdotal evidence. This study subjectively and objectively measured the effects of the PBB on balance in normal participants. A prospective, single-blind, randomized, triple placebo-controlled crossover study was undertaken. Twenty participants underwent measurement using the modified Test of Sensory Interaction on Balance (mCTSIB) and gave subjective feedback (visual analogue scale [VAS]) for each of four band conditions: no band, a silicone band, a deactivated PBB, and the PBB. Participants acted as their own controls. The mean of the four mCTSIB conditions (eyes open and closed on both firm and compliant surfaces) was calculated. This mean value and condition 4 of the mCTSIB were compared between band conditions using path length (PL) and root mean square (RMS) as outcome measures. No significant differences were found between band conditions for PL (p  =  .91 and p  =  .94, respectively) and RMS (p  =  .85 and p  =  .96, respectively). VASs also showed no difference between bands (p  =  .25). The PBB appears to have no effect on mCTSIB or VAS measurements of balance.

Impact of acute administration of escitalopram on the processing of emotional and neutral images: a randomized crossover fMRI study of healthy women.

PubMed

Outhred, Tim; Das, Pritha; Felmingham, Kim L; Bryant, Richard A; Nathan, Pradeep J; Malhi, Gin S; Kemp, Andrew H

2014-07-01

Acute neural effects of antidepressant medication on emotion processing biases may provide the foundation on which clinical outcomes are based. Along with effects on positive and negative stimuli, acute effects on neutral stimuli may also relate to antidepressant efficacy, yet these effects are still to be investigated. The present study therefore examined the impact of a single dose of the selective serotonin reuptake inhibitor escitalopram (20 mg) on positive, negative and neutral stimuli using pharmaco-fMRI. Within a double-blind, randomized, placebo-controlled crossover design, healthy women completed 2 sessions of treatment administration and fMRI scanning separated by a 1-week washout period. We enrolled 36 women in our study. When participants were administered escitalopram relative to placebo, left amygdala activity was increased and right inferior frontal gyrus (IFG) activity was decreased during presentation of positive pictures (potentiation of positive emotion processing). In contrast, escitalopram was associated with decreased left amygdala and increased right IFG activity during presentation of negative pictures (attenuation of negative emotion processing). In addition, escitalopram decreased right IFG activity during the processing of neutral stimuli, akin to the effects on positive stimuli (decrease in negative appraisal). Although we used a women-only sample to reduce heterogeneity, our results may not generalize to men. Potential unblinding, which was related to the subjective occurrence of side effects, occurred in the study; however, manipulation check analyses demonstrated that results were not impacted. These novel findings demonstrate that a single dose of the commonly prescribed escitalopram facilitates a positive information processing bias. These findings provide an important lead for better understanding effects of antidepressant medication.

Comparison of the urinary excretion of quercetin glycosides from red onion and aglycone from dietary supplements in healthy subjects: a randomized, single-blinded, cross-over study.

PubMed

Shi, Yuanlu; Williamson, Gary

2015-05-01

Some intervention studies have shown that quercetin supplementation can regulate certain biomarkers, but it is not clear how the doses given relate to dietary quercetin (e.g. from onion). We conducted a two-period, two-sequence crossover study to compare the bioavailability of quercetin when administered in the form of a fresh red onion meal (naturally glycosylated quercetin) or dietary supplement (aglycone quercetin) under fasting conditions. Six healthy, non-smoking, adult males with BMI 22.7 ± 4.0 kg m(-2) and age 35.3 ± 12.3 y were grouped to take the two study meals in random order. In each of the 2 study periods, one serving of onion soup (made from 100 g fresh red onion, providing 156.3 ± 3.4 μmol (47 mg) quercetin) or a single dose of a quercetin dihydrate tablet (1800 ± 150 μmol (544 mg) of quercetin) were administered following 3 d washout. Urine samples were collected up to 24 h, and after enzyme deconjugation, quercetin was quantified by LC-MS. The 24 h urinary excretion of quercetin (1.69 ± 0.79 μmol) from red onion in soup was not significantly different to that (1.17 ± 0.44 μmol) for the quercetin supplement tablet (P = 0.065, paired t-test). This means that, in practice, 166 mg of quercetin supplement would be comparable to about 10 mg of quercetin aglycone equivalents from onion. These data allow intervention studies on quercetin giving either food or supplements to be more effectively compared.

Deep brain stimulation for treatment-resistant major depressive disorder: a comparison of two targets and long-term follow-up

PubMed Central

Raymaekers, S; Luyten, L; Bervoets, C; Gabriëls, L; Nuttin, B

2017-01-01

We previously found that electrical stimulation in the anterior limb of the internal capsule/bed nucleus of the stria terminalis (IC/BST) alleviates depressive symptoms in severe treatment-resistant obsessive-compulsive disorder (OCD) patients. Here we tested the hypothesis that electrical stimulation in either IC/BST or in the inferior thalamic peduncle (ITP) effectively reduces depressive symptoms in treatment-resistant major depressive disorder (TRD). In a double-blind crossover design, the effects of electrical stimulation at both targets were compared in TRD patients. The 17-item Hamilton Depression Rating scale (HAM-D) was the primary outcome measure. During the first crossover, patients received IC/BST stimulation versus no stimulation in random order (2 × 1 weeks). During the second crossover (3 × 2 months), patients received IC/BST versus ITP versus no stimulation. Patients and evaluators were blinded for stimulation conditions. All patients (n=7) were followed up for at least 3 years (3–8 years) after implantation. Six patients completed the first crossover and five patients completed the second. During the first crossover, mean (s.d.) HAM-D scores were 21.5 (2.7) for no stimulation and 11.5 (8.8) for IC/BST stimulation. During the second crossover, HAM-D scores were 15.4 (7.5) for no stimulation, 7.6 (3.8) for IC/BST stimulation and 11.2 (7.5) for ITP stimulation. The final sample size was too small to statistically analyze this second crossover. At last follow-up, only one patient preferred ITP over IC/BST stimulation. Two patients, with a history of suicide attempts before implantation, committed suicide during the follow-up phases of this study. Our data indicate that, in the long term, both ITP and IC/BST stimulation may alleviate depressive symptoms in patients suffering from TRD. PMID:29087373

Deep brain stimulation for treatment-resistant major depressive disorder: a comparison of two targets and long-term follow-up.

PubMed

Raymaekers, S; Luyten, L; Bervoets, C; Gabriëls, L; Nuttin, B

2017-10-31

We previously found that electrical stimulation in the anterior limb of the internal capsule/bed nucleus of the stria terminalis (IC/BST) alleviates depressive symptoms in severe treatment-resistant obsessive-compulsive disorder (OCD) patients. Here we tested the hypothesis that electrical stimulation in either IC/BST or in the inferior thalamic peduncle (ITP) effectively reduces depressive symptoms in treatment-resistant major depressive disorder (TRD). In a double-blind crossover design, the effects of electrical stimulation at both targets were compared in TRD patients. The 17-item Hamilton Depression Rating scale (HAM-D) was the primary outcome measure. During the first crossover, patients received IC/BST stimulation versus no stimulation in random order (2 × 1 weeks). During the second crossover (3 × 2 months), patients received IC/BST versus ITP versus no stimulation. Patients and evaluators were blinded for stimulation conditions. All patients (n=7) were followed up for at least 3 years (3-8 years) after implantation. Six patients completed the first crossover and five patients completed the second. During the first crossover, mean (s.d.) HAM-D scores were 21.5 (2.7) for no stimulation and 11.5 (8.8) for IC/BST stimulation. During the second crossover, HAM-D scores were 15.4 (7.5) for no stimulation, 7.6 (3.8) for IC/BST stimulation and 11.2 (7.5) for ITP stimulation. The final sample size was too small to statistically analyze this second crossover. At last follow-up, only one patient preferred ITP over IC/BST stimulation. Two patients, with a history of suicide attempts before implantation, committed suicide during the follow-up phases of this study. Our data indicate that, in the long term, both ITP and IC/BST stimulation may alleviate depressive symptoms in patients suffering from TRD.

Rationale and design of a randomized controlled trial of allogeneic mesenchymal stem cells in patients with nonischemic cardiomyopathy.

PubMed

Greene, Stephen J; Epstein, Stephen E; Kim, Raymond J; Quyyumi, Arshed A; Cole, Robert T; Anderson, Allen S; Wilcox, Jane E; Skopicki, Hal A; Sikora, Sergey; Verkh, Lev; Tankovich, Nikolai I; Gheorghiade, Mihai; Butler, Javed

2017-04-01

This article describes an ongoing study investigating the safety and efficacy of ischemia-tolerant mesenchymal stem cell (MSC) therapy in patients with nonischemic heart failure and dysfunctional viable myocardium without scarring. This study will follow principles of the previously described mechanistic translational-phase concept whereby the effect of the study agent on laboratory and imaging markers of cardiac structure and function will be tested in a small homogenous cohort with the goal to enhance the understanding of the effect of interventions on cardiac remodeling and performance. This single-blind, placebo-controlled, crossover, multicenter, randomized study will assess the safety, tolerability, and preliminary efficacy of a single intravenous (i.v.) dose of allogeneic ischemia-tolerant MSCs in individuals with heart failure of nonischemic cause, ejection fraction 40% or less, and dysfunctional viable myocardium who have been receiving guideline-directed medical therapy. Eligible patients will have no evidence of baseline replacement scarring on delayed-enhancement cardiac magnetic resonance (CMR). Approximately 20 patients will be randomized in a 1 : 1 ratio to receive an i.v. infusion of ischemia-tolerant MSCs or placebo. At 90 days, the two groups will undergo crossover and received the alternative treatment. The primary endpoint is safety, as evaluated through at least 1-year post-MSC infusion. Additional efficacy endpoints will include measures of cardiac structure and function, as evaluated by serial cine-CMR and transthoracic echocardiography at 90 and 180 days post-initial infusion. This pilot study will explore the safety and effects on cardiac structure and function of i.v. injection of ischemia-tolerant MSCs in a small homogenous cohort of nonischemic heart failure patients with reduced ejection fraction and absent replacement scarring on CMR. This study also represents a prospective mechanistic translational-phase study using baseline and serial CMR imaging in heart failure patients and serves as a potential model for design of future heart failure trials (ClinicalTrials.gov identifier: NCT02467387).

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

Low-dose hydrocortisone replacement improves wellbeing and pain tolerance in chronic pain patients with opioid-induced hypocortisolemic responses. A pilot randomized, placebo-controlled trial.

PubMed

Nenke, Marni A; Haylock, Clare L; Rankin, Wayne; Inder, Warrick J; Gagliardi, Lucia; Eldridge, Crystal; Rolan, Paul; Torpy, David J

2015-06-01

Long-term opioid therapy has been associated with low cortisol levels due to central suppression of the hypothalamic-pituitary-adrenal axis. The implications of hypocortisolism on wellbeing have not been established. Our aim was to determine whether intervention with physiologic glucocorticoid replacement therapy improves wellbeing and analgesic responses in patients with chronic non-cancer pain on long-term opioid therapy with mild cortisol deficiency. We performed a pilot randomized, double-blind, placebo-controlled crossover study of oral hydrocortisone replacement therapy in 17 patients recruited from a Pain Clinic at a single tertiary center in Adelaide, Australia. Patients were receiving long-term opioid therapy (≥ 20 mg morphine equivalents per day for ≥ 4 weeks) for chronic non-cancer pain with mild hypocortisolism, as defined by a plasma cortisol response ≤ 350 nmol/L at 60 min following a cold pressor test. The crossover intervention included 28-day treatment with either 10mg/m(2)/day of oral hydrocortisone in three divided doses or placebo. Improvement in wellbeing was assessed using Version 2 of the Short Form-36 (SF-36v2), Brief Pain Inventory-Short Form, and Addison's disease quality of life questionnaires; improvement in analgesic response was assessed using cold pressor threshold and tolerance times. Following treatment with hydrocortisone, the bodily pain (P=0.042) and vitality (P=0.013) subscales of the SF-36v2 were significantly better than scores following treatment with placebo. There was also an improvement in pain interference on general activity (P=0.035), mood (P=0.03) and work (P=0.04) following hydrocortisone compared with placebo. This is the first randomized, double-blind placebo-controlled trial of glucocorticoid replacement in opioid users with chronic non-cancer pain and mild hypocortisolism. Our data suggest that physiologic hydrocortisone replacement produces improvements in vitality and pain experiences in this cohort compared with placebo. Therapeutic Goods Administration Clinical Trials Notification Scheme (Drugs), Trial Number 2012/0476. Copyright © 2015 Elsevier Ltd. All rights reserved.

Dietary strawberries increase proliferative response of CD3/CD28-activated CD8+ T cells and production of TNF-alpha in lipopolysaccharide-stimulated monocytes from obese human subjects

USDA-ARS?s Scientific Manuscript database

Obesity increases the risk of developing bacterial and viral infections compared to normal weight. In a 7 wk double-blind, randomized, crossover trial, twenty obese volunteers (20-50 y old, BMI between 30-40 kg/m2) were fed freeze-dried strawberry powder or strawberry-flavored placebo preparations ...

In Vitro and in vivo antioxidant and anti-inflammatory capacities of an antioxidant-rich fruit and berry juice blend. Results of a pilot and randomized, double-blinded, placebo-controlled, crossover study

USDA-ARS?s Scientific Manuscript database

This study investigated the in vitro and in vivo antioxidant and anti-inflammatory properties of a juice blend (JB), MonaVie Active, containing a mixture of fruits and berries with known antioxidant activity, including acai, a palm fruit, as the predominant ingredient. The phytochemical antioxidants...

Phenol-enriched olive oils improve HDL antioxidant content in hypercholesterolemic subjects. A randomized, double-blind, cross-over, controlled trial.

PubMed

Farràs, Marta; Fernández-Castillejo, Sara; Rubió, Laura; Arranz, Sara; Catalán, Úrsula; Subirana, Isaac; Romero, Mari-Paz; Castañer, Olga; Pedret, Anna; Blanchart, Gemma; Muñoz-Aguayo, Daniel; Schröder, Helmut; Covas, Maria-Isabel; de la Torre, Rafael; Motilva, Maria-José; Solà, Rosa; Fitó, Montserrat

2018-01-01

At present, high-density lipoprotein (HDL) function is thought to be more relevant than HDL cholesterol quantity. Consumption of olive oil phenolic compounds (PCs) has beneficial effects on HDL-related markers. Enriched food with complementary antioxidants could be a suitable option to obtain additional protective effects. Our aim was to ascertain whether virgin olive oils (VOOs) enriched with (a) their own PC (FVOO) and (b) their own PC plus complementary ones from thyme (FVOOT) could improve HDL status and function. Thirty-three hypercholesterolemic individuals ingested (25 ml/day, 3 weeks) (a) VOO (80 ppm), (b) FVOO (500 ppm) and (c) FVOOT (500 ppm) in a randomized, double-blind, controlled, crossover trial. A rise in HDL antioxidant compounds was observed after both functional olive oil interventions. Nevertheless, α-tocopherol, the main HDL antioxidant, was only augmented after FVOOT versus its baseline. In conclusion, long-term consumption of phenol-enriched olive oils induced a better HDL antioxidant content, the complementary phenol-enriched olive oil being the one which increased the main HDL antioxidant, α-tocopherol. Complementary phenol-enriched olive oil could be a useful dietary tool for improving HDL richness in antioxidants. Copyright © 2017. Published by Elsevier Inc.

Supplementation with a Polyphenol-Rich Extract, PerfLoad®, Improves Physical Performance during High-Intensity Exercise: A Randomized, Double Blind, Crossover Trial

PubMed Central

Cases, Julien; Romain, Cindy; Marín-Pagán, Cristian; Chung, Linda H.; Rubio-Pérez, José Miguel; Laurent, Caroline; Gaillet, Sylvie; Prost-Camus, Emmanuelle; Prost, Michel; Alcaraz, Pedro E.

2017-01-01

Workout capacity is energy-production driven. To produce peak metabolic power outputs, the organism predominantly relies more on anaerobic metabolism, but this undoubtedly has a negative and limiting impact on muscle function and performance. The aim of the study was to evaluate if an innovative polyphenol-based food supplement, PerfLoad®, was able to improve metabolic homeostasis and physical performance during high-intensity exercises under anaerobic conditions. The effect of a supplementation has been investigated on fifteen recreationally-active male athletes during a randomized, double-blind and crossover clinical investigation. The Wingate test, an inducer of an unbalanced metabolism associated to oxidative stress, was used to assess maximum anaerobic power during a high-intensity exercise on a cycle ergometer. Supplementation with PerfLoad® correlated with a significant increase in total power output (5%), maximal peak power output (3.7%), and average power developed (5%), without inducing more fatigue or greater heart rate. Instead, oxidative homeostasis was stabilized in supplemented subjects. Such results demonstrated that PerfLoad® is a natural and efficient solution capable of, similarly to training benefits, helping athletes to improve their physical performance, while balancing their metabolism and reducing exercise-induced oxidative stress. PMID:28441760

A Randomized Crossover Trial Comparing Autotitrating and Continuous Positive Airway Pressure in Subjects With Symptoms of Aerophagia: Effects on Compliance and Subjective Symptoms

PubMed Central

Shirlaw, Teresa; Hanssen, Kevin; Duce, Brett; Hukins, Craig

2017-01-01

Study Objectives: To assess the benefit and tolerance of autotitrating positive airway pressure (APAP) versus continuous positive airway pressure (CPAP) in subjects who experience aerophagia. Methods: This is the report of a prospective, two-week, double-blinded, randomized crossover trial set in an Australian clinical sleep laboratory in a tertiary hospital. Fifty-six subjects who reported symptoms of aerophagia that they attributed to CPAP were recruited. Full face masks were used by 39 of the 56 subjects recruited. Subjects were randomly and blindly allocated to either CPAP at their treatment recommended pressure or APAP 6–20 cm H2O, in random order. Subjects spent two weeks on each therapy mode. Therapy usage hours, 95th centile pressure, maximum pressure, 95th centile leak, and residual apnea-hypopnea index (AHI) were reported at the end of each two-week treatment period. Functional Outcome of Sleepiness Questionnaire, Epworth Sleepiness Scale, and visual analog scale to measure symptoms of aerophagia were also completed at the end of each 2-week treatment arm. Results: The median pressure (P < .001) and 95th centile pressure (P < .001) were reduced with APAP but no differences in compliance (P = .120) and residual AHI were observed. APAP reduced the symptoms of bloating (P = .011), worst episode of bloating (P = .040), flatulence (P = .010), and belching (P = .001) compared to CPAP. There were no differences in Epworth Sleepiness Scale or Functional Outcome of Sleepiness Questionnaire outcomes between CPAP and APAP. Conclusions: APAP therapy reduces the symptoms of aerophagia while not affecting compliance when compared with CPAP therapy. Clinical Trial Registration: Australian and New Zealand Clinical Trials Registry at https://www.anzctr.org.au, trial number ACTRN12611001250921. Commentary: A commentary on this article appears in this issue on page 859. Citation: Shirlaw T, Hanssen K, Duce B, Hukins C. A randomized crossover trial comparing autotitrating and continuous positive airway pressure in subjects with symptoms of aerophagia: effects on compliance and subjective symptoms. J Clin Sleep Med. 2017;13(7):881–888. PMID:28558864

An Herbal Drug, Gongjin-dan, Ameliorates Acute Fatigue Caused by Short-Term Sleep-Deprivation: A Randomized, Double-Blinded, Placebo-Controlled, Crossover Clinical Trial.

PubMed

Son, Mi Ju; Im, Hwi-Jin; Ku, Boncho; Lee, Jun-Hwan; Jung, So Young; Kim, Young-Eun; Lee, Sung Bae; Kim, Jun Young; Son, Chang-Gue

2018-01-01

Introduction: Gongjin-dan (GJD) is an herbal drug commonly used in Korea and China to combat fatigue, but there are only few clinical studies on its effectiveness and experimental studies on its mechanism of action, and no randomized controlled trial of GJD on the efficacy and mechanism of action has been reported. Here, we performed an exploratory study to evaluate both questions regarding GJD use in humans. Methods: A randomized, double-blinded, placebo-controlled, crossover clinical trial was conducted in the Republic of Korea. Healthy male participants were recruited and randomly allocated to groups receiving GJD-placebo or placebo-GJD in sequence. Fatigue was artificially induced by sleep deprivation for 2 nights. The primary outcome was a change in serum cortisol level; levels of biomarkers for stress hormones as well as oxidative stress and immunologic factors were also assessed, and questionnaires on fatigue and sleep quality were conducted. Results: Twelve and 11 participants were assigned to the GJD-placebo and placebo-GJD groups, respectively. Of all 23 participants, depending on crossover design, we analyzed a total of 20 participants for GJD, and 21 for placebo. An increase in serum cortisol appeared to be attenuated by GJD administration ( p = 0.25), but the effect was not statistically significant; a similar pattern was observed in salivary cortisol levels ( p = 0.14). Overall, GJD showed a tendency to reduce fatigue according to the Brief Fatigue Inventory (BFI, p = 0.07) and the Fatigue Severity Scale (FSS, p = 0.13) questionnaires. BFI and FSS scores in the first stage (before the crossover), however, were significantly improved (BFI, p = 0.02; FSS, p = 0.05) after GJD treatment (relative to placebo). GJD also seemed to improve sleep quality as assessed by the Leeds Sleep Evaluation Questionnaire ( p = 0.06), with a significant improvement specifically in the condition "Getting To Sleep" ( p = 0.02). Five participants experienced minor adverse events, but no adverse events were specific to the GJD administration period. Conclusions: This trial produced the first clinical evidence that GJD might have anti-fatigue properties, especially under sleep deprivation; however, the investigation of cortisol-mediated mechanisms requires further larger-scale studies in the future. World Health Organization International Clinical Trials Registry Platform KCT0001681 (http://apps.who.int/trialsearch/Trial2.aspx?TrialID=KCT0001681).

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

PubMed

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

2012-09-15

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

Comparison of Metallic Foreign-Body Removal between Dynamic Ultrasound and Static Radiography in a Pigs' Feet Model

PubMed Central

Manson, William C; Ryan, James G; Ladner, Heidi; Gupta, Sanjey

2011-01-01

Introduction We compared the immediate cosmetic outcome of metallic foreign-body removal by emergency medicine (EM) residents with ultrasound guidance and conventional radiography. Methods This single-blinded, randomized, crossover study evaluated the ability of EM residents to remove metallic pins embedded in pigs' feet. Before the experiment, we embedded 1.5-cm metallic pins into numbered pigs' feet. We randomly assigned 14 EM residents to use either ultrasound or radiography to help remove the foreign body. Residents had minimal ultrasound experience. After a brief lecture, we provided residents with a scalpel, laceration kit, a bedside portable ultrasound machine, nipple markers, paper clips, a dedicated radiograph technician, and radiograph machine 20 feet away. After removal, 3 board-certified emergency physicians, who were blinded to the study group, evaluated the soft-tissue model by using a standardized form. They recorded incision length and cosmetic appearance on the Visual Analog Scale. Results In total, 28 foreign bodies were removed. No significant difference in the time of removal (P = 0.12), cosmetic appearance (P = 0.96), or incision length (P = 0.76) was found. Conclusion This study showed no difference between bedside ultrasound and radiography in assisting EM residents with metallic foreign-body removal from soft tissue. No significant difference was found in removal time or cosmetic outcome when comparing ultrasound with radiography. PMID:22224139

Slow-release L-cysteine capsule prevents gastric mucosa exposure to carcinogenic acetaldehyde: results of a randomised single-blinded, cross-over study of Helicobacter-associated atrophic gastritis.

PubMed

Hellström, Per M; Hendolin, Panu; Kaihovaara, Pertti; Kronberg, Leif; Meierjohann, Axel; Millerhovf, Anders; Paloheimo, Lea; Sundelin, Heidi; Syrjänen, Kari; Webb, Dominic-Luc; Salaspuro, Mikko

2017-02-01

Helicobacter-induced atrophic gastritis with a hypochlorhydric milieu is a risk factor for gastric cancer. Microbes colonising acid-free stomach oxidise ethanol to acetaldehyde, a recognised group 1 carcinogen. To assess gastric production of acetaldehyde and its inert condensation product, non-toxic 2-methyl-1,3-thiazolidine-4-carboxylic acid (MTCA), after alcohol intake under treatment with slow-release L-cysteine or placebo. Seven patients with biopsy-confirmed atrophic gastritis, low serum pepsinogen and high gastrin-17 were studied in a cross-over single-blinded design. On separate days, patients randomly received 200 mg slow-release L-cysteine or placebo with intragastric instillation of 15% (0.3 g/kg) ethanol. After intake, gastric concentrations of ethanol, acetaldehyde, L-cysteine and MTCA were analysed. Administration of L-cysteine increased MTCA (p < .0004) and decreased gastric acetaldehyde concentrations by 68% (p < .0001). The peak L-cysteine level was 7552 ± 2687 μmol/L at 40 min and peak MTCA level 196 ± 98 μmol/L at 80 min after intake. Gastric L-cysteine and MTCA concentrations were maintained for 3 h. The AUC for MTCA was 11-fold higher than acetaldehyde, indicating gastric first-pass metabolism of ethanol. With placebo, acetaldehyde remained elevated also at low ethanol concentrations representing 'non-alcoholic' beverages and food items. After gastric ethanol instillation, slow-release L-cysteine eliminates acetaldehyde to form inactive MTCA, which remains in gastric juice for up to 3 h. High acetaldehyde levels indicate a marked gastric first-pass metabolism of ethanol resulting in gastric accumulation of carcinogenic acetaldehyde. Local exposure of the gastric mucosa to acetaldehyde can be mitigated by slow-release L-cysteine capsules.

Oxygen therapy for cluster headache. A mask comparison trial. A single-blinded, placebo-controlled, crossover study.

PubMed

Petersen, Anja S; Barloese, Mads Cj; Lund, Nunu Lt; Jensen, Rigmor H

2017-03-01

Purpose The purpose of this article is to investigate possible differences in effect between three types of masks in the acute treatment of cluster headache (CH). Patients and methods Fifty-seven CH patients according to ICHD-II-criteria participated in a single-blinded, semi-randomized, placebo-controlled, crossover inpatient study, and 102 CH attacks were treated with 100% oxygen delivered by demand valve oxygen (DVO), O 2 ptimask or simple mask (15 liters/min) or placebo delivered by DVO for 15 minutes. Primary endpoint: Two-point decrease of pain on a five-point rating scale within 15 minutes. Results Only 10 CH patients had multiple attacks and reached the point of placebo. There were no significant differences between masks in the primary endpoints ( p = 0.412). After 15 minutes 48% had a two-point decrease using the DVO compared to 45% with placebo ( p = 0.867). After 30 minutes 68% were pain free or had pain relief using DVO and 45% by placebo ( p = 0.061). The DVO was preferred by 62% compared to 5% and 33% for simple mask ( p < 0.0001) and O 2 ptimask ( p = 0.061). In the first attack the DVO was significantly better at achieving pain relief at 15 minutes ( p = 0.018). Treatment with DVO or O 2 ptimask reduced the need for rescue medication compared to the simple mask (23%, 19%, 50%, respectively). No treatment-related adverse events were observed. Conclusion The primary endpoint with pain relief at 15 minutes was non-significant; however, a post hoc analysis of the first attack significantly favored DVO. Further, therapy by O 2 ptimask and DVO resulted in a decreased need for rescue medication. We recommend that CH patients be offered DVO or O 2 ptimask before oxygen therapy is abandoned.

The Effect of Isomaltulose Together with Green Tea on Glycemic Response and Antioxidant Capacity: A Single-Blind, Crossover Study in Healthy Subjects.

PubMed

Suraphad, Passakorn; Suklaew, Phim On; Ngamukote, Sathaporn; Adisakwattana, Sirichai; Mäkynen, Kittana

2017-05-06

Isomaltulose, a naturally-occurring isomer of sucrose, is commonly used as an alternative sweetener in foods and beverages. The goal of this study was to determine the effect of isomaltulose together with green tea on postprandial plasma glucose and insulin concentration, as well as antioxidant capacity in healthy subjects. In a randomized, single-blind, crossover study, 15 healthy subjects (eight women and seven men; ages 23.5 ± 0.7 years; with body mass index of 22.6 ± 0.4 kg/m²) consumed five beverages: (1) 50 g sucrose in 400 mL water; (2) 50 g isomaltulose in 400 mL of water; (3) 400 mL of green tea; (4) 50 g sucrose in 400 mL of green tea; and (5) 50 g isomaltulose in 400 mL of green tea. Incremental area under postprandial plasma glucose, insulin, ferric reducing ability of plasma (FRAP) and malondialdehyde (MDA) concentration were determined during 120 min of administration. Following the consumption of isomaltulose, the incremental 2-h area under the curve (AUC 0-2 h ) indicated a higher reduction of postprandial glucose (43.4%) and insulin concentration (42.0%) than the consumption of sucrose. The addition of green tea to isomaltulose produced a greater suppression of postprandial plasma glucose (20.9%) and insulin concentration (37.7%). In accordance with antioxidant capacity, consumption of sucrose (40.0%) and isomaltulose (28.7%) caused the reduction of green tea-induced postprandial increases in FRAP. A reduction in postprandial MDA after drinking green tea was attenuated when consumed with sucrose (34.7%) and isomaltulose (17.2%). In conclusion, green tea could enhance the reduction of postprandial glucose and insulin concentration when consumed with isomaltulose. In comparison with sucrose, isomaltulose demonstrated less alteration of plasma antioxidant capacity after being consumed with green tea.

Acute effects of beer on endothelial function and hemodynamics: a single-blind, crossover study in healthy volunteers.

PubMed

Karatzi, Kalliopi; Rontoyanni, Victoria G; Protogerou, Athanase D; Georgoulia, Aggeliki; Xenos, Konstantinos; Chrysou, John; Sfikakis, Petros P; Sidossis, Labros S

2013-09-01

Moderate consumption of beer is associated with lower cardiovascular (CV) risk. The goal of this study was to determine the effect of beer consumption on CV risk. To explore the underlying mechanisms, we studied the acute effects of the constituents of beer (alcohol and antioxidants), on established predictors of CV risk: endothelial function, aortic stiffness, pressure wave reflections and aortic pressure. In a randomized, single-blind, crossover study, 17 healthy, non-smoking, men (ages 28.5 ± 5.2 y with body mass index 24.4 ± 2.5 kg/m(2)) consumed on three separate occasions, at least 1 wk apart: 1. 400 mL of beer and 400 mL water, 2. 800 mL of dealcoholized beer (same amount of polyphenols as in the 400 mL of beer), and 3. 67 mL of vodka and 733 mL water (same amount of alcohol as in the 400 mL of beer). Each time aortic stiffness (pulse wave velocity), pressure wave reflections (AΙx), aortic and brachial pressure (Sphygmocor device), and endothelial function (brachial flow mediated dilatation) were assessed at fast and 1 and 2 h postprandial. Aortic stiffness was significantly and similarly reduced by all three interventions. However, endothelial function was significantly improved only after beer consumption (average 1.33%, 95% confidence interval [CI] 0.15-2.53). Although wave reflections were significantly reduced by all three interventions (average of beer: 9.1%, dealcoholized beer: 2.8%, vodka 8.5%, all CI within limits of significance), the reduction was higher after beer consumption compared with dealcoholized beer (P = 0.018). Pulse pressure amplification (i.e., brachial/aortic) was increased by all three test drinks. Beer acutely improves parameters of arterial function and structure, in healthy non-smokers. This benefit seems to be mediated by the additive or synergistic effects of alcohol and antioxidants and merits further investigation. Copyright © 2013 Elsevier Inc. All rights reserved.

A Prospective, Randomized, Double-Blind Comparison of 2% Mepivacaine With 1 : 20,000 Levonordefrin Versus 2% Lidocaine With 1 : 100,000 Epinephrine for Maxillary Infiltrations

PubMed Central

Lawaty, Ingrid; Drum, Melissa; Reader, Al; Nusstein, John

2010-01-01

The purpose of this prospective, randomized, double-blind crossover study was to compare the anesthetic efficacy of 2% mepivacaine with 1 : 20,000 levonordefrin versus 2% lidocaine with 1 : 100,000 epinephrine in maxillary central incisors and first molars. Sixty subjects randomly received, in a double-blind manner, maxillary central incisor and first molar infiltrations of 1.8 mL of 2% mepivacaine with 1 : 20,000 levonordefrin and 1.8 mL of 2% lidocaine with 1 : 100,000 epinephrine at 2 separate appointments spaced at least 1 week apart. The teeth were electric pulp tested in 2-minute cycles for a total of 60 minutes. Anesthetic success (obtaining 2 consecutive 80 readings with the electric pulp tester within 10 minutes) was not significantly different between 2% mepivacaine with 1 : 20,000 levonordefrin and 2% lidocaine with 1 : 100,000 epinephrine for the central incisor and first molar. However, neither anesthetic agent provided an hour of pulpal anesthesia. PMID:21174567

Pharmacokinetics and Bioequivalence Evaluation of 2 Loxoprofen Tablets in Healthy Egyptian Male Volunteers.

PubMed

Helmy, Sally A

2013-04-01

The objective of this study was to assess the in vitro dissolution and to evaluate the bioavailability of two brands of Loxoprofen sodium dihydrate tablets. Loxoprofen tablets (68.1 mg loxoprofen sodium dihydrate equivalent to 60 mg loxoprofen; test) relative to Roxonin tablets (68.1 mg loxoprofen sodium dihydrate equivalent to 60 mg loxoprofen; reference). In vitro study was adopted to determine and compare the dissolution behavior of both products. In vivo study was conducted according to a single-center, randomized, single-dose, and laboratory-blinded, 2-period, 2-sequence, crossover design with a washout period of 1 week. Under fasting conditions, 24 healthy Egyptian adult male volunteers were randomly allocated to receive a single dose of either test or reference product. Blood samples were collected at specified time intervals, and plasma was analyzed for loxoprofen concentrations using a validated high-performance liquid chromatography assay method. The pharmacokinetic parameters Cmax , AUC0-t , AUC0-∞ , tmax , and t1/2 were determined from plasma concentration-time profiles. The 90% confidence intervals for the ratio Cmax , AUC0-t , and AUCt-∞ of the test product over those of reference were within the acceptable range (0.8-1.25) for bioequivalence. On the basis of these results, the two-loxoprofen formulations are considered bioequivalent. © The Author(s) 2013.

Repeated dose comparison of nomifensine, imipramine and placebo on subjective assessments of sleep and objective measures of psychomotor performance

PubMed Central

Hindmarch, I.; Parrott, A. C.

1977-01-01

1 Nine normal subjects volunteered to participate in a randomized single-blind crossover study of nomifensine 75 mg and two comparators, imipramine 75 mg and placebo. 2 Each volunteer received placebo for 3 d, then the first test drug for 4 days. This sequence was repeated twice more, so that each subject received each comparator. All medication was taken three times daily. 3 Assessments were made on days 3, 5 and 7 of each sequence, and consisted of a Sleep Evaluation Questionnaire, a test of Critical Flicker Fusion and a measurement of Complex Reaction Time (CRT). 4 There were no significant differences in the CRT. There was a significant increase in critical flicker fusion with nomifensine. 5 Although both nomifensine and imipramine disturbed the quality of sleep, only imipramine produced a hangover. PMID:334219

Randomized, Double-Blinded, Placebo-Controlled Crossover Trial of Treating Erectile Dysfunction with Sildenafil After Radiotherapy and Short-Term Androgen Deprivation Therapy: Results of RTOG 0215

PubMed Central

Bruner, Deborah Watkins; James, Jennifer L.; Bryan, Charlene J.; Pisansky, Thomas M.; Rotman, Marvin; Corbett, Thomas; Speight, Joycelyn; Byhardt, Roger; Sandler, Howard; Bentzen, Søren; Kachnic, Lisa; Berk, Lawrence

2013-01-01

Introduction Erectile dysfunction (ED) may be the most commonly observed adverse event (AE) associated with the combination of radiation therapy (RT) and androgen deprivation therapy (ADT). A significant number of men are trying phosphodiesterase type 5 inhibitors (PDE5s) such as sildenafil to treat ED, yet sildenafil studies to date shed little light on the response to ED after ADT. Aim The purpose of this trial was to evaluate sildenafil in the treatment of ED in prostate cancer patients previously treated with external beam RT and neoadjuvant and concurrent ADT. Methods In this randomized, double-blinded crossover trial, eligible patients received RT/ADT for intermediate risk prostate cancer and currently had ED as defined by the International Index of Erectile Function (IIEF). Patients were randomized to 12 weeks of sildenafil or placebo followed by 1 week of no treatment then 12 weeks of the alternative. Treatment differences were evaluated using a marginal model for binary crossover data. Main Outcome Measures The primary end point was improved erectile function, as measured by the IIEF. Results The study accrued 115 patients and 61 (55%) completed all three IIEF assessments. Sildenafil effect was significant (P = 0.009) with a difference in probabilities of erectile response of 0.17 (95% confidence interval: 0.06, 0.29), and 0.21 (0.06, 0.38) for patients receiving ≤120 days of ADT. However, as few as 21% of patients had a treatment-specific response, only improving during sildenafil but not during the placebo phase. Conclusions This is the first controlled trial to suggest a positive sildenafil response for ED treatment in patients previously treated with RT/ADT, however, only a minority of patients responded to treatment. ADT duration may be associated with response and requires further study. The overall low response rate suggests the need for study of additional or preventative strategies for ED after RT/ADT for prostate cancer. PMID:21235716

Comparison of Sleep Latency and Number of SOREMPs in the Home and Hospital With a Modified Multiple Sleep Latency Test: A Randomized Crossover Study.

PubMed

Beiske, Kornelia K; Sand, Trond; Rugland, Eyvind; Stavem, Knut

2017-05-01

Comparison of mean sleep latencies and number of sleep-onset rapid eye movement periods (SOREMPs) between modified multiple sleep latency test (MSLT) performed in the unattended home and in-hospital laboratory setting. A randomized crossover single-blinded design. Thirty-four subjects referred to MSLT for suspected hypersomnia or narcolepsy were included. Participants were randomized to perform modified MSLT in the unattended home or in the hospital first. Scores in the two settings were compared using Wilcoxon signed-rank test or exact McNemar test. Agreement between home and hospital categorized mean sleep latency and number of SOREMPs was assessed using simple kappa (κ) and proportion agreement. Agreement between home and hospital mean sleep latency was assessed using a Bland-Altman plot and an intraclass correlation coefficient. There was no difference between home and hospital assessment of mean sleep latency (P = 0.86). Two or more SOREMPs were found more frequently on modified MSLTs performed at home compared with those at the hospital (7 and 2, respectively; P = 0.025). Agreement was moderate for categorized sleep latency (κ = 0.53) and fair for categorized SOREMPs (κ = 0.39) in the 2 settings. Analysis of mean sleep latency using intraclass correlation coefficient showed a very good agreement between the two settings. Group mean sleep latency for home modified MSLTs seems to be reliable compared with that for the attended sleep-laboratory setting. Higher rate of SOREMP in the unattended home suggests that napping in a familiar environment facilitates the transition into REM sleep. Further studies are needed to assess the normal limit, sensitivity, and specificity for SOREMP at home before the clinical utility of home-based napping can be determined.

Pilot Randomized Controlled Trial of Titrated Subcutaneous Ketamine in Older Patients with Treatment-Resistant Depression.

PubMed

George, Duncan; Gálvez, Verònica; Martin, Donel; Kumar, Divya; Leyden, John; Hadzi-Pavlovic, Dusan; Harper, Simon; Brodaty, Henry; Glue, Paul; Taylor, Rohan; Mitchell, Philip B; Loo, Colleen K

2017-11-01

To assess the efficacy and safety of subcutaneous ketamine for geriatric treatment-resistant depression. Secondary aims were to examine if repeated treatments were safe and more effective in inducing or prolonging remission than a single treatment. In this double-blind, controlled, multiple-crossover study with a 6-month follow-up (randomized controlled trial [RCT] phase), 16 participants (≥60 years) with treatment-resistant depression who relapsed after remission or did not remit in the RCT were administered an open-label phase. Up to five subcutaneous doses of ketamine (0.1, 0.2, 0.3, 0.4, and 0.5 mg/kg) were administered in separate sessions (≥1 week apart), with one active control (midazolam) randomly inserted (RCT phase). Twelve ketamine treatments were given in the open-label phase. Mood, hemodynamic, and psychotomimetic outcomes were assessed by blinded raters. Remitters in each phase were followed for 6 months. Seven of 14 RCT-phase completers remitted with ketamine treatment. Five remitted at doses below 0.5 mg/kg. Doses ≥ 0.2 mg/kg were significantly more effective than midazolam. Ketamine was well tolerated. Repeated treatments resulted in higher likelihood of remission or longer time to relapse. Results provide preliminary evidence for the efficacy and safety of ketamine in treating elderly depressed. Dose titration is recommended for optimizing antidepressant and safety outcomes on an individual basis. Subcutaneous injection is a practical method for giving ketamine. Repeated treatments may improve remission rates (clinicaltrials.gov; NCT01441505). Copyright © 2017 American Association for Geriatric Psychiatry. All rights reserved.

A randomized, double-blind, crossover, placebo-controlled comparative clinical trial of arginine aspartate plus adenosine monophosphate for the intermittent treatment of male erectile dysfunction.

PubMed

Neuzillet, Y; Hupertan, V; Cour, F; Botto, H; Lebret, T

2013-03-01

Efficacy and safety of l-arginine aspartate 8 g combined with 200 mg of adenosine monophosphate (AA) with placebo (PL) alone for intermittent treatment of mild-to-moderate erectile dysfunction (ED) were compared. The study design was a double-blind, PL-controlled, two-way crossover randomized clinical trial with 26 patients. Efficacy was assessed by International Index of Erectile Function (IIEF) and two additional validated questionnaires [the Erection Hardness Score (EHS) and the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS). During each crossover period, separated by a 2-week wash-out period, drugs were administered orally, 1-2 h before sexual intercourse. Primary endpoint was a change in the IIEF. Secondary endpoints were patient and investigator assessments of treatment success. Investigators' and patients' assessment of efficacy was significantly improved by the combination vs. PL (p = 0.01 and p = 0.04 respectively]. EHS and EDITS questionnaires were both improved by the combination (p = 0.015 and p = 0.017 respectively). There was no significant difference in terms of tolerance between AA and PL or severe adverse events. ED patients demonstrated significant improvements in all IIEF domains with the exception of the Sexual Desire and Orgasmic Domains when treated with AA compared with PL. This pilot phase II study showed that the on-demand oral administration at a high dosage of l-arginine aspartate-adenosine monophosphate combination may be effective in patients with mild-to-moderate ED, is very well tolerated and could be tested as a safe first-line therapy in a larger size phase III study. © 2012 American Society of Andrology and European Academy of Andrology.

Comparative Evaluation of Neem Mouthwash on Plaque and Gingivitis: A Double-blind Crossover Study.

PubMed

Jalaluddin, Md; Rajasekaran, U B; Paul, Sam; Dhanya, R S; Sudeep, C B; Adarsh, V J

2017-07-01

The present study aimed at evaluating the impact of neem-containing mouthwash on plaque and gingivitis. This randomized, double-blinded, crossover clinical trial included 40 participants aged 18 to 35 years with washout period of 1 week between the crossover phases. A total of 20 participants, each randomly allocated into groups I and II, wherein in the first phase, group I was provided with 0.2% chlorhexidine gluconate and group II with 2% neem mouthwash. After the scores were recorded, 1-week time period was given to the participants to carry over the effects of the mouthwashes and then the second phase of the test was performed. The participants were instructed to use the other mouthwash through the second test phase. There was a slight reduction of plaque level in the first phase as well as in the second phase. When comparison was made between the groups, no statistically significant difference was seen. Both the groups showed reduction in the gingival index (GI) scores in the first phase, and there was a statistically significant difference in both groups at baseline and after intervention (0.005 and 0.01 respectively). In the second phase, GI scores were reduced in both groups, but there was a statistically significant difference between the groups only at baseline scores (0.01). In the present study, it has been concluded that neem mouthwash can be used as an alternative to chlorhexidine mouthwash based on the reduced scores in both the groups. Using neem mouthwash in maintaining oral hygiene might have a better impact in prevention as well as pervasiveness of oral diseases as it is cost-effective and easily available.

Hyperbaric Oxygen Environment Can Enhance Brain Activity and Multitasking Performance

PubMed Central

Vadas, Dor; Kalichman, Leonid; Hadanny, Amir; Efrati, Shai

2017-01-01

Background: The Brain uses 20% of the total oxygen supply consumed by the entire body. Even though, <10% of the brain is active at any given time, it utilizes almost all the oxygen delivered. In order to perform complex tasks or more than one task (multitasking), the oxygen supply is shifted from one brain region to another, via blood perfusion modulation. The aim of the present study was to evaluate whether a hyperbaric oxygen (HBO) environment, with increased oxygen supply to the brain, will enhance the performance of complex and/or multiple activities. Methods: A prospective, double-blind randomized control, crossover trial including 22 healthy volunteers. Participants were asked to perform a cognitive task, a motor task and a simultaneous cognitive-motor task (multitasking). Participants were randomized to perform the tasks in two environments: (a) normobaric air (1 ATA 21% oxygen) (b) HBO (2 ATA 100% oxygen). Two weeks later participants were crossed to the alternative environment. Blinding of the normobaric environment was achieved in the same chamber with masks on while hyperbaric sensation was simulated by increasing pressure in the first minute and gradually decreasing to normobaric environment prior to tasks performance. Results: Compared to the performance at normobaric conditions, both cognitive and motor single tasks scores were significantly enhanced by HBO environment (p < 0.001 for both). Multitasking performance was also significantly enhanced in HBO environment (p = 0.006 for the cognitive part and p = 0.02 for the motor part). Conclusions: The improvement in performance of both single and multi-tasking while in an HBO environment supports the hypothesis which according to, oxygen is indeed a rate limiting factor for brain activity. Hyperbaric oxygenation can serve as an environment for brain performance. Further studies are needed to evaluate the optimal oxygen levels for maximal brain performance. PMID:29021747

Hyperbaric Oxygen Environment Can Enhance Brain Activity and Multitasking Performance.

PubMed

Vadas, Dor; Kalichman, Leonid; Hadanny, Amir; Efrati, Shai

2017-01-01

Background: The Brain uses 20% of the total oxygen supply consumed by the entire body. Even though, <10% of the brain is active at any given time, it utilizes almost all the oxygen delivered. In order to perform complex tasks or more than one task (multitasking), the oxygen supply is shifted from one brain region to another, via blood perfusion modulation. The aim of the present study was to evaluate whether a hyperbaric oxygen (HBO) environment, with increased oxygen supply to the brain, will enhance the performance of complex and/or multiple activities. Methods: A prospective, double-blind randomized control, crossover trial including 22 healthy volunteers. Participants were asked to perform a cognitive task, a motor task and a simultaneous cognitive-motor task (multitasking). Participants were randomized to perform the tasks in two environments: (a) normobaric air (1 ATA 21% oxygen) (b) HBO (2 ATA 100% oxygen). Two weeks later participants were crossed to the alternative environment. Blinding of the normobaric environment was achieved in the same chamber with masks on while hyperbaric sensation was simulated by increasing pressure in the first minute and gradually decreasing to normobaric environment prior to tasks performance. Results: Compared to the performance at normobaric conditions, both cognitive and motor single tasks scores were significantly enhanced by HBO environment ( p < 0.001 for both). Multitasking performance was also significantly enhanced in HBO environment ( p = 0.006 for the cognitive part and p = 0.02 for the motor part). Conclusions: The improvement in performance of both single and multi-tasking while in an HBO environment supports the hypothesis which according to, oxygen is indeed a rate limiting factor for brain activity. Hyperbaric oxygenation can serve as an environment for brain performance. Further studies are needed to evaluate the optimal oxygen levels for maximal brain performance.

Effect of a single brushing with two Zn-containing toothpastes on VSC in morning breath: a 12 h, randomized, double-blind, cross-over clinical study.

PubMed

Young, A; Jonski, G

2011-12-01

This randomized, double-blind, 12 h clinical study tested the effect of a single brushing with two Zn-containing toothpastes on volatile sulfur compound (VSC) levels in morning breath. The following toothpastes were each tested by all 28 participants: A-Zn toothpaste, B--experimental toothpaste (Zn citrate + PVM/MA copolymer) and C--control toothpaste without Zn. The evening prior to test days participants brushed their teeth for 2 min with 1 g toothpaste. 12 h later and prior to eating or performing oral hygiene, morning breath levels of VSC (H(2)S, CH(3)SH) were analysed by gas chromatography. Subjects then rinsed for 30 s with 5 ml cysteine and breath samples were analysed for H(2)S (H(2)S(cys)). Median VSC (area under the curve) values were compared for A, B and C and the effects of A and B on VSC were compared with C. Toothpaste B was more effective than both toothpastes A and C in reducing H(2)S, CH(3)SH and H(2)S(cys) (p < 0.05). Compared with toothpaste C, toothpastes A and B reduced H(2)S by 35% and 68%, respectively (p = 0.003), and CH(3)SH by 12% and 47%, respectively (p = 0.002). Toothpaste B reduced H(2)S(cys) by 48% compared with toothpaste C (p = 0.001). It is suggested that the superior effect of the experimental toothpaste was most likely due to a higher Zn concentration combined with longer retention of Zn due to the PVM/MA copolymer.

Comparison between self-formulation and compounded-formulation dexamethasone mouth rinse for oral lichen planus: a pilot, randomized, cross-over trial.

PubMed

Hambly, Jessica L; Haywood, Alison; Hattingh, Laetitia; Nair, Raj G

2017-08-01

There is a lack of appropriate, commercially-available topical corticosteroid formulations for use in oral lichen planus (OLP) and oral lichenoid reaction. Current therapy includes crushing a dexamethasone tablet and mixing it with water for use as a mouth rinse. This formulation is unpleasant esthetically and to use in the mouth, as it is a bitter and gritty suspension, resulting in poor compliance. Thus, the present study was designed to formulate and pilot an effective, esthetically-pleasing formulation. A single-blinded, cross-over trial was designed with two treatment arms. Patients were monitored for 7 weeks. Quantitative and qualitative data was assessed using VAS, numeric pain scales, the Treatment Satisfaction Questionnaire for Medication-9, and thematic analysis to determine primary patient-reported outcomes, including satisfaction, compliance, quality of life, and symptom relief. Nine patients completed the pilot trial. Data analysis revealed the new compounded formulation to be superior to existing therapy due to its convenience, positive contribution to compliance, patient-perceived faster onset of action, and improved symptom relief. Topical dexamethasone is useful in the treatment of OLP. When carefully formulated into a compounded mouth rinse, it improves patient outcomes. © 2016 John Wiley & Sons Australia, Ltd.

Effect of muscle activity immediately after botulinum toxin injection for writer's cramp.

PubMed

Chen, R; Karp, B I; Goldstein, S R; Bara-Jimenez, W; Yaseen, Z; Hallett, M

1999-03-01

Animal and human studies have shown that nerve stimulation enhances some effects of botulinum toxin (btx A) injection. Voluntary muscle activity might work similarly and would focus the effect of an injection into the active muscles. We studied the effects of exercise immediately after btx A injection in eight patients with writer's cramp with established response to btx A over two injection cycles with a single-blinded, randomized, crossover design. Immediately after the first study injection, they were randomly assigned to write continuously for 30 min or have their hand and forearm immobilized for 30 min. Following the second injection, they were assigned the alternate condition. Patients were assessed just before each injection, and at 2 weeks, 6 weeks, and 3 months post-injection. Assessment included objective strength testing, self-reported rating of benefit and weakness, and blinded evaluation of videotapes and writing samples of the patients writing a standard passage. Strength testing showed that the maximum weakness occurred at 2 weeks post-injection, but the benefit was maximum at 6 weeks post-injection. The "write" condition resulted in greater reduction in strength than the "rest" condition. Btx A treatment led to improvement in self-reported ratings, writer's cramp rating scale scores by blinded raters, and reduction in writing time, but the differences between the "write" and "rest" conditions were not significant. We conclude that voluntary muscle activity immediately after btx A injection leads to greater reduction in muscle strength. Our findings raise the possibility that voluntary muscle activation may allow reduction of btx A doses and favorably alter the balance of benefit and side effects of btx A injections.

Treatment of fatigue with methylphenidate, modafinil and amantadine in multiple sclerosis (TRIUMPHANT-MS): Study design for a pragmatic, randomized, double-blind, crossover clinical trial.

PubMed

Nourbakhsh, Bardia; Revirajan, Nisha; Waubant, Emmanuelle

2018-01-01

Fatigue is the most common symptom of multiple sclerosis (MS). Amantadine, modafinil and amphetamine-like stimulants are commonly used in clinical practice for treatment of fatigue; however, the evidence supporting their effectiveness is sparse and conflicting. To describe the design of a trial study funded by Patient-Centered Outcome Research Institute (PCORI) that will compare the efficacy of commonly used fatigue medications in patients with MS. The study is a randomized, placebo-controlled, crossover, four-sequence, four-period, double-blind, multicenter trial of three commonly used medications for the treatment of MS-related fatigue (amantadine, modafinil, methylphenidate) versus placebo in fatigued subjects with MS. Adult patients with MS, with an Expanded Disability Status Scale of <7.0 are eligible to participate. Participants will be randomized to one of four predefined sequences of medication administration. Each sequence comprises four 6-week periods of treatment with one of the 3 study drugs or placebo, and three 2-week washout periods between medication periods. 136 participants will be randomized over two years in two academic centers in the United States starting in the Summer 2017. Complete enrollment is expected by early 2019. The primary outcome of the study is the modified fatigue impact scale (MFIS) score while participants receive the maximally tolerated dose of each study medication (or placebo). Safety and tolerability of the medications and heterogeneity of treatment effect will also be assessed. Results of the proposed study will provide evidence-based and personalized treatment options for patients affected by MS-related fatigue. Clinicaltrials.gov registration number: NCT03185065. Copyright © 2017 Elsevier Inc. All rights reserved.

Beneficial effect of tagatose consumption on postprandial hyperglycemia in Koreans: a double-blind crossover designed study.

PubMed

Kwak, Jung Hyun; Kim, Min Sun; Lee, Jin Hee; Yang, Yoon Jung; Lee, Ki Ho; Kim, Oh Yoen; Lee, Jong Ho

2013-08-01

The present study determined the effect of tagatose supplementation on postprandial hyperglycemia in normal (n = 54) and hyperglycemic subjects [n = 40, impaired fasting glucose (IFG) and newly diagnosed type 2 diabetes]. In a double-blind crossover designed study, study subjects were randomly assigned to consume a sucralose-erythritol drink (the placebo) or a tagatose-containing drink (the test) with a seven-day interval. Finally, 85 subjects completed the study (normal, n = 52; hyperglycemic, n = 33). Blood samples were collected at 0, 30, 60 and 120 min after ingestion and analyzed for fasting and postprandial levels of glucose, insulin and C-peptide. Basic anthropometric parameters and lipid files were also measured. Hyperglycemic subjects were basically older and heavier, and showed higher levels of triglyceride, total- and LDL-cholesterols and apolipoprotein AI and B compared with normal subjects. After consuming the tagatose (5 g)-containing drink, hyperglycemic subjects had a significant reduction in serum levels of glucose at 120 min (p = 0.019) and glucose area under the curve (AUC) (p = 0.017), however these were not observed in normal subjects. When ages were matched between the two groups, the glucose response patterns were shown to be similar. Additionally, normal subjects who received a high-dose of tagatose-containing drinks (10 g) showed significantly lower levels of insulin at 30 min (p = 0.004) and 60 min (p = 0.011), insulin AUC (p = 0.009), and C-peptide at 30 min (p = 0.004), 60 min (p = 0.011) and C-peptide AUC (p = 0.023). In conclusion, a single dietary supplement in the form of a tagatose-containing drink may be beneficial for controlling postprandial glycemic response in Koreans.

Next-day residual effects of gabapentin, diphenhydramine, and triazolam on simulated driving performance in healthy volunteers: a phase 3, randomized, double-blind, placebo-controlled, crossover trial.

PubMed

Kay, Gary G; Schwartz, Howard I; Wingertzahn, Mark A; Jayawardena, Shyamalie; Rosenberg, Russell P

2016-05-01

Next-day residual effects of a nighttime dose of gabapentin 250 mg were evaluated on simulated driving performance in healthy participants in a randomized, placebo-controlled, double-blind, multicenter, four-period crossover study that included diphenhydramine citrate 76 mg and triazolam 0.5 mg. At treatment visits, participants (n = 59) were dosed at ~23:30, went to bed immediately, and awakened 6.5 h postdose for evaluation. The primary endpoint was the standard deviation of lateral position for the 100-km driving scenario. Additional measures of driving, sleepiness, and cognition were included. Study sensitivity was established with triazolam, which demonstrated significant next-day impairment on all driving endpoints, relative to placebo (p < 0.001). Gabapentin demonstrated noninferiority to placebo on standard deviation of lateral position and speed deviation but not for lane excursions. Diphenhydramine citrate demonstrated significant impairment relative to gabapentin and placebo on speed deviation (p < 0.05). Other comparisons were either nonsignificant or statistically ineligible per planned, sequential comparisons. Secondary endpoints for sleepiness and cognitive performance were supportive of these conclusions. Together, these data suggest that low-dose gabapentin had no appreciable next-day effects on simulated driving performance or cognitive functioning. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Effective cross-over to granisetron after failure to ondansetron, a randomized double blind study in patients failing ondansetron plus dexamethasone during the first 24 hours following highly emetogenic chemotherapy

PubMed Central

de Wit, R; de Boer, A C; vd Linden, G H M; Stoter, G; Sparreboom, A; Verweij, J

2001-01-01

In view of the similarity in chemical structure of the available 5HT3-receptor antagonists it is assumed, whilst these agents all act at the same receptor, that failure to one agent would predict subsequent failure to all 5HT3-receptor antagonists. We conducted a randomized double blind trial of granisetron 3 mg plus dexamethasone 10 mg versus continued treatment with ondansetron 8 mg plus dexamethasone 10 mg in patients with protection failure on ondansetron 8 mg plus dexamethasone 10 mg during the first 24 hours following highly emetogenic chemotherapy. Of 40 eligible patients, 21 received ondansetron + dexamethasone and 19 received granisetron + dexamethasone. We found a significant benefit from crossing-over to granisetron after failure on ondansetron. Of the 19 patients who crossed over to granisetron, 9 patients obtained complete protection, whereas this was observed in 1 of the 21 patients continuing ondansetron, P = 0.005. These results indicate that there is no complete cross-resistance between 5HT3-receptor antagonists, and that patients who have acute protection failure on one 5HT3-receptor antagonist should be offered cross-over to another 5HT3-receptor antagonist. © 2001 Cancer Research Campaign  http://www.bjcancer.com PMID:11710819

Auricular Acupuncture for Exam Anxiety in Medical Students—A Randomized Crossover Investigation

PubMed Central

Klausenitz, Catharina; Hacker, Henriette; Hesse, Thomas; Kohlmann, Thomas; Endlich, Karlhans; Hahnenkamp, Klaus; Usichenko, Taras

2016-01-01

Auricular acupuncture (AA) is effective in the treatment of preoperative anxiety. The aim was to investigate whether AA can reduce exam anxiety as compared to placebo and no intervention. Forty-four medical students were randomized to receive AA, placebo, or no intervention in a crossover manner and subsequently completed three comparable oral anatomy exams with an interval of 1 month between the exams/interventions. AA was applied using indwelling fixed needles bilaterally at points MA-IC1, MA-TF1, MA-SC, MA-AT1 and MA-TG one day prior to each exam. Placebo needles were used as control. Levels of anxiety were measured using a visual analogue scale before and after each intervention as well as before each exam. Additional measures included the State-Trait-Anxiety Inventory, duration of sleep at night, blood pressure, heart rate and the extent of participant blinding. All included participants finished the study. Anxiety levels were reduced after AA and placebo intervention compared to baseline and the no intervention condition (p < 0.003). AA was better at reducing anxiety than placebo in the evening before the exam (p = 0.018). Participants were able to distinguish between AA and placebo intervention. Both AA and placebo interventions reduced exam anxiety in medical students. The superiority of AA over placebo may be due to insufficient blinding of participants. PMID:28033320

Cranberry (poly)phenol metabolites correlate with improvements in vascular function: A double-blind, randomized, controlled, dose-response, crossover study.

PubMed

Rodriguez-Mateos, Ana; Feliciano, Rodrigo P; Boeres, Albert; Weber, Timon; Dos Santos, Claudia Nunes; Ventura, M Rita; Heiss, Christian

2016-10-01

Cranberries are rich in potentially bioactive (poly)phenols. The aim of this paper was to investigate whether cranberry juice intake can improve vascular function in healthy men in a dose- and time-dependent manner, and to understand which of the circulating (poly)phenol metabolites correlate with vascular effects. A double-blind randomized controlled crossover trial was conducted in ten healthy males. Flow-mediated dilation (FMD), blood pressure, pulse wave velocity and augmentation index were investigated at baseline, 1, 2, 4, 6, and 8 h post-consumption of cranberry juices containing 409, 787, 1238, 1534, and 1910 mg of total cranberry (poly)phenols (TP), and a control drink. Plasma (poly)phenol metabolites were analyzed by UPLC-Q-TOF MS using authentic standards. We observed dose-dependent increases in FMD at 1, 2, 4, 6, and 8 h with a peak at 4 h and maximal effects with juice containing 1238 mg TP. A total of 60 metabolites were quantified in plasma after cranberry consumption. Twelve (poly)phenol metabolites significantly correlated with the increases in FMD, including ferulic and caffeic acid sulfates, quercetin-3-O-ß-D-glucuronide and a γ-valerolactone sulfate. (Poly)phenols in cranberry juice can improve vascular function in healthy males and this is linked to the presence of specific newly identified plasma metabolites. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effect of Pregabalin on Cardiovascular Responses to Exercise and Postexercise Pain and Fatigue in Fibromyalgia: A Randomized, Double-Blind, Crossover Pilot Study

PubMed Central

White, Andrea T.; Light, Kathleen C.; Bateman, Lucinda; Hughen, Ronald W.; Vanhaitsma, Timothy A.; Light, Alan R.

2015-01-01

Pregabalin, an approved treatment for fibromyalgia (FM), has been shown to decrease sympathetic nervous system (SNS) activity and inhibit sympathetically maintained pain, but its effects on exercise responses have not been reported. Methods. Using a randomized double-blind crossover design, we assessed the effect of 5 weeks of pregabalin (versus placebo) on acute cardiovascular and subjective responses to moderate exercise in 19 FM patients. Blood pressure (BP), heart rate (HR), and ratings of perceived exertion (RPE) during exercise and ratings of pain, physical fatigue, and mental fatigue before, during, and for 48 hours after exercise were compared in patients on pregabalin versus placebo and also versus 18 healthy controls. Results. On placebo, exercise RPE and BP were significantly higher in FM patients than controls (p < 0.04). Pregabalin responders (n = 12, defined by patient satisfaction and symptom changes) had significantly lower exercise BP, HR, and RPE on pregabalin versus placebo (p < 0.03) and no longer differed from controls (p > 0.26). Cardiovascular responses of nonresponders (n = 7) were not altered by pregabalin. In responders, pregabalin improved ratings of fatigue and pain (p < 0.04), but negative effects on pain and fatigue were seen in nonresponders. Conclusions. These preliminary findings suggest that pregabalin may normalize cardiovascular and subjective responses to exercise in many FM patients. PMID:27026828

Bovine colostrum to children with short bowel syndrome: a randomized, double-blind, crossover pilot study.

PubMed

Aunsholt, Lise; Jeppesen, Palle Bekker; Lund, Pernille; Sangild, Per Torp; Ifaoui, Inge Bøtker Rasmussen; Qvist, Niels; Husby, Steffen

2014-01-01

Management of short bowel syndrome (SBS) aims to achieve intestinal autonomy to prevent fluid, electrolyte, and nutrient deficiencies and maintain adequate development. Remnant intestinal adaptation is required to obtain autonomy. In the newborn pig, colostrum has been shown to support intestinal development and hence adaptive processes. The efficacy of bovine colostrum to improve intestinal function in children with SBS was evaluated by metabolic balance studies. Nine children with SBS were included in a randomized, double-blind, crossover study. Twenty percent of enteral fluid intake was replaced with bovine colostrum or a mixed milk diet for 4 weeks, separated by a 4-week washout period. Intestinal absorption of energy and wet weight was used to assess intestinal function and the efficacy of colostrum. Colostrum did not improve energy or wet weight absorption compared with the mixed milk diet (P = 1.00 and P = .93, respectively). Growth as measured by weight and knemometry did not differ between diets (P = .93 and P = .28). In these patients, <150% enteral energy absorption of basal metabolic rate and 50% enteral fluid absorption of basal fluid requirement suggested intestinal failure and a need for parenteral nutrition (PN). Inclusion of bovine colostrum to the diet did not improve intestinal function. Metabolic nutrient and wet weight balance studies successfully assessed intestinal function, and this method may distinguish between intestinal insufficiency (non-PN-dependent) and intestinal failure (PN-dependent) patients.

Simvastatin Treatment Does Not Affect Serum Vitamin D Concentrations in Patients with Dyslipidemia: A Randomized Double-blind Placebo-controlled Cross-over Trial.

PubMed

Mazidi, Mohsen; Rokni, Haleh; Sahebkar, Amir Hossein; Mohammadi, Akram; Ghayour-Mobarhan, Majid; Ferns, Gordon A

2016-01-01

Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) are antihyperlipidemic drugs with an established efficacy in stabilizing atherosclerotic plaques and preventing atherogenesis and reducing cardiovascular events. The purpose of this study was to determine the effect of simvastatin on serum Vitamin D status in dyslipidemic patients as Vitamin D status has an impact on monocyte/macrophage function and may also contribute to cardiovascular risk. Selected individuals (n = 102) were treated with simvastatin (40 mg/day), or matching placebo in a randomized, double-blind, placebo-controlled, crossover trial. Each treatment period (with simvastatin or placebo) lasted for 30 days and was separated by a 2-week washout phase. Serum Vitamin D concentration was assessed pre- and post-treatment. Seventy-seven completed the trial, noncompliance with the study protocol and drug intolerance or relocation were the causes for drop-out. No significant carry-over effect was observed for the assessed parameters. There was a reduction in the serum levels of low-density lipoprotein cholesterol (P < 0.001), total cholesterol (P < 0.001), and triglycerides (P < 0.05). Nevertheless, simvastatin therapy did not significantly affect serum level of high-density lipoprotein cholesterol and Vitamin D level (P > 0.05). Short-term treatment with simvastatin (40 mg/day) does not have a significant affect on serum levels of Vitamin D.

QT effect of semagacestat at therapeutic and supratherapeutic doses.

PubMed

Zhang, Wei; Ayan-Oshodi, Mosun; Willis, Brian A; Annes, William; Hall, Stephen D; Chiesa, Joseph; Seger, Mary

2012-04-01

This thorough QT/ QT interval corrected for heart rate (QTc) study was designed to assess the potential of semagacestat, a functional gamma-secretase inhibitor, to delay cardiac repolarization. In this Phase I, single-dose, randomized, 4-period crossover study, semagacestat was compared with placebo in 54 healthy male and female subjects between the ages of 19 and 63 years, inclusive. Each study period included single oral-dose administrations of semagacestat 140 mg, semagacestat 280 mg, moxifloxacin 400 mg, or placebo. Study subjects and the investigator were blinded to the identity of semagacestat and placebo; however, moxifloxacin was administered as open-label. Moxifloxacin was compared with placebo for assay sensitivity analysis. Pharmacokinetic parameters were also assessed. For each QTc, the upper bound of the 2-sided 90% confidence interval (CI) for the least squares mean difference between semagacestat (at both the 140- and 280-mg dose levels) and placebo was < 10 msec at all time points, and thus, within the limits set for clinical relevance in regulatory guidelines. The results of this study indicate that single doses of 140 and 280 mg semagacestat did not prolong QTc to a clinically significant degree.

Double-Blind, Placebo-Controlled, Crossover Study of the Efficacy and Safety of Lisdexamfetamine Dimesylate in College Students with ADHD

ERIC Educational Resources Information Center

DuPaul, George J.; Weyandt, Lisa L.; Rossi, Joseph S.; Vilardo, Brigid A.; O'Dell, Sean M.; Carson, Kristen M.; Verdi, Genevieve; Swentosky, Anthony

2012-01-01

Objective: To evaluate stimulant medication on symptoms and functioning for college students with ADHD using double-blind, placebo-controlled, crossover design. Method: Participants included 24 college students with ADHD and 26 college students without psychopathology. Lisdexamfetamine dimesylate (LDX) was examined for ADHD participants over five…

A randomized, double-blind, placebo-controlled, crossover trial evaluating the effect of intranasal insulin on cognition and mood in individuals with treatment-resistant major depressive disorder.

PubMed

Cha, Danielle S; Best, Michael W; Bowie, Christopher R; Gallaugher, Laura Ashley; Woldeyohannes, Hanna O; Soczynska, Joanna K; Lewis, Gary; MacQueen, Glenda; Sahakian, Barbara J; Kennedy, Sidney H; Lui, Jane P; Mansur, Rodrigo B; McIntyre, Roger S

2017-03-01

Cognitive dysfunction in major depressive disorder (MDD) is identified as a primary therapeutic target; no current treatment is approved for the treatment of cognitive dysfunction in MDD. We examined whether intranasal insulin offered a beneficial effect across measures of cognitive function in adults with MDD. Thirty-five adults (18-65 years of age: 47.09±9.89) meeting criteria for a major depressive episode as per the Diagnostic and Statistical Manual (DSM)-IV-Treatment Revised were included in this randomized, double blind, placebo-controlled, crossover design study. Subjects were not stratified based on baseline cognitive deficit. Subjects were randomized to 4 weeks of either intranasal insulin 40 International Units (IU) taken four times a day (i.e., morning, afternoon, evening, and before bed) (QID) (n=19) or placebo (n=16). No between group differences were observed in change from baseline on total Montgomery Åsberg Depression Rating Scale (MADRS) score (25.98±2.81), in either of the Positive or Negative subscales of the Positive and Negative Affect Schedule (PANAS), or on a global index of neurocognition. The possibility of practice and/or carry over effect could not be excluded. Methodological refinement (e.g., stratification of subjects based on baseline cognitive deficit) may have augmented assay sensitivity. Intranasal insulin did not demonstrate statistically significant improvements on overall mood, aspects of emotional processing, neurocognitive function, or self-reported quality of life patient reported outcomes. Copyright © 2016 Elsevier B.V. All rights reserved.

A randomized, double-blind, cross-over, phase IV trial of oros-methylphenidate (CONCERTA(®)) and generic novo-methylphenidate ER-C (NOVO-generic).

PubMed

Fallu, Angelo; Dabouz, Farida; Furtado, Melissa; Anand, Leena; Katzman, Martin A

2016-08-01

Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral disorder with onset during childhood. Multiple aspects of a child's development are hindered, in both home and school settings, with negative impacts on social, emotional, and cognitive functioning. If left untreated, ADHD is commonly associated with poor academic achievement and low occupational status, as well as increased risk of substance abuse and delinquency. The objective of this study was to evaluate adult ADHD subject reported outcomes when switched from a stable dose of CONCERTA(®) to the same dose of generic Novo-methylphenidate ER-C(®). Randomized, double-blind, cross-over, phase IV trial consisted of two phases in which participants with a primary diagnosis of ADHD were randomized in a 1:1 ratio to 3 weeks of treatment with CONCERTA or generic Novo-Methylphenidate ER-C. Following 3 weeks of treatment, participants were crossed-over to receive the other treatment for an additional 3 weeks. Primary efficacy was assessed through the use of the Treatment Satisfaction Questionnaire for Medication, Version II (TSQM-II). Participants with ADHD treated with CONCERTA were more satisfied in terms of efficacy and side effects compared to those receiving an equivalent dose of generic Novo-Methylphenidate ER-C. All participants chose to continue with CONCERTA treatment at the conclusion of the study. Although CONCERTA and generic Novo-Methylphenidate ER-C have been deemed bioequivalent, however the present findings demonstrate clinically and statistically significant differences between generic and branded CONCERTA. Further investigation of these differences is warranted.

Cognitive changes after saline or plasmalyte infusion in healthy volunteers: a multiple blinded, randomized, cross-over trial.

PubMed

Story, David A; Lees, Lucy; Weinberg, Laurence; Teoh, Soon-Yee; Lee, Katherine J; Velissaris, Sarah; Bellomo, Rinaldo; Wilson, Sarah J

2013-09-01

In an incidental finding, during a study of plasma chemistry after crystalloid infusion, participants reported subjective cognitive changes, particularly slower thinking, after saline but not Hartmann's (Ringer's lactate) solution. The authors tested the hypothesis that saline infusion would produce greater adverse cognitive changes than Plasmalyte infusion. The authors conducted a randomized, cross-over, multiple blinded study of healthy adult volunteers. On separate days, participants received 30 ml/kg over 1 h of either 0.9% saline or Plasmalyte with the order randomly allocated. Plasma chemistry was tested on venous samples. As part of a battery of cognitive tests our primary endpoint was the reaction time index after infusion. The authors studied 25 participants. Plasma chloride was greater after saline than after Plasmalyte: mean difference 5.4 mM (95% CI, 4.1-6.6 mM; P < 0.001). Saline was also associated with greater metabolic acidosis: base-excess 2.5 mM more negative (95% CI, 1.9-3.0 mM more negative; P < 0.001). There was no evidence of a difference in the reaction time index between the two interventions: mean reaction time index 394 ms (SD, 72) after saline versus 385 ms (SD, 55) after Plasmalyte. Difference: saline 9 ms slower (95% CI, 30 ms slower to 12 ms faster; P = 0.39). There were minimal differences in the other cognitive and mood tests. Despite expected differences in plasma chemistry, the authors found that measures of cognition did not differ after infusions of Plasmalyte or saline.

Modafinil improves real driving performance in patients with hypersomnia: a randomized double-blind placebo-controlled crossover clinical trial.

PubMed

Philip, Pierre; Chaufton, Cyril; Taillard, Jacques; Capelli, Aurore; Coste, Olivier; Léger, Damien; Moore, Nicholas; Sagaspe, Patricia

2014-03-01

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. 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. 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. 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). 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.

In Vitro Activation of eNOS by Mangifera indica (Careless™) and Determination of an Effective Dosage in a Randomized, Double-Blind, Human Pilot Study on Microcirculation.

PubMed

Gerstgrasser, Alexandra; Röchter, Sigrid; Dressler, Dirk; Schön, Christiane; Reule, Claudia; Buchwald-Werner, Sybille

2016-03-01

Mangifera indica fruit preparation (Careless™) activates the evolutionary conserved metabolic sensors sirtuin 1 and adenosine monophosphate-activated protein kinase, which have been identified as playing a key role in microcirculation and endothelial function. Here, an acute effect of a single dose of 100 mg or 300 mg Careless™ on microcirculation was investigated in a randomized, double-blind, crossover pilot study in ten healthy women to determine the effective dosage. Microcirculation and endothelial function were assessed by the Oxygen-to-see system and pulse amplitude tonometry (EndoPAT™), respectively. Cutaneous blood flow was increased over time by 100 mg (54% over pre-values, p = 0.0157) and 300 mg (35% over pre-value, p = 0.209) Careless™. The EndoPAT™ reactive hyperemia response was slightly improved 3 h after intake compared to pretesting with 300 mg Careless™. Furthermore, activation of endothelial nitric oxide synthase, as an important regulator for endothelial function, was tested in vitro in primary human umbilical vein endothelial cells. Careless™, after simulation of digestion, increased the activated form of endothelial nitric oxide synthase dose-dependently by 23% (300 µg/mL), 42% (1500 µg/mL), and 60% (3000 µg/mL) compared to the untreated control. In conclusion, the study suggests moderate beneficial effects of Careless™ on microcirculation, which is at least partly mediated by endothelial nitric oxide synthase activation. Georg Thieme Verlag KG Stuttgart · New York.

No Acute Effects of Cannabidiol on the Sleep-Wake Cycle of Healthy Subjects: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study

PubMed Central

Linares, Ila M. P.; Guimaraes, Francisco S.; Eckeli, Alan; Crippa, Ana C. S.; Zuardi, Antonio W.; Souza, Jose D. S.; Hallak, Jaime E.; Crippa, José A. S.

2018-01-01

Cannabidiol (CBD) is a component of Cannabis sativa that has a broad spectrum of potential therapeutic effects in neuropsychiatric and other disorders. However, few studies have investigated the possible interference of CBD on the sleep-wake cycle. The aim of the present study was to evaluate the effect of a clinically anxiolytic dose of CBD on the sleep-wake cycle of healthy subjects in a crossover, double-blind design. Twenty-seven healthy volunteers that fulfilled the eligibility criteria were selected and allocated to receive either CBD (300 mg) or placebo in the first night in a double-blind randomized design (one volunteer withdrew from the study). In the second night, the same procedure was performed using the substance that had not been administered in the previous occasion. CBD or placebo were administered 30 min before the start of polysomnography recordings that lasted 8 h. Cognitive and subjective measures were performed immediately after polysomnography to assess possible residual effects of CBD. The drug did not induce any significant effect (p > 0.05). Different from anxiolytic and antidepressant drugs such as benzodiazepines and selective serotonin reuptake inhibitors, acute administration of an anxiolytic dose of CBD does not seem to interfere with the sleep cycle of healthy volunteers. The present findings support the proposal that CBD do not alter normal sleep architecture. Future studies should address the effects of CBD on the sleep-wake cycle of patient populations as well as in clinical trials with larger samples and chronic use of different doses of CBD. Such studies are desirable and opportune. PMID:29674967

Crossover clinical investigation of a whitening chewing gum for inhibiting dental stain formation in conjunction with tooth brushing.

PubMed

Milleman, Jeffery L; Milleman, Kimberly R; Kleber, Carl J; Proskin, Howard M; Dodds, Michael; Kelley, Michael; Ramirez, Lilian

2014-01-01

The purpose of this clinical investigation was to evaluate the effectiveness of a marketed whitening chewing gum compared to a no-gum control in preventing the formation of extrinsic stains on the teeth of stain-forming subjects when chewed over a 12-week period of regular unsupervised use in conjunction with daily tooth brushing. This was a single-center, examiner-blind, randomized, 12-week crossover clinical trial. Stain-forming (after smoking or drinking coffee or tea) adults, starting with a stain-free baseline, either chewed the test gum (Orbit White) unsupervised four times per day, 15 minutes/chew, or used no gum along with daily brushing with a commercially available toothbrush and dentifrice for 12 weeks. At the crossover, all procedures were repeated with subjects assigned the opposite treatment. Extrinsic stain was measured at six and 12 weeks by both the Lobene Stain Index (LSI) and the Modified Lobene Stain Index (MLSI) using separate experienced examiners. After 12 weeks, LSI stain scores showed a significant 25% reduction (p = 0.0008) in new stain formation for subjects using the test chewing gum along with tooth brushing versus tooth brushing alone (no-gum control). The corresponding MLSI stain scores demonstrated a 36% reduction (p < 0.0001) in the formation of extrinsic stain on the teeth. The overall findings of this clinical study demonstrated that regular use of Orbit White chewing gum, soon after smoking or drinking coffee or tea, will supplement daily tooth brushing in preventing unsightly stains from forming on the anterior teeth compared to brushing alone.

A dose-response evaluation of freeze-dried strawberries independent of fiber content on metabolic indices in abdominally obese individuals with insulin resistance in a randomized, single-blinded, diet-controlled crossover trial.

PubMed

Park, Eunyoung; Edirisinghe, Indika; Wei, Hequn; Vijayakumar, Lakshmi Prabha; Banaszewski, Katarzyna; Cappozzo, Jack C; Burton-Freeman, Britt

2016-05-01

This study evaluated the dose-response relationship of strawberries, an anthocyanin-rich fruit, on postprandial glucose and insulin concentrations in individuals with insulin resistance (IR), including changes in plasma anthocyanins, markers of oxidative stress, and inflammation. In a randomized controlled, four-arm, dose-response, crossover trial, 21 adults with IR consumed a high-carbohydrate, high-fat meal with one of four beverages containing 0 g freeze-dried whole strawberry powder (0g FDS, control), 10, 20, or 40 g FDS, controlled for fiber. Blood was collected at 0 min and at 30 min intervals postmeal until 2 h, then hourly until 6 h. Postmeal insulin concentrations (6 h) were significantly reduced after the 40-g FDS beverage compared to other beverages (p < 0.05). Postmeal 6 h glucose concentrations were not different, although mean insulin:glucose ratio was significantly different among beverages (p < 0.05). Pelargonidin-glucuronide was inversely associated with mean insulin concentrations after the 20 and 40 g FDS (p < 0.05). Oxidized low-density lipoprotein was reduced after 20 g FDS (p < 0.05) and IL-6 was not different among treatments. Strawberry intake reduced the insulin demand to manage postmeal glucose in obese individuals with IR, which was related to plasma anthocyanin/pelargonidin concentrations. The data support a role of strawberries in improving insulin sensitivity in people with IR. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A randomized, double crossover study to investigate the influence of saline infusion on sleep apnea severity in men.

PubMed

Yadollahi, Azadeh; Gabriel, Joseph M; White, Laura H; Taranto Montemurro, Luigi; Kasai, Takatoshi; Bradley, T Douglas

2014-10-01

Obstructive sleep apnea (OSA) is commoner in patients with fluid-retaining states than in those without fluid retention, in men than in women, and worsens with aging. In men, OSA severity is related to the amount of fluid shifting out of the legs overnight, but a cause-effect relationship is not established. Our objective was to test the hypothesis that mimicking fluid overload during sleep would increase severity of OSA more in older (≥ 40 years) than in younger men (< 40 years). Randomized, single-blind, double crossover study. Research sleep laboratory. Seven older and 10 younger men with non-severe or no sleep apnea, matched for body mass index. During the control arm, normal saline was infused to keep the vein open. During intervention, subjects received an intravenous bolus of normal saline (22 mL/kg body weight) after sleep onset while they were wearing compression stockings to prevent fluid accumulation in the legs. Compared to younger men, infusion of similar amounts of saline in older men caused a greater increase in neck circumference (P < 0.05) and in the AHI (32.2 ± 22.1 vs. 2.2 ± 7.1, P = 0.002). Older men are more susceptible to the adverse effects of intravenous fluid loading on obstructive sleep apnea severity than younger men. This may be due to age-related differences in the amount of fluid accumulating in the neck or upper airway collapsibility in response to intravenous fluid loading. These possibilities remain to be tested in future studies. © 2014 Associated Professional Sleep Societies, LLC.

The NUTRAOLEOUM Study, a randomized controlled trial, for achieving nutritional added value for olive oils.

PubMed

Biel, Sara; Mesa, Maria-Dolores; de la Torre, Rafael; Espejo, Juan-Antonio; Fernández-Navarro, Jose-Ramón; Fitó, Montserrat; Sánchez-Rodriguez, Estefanía; Rosa, Carmen; Marchal, Rosa; Alche, Juan de Dios; Expósito, Manuela; Brenes, Manuel; Gandul, Beatriz; Calleja, Miguel Angel; Covas, María-Isabel

2016-10-22

Virgin olive oil, a recognized healthy food, cannot be consumed in great quantities. We aim to assess in humans whether an optimized virgin olive oil with high phenolic content (OVOO, 429 mg/Kg) and a functional one (FOO), both rich in phenolic compounds (429 mg/Kg) and triterpenic acids (389 mg/kg), could provide health benefits additional to those supplied a by a standard virgin olive oil (VOO). A randomized, double-blind, crossover, controlled study will be conducted. Healthy volunteers (aged 20 to 50) will be randomized into one of three groups of daily raw olive oil consumption: VOO, OVOO, and FOO (30 mL/d). Olive oils will be administered over 3-week periods preceded by 2-week washout ones. The main outcomes will be markers of lipid and DNA oxidation, inflammation, and vascular damage. A bioavailability and dose-response study will be nested within this sustained- consumption one. It will be made up of 18 volunteers and be performed at two stages after a single dose of each olive oil. Endothelial function and nitric oxide will be assessed at baseline and at 4 h and 6 h after olive oil single dose ingestion. For the first time the NUTRAOLEUM Study will provide first level evidence on the health benefits in vivo in humans of olive oil triterpenes (oleanolic and maslinic acid) in addition to their bioavailability and disposition. The Trial has been registered in ClinicalTrials.gov ID: NCT02520739 .

Acute dark chocolate and cocoa ingestion and endothelial function: a randomized controlled crossover trial.

PubMed

Faridi, Zubaida; Njike, Valentine Yanchou; Dutta, Suparna; Ali, Ather; Katz, David L

2008-07-01

Studies suggest cardioprotective benefits of dark chocolate containing cocoa. This study examines the acute effects of solid dark chocolate and liquid cocoa intake on endothelial function and blood pressure in overweight adults. Randomized, placebo-controlled, single-blind crossover trial of 45 healthy adults [mean age: 53 y; mean body mass index (in kg/m(2)): 30]. In phase 1, subjects were randomly assigned to consume a solid dark chocolate bar (containing 22 g cocoa powder) or a cocoa-free placebo bar (containing 0 g cocoa powder). In phase 2, subjects were randomly assigned to consume sugar-free cocoa (containing 22 g cocoa powder), sugared cocoa (containing 22 g cocoa powder), or a placebo (containing 0 g cocoa powder). Solid dark chocolate and liquid cocoa ingestion improved endothelial function (measured as flow-mediated dilatation) compared with placebo (dark chocolate: 4.3 +/- 3.4% compared with -1.8 +/- 3.3%; P < 0.001; sugar-free and sugared cocoa: 5.7 +/- 2.6% and 2.0 +/- 1.8% compared with -1.5 +/- 2.8%; P < 0.001). Blood pressure decreased after the ingestion of dark chocolate and sugar-free cocoa compared with placebo (dark chocolate: systolic, -3.2 +/- 5.8 mm Hg compared with 2.7 +/- 6.6 mm Hg; P < 0.001; and diastolic, -1.4 +/- 3.9 mm Hg compared with 2.7 +/- 6.4 mm Hg; P = 0.01; sugar-free cocoa: systolic, -2.1 +/- 7.0 mm Hg compared with 3.2 +/- 5.6 mm Hg; P < 0.001; and diastolic: -1.2 +/- 8.7 mm Hg compared with 2.8 +/- 5.6 mm Hg; P = 0.014). Endothelial function improved significantly more with sugar-free than with regular cocoa (5.7 +/- 2.6% compared with 2.0 +/- 1.8%; P < 0.001). The acute ingestion of both solid dark chocolate and liquid cocoa improved endothelial function and lowered blood pressure in overweight adults. Sugar content may attenuate these effects, and sugar-free preparations may augment them.

Effect of extended-release dexmethylphenidate and mixed amphetamine salts on sleep: a double-blind, randomized, crossover study in youth with attention-deficit hyperactivity disorder.

PubMed

Santisteban, J A; Stein, M A; Bergmame, L; Gruber, R

2014-09-01

We sought to determine the dose-response effects of extended-release (ER) dexmethylphenidate (d-MPH) and ER mixed amphetamine salts (MAS) on objective measures of sleep. This was an 8-week, double-blind, placebo-controlled, randomized, two period, crossover study of youth with attention-deficit hyperactivity disorder (ADHD) as confirmed by the Kiddie Schedule for Affective Disorders for School-Age Children-Present and Lifetime version (K-SADS-PL). Children aged 10-17 years were recruited from clinical practice, colleague referrals, and flyers. Participants were randomized to initially receive either d-MPH or MAS. During each 4-week drug period, children received three dose levels (10, 20, and 25/30 mg) in ascending order, with placebo substituted for active medication in a randomized fashion during 1 week of the study. After 4 weeks, participants were switched to the alternative medication for another 4 weeks of treatment. The main outcome measure was sleep duration as measured by actigraphy. Children, parents, and researchers were blinded to drug, dose, and placebo status. Sixty-five participants met the inclusion criteria and were enrolled in the study. Of these, 37 participants with sufficient sleep data for analysis were included. Sleep schedule measures showed a significant effect for dose on sleep start time (F(1,36) = 6.284; p < 0.05), with a significantly later sleep start time when children were receiving 20- or 30-mg doses, compared with placebo (p < 0.05). A significant dose effect was found on actual sleep duration (F(1,36) = 8.112; p < 0.05), with significantly shorter actual sleep duration for subjects receiving 30 mg compared with those receiving placebo (p < 0.05). There were no significant differences on sleep duration or sleep schedule between the two stimulant medications. The trial is complete and closed to follow-up. Higher stimulant doses were associated with reduced sleep duration and later sleep start times, regardless of medication class. ClinicalTrials.gov: NCT00393042.

A Randomized, Double-Blind, Placebo-Controlled Crossover Study of the Anti-Inflammatory Compound Anatabine to Treat Pain in GWI Patients

DTIC Science & Technology

2016-10-01

inflammation. Over the last few years we have carried out extensive work on the dietary supplement Anatabine (Rock Creek Pharmaceuticals Inc.), which is a...minor adverse effects reported. Anatabine products are no longer available as dietary supplements as the compound company is pursuing pharmaceutical use...compound, which was available from Rock Creek Pharmaceuticals (RCP) for several years (2010-2014) as a dietary supplement . It is no longer being sold as a

Postprandial serum endotoxin in healthy humans is modulated by dietary fat in a randomized, controlled, cross-over study.

PubMed

Lyte, Joshua M; Gabler, Nicholas K; Hollis, James H

2016-11-05

High-fat diets may contribute to metabolic disease via postprandial changes in serum endotoxin and inflammation. It is unclear how dietary fat composition may alter these parameters. We hypothesized that a meal rich in n-3 (ω3) fatty acids would reduce endotoxemia and associated inflammation but a saturated or n-6 (ω6) fatty acid-rich meal would increase postprandial serum endotoxin concentrations and systemic inflammation in healthy adults. Healthy adults (n = 20; mean age 25 ± 3.2 S.D. years) were enrolled in this single-blind, randomized, cross-over study. Participants were randomized to treatment and reported to the laboratory, after an overnight fast, on four occasions separated by at least one week. Participants were blinded to treatment meal and consumed one of four isoenergetic meals that provided: 1) 20 % fat (control; olive oil) or 35 % fat provided from 2) n-3 (ω3) (DHA = 500 mg; fish oil); 3) n-6 (ω6) (7.4 g; grapeseed oil) or 4) saturated fat (16 g; coconut oil). Baseline and postprandial blood samples were collected. Primary outcome was defined as the effect of treatment meal on postprandial endotoxemia. Serum was analyzed for metabolites, inflammatory markers, and endotoxin. Data from all 20 participants were analyzed using repeated-measures ANCOVA. Participant serum endotoxin concentration was increased during the postprandial period after the consumption of the saturated fat meal but decreased after the n-3 meal (p < 0.05). The n-6 meal did not effect a different outcome in participant postprandial serum endotoxin concentration from that of the control meal (p > 0.05). There was no treatment meal effect on participant postprandial serum biomarkers of inflammation. Postprandial serum triacylglycerols were significantly elevated following the n-6 meal compared to the n-3 meal. Non-esterified fatty acids were significantly increased after consumption of the saturated fat meal compared to other treatment meals. Meal fatty acid composition modulates postprandial serum endotoxin concentration in healthy adults. However, postprandial endotoxin was not associated with systemic inflammation in vivo. This study was retrospectively registered at clinicaltrials.gov as NCT02521779 on July 28, 2015.

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 of response. Pregabalin CR was well tolerated in most patients. Generalizability may be limited by study duration and selective population.

Evaluation of the acceptability, feasibility and effectiveness of two methods of involving patients with disability in developing clinical guidelines: study protocol of a randomized pragmatic pilot trial.

PubMed

Lamontagne, Marie-Eve; Perreault, Kadija; Gagnon, Marie-Pierre

2014-04-10

Despite growing interest in the importance of, and challenges associated with the involvement of patient and population (IPP) in the process of developing and adapting clinical practice guidelines (CPGs), there is a lack of knowledge about the best method to use. This is especially problematic in the field of rehabilitation, where individuals with disabilities might face many barriers to their involvement in the guideline development and adaptation process. The goal of this pilot trial is to document the acceptability, feasibility and effectiveness of two methods of involving patients with a disability (traumatic brain injury) in CPG development. A single-blind, randomized, crossover pragmatic trial will be performed with 20 patients with traumatic brain injury (TBI). They will be randomized into two groups, and each will try two alternative methods of producing recommendations; a discussion group (control intervention) and a Wiki, a webpage that can be modified by those who have access to it (experimental intervention). The participants will rate the acceptability of the two methods, and feasibility will be assessed using indicators such as the number of participants who accessed and completed the two methods, and the number of support interventions required. Twenty experts, blinded to the method of producing the recommendations, will independently rate the recommendations produced by the participants for clarity, accuracy, appropriateness and usefulness. Our trial will allow for the use of optimal IPP methods in a larger project of adapting guidelines for the rehabilitation of individuals with TBI. Ultimately the results will inform the science of CPG development and contribute to the growing knowledge about IPP in rehabilitation settings. Clinical trial KT Canada 87776.

A double-blind randomized discontinuation phase II study of sorafenib (BAY 43-9006) in previously treated non-small cell lung cancer patients: Eastern Cooperative Oncology Group study E2501

PubMed Central

Wakelee, Heather A.; Lee, Ju-Whei; Hanna, Nasser H.; Traynor, Anne M.; Carbone, David P.; Schiller, Joan H.

2012-01-01

Introduction Sorafenib is a raf kinase and angiogenesis inhibitor with activity in multiple cancers. This phase II study in heavily pretreated non-small cell lung cancer (NSCLC) patients (≥ two prior therapies) utilized a randomized discontinuation design. Methods Patients received 400 mg of sorafenib orally twice daily for two cycles (two months) (Step 1). Responding patients on Step 1 continued on sorafenib; progressing patients went off study, and patients with stable disease were randomized to placebo or sorafenib (Step 2), with crossover from placebo allowed upon progression. The primary endpoint of this study was the proportion of patients having stable or responding disease two months after randomization. Results : There were 299 patients evaluated for Step 1 with 81 eligible patients randomized on Step 2 who received sorafenib (n=50) or placebo (n=31). The two-month disease control rates following randomization were 54% and 23% for patients initially receiving sorafenib and placebo respectively, p=0.005. The hazard ratio for progression on Step 2 was 0.51 (95% CI 0.30, 0.87, p=0.014) favoring sorafenib. A trend in favor of overall survival with sorafenib was also observed (13.7 versus 9.0 months from time of randomization), HR 0.67 (95% CI 0.40-1.11), p=0.117. A dispensing error occurred which resulted in unblinding of some patients, but not before completion of the 8 week initial step 2 therapy. Toxicities were manageable and as expected. Conclusions : The results of this randomized discontinuation trial suggest that sorafenib has single agent activity in a heavily pretreated, enriched patient population with advanced NSCLC. These results support further investigation with sorafenib as a single agent in larger, randomized studies in NSCLC. PMID:22982658

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

PubMed

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

2016-05-20

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

Antioxidants intake and dry eye syndrome: a crossover, placebo-controlled, randomized trial.

PubMed

Drouault-Holowacz, Sophie; Bieuvelet, Séverine; Burckel, André; Rigal, Danièle; Dubray, Claude; Lichon, Jean-Louis; Bringer, Paul; Pilon, Francois; Chiambaretta, Frédéric

2009-01-01

To assess whether an orally administered antioxidant dietary supplement could improve the objective clinical signs and alleviate the subjective symptoms of dry eye syndrome. Twenty-four subjects diagnosed with dry eye syndrome were randomized in a crossover, double-blind, controlled, randomized study to receive a placebo or an antioxidants combination (Oxybiane) for 12 weeks. In all subjects, break-up time (BUT) test, Schirmer test, ocular symptoms (sore eyes, burning, itching, sensation of foreign object in the eye, photophobia, sticky eyes, and redness), visual comfort, and general well-being were evaluated weekly. After 12 weeks of supplementation with Oxybiane, both the BUT scores (27.3%+/-8.4% with Oxybiane versus 3.61%+/-4.3% with the placebo, p=0.017) and the Schirmer scores (26.9%+/-14.2% with Oxybiane versus -4.7%+/-3.4% with the placebo, p=0.037) were significantly increased. A significantly improvement was also observed considering subjective clinical symptoms such as burning (p=0.031), itching (p=0.027), sensation of foreign body in eye (p=0.030), and redness (p=0.043). CONCLUSIONS. Supplementation with oral antioxidants can improve both tear stability and quantity but also subjective clinical signs.

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2016-11-01

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

Effect of Spinal Manipulative Therapy on the Singing Voice.

PubMed

Fachinatto, Ana Paula A; Duprat, André de Campos; Silva, Marta Andrada E; Bracher, Eduardo Sawaya Botelho; Benedicto, Camila de Carvalho; Luz, Victor Botta Colangelo; Nogueira, Maruan Nogueira; Fonseca, Beatriz Suster Gomes

2015-09-01

This study investigated the effect of spinal manipulative therapy (SMT) on the singing voice of male individuals. Randomized, controlled, case-crossover trial. Twenty-nine subjects were selected among male members of the Heralds of the Gospel. This association was chosen because it is a group of persons with similar singing activities. Participants were randomly assigned to two groups: (A) chiropractic SMT procedure and (B) nontherapeutic transcutaneous electrical nerve stimulation (TENS) procedure. Recordings of the singing voice of each participant were taken immediately before and after the procedures. After a 14-day period, procedures were switched between groups: participants who underwent SMT on the first day were subjected to TENS and vice versa. Recordings were subjected to perceptual audio and acoustic evaluations. The same recording segment of each participant was selected. Perceptual audio evaluation was performed by a specialist panel (SP). Recordings of each participant were randomly presented thus making the SP blind to intervention type and recording session (before/after intervention). Recordings compiled in a randomized order were also subjected to acoustic evaluation. No differences in the quality of the singing on perceptual audio evaluation were observed between TENS and SMT. No differences in the quality of the singing voice of asymptomatic male singers were observed on perceptual audio evaluation or acoustic evaluation after a single spinal manipulative intervention of the thoracic and cervical spine. Copyright © 2015 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Safety, tolerability, and pharmacokinetics of sumatriptan suppositories following single and multiple doses in healthy volunteers.

PubMed

Kunka, R L; Hussey, E K; Shaw, S; Warner, P; Aubert, B; Richard, I; Fowler, P A; Pakes, G E

1997-06-01

A suppository formulation of the 5HT1 agonist sumatriptan could prove an important therapeutic option in migraine patients who dislike or poorly tolerate injectable therapy and where oral tablet administration is unsuitable because of severe migraine-related vomiting. Two independent double-blind, randomized clinical studies were conducted to evaluate the safety, tolerability and pharmacokinetics of sumatriptan suppositories following ascending single doses (four different dose levels) and multiple doses. In the four-period, crossover, single-dose study, 24 healthy male subjects were randomized to receive a suppository containing 12.5, 25, 50, or 100 mg on separate occasions 3-14 days apart. The suppositories were generally well tolerated; transient asthenia, drowsiness, and headache were the most frequently reported adverse events, and these were not dose-related. Peak plasma concentrations (Cmax) of sumatriptan were proportional to dose from 25 to 100 mg; area under the plasma concentration-time curve (AUC infinity) values were proportional to dose except at the highest doses, when they were greater than those predicted from lower doses. For all doses, the tmax of sumatriptan occurred within 2.5 h, and the t1/2 was approximately 2 h. In the two-period, placebo-controlled, crossover, repeat-dose study, 12 healthy adult male subjects were randomized to receive either a 50-mg sumatriptan suppository or placebo suppository, administered rectally twice a day, for 11 doses (5 1/2 days). Adverse events were no more frequent with sumatriptan than with placebo, and stool guaiac, rectal examinations, and physical examinations remained normal. No significant differences were noted between Day 1 and Day 6 values in the AUC, Cmax, time of peak serum concentration (tmax), elimination half-life (t 1/2), fraction of the dose excreted in the urine (fe), or renal clearance (Clr) of sumatriptan or its pharmacologically inactive indole acetic acid metabolite. Serum metabolite concentrations were two to three-fold higher than corresponding sumatriptan concentrations. No clinically significant accumulation of sumatriptan or its metabolite occurred. Overall, these studies show that sumatriptan administration via a suppository formulation is well tolerated, allows rapid absorption of sumatriptan, results in sumatriptan Cmax values that are proportional to dose from 25 to 100 mg, and is not associated with accumulation of sumatriptan or its metabolite.

Headache and mechanical sensitization of human pericranial muscles after repeated intake of monosodium glutamate (MSG).

PubMed

Shimada, Akiko; Cairns, Brian E; Vad, Nynne; Ulriksen, Kathrine; Pedersen, Anne Marie Lynge; Svensson, Peter; Baad-Hansen, Lene

2013-01-24

A single intake of monosodium glutamate (MSG) may cause headache and increased muscle sensitivity. We conducted a double-blinded, placebo-controlled, crossover study to examine the effect of repeated MSG intake on spontaneous pain, mechanical sensitivity of masticatory muscles, side effects, and blood pressure. Fourteen healthy subjects participated in 5 daily sessions for one week of MSG intake (150 mg/kg) or placebo (24 mg/kg NaCl) (randomized, double-blinded). Spontaneous pain, pressure pain thresholds and tolerance levels for the masseter and temporalis muscles, side effects, and blood pressure were evaluated before and 15, 30, and 50 min after MSG intake. Whole saliva samples were taken before and 30 min after MSG intake to assess glutamate concentrations. Headache occurred in 8/14 subjects during MSG and 2/14 during placebo (P = 0.041). Salivary glutamate concentrations on Day 5 were elevated significantly (P < 0.05). Pressure pain thresholds in masseter muscle were reduced by MSG on Day 2 and 5 (P < 0.05). Blood pressure was significantly elevated after MSG (P < 0.040). In conclusion, MSG induced mechanical sensitization in masseter muscle and adverse effects such as headache and short-lasting blood pressure elevation for which tolerance did not develop over 5 days of MSG intake.

Choline magnesium trisalicylate in patients with aspirin-induced asthma.

PubMed

Szczeklik, A; Nizankowska, E; Dworski, R

1990-05-01

Treatment of inflammatory diseases of asthmatics can be a serious problem since some patients show intolerance to aspirin and other non-steroidal, anti-inflammatory drugs that are cyclooxygenase inhibitors. Salicylates were believed to be well tolerated, but recent reports have demonstrated that diflunisal and salicylsalicylic acid can precipitate asthma attacks in aspirin-intolerant patients. This study was designed to determine the tolerance of choline magnesium trisalicylate (CMT), a nonacetylated salicylate with potent analgesic and anti-inflammatory activity, in 23 asthmatics with aspirin hypersensitivity confirmed by oral challenge. The study consisted of three phases: 1) patients received increasing doses (50-1,500 mg) of CMT under a single-blind protocol; 2) patients received either a placebo or CMT challenge in a double-blind, randomized, cross-over design; 3) patients received CMT at daily 3,000 mg doses for 1 week. Throughout the study, pulmonary function tests, peak nasal inspiratory flow, and serum salicylate and thromboxane B2 (TXB2) levels were monitored. Results showed no airway obstruction, nasal congestion or rhinorrhea after CMT. There was no significant decrease in serum TXB2 levels, indicating the absence of cyclooxygenase inhibition with CMT. We conclude that choline magnesium trisalicylate is a safe drug for treatment of different anti-inflammatory disorders in asthmatics with aspirin hypersensitivity.

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

PubMed

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

2015-01-01

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

Psyllium supplementation in adolescents improves fat distribution & lipid profile: a randomized, participant-blinded, placebo-controlled, crossover trial.

PubMed

de Bock, Martin; Derraik, José G B; Brennan, Christine M; Biggs, Janene B; Smith, Greg C; Cameron-Smith, David; Wall, Clare R; Cutfield, Wayne S

2012-01-01

We aimed to assess the effects of psyllium supplementation on insulin sensitivity and other parameters of the metabolic syndrome in an at risk adolescent population. This study encompassed a participant-blinded, randomized, placebo-controlled, crossover trial. Subjects were 47 healthy adolescent males aged 15-16 years, recruited from secondary schools in lower socio-economic areas with high rates of obesity. Participants received 6 g/day of psyllium or placebo for 6 weeks, with a two-week washout before crossing over. Fasting lipid profiles, ambulatory blood pressure, auxological data, body composition, activity levels, and three-day food records were collected at baseline and after each 6-week intervention. Insulin sensitivity was measured by the Matsuda method using glucose and insulin values from an oral glucose tolerance test. 45 subjects completed the study, and compliance was very high: 87% of participants took >80% of prescribed capsules. At baseline, 44% of subjects were overweight or obese. 28% had decreased insulin sensitivity, but none had impaired glucose tolerance. Fibre supplementation led to a 4% reduction in android fat to gynoid fat ratio (p = 0.019), as well as a 0.12 mmol/l (6%) reduction in LDL cholesterol (p = 0.042). No associated adverse events were recorded. Dietary supplementation with 6 g/day of psyllium over 6 weeks improves fat distribution and lipid profile (parameters of the metabolic syndrome) in an at risk population of adolescent males. Australian New Zealand Clinical Trials Registry ACTRN12609000888268.

BounceBack capsules for reduction of DOMS after eccentric exercise: a randomized, double-blind, placebo-controlled, crossover pilot study.

PubMed

Udani, Jay K; Singh, Betsy B; Singh, Vijay J; Sandoval, Elizabeth

2009-06-05

Delayed onset muscle soreness (DOMS) is muscle pain and discomfort experienced approximately one to three days after exercise. DOMS is thought to be a result of microscopic muscle fiber tears that occur more commonly after eccentric exercise rather than concentric exercise. This study sought to test the efficacy of a proprietary dietary supplement, BounceBack, to alleviate the severity of DOMS after standardized eccentric exercise. The study was a randomized, double-blind, placebo-controlled, crossover study. Ten healthy community-dwelling untrained subjects, ranging in age from 18-45 years, were enrolled. Mean differences within and between groups were assessed inferentially at each data collection time-point using t-tests for all outcome measures. In this controlled pilot study, intake of BounceBack capsules for 30 days resulted in a significant reduction in standardized measures of pain and tenderness post-eccentric exercise compared to the placebo group. There were trends towards reductions in plasma indicators of inflammation (high sensitivity C-reactive protein) and muscle damage (creatine phosphokinase and myoglobin). BounceBack capsules were able to significantly reduce standardized measures of pain and tenderness at several post-eccentric exercise time points in comparison to placebo. The differences in the serological markers of DOMS, while not statistically significant, appear to support the clinical findings. The product appears to have a good safety profile and further study with a larger sample size is warranted based on the current results.

BounceBack™ capsules for reduction of DOMS after eccentric exercise: a randomized, double-blind, placebo-controlled, crossover pilot study

PubMed Central

Udani, Jay K; Singh, Betsy B; Singh, Vijay J; Sandoval, Elizabeth

2009-01-01

Background Delayed onset muscle soreness (DOMS) is muscle pain and discomfort experienced approximately one to three days after exercise. DOMS is thought to be a result of microscopic muscle fiber tears that occur more commonly after eccentric exercise rather than concentric exercise. This study sought to test the efficacy of a proprietary dietary supplement, BounceBack™, to alleviate the severity of DOMS after standardized eccentric exercise. Methods The study was a randomized, double-blind, placebo-controlled, crossover study. Ten healthy community-dwelling untrained subjects, ranging in age from 18–45 years, were enrolled. Mean differences within and between groups were assessed inferentially at each data collection time-point using t-tests for all outcome measures. Results In this controlled pilot study, intake of BounceBack™ capsules for 30 days resulted in a significant reduction in standardized measures of pain and tenderness post-eccentric exercise compared to the placebo group. There were trends towards reductions in plasma indicators of inflammation (high sensitivity C-reactive protein) and muscle damage (creatine phosphokinase and myoglobin). Conclusion BounceBack™ capsules were able to significantly reduce standardized measures of pain and tenderness at several post-eccentric exercise time points in comparison to placebo. The differences in the serological markers of DOMS, while not statistically significant, appear to support the clinical findings. The product appears to have a good safety profile and further study with a larger sample size is warranted based on the current results. PMID:19500355

An evaluation of the cognitive and mood effects of an energy shot over a 6h period in volunteers: a randomized, double-blind, placebo controlled, cross-over study.

PubMed

Wesnes, Keith A; Barrett, Marilyn L; Udani, Jay K

2013-08-01

Energy drinks are widely available mostly containing glucose, and several have been demonstrated to improve alertness and cognitive function; these effects generally being identified 30-60min after administration. The present study assessed whether an energy shot without carbohydrates would affect major aspects of cognitive function and also mood in volunteers over a 6h time period. This randomized, double-blind, placebo-controlled,crossover study compared the acute effects of the energy shot with a matching placebo in 94 healthy volunteers. Cognitive function was assessed with a widely used set of automated tests of attention and memory. Mood was assessed with the Bond-Lader, Beck Anxiety Index, Beck Depression Index, Chalder Fatigue Scales (CFS), and the POMS. The volunteers were requested to limit their sleep to between 3 and 6h the night before each testing day. Compared to the placebo, the energy shot significantly improved 6 validated composite cognitive function measures from the CDR System as well as self-rated alertness; the benefits on 4 of the cognitive measures still remaining at 6h. The overall effect sizes of the performance improvements were in the small to medium range and thus notable in this field. In conclusion, an energy shot can significantly improve important aspects of cognitive function for up to 6h compared to placebo in partially sleep-deprived healthy volunteers. Copyright © 2013 Elsevier Ltd. All rights reserved.

Antispasmodic/analgesic associations in primary dysmenorrhea double-blind crossover placebo-controlled clinical trial.

PubMed

de los Santos, A R; Zmijanovich, R; Pérez Macri, S; Martí, M L; Di Girolamo, G

2001-01-01

We studied 125 patients with primary dysmenorrhea in a prospective randomized double-blind crossover study. After an admission pretreatment period without medication, the patients completed three consecutive randomized treatment phases with lysine clonixinate 125 mg plus propinox 10 mg or paracetamol 500 mg plus hyoscine N-butylbromide 10 mg or placebo, according to a fixed-dose schedule of 1 tablet every 6 h, 3 days before onset of menses and for 5 days thereafter. Changes in menstrual pain intensity and duration, amount of bleeding measured according to the number of daily pads used and concomitant symptoms were assessed on the fifth day of each cycle. Every night, the patients recorded the average intensity of menstrual pain during the first 4 days of menstruation in a diary The follow-up visit carried out at day 5 showed significant reduction in pain intensity with both active treatments vs. the other two phases: baseline: 2.72 +/- 0.61; placebo: 1.85 +/- 0.87; lysine clonixinate plus propinox 1.36 +/- 0.81, and paracetamol plus hyosine N-butylbromide: 1.45 +/- 0.87. The patients' diaries showed increasingly lower pain intensities starting from day 1 with the three treatments. Active treatments revealed significantly higher analgesic efficacy from the outset compared with baseline and placebo; however, only the lysine clonixinate plus propinox combination reached a statistically significant difference by days 3 and 4. No changes in duration or intensity of menstrual bleeding or in the incidence of adverse effects were observed during the four study periods.

Intranasal Pharmacokinetics of Morphine ARER, a Novel Abuse-Deterrent Formulation: Results from a Randomized, Double-Blind, Four-Way Crossover Study in Nondependent, Opioid-Experienced Subjects

PubMed Central

Pantaleon, Carmela; Iverson, Matthew; Smith, Michael D.; Kinzler, Eric R.; Aigner, Stefan

2018-01-01

Objective To investigate the pharmacokinetics (PK) of Morphine ARER, an extended-release (ER), abuse-deterrent formulation of morphine sulfate after oral and intranasal administration. Methods This randomized, double-blind, double-dummy, placebo-controlled, four-way crossover study assessed the PK of morphine and its active metabolite, M6G, from crushed intranasal Morphine ARER and intact oral Morphine ARER compared with crushed intranasal ER morphine following administration to nondependent, recreational opioid users. The correlation between morphine PK and the pharmacodynamic parameter of drug liking, a measure of abuse potential, was also evaluated. Results Mean maximum observed plasma concentration (Cmax) for morphine was lower with crushed intranasal Morphine ARER (26.2 ng/mL) and intact oral Morphine ARER (18.6 ng/mL), compared with crushed intranasal ER morphine (49.5 ng/mL). The time to Cmax (Tmax) was the same for intact oral and crushed intranasal Morphine ARER (1.6 hours) and longer for crushed intranasal morphine ER (1.1 hours). Higher mean maximum morphine Cmax, Tmax, and abuse quotient (Cmax/Tmax) were positively correlated with maximum effect for drug liking (R2 ≥ 0.9795). Conclusion These data suggest that Morphine ARER maintains its ER profile despite physical manipulation and intranasal administration, which may be predictive of a lower intranasal abuse potential compared with ER morphine.

Effects of 5-aminolevulinic acid supplementation on home-based walking training achievement in middle-aged depressive women: randomized, double-blind, crossover pilot study.

PubMed

Suzuki, Hiroshi; Masuki, Shizue; Morikawa, Akiyo; Ogawa, Yu; Kamijo, Yoshi-Ichiro; Takahashi, Kiwamu; Nakajima, Motowo; Nose, Hiroshi

2018-05-08

Depressive patients often experience difficulty in performing exercise due to physical and psychological barriers. We examined the effects of 5-aminolevulinic acid (ALA) with sodium ferrous citrate (SFC) supplementation during home-based walking training in middle-aged depressive women. Nine outpatients [53 ± 8 (SD) yr] with major depressive disorder participated in the pilot study with randomized, placebo-controlled, double-blind crossover design. They underwent two trials for 7 days, each performing interval walking training (IWT) with ALA + SFC (ALA + SFC) or placebo supplement intake (PLC) intermittently with >a 10-day washout period. For the first 6 days of each trial, exercise intensity for IWT was measured by accelerometry. Before and after each trial, subjects underwent a graded cycling test, and lactate concentration in plasma ([Lac - ] p ), oxygen consumption rate ([Formula: see text]), and carbon dioxide production rate ([Formula: see text]) were measured with depression severity by the Montgomery-Åsberg Depression Rating Scale (MADRS). We found that the increases in [Lac - ] p , [Formula: see text] and [Formula: see text] during the test were attenuated only in ALA + SFC ([before vs. after] × workload; all, P < 0.01), accompanied by increased training days, impulse, and time at fast walking during IWT (all, P < 0.05) with decreased MADRS-score (P = 0.001). Thus, ALA + SFC supplementation increased IWT achievement to improve depressive symptoms in middle-aged women.

Double-blind crossover study of branched-chain amino acid therapy in patients with spinocerebellar degeneration.

PubMed

Mori, Masatada; Adachi, Yoshiki; Mori, Nozomi; Kurihara, Saiko; Kashiwaya, Yoshihiro; Kusumi, Masayoshi; Takeshima, Takao; Nakashima, Kenji

2002-03-30

To determine whether treatment with branched-chain amino acids (BCAA) can improve the condition of patients with ataxia, a double-blind crossover study of BCAA therapy was performed in 16 patients with spinocerebellar degeneration (SCD). The patients were treated with BCAA in oral doses of 1.5, 3.0, or 6.0 g or with placebo daily for 4 weeks in each study phase. The order of treatment phases (placebo or BCAA) was assigned randomly. An International Cooperative Ataxia Rating Scale (ICARS) was used to quantify the severity of symptoms of SCD. The mean ICARS score improved significantly with BCAA treatment compared with the mean pretreatment score (p<0.01). In addition, the improvement in the mean global ICARS score was significant in the middle-dose group compared with that in the placebo group (p<0.02). The estimated improvement in kinetic functions compared with pretreatment (p<0.01) was significant after treatment with BCAA, 1.5 and 3.0 g. All of the responders manifested predominantly cerebellar symptoms, especially those with spinocerebellar ataxia type 6 (SCA6). Thus, treatment with BCAA may be effective in patients with the cerebellar form of SCD.

Effect of sodium chloride- and sodium bicarbonate-rich mineral water on blood pressure and metabolic parameters in elderly normotensive individuals: a randomized double-blind crossover trial.

PubMed

Schorr, U; Distler, A; Sharma, A M

1996-01-01

To examine the effect of sodium chloride- and sodium bicarbonate-rich mineral water on blood pressure and parameters of glucose and lipid metabolism in elderly normotensive individuals. We examined 21 healthy men and women aged 60-72 years in a randomized, placebo-controlled, double-blind crossover trial. After reducing dietary salt intake to below 100 mmol/day, study participants were randomly assigned to drink 1.5 l daily of a sodium chloride-rich (sodium 84.5 mmol/l, chloride 63.7 mmol/l, bicarbonate 21.9 mmol/l), a sodium bicarbonate-rich (sodium 39.3 mmol/l, chloride 6.5 mmol/l, bicarbonate 48.8 mmol/l) and a low-sodium (placebo: sodium, chloride and bicarbonate < 0.02 mmol/l) mineral water for 4 weeks each in a three-phase crossover order. Each phase was separated by a 2-week washout period in which the study participants remained on a low-salt diet. Compliance was assessed by biweekly urinary electrolyte excretion and five study participants were excluded from analysis for failing to complete the trial or to fulfil the compliance criteria. Mean arterial blood pressure was significantly lower during the periods of consuming low-sodium -7.0 +/- 7.2 mmHg, P < 0.001) or sodium bicarbonate-rich (-5.7 +/- 6.4 mmHg, P < 0.05) water than at baseline. In contrast, blood pressure during the phase of drinking sodium chloride-rich water was identical to that at baseline. Ambulatory 24 h blood pressure, oral glucose tolerance and plasma lipids were not affected by the different regimens. Urinary calcium excretion was significantly reduced by drinking low-sodium or sodium bicarbonate-rich water but was unchanged under the sodium chloride-rich water. Consumption of sodium chloride-rich mineral water can abolish the blood pressure reduction induced by dietary salt restriction in elderly individuals. Sodium bicarbonate-rich mineral water in conjunction with a low-salt diet may have a beneficial effect on calcium homeostasis.

Effects of a new combination of nutraceuticals with Morus alba on lipid profile, insulin sensitivity and endotelial function in dyslipidemic subjects. A cross-over, randomized, double-blind trial.

PubMed

Trimarco, Valentina; Izzo, Raffaele; Stabile, Eugenio; Rozza, Francesco; Santoro, Mario; Manzi, Maria Virginia; Serino, Federica; Schiattarella, Gabriele Giacomo; Esposito, Giovanni; Trimarco, Bruno

2015-06-01

Nutraceuticals (NUT) are forms of compounds with biological activity commonly used to improve health in dosage largely exceeding those obtainable in food. We compared, in a double blind randomized cross-over trial, the effects of two NUT combinations on the control of glico-lipidic metabolism in patients with hypercholesterolemia not on statins. At study start patients were given dietary counseling and received placebo for 2 weeks. After this run-in period, patients were randomized: (1) Combination A [Policosanol, Red yeast rice (Monakolin K 3 mg), Berberine 500 mg, Astaxantine, Folic Acid and Coenzyme Q10] for 4 weeks followed by 4 weeks of Combination B [Red yeast rice (Monakolin K 3.3 mg), Berberine 531.25 mg and leaf extract of Morus alba]; (2) Combination B for 4 weeks followed by 4 weeks of Combination A. Combination B reduced LDL cholesterol below 130 mg/dl in 56.5 % of the patients, and Cambination A only in 21.7 % of them (p ≤ 0.027). Both treatments reduced plasma levels of triglycerides, total and LDL cholesterol and increased HDL cholesterol (all p < 0.03). Total and LDL cholesterol reduction was more pronounced in patients taking Combination B (p < 0.005). Combination B reduced also glycated hemoglobin, fasting glucose and insulin plasma levels as well as HOMA index (p < 0.005). An increased content of Berberin and Monacolin K and the addition of Morus alba extract improves the effect on plasma cholesterol and on glucose metabolism of the NUT Combination. These effects may allow the speculation of a more marked improvement in cardiovascular prognosis.

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.

Low-dose naltrexone for the treatment of fibromyalgia: findings of a small, randomized, double-blind, placebo-controlled, counterbalanced, crossover trial assessing daily pain levels.

PubMed

Younger, Jarred; Noor, Noorulain; McCue, Rebecca; Mackey, Sean

2013-02-01

To determine whether low dosages (4.5 mg/day) of naltrexone reduce fibromyalgia severity as compared with the nonspecific effects of placebo. In this replication and extension study of a previous clinical trial, we tested the impact of low-dose naltrexone on daily self-reported pain. Secondary outcomes included general satisfaction with life, positive mood, sleep quality, and fatigue. Thirty-one women with fibromyalgia participated in the randomized, double-blind, placebo-controlled, counterbalanced, crossover study. During the active drug phase, participants received 4.5 mg of oral naltrexone daily. An intensive longitudinal design was used to measure daily levels of pain. When contrasting the condition end points, we observed a significantly greater reduction of baseline pain in those taking low-dose naltrexone than in those taking placebo (28.8% reduction versus 18.0% reduction; P = 0.016). Low-dose naltrexone was also associated with improved general satisfaction with life (P = 0.045) and with improved mood (P = 0.039), but not improved fatigue or sleep. Thirty-two percent of participants met the criteria for response (defined as a significant reduction in pain plus a significant reduction in either fatigue or sleep problems) during low-dose naltrexone therapy, as contrasted with an 11% response rate during placebo therapy (P = 0.05). Low-dose naltrexone was rated equally tolerable as placebo, and no serious side effects were reported. The preliminary evidence continues to show that low-dose naltrexone has a specific and clinically beneficial impact on fibromyalgia pain. The medication is widely available, inexpensive, safe, and well-tolerated. Parallel-group randomized controlled trials are needed to fully determine the efficacy of the medication. Copyright © 2013 by the American College of Rheumatology.

A double-blind, crossover, randomized comparison of granisetron and ramosetron for the prevention of acute and delayed cisplatin-induced emesis in patients with gastrointestinal cancer: is patient preference a better primary endpoint?

PubMed

Koizumi, Wasaburo; Tanabe, Satoshi; Nagaba, Shizuka; Higuchi, Katsuhiko; Nakayama, Norisuke; Saigenji, Katsunori; Nonaka, Miwa; Yago, Kazuo

2003-12-01

Serotonin receptor antagonists are recommended by the American Society of Clinical Oncology for the prevention of acute and delayed chemotherapy-induced emesis. However, the most effective agent in this class of antiemetic drugs for preventing emesis has not been clearly defined. We therefore performed a double-blind, crossover, randomized, controlled trial comparing the efficacy of granisetron and ramosetron, using patient preference as the primary endpoint. Thirty patients receiving two courses of combined chemotherapy (including > or =60 mg/m(2) cisplatin) for gastric or esophageal cancer were randomly assigned to the granisetron-ramosetron group (treatment phase 1: granisetron, 3 mg; treatment phase 2: ramosetron, 0.3 mg) or the ramosetron-granisetron group (treatment phase 1: ramosetron, 0.3 mg; treatment phase 2: granisetron, 3 mg). All patients received methylprednisolone sodium, 250 mg i.v., during each treatment phase. The efficacy of granisetron and ramosetron was similar in terms of the suppression of emesis and appetite status. However, the majority of patients (19/30, 63.3%) expressed a preference for granisetron, as compared with 9 patients (30.0%) who preferred ramosetron; 2 patients (6.7%) had no preference (chi(2) test: p = 0.008; Fisher's exact test: p = 0.015). (1) A significant proportion of patients prefer granisetron over ramosetron for the prevention of chemotherapy-induced emesis. (2) Granisetron and ramosetron possess similar effectiveness for the suppression of emesis. (3) The variable of 'patient preference' should be accepted as a primary endpoint of antiemetic drug efficacy. Copyright 2003 S. Karger AG, Basel

Salvia Miltiorrhiza Root Water-Extract (Danshen) Has No Beneficial Effect on Cardiovascular Risk Factors. A Randomized Double-Blind Cross-Over Trial

PubMed Central

van Poppel, Pleun C. M.; Breedveld, Pauline; Abbink, Evertine J.; Roelofs, Hennie; van Heerde, Waander; Smits, Paul; Lin, Wenzhi; Tan, Aaitje H.; Russel, Frans G.; Donders, Rogier; Tack, Cees J.; Rongen, Gerard A.

2015-01-01

Purpose Danshen is the dried root extract of the plant Salvia Miltiorrhiza and it is used as traditional Chinese medicinal herbal product to prevent and treat atherosclerosis. However, its efficacy has not been thoroughly investigated. This study evaluates the effect of Danshen on hyperlipidemia and hypertension, two well known risk factors for the development of atherosclerosis. Methods This was a randomized, placebo-controlled, double-blind crossover study performed at a tertiary referral center. Participants were recruited by newspaper advertisement and randomized to treatment with Danshen (water-extract of the Salvia Miltiorrhiza root) or placebo for 4 consecutive weeks. There was a wash out period of 4 weeks. Of the 20 analysed participants, 11 received placebo first. Inclusion criteria were: age 40-70 years, hyperlipidemia and hypertension. At the end of each treatment period, plasma lipids were determined (primary outcome), 24 hours ambulant blood pressure measurement (ABPM) was performed, and vasodilator endothelial function was assessed in the forearm. Results LDL cholesterol levels were 3.82±0.14 mmol/l after Danshen and 3.52±0.16 mmol/l after placebo treatment (mean±SE; p<0.05 for treatment effect corrected for baseline). Danshen treatment had no effect on blood pressure (ABPM 138/84 after Danshen and 136/87 after placebo treatment). These results were further substantiated by the observation that Danshen had neither an effect on endothelial function nor on markers of inflammation, oxidative stress, glucose metabolism, hemostasis and blood viscosity. Conclusion Four weeks of treatment with Danshen (water-extract) slightly increased LDL-cholesterol without affecting a wide variety of other risk markers. These observations do not support the use of Danshen to prevent or treat atherosclerosis. Trial Registration ClinicalTrials.gov NCT01563770 PMID:26192328

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.


Intrathecal analgesia by bupivacaine is not enhanced by coadministration of morphine in patients with severe cancer-related pain: a randomized double-blind cross-over study.

PubMed

Reif, Ingalill; Wincent, Anders; Stiller, Carl-Olav

2017-06-01

The objective of this randomized double blind cross-over trial was to determine if patients with severe cancer-related pain and inadequate response to systemic opioids prefer intrathecal (IT) pain relief with a combination of bupivacaine and morphine or bupivacaine only. Adult patients with cancer-related pain (n = 23) scheduled for IT analgesia at the Pain Center at the Karo-linska University Hospital Solna, Stockholm, Sweden, were included. The optimal individual flow rate of IT bupivacaine (2 mg/mL) in addition to bolus doses was titrated and maintained for 4 days. Morphine (1 mg/mL) was added to bupivacaine either on day 2 or 4 according to a randomization protocol. Expression of pain relief preference for morphine instead of control (bupivacaine only) was the primary outcome. Secondary outcomes were difference in pain intensity, pain relief, total use of bupivacaine per 24 hours and number of requested bolus doses. Eight patients dropped out during the 4-day study period for reasons not related to the trial. IT bupivacaine significantly decreased median (interquartile range) pain intensity from 5 (3 - 7) at baseline (before catheter insertion) to 1 (0 - 1) (p = 0.0001; Wilcoxon test). Only 1 patient of 15 with 4-day data expressed any preference for morphine. The addition of IT morphine did not result in any significant change of pain intensity, pain relief score, total use of bupivacaine per 24 hours, or number of requested bolus doses. These results suggest that patients with cancer-related pain treated with high doses of systemic opioids, may start IT treatment with an optimal dose of IT bupivacaine without morphine.
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Efficacy evaluation of a pollen blocker cream against dust-mite allergy: A multicenter, randomized, double-blind, placebo-controlled crossover trial.

PubMed

Li, Yanqing; Cheng, Lei; Chen, Xiaoning; Yang, Beibei; Wang, Dehui

2015-01-01

To further evaluate the efficacy and safety of a pollen blocker cream against dust-mite allergy. A multicenter, randomized, double-blind, placebo-controlled, crossover trial was conducted in a Chinese population. Patients diagnosed with perennial allergic rhinitis, sensitive to dust-mite allergy including Dermatophagoides farinae and Dermatophagoides pteronyssinus were randomly allocated to receive a pollen blocker cream or placebo, which was applied and spread evenly to the lower internal nose region three times daily for a total of 30 days. The primary outcome measurements for efficacy were total nasal symptom score (TNSS) and individual nasal symptom score (iNSS). Adverse events were also monitored. After application of a pollen blocker, the mean TNSS decreased from 23.1 to 13.8, the decrease of the pollen blocker group (9.3) was highly significant compared with the placebo group (5.2; p < 0.001). Similarly, the decreases in iNSSs (rhinorrhea, congestion, sneezing, and itching) between the pollen blocker group and the placebo group were also significant (p < 0.05). In addition, in adults, the pollen blocker led to a remarkably significant decrease in TNSS (9.5) compared with placebo (5.4; p < 0.001); in children, the pollen blocker led to a significant decrease in TNSS (8.6) compared with placebo (4.8; p < 0.05). No statistical difference was found in the incidence of adverse events between the two groups (p > 0.05), and no severe systematic reactions were observed. Pollen Blocker is a safe and effective alternative to the drugs for treatment of AR, especially for Chinese people allergic to dust-mite allergy.

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.

Effects of Silexan on the Serotonin-1A Receptor and Microstructure of the Human Brain: A Randomized, Placebo-Controlled, Double-Blind, Cross-Over Study with Molecular and Structural Neuroimaging

PubMed Central

Baldinger, Pia; Höflich, Anna S.; Mitterhauser, Markus; Hahn, Andreas; Rami-Mark, Christina; Spies, Marie; Wadsak, Wolfgang; Lanzenberger, Rupert

2015-01-01

Background: Recently, Silexan, a patented active substance comprised of an essential oil produced from Lavandula angustifolia flowers, has been authorized in Germany as a medicinal product for the treatment of states of restlessness related to anxious mood. Its efficacy has been shown in several forms of anxiety disorders. Findings from preclinical and clinical studies attribute a major role to the serotonin-1A receptor in the pathogenesis and treatment of anxiety. Methods: To elucidate the effect of Silexan on serotonin-1A receptor binding, 17 healthy men underwent 2 positron emission tomography measurements using the radioligand [carbonyl-11C]WAY-100635 following the daily intake of 160mg Silexan or placebo for a minimum of 8 weeks (randomized, double-blind, cross-over design). Additionally, structural magnetic resonance imaging and voxel-based morphometry analysis was performed to determine potential effects on gray matter microstructure. Results: Serotonin-1A receptor binding potential was shown to be significantly reduced following the intake of Silexan compared with placebo in 2 large clusters encompassing the temporal gyrus, the fusiform gyrus and the hippocampus on one hand as well as the insula and anterior cingulate cortex on the other hand. No effects of Silexan on gray matter volume could be detected in this investigation. Conclusion: This positron emission tomography study proposes an involvement of the serotonin-1A receptor in the anxiolytic effects of Silexan. The study was registered in the International Standard Randomized Controlled Trial Number Register as ISRCTN30885829 (http://www.controlled-trials.com/isrctn/). PMID:25522403

Impact of Virgin Olive Oil and Phenol-Enriched Virgin Olive Oils on the HDL Proteome in Hypercholesterolemic Subjects: A Double Blind, Randomized, Controlled, Cross-Over Clinical Trial (VOHF Study)

PubMed Central

Pedret, Anna; Catalán, Úrsula; Fernández-Castillejo, Sara; Farràs, Marta; Valls, Rosa-M; Rubió, Laura; Canela, Núria; Aragonés, Gerard; Romeu, Marta; Castañer, Olga; de la Torre, Rafael; Covas, Maria-Isabel; Fitó, Montse; Motilva, Maria-José; Solà, Rosa

2015-01-01

The effects of olive oil phenolic compounds (PCs) on HDL proteome, with respect to new aspects of cardioprotective properties, are still unknown. The aim of this study was to assess the impact on the HDL protein cargo of the intake of virgin olive oil (VOO) and two functional VOOs, enriched with their own PCs (FVOO) or complemented with thyme PCs (FVOOT), in hypercholesterolemic subjects. Eligible volunteers were recruited from the IMIM-Hospital del Mar Medical Research Institute (Spain) from April 2012 to September 2012. Thirty-three hypercholesterolemic participants (total cholesterol >200mg/dL; 19 men and 14 women; aged 35 to 80 years) were randomized in the double-blind, controlled, cross-over VOHF clinical trial. The subjects received for 3 weeks 25 mL/day of: VOO, FVOO, or FVOOT. Using a quantitative proteomics approach, 127 HDL-associated proteins were identified. Among these, 15 were commonly differently expressed after the three VOO interventions compared to baseline, with specific changes observed for each intervention. The 15 common proteins were mainly involved in the following pathways: LXR/RXR activation, acute phase response, and atherosclerosis. The three VOOs were well tolerated by all participants. Consumption of VOO, or phenol-enriched VOOs, has an impact on the HDL proteome in a cardioprotective mode by up-regulating proteins related to cholesterol homeostasis, protection against oxidation and blood coagulation while down-regulating proteins implicated in acute-phase response, lipid transport, and immune response. The common observed protein expression modifications after the three VOOs indicate a major matrix effect. Trial Registration International Standard Randomized Controlled Trials ISRCTN77500181. PMID:26061039

Impact of Virgin Olive Oil and Phenol-Enriched Virgin Olive Oils on the HDL Proteome in Hypercholesterolemic Subjects: A Double Blind, Randomized, Controlled, Cross-Over Clinical Trial (VOHF Study).

PubMed

Pedret, Anna; Catalán, Úrsula; Fernández-Castillejo, Sara; Farràs, Marta; Valls, Rosa-M; Rubió, Laura; Canela, Núria; Aragonés, Gerard; Romeu, Marta; Castañer, Olga; de la Torre, Rafael; Covas, Maria-Isabel; Fitó, Montse; Motilva, Maria-José; Solà, Rosa

2015-01-01

The effects of olive oil phenolic compounds (PCs) on HDL proteome, with respect to new aspects of cardioprotective properties, are still unknown. The aim of this study was to assess the impact on the HDL protein cargo of the intake of virgin olive oil (VOO) and two functional VOOs, enriched with their own PCs (FVOO) or complemented with thyme PCs (FVOOT), in hypercholesterolemic subjects. Eligible volunteers were recruited from the IMIM-Hospital del Mar Medical Research Institute (Spain) from April 2012 to September 2012. Thirty-three hypercholesterolemic participants (total cholesterol >200 mg/dL; 19 men and 14 women; aged 35 to 80 years) were randomized in the double-blind, controlled, cross-over VOHF clinical trial. The subjects received for 3 weeks 25 mL/day of: VOO, FVOO, or FVOOT. Using a quantitative proteomics approach, 127 HDL-associated proteins were identified. Among these, 15 were commonly differently expressed after the three VOO interventions compared to baseline, with specific changes observed for each intervention. The 15 common proteins were mainly involved in the following pathways: LXR/RXR activation, acute phase response, and atherosclerosis. The three VOOs were well tolerated by all participants. Consumption of VOO, or phenol-enriched VOOs, has an impact on the HDL proteome in a cardioprotective mode by up-regulating proteins related to cholesterol homeostasis, protection against oxidation and blood coagulation while down-regulating proteins implicated in acute-phase response, lipid transport, and immune response. The common observed protein expression modifications after the three VOOs indicate a major matrix effect. International Standard Randomized Controlled Trials ISRCTN77500181.

Comparison of Low-Dose Higher-Relaxivity and Standard-Dose Lower-Relaxivity Contrast Media for Delayed-Enhancement MRI: A Blinded Randomized Crossover Study.

PubMed

Cheong, Benjamin Y C; Duran, Cihan; Preventza, Ourania A; Muthupillai, Raja

2015-09-01

The gadolinium-based MRI contrast agent gadobenate dimeglumine has nearly twice the MR relaxivity of gadopentetate dimeglumine at 1.5 T. The purpose of this study was to determine whether a lower dose (0.1 mmol/kg) of gadobenate dimeglumine can be used to obtain delayed-enhancement MR images comparable to those obtained with a standard dose (0.2 mmol/kg) of gadopentetate dimeglumine. In this blinded randomized crossover study, 20 patients with known myocardial infarction underwent two separate delayed-enhancement MRI examinations after receiving 0.1 mmol/kg gadobenate dimeglumine and 0.2 mmol/kg gadopentetate dimeglumine (random administration). The conspicuity of lesion enhancement 5, 10, and 20 minutes after contrast administration was quantified as relative enhancement ratio (RER). With either gadolinium-based contrast agent, damaged myocardium had higher signal intensity than normal remote myocardium (RER > 4) on delayed-enhancement MR images, and the blood RER declined over time after contrast administration. The blood RER was not significantly higher for gadobenate dimeglumine than for gadopentetate dimeglumine at 5 and 10 minutes. Nevertheless, there was a larger reduction in blood RER for gadobenate dimeglumine than for gadopentetate dimeglumine between 5 and 10 minutes and between 10 and 20 minutes. The volumes of enhancement were similar for gadobenate dimeglumine (13.6 ± 8.8 cm(3)) and gadopentetate dimeglumine (13.5 ± 8.9 cm(3)) (p = 0.98). The mean difference in Bland-Altman analysis for delayed-enhancement volume between the agents was 0.1 cm(3). Qualitatively and quantitatively, delayed-enhancement MR images of ischemic myocardium obtained with 0.1 mmol/kg gadobenate dimeglumine are comparable to those obtained with 0.2 mmol/kg gadopentetate dimeglumine 5, 10, and 20 minutes after contrast administration.

Does topical amethocaine gel reduce pain from heel prick blood sampling in premature infants? A randomized double-blind cross-over controlled study

PubMed Central

Patel, Amita; Czerniawski, Barbara; Gray, Shari; Lui, Eric

2003-01-01

BACKGROUND: Heel prick blood sampling is the most common painful invasive procedure performed on neonates. Currently, there are no effective ways to provide pain relief from this painful procedure. OBJECTIVE: To assess the efficacy of the topical anesthetic amethocaine 4% gel (Ametop, Smith & Nephew Inc, St Laurent) in reducing the pain of heel prick blood sampling in neonates. METHODS: A randomized, double-blind, placebo controlled, crossover trial was conducted. Neonates between 33 to 37 weeks’ gestational age in their first seven days of life were eligible. Heel prick blood sampling was performed on each participant twice. Each infant was randomly assigned to receive either amethocaine 4% gel or placebo to the heel for the first prick, and then received the alternative agent for the second prick. Prick pain was assessed using both Premature Infant Pain Profile (PIPP) and Neonatal Infant Pain Scale (NIPS). Squeeze pain was assessed by NIPS. RESULTS: Ten babies were recruited. There were no significant differences in the average PIPP and NIPS scores between the treatment and placebo groups for both prick and squeeze pains from heel prick blood sampling. For prick pain, linear-regression showed significant correlation between the PIPP and NIPS scores. No adverse reactions were observed after application of either the active or placebo agents. CONCLUSION: Topical amethocaine 4% gel is not shown to reduce prick and squeeze pains significantly from heel prick blood sampling in neonates between 33 to 37 weeks’ gestational age. Further studies are needed to find ways to provide effective pain relief from this common procedure. PMID:20020001

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.

Acute psychotropic effects of oral cannabis extract with a defined content of Delta9-tetrahydrocannabinol (THC) in healthy volunteers.

PubMed

Kaufmann, R M; Kraft, B; Frey, R; Winkler, D; Weiszenbichler, S; Bäcker, C; Kasper, S; Kress, H G

2010-01-01

The medical use of cannabinoids is limited mainly by their undesirable effects. With respect to acute psychotropic effects, the aim of this study is the comparison of an oral cannabis extract and low-dose diazepam in a cross-over experiment in drug-naïve healthy women. Sixteen healthy females participated in this randomized, double-blind, active comparator-controlled, single-dose, balanced 2-way cross-over study. Cannabis extract with standardised Delta (9)-tetrahydrocannabinol (THC) content (20 mg) or active placebo (5 mg diazepam) was administered orally. Subjects were assessed by self- and observer-rated visual analogue scales (VAS), the BRIEF PSYCHIATRIC RATING SCALE (BPRS) and three psychomotor tests up to 6 h after administration. VAS showed significantly elevated fatigue, drowsiness, dizziness, and "feeling high" after cannabis as compared to baseline and diazepam. BPRS scores were significantly higher after cannabis intake. Only in one psychomotor test a decrease of psychomotor activity after cannabis was evident. One subject in the cannabis condition experienced severe transient psychotic symptoms. Orally administered cannabis produced significant central depressant side-effects compared to diazepam, mostly subjective effects (VAS) but marginal effects in psychomotor performance in 15 healthy females. Regarding the medical use of cannabis, a rigorous benefit-risk analysis and an exact psychiatric assessment before and during treatment are necessary. (c) Georg Thieme Verlag KG Stuttgart . New York.

Pharmacokinetic-pharmacodynamic analysis of mnesic effects of lorazepam in healthy volunteers.

PubMed

Blin, O; Jacquet, A; Callamand, S; Jouve, E; Habib, M; Gayraud, D; Durand, A; Bruguerolle, B; Pisano, P

1999-10-01

To describe the pharmacokinetic-pharmacodynamic modelling of the psychomotor and mnesic effects of a single 2 mg oral dose of lorazepam in healthy volunteers. This was a randomized double-blind, placebo-controlled two-way cross-over study. The effect of lorazepam was examined with the following tasks: choice reaction time, immediate and delayed cued recall of paired words and immediate and delayed free recall and recognition of pictures. The mean calculated EC50 values derived from the PK/PD modelling of the different tests ranged from 12.2 to 15.3 ng ml-1. On the basis of the statistical comparison of the EC50 values, the delayed recall trials seemed to be more impaired than the immediate recall trials; similar observations were made concerning the recognition vs recall tasks. The parameter values derived from PK/PD modelling, and especially the EC50 values, may provide sensitive indices that can be used, rather than the raw data derived from pharmacodynamic measurements, to compare CNS effects of benzodiazepines.

A randomized trial on the acute and steady-state effects of a new antidepressant, vortioxetine (Lu AA21004), on actual driving and cognition.

PubMed

Theunissen, E L; Street, D; Højer, A-M; Vermeeren, A; van Oers, A; Ramaekers, J G

2013-06-01

The aim of this study was to assess the effects of a novel antidepressant, vortioxetine 10 mg, on driving, cognitive, and psychomotor performance in 24 healthy subjects in a double-blind, placebo-controlled, three-way crossover design. Mirtazapine 30 mg was included as an active comparator. Drugs were administered in the evening of 15 consecutive days. Performance was measured in the morning of days 2 and 16, using standardized tests measuring on-the-road driving, memory, tracking, divided attention, and vigilance. The statistical analysis on the primary measure of driving, i.e., SD of lateral position showed noninferiority of vortioxetine on days 2 and 16, and inferiority for mirtazapine on day 2. Vortioxetine did not cause cognitive or psychomotor impairment. Mirtazapine, however, impaired cognitive and psychomotor performance on day 2. Most of these effects disappeared after multiple doses of mirtazapine. To conclude, vortioxetine did not impair driving, cognitive, or psychomotor performance after single or multiple doses.

The effect of topiramate plasma concentration on linguistic behavior, verbal recall and working memory.

PubMed

Marino, S E; Pakhomov, S V S; Han, S; Anderson, K L; Ding, M; Eberly, L E; Loring, D W; Hawkins-Taylor, C; Rarick, J O; Leppik, I E; Cibula, J E; Birnbaum, A K

2012-07-01

This is the first study of the effect of topiramate on linguistic behavior and verbal recall using a computational linguistics system for automated language and speech analysis to detect and quantify drug-induced changes in speech recorded during discourse-level tasks. Healthy volunteers were administered a single, 100-mg oral dose of topiramate in two double-blind, randomized, placebo-controlled, crossover studies. Subjects' topiramate plasma levels ranged from 0.23 to 2.81 μg/mL. We found a significant association between topiramate levels and impairment on measures of verbal fluency elicited during a picture description task, correct number of words recalled on a paragraph recall test, and reaction time recorded during a working memory task. Using the tools of clinical pharmacology and computational linguistics, we elucidated the relationship between the determinants of a drug's disposition as reflected in plasma concentrations and their impact on cognitive functioning as reflected in spoken language discourse. Copyright © 2012 Elsevier Inc. All rights reserved.

CK-2127107 amplifies skeletal muscle response to nerve activation in humans.

PubMed

Andrews, Jinsy A; Miller, Timothy M; Vijayakumar, Vipin; Stoltz, Randall; James, Joyce K; Meng, Lisa; Wolff, Andrew A; Malik, Fady I

2018-05-01

Three studies evaluated safety, tolerability, pharmacokinetics, and pharmacodynamics of CK-2127107 (CK-107), a next-generation fast skeletal muscle troponin activator (FSTA), in healthy participants. We tested the hypothesis that CK-107 would amplify the force-frequency response of muscle in humans. To assess the force-frequency response, participants received single doses of CK-107 and placebo in a randomized, double-blind, 4-period, crossover study. The force-frequency response of foot dorsiflexion following stimulation of the deep fibular nerve to activate the tibialis anterior muscle was assessed. CK-107 significantly increased tibialis anterior muscle response with increasing dose and plasma concentration in a frequency-dependent manner; the largest increase in peak force was ∼60% at 10 Hz. CK-107 appears more potent and produced larger increases in force than tirasemtiv-a first-generation FSTA-in a similar pharmacodynamic study, thereby supporting its development for improvement of muscle function of patients. Muscle Nerve 57: 729-734, 2018. © 2017 The Authors. Muscle & Nerve published by Wiley Periodicals, Inc.

Effects of methylphenidate on working memory components: influence of measurement.

PubMed

Bedard, Anne-Claude; Jain, Umesh; Johnson, Sheilah Hogg; Tannock, Rosemary

2007-09-01

To investigate the effects of methylphenidate (MPH) on components of working memory (WM) in attention-deficit hyperactivity disorder (ADHD) and determine the responsiveness of WM measures to MPH. Participants were a clinical sample of 50 children and adolescents with ADHD, aged 6 to 16 years old, who participated in an acute randomized, double-blind, placebo-controlled, crossover trial with single challenges of three MPH doses. Four components of WM were investigated, which varied in processing demands (storage versus manipulation of information) and modality (auditory-verbal; visual-spatial), each of which was indexed by a minimum of two separate measures. MPH improved the ability to store visual-spatial information irrespective of instrument used, but had no effects on the storage of auditory-verbal information. By contrast, MPH enhanced the ability to manipulate both auditory-verbal and visual-spatial information, although effects were instrument specific in both cases. MPH effects on WM are selective: they vary as a function of WM component and measurement.

The effect of histamine on changes in mental energy and fatigue after a single bout of exercise.

PubMed

Loy, Bryan D; O'Connor, Patrick J

2016-01-01

The purpose of this research was to determine if histamine, acting on brain H1 receptors, influences changes in feelings of energy and fatigue or cognitive test performance after acute exercise. Women (n=20) with low vigor and high fatigue were administered the H1 antagonist drug doxepin hydrocholoride (6 mg) in tomato juice and tomato juice alone (placebo) in a randomized, double-blinded, cross-over experiment before performing 30 min of light intensity cycling exercise and completing energy, fatigue, sleepiness, and motivation scales, and cognitive tasks. After exercise, mental fatigue increased for the doxepin condition (p=0.014) but not placebo (p=0.700), while mental energy decreased for both PLA and DOX (p<0.001) and cognitive task performance was unaffected. It is inferred that histamine binding to H1 receptors in the brain has a role in exercise-induced reductions in mental fatigue, but not increases in energy. Copyright © 2015 Elsevier Inc. All rights reserved.

[Relative bioavailability study of two oral formulations of mycophenolate mofetil in healthy volunteers].

PubMed

Saavedra S, Iván; Sasso A, Jaime; Quiñones S, Luis; Saavedra B, Mónica; Gaete G, Leonardo; Boza T, Ignacio; Carvajal H, Cristóbal; Soto L, Jorge

2011-07-01

The bioequivalence of different formulations of a same pharmaceutical product must be tested empirically. To evaluate the relative bioavailability for an oralformulation of mycophenolate mofetil (MMF) (Linfonex™) compared to the reference formulation (Cellcept™) to determine the bioequivalence between both formulations. A randomized, crossover, double-blind trial in 22 healthy male volunteers, who received a single oral dose of 1000 mg of Linfonex and Cellcept with a washout period of 10 days. Plasma levels of the drug were determined by high performance liquid chr ornatography. Plasma concentrations were plotted and maximum concentration, area under the plasma concentration versus time between 0 and 12 hours after administration and área under plasma concentration curve versus time after administration between 0 and infinity, were calculated for both products. The active compound, mycophenolic acid, was similarly absorbed in both formulations. No statistically significant differences were found in calculated pharmacokinetic parameters between both formulations. Linfonex™ 500 mg is bioequivalent to Cellcept™ 500 mg.

The efficacy of choline magnesium trisalicylate (CMT) in the management of metastatic bone pain: a pilot study.

PubMed

Johnson, J R; Miller, A J

1994-01-01

Twenty-six patients with painful, bony metastases were recruited into a randomized, double-blind, single dose, two-treatment, three-part crossover study of choline magnesium trisalicylate (CMT) and placebo. Assessments were made prior to and at one, two, three and four hours after dosing. Bone pain caused by metastatic cancer was significantly relieved one hour after the administration of 1500 mg CMT (p = 0.04). At all four time points the pain was less than baseline with CMT and at three time points greater than baseline with placebo but these results did not reach statistical significance. The summed pain intensity difference for patients was greater with CMT than with placebo, but this also did not reach significance. The incidence of volunteered side-effects was similar for both treatments. The results suggest that a nonacetylating, nonsteroidal anti-inflammatory drug may have a role complementary to that of an opioid in the management of metastatic bone pain.

Randomized Crossover Comparison of the Short-Term Efficacy and Safety of Single Half-Dose Silodosin and Tamsulosin Hydrochoride in Men With Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia.

PubMed

Takeshita, Hideki; Moriyama, Shingo; Arai, Yoshiaki; Washino, Satoshi; Saito, Kimitoshi; Chiba, Koji; Horiuchi, Susumu; Noro, Akira

2016-01-01

To compare the efficacy and safety of single half-dose silodosin and single full-dose tamsulosin in Japanese men with lower urinary tract symptoms secondary to benign prostatic hyperplasia (LUTS/BPH). Japanese men aged ≥50 years with LUTS/BPH and an International Prostate Symptom Score (IPSS) of ≥8 were enrolled in the randomized crossover study and divided into silodosin-preceding (S-T) and tamsulosin-preceding (T-S) groups. The S-T group received 4 mg silodosin once daily for 4 weeks followed by 0.2 mg tamsulosin once daily for 4 weeks. The T-S group received the reverse treatment sequence. A washout period prior to drug crossover was not included. Subjective and objective efficacy parameters including IPSS, quality of life (QOL) index, uroflowmetry, and safety were compared between the two groups. Thirty of 34 men (S-T group n = 16; T-S group n = 14) completed the study. Both drugs significantly improved all IPSS items and QOL index in the first treatment period. Subjective improvement in nocturia by silodosin was observed in both the first and crossover treatment periods. Objective improvement in maximum flow rate by silodosin was only observed in the first treatment period. Adverse events occurred more frequently with silodosin than with tamsulosin; however, none of the adverse events required treatment discontinuation. Ejaculation disorders occurred in three participants (10%) and were associated with silodosin use. Single half-dose silodosin has a similar efficacy to full-dose tamsulosin in Japanese men with LUTS/BPH and thus, may represent an effective, safe, and affordable treatment option. © 2015 Wiley Publishing Asia Pty Ltd.

Effects of Guided Imagery on Postoperative Outcomes in Patients Undergoing Same-Day Surgical Procedures: A Randomized, Single-Blind Study

DTIC Science & Technology

2010-06-01

2O0O;9Ot3):706-712. 20. Bertrand P, Maye J. A description of the indices of heart rate variabil- ity in orofacial pain paticnis. Bcihcsda, MD: National...neck proce- dures were randomly assigned into 2 groups for this single-blind investigation. Anxiety and baseline pain levels were documented...control group patients received no intervention. Data were collected on pain and nar- cotic consumption at 7- and 2-hour postoperative inter- vals. In

Polydextrose: its impact on short-term food intake and subjective feelings of satiety in males-a randomized controlled cross-over study.

PubMed

Ranawana, Viren; Muller, Adelaide; Henry, C Jeya K

2013-04-01

Polydextrose is a low-calorie highly branched-chain glucose polymer that is poorly digested in the upper gastrointestinal tract and therefore demonstrates fibre-like properties. Fibre has been shown to increase satiety and possibly reduce food intake. Therefore, the objective of the current study was to examine the effects of polydextrose on short-term satiety and energy intake. In a repeated-measures randomized blind cross-over design, 26 healthy males consumed a 400-g fruit smoothie containing 12 g (3 %) of polydextrose, and a buffet lunch 60 min after the smoothie. Motivational ratings for satiety and palatability and lunch energy intake were measured. The effects of the polydextrose-containing smoothie were compared against a polydextrose-free control smoothie. Polydextrose did not significantly alter the taste and palatability of the fruit smoothie. Consuming the polydextrose-containing smoothie resulted in a significantly lower energy intake at lunch (102 kcal less) compared to the control. Polydextrose may be a good fortificant for reducing short-term food intake.

The effect of oxytocin nasal spray on social interaction deficits observed in young children with autism: a randomized clinical crossover trial.

PubMed

Yatawara, C J; Einfeld, S L; Hickie, I B; Davenport, T A; Guastella, A J

2016-09-01

Interventions for autism are limited. The synthetic hormone oxytocin may provide a potential treatment to improve core social and behavioral difficulties in autism, but its efficacy has yet to be evaluated in young children who potentially may benefit to a greater extent. We investigated the efficacy, tolerability and safety of oxytocin treatment in young children with autism using a double-blind, randomized, placebo-controlled, crossover, clinical trial. Thirty-one children with autism received 12 International Units (IU) of oxytocin and placebo nasal spray morning and night (24 IU per day) for 5 weeks, with a 4-week washout period between each treatment. Compared with placebo, oxytocin led to significant improvements on the primary outcome of caregiver-rated social responsiveness. Overall, nasal spray was well tolerated, and the most common reported adverse events were thirst, urination and constipation. This study is the first clinical trial to support the potential of oxytocin as an early intervention for young children with autism to help improve social interaction deficits.

The effect of oxytocin nasal spray on social interaction deficits observed in young children with autism: a randomized clinical crossover trial

PubMed Central

Yatawara, C J; Einfeld, S L; Hickie, I B; Davenport, T A; Guastella, A J

2016-01-01

Interventions for autism are limited. The synthetic hormone oxytocin may provide a potential treatment to improve core social and behavioral difficulties in autism, but its efficacy has yet to be evaluated in young children who potentially may benefit to a greater extent. We investigated the efficacy, tolerability and safety of oxytocin treatment in young children with autism using a double-blind, randomized, placebo-controlled, crossover, clinical trial. Thirty-one children with autism received 12 International Units (IU) of oxytocin and placebo nasal spray morning and night (24 IU per day) for 5 weeks, with a 4-week washout period between each treatment. Compared with placebo, oxytocin led to significant improvements on the primary outcome of caregiver-rated social responsiveness. Overall, nasal spray was well tolerated, and the most common reported adverse events were thirst, urination and constipation. This study is the first clinical trial to support the potential of oxytocin as an early intervention for young children with autism to help improve social interaction deficits. PMID:26503762

Bupivacaine 0.5 % versus articaine 4 % for the removal of lower third molars. A crossover randomized controlled trial

PubMed Central

Sancho-Puchades, Manuel; Vílchez-Pérez, Miguel A.; Paredes-García, Jordi; Berini-Aytés, Leonardo; Gay-Escoda, Cosme

2012-01-01

Objective: To compare the anesthetic action of 0.5% bupivacaine in relation to 4% articaine, both with 1:200,000 epinephrine, in the surgical removal of lower third molars. As a secondary objective hemodynamic changes using both anesthetics were analyzed. Study Design: Triple-blind crossover randomized clinical trial. Eighteen patients underwent bilateral removal of impacted lower third molars using 0.5% bupivacaine or 4% articaine in two different appointments. Preoperative, intraoperative and postoperative variables were recorded. Differences were assessed with McNemar tests and repeated measures ANOVA tests. Results: Both solutions exhibited similar latency times and intraoperative efficacy. Statistical significant lower pain levels were observed with bupivacaine between the fifth (p=0.011) and the ninth (p=0.007) postoperative hours. Bupivacaine provided significantly longer lasting soft tissue anesthesia (p<0.05). Systolic blood pressure and heart rate values were significantly higher with articaine. Conclusions: Bupivacaine could be a valid alternative to articaine especially due to its early postoperative pain prevention ability. Key words:Bupivacaine, articaine, third molar, anesthesia, postoperative pain. PMID:22143739

The impact of dark chocolate intake on arterial elasticity in individuals with HIV/AIDS undergoing ART: a randomized, double-blind, crossover trial.

PubMed

Teixeira, Andrea Mariana Nunes da Costa; Luzia, Liania Alves; de Souza, Suelen Jorge; de Almeida Petrilli, Aline; Pontilho, Patrícia de Moraes; de Souza, Jose Maria Pacheco; Segurado, Aluísio Augusto Cotrim; Efraim, Priscila; Picone, Camila de Melo; Rondo, Patrícia Helen de Carvalho

2017-06-21

An increase in the frequency of cardiovascular diseases has been observed in the HIV/AIDS population. Studies involving healthy subjects or subjects with other diseases have shown benefits of chocolate supplementation on endothelial function and vasodilation. We evaluate the impact of chocolate consumption on arterial elasticity in people living with human immunodeficiency virus - PLHIV. A double-blind, crossover trial including 110 PLHIV (19 to 59 years) on antiretroviral therapy - ART for at least 6 months and with a viral load of <500 copies per mL was conducted. All subjects were randomly assigned to 15-d dietary supplements containing dark chocolate or placebo with a 15-d washout period. Each participant received one of the two sequences: A (dark chocolate, placebo chocolate); B (placebo chocolate, dark chocolate). Arterial elasticity was measured using the HDI/PulseWave™ CR-2000 CardioVascular Profiling System®. Body composition, lipid profile, C-reactive protein, and thiobarbituric acid reactive substances were also assessed. Analysis of variance (ANOVA) for repeated measures using the Stata 11.0® program was used for cross-over analysis. Most subjects were men (59.0%) and Caucasian (46.1%) and the mean age was 44.6 ± 7.1 years. The mean time since diagnosis of HIV infection was 13.7 ± 5.3 years and the mean duration of ART was 12.9 ± 4.2 years. Chocolate consumption resulted in significant alterations in the large artery elasticity index - LAEI (p = 0.049) and the mean concentration of HDL-c was higher after supplementation with dark chocolate (p = 0.045). This is the first study to evaluate the effect of chocolate on arterial elasticity in PLHIV. The results showed that dark chocolate consumption for 15 days improved the elastic properties of the LAEI in PLHIV. These findings, added to the noninvasive method used, may expand the knowledge of CVDs in this population.

Efficacy of topical Rose (Rosa damascena Mill.) oil for migraine headache: A randomized double-blinded placebo-controlled cross-over trial.

PubMed

Niazi, Maria; Hashempur, Mohammad Hashem; Taghizadeh, Mohsen; Heydari, Mojtaba; Shariat, Abdolhamid

2017-10-01

To evaluate the effect of topical formulation of Rosa damascena Mill. (R. damascena) oil on migraine headache, applying syndrome diffrentiation model. Forty patients with migraine headache were randomly assigned to 2 groups of this double-blind, placebo-controlled cross-over trial. The patients were treated for the first 2 consecutive migraine headache attacks by topical R. damascena oil or placebo. Then, after one week of washout period, cross-over was done. Pain intensity of the patients' migraine headache was recorded at the beginnig and ten-sequence time schadule of attacks up to 24h. In addition, photophobia, phonophobia, and nausea and/or vomitting (N/V) of the patients were recorded as secondary outcomes. Finally, gathered data were analysed in a syndrome differentiation manner to assess the effect of R. damascena oil on Hot- and Cold-type migraine headache. Mean pain intensity of the patients' migraine headache in the different time-points after R. damascena oil or placebo use, was not significantly different. Additionally, regarding mean scores of N/V, photophobia, and phonophobia severity of the patients, no significant differences between the two groups were observed. Finally, applying syndrome differentiation model, the mean score of migraine headache pain intensity turned out to be significantly lower in patients with "hot" type migraine syndrome at in 30, 45, 60, 90, and 120min after R. damascena oil application compared to "cold" types (P values: 0.001, 0.001, <0.001, <0.001, and 0.02; respectively). It seems that syndrome differentiation can help in selection of patients who may benefit from the topical R. damascena oil in short-term relief of pain intensity in migraine headache. Further studies of longer follow-up and larger study population, however, are necessitated for more scientifically rigorous judgment on efficacy of R. damascena oil for patients with migraine headache. Copyright © 2017 Elsevier Ltd. All rights reserved.

Efficacy of piracetam in the treatment of tardive dyskinesia in schizophrenic patients: a randomized, double-blind, placebo-controlled crossover study.

PubMed

Libov, Igor; Miodownik, Chanoch; Bersudsky, Yuly; Dwolatzky, Tzvi; Lerner, Vladimir

2007-07-01

Piracetam is a potent antioxidant, a cerebral neuroprotector, a neuronal metabolic enhancer, and a brain integrative agent. More than 20 years ago, an intravenous preparation of piracetam demonstrated an improvement in the symptoms of tardive dyskinesia. The aim of our study was to reexamine the efficacy of piracetam in the treatment of tardive dyskinesia using an oral preparation. The study was conducted at the Be'er Sheva Mental Health Center from May 2003 to December 2004 and involved a 9-week, double-blind, crossover, placebo-controlled trial assessing 40 DSM-IV schizophrenic and schizo-affective patients with DSM-IV-TR tardive dyskinesia. All study subjects received their usual antipsychotic treatment. Initially, subjects were randomly assigned to receive 4 weeks of treatment with either piracetam (4800 mg/day) or placebo. Thereafter, following a washout period of 1 week, they entered the crossover phase of the study for a further 4 weeks. The change in score of the Extrapyramidal Symptom Rating Scale from baseline to the study endpoint was the primary outcome measure. The mean decrease in score from baseline to endpoint in the clinical global impression subscale in patients treated with piracetam was 1.1 points compared to 0.1 points in the placebo group (p = .004). The mean decrease in the tardive parkinsonism subscale was 8.7 points in patients treated with piracetam and 0.6 points in those on placebo (p = .001). The mean decrease in the tardive dyskinesia subscale was 3.0 points in the piracetam group in contrast to deterioration of condition in the placebo group by -0.2 points (p = .003). Piracetam appears to be effective in reducing symptoms of tardive dyskinesia. The specific mechanism by which piracetam may attenuate symptoms of tardive dyskinesia needs to be further evaluated. ClinicalTrials.gov identifier NCT00190008.

Acute and subchronic effects of bilastine (20 and 40 mg) and hydroxyzine (50 mg) on actual driving performance in healthy volunteers.

PubMed

Conen, Silke; Theunissen, Eef L; Van Oers, Anita C M; Valiente, Román; Ramaekers, Johannes G

2011-11-01

Bilastine is a new second-generation H1 antagonist. Although bilastine has been demonstrated to produce little or no performance impairment in laboratory tests, it cannot be excluded that it produces impairments in real-life performance such as driving. This study aims to assess the effects of two doses of bilastine (20 and 40 mg) on actual driving after single and repeated administration. Hydroxyzine 50 mg was included as an active control. Twenty-two participants (11 females, 11 males) were tested in a placebo-controlled, randomized, double-blind, four-way cross-over design. Participants were treated with once-daily doses for eight consecutive days. On day 1 and 8 of each treatment period participants performed an actual highway driving test. The primary variable was standard deviation of lateral position (SDLP), a measure of weaving. Results demonstrated that hydroxyzine significantly increased SDLP on days 1 and 8 of treatment. Bilastine did not affect SDLP. It is concluded that hydroxyzine produces severe driving impairment after single doses and that this impairment only partly mitigates over time due to a lack of complete tolerance. Bilastine did not produce any driving impairment after single and repeated doses and can be safely used in traffic in doses up to 40 mg.

Immediate effects of reiki on heart rate variability, cortisol levels, and body temperature in health care professionals with burnout.

PubMed

Díaz-Rodríguez, Lourdes; Arroyo-Morales, Manuel; Fernández-de-las-Peñas, Cesar; García-Lafuente, Francisca; García-Royo, Carmen; Tomás-Rojas, Inmaculada

2011-10-01

Burnout is a work-related mental health impairment comprising three dimensions: emotional exhaustion, depersonalization, and reduced personal accomplishment. Reiki aims to help replenish and rebalance the body's energetic system, thus stimulating the healing process. The objective of this placebo-controlled, repeated measures, crossover, single-blind, randomized trial was to analyze the immediate effects of Reiki on heart rate variability (HRV), body temperature, and salivary flow rate and cortisol level in health care professionals with burnout syndrome (BS). Participants included 21 health care professionals with BS, who were asked to complete two visits to the laboratory with a 1-week interval between sessions. They were randomly assigned the order in which they would receive a Reiki session applied by an experienced therapist and a placebo treatment applied by a therapist with no knowledge of Reiki, who mimicked the Reiki treatment. Temperature, Holter ECG recordings (standard deviation of the normal-to-normal interval [SDNN], square root of mean squared differences of successive NN intervals [RMSSD], HRV index, low frequency component [LF], and high frequency component [HF]), salivary flow rate and cortisol levels were measured at baseline and postintervention by an assessor blinded to allocation group. SDNN and body temperature were significantly higher after the Reiki treatment than after the placebo. LF was significantly lower after the Reiki treatment. The decrease in the LF domain was associated with the increase in body temperature. These results suggest that Reiki has an effect on the parasympathetic nervous system when applied to health care professionals with BS.

Low-dose oxytocin delivered intranasally with Breath Powered device affects social-cognitive behavior: a randomized four-way crossover trial with nasal cavity dimension assessment

PubMed Central

Quintana, D S; Westlye, L T; Rustan, Ø G; Tesli, N; Poppy, C L; Smevik, H; Tesli, M; Røine, M; Mahmoud, R A; Smerud, K T; Djupesland, P G; Andreassen, O A

2015-01-01

Despite the promise of intranasal oxytocin (OT) for modulating social behavior, recent work has provided mixed results. This may relate to suboptimal drug deposition achieved with conventional nasal sprays, inter-individual differences in nasal physiology and a poor understanding of how intranasal OT is delivered to the brain in humans. Delivering OT using a novel ‘Breath Powered' nasal device previously shown to enhance deposition in intranasal sites targeted for nose-to-brain transport, we evaluated dose-dependent effects on social cognition, compared response with intravenous (IV) administration of OT, and assessed nasal cavity dimensions using acoustic rhinometry. We adopted a randomized, double-blind, double-dummy, crossover design, with 16 healthy male adults completing four single-dose treatments (intranasal 8 IU (international units) or 24 IU OT, 1 IU OT IV and placebo). The primary outcome was social cognition measured by emotional ratings of facial images. Secondary outcomes included the pharmacokinetics of OT, vasopressin and cortisol in blood and the association between nasal cavity dimensions and emotional ratings. Despite the fact that all the treatments produced similar plasma OT increases compared with placebo, there was a main effect of treatment on anger ratings of emotionally ambiguous faces. Pairwise comparisons revealed decreased ratings after 8 IU OT in comparison to both placebo and 24 IU OT. In addition, there was an inverse relationship between nasal valve dimensions and anger ratings of ambiguous faces after 8-IU OT treatment. These findings provide support for a direct nose-to-brain effect, independent of blood absorption, of low-dose OT delivered from a Breath Powered device. PMID:26171983

Low-dose oxytocin delivered intranasally with Breath Powered device affects social-cognitive behavior: a randomized four-way crossover trial with nasal cavity dimension assessment.

PubMed

Quintana, D S; Westlye, L T; Rustan, Ø G; Tesli, N; Poppy, C L; Smevik, H; Tesli, M; Røine, M; Mahmoud, R A; Smerud, K T; Djupesland, P G; Andreassen, O A

2015-07-14

Despite the promise of intranasal oxytocin (OT) for modulating social behavior, recent work has provided mixed results. This may relate to suboptimal drug deposition achieved with conventional nasal sprays, inter-individual differences in nasal physiology and a poor understanding of how intranasal OT is delivered to the brain in humans. Delivering OT using a novel 'Breath Powered' nasal device previously shown to enhance deposition in intranasal sites targeted for nose-to-brain transport, we evaluated dose-dependent effects on social cognition, compared response with intravenous (IV) administration of OT, and assessed nasal cavity dimensions using acoustic rhinometry. We adopted a randomized, double-blind, double-dummy, crossover design, with 16 healthy male adults completing four single-dose treatments (intranasal 8 IU (international units) or 24 IU OT, 1 IU OT IV and placebo). The primary outcome was social cognition measured by emotional ratings of facial images. Secondary outcomes included the pharmacokinetics of OT, vasopressin and cortisol in blood and the association between nasal cavity dimensions and emotional ratings. Despite the fact that all the treatments produced similar plasma OT increases compared with placebo, there was a main effect of treatment on anger ratings of emotionally ambiguous faces. Pairwise comparisons revealed decreased ratings after 8 IU OT in comparison to both placebo and 24 IU OT. In addition, there was an inverse relationship between nasal valve dimensions and anger ratings of ambiguous faces after 8-IU OT treatment. These findings provide support for a direct nose-to-brain effect, independent of blood absorption, of low-dose OT delivered from a Breath Powered device.

Canagliflozin triggers the FGF23/1,25-dihydroxyvitamin D/PTH axis in healthy volunteers in a randomized crossover study.

PubMed

Blau, Jenny E; Bauman, Viviana; Conway, Ellen M; Piaggi, Paolo; Walter, Mary F; Wright, Elizabeth C; Bernstein, Shanna; Courville, Amber B; Collins, Michael T; Rother, Kristina I; Taylor, Simeon I

2018-04-19

Sodium glucose cotransporter-2 (SGLT2) inhibitors are the most recently approved class of drugs for type 2 diabetes and provide both glycemic efficacy and cardiovascular risk reduction. A number of safety issues have been identified, including treatment-emergent bone fractures. To understand the overall clinical profile, these safety issues must be balanced against an attractive efficacy profile. Our study was designed to investigate pathophysiological mechanisms mediating treatment-emergent adverse effects on bone health. We conducted a single-blind randomized crossover study in hospitalized healthy adults (n = 25) receiving either canagliflozin (300 mg/d) or placebo for 5 days. The primary end-point was the drug-induced change in AUC for plasma intact fibroblast growth factor 23 (FGF23) immunoactivity between 24 and 72 hours. Canagliflozin administration increased placebo-subtracted mean levels of serum phosphorus (+16%), plasma FGF23 (+20%), and plasma parathyroid hormone (PTH) (+25%), while decreasing the level of 1,25-dihydroxyvitamin D (-10%). There was substantial interindividual variation in the magnitude of each of these pharmacodynamic responses. The increase in plasma FGF23 was correlated with the increase in serum phosphorus, and the decrease in plasma 1,25-dihydroxyvitamin D was correlated with the increase in plasma FGF23. Canagliflozin induced a prompt increase in serum phosphorus, which triggers downstream changes in FGF23, 1,25-dihydroxyvitamin D, and PTH, with potential to exert adverse effects on bone health. These pharmacodynamic data provide a foundation for future research to elucidate pathophysiological mechanisms of adverse effects on bone health, with the objective of devising therapeutic strategies to mitigate the drug-associated fracture risk. ClinicalTrial.gov (NCT02404870). Supported by the Intramural Program of NIDDK.

Canagliflozin triggers the FGF23/1,25-dihydroxyvitamin D/PTH axis in healthy volunteers in a randomized crossover study

PubMed Central

Blau, Jenny E.; Bauman, Viviana; Conway, Ellen M.; Walter, Mary F.; Wright, Elizabeth C.; Bernstein, Shanna; Courville, Amber B.; Collins, Michael T.; Rother, Kristina I.

2018-01-01

BACKGROUND. Sodium glucose cotransporter-2 (SGLT2) inhibitors are the most recently approved class of drugs for type 2 diabetes and provide both glycemic efficacy and cardiovascular risk reduction. A number of safety issues have been identified, including treatment-emergent bone fractures. To understand the overall clinical profile, these safety issues must be balanced against an attractive efficacy profile. Our study was designed to investigate pathophysiological mechanisms mediating treatment-emergent adverse effects on bone health. METHODS. We conducted a single-blind randomized crossover study in hospitalized healthy adults (n = 25) receiving either canagliflozin (300 mg/d) or placebo for 5 days. The primary end-point was the drug-induced change in AUC for plasma intact fibroblast growth factor 23 (FGF23) immunoactivity between 24 and 72 hours. RESULTS. Canagliflozin administration increased placebo-subtracted mean levels of serum phosphorus (+16%), plasma FGF23 (+20%), and plasma parathyroid hormone (PTH) (+25%), while decreasing the level of 1,25-dihydroxyvitamin D (–10%). There was substantial interindividual variation in the magnitude of each of these pharmacodynamic responses. The increase in plasma FGF23 was correlated with the increase in serum phosphorus, and the decrease in plasma 1,25-dihydroxyvitamin D was correlated with the increase in plasma FGF23. CONCLUSIONS. Canagliflozin induced a prompt increase in serum phosphorus, which triggers downstream changes in FGF23, 1,25-dihydroxyvitamin D, and PTH, with potential to exert adverse effects on bone health. These pharmacodynamic data provide a foundation for future research to elucidate pathophysiological mechanisms of adverse effects on bone health, with the objective of devising therapeutic strategies to mitigate the drug-associated fracture risk. TRIAL REGISTRATION. ClinicalTrial.gov (NCT02404870). FUNDING. Supported by the Intramural Program of NIDDK. PMID:29669938

Comparison between Steroid Injection and Stretching Exercise on the Scalene of Patients with Upper Extremity Paresthesia: Randomized Cross-Over Study.

PubMed

Kim, Yong Wook; Yoon, Seo Yeon; Park, Yongbum; Chang, Won Hyuk; Lee, Sang Chul

2016-03-01

To compare the therapeutic effects on upper extremity paresthesia of intra-muscular steroid injections into the scalene muscle with those of stretching exercise only. Twenty patients with upper extremity paresthesia who met the criteria were recruited to participate in this single-blind, crossover study. Fourteen of 20 patients were female. The average age was 45.0 ± 10.5 years and duration of symptom was 12.2 ± 8.7 months. Each participant completed one injection and daily exercise program for 2 weeks. After randomization, half of all patients received ultrasound-guided injection of scalene muscles before exercise, while the other was invested for the other patients. After two weeks, there was a significant decrease of the visual analog scale score of treatment effect compared with baseline in both groups (6.90 to 2.85 after injection and 5.65 to 4.05 after stretching exercise, p<0.01). However, injection resulted in greater improvements than stretching exercise (p<0.01). The number of patients with successful treatment, defined as >50% reduction in post-treatment visual analog scale, was 18 of 20 (90.0%) after injection, compared to 5 of 20 (25.0%) after stretching exercise. There were no cases of unintended brachial plexus block after injection. Ultrasound-guided steroid injection or stretching exercise of scalene muscles led to reduced upper extremity paresthesia in patients who present with localized tenderness in the scalene muscle without electrodiagnostic test abnormalities, although injection treatment resulted in more improvements. The results suggest that symptoms relief might result from injection into the muscle alone not related to blockade of the brachial plexus.

Comparison between Steroid Injection and Stretching Exercise on the Scalene of Patients with Upper Extremity Paresthesia: Randomized Cross-Over Study

PubMed Central

Kim, Yong Wook; Yoon, Seo Yeon; Park, Yongbum; Chang, Won Hyuk

2016-01-01

Purpose To compare the therapeutic effects on upper extremity paresthesia of intra-muscular steroid injections into the scalene muscle with those of stretching exercise only. Materials and Methods Twenty patients with upper extremity paresthesia who met the criteria were recruited to participate in this single-blind, crossover study. Fourteen of 20 patients were female. The average age was 45.0±10.5 years and duration of symptom was 12.2±8.7 months. Each participant completed one injection and daily exercise program for 2 weeks. After randomization, half of all patients received ultrasound-guided injection of scalene muscles before exercise, while the other was invested for the other patients. Results After two weeks, there was a significant decrease of the visual analog scale score of treatment effect compared with baseline in both groups (6.90 to 2.85 after injection and 5.65 to 4.05 after stretching exercise, p<0.01). However, injection resulted in greater improvements than stretching exercise (p<0.01). The number of patients with successful treatment, defined as >50% reduction in post-treatment visual analog scale, was 18 of 20 (90.0%) after injection, compared to 5 of 20 (25.0%) after stretching exercise. There were no cases of unintended brachial plexus block after injection. Conclusion Ultrasound-guided steroid injection or stretching exercise of scalene muscles led to reduced upper extremity paresthesia in patients who present with localized tenderness in the scalene muscle without electrodiagnostic test abnormalities, although injection treatment resulted in more improvements. The results suggest that symptoms relief might result from injection into the muscle alone not related to blockade of the brachial plexus. PMID:26847305

Effects of Home-Based Versus Clinic-Based Rehabilitation Combining Mirror Therapy and Task-Specific Training for Patients With Stroke: A Randomized Crossover Trial.

PubMed

Hsieh, Yu-Wei; Chang, Ku-Chou; Hung, Jen-Wen; Wu, Ching-Yi; Fu, Mu-Hui; Chen, Chih-Chi

2018-04-25

We investigated the treatment effects of a home-based rehabilitation program compared with clinic-based rehabilitation in patients with stroke. A single-blinded, 2-sequence, 2-period, crossover-designed study. Rehabilitation clinics and participant's home environment. Individuals with disabilities poststroke. During each intervention period, each participant received 12 training sessions, with a 4-week washout phase between the 2 periods. Participants were randomly allocated to home-based rehabilitation first or clinic-based rehabilitation first. Intervention protocols included mirror therapy and task-specific training. Outcome measures were selected based on the International Classification of Functioning, Disability and Health. Outcomes of impairment level were the Fugl-Meyer Assessment, Box and Block Test, and Revised Nottingham Sensory Assessment. Outcomes of activity and participation levels included the Motor Activity Log, 10-meter walk test, sit-to-stand test, Canadian Occupational Performance Measure, and EuroQoL-5D Questionnaire. Pretest analyses showed no significant evidence of carryover effect. Home-based rehabilitation resulted in significantly greater improvements on the Motor Activity Log amount of use subscale (P=.01) and the sit-to-stand test (P=.03) than clinic-based rehabilitation. The clinic-based rehabilitation group had better benefits on the health index measured by the EuroQoL-5D Questionnaire (P=.02) than the home-based rehabilitation group. Differences between the 2 groups on the other outcomes were not statistically significant. The home-based and clinic-based rehabilitation groups had comparable benefits in the outcomes of impairment level but showed differential effects in the outcomes of activity and participation levels. Copyright © 2018 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Spa therapy adjunct to pharmacotherapy is beneficial in rheumatoid arthritis: a crossover randomized controlled trial

NASA Astrophysics Data System (ADS)

Karagülle, Mine; Kardeş, Sinan; Dişçi, Rian; Karagülle, Müfit Zeki

2018-02-01

This study aims to investigate whether 2-week spa therapy, as an adjunct to usual pharmacological therapy, has any beneficial effect in patients with rheumatoid arthritis (RA). In this single-blind crossover study, 50 patients were randomly assigned in a 1:1 manner to receive usual pharmacological therapy plus 2-week spa therapy or usual pharmacological therapy alone (period 1.6 months); after a 9-month washout, patients were crossed over to the opposite assignment (period 2.6 months). Spa therapy program included a daily saline balneotherapy session at 36-37 °C for 20 min except Sundays. The clinical outcomes were evaluated at baseline, after spa therapy (2 weeks) and 3 and 6 months after the spa therapy in both period and were pain (Visual Analogue Scale (VAS)), patient and physician global assessments (VAS), Health Assessment Questionnaire (HAQ), and Disease Activity Score (DAS28). Spa therapy was superior to control therapy in improving all the assessed clinical outcomes at the end of the spa therapy. This superiority persisted significantly in physician global assessment ( p = 0.010) and with a trend in favor of spa group in patient global assessment ( p = 0.058), function ( p = 0.092), and disease activity ( p = 0.098) at 3 months. Statistically significant improvements were found in spa therapy compared to control in disease activity ( p = 0.006) and patient ( p = 0.020) and physician global ( p = 0.011) assessments, and a trend toward improvements in pain ( p = 0.069) and swollen joints ( p = 0.070) at 6 months. A 2-week spa therapy adjunct to usual pharmacological therapy provided beneficial clinical effects compared to usual pharmacological therapy alone, in RA patients treated with traditional disease-modifying antirheumatic drugs. These beneficial effects may last for 6 months.

Substance P-induced skin inflammation is not modulated by a single dose of sitagliptin in human volunteers.

PubMed

Grouzmann, Eric; Bigliardi, Paul; Appenzeller, Monique; Pannatier, André; Buclin, Thierry

2011-03-01

Substance P (SP), an undecapeptide belonging to the tachykinin family, is released during the activation of sensory nerves, and causes vasodilation, edema and pain through activation of tissular Neurokinin 1 receptors. SP proinflammatory effects are terminated by angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP), while the aminopeptidase dipeptidylpeptidase IV (DPPIV) can also play a role. The aim of this randomized, crossover, double-blind study was to assess the cutaneous vasoreactivity (flare and wheal reaction, burning pain sensation) to intradermal injection of ascending doses of SP in six volunteers receiving a single therapeutic dose of the DPPIV inhibitor sitagliptin or a matching placebo. Cutaneous SP challenges produced the expected, dose-dependent flare and wheal response, while eliciting mild to moderate local pain sensation with little dose dependency. However, no differences were shown in the responses observed under sitagliptin compared with placebo, while the study would have been sufficiently powered to detect a clinically relevant increase in sensitivity to SP. The results of this pilot study are in line with proteolytic cleavage of SP by ACE and NEP compensating the blockade of DPPIV to prevent an augmentation of its proinflammatory action.

Guanidinoacetic acid versus creatine for improved brain and muscle creatine levels: a superiority pilot trial in healthy men.

PubMed

Ostojic, Sergej M; Ostojic, Jelena; Drid, Patrik; Vranes, Milan

2016-09-01

In this randomized, double-blind, crossover trial, we evaluated whether 4-week supplementation with guanidinoacetic acid (GAA) is superior to creatine in facilitating creatine levels in healthy men (n = 5). GAA (3.0 g/day) resulted in a more powerful rise (up to 16.2%) in tissue creatine levels in vastus medialis muscle, middle-cerebellar peduncle, and paracentral grey matter, as compared with creatine (P < 0.05). These results indicate that GAA as a preferred alternative to creatine for improved bioenergetics in energy-demanding tissues.

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 radiation necrosis secondary to the treatment of head-and-neck cancer and brain cancer.« less

The patient general satisfaction of mandibular single-implant overdentures and conventional complete dentures: Study protocol for a randomized crossover trial.

PubMed

Kanazawa, Manabu; Tanoue, Mariko; Miyayasu, Anna; Takeshita, Shin; Sato, Daisuke; Asami, Mari; Lam, Thuy Vo; Thu, Khaing Myat; Oda, Ken; Komagamine, Yuriko; Minakuchi, Shunsuke; Feine, Jocelyne

2018-05-01

Mandibular overdentures retained by a single implant placed in the midline of edentulous mandible have been reported to be more comfortable and function better than complete dentures. Although single-implant overdentures are still more costly than conventional complete dentures, there are a few studies which investigated whether mandibular single-implant overdentures are superior to complete dentures when patient general satisfaction is compared. The aim of this study is to assess patient general satisfaction with mandibular single-implant overdentures and complete dentures. This study is a randomized crossover trial to compare mandibular single-implant overdentures and complete dentures in edentulous individuals. Participant recruitment is ongoing at the time of this submission. Twenty-two participants will be recruited. New mandibular complete dentures will be fabricated. A single implant will be placed in the midline of the edentulous mandible. The mucosal surface of the complete denture around the implant will be relieved for 3 months. The participants will then be randomly allocated into 2 groups according to the order of the interventions; group 1 will receive single-implant overdentures first and will wear them for 2 months, followed by complete dentures for 2 months. Group 2 will receive the same treatments in a reverse order. After experiencing the 2 interventions, the participants will choose one of the mandibular prostheses, and yearly follow-up visits are planned for 5 years. The primary outcome of this trial is patient ratings of general satisfaction on 100 mm visual analog scales. Assessments of the prostheses and oral health-related quality of life will also be recorded as patient-reported outcomes. The secondary outcomes are cost and time for treatment. Masticatory efficiency and cognitive capacity will also be recorded. Furthermore, qualitative research will be performed to investigate the factors associated with success of these mandibular denture types. Clinical outcomes, such as implant survival rate, marginal bone loss, and prosthodontic complications, will also be recorded. The results of this randomized crossover trial will clarify whether mandibular single implants and overdentures for edentulous individuals provide better patient general satisfaction when compared to conventional complete dentures. This clinical trial was registered at the University Hospital Medical Information Network (UMIN) Center (UMIN000017883).

Validation of Placebo in a Manual Therapy Randomized Controlled Trial

PubMed Central

Chaibi, Aleksander; Šaltytė Benth, Jūratė; Bjørn Russell, Michael

2015-01-01

At present, no consensus exists among clinical and academic experts regarding an appropriate placebo for randomized controlled trials (RCTs) of spinal manipulative therapy (SMT). Therefore, we investigated whether it was possible to conduct a chiropractic manual-therapy RCT with placebo. Seventy migraineurs were randomized to a single-blinded placebo-controlled clinical trial that consisted of 12 treatment sessions over 3 months. The participants were randomized to chiropractic SMT or placebo (sham manipulation). After each session, the participants were surveyed on whether they thought they had undergone active treatment (“yes” or “no”) and how strongly they believed that active treatment was received (numeric rating scale 0–10). The outcome measures included the rate of successful blinding and the certitude of the participants’ beliefs in both treatment groups. At each treatment session, more than 80% of the participants believed that they had undergone active treatment, regardless of group allocation. The odds ratio for believing that active treatment was received was >10 for all treatment sessions in both groups (all p < 0.001). The blinding was maintained throughout the RCT. Our results strongly demonstrate that it is possible to conduct a single-blinded manual-therapy RCT with placebo and to maintain the blinding throughout 12 treatment sessions given over 3 months. PMID:26145718

Efficacy of a Mandibular Advancement Appliance on Sleep Disordered Breathing in Children: A Study Protocol of a Crossover Randomized Controlled Trial.

PubMed

Idris, Ghassan; Galland, Barbara; Robertson, Christopher J; Farella, Mauro

2016-01-01

Sleep-Disordered Breathing (SDB) varies from habitual snoring to partial or complete obstruction of the upper airway and can be found in up to 10% of children. SDB can significantly affect children's wellbeing, as it can cause growth disorders, educational and behavioral problems, and even life-threatening conditions, such as cardiorespiratory failure. Adenotonsillectomy represents the primary treatment for pediatric SDB where adeno-tonsillar hypertrophy is indicated. For those with craniofacial anomalies, or for whom adenotonsillectomy or other treatment modalities have failed, or surgery is contra-indicated, mandibular advancement splints (MAS) may represent a viable treatment option. Whilst the efficacy of these appliances has been consistently demonstrated in adults, there is little information about their effectiveness in children. To determine the efficacy of mandibular advancement appliances for the management of SDB and related health problems in children. The study will be designed as a single-blind crossover randomized controlled trial with administration of both an "Active MAS" (Twin-block) and a "Sham MAS." Eligible participants will be children aged 8-12 years whose parents report they snore ≥3 nights per week. Sixteen children will enter the full study after confirming other inclusion criteria, particularly Skeletal class I or class II confirmed by lateral cephalometric radiograph. Each child will be randomly assigned to either a treatment sequence starting with the Active or the Sham MAS. Participants will wear the appliances for 3 weeks separated by a 2-week washout period. For each participant, home-based polysomnographic data will be collected four times; once before and once after each treatment period. The Apnea Hypopnea Index (AHI) will represent the main outcome variable. Secondary outcomes will include, snoring frequency, masseter muscle activity, sleep symptoms, quality of life, daytime sleepiness, children behavior, and nocturnal enuresis. In addition, blood samples will be collected to assess growth hormone changes. This study was registered in the Australian New Zealand Clinical Trials Registry (ANZCTR): [ACTRN12614001013651].

A Randomized Crossover Trial Comparing Autotitrating and Continuous Positive Airway Pressure in Subjects With Symptoms of Aerophagia: Effects on Compliance and Subjective Symptoms.

PubMed

Shirlaw, Teresa; Hanssen, Kevin; Duce, Brett; Hukins, Craig

2017-07-15

To assess the benefit and tolerance of autotitrating positive airway pressure (APAP) versus continuous positive airway pressure (CPAP) in subjects who experience aerophagia. This is the report of a prospective, two-week, double-blinded, randomized crossover trial set in an Australian clinical sleep laboratory in a tertiary hospital. Fifty-six subjects who reported symptoms of aerophagia that they attributed to CPAP were recruited. Full face masks were used by 39 of the 56 subjects recruited. Subjects were randomly and blindly allocated to either CPAP at their treatment recommended pressure or APAP 6-20 cm H 2 O, in random order. Subjects spent two weeks on each therapy mode. Therapy usage hours, 95th centile pressure, maximum pressure, 95th centile leak, and residual apnea-hypopnea index (AHI) were reported at the end of each two-week treatment period. Functional Outcome of Sleepiness Questionnaire, Epworth Sleepiness Scale, and visual analog scale to measure symptoms of aerophagia were also completed at the end of each 2-week treatment arm. The median pressure ( P < .001) and 95th centile pressure ( P < .001) were reduced with APAP but no differences in compliance ( P = .120) and residual AHI were observed. APAP reduced the symptoms of bloating ( P = .011), worst episode of bloating ( P = .040), flatulence ( P = .010), and belching ( P = .001) compared to CPAP. There were no differences in Epworth Sleepiness Scale or Functional Outcome of Sleepiness Questionnaire outcomes between CPAP and APAP. APAP therapy reduces the symptoms of aerophagia while not affecting compliance when compared with CPAP therapy. Australian and New Zealand Clinical Trials Registry at https://www.anzctr.org.au, trial number ACTRN12611001250921. A commentary on this article appears in this issue on page 859. © 2017 American Academy of Sleep Medicine

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 meaningful improvement in cognitive function in CMI or other neuropsychiatric conditions associated with HPA axis dysregulation. Published by Elsevier Ltd.

Intravenous nicorandil versus adenosine for fractional flow reserve measurement: a crossover, randomized study.

PubMed

Nishi, Takeshi; Kitahara, Hideki; Fujimoto, Yoshihide; Nakayama, Takashi; Nagashima, Kengo; Hanaoka, Hideki; Kobayashi, Yoshio

2018-06-01

Nicorandil has vasodilatory effects on both the epicardial coronary arteries and the coronary microvasculature, thereby increasing coronary blood flow. The objective of the present study was to investigate the effectiveness of intravenous (IV) nicorandil infusion for fractional flow reserve (FFR) measurement. In this crossover randomized study, 49 patients underwent FFR measurement with a consecutive randomized order of patient-blind infusions of continuous IV adenosine administration and a single bolus IV administration of nicorandil. The primary endpoint was the difference between the FFR by nicorandil and the FFR by adenosine, as assessed by the Bland-Altman method. The mean FFR value measured by nicorandil was not significantly different from that measured by adenosine [0.8125 ± 0.1349 vs. 0.7978 ± 0.124; mean difference, 0.0147 (95% confidence interval - 0.0373, 0.0667); P = 0.58]. There was no clinically significant diagnostic discordance, with the FFR by nicorandil > 0.80 and that by adenosine < 0.75. Hyperemia was achieved earlier using nicorandil than adenosine (34 ± 13 vs. 58 ± 15, P < 0.001). The duration of hyperemia after IV nicorandil was variable (6-570 s, mean 89 ± 98 s). IV nicorandil decreased systolic blood pressure by 32 ± 16 mm Hg (24 ± 10%) from baseline. Linear regression analysis showed that the average FFR value and the difference in systolic blood pressure were significantly associated with the bias in the FFR value between the two drugs. In conclusions, the results of the present study suggest that IV nicorandil can achieve maximal hyperemia easily and rapidly, providing an acceptable diagnostic performance for FFR assessment. However, a wide range of variation in hyperemic plateau and a decrease in blood pressure are the major limitations of this method.

High phenylalanine levels directly affect mood and sustained attention in adults with phenylketonuria: a randomised, double-blind, placebo-controlled, crossover trial.

PubMed

ten Hoedt, Amber E; de Sonneville, Leo M J; Francois, Baudouin; ter Horst, Nienke M; Janssen, Mirian C H; Rubio-Gozalbo, M Estela; Wijburg, Frits A; Hollak, Carla E M; Bosch, Annet M

2011-02-01

The main debate in the treatment of Phenylketonuria (PKU) is whether adult patients need the strict phenylalanine (Phe)-restricted diet. Physicians and patients lack evidence-based guidelines to help them make well-informed choices. We have carried out the first randomised double-blind placebo-controlled trial into the effects of short-term elevation of Phe levels on neuropsychological functions and mood of adults with PKU. Nine continuously treated adults with PKU underwent two 4-week supplementation periods: one with Phe, mimicking normal dietary intake, and one with placebo in randomly allocated order via a randomisation coding list in a double-blind cross-over design. A set of neuropsychological tests (Amsterdam Neuropsychological Tasks) was administered at the end of each study period. In addition, patients and for each patient a friend or relative, completed weekly Profile of Mood States (POMS) questionnaires, evaluating the patients' mood. Phe levels were measured twice weekly. Mean plasma Phe levels were significantly higher during Phe supplementation compared with placebo (p = 0.008). Neuropsychological tests demonstrated an impairment in sustained attention during Phe supplementation (p = 0.029). Both patients and their friend or relative reported lower scores on the POMS questionnaires during Phe supplementation (p = 0.017 and p = 0.040, respectively). High plasma Phe levels have a direct negative effect on both sustained attention and on mood in adult patients with PKU. A Phe-restricted "diet for life" might be an advisable option for many.

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 communicans for lumbar disc pain was conducted. The null hypothesis of no difference in pain reduction and in Global Perceived Effect between the treatment and sham group cannot be rejected. © 2016 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC®.

Modafinil In Debilitating fatigue After Stroke (MIDAS): study protocol for a randomised, double-blinded, placebo-controlled, crossover trial.

PubMed

Lillicrap, Thomas; Krishnamurthy, Venkatesh; Attia, John; Nilsson, Michael; Levi, Christopher R; Parsons, Mark W; Bivard, Andrew

2016-08-17

Fatigue is a common symptom in stroke survivors for which there is currently no proven therapy. Modafinil is a wakefulness-promoting agent with established benefits in other disease models. We aim to test if modafinil will improve patient's self-reported fatigue scores when compared to placebo and if therapy results in increased quality of life. MIDAS is a phase II, single-centre, prospective, double-blinded, randomised, crossover trial of modafinil for the treatment of persistent fatigue in survivors of ischaemic stroke. The inclusion criteria will require an average score of 12 or more across all domains of the Multi-dimensional Fatigue Inventory (MFI-20) and the diagnosis of a stroke more than 6 months prior. Patients will be randomised 1:1 to receive either modafinil 200 mg daily or placebo for a period of 6 weeks, after which a crossover will occur where patients who are on modafinil will begin taking placebo and vice versa. The primary outcome will be improvement in fatigue as measured by the MFI-20. Secondary outcomes will include changes in the Fatigue Severity Scale, improved cognition measured using the Montreal Cognitive Assessment, improvement in mood as determined by the Depression, Anxiety and Stress Scale and improvement in each patient's stroke-specific quality of life score. All participants will also undergo magnetic resonance imaging (MRI) at baseline, crossover and study conclusion to measure cerebral blood flow on arterial spin labelling and brain activity on resting state functional MRI. This study will comply with the CONSORT guidelines. The projected sample size requirement is 36 participants in a crossover trial giving a power of 80 % and a type-1 error rate of 0.05. MIDAS seeks to enhance the quality of life in stroke survivors by assisting or resolving stroke-associated fatigue. ACTRN12615000350527 , registered on the 17 April 2015. Protocol version 3, approved 16 June 2015.

Safety, tolerability and pharmacokinetics of the histamine H3 receptor antagonist, ABT-288, in healthy young adults and elderly volunteers

PubMed Central

Othman, Ahmed A; Haig, George; Florian, Hana; Locke, Charles; Zhang, Jun; Dutta, Sandeep

2013-01-01

Aim The objective of this work was to characterize the safety, tolerability and pharmacokinetics of ABT-288, a highly selective histamine H3 receptor antagonist, in healthy young adults and elderly subjects following single and multiple dosing in a phase 1 setting. Methods Single doses (0.1, 0.3, 1, 3, 10, 20 and 40 mg ABT-288) and multiple doses (0.5, 1.5, 3 and 6 mg ABT-288 once-daily for 14 days) were evaluated in young adults and multiple doses (0.5, 1.5, 3 and 5 mg ABT-288 once-daily for 12 days) were evaluated in elderly subjects using randomized, double-blind, placebo-controlled, dose-escalating study designs. The effect of food on ABT-288 pharmacokinetics (5 mg single dose) was evaluated using an open label, randomized, crossover design. Results ABT-288 safety, tolerability and pharmacokinetics were comparable in young and elderly subjects. Single doses up to 40 mg and multiple doses up to 3 mg once-daily were generally safe and well tolerated. The most frequently reported adverse events were hot flush, headache, abnormal dreams, insomnia, nausea and dizziness. ABT-288 exposure (AUC) was dose-proportional over the evaluated dose ranges. The mean elimination half-life ranged from 40 to 61 h across dose groups. Steady state was achieved by day 10 of once-daily dosing with 3.4- to 4.2-fold accumulation. Food did not have a clinically meaningful effect on ABT-288 exposure. Conclusions Based on the above results, 1 and 3 mg once-daily doses of ABT-288 were advanced to phase 2 evaluation in Alzheimer's patients. PMID:23016924

Safety, tolerability and pharmacokinetics of the histamine H3 receptor antagonist, ABT-288, in healthy young adults and elderly volunteers.

PubMed

Othman, Ahmed A; Haig, George; Florian, Hana; Locke, Charles; Zhang, Jun; Dutta, Sandeep

2013-05-01

The objective of this work was to characterize the safety, tolerability and pharmacokinetics of ABT-288, a highly selective histamine H3 receptor antagonist, in healthy young adults and elderly subjects following single and multiple dosing in a phase 1 setting. Single doses (0.1, 0.3, 1, 3, 10, 20 and 40 mg ABT-288) and multiple doses (0.5, 1.5, 3 and 6 mg ABT-288 once-daily for 14 days) were evaluated in young adults and multiple doses (0.5, 1.5, 3 and 5 mg ABT-288 once-daily for 12 days) were evaluated in elderly subjects using randomized, double-blind, placebo-controlled, dose-escalating study designs. The effect of food on ABT-288 pharmacokinetics (5 mg single dose) was evaluated using an open label, randomized, crossover design. ABT-288 safety, tolerability and pharmacokinetics were comparable in young and elderly subjects. Single doses up to 40 mg and multiple doses up to 3 mg once-daily were generally safe and well tolerated. The most frequently reported adverse events were hot flush, headache, abnormal dreams, insomnia, nausea and dizziness. ABT-288 exposure (AUC) was dose-proportional over the evaluated dose ranges. The mean elimination half-life ranged from 40 to 61 h across dose groups. Steady state was achieved by day 10 of once-daily dosing with 3.4- to 4.2-fold accumulation. Food did not have a clinically meaningful effect on ABT-288 exposure. Based on the above results, 1 and 3 mg once-daily doses of ABT-288 were advanced to phase 2 evaluation in Alzheimer's patients. © 2012 Abbott Laboratories. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

Increased prandial insulin secretion after administration of a single preprandial oral dose of repaglinide in patients with type 2 diabetes.

PubMed

Owens, D R; Luzio, S D; Ismail, I; Bayer, T

2000-04-01

To examine the dose-related pharmacodynamics and pharmacokinetics of a single preprandial oral dose of repaglinide in patients with type 2 diabetes. A total of 16 Caucasian men with type 2 diabetes participated in two placebo-controlled double-blind randomized cross-over studies. Patients were randomized to receive a single oral dose of repaglinide (0.5, 1.0, and 2.0 mg in study 1 and 4.0 mg in study 2) or placebo (both studies) administered 15 min before the first of two sequential identical standard meals (breakfast and lunch) that were 4 h apart. During each of the study days, which were 1 week apart, blood samples were taken at frequent intervals over a period of approximately 8 h for measurement of plasma glucose, insulin, C-peptide, and repaglinide concentrations. During the first meal period (0-240 min), administration of repaglinide reduced significantly the area under the curve (AUC) for glucose concentration and significantly increased the AUC for insulin levels, C-peptide levels, and the insulin secretion rate. These results, compared with those of administering placebo, were dose dependent and log linear. The effect of repaglinide administration on insulin secretion was most pronounced in the early prandial period. Within 30 min, it caused a relative increase in insulin secretion of up to 150%. During the second meal period (240-480 min), there was no difference between repaglinide and placebo administration in the AUC for glucose concentration, C-peptide concentration, and the estimated insulin secretion rate. A single dose of repaglinide (0.5-4.0 mg) before breakfast improves insulin secretion and reduces prandial hyperglycemia dose-dependently Administration of repaglinide had no effect on insulin secretion with the second meal, which was consumed 4 h after breakfast.

The Impact of Virtual Reality Distraction on Pain and Anxiety during Dental Treatment in 4-6 Year-Old Children: a Randomized Controlled Clinical Trial.

PubMed

Asl Aminabadi, Naser; Erfanparast, Leila; Sohrabi, Azin; Ghertasi Oskouei, Sina; Naghili, Armaghan

2012-01-01

Dental practitioners have numerous methods to control anxiety and pain in children, and distracting the child appears to be the most common technique used for behavior management during dental procedures. The aim of the present study was to evaluate the influence of using virtual reality eyeglasses on severity of pain and anxiety during dental procedures in pediatric patients. This study included 120 healthy children aged 4-6 years. Children with no previous anxiety disorder were randomly divided into two groups, each consisting of 60 children. The study consisted of 3 consecutive treatment sessions. During the first visit fluoride therapy was carried out in both groups. In the next sessions, the groups received restorative treatment with and without virtual reality eyeglasses in a randomized single-blind-controlled crossover fashion. Then at the end of each session the subjects' pain severity was assessed using Wong Baker FACES Pain Rating Scale and state anxiety was measured by Faces version of the Modified Child Dental Anxiety Scale [MCDAS (f)]. There was a significant decrease in pain perception (P < 0.001) and state anxiety scores (P < 0.001) with the use of virtual reality eyeglasses during dental treatment. Results of this study showed that virtual reality eyeglasses can successfully decrease pain perception and state anxiety during dental treatment. 201103126036N1.

Comparison of urodynamic volume measurements using room and body temperature saline: a double-blinded randomized crossover study design.

PubMed

Gehrich, Alan Paul; Hill, Micah J; McWilliams, Grant D E; Larsen, Wilma; McCartin, Tamarin

2012-01-01

Urodynamic studies, routinely performed in women with lower urinary tract symptoms, have a large impact on clinical decision making. Unfortunately, these studies are insensitive in reproducing idiopathic detrusor overactivity (IDO). We set out to examine whether serial cystometry with different distending fluid temperatures could better reproduce symptoms. Eighty-six women were enrolled in a double-blinded, randomized, crossover study. Two cystometries were performed in series, starting with either body temperature fluid (BTF) or room temperature fluid (RTF) and then repeating cystometry with the other temperature fluid. Primary outcomes included first sensation, first urge, and maximum cystometric capacity. Secondary outcomes included subjective sensation of bladder discomfort and the incidence of IDO. In aggregate, the temperature of the fluid did not affect volumes of bladder sensation. There were no differences in self-reported bladder irritation or IDO between the different temperature fluids. There was a significant carryover effect with BTF. BTF administered first reached sensory thresholds at lower volumes than when it was administered second after RTF. Room temperature fluid cystometry showed no statistical difference in volume between first fill and second fill. Idiopathic detrusor overactivity contractions were seen in 9% of studies and were not affected by period or temperature. These data suggest that BTF and RTF independently do not affect bladder sensory thresholds. The periodicity in combination with varying fluid temperature is of greater impact. This study documents that changes in temperature of the distending fluid from BTF to RTF or vice versa likely do not provoke IDO contractions.

A double-blind, randomized, placebo/active controlled crossover evaluation of the efficacy and safety of Ritalin ® LA in children with attention-deficit/hyperactivity disorder in a laboratory classroom setting.

PubMed

Schulz, Eberhard; Fleischhaker, Christian; Hennighausen, Klaus; Heiser, Philip; Oehler, Klaus-Uwe; Linder, Martin; Haessler, Frank; Huss, Michael; Warnke, Andreas; Schmidt, Martin; Schulte-Markworth, Michael; Sieder, Christian; Klatt, Jan; Tracik, Ferenc

2010-10-01

The primary objective of this study was to demonstrate efficacy of Ritalin(®) LA 20 mg by showing superiority to placebo and noninferiority to Medikinet(®) Retard in a laboratory classroom setting. Secondary objectives included safety/tolerability and further efficacy parameters. A total of 147 children with attention-deficit/hyperactivity disorder (ADHD) diagnosed by the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS) and aged 6-14 (81% males) and known to be methylphenidate (MPH) responders were enrolled in this multicenter, double-blind, randomized, placebo/active-controlled, three-period (7 days each) crossover study. The Swanson, Kotlin, Agler, M-Flynn, and Pelham (SKAMP) scale was used for efficacy ratings. The mean of SKAMP Combined ratings performed at 10:30 a.m., at 12:00 a.m., and at 1:30 p.m. was defined as the primary parameter. In all, 146 patients completed all treatment periods. Intensity and frequency of adverse events were comparable between the two formulations. Ritalin(®) LA demonstrated superiority compared to placebo (p<0.0001). The observed difference in the SKAMP scores between Ritalin(®) LA and Medikinet(®) Retard between the hours 1.5 until 4.5 did not exceed the noninferiority margin (p=0.0003); therefore, the difference is regarded as not clinically relevant. Similar results were obtained for the secondary efficacy variables. Ritalin(®) LA is an efficacious, well-tolerated treatment option for children aged 6-14 with ADHD.

A randomized, double-blind, placebo-controlled, crossover study to evaluate the subjective abuse potential and cognitive effects of nabiximols oromucosal spray in subjects with a history of recreational cannabis use.

PubMed

Schoedel, Kerri Alexandra; Chen, Nancy; Hilliard, Annie; White, Linda; Stott, Colin; Russo, Ethan; Wright, Stephen; Guy, Geoffrey; Romach, Myroslava K; Sellers, Edward M

2011-04-01

This study aimed to evaluate the abuse potential and cognitive effects of nabiximols (Sativex, GW Pharma Ltd. Salisbury, UK), an oromucosal spray primarily containing delta‐9‐tetrahydrocannabinol (THC) and cannabidiol (CBD). This was a single‐dose, randomized, double‐blind, crossover study comparing nabiximols (4, 8, and 16 consecutive sprays: 10.8, 21.6, and 43.2 mg THC, respectively) with dronabinol 20 and 40 mg (synthetic THC: Marinol, Solvay Pharmaceuticals, Brussels, Belgium) and matching placebos in 23 recreational cannabis users. Subjective and cognitive/psychomotor measures were administered over 24 h post‐dose. Dronabinol was significantly different from placebo on abuse potential measures, thereby confirming study validity. Nabiximols 10.8 mg was not significantly different from placebo on primary measures but was different on some secondary measures. Nabiximols 21.6 mg was significantly greater than placebo on some primary/secondary measures, whereas nabiximols 43.2 mg showed significant effects on most measures. Nabiximols 10.8 mg was significantly lower than dronabinol doses on most measures ( p < 0.05). Dronabinol 20 mg effects were numerically higher than nabiximols 21.6 mg but were statistically significant only for some measures. Dronabinol 40 mg and nabiximols 43.2 mg were generally not statistically different. Both dronabinol and nabiximols had significant abuse potential compared with placebo at higher doses. Nabiximols showed similar or slightly less abuse potential compared with dronabinol. Therefore, the abuse potential of nabiximols should be no higher than that of dronabinol.

Psychomotor and subjective effects of bilastine, hydroxyzine, and cetirizine, in combination with alcohol: a randomized, double-blind, crossover, and positive-controlled and placebo-controlled Phase I clinical trials.

PubMed

García-Gea, Consuelo; Martínez, Joan; Ballester, Maria Rosa; Gich, Ignasi; Valiente, Román; Antonijoan, Rosa Maria

2014-03-01

The aim of this study was to compare the effects of concomitant administration of alcohol and bilastine versus alcohol alone on the central nervous system. Twenty-four healthy young volunteers of both sexes participated in a randomized, double-blind, double-dummy, crossover, and positive-controlled and placebo-controlled clinical trials. At 1-week intervals, subjects received six different treatments: (i) placebo; (ii) alcohol 0.8 g/kg alone (ALC); (iii) ALC in combination with: bilastine 20 mg (B20 + A); (iv) bilastine 80 mg (B80 + A); (v) cetirizine 10 mg (CET + A); and (vi) hydroxyzine 25 mg (HYD + A). Psychomotor performance tests (fine motor, finger tapping, nystagmus, critical flicker-fusion frequency, temporal estimation, 'd2' cancellation, and simple reaction time) and subjective self-reports (drunkenness, drowsiness, mental slowness, clumsiness, anger, attentiveness, competence, happiness, hostility, interest, and extroversion) were carried out at baseline and multiple points thereafter. All active treatments induced a significant psychomotor impairment. The greatest and most lasting impairment was observed with HYD + A followed by B80 + A and CET + A. In contrast, objective measures showed less impairment with B20 + A and ALC, both with a similar magnitude. Self-reports showed a subjective perception of performance impairment in all active treatments. Concomitant administration of bilastine (at therapeutic dose) and alcohol does not produce greater central nervous system depressant effects than ACL alone. Copyright © 2014 John Wiley & Sons, Ltd.

Evaluation of the effect of topical chamomile (Matricaria chamomilla L.) oleogel as pain relief in migraine without aura: a randomized, double-blind, placebo-controlled, crossover study.

PubMed

Zargaran, Arman; Borhani-Haghighi, Afshin; Salehi-Marzijarani, Mohammad; Faridi, Pouya; Daneshamouz, Saeid; Azadi, Amir; Sadeghpour, Hossein; Sakhteman, Amirhossein; Mohagheghzadeh, Abdolali

2018-05-28

Phytotherapy is a source of finding new remedies for migraine. Traditional chamomile oil (chamomile extraction in sesame oil) is a formulation in Persian medicine (PM) for pain relief in migraine. An oleogel preparation of reformulated traditional chamomile oil was prepared and then standardized based on chamazulene (as a marker in essential oil) and apigenin via gas chromatography (GC) and high-performance liquid chromatography (HPLC) methods, respectively. A crossover double-blind clinical trial was performed with 100 patients. Each patient took two tubes of drug and two tubes of placebo during the study. Visual analog scale (VAS) questionnaires were filled in by the patients and scores were given, ranging from 0 to 10 (based on the severity of pain) during 24 h. Other complications like nausea, vomiting, photophobia, and phonophobia were also monitored. There was 4.48 ± 0.01 μl/ml of chamazulene and 0.233 mg/g of apigenin in the preparation (by correcting the amount with extraction ratio). Thirty-eight patients in the drug-placebo and 34 patients in the placebo-drug groups (a total number of 72 patients as per protocol) completed the process in the randomized controlled trial (RCT). Adapted results from the questionnaires showed that pain, nausea, vomiting, photophobia, and phonophobia significantly (p < 0.001) decreased by using chamomile oleogel on the patients after 30 min. Results supported the efficacy of chamomile oleogel as a pain relief in migraine without aura.

Short-term effect of strontium- and zinc-containing toothpastes and mouthrinses on volatile sulphur compounds in morning breath: a randomized, double-blind, cross-over clinical study.

PubMed

Soares, Léo G; Jonski, Grazyna; Tinoco, Eduardo M B; Young, Alix

2015-04-01

Zinc (Zn) reduces the formation of volatile sulphur compounds (VSCs) associated with oral malodour. Although strontium (Sr) is included in some products for reducing dental hypersensitivity, it may also have anti-halitosis properties. This randomized, double-blind, cross-over clinical study compared the anti-VSC effect of brushing with commercial toothpastes and rinses containing Zn and Sr. The volunteers (n = 30) either brushed/rinsed with/without tongue brushing using Zn-containing toothpaste/rinse, Sr-containing toothpaste/rinse, or placebo (control). Volatile sulphur compounds [hydrogen sulphide (H2 S) and methyl mercaptan (CH3 SH)] were measured, in morning breath, using gas chromatography. The anti-VSC effects of the test toothpastes and test rinses were significantly better than the anti-VSC effects of the respective controls. Toothbrushing with test toothpastes gave median reductions, compared with the control, of 70% for H2 S and 55-57% for CH3 SH. Rinsing with the Sr- and Zn-containing solutions had the same anti-VSC effect as toothbrushing and tooth- and tongue brushing with the Sr- and Zn-containing toothpastes. Zinc-containing rinse resulted in a significantly higher median salivary level of Zn compared with brushing with Zn-containing toothpaste, although this effect did not correlate with the anti-VSC effect. It can be concluded that the Sr- and Zn-containing toothpastes and the Zn- and Sr-containing rinses, when used in the evening, are equally effective in reducing morning-breath VSCs the following day. © 2015 Eur J Oral Sci.

Turo (qi dance) Program for Parkinson's Disease Patients: Randomized, Assessor Blind, Waiting-List Control, Partial Crossover Study.

PubMed

Lee, Hwa-Jin; Kim, Song-Yi; Chae, Younbyoung; Kim, Mi-Young; Yin, Changshik; Jung, Woo-Sang; Cho, Ki-Ho; Kim, Seung-Nam; Park, Hi-Joon; Lee, Hyejung

2018-03-01

Qigong, Tai-chi and dancing have all been proven effective for Parkinson's disease (PD); however, no study has yet assessed the efficacy of Turo, a hybrid qigong dancing program developed to relieve symptoms in PD patients. To determine whether Turo may provide benefit in addressing the symptoms of PD patients. Randomized, assessor blind, waiting-list control, partial crossover study. Kyung Hee University Korean Medicine Hospital, Seoul, Republic of Korea. A total of 32 PD patients (mean age 65.7 ± 6.8). Participants were assigned to the Turo group or the waiting-list control group. The Turo group participated in an 8-week Turo training program (60-minute sessions twice a week). The waiting-list control group received no additional treatment during the same period; then underwent the same 8-week Turo training. The primary outcome was a score on the Unified Parkinson's Disease Rating Scale (UPDRS), and the secondary outcomes included the perceived health status assessed using the Parkinson's disease Quality of Life questionnaire (PDQL), balance function as assessed by the Berg Balance Scale (BBS) and the results of the Beck Depression Inventory (BDI). The Turo group showed statistically significant improvements in the UPDRS (P < 0.01) and PDQL (P < 0.05) as compared to the control group. The changes in BBS scores displayed a tendency toward improvement, but was not statistically significant (P = 0.051). These findings suggest that Turo PD training might improve the symptoms of PD patients. Copyright © 2018. Published by Elsevier Inc.

Memantine augmentation in clozapine-refractory schizophrenia: a randomized, double-blind, placebo-controlled crossover study.

PubMed

Veerman, S R T; Schulte, P F J; Smith, J D; de Haan, L

2016-07-01

Dysfunction of neuroplasticity due to N-methyl-d-aspartate (NMDA) receptor hypofunction may be a causal factor for memory and executive dysfunctioning in schizophrenia. Deregulation of NMDA transmission in the prefrontal cortex may also explain negative and positive symptoms. Clozapine augmentation with memantine targets altered NMDA receptor-mediated neurotransmission in schizophrenia and showed substantial beneficial effects on several symptom domains in a small proof-of-concept study. We evaluate effects of memantine add-on treatment to clozapine for memory and executive function, and negative and positive symptoms in schizophrenia. Clozapine-treated patients with refractory schizophrenia were randomly assigned to 12 weeks of double-blind adjunctive treatment with memantine (n = 26) or placebo (n = 26). Crossover occurred after a 2-week placebo wash-out period. Primary endpoints were change from baseline to 12 weeks treatment and 14 weeks to 26 weeks treatment on memory and executive function using the Cambridge Neuropsychological Test Automated Battery (CANTAB), Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impression Severity Scale (CGI-S). Side effects were assessed using the Liverpool University Neuroleptic Side-Effect Rating Scale. When compared with placebo, memantine improved a composite memory score comprising verbal recognition memory and paired associates learning task scores on the CANTAB (effect size = 0.30) and PANSS negative subscale score (effect size = 0.29). Side effects were mild and transient. In patients with clozapine-treated refractory schizophrenia, memantine addition significantly improved verbal and visual memory and negative symptoms without serious adverse effects. These results justify further investigations on long-term memantine augmentation to clozapine in treatment-resistant schizophrenia.

Effect of Persian Medicine Remedy on Chemotherapy Induced Nausea and Vomiting in Breast Cancer: A Double Blind, Randomized, Crossover Clinical Trial

PubMed Central

Nazari, Mohammad; Taghizadeh, Ali; Bazzaz, Mojtaba Mousavi; Rakhshandeh, Hassan; Shokri, Sadegh

2017-01-01

Background Chemotherapy induced nausea and vomiting (CINV) is a side effect, and has negative effect on quality of life and continuation of chemotherapy. Despite new regimen and drugs, the problems still remain and standard guidelines, effective treatment and supportive care for refractory CINV are still not yet established. Persian medicine, the old Iranian medical school, offer Persumac (prepared from Rhus Coriaria and Bunium Persicum Boiss). Objective The specific objectives were to assess the effect of Persumac on the number and severity of nausea and vomiting in refractory CINV in acute and delayed phase. Methods This randomized, double blind, crossover clinical trial study was carried out on 93 patients with breast cancer and refractory CINV, who received outpatient high emetogenic chemotherapy in Imam Reza hospital, Mashhad, Iran from October 2015 to May 2016. The study has three stages: in stage I patients received a questionaire and completed it after chemotherapy. In stage II they were randomly divided into intervention group with Persumac and control group with placebo (lactose were used). In stage III, wash out and crossover was conducted. Both groups in all stages received standard antiemetic therapy for CINV. The following were set as the inclusion criteria of the study: female, Age ≥18 years, clinical diagnosis of breast cancer, history of refractory CINV, normal blood tests and at least three courses of chemotherapy remaining. Exclusion criteria of this study were: Total or upper abdominal radiation therapy along with chemotherapy, drugs/therapy for nausea and vomiting not prescribed in this study, hypersensitivity to Sumac or Bunium Persicum, use of sumac and Bunium Persicum in seven days prior to the intervention, clinical diagnosis of digestion disorders, non-chemotherapy induced nausea and vomiting, milk allergy, loss of two consecutive or three intermittent doses of Persumac or placebo. Outcomes were gathered by Persian questionnaire. Number and severity of nausea and vomiting was measured with a self-reporting tool; visual analog scale. Results Demographic data and other characters in both groups have no significant diffrence. Eighty of 93 eligible patients in stage I completed the study and in stage II, eleven declined participation for stage III (crossover). P value of carry over, period and treatment effects demonstrated that they had not affected the results before and after crossover. The mean severity of nausea in acute phase was in stage I: 4.83 ± 1.40, stage II: 4.54 ± 2.0 and stage III: 4.15 ± 0.92 in sequence AB (first Persumac and then placebo in crossover), and in sequence BA (first placebo and then Persumac in crossover) was respectively 4.83 ± 1.40, 4.54 ± 2.0, 4.15 ± 0.92 with p value of carry over effect: 0.03 and period effect: 0.22. Except for severity of nausea in acute phase, the mean number and severity of nausea and vomiting scores significantly decreased in acute and delayed phase of CINV. Conclusion Persumac may control the refractory CINV. The implicable and clinical importance of this research is that another option exists for refractory CINV. Higher doses, different cancers, patients with more various features, and more complete methodology and tools can provide appropriate designs for new research on this topic. Trial registration This trial was registered at the Clinical Trials.gov ID: NCT02787707. Funding This study is part of a Ph.D. thesis and under grant; No: 930735 of Research Chancellery of MUMS. PMID:28243404

Randomized controlled trial of nettle sting for treatment of base-of-thumb pain.

PubMed Central

Randall, C; Randall, H; Dobbs, F; Hutton, C; Sanders, H

2000-01-01

There are numerous published references to use of nettle sting for arthritis pain but no randomized controlled trials have been reported. We conducted a randomized controlled double-blind crossover study in 27 patients with osteoarthritic pain at the base of the thumb or index finger. Patients applied stinging nettle leaf (Urtica dioica) daily for one week to the painful area. The effect of this treatment was compared with that of placebo, white deadnettle leaf (Lamium album), for one week after a five-week washout period. Observations of pain and disability were recorded for the twelve weeks of the study. After one week's treatment with nettle sting, score reductions on both visual analogue scale (pain) and health assessment questionnaire (disability) were significantly greater than with placebo (P = 0.026 and P = 0.0027). PMID:10911825

Does the nature of the definitive impression material influence the outcome of (mandibular) complete dentures?

PubMed

McCord, J Fraser; McNally, Lisa M; Smith, Philip W; Grey, Nicholas J A

2005-09-01

The effects of impression materials on the outcome of complete dentures are poorly understood. This double-blind cross-over randomized controlled trial investigated eleven adult edentulous patients. Each received a maxillary denture and three mandibular dentures (which differed only in the three materials used to record the definitive impressions). The three mandibular dentures were given in a random order. Patients' opinions of each denture were recorded using a Linear Analogue Scale. There was a statistically-significant difference between the outcome of the dentures constructed when zinc-oxide eugenol was used, this material being least favoured (p < 0.001). It would therefore appear that care should be exercised when selecting impression materials when constructing mandibular complete dentures.

Role of dominant versus non-dominant hand position during uninterrupted chest compression CPR by novice rescuers: a randomized double-blind crossover study.

PubMed

Nikandish, Reza; Shahbazi, Sharbanoo; Golabi, Sedigheh; Beygi, Najimeh

2008-02-01

Previous research has suggested improved quality of chest compressions when the dominant hand was in contact with the sternum. However, the study was in health care professionals and during conventional chest compression-ventilation CPR. The aim of this study was to test the hypothesis, in null form, that the quality of external chest compressions (ECC) in novice rescuers during 5min of uninterrupted chest compression CPR (UCC-CPR) is independent of the hand in contact with the sternum. Confirmation of the hypothesis would allow the use of either hand by the novice rescuers during UCC-CPR. Fifty-nine first year public heath students participated in this randomised double-blind crossover study. After completion of a standard adult BLS course, they performed single rescuer adult UCC-CPR for 5 min on a recording Resusci Anne. One week later they changed the hand of contact with the sternum while performing ECC. The quality of ECC was recorded by the skill meter for the dominant and non-dominant hand during 5 min ECC. The total number of correct chest compressions in the dominant hand group (DH), mean 183+/-152, was not statistically different from the non-dominant hand group (NH), mean 152+/-135 (P=0.09). The number of ECC with inadequate depth in the DH group, mean 197+/-174 and NH group, mean 196+/-173 were comparable (P=0.1). The incidence of ECC exceeding the recommended depth in the DH group, mean 51+/-110 and NH group, mean 32+/-75 were comparable (P=0.1). Although there is a trend to increased incidence of correct chest compressions with positioning the dominant hand in contact with the sternum, it does not reach statistical significance during UCC-CPR by the novice rescuers for 5 min.

Interstage Outcomes in Infants With Single Ventricle Heart Disease Comparing Home Monitoring Technology to Three-Ring Binder Documentation: A Randomized Crossover Study.

PubMed

Bingler, Michael; Erickson, Lori A; Reid, Kimberly J; Lee, Brian; O'Brien, James; Apperson, Johnathan; Goggin, Kathy; Shirali, Girish

2018-05-01

Interstage outcomes for infants with single ventricle remain suboptimal. We have previously described a tablet PC-based platform Cardiac High Acuity Monitoring Program (CHAMP) for remote monitoring which provides immediate access to data, videos, and instant alerts to our single ventricle care team. This study compares traditional three-ring binder monitoring (Binder) to CHAMP using a randomized crossover design to evaluate mortality, resource utilization, and caregiver experience. At discharge, all single ventricle infants were monitored using Binder and randomized to receive CHAMP at either one or two months postdischarge. One month after randomization, caregivers could choose either Binder or CHAMP for the remainder of the interstage period. Caregivers experience was recorded using surveys. Enrollment included 31 single ventricle infants from May 2014 to June 2015. There was no interstage mortality over 4,911 total interstage days (median: 144/patient). Of 73 readmissions, 45 were unplanned. Of the initial 23 unplanned readmissions, 13 were found to have been based on data obtained exclusively through CHAMP (as instant alerts or based on data review) rather than caregiver concerns. Due to concerns regarding patient safety, additional enrollment was stopped. The CHAMP use was associated with significantly fewer unplanned intensive care unit days/100 interstage days, shorter delays in care, lower resource utilization at readmissions, and lower incidence of interstage growth failure and was preferred by a majority of caregivers. These findings suggest that CHAMP may offer benefits over Binder (improved interstage outcomes, delays in care, and caregiver experience). These findings should be tested across multiple centers in larger populations.

Efficacy of naproxen with or without esomeprazole for pain and inflammation in patients after bilateral third molar extractions: A double blinded crossover study.

PubMed

Weckwerth, G-M; Simoneti, L-F; Zupelari-Gonçalves, P; Calvo, A-M; Brozoski, D-T; Dionísio, T-J; Torres, E-A; Lauris, J-R-P; Faria, F-A-C; Santos, C-F

2017-01-01

Using a double-blinded randomized crossover design, this study aimed to evaluate acute postoperative pain management, swelling and trismus in 46 volunteers undergoing extractions of the two lower third molars, in similar positions, at two different appointments who consumed a tablet of either NE (naproxen 500 mg + esomepraz ole 20 mg) or only naproxen (500 mg) every 12 hours for 4 days. Parameters were analyzed: self-reported pain intensity using a visual analog scale (VAS) pre- and postoperative mouth opening; incidence, type and severity of adverse reactions; total quantity consumed of rescue medication; and pre- and postoperative swelling. Female volunteers reported significantly more postoperative pain at 1, 1.5, 2, 3 and 4hrs after surgery while also taking their first rescue medication at a time significantly earlier when consuming NE when compared to naproxen (3.7hrs and 6.7hrs). Conversely, no differences were found between each drug group in males. In conclusion, throughout the entire study, pain was mild after using either drug in both men and women with pain scores on average well below 40mm (VAS), although in women naproxen improved acute postoperative pain management when compared to NE.

Phase I clinical studies of the advanced glycation end-product (AGE)-breaker TRC4186: safety, tolerability and pharmacokinetics in healthy subjects.

PubMed

Chandra, Kumar P; Shiwalkar, Ajay; Kotecha, Jignesh; Thakkar, Purav; Srivastava, Ambrish; Chauthaiwale, Vijay; Sharma, Sanjay K; Cross, Maurice R; Dutt, Chaitanya

2009-01-01

Advanced glycation end-products (AGEs) have been implicated in the pathogenesis of diabetic complications through a variety of mechanisms including endothelial dysfunction and structural abnormalities in the vasculature and myocardium. Reducing the AGEs burden and their ensuing pro-inflammatory, pro-oxidative and pro-coagulant effect with associated dysfunctional proteins in various target tissues may retard the progression of and even reverse diabetic macro- and microvascular complications. Pyridinium, 3-[[2-(methylsulfonyl) hydrazino] carbonyl]-1-[2-oxo-2-2-thienyl) ethyl]-chloride (TRC4186) has demonstrated AGE-breaking activities in in vitro experiments and improvement in the endothelial and myocardial function in animal models of diabetes mellitus with reduction of AGEs accumulation in tissues over time. The safety of TRC4186 has been established in in vitro and in vivo preclinical studies. Thus, this drug is being developed for the treatment of complications associated with diabetes. This investigation set out to evaluate the safety, tolerability and pharmacokinetics of TRC4186 in healthy human subjects after single and multiple ascending doses, fixed doses in elderly male and female subjects, and with food and different formulations of the compound. Four studies were conducted during phase I clinical development of TRC4186. These were: (i) a randomized, double-blind, placebo-controlled, single-dose, dose-ascending study in healthy male subjects with doses of TRC4186 ranging from 250 to 2500 mg administered as an oral solution (total six doses); (ii) a randomized, double-blind, placebo-controlled, multiple-dose, dose-ascending study in healthy male subjects with three doses of TRC4186 ranging from 500 to 2000 mg twice daily for 6 days with a final single dose on day 7; (iii) a randomized, open-label, three-way crossover study to assess the effect of food (fasted vs fed) and formulation (solution vs tablet) with TRC4186 500 mg; (iv) a randomized, double-blind, placebo-controlled, single-dose, dose-ascending study in elderly male and female subjects at a dose of TRC4186 500 mg followed by TRC4186 1000 mg after a 7-day washout period. The safety and tolerability of TRC4186 were assessed by considering adverse events (AEs), ECG findings, vital signs and laboratory investigation results. TRC4186 was rapidly absorbed, with maximum plasma concentrations (C(max)) attained within 1-4 hours. C(max) and area under the plasma concentration-time curve (AUC) were dose proportional over the range 250-2500 mg for a single dose and 500-2000 mg for multiple doses with twice-daily administration. Steady-state conditions were attained within 6 days at different dose levels. C(max) and AUC were not affected by age, sex, race or type of formulation. The tablet formulation of TRC4186 was bioequivalent with the solution form of the drug under fasting conditions and systemic availability of the tablet formulation was reduced by 40% when administered under fed conditions. Terminal elimination and renal clearance in the elderly male (age 69.1 +/- 6.0 years) were not significantly different compared with younger subjects (age 31 +/- 8.6 years). TRC4186 was safe and well tolerated when administered orally with either a single or multiple doses across the different ages, sexes, races and formulations studied. A dose-proportional increase in plasma TRC4186 concentration was seen, with steady state being achieved within 6 days.

Blind quantum computing with weak coherent pulses.

PubMed

Dunjko, Vedran; Kashefi, Elham; Leverrier, Anthony

2012-05-18

The universal blind quantum computation (UBQC) protocol [A. Broadbent, J. Fitzsimons, and E. Kashefi, in Proceedings of the 50th Annual IEEE Symposiumon Foundations of Computer Science (IEEE Computer Society, Los Alamitos, CA, USA, 2009), pp. 517-526.] allows a client to perform quantum computation on a remote server. In an ideal setting, perfect privacy is guaranteed if the client is capable of producing specific, randomly chosen single qubit states. While from a theoretical point of view, this may constitute the lowest possible quantum requirement, from a pragmatic point of view, generation of such states to be sent along long distances can never be achieved perfectly. We introduce the concept of ϵ blindness for UBQC, in analogy to the concept of ϵ security developed for other cryptographic protocols, allowing us to characterize the robustness and security properties of the protocol under possible imperfections. We also present a remote blind single qubit preparation protocol with weak coherent pulses for the client to prepare, in a delegated fashion, quantum states arbitrarily close to perfect random single qubit states. This allows us to efficiently achieve ϵ-blind UBQC for any ϵ>0, even if the channel between the client and the server is arbitrarily lossy.

Blind Quantum Computing with Weak Coherent Pulses

NASA Astrophysics Data System (ADS)

Dunjko, Vedran; Kashefi, Elham; Leverrier, Anthony

2012-05-01

The universal blind quantum computation (UBQC) protocol [A. Broadbent, J. Fitzsimons, and E. Kashefi, in Proceedings of the 50th Annual IEEE Symposiumon Foundations of Computer Science (IEEE Computer Society, Los Alamitos, CA, USA, 2009), pp. 517-526.] allows a client to perform quantum computation on a remote server. In an ideal setting, perfect privacy is guaranteed if the client is capable of producing specific, randomly chosen single qubit states. While from a theoretical point of view, this may constitute the lowest possible quantum requirement, from a pragmatic point of view, generation of such states to be sent along long distances can never be achieved perfectly. We introduce the concept of ɛ blindness for UBQC, in analogy to the concept of ɛ security developed for other cryptographic protocols, allowing us to characterize the robustness and security properties of the protocol under possible imperfections. We also present a remote blind single qubit preparation protocol with weak coherent pulses for the client to prepare, in a delegated fashion, quantum states arbitrarily close to perfect random single qubit states. This allows us to efficiently achieve ɛ-blind UBQC for any ɛ>0, even if the channel between the client and the server is arbitrarily lossy.

Headache and mechanical sensitization of human pericranial muscles after repeated intake of monosodium glutamate (MSG)

PubMed Central

2013-01-01

Background A single intake of monosodium glutamate (MSG) may cause headache and increased muscle sensitivity. We conducted a double-blinded, placebo-controlled, crossover study to examine the effect of repeated MSG intake on spontaneous pain, mechanical sensitivity of masticatory muscles, side effects, and blood pressure. Methods Fourteen healthy subjects participated in 5 daily sessions for one week of MSG intake (150 mg/kg) or placebo (24 mg/kg NaCl) (randomized, double-blinded). Spontaneous pain, pressure pain thresholds and tolerance levels for the masseter and temporalis muscles, side effects, and blood pressure were evaluated before and 15, 30, and 50 min after MSG intake. Whole saliva samples were taken before and 30 min after MSG intake to assess glutamate concentrations. Results Headache occurred in 8/14 subjects during MSG and 2/14 during placebo (P = 0.041). Salivary glutamate concentrations on Day 5 were elevated significantly (P < 0.05). Pressure pain thresholds in masseter muscle were reduced by MSG on Day 2 and 5 (P < 0.05). Blood pressure was significantly elevated after MSG (P < 0.040). Conclusion In conclusion, MSG induced mechanical sensitization in masseter muscle and adverse effects such as headache and short-lasting blood pressure elevation for which tolerance did not develop over 5 days of MSG intake. PMID:23565943

Nonclinical and clinical pharmacology evidence for cardiovascular safety of saxagliptin.

PubMed

Pollack, Pia S; Chadwick, Kristina D; Smith, David M; Billger, Martin; Hirshberg, Boaz; Iqbal, Nayyar; Boulton, David W

2017-09-13

In the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus (SAVOR) trial in patients with type 2 diabetes mellitus (T2D) at high risk of cardiovascular (CV) disease, saxagliptin did not increase the risk for major CV adverse events. However, there was an unexpected imbalance in events of hospitalization for heart failure (hHF), one of six components of the secondary CV composite endpoint, with a greater number of events observed with saxagliptin. Here, we examined findings from nonclinical safety and clinical pharmacology studies of saxagliptin with the aim of identifying any potential signals of myocardial injury. In vitro and in vivo (rat, dog, monkey) safety pharmacology and toxicology studies evaluating the potential effects of saxagliptin and its major active metabolite, 5-hydroxy saxagliptin, on the CV system are reviewed. In addition, results from saxagliptin clinical studies are discussed: one randomized, 2-period, double-blind, placebo-controlled single-ascending-dose study (up to 100 mg); one randomized, double-blind, placebo-controlled, sequential, multiple-ascending-high-dose study (up to 400 mg/day for 14 days); and one randomized, double-blind, 4-period, 4-treatment, cross-over thorough QTc study (up to 40 mg/day for 4 days) in healthy volunteers; as well as one randomized, placebo-controlled, sequential multiple-ascending-dose study in patients with T2D (up to 50 mg/day for 14 days). Neither saxagliptin nor 5-hydroxy saxagliptin affected ligand binding to receptors and ion channels (e.g. potassium channels) or action potential duration in in vitro studies. In animal toxicology studies, no changes in the cardiac conduction system, blood pressure, heart rate, contractility, heart weight, or heart histopathology were observed. In healthy participants and patients with T2D, there were no findings suggestive of myocyte injury or fluid overload. Serum chemistry abnormalities indicative of cardiac injury, nonspecific muscle damage, or fluid homeostasis changes were infrequent and balanced across treatment groups. There were no QTc changes associated with saxagliptin. No treatment-emergent adverse events suggestive of heart failure or myocardial damage were reported. The saxagliptin nonclinical and clinical pharmacology programs did not identify evidence of myocardial injury and/or CV harm that may have predicted or may explain the unexpected imbalance in the rate of hHF observed in SAVOR.

A single dose comparison of a combination of fenoterol and ipratropium aerosols in bronchial asthma.

PubMed Central

Lawford, P.; Palmer, K. N.

1983-01-01

Nine patients with reversible obstructive airways disease were studied to compare the bronchodilator response to a combination of fenoterol and ipratropium aerosols with two dose levels of fenoterol alone. Using a double-blind, cross-over, single dose regime, 200 micrograms fenoterol hydrobromide and 80 micrograms ipratropium bromide was compared to 400 micrograms fenoterol + placebo, and to 200 micrograms fenoterol + placebo. There was no significant difference between the combination and either dose of fenoterol in terms of peak or duration of response as determined by absolute or percent change in forced expiratory volume in one second, or forced vital capacity, over baseline. PMID:6223289

Neuronal effects of nicotine during auditory selective attention.

PubMed

Smucny, Jason; Olincy, Ann; Eichman, Lindsay S; Tregellas, Jason R

2015-06-01

Although the attention-enhancing effects of nicotine have been behaviorally and neurophysiologically well-documented, its localized functional effects during selective attention are poorly understood. In this study, we examined the neuronal effects of nicotine during auditory selective attention in healthy human nonsmokers. We hypothesized to observe significant effects of nicotine in attention-associated brain areas, driven by nicotine-induced increases in activity as a function of increasing task demands. A single-blind, prospective, randomized crossover design was used to examine neuronal response associated with a go/no-go task after 7 mg nicotine or placebo patch administration in 20 individuals who underwent functional magnetic resonance imaging at 3T. The task design included two levels of difficulty (ordered vs. random stimuli) and two levels of auditory distraction (silence vs. noise). Significant treatment × difficulty × distraction interaction effects on neuronal response were observed in the hippocampus, ventral parietal cortex, and anterior cingulate. In contrast to our hypothesis, U and inverted U-shaped dependencies were observed between the effects of nicotine on response and task demands, depending on the brain area. These results suggest that nicotine may differentially affect neuronal response depending on task conditions. These results have important theoretical implications for understanding how cholinergic tone may influence the neurobiology of selective attention.

The impact of blackcurrant juice on attention, mood and brain wave spectral activity in young healthy volunteers.

PubMed

Watson, A W; Okello, E J; Brooker, H J; Lester, S; McDougall, G J; Wesnes, K A

2018-01-17

There is a growing body of evidence from randomized controlled trials which indicates that consumption of berries has a positive effect upon the cognitive function of healthy adults. It has been recommended that studies combining cognitive and physiological measures be undertaken in order to strengthen the evidence base for the putative effects of flavonoid consumption on cognitive outcomes. This pilot study utilized a randomized, double-blind and placebo controlled crossover design to assess the influence of the acute administration of anthocyanin-rich blackcurrant juice, standardized at 500 mg of polyphenols, on mood and attention. Additionally, this trial used electroencephalography (EEG) to assess if any changes in cognitive performance are associated with changes in localized prefrontal cortex neuronal activity in nine healthy young adults. Outcomes from the pilot EEG data highlight an anxiolytic effect of the consumption of a single serve blackcurrant juice, as indexed by a suppression of α spectral power, and an increase in the slow wave δ and θ spectral powers. There was also an indication of greater alertness and lower fatigue, as indexed by an increase in β power and suppression of α spectral power. Outcomes from the CogTrack™ system indicated a small acute increase in reaction times during the digit vigilance task.

Effect of an essential oil-containing mouth rinse on VSC-producing bacteria on the tongue.

PubMed

Thaweboon, Sroisiri; Thaweboon, Boonyanit

2011-03-01

The objective of the present study was to investigate the inhibitory effect of a commercially available essential oil-containing mouth rinse 12 hours after a single rinse and two weeks of twice daily rinsing, on volatile sulphur compounds (VSC) producing bacteria on the tongue. The study was a randomized, double-blind, controlled crossover design. Thirty-six healthy subjects, aged 20-48 years, volunteered to participate in the study. Subjects were randomly assigned to rinse twice daily with either an essential oil-containing mouth rinse (Cool Mint Listerine Antiseptic) or a negative control rinse. Bacteria samples were taken from the dorsum of the tongue at baseline, after the first rinse and two weeks later. They were plated on OOPS medium to enumerate the VSC-producing bacteria. Intergroup comparisons of log10 transformed colony-forming units of the samples were made using analysis of covariance. Each comparison was performed at a 5% significance level. The mean VSC-producing bacteria in subjects using the essential oil mouth rinse were significantly lower than those using the control rinse twice daily. In healthy subjects, rinsing with an essential oil-containing mouth rinse can have a significant effect on VSC-producing bacteria on the tongue and may be useful for controlling intrinsic oral malodor over prolonged periods.

Effects of 7.5% CO2 challenge in generalized anxiety disorder.

PubMed

Seddon, Kate; Morris, Kelly; Bailey, Jayne; Potokar, John; Rich, Ann; Wilson, Sue; Bettica, Paolo; Nutt, David J

2011-01-01

We have previously developed a putative model of generalized anxiety disorder in healthy volunteers using a 20-minute 7.5% carbon dioxide (CO(2)) inhalation challenge. The aim of this study was to validate the 7.5% CO(2) paradigm by assessing its effects in patients with generalized anxiety disorder in a test-retest design. Twelve medication-free generalized anxiety disorder patients attended our lab for two study days. On each study day placebo (compressed air) and 7.5% CO(2) mixture were randomly administered over 20 min, at least 30 min apart, in a single blind, randomized, placebo-controlled cross-over design. Subjective ratings, cardiovascular measures and cortisol levels were collected throughout. CO(2) challenge significantly increased ratings for anxiety and other subjective symptoms associated with generalized anxiety disorder, compared with air. It also significantly increased systolic blood pressure on day 2, indicating increased autonomic arousal. There was no change between the two test days in mean anxiety rating scores, and there also appeared to be a correlation for individual scores on a number of the subjective measures. In conclusion, 20 min of 7.5% CO(2) gas inhalation increases anxiety responses in patients with generalized anxiety disorder, and this is reliable over time.

Methylphenidate, cognition, and epilepsy: A double-blind, placebo-controlled, single-dose study.

PubMed

Adams, Jesse; Alipio-Jocson, Valerie; Inoyama, Katherine; Bartlett, Victoria; Sandhu, Saira; Oso, Jemima; Barry, John J; Loring, David W; Meador, Kimford

2017-01-31

To evaluate the potential efficacy of immediate-release methylphenidate (MPH) for treating cognitive deficits in epilepsy. This was a double-blind, randomized, single-dose, 3-period crossover study in patients with epilepsy and chronic cognitive complaints comparing the effects of placebo and MPH 10 and 20 mg given 1 week apart. Cognitive outcome was evaluated on the basis of an omnibus z score calculated from performance on the Conners Continuous Performance Test 3 (ability to discriminate between target and nontarget stimuli [d'] and hit reaction time standard deviation), Symbol-Digit Modalities Test, and Medical College of Georgia Paragraph Memory Test. Adverse events and seizure frequency were monitored. An open-label follow-up is reported elsewhere. Thirty-five adult patients with epilepsy participated, of whom 31 finished. Demographics included the following: mean age = 35.3 years (range 20-62 years), 13 men and 18 women, and baseline seizure frequency of 2.8 per month. Epilepsy types were focal (n = 24), generalized (n = 6), or unclassified (n = 1). Mean epilepsy duration was 12.5 years. A statistically significant performance benefit was present at both 10-mg (p = 0.030) and 20-mg (p = 0.034) MPH doses. No seizures were associated with either MPH dose. Adverse effects leading to withdrawal included cognitive "fogginess" (n = 1 on 20 mg), anxiety/agitation (n = 1 on 10 mg), and tachycardia (n = 1). One participant was lost to follow-up after one 20-mg dose without side effect. This single-dose study suggests that MPH may be effective in ameliorating some cognitive deficits in patients with epilepsy. Additional studies are required. NCT02178995. This study provides Class II evidence that single doses of MPH improve cognitive performance on some measures of attention and processing speed in patients with epilepsy and cognitive complaints. © 2016 American Academy of Neurology.

Design, conduct, and analyses of Breast International Group (BIG) 1-98: a randomized, double-blind, phase-III study comparing letrozole and tamoxifen as adjuvant endocrine therapy for postmenopausal women with receptor-positive, early breast cancer.

PubMed

Giobbie-Hurder, Anita; Price, Karen N; Gelber, Richard D

2009-06-01

Aromatase inhibitors provide superior disease control when compared with tamoxifen as adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer. To present the design, history, and analytic challenges of the Breast International Group (BIG) 1-98 trial: an international, multicenter, randomized, double-blind, phase-III study comparing the aromatase inhibitor letrozole with tamoxifen in this clinical setting. From 1998-2003, BIG 1-98 enrolled 8028 women to receive monotherapy with either tamoxifen or letrozole for 5 years, or sequential therapy of 2 years of one agent followed by 3 years of the other. Randomization to one of four treatment groups permitted two complementary analyses to be conducted several years apart. The first, reported in 2005, provided a head-to-head comparison of letrozole versus tamoxifen. Statistical power was increased by an enriched design, which included patients who were assigned sequential treatments until the time of the treatment switch. The second, reported in late 2008, used a conditional landmark approach to test the hypothesis that switching endocrine agents at approximately 2 years from randomization for patients who are disease-free is superior to continuing with the original agent. The 2005 analysis showed the superiority of letrozole compared with tamoxifen. The patients who were assigned tamoxifen alone were unblinded and offered the opportunity to switch to letrozole. Results from other trials increased the clinical relevance about whether or not to start treatment with letrozole or tamoxifen, and analysis plans were expanded to evaluate sequential versus single-agent strategies from randomization. Due to the unblinding of patients assigned tamoxifen alone, analysis of updated data will require ascertainment of the influence of selective crossover from tamoxifen to letrozole. BIG 1-98 is an example of an enriched design, involving complementary analyses addressing different questions several years apart, and subject to evolving analytic plans influenced by new data that emerge over time.

Vitamin C with metabolites reduce oxalate levels compared to ascorbic acid: a preliminary and novel clinical urologic finding.

PubMed

Moyad, Mark A; Combs, Maile A; Crowley, David C; Baisley, Joshua E; Sharma, Prachi; Vrablic, Angelica S; Evans, Malkanthi

2009-01-01

The incidence and prevalence of kidney stones are notable and are projected to increase over the next decade. Risk factors for kidney stones abound, but a prominent risk factor is hyperoxaluria, which has numerous etiologies, including vitamin C (ascorbic acid) dietary supplement intake. This randomized, double-blind, crossover study examined the effects of two different vitamin C formulations and found that vitamin C with metabolites (Ester-C) significantly reduced urine oxalate levels compared to ascorbic acid. This is a potential novel finding that requires further clinical evaluation.

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

PubMed Central

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

2012-01-01

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

Inhaled albuterol does not protect against ozone toxicity in nonasthmatic athletes

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

Gong, H. Jr.; Bedi, J.F.; Horvath, S.M.

1988-01-01

We evaluated the acute prophylactic efficacy of albuterol aerosol in protecting nonasthmatic athletes from the untoward effects of 0.21 ppm ozone (O/sub 3/) on symptoms, pulmonary function, exercise performance, and post-exposure histamine bronchoprovocation. Fifteen trained competitive cyclists participated in a randomized crossover study consisting of double-blinded inhalations of albuterol (180 micrograms) and placebo approximately 30 min prior to heavy continuous exercise (minute ventilation, (VE) greater than or equal to 80 L/min) for 60 min, followed by a maximal sprint (peak VE greater than 140 L/min) until exhaustion. Each subject was exposed randomly to either 0.21 ppm O/sub 3/ or filteredmore » air (FA) during the four single-blinded exposure sessions. Albuterol pretreatment resulted in modest but significant bronchodilation as compared to placebo. However, albuterol did not prevent O/sub 3/-induced respiratory symptoms, decrements in forced vital capacity (FVC), forced expired volume in one second (FEV1.0), and maximum midexpiratory flow rate (FEF25-75%), and positive histamine challenges as compared to that with placebo/O/sub 3/. There were no statistically significant differences in the metabolic data or ride times across all drugs and exposures, although the peak VE was significantly lower with O/sub 3/ than FA (142.3 vs. 150.7 L/min, respectively) regardless of drug. The results indicate that acute pretreatment with inhaled albuterol is unable to prevent or ameliorate O/sub 3/-induced symptoms and alterations in pulmonary function and exercise performance. The contribution of beta-adrenergic mechanisms in the acute airway responses to O/sub 3/ appears to be minimal.« less

Inhaled albuterol does not protect against ozone toxicity in nonasthmatic athletes

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

Gong, H. Jr.; Bedi, J.F.; Horvath, S.M.

We evaluated the acute prophylactic efficacy of albuterol aerosol in protecting nonasthmatic athletes from the untoward effects of 0.21 ppm ozone (O/sub 3/) on symptoms, pulmonary function, exercise performance, and post-exposure histamine bronchoprovocation. Fifteen trained competitive cyclists participated in a randomized crossover study consisting of double-blinded inhalations of albuterol (180 micrograms) and placebo approximately 30 min prior to heavy continuous exercise (minute ventilation, (VE) greater than or equal to 80 L/min) for 60 min, followed by a maximal sprint (peak VE greater than 140 L/min) until exhaustion. Each subject was exposed randomly to either 0.21 ppm O/sub 3/ or filteredmore » air (FA) during the four single-blinded exposure sessions. Albuterol pretreatment resulted in modest but significant bronchodilation as compared to placebo. However, albuterol did not prevent O/sub 3/-induced respiratory symptoms, decrements in forced vital capacity (FVC), forced expired volume in one second (FEV1.0), and maximum midexpiratory flow rate (FEF25-75%), and positive histamine challenges as compared to that with placebo/O/sub 3/. There were no statistically significant differences in the metabolic data or ride times across all drugs and exposures, although the peak VE was significantly lower with O/sub 3/ than FA (142.3 vs. 150.7 L/min, respectively) regardless of drug. The results indicate that acute pretreatment with inhaled albuterol is unable to prevent or ameliorate O/sub 3/-induced symptoms and alterations in pulmonary function and exercise performance. The contribution of beta-adrenergic mechanisms in the acute airway responses to O/sub 3/ appears to be minimal.« less

Notes on testing equality and interval estimation in Poisson frequency data under a three-treatment three-period crossover trial.

PubMed

Lui, Kung-Jong; Chang, Kuang-Chao

2016-10-01

When the frequency of event occurrences follows a Poisson distribution, we develop procedures for testing equality of treatments and interval estimators for the ratio of mean frequencies between treatments under a three-treatment three-period crossover design. Using Monte Carlo simulations, we evaluate the performance of these test procedures and interval estimators in various situations. We note that all test procedures developed here can perform well with respect to Type I error even when the number of patients per group is moderate. We further note that the two weighted-least-squares (WLS) test procedures derived here are generally preferable to the other two commonly used test procedures in the contingency table analysis. We also demonstrate that both interval estimators based on the WLS method and interval estimators based on Mantel-Haenszel (MH) approach can perform well, and are essentially of equal precision with respect to the average length. We use a double-blind randomized three-treatment three-period crossover trial comparing salbutamol and salmeterol with a placebo with respect to the number of exacerbations of asthma to illustrate the use of these test procedures and estimators. © The Author(s) 2014.

Meige syndrome: double-blind crossover study of sodium valproate.

PubMed Central

Snoek, J W; van Weerden, T W; Teelken, A W; van den Burg, W; Lakke, J P

1987-01-01

A double-blind crossover study of sodium valproate and placebo was conducted in five patients with Meige syndrome. CSF neurotransmitter studies were performed at the end of each treatment period. GABA levels were not influenced by the administration of sodium valproate. An increase in HVA levels was observed in every patient, which may reflect an increase in central dopaminergic activity. This finding may explain the trend towards clinical deterioration which was observed during treatment with sodium valproate. Sodium valproate appears to be ineffective in Meige syndrome. PMID:3121795

Comparative study of 2 electric and 2 manual toothbrushes in patients with fixed orthodontic appliances.

PubMed

Thienpont, V; Dermaut, L R; Van Maele, G

2001-10-01

The objective of this prospective single-blind crossover clinical trial was to evaluate the efficacy of 4 toothbrushes in 33 children undergoing fixed appliance orthodontic therapy. The toothbrushes included in this study were the Braun Oral-B 3D Plaque Remover (Kronberg, Germany), the Philips-Jordan HP 510 (Philips Domestic Appliances, Groningen, The Netherlands), the Lactona orthodontic toothbrush (Bergen op Zoom, The Netherlands), and the Oral-B Advantage Control Grip (Braun); the first 2 are electric, and the last 2 are manual. Every patient tested each type of toothbrush in a randomly designed sequence. Plaque and gingival scores were recorded at baseline and after every 4-week test period. All patients received professional prophylaxis after each clinical evaluation. The data were analyzed with the Friedman test, which showed no significant differences among the 4 brushes for any of the parameters measured. The Wilcoxon signed rank test, comparing the plaque and the gingival scores between the upper and lower jaw for each brush, indicated that plaque removal was more efficient in the lower jaw than in the upper.

Celecoxib, a specific COX-2 inhibitor, has no significant effect on methotrexate pharmacokinetics in patients with rheumatoid arthritis.

PubMed

Karim, A; Tolbert, D S; Hunt, T L; Hubbard, R C; Harper, K M; Geis, G S

1999-12-01

To determine the effects of celecoxib, a specific inhibitor of cyclooxygenase 2 (COX-2) on the renal clearance and plasma pharmacokinetic profile of stable methotrexate (MTX) doses in patients with rheumatoid arthritis (RA). Fourteen adult female patients with RA taking a stable weekly dose of MTX (5 to 15 mg/wk) for a minimum of 3 months were randomized to receive concomitantly either celecoxib (200 mg BID) or placebo for a period of 7 days in a single blind, 2 period crossover study of MTX pharmacokinetics and renal clearance. The plasma pharmacokinetic profile of MTX did not change significantly when celecoxib or a placebo was coadministered. The mean renal clearance of MTX alone, 7.98+/-2.18 l/h, was virtually unchanged by coadministration of celecoxib (7.94+/-1.61 l/h) or placebo (7.97+/-1.19 l/h). Celecoxib has no significant effect on the pharmacokinetics or renal clearance of MTX in patients with RA, although these results should be confirmed in prospective studies of elderly and renally impaired patients.

Residual effects of middle-of-the-night administration of zaleplon and zolpidem on driving ability, memory functions, and psychomotor performance.

PubMed

Verster, Joris C; Volkerts, Edmund R; Schreuder, Antonia H C M L; Eijken, Erik J E; van Heuckelum, Janet H G; Veldhuijzen, Dieuwke S; Verbaten, Marinus N; Paty, Isabelle; Darwish, Mona; Danjou, Philippe; Patat, Alain

2002-12-01

Thirty healthy volunteers participated in this two-part study. Part 1 was a single-blind, two-period crossover design to determine the effects of a single dose of ethanol (0.03% < BAC < 0.05%) or ethanol-placebo on driving ability, memory, and psychomotor performance. Part 2 was a double-blind, five-period crossover design to measure the effects of a middle-of-the-night administration of zaleplon 10 or 20 mg, zolpidem 10 or 20 mg, or placebo on driving ability 4 hours after administration and memory and psychomotor performance 6 hours after administration. The on-the-road driving test consisted of operating an instrumented automobile over a 100-km highway circuit at a constant speed (95 km/h) while maintaining a steady lateral position between the right lane boundaries. The standard deviation of lateral position (SDLP) was the primary performance parameter of the driving test. The psychomotor and memory test battery consisted of the Word Learning Test, the Critical Tracking Test, the Divided Attention Test, and the Digit Symbol Substitution Test. Data for each part were analyzed separately using ANOVA for crossover designs. Zaleplon 10 and 20 mg did not significantly impair driving ability 4 hours after middle-of-the-night administration. Relative to placebo, after zolpidem 10 mg, SDLP was significantly elevated, but the magnitude of the difference was small and not likely to be of clinical importance. Memory and psychomotor test performance was unaffected after both doses of zaleplon and zolpidem 10 mg. In contrast, zolpidem 20 mg significantly increased SDLP and speed variability. Further, zolpidem 20 mg significantly impaired performance on all psychomotor and memory tests. Finally, driving performance, Digit Symbol Substitution Test, Divided Attention Test, and immediate and delayed free recall of the Word Learning Test were significantly impaired after ethanol. The results show that zaleplon (10 and 20 mg) is a safe hypnotic devoid of next-morning residual impairment when used in the middle of the night.

Hormone-Balancing Effect of Pre-Gelatinized Organic Maca (Lepidium peruvianum Chacon): (III) Clinical responses of early-postmenopausal women to Maca in double blind, randomized, Placebo-controlled, crossover configuration, outpatient study

PubMed Central

Meissner, H. O.; Mscisz, A.; Reich-Bilinska, H.; Mrozikiewicz, P.; Bobkiewicz-Kozlowska, T.; Kedzia, B.; Lowicka, A.; Barchia, I.

2006-01-01

This is the second, conclusive part of the clinical study on clinical responses of early-postmenopausal women to standardized doses of pre-Gelatinized Organic Maca (Maca-GO). Total of 34 Caucasian women volunteers participated in a double-blind, randomized, four months outpatient crossover configuration Trial. After fulfilling the criteria of being early-postmenopausal: blood Estrogen (E2<40 pg/ml) and Follicle Stimulating Hormone (FSH>30 IU/ml) at admission, they were randomly allocated to Placebo (P) and Maca-GO (M) treatments (2 groups of 11 participants each). Two 500 mg vegetable hard gel capsules with Maca-GO or Placebo powder were self-administered twice daily with meals (total 2 g/day). At admission and follow-up monthly intervals, body mass index (BMI), blood pressure, levels of gonadal, pituitary, thyroid and adrenal hormones, lipids and key minerals were measured. Bone markers were determined after four months M and P use in 12 participants. Menopausal symptoms were assessed according to Greene’s Score (GMS) and Kupperman’s Index (KMI). Data were analyzed using multivariate technique on blocs of monthly. Results and canonical variate technique was applied to GMS and KMI matrices. Two months application of Maca-GO stimulated (P<0.05) production of E2, suppressed (P<0.05) blood FSH, Thyroid (T3) and Adrenocorticotropic hormones, Cortisol, and BMI, increased (P<0.05) low density lipoproteins, blood Iron and alleviated (P<0.001) menopausal symptoms. Maca-GO noticeably increased bone density markers. In conclusion, Maca-GO applied to early-postmenopausal women (i) acted as a toner of hormonal processes along the Hypothalamus-Pituitary-Ovarian axis, (ii) balanced hormone levels and (iii) relieved symptoms of menopausal discomfort, (hot flushes and night sweating in particular), thus, (iv) exhibited a distinctive function peculiar to adaptogens, providing an alternative non-hormonal plant option to reduce dependence on hormone therapy programs (HRT). PMID:23675006

Hormone-Balancing Effect of Pre-Gelatinized Organic Maca (Lepidium peruvianum Chacon): (III) Clinical responses of early-postmenopausal women to Maca in double blind, randomized, Placebo-controlled, crossover configuration, outpatient study.

PubMed

Meissner, H O; Mscisz, A; Reich-Bilinska, H; Mrozikiewicz, P; Bobkiewicz-Kozlowska, T; Kedzia, B; Lowicka, A; Barchia, I

2006-12-01

This is the second, conclusive part of the clinical study on clinical responses of early-postmenopausal women to standardized doses of pre-Gelatinized Organic Maca (Maca-GO). Total of 34 Caucasian women volunteers participated in a double-blind, randomized, four months outpatient crossover configuration Trial. After fulfilling the criteria of being early-postmenopausal: blood Estrogen (E2<40 pg/ml) and Follicle Stimulating Hormone (FSH>30 IU/ml) at admission, they were randomly allocated to Placebo (P) and Maca-GO (M) treatments (2 groups of 11 participants each). Two 500 mg vegetable hard gel capsules with Maca-GO or Placebo powder were self-administered twice daily with meals (total 2 g/day). At admission and follow-up monthly intervals, body mass index (BMI), blood pressure, levels of gonadal, pituitary, thyroid and adrenal hormones, lipids and key minerals were measured. Bone markers were determined after four months M and P use in 12 participants. Menopausal symptoms were assessed according to Greene's Score (GMS) and Kupperman's Index (KMI). Data were analyzed using multivariate technique on blocs of monthly. Results and canonical variate technique was applied to GMS and KMI matrices. Two months application of Maca-GO stimulated (P<0.05) production of E2, suppressed (P<0.05) blood FSH, Thyroid (T3) and Adrenocorticotropic hormones, Cortisol, and BMI, increased (P<0.05) low density lipoproteins, blood Iron and alleviated (P<0.001) menopausal symptoms. Maca-GO noticeably increased bone density markers. In conclusion, Maca-GO applied to early-postmenopausal women (i) acted as a toner of hormonal processes along the Hypothalamus-Pituitary-Ovarian axis, (ii) balanced hormone levels and (iii) relieved symptoms of menopausal discomfort, (hot flushes and night sweating in particular), thus, (iv) exhibited a distinctive function peculiar to adaptogens, providing an alternative non-hormonal plant option to reduce dependence on hormone therapy programs (HRT).

Effects of a Gentle, Self-Administered Stimulation of Perineal Skin for Nocturia in Elderly Women: A Randomized, Placebo-Controlled, Double-Blind Crossover Trial.

PubMed

Iimura, Kaori; Watanabe, Nobuhiro; Masunaga, Koichi; Miyazaki, Shogo; Hotta, Harumi; Kim, Hunkyung; Hisajima, Tatsuya; Takahashi, Hidenori; Kasuya, Yutaka

2016-01-01

Somatic afferent nerve stimuli are used for treating an overactive bladder (OAB), a major cause of nocturia in the elderly. Clinical evidence for this treatment is insufficient because of the lack of appropriate control stimuli. Recent studies on anesthetized animals show that gentle stimuli applied to perineal skin with a roller could inhibit micturition contractions depending on the roller's surface material. We examined the efficacy of gentle skin stimuli for treating nocturia. The study was a cross-over, placebo-controlled, double-blind randomized clinical study using two rollers with different effects on micturition contractions. Participants were elderly women (79-89 years) with nocturia. Active (soft elastomer roller) or placebo (hard polystyrene roller) stimuli were applied to perineal skin by participants for 1 min at bedtime. A 3-day baseline assessment period was followed by 3-day stimulation and 4-day resting periods, after which the participants were subjected to other stimuli for another 3 days. The primary outcome was change in the frequency of nighttime urination, for which charts were maintained during each 3-day period. Twenty-four participants were randomized, of which 22 completed all study protocols. One participant discontinued treatment because of an adverse event (abdominal discomfort). In participants with OAB (n = 9), change from baseline in the mean frequency of urination per night during the active stimuli period (mean ± standard deviation, -0.74 ± 0.7 times) was significantly greater than that during placebo stimuli periods (-0.15 ± 0.8 times [p < 0.05]). In contrast, this difference was not observed in participants without OAB (n = 13). These results suggest that gentle perineal stimulation with an elastomer roller is effective for treating OAB-associated nocturia in elderly women. Here the limitation was a study period too short to assess changes in the quality of sleep and life. UMIN Clinical Trial Registry (CTR) UMIN000015809.

Cardiopulmonary Benefits of Reducing Indoor Particles of Outdoor Origin: a Randomized Double-Blind Crossover Trial of Air Purifiers

PubMed Central

Chen, Renjie; Zhao, Ang; Chen, Honglei; Zhao, Zhuohui; Cai, Jing; Wang, Cuicui; Yang, Changyuan; Li, Huichu; Xu, Xiaohui; Ha, Sandie; Li, Tiantian; Kan, Haidong

2017-01-01

Background Indoor exposure to fine particulate matter (PM2.5) from outdoor sources is a major health concern, especially in highly polluted developing countries, such as China. Few studies have evaluated the effectiveness of indoor air purification on the improvement of cardiopulmonary health in these areas. Objectives To evaluate whether a short-term indoor air purifier intervention improves cardiopulmonary health. Methods We conducted a randomized double-blind crossover trial among 35 healthy college students in Shanghai, China in 2014. These students lived in dormitories that were randomized into 2 groups and alternated the use of true or sham air purifiers for 48 h with a 2-week washout interval. We measured 14 circulating biomarkers of inflammation, coagulation and vasoconstriction, lung function, blood pressure (BP), and fractional exhaled nitric oxide (FeNO). We applied linear mixed-effect models to evaluate the effect of the intervention on health outcome variables. Results On average, air purification resulted in a 57% reduction in PM2.5 concentration from 96.2 to 41.3 μg/m3 within hours of operation. Air purification was significantly associated with decreases in geometric means of several circulating inflammatory and thrombogenic biomarkers, including 17.5% in monocyte chemoattractant protein-1, 68.1% in interleukin-1β, 32.8% in myeloperoxidase and 64.9% in soluble CD40 ligand. Further, systolic BP, diastolic BP, and FeNO were significantly decreased by 2.7%, 4.8%, and 17.0% in geometric mean, respectively. The impacts on lung function and vasoconstriction biomarkers were beneficial, but not statistically significant. Conclusion This intervention study demonstrated clear cardiopulmonary benefits of indoor air purification among young, healthy adults in a Chinese city with severe ambient particulate air pollution. (Intervention Study on the Health Impact of Air Filters in Chinese Adults; NCT02239744) PMID:26022815

Comparison of the effect of topiramate and sodium valporate in migraine prevention: a randomized blinded crossover study.

PubMed

Shaygannejad, Vahid; Janghorbani, Mohsen; Ghorbani, Abbas; Ashtary, Fereshteh; Zakizade, Naser; Nasr, Vida

2006-04-01

Topiramate and sodium valporate are anticonvulsants, demonstrated to be effective as monotherapy for migraine prevention in placebo-controlled trials. To compare the relative efficacy of topiramate and sodium valporate in the prevention of migraine. A 24-week, randomized, double-blind, crossover, clinical trial was conducted from October 2003 to September 2004. A total of 64 patients with migraine headache, aged 14 to 57 years, were randomly allocated to the 2 treatment groups. The first group received topiramate (25 mg daily increment over 1 week to 50 mg) for a total of 2 months. The second group received sodium valporate (200 mg daily increment over 1 week to 400 mg) for 2 months. Response to treatment was assessed at 0, 1, 8, 16, and 24 weeks after start of therapy. Topiramate appeared to be equivalent in efficacy and safety to sodium valporate. A significant decrease in duration, monthly frequency, and intensity of headache occurred in both groups. Of the 32 patients treated with sodium valporate, the mean standard deviation (SD) of monthly migraine frequency decreased from 5.4 (2.5) to 4.0 (2.8) episode per month, headache intensity from 7.7 (1.2) to 5.8 (1.7) by visual analog scale (VAS), and headache duration from 21.3 (14.6) to 12.3 (10.7) hours (P < .001). Correspondingly, in the 32 patients treated with topiramate, the mean SD of monthly headache frequency decreased from 5.4 (2.0) to 3.2 (1.9) per month, headache intensity from 6.9 (1.2) to 3.7 (1.3), and headache duration from 17.3 (8.4) to 3.9 (2.7) hours (P < .001). This study demonstrates that treatment with topiramate and sodium valporate both significantly reduce migraine headache. This effect of topiramate and sodium valporate has previously been shown to reduce migraine headache, and we postulate that treatment with topiramate and sodium valporate may have a similar benefit.

A randomized, rater-blinded, crossover study of the effects of oxymorphone extended release, fed versus fasting, on cognitive performance as tested with CANTAB in opioid-tolerant subjects.

PubMed

Spierings, Egilius L H; Volkerts, Edmund R; Heitland, Ivo; Thomson, Heather

2014-02-01

The maximum plasma concentration (Cmax ) of oxymorphone extended release (ER) 20 mg and 40 mg is approximately 50% higher in fed than in fasted subjects, with most of the difference in area-under-the-curve (AUC) occurring in the first 4 hours post-dose. Hence, the US FDA recommends in the approved labeling that oxymorphone ER is taken at least 1 hour before or 2 hours after eating. In order to determine the potential impact on cognitive performance of the increased absorption of oxymorphone ER, fed versus fasting, we conducted a randomized, rater-blinded, crossover study in 30 opioid-tolerant subjects, using tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB). The subjects randomly received 40 mg oxymorphone ER after a high-fat meal of approximately 1,010 kCal or after fasting for 8-12 hours, and were tested 1 hour and 3 hours post-dose. The CANTAB tests, Spatial Recognition Memory (SRM) and Spatial Working Memory (SWM), showed no statistically significant differences between the fed and fasting conditions. However, sustained attention, as measured by the Rapid Visual Information Processing (RVP) CANTAB test, showed a statistically significant interaction of fed versus fasting and post-dose time of testing (F[1,28] = 6.88, P = 0.01), suggesting that 40 mg oxymorphone ER after a high-fat meal versus fasting mitigates the learning effect in this particular cognition domain from 1 hour to 3 hours post-dose. Oxymorphone 40 mg ER affected cognitive performance similarly within 3 hours post-dose, whether given on an empty stomach or after a high-fat meal, suggesting that the effect of food on plasma concentration may not be relevant in the medication's impact on cognition. Wiley Periodicals, Inc.

Cardiopulmonary benefits of reducing indoor particles of outdoor origin: a randomized, double-blind crossover trial of air purifiers.

PubMed

Chen, Renjie; Zhao, Ang; Chen, Honglei; Zhao, Zhuohui; Cai, Jing; Wang, Cuicui; Yang, Changyuan; Li, Huichu; Xu, Xiaohui; Ha, Sandie; Li, Tiantian; Kan, Haidong

2015-06-02

Indoor exposure to fine particulate matter (PM2.5) from outdoor sources is a major health concern, especially in highly polluted developing countries such as China. Few studies have evaluated the effectiveness of indoor air purification on the improvement of cardiopulmonary health in these areas. This study sought to evaluate whether a short-term indoor air purifier intervention improves cardiopulmonary health. We conducted a randomized, double-blind crossover trial among 35 healthy college students in Shanghai, China, in 2014. These students lived in dormitories that were randomized into 2 groups and alternated the use of true or sham air purifiers for 48 h with a 2-week washout interval. We measured 14 circulating biomarkers of inflammation, coagulation, and vasoconstriction; lung function; blood pressure (BP); and fractional exhaled nitric. We applied linear mixed-effect models to evaluate the effect of the intervention on health outcome variables. On average, air purification resulted in a 57% reduction in PM2.5 concentration, from 96.2 to 41.3 μg/m3, within hours of operation. Air purification was significantly associated with decreases in geometric means of several circulating inflammatory and thrombogenic biomarkers, including 17.5% in monocyte chemoattractant protein-1, 68.1% in interleukin-1β, 32.8% in myeloperoxidase, and 64.9% in soluble CD40 ligand. Furthermore, systolic BP, diastolic BP, and fractional exhaled nitrous oxide were significantly decreased by 2.7%, 4.8%, and 17.0% in geometric mean, respectively. The impacts on lung function and vasoconstriction biomarkers were beneficial but not statistically significant. This intervention study demonstrated clear cardiopulmonary benefits of indoor air purification among young, healthy adults in a Chinese city with severe ambient particulate air pollution. (Intervention Study on the Health Impact of Air Filters in Chinese Adults; NCT02239744). Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Therapeutic Effects of Standardized Formulation of Stachys lavandulifolia Vahl on Primary Dysmenorrhea: A Randomized, Double-Blind, Crossover, Placebo-Controlled Pilot Study.

PubMed

Monji, Faezeh; Hashemian, Farshad; Salehi Surmaghi, Mohammad-Hossein; Mohammadyari, Fatemeh; Ghiyaei, Saeid; Soltanmohammadi, Alireza

2018-05-09

In Iranian folklore medicine, boiled extract of Stachys lavandulifolia Vahl is reputed to have therapeutic effects in painful disorders. This study evaluated the efficacy of the standardized formulation of S. lavandulifolia Vahl in reducing pain in primary dysmenorrhea, which is known to be a common disorder with significant impact on quality of life. A randomized, double blind, crossover, placebo-controlled pilot study. Bu-Ali Hospital affiliated with Tehran Medical Branch, Islamic Azad University. Twenty-nine patients with primary dysmenorrhea. Patients were enrolled according to medical history and gynecologic sonography. Standardized capsules of S. lavandulifolia were prepared. All the patients were allowed to take mefenamic acid up to 250 mg/q6h if they needed, in the first menstruation cycle to estimate the analgesic consumption at baseline. By the use of an add-on design in the next cycle, they were randomly assigned to receive either herbal or placebo capsules every 4-6 h. Then, they were crossed over to the other group during the course of the trial. At the end of the fourth day of each cycle, the intensity of pain was measured by visual analogue scale and McGill pain questionnaire. Statistical significance was evaluated using repeated-measures one-way analysis of variance. Pain intensity was significantly decreased during consumption of Stachys lavandulifolia capsules in comparison with basic and placebo cycles (p < 0.05). Interestingly, the consumption of mefenamic acid capsules was reduced dramatically in the S. lavandulifolia cycle in comparison with basic and placebo cycles (p < 0.001). It was demonstrated that S. lavandulifolia-prepared formulation can reduce menstrual pain, and can probably be recommended as an add-on therapy or even an alternative remedy to nonsteroidal anti-inflammatory drugs (NSAIDs) with fewer side effects in primary dysmenorrhea.

Ketamine for Social Anxiety Disorder: A Randomized, Placebo-Controlled Crossover Trial.

PubMed

Taylor, Jerome H; Landeros-Weisenberger, Angeli; Coughlin, Catherine; Mulqueen, Jilian; Johnson, Jessica A; Gabriel, Daniel; Reed, Margot O; Jakubovski, Ewgeni; Bloch, Michael H

2018-01-01

Many patients with social anxiety disorder (SAD) experience inadequate symptom relief from available treatments. Ketamine is a potent N-methyl-D-aspartate receptor antagonist with a potentially novel mechanism of action for the treatment of anxiety disorders. Therefore, we conducted a double-blind, randomized, placebo-controlled crossover trial in 18 adults with DSM-5 SAD and compared the effects between intravenous ketamine (0.5 mg/kg over 40 min) and placebo (normal saline) on social phobia symptoms. Ketamine and placebo infusions were administered in a random order with a 28-day washout period between infusions. Ratings of anxiety were assessed 3-h post-infusion and followed for 14 days. We used linear mixed models to assess the impact of ketamine and placebo on anxiety symptoms. Outcomes were blinded ratings on the Liebowitz Social Anxiety Scale (LSAS) and self-reported anxiety on a visual analog scale (VAS-Anxiety). We also used the Wilcoxon signed-rank test to compare the proportion of treatment responders. Based on prior studies, we defined response as a greater than 35% LSAS reduction and 50% VAS-Anxiety reduction. We found ketamine resulted in a significantly greater reduction in anxiety relative to placebo on the LSAS (Time × Treatment: F 9,115 =2.6, p=0.01) but not the VAS-Anxiety (Time × Treatment: F 10,141 =0.4, p=0.95). Participants were significantly more likely to exhibit a treatment response after ketamine infusion relative to placebo in the first 2 weeks following infusion measured on the LSAS (33.33% response ketamine vs 0% response placebo, Wilcoxon signed-rank test z=2.24, p=0.025) and VAS (88.89% response ketamine vs 52.94% response placebo, Wilcoxon signed-rank test z=2.12, p=0.034). In conclusion, this proof-of-concept trial provides initial evidence that ketamine may be effective in reducing anxiety.

Intranasal abuse potential of an abuse-deterrent oxycodone formulation compared to oxycodone immediate release and placebo in nondependent, recreational opioid users.

PubMed

Setnik, Beatrice; Schoedel, Kerri; Bartlett, Cindy; Dick, Chris; Hakim, Nasrat; Geoffroy, Pierre

To assess the intranasal (IN) human abuse potential of ELI-200, a novel immediate-release (IR) oxycodone formulation containing sequestered naltrexone. Randomized, double-blind, double-dummy, active and placebo-controlled, five-way crossover study. Pharmacodynamics, safety, and pharmacokinetics (PKs) were evaluated for up to 36 hours postdose. Single site in Canada (INC Research Toronto). Healthy male and female nondependent recreational opioid users underwent a naloxone challenge and drug discrimination qualification test. Single IN dose of ground ELI-200 (30-mg oxycodone hydrochloride [HCl]/3-mg naltrexone HCl), crushed 30-mg oxycodone HCl IR (Roxicodone®), placebo, fixed placebo, and single oral dose of intact ELI-200 (30mg/3mg). Peak effect (E max ) for bipolar Drug Liking (0-100 point visual analog scale). Of the 44 randomized subjects, 37 completed all five treatment periods. All active treatments showed significantly higher (p<0.001) median Drug Liking E max relative to placebo. Significant reductions (p<0.001) in median Drug Liking [E max ] were observed for IN ELI-200 [56.0] compared to IN oxycodone IR [100.0]. Secondary positive or objective measures (High, Good Drug Effects, Overall Drug Liking, Take Drug Again, and maximum pupil constriction) showed significantly lower E max for IN ELI-200 (p<0.001) compared to IN oxycodone IR. IN administration of ELI-200 demonstrated significantly decreased effects on subjective and physiologic measures, and greater nasal irritation, compared to IN oxycodone IR. These findings, along with the PK profile of naltrexone, demonstrated that when ELI-200 capsules were ground and administered intranasally, the naltrexone component was rapidly released and conferred meaningful abuse-deterrent properties.

Single-dose effects of isosorbide mononitrate alone or in combination with losartan on central blood pressure.

PubMed

Kaufman, Rhonda; Nunes, Irene; Bolognese, James A; Miller, Deborah L; Salotti, Dennis; McCarthy, Jennifer M; Smith, William B; Herman, Gary A; Feig, Peter U

2010-01-01

Antihypertensive drugs can have different effects on central and brachial blood pressures, which may affect outcomes. Nitric oxide donors have acute effects on central blood pressure but have not been assessed with renin-angiotensin system blockade. Thirteen patients with prehypertensive/Stage 1 hypertension were randomized to five single-dose treatments separated by ≤4 days using a double-blind, crossover study design: angiotensin receptor blocker (ARB) losartan 100 mg, isosorbide mononitrate (ISMN) 60 mg, losartan 100 mg + ISMN 15 mg, losartan 100 mg + ISMN 60 mg, and placebo. Central and brachial blood pressures were measured throughout 10 hours. Mean placebo-subtracted decrease from baseline in augmentation index (AIx) approximately 1% for losartan 100 mg, 26% for ISMN 60 mg, 19% for losartan 100 mg + ISMN 15 mg, and 24% for losartan 100 mg + ISMN 60 mg. Administered with losartan 100 mg or alone, ISMN lowered AIx, demonstrating that acute effects of a nitrate donor are much larger than those of an ARB even when administered with an ARB. Differences from placebo were statistically significant except for losartan 100 mg. AIx is a good biomarker of acute hemodynamic effects of nitric oxide in prehypertensive/Stage 1 hypertension. 2010 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Single therapeutic and supratherapeutic doses of corifollitropin alfa, a sustained follicle stimulant, do not prolong the QTcF-interval in healthy postmenopausal volunteers.

PubMed

de Kam, Pieter-Jan; van Kuijk, Jacqueline H M; Zandvliet, Anthe S; Thomsen, Torben

2015-09-01

Corifollitropin alfa (Elonva®) is the first hybrid follicle-stimulating hormone molecule with demonstrated sustained follicle-stimulating activity after a single subcutaneous injection. This trial evaluated if corifollitropin alfa is associated with QT/QTc prolongation and/ or proarrhythmic potential as compared to placebo in healthy post-menopausal women. Participants were healthy, postmenopausal women. Study treatments were corifollitropin alfa 150 μg, corifollitropin alfa 240 μg, and moxifloxacin 400 mg with placebo. This randomized, double blind, double-dummy, 4-period crossover trial compared single doses of corifollitropin alfa 150 μg (therapeutic dose), corifollitropin alfa 240 μg (supratherapeutic dose), and moxifloxacin 400 mg (positive control) with placebo. Corifollitropin alfa was administered on day 1 and moxifloxacin on day 2. The largest time-matched mean QTcF difference versus placebo for the therapeutic dose of corifollitropin alfa was 1.4 ms (upper limit of 1-sided 95% confidence interval (UL 95% CI) = 3.4 ms), and for the supratherapeutic dose was 1.2 ms (UL 95% CI = 3.6 ms). For both the therapeutic and the supratherapeutic dose of corifollitropin alfa and at all time points, the UL 95% CI for the time matched QTcF differences compared with placebo was below 10 ms, the threshold of relevance defined by the ICH E14 guideline. Single therapeutic and supratherapeutic doses of corifollitropin alfa are not associated with clinically relevant QT/QTc-interval prolongation in healthy post-menopausal women.

Anxiety and methylphenidate in attention deficit hyperactivity disorder: a double-blind placebo-drug trial.

PubMed

Moshe, Keren; Karni, Avi; Tirosh, Emanuel

2012-09-01

To examine the relationship between attention and anxiety and the response to methylphenidate in children with attention deficit hyperactivity disorder (ADHD), a total of 57 boys, between the ages of 7-12 years, were assessed for their attention and level of anxiety. Methylphenidate was administered for a week in a randomized double-blind drug/placebo-drug cross-over design. The levels of anxiety were evenly distributed between the inattentive and hyperactive/impulsive types. Anxiety was significantly correlated with the attention as reported by both teachers and parents. The response to methylphenidate was inversely correlated with the reported anxiety level only in boys with the hyperactive/impulsive and combined types. The higher the level of anxiety, the lower level of response to methylphenidate was observed. In the assessment and treatment of children with ADHD, the level of anxiety should be evaluated and taken into account while planning and monitoring treatment regiment.

Analgesic Effect of Topical Sodium Diclofenac before Retinal Photocoagulation for Diabetic Retinopathy: A Randomized Double-masked Placebo-controlled Intraindividual Crossover Clinical Trial.

PubMed

Ramezani, Alireza; Entezari, Morteza; Shahbazi, Mohammad Mehdi; Semnani, Yosef; Nikkhah, Homayoun; Yaseri, Mehdi

2017-04-01

To evaluate the analgesic effect of topical sodium diclofenac 0.1% before retinal laser photocoagulation for diabetic retinopathy. Diabetic patients who were candidates for peripheral laser photocoagulation were included in a randomized, placebo-controlled, intraindividual, two-period, and crossover clinical trial. At the first session and based on randomization, one eye received topical sodium diclofenac 0.1% and the other eye received an artificial tear drop (as placebo) three times before laser treatment. At the second session, eyes were given the alternate drug. Patients scored their pain using visual analogue scale (max, 10 cm) at both sessions. Patients and the surgeon were blinded to the drops given. Difference of pain level was the main outcome measure. A total of 200 eyes of 100 patients were enrolled. Both treatments were matched regarding the applied laser. Pain sensation based on visual analogue scale was 5.6 ± 3.0 in the treated group and 5.5 ± 3.0 in the control group. The calculated treatment effect was 0.15 (95% confidence interval, -0.27 to 0.58; p = 0.486). The estimated period effect was 0.24 ( p = 0.530) and the carryover effect was not significant ( p = 0.283). Pretreatment with topical sodium diclofenac 0.1% does not have any analgesic effect during peripheral retinal laser photocoagulation in diabetic patients.

The effect of recommending a CPP-ACPF product on salivary and plaque pH levels in orthodontic patients: a randomized cross-over clinical trial.

PubMed

Heshmat, Haleh; Banava, Sepideh; Mohammadi, Ebrahim; Kharazifard, Mohammad Javad; Mojtahedzadeh, Faramarz

2014-11-01

Along with their re-mineralizing capacity, calcium phosphopeptide-amorphous calcium phosphate products combined with fluoride (CPP-ACPF) could also be beneficial by neutralizing acidic salivary and plaque pH. The purpose was to evaluate the effect of CPP-ACPF on salivary and plaque pH in orthodontic patients. As a triple-blind, cross-over randomized trial, 30 orthodontic patients with fixed appliances (age range = 15.70 ± 4.08 years) were recruited and randomly assigned to two groups. A CPP-ACPF paste (MI Paste Plus, GC America, Alsip, IL) was used by group 1 (n = 15) and a placebo by group 2 (n = 15) for 1 month. After a 1 month washout period, patients used the alternative paste for another month. Plaque and salivary pH levels were measured at all before and after periods. By applying MI Paste Plus, the plaque pH increased from 5.81 ± 0.45 to 6.60 ± 0.38 (p < 0.05), whereas the before and after salivary pH recordings, which were 6.72 ± 0.43 and 6.71 ± 0.38, respectively, remained statistically unchanged (p > 0.05). MI Paste Plus can be clinically beneficial in increasing plaque pH levels, but has no effect on the salivary pH.

1% hydrocortisone ointment is an effective treatment of pruritus ani: a pilot randomized controlled crossover trial.

PubMed

Al-Ghnaniem, R; Short, K; Pullen, A; Fuller, L C; Rennie, J A; Leather, A J M

2007-12-01

Pruritus ani (PA) is a common condition which is difficult to treat in the absence of obvious predisposing factors. There is paucity of evidence-based guidelines on the treatment of this condition. We examined whether 1% hydrocortisone ointment is an effective treatment for PA. A pilot randomized, double-blind, placebo-controlled, crossover trial was carried out. Eleven patients consented to take part in the trial and ten completed the study. After a 2-week run-in period, patients with primary PA were randomly allocated to receive 1% hydrocortisone ointment or placebo for 2 weeks followed by the opposite treatment for a further 2-week period. There was a washout period of 2 weeks between treatments. The primary outcome measure was reduction in itch using a visual analogue score (VAS). The secondary outcome measures were improvement in quality of life measured using a validated questionnaire (Dermatology Life Quality Index, DLQI) and improvement in clinical appearance of the perianal skin using the Eczema Area and Severity Index (EASI) score. Treatment with 1% hydrocortisone ointment resulted in a 68% reduction in VAS compared with placebo (P=0.019), a 75% reduction in DLQI score (P=0.067), and 81% reduction in EASI score (P=0.01). A short course of mild steroid ointment is an effective treatment for PA.

Adjunctive treatment with lodenafil carbonate for erectile dysfunction in outpatients with schizophrenia and spectrum: a randomized, double-blind, crossover, placebo-controlled trial.

PubMed

Nunes, Luciana Vargas Alves; Lacaz, Fernando Sargo; Bressan, Rodrigo Affonseca; Nunes, Sandra Odebrecht Vargas Alves; Mari, Jair de Jesus

2013-04-01

INTRODUCTION.: Evidence is accumulating to support the presence of erectile dysfunction in patients with schizophrenia. This dysregulation may be amenable to therapeutic intervention to improve adherence and quality of life of patients who suffer from schizophrenia and schizoaffective disorders. AIM.: We aimed to evaluate the use of adjunctive medication lodenafil for the treatment of erectile dysfunction in outpatients with schizophrenia and spectrum. METHODS.: The design was a randomized, double-blind, crossover, placebo-controlled trial with lodenafil and it was carried at the Schizophrenia Outpatients Program. MAIN OUTCOME MEASURES.: The measures used to assess sexual dysfunction were Arizona Sexual Experiences Scale (ASEX) and International Index of Erectile Function (IIEF). The Positive and Negative Syndrome Scale (PANSS) and the Quality of Life Scale (QLS) were also used. The measures included the levels of prolactin, estradiol, luteinizing hormone, sex hormone-binding globulin, free testosterone, and total testosterone at baseline and end point. Lodenafil and placebo pills were used by the patients for 16 weeks. RESULTS.: Fifty male outpatients fulfilled the criteria and 94% of the participants completed the study. Lodenafil and placebo produced improvement in ASEX, IIEF scale, PANSS, and QLS, and there was no statistical difference between lodenafil and placebo groups in all sexual domains in the results of PANSS and QLS and in the results of hormone levels. CONCLUSION.: These results indicate that both lodenafil and placebo were effective in the treatment of erectile dysfunction for schizophrenia. Placebo effect is very important in patients with schizophrenia and this study showed the importance of discussing sexuality and trying to treat these patients. Further studies designed to test treatments of erectile dysfunction in patients who suffer from schizophrenia are necessary. © 2013 International Society for Sexual Medicine.

Treatment of erectile dysfunction with sildenafil citrate in renal allograft recipients: a randomized, double-blind, placebo-controlled, crossover trial.

PubMed

Sharma, Raj K; Prasad, Narayan; Gupta, Amit; Kapoor, Rakesh

2006-07-01

Erectile dysfunction (ED) is observed frequently in patients with end-stage renal disease, hemodialysis patients, and renal allograft recipients. There are few studies of sildenafil use in renal allograft recipients. The study is designed as a randomized, double-blind, placebo-controlled, crossover trial. Efficacy was assessed by using the self-administered International Index of Erectile Function (IIEF), a 15-question validated measure of ED, and a global efficacy question (Did the treatment improve your erection?). Thirty-two eligible renal transplant recipients were included in this study. After treatment with sildenafil citrate, patients had significantly better scores in 13 of 15 questions, except for questions 11 (desire frequency; P = 0.39) and 12 (desire level; P = 0.61). Treatment efficacy assessed through questions 3 (penetration ability; P < 0.001) and 4 (maintenance frequency; P < 0.001) was significantly better after sildenafil therapy. There were no significant differences between baseline and post-placebo treatment scores, except for question 13 (relationship satisfaction). Patients treated with sildenafil had significantly better scores in 4 domains compared with baseline, but a difference was not observed in the sexual desire domain (P = 0.32). There were no significant differences in scores between placebo and baseline in any domain. On the global efficacy question, 81.3% of patients showed improvement compared with 18.7% with placebo. There were no differences in areas under the curve and maximum cyclosporine concentrations before and after sildenafil therapy. No patient discontinued the drug because of side effects except for 1 patient with visual hallucination. Treatment with sildenafil in renal transplant recipients is a valid option with an effective response.

Double-blind, randomized crossover study of intravenous infusion of magnesium sulfate versus 5% dextrose on depressive symptoms in adults with treatment-resistant depression.

PubMed

Mehdi, Syed M A; Atlas, Steven E; Qadir, Sidra; Musselman, Dominique; Goldberg, Sharon; Woolger, Judi M; Corredor, Raul; Abbas, Muhammad H; Arosemena, Leopoldo; Caccamo, Simone; Campbell, Carmen S G; Farooqi, Ashar; Gao, Jinrun; Konefal, Janet; Lages, Lucas C; Lantigua, Laura; Lopez, Johanna; Padilla, Vanessa; Rasul, Ammar; Ray, Anna M; Simões, Herbert G; Tiozzo, Eduard; Lewis, John E

2017-03-01

Treatment-resistant depression patients are more likely to suffer from comorbid physical and mental disorders, experience marked and protracted functional impairment, and incur higher health-care costs than non-affected individuals. Magnesium sulfate is a treatment option that may offer great potential for patients with treatment-resistant depression based on prior work in animals and humans. Twelve subjects with mild or moderate treatment-resistant depression were randomized into a double-blind crossover trial to receive an infusion of 4 g of magnesium sulfate in 5% dextrose or placebo infusion of 5% dextrose with a 5-day washout in between the 8-day intervention period. Subjects were assessed before and after the intervention for serum and urine magnesium, lipid panel, the Hamilton Rating Scale for Depression, and the Patient Health Questionnaire-9. We found a difference in serum magnesium from day 2 to 8 (pre-infusion) (P < 0.002) and from baseline to day 8 (P < 0.02). No changes were noted on the Hamilton Rating Scale for Depression or the Patient Health Questionnaire-9 24 h post-treatment, but as serum magnesium increased from baseline to day 7, the Patient Health Questionnaire-9 decreased from baseline to day 7 (P = 0.02). Magnesium sulfate did not significantly affect depression 24 h post-infusion, but other results were consistent with the literature. The association between changes in serum magnesium and the Patient Health Questionnaire-9 supports the idea that magnesium sulfate may be used to address treatment-resistant depression, an ongoing medical challenge. © 2016 The Authors Psychiatry and Clinical Neurosciences © 2016 Japanese Society of Psychiatry and Neurology.

Pharmacokinetic interaction between domperidone and ketoconazole leads to QT prolongation in healthy volunteers: a randomized, placebo-controlled, double-blind, crossover study

PubMed Central

Boyce, Malcolm J; Baisley, Kathy J; Warrington, Steven J

2012-01-01

AIMS To assess the steady-state pharmacokinetic and QTc effects of domperidone and ketoconazole, given alone and together. METHODS A randomized, placebo-controlled, double-blind, crossover study was carried out. Healthy subjects (14 men, 10 women; age 18–39 years; mean weight 73.5 kg, range 53.8–98.8 kg; 23 Europid, 1 Afro-Caribbean) received orally, for 7 days each, placebo, domperidone 10 mg, four doses daily, at 4 h intervals, ketoconazole 200 mg 12-hourly and domperidone and ketoconazole together. The washout period was 15 days. Pharmacokinetics and serial 12-lead ECGs were assessed on day 7, and serial ECGs on day −1 and at follow-up. Two subjects withdrew before the third treatment period, so data were available for 22–24 subjects. RESULTS Ketoconazole tripled domperidone concentrations at steady-state. Domperidone, ketoconazole and their combination significantly increased QTcF in men. Overall adjusted mean differences from placebo were 4.20 (95% CI 0.77, 7.63), 9.24 (95% CI 5.85, 12.63) and 15.90 (95% CI 12.47, 19.33) ms, respectively. In women, QTcF was not significantly different from placebo on either domperidone or ketoconazole alone, or in combination. However, QTc was positively correlated with plasma drug concentrations, in both men and women. ΔQTcF increased by about 2 ms per 10 ng ml–1 rise in domperidone concentration, and per 1 µg ml–1 rise in ketoconazole concentration. CONCLUSIONS Ketoconazole tripled the plasma concentrations of domperidone. Domperidone and ketoconazole increased QTcF in men, whether given together or separately. The effect of domperidone alone was below the level of clinical importance. The negative result in women is unexplained. PMID:21883386

Intake and time dependence of blueberry flavonoid-induced improvements in vascular function: a randomized, controlled, double-blind, crossover intervention study with mechanistic insights into biological activity.

PubMed

Rodriguez-Mateos, Ana; Rendeiro, Catarina; Bergillos-Meca, Triana; Tabatabaee, Setareh; George, Trevor W; Heiss, Christian; Spencer, Jeremy Pe

2013-11-01

There are very limited data regarding the effects of blueberry flavonoid intake on vascular function in healthy humans. We investigated the impact of blueberry flavonoid intake on endothelial function in healthy men and assessed potential mechanisms of action by the assessment of circulating metabolites and neutrophil NADPH oxidase activity. Two randomized, controlled, double-blind, crossover human-intervention trials were conducted with 21 healthy men. Initially, the impact of blueberry flavonoid intake on flow-mediated dilation (FMD) and polyphenol absorption and metabolism was assessed at baseline and 1, 2, 4, and 6 h after consumption of blueberry containing 766, 1278, and 1791 mg total blueberry polyphenols or a macronutrient- and micronutrient-matched control drink (0 mg total blueberry polyphenols). Second, an intake-dependence study was conducted (from baseline to 1 h) with 319, 637, 766, 1278, and 1791 mg total blueberry polyphenols and a control. We observed a biphasic time-dependent increase in FMD, with significant increases at 1-2 and 6 h after consumption of blueberry polyphenols. No significant intake-dependence was observed between 766 and 1791 mg. However, at 1 h after consumption, FMD increased dose dependently to ≤766 mg total blueberry polyphenol intake, after which FMD plateaued. Increases in FMD were closely linked to increases in circulating metabolites and by decreases in neutrophil NADPH oxidase activity at 1-2 and 6 h. Blueberry intake acutely improves vascular function in healthy men in a time- and intake-dependent manner. These benefits may be mechanistically linked to the actions of circulating phenolic metabolites on neutrophil NADPH oxidase activity. This trial was registered at clinicaltrials.gov as NCT01292954 and NCT01829542.

Acute Caffeinated Coffee Consumption Does not Improve Time Trial Performance in an 800-m Run: A Randomized, Double-Blind, Crossover, Placebo-Controlled Study.

PubMed

Marques, Alexandre C; Jesus, Alison A; Giglio, Bruna M; Marini, Ana C; Lobo, Patrícia C B; Mota, João F; Pimentel, Gustavo D

2018-05-23

Studies evaluating caffeinated coffee (CAF) can reveal ergogenic effects; however, studies on the effects of caffeinated coffee on running are scarce and controversial. To investigate the effects of CAF consumption compared to decaffeinated coffee (DEC) consumption on time trial performances in an 800-m run in overnight-fasting runners. A randomly counterbalanced, double-blind, crossover, placebo-controlled study was conducted with 12 healthy adult males with experience in amateur endurance running. Participants conducted two trials on two different occasions, one day with either CAF or DEC, with a one-week washout. After arriving at the data collection site, participants consumed the soluble CAF (5.5 mg/kg of caffeine) or DEC and after 60 min the run was started. Before and after the 800-m race, blood pressure and lactate and glucose concentrations were measured. At the end of the run, the ratings of perceived exertion (RPE) scale was applied. The runners were light consumers of habitual caffeine, with an average ingestion of 91.3 mg (range 6⁻420 mg/day). Time trial performances did not change between trials (DEF: 2.38 + 0.10 vs. CAF: 2.39 + 0.09 min, p = 0.336), nor did the RPE (DEC: 16.5 + 2.68 vs. CAF: 17.0 + 2.66, p = 0.326). No difference between the trials was observed for glucose and lactate concentrations, or for systolic and diastolic blood pressure levels. CAF consumption failed to enhance the time trial performance of an 800-m run in overnight-fasting runners, when compared with DEC ingestion. In addition, no change was found in RPE, blood pressure levels, or blood glucose and lactate concentrations between the two trials.

A randomized, controlled, double-blind crossover study on the effects of 2-L infusions of 0.9% saline and plasma-lyte® 148 on renal blood flow velocity and renal cortical tissue perfusion in healthy volunteers.

PubMed

Chowdhury, Abeed H; Cox, Eleanor F; Francis, Susan T; Lobo, Dileep N

2012-07-01

We compared the effects of intravenous infusions of 0.9% saline ([Cl] 154 mmol/L) and Plasma-Lyte 148 ([Cl] 98 mmol/L, Baxter Healthcare) on renal blood flow velocity and perfusion in humans using magnetic resonance imaging (MRI). Animal experiments suggest that hyperchloremia resulting from 0.9% saline infusion may affect renal hemodynamics adversely, a phenomenon not studied in humans. Twelve healthy adult male subjects received 2-L intravenous infusions over 1 hour of 0.9% saline or Plasma-Lyte 148 in a randomized, double-blind manner. Crossover studies were performed 7 to 10 days apart. MRI scanning proceeded for 90 minutes after commencement of infusion to measure renal artery blood flow velocity and renal cortical perfusion. Blood was sampled and weight recorded hourly for 4 hours. Sustained hyperchloremia was seen with saline but not with Plasma-Lyte 148 (P < 0.0001), and fall in strong ion difference was greater with the former (P = 0.025). Blood volume changes were identical (P = 0.867), but there was greater expansion of the extravascular fluid volume after saline (P = 0.029). There was a significant reduction in mean renal artery flow velocity (P = 0.045) and renal cortical tissue perfusion (P = 0.008) from baseline after saline, but not after Plasma-Lyte 148. There was no difference in concentrations of urinary neutrophil gelatinase-associated lipocalin after the 2 infusions (P = 0.917). This is the first human study to demonstrate that intravenous infusion of 0.9% saline results in reductions in renal blood flow velocity and renal cortical tissue perfusion. This has implications for intravenous fluid therapy in perioperative and critically ill patients. NCT01087853.

Comparative effect of a new mouthrinse containing chlorhexidine, triclosan and zinc on volatile sulphur compounds: a randomized, crossover, double-blind study.

PubMed

Mendes, L; Coimbra, J; Pereira, A L; Resende, M; Pinto, M G

2016-08-01

The aims of this study were to compare the volatile sulphur compounds (VSC)-reducing effect of two commercial mouthrinses using a morning bad breath model and to assess the role of mechanical plaque control (MPC) when performed previously to mouthrinse use. Eleven volunteers with good oral health were enrolled in a double-blind, randomized, six-step crossover design study with a 7-day washout period. Two commercial mouthrinses were tested using a saline solution (NaCl 0.9%) as a negative control: one mouthrinse contained 0.05% chlorhexidine, 0.05% cetylpyridinium chloride and 0.14% zinc lactate (CHX-CPC-Zn), while the other contained 0.05% chlorhexidine, 0.15% triclosan and 0.18% zinc pidolate (CHX-triclosan-Zn). A portable sulphide monitor (Halimeter(®) ) was used for VSC quantification. Measurements were made at baseline, and 1, 3 and 5 h after rinsing. Significant differences were detected by analysis of variance. No significant differences between groups were detected at baseline. We were unable to demonstrate a significant influence of mechanical plaque control on the reduction of VSC levels when performed before mouthrinse use (P = 0.631). Both mouthrinses effectively lowered VSC levels in all test intervals (P < 0.05). No statistically significant differences were found between mouthrinses in any of the test intervals (P = 0.629, 0.069 and 0.598 at 1, 3 and 5 h). This study demonstrated that CHX-CPC-Zn and CHX-triclosan-Zn have significant and similar effects in reducing VSC levels, which persist for at least 5 h. Such effects were independent of previous MPC, which failed to improve on the results of mouthrinse use alone. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effect of xylitol on cariogenic and beneficial oral streptococci: a randomized, double-blind crossover trial

PubMed Central

Bahador, A; Lesan, S; Kashi, N

2012-01-01

Background/purpose Although habitual consumption of xylitol reduces cariogenic streptococci levels, its effect on beneficial oral streptococci is less clear. The main aim of the study is to investigate the effect of short-term xylitol consumption on the oral beneficial streptococci level of saliva, Streptococcus sanguinis and S. mitis. Material and Methods Twenty four volunteers with a median age of 23.7 years (range: 20-28) harboring Streptococcus mutans, S. sobrinus, S. sanguinis and S. mitis participated in the randomized, double-blind, cross-over study. The experimental chewing gum (1.5 g/pellet) contained 70% xylitol w/w while the control gum contained 63% sorbitol w/w. Saliva samples were collected before and after two three-week test periods with a four-week washout interval. Colony-forming units (CFU)/ml were enumerated for the estimation of S. mutans levels on Mitis Salivarius-Mutans valinomycin (MS-MUTV), S. sobrinus on Mitis Salivarius-Sobrinus (MS-SOB), S. sanguinis on Modified Medium 10-Sucrose (MM10-S) and S. mitis on Mitis Salivarius Agar with Tellurite (MSAT) media. Results The S. mutans and S. sobrinus counts of the saliva samples decreased significantly (p = 0.01 and p = 0.011, respectively) in the xylitol gum group but not in the sorbitol gum group. The salivary S. sanguinis and S. mitis counts did not decrease in both xylitol and sorbitol gum groups. Conclusions Based on the findings of this study, xylitol consumption reduced S. mutans and S. sobrinus counts in saliva but appeared not to effect numbers of S. sanguinis and S. mitis in saliva. So, habitual consumption of xylitol reduces cariogenic streptococci levels without any effect on beneficial sterptococci for the oral cavity. PMID:22973473

Effects of rose hip intake on risk markers of type 2 diabetes and cardiovascular disease: a randomized, double-blind, cross-over investigation in obese persons

PubMed Central

Andersson, U; Berger, K; Högberg, A; Landin-Olsson, M; Holm, C

2012-01-01

BACKGROUND/OBJECTIVES: In studies performed in mice, rose hip powder has been shown to both prevent and reverse high-fat diet-induced obesity and glucose intolerance as well as reduce plasma levels of cholesterol. The aim of this study was to investigate whether daily intake of rose hip powder over 6 weeks exerts beneficial metabolic effects in obese individuals. SUBJECTS/METHODS: A total of 31 obese individuals with normal or impaired glucose tolerance were enrolled in a randomized, double-blind, cross-over study in which metabolic effects of daily intake of a rose hip powder drink over 6 weeks was compared with a control drink. Body weight, glucose tolerance, blood pressure, blood lipids and markers of inflammation were assessed in the subjects. RESULTS: In comparison with the control drink, 6 weeks of daily consumption of the rose hip drink resulted in a significant reduction of systolic blood pressure (−3.4% P=0.021), total plasma cholesterol (−4.9% P=0.0018), low-density lipoprotein (LDL) cholesterol (−6.0% P=0.012) and LDL/HDL ratio (−6.5% P=0.041). The Reynolds risk assessment score for cardiovascular disease was decreased in the rose hip group compared with the control group (−17% P=0.007). Body weight, diastolic blood pressure, glucose tolerance, and plasma levels of high-density lipoprotein (HDL) cholesterol, triglycerides, incretins and markers of inflammation did not differ between the two groups. CONCLUSIONS: Daily consumption of 40 g of rose hip powder for 6 weeks can significantly reduce cardiovascular risk in obese people through lowering of systolic blood pressure and plasma cholesterol levels. PMID:22166897

Acute effects of beer on endothelial function and haemodynamics: a single-blind, cross-over study in healthy volunteers

PubMed Central

Karatzi, Kalliopi; Rontoyanni, Victoria G.; Protogerou, Athanase D.; Georgoulia, Aggeliki; Xenos, Konstantinos; Chrysou, John; Sfikakis, Petros P.; Sidossis, Labros S.

2015-01-01

Objective Moderate consumption of beer is associated with lower cardiovascular (CV) risk. To explore the underlying mechanisms we studied the acute effects of the constituents of beer (alcohol and antioxidants), on established predictors of CV risk: endothelial function, aortic stiffness, pressure wave reflections and aortic pressure. Research Methods & Proceedures In a randomized, single – blind, cross - over study 17 healthy, non-smoking, volunteers (28.5±5.2 years and 24.4±2.5 BMI) consumed in 3 separate days, at least one week apart: a) 400 ml of beer & 400 ml water, b) 800 ml of dealcoholized beer (same amount of polyphenols), and c) 67 ml of vodka & 733 ml water (same amount of alcohol). Each time aortic stiffness (pulse wave velocity, pressure wave reflections (Aix), aortic and brachial pressure (Sphygmocor device) and endothelial function (brachial flow mediated dilatation) were assessed at fast and 1 and 2 hours postprandial. Results Aortic stiffness was significantly and similarly reduced by all 3 interventions. However, endothelial function was significantly improved only after beer consumption (average of 1.33%, CI 0.15-2.53). Although wave reflections were significantly reduced by all 3 interventions (average of beer: 9.1%, dealcoholized beer: 2.8%, vodka 8.5%, all CI within limits of significance), the reduction was higher after beer consumption compared todealcoholized beer (p=0.018). Pulse pressure amplification (i.e. brachial/aortic) was increased by all 3 test drinks. Conclusions Beer improves acutely parameters of arterial function and structure, in healthy non-smokers. This benefit seems to be mediated by the additive or synergistic effects of alcohol and anti-oxidants and merits further investigation. PMID:23810643

Comparative Pharmacodynamics and Plasma Concentrations of D-Threo-Methylphenidate Hydrochloride after Single Doses of D-Threo-Methylphenidate Hydrochloride and D,l-Threo-Methylphenidate Hydrochloride in a Double-Blind, Placebo-Controlled, Crossover Laboratory School Study in Children with Attention-Deficit/hyperactivity Disorder

ERIC Educational Resources Information Center

Quinn, Declan; Wigal, Sharon; Swanson, James; Hirsch, Sharon; Ottolini, Yvonne; Dariani, Maghsoud; Roffman, Mark; Zeldis, Jerome; Cooper, Thomas

2004-01-01

Objective: Methylphenidate has four optical isomers due to two asymmetries (erythro-threo and dextro-levo). The initial commercial formulation eliminated the erythro isomer, but the dextro-levo asymmetry was racemic, with equal amounts of d and l-threo isomers (d,l-MPH). Previous work has suggested that the d-threo isomer methylphenidate (d-MPH)…

Apixaban, an oral, direct factor Xa inhibitor: single dose safety, pharmacokinetics, pharmacodynamics and food effect in healthy subjects

PubMed Central

Frost, Charles; Wang, Jessie; Nepal, Sunil; Schuster, Alan; Barrett, Yu Chen; Mosqueda-Garcia, Rogelio; Reeves, Richard A; LaCreta, Frank

2013-01-01

Aims To evaluate apixaban single dose safety, tolerability, pharmacokinetics and pharmacodynamics and assess the effect of food on apixaban pharmacokinetics. Methods A double-blind, placebo-controlled, single ascending-dose, first-in-human study assessed apixaban safety, pharmacokinetics and pharmacodynamics in healthy subjects randomized to oral apixaban (n = 43; 0.5–2.5 mg as solution or 5–50 mg as tablets) or placebo (n = 14) under fasted conditions. An open label, randomized, two treatment crossover study investigated apixaban pharmacokinetics/pharmacodynamics in healthy subjects (n = 21) administered apixaban 10 mg in fasted and fed states. Both studies measured apixaban plasma concentration, international normalized ratio (INR), activated partial thromboplastin time (aPTT) and prothrombin time (PT) or a modified PT (mPT). Results In the single ascending-dose study increases in apixaban exposure appeared dose-proportional. Median tmax occurred 1.5–3.3 h following oral administration. Mean terminal half-life ranged between 3.6 and 6.8 h following administration of solution doses ≤2.5 mg and between 11.1 and 26.8 h for tablet doses ≥5 mg. Concentration-related changes in pharmacodynamic assessments were observed. After a 50 mg dose, peak aPTT, INR and mPT increased by 1.2-, 1.6- and 2.9-fold, respectively, from baseline. In the food effect study: 90% confidence intervals of geometric mean ratios of apixaban Cmax and AUC in a fed vs. fasted state were within the predefined no effect (80–125%) range. Apixaban half-life was approximately 11.5 h. The effect of apixaban on INR, PT and aPTT was comparable following fed and fasted administration. Conclusions Single doses of apixaban were well tolerated with a predictable pharmacokinetic/pharmacodynamic profile and a half-life of approximately 12 h. Apixaban can be administered with or without food. PMID:22759198

Upper limb robot-assisted therapy in cerebral palsy: a single-blind randomized controlled trial.

PubMed

Gilliaux, Maxime; Renders, Anne; Dispa, Delphine; Holvoet, Dominique; Sapin, Julien; Dehez, Bruno; Detrembleur, Christine; Lejeune, Thierry M; Stoquart, Gaëtan

2015-02-01

Several pilot studies have evoked interest in robot-assisted therapy (RAT) in children with cerebral palsy (CP). To assess the effectiveness of RAT in children with CP through a single-blind randomized controlled trial. Sixteen children with CP were randomized into 2 groups. Eight children performed 5 conventional therapy sessions per week over 8 weeks (control group). Eight children completed 3 conventional therapy sessions and 2 robot-assisted sessions per week over 8 weeks (robotic group). For both groups, each therapy session lasted 45 minutes. Throughout each RAT session, the patient attempted to reach several targets consecutively with the REAPlan. The REAPlan is a distal effector robot that allows for displacements of the upper limb in the horizontal plane. A blinded assessment was performed before and after the intervention with respect to the International Classification of Functioning framework: body structure and function (upper limb kinematics, Box and Block test, Quality of Upper Extremity Skills Test, strength, and spasticity), activities (Abilhand-Kids, Pediatric Evaluation of Disability Inventory), and participation (Life Habits). During each RAT session, patients performed 744 movements on average with the REAPlan. Among the variables assessed, the smoothness of movement (P < .01) and manual dexterity assessed by the Box and Block test (P = .04) improved significantly more in the robotic group than in the control group. This single-blind randomized controlled trial provides the first evidence that RAT is effective in children with CP. Future studies should investigate the long-term effects of this therapy. © The Author(s) 2014.

Effect of single-dose low-level helium-neon laser irradiation on orthodontic pain: a split-mouth single-blind placebo-controlled randomized clinical trial.

PubMed

Sobouti, Farhad; Khatami, Maziar; Chiniforush, Nasim; Rakhshan, Vahid; Shariati, Mahsa

2015-01-01

Pain is the most common complication of orthodontic treatment. Low-level laser therapy (LLLT) has been suggested as a new analgesic treatment free of the adverse effects of analgesic medications. However, it is not studied thoroughly, and the available studies are quite controversial. Moreover, helium neon (He-Ne) laser has not been assessed before. This split-mouth placebo-controlled randomized clinical trial was performed on 16 male and 14 female orthodontic patients requiring bilateral upper canine retraction. The study was performed at a private clinic in Sari, Iran, in 2014. It was single blind: patients, orthodontist, and personnel were blinded of the allocations, but the laser operator (periodontist) was not blinded. Once canine retractor was activated, a randomly selected maxillary quarter received a single dose of He-Ne laser irradiation (632.8 nm, 10 mw, 6 j/cm(2) density). The other quarter served as the placebo side, treated by the same device but powered off. In the first, second, fourth, and seventh days, blinded patients rated their pain sensed on each side at home using visual analog scale (VAS) questionnaires. There was no harm identified during or after the study. Pain changes were analyzed using two- and one-way repeated-measures ANOVA, Bonferroni, and t-test (α = 0.01, β > 0.99). This trial was not registered. It was self-funded by the authors. Sixteen males and 11 females remained in the study (aged 12-21). Average pain scores sensed in all 4 intervals on control and laser sides were 4.06 ± 2.85 and 2.35 ± 1.77, respectively (t-test P < 0.0001). One-way ANOVA showed significant pain declines over time, in each group (P < 0.0001). Two-way ANOVA showed significant effects for LLLT (P < 0.0001) and time (P = <0.0001). Single-dose He-Ne laser therapy might reduce orthodontic pain caused by retracting maxillary canines.

Comparison of 4 supraglotttic devices used by paramedics during simulated CPR : a randomized controlled crossover trial.

PubMed

Szarpak, Łukasz; Kurowski, Andrzej; Truszewski, Zenon; Robak, Oliver; Frass, Michael

2015-08-01

Ensuring an open airway during cardiopulmonary resuscitation is fundamental. The aim of this study was to determine the success rate of blind intubation during simulated cardiopulmonary resuscitation by untrained personnel. Four devices were compared in a simulated resuscitation scenario: ILMA (Intavent Direct Ltd, Buckinghamshire, United Kingdom), Cobra PLA (Engineered Medical Systems Inc, Indianapolis, IN), Supraglottic Airway Laryngopharyngeal Tube (SALT) (ECOLAB, St. Paul, MN), and Air-Q (Mercury Medical, Clearwater, FL). A group of 210 paramedics intubated a manikin with continuous chest compressions. The mean times to intubation were 40.46 ± 4.64, 33.96 ± 6.23, 17.2 ± 4.63, and 49.23 ± 13.19 seconds (SALT vs ILMA, Cobra PLA, and Air-Q; P < .05). The success ratios of blind intubation for the devices were 86.7%, 85.7%, 100%, and 71.4% (SALT vs ILMA, Cobra PLA, and Air-Q; P < .05). The study showed that the most efficient device with the shortest blind intubation time was the SALT device. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of conjugated linoleic acid and high oleic acid safflower oil in the treatment of children with HPV-induced laryngeal papillomatosis: a randomized, double-blinded and crossover preliminary study.

PubMed

Louw, Louise

2012-10-12

Surgery is the mainstay therapy for HPV-induced laryngeal papillomatosis (LP) and adjuvant therapies are palliative at best. Research revealed that conjugated-linoleic acid (CLA) may improve the outcome of virally-induced diseases. The effects of Clarinol™ G-80 (CLA) and high oleic safflower oil (HOSF) on children with LP (concomitant with surgery) were evaluated. A randomized, double-blinded, crossover and reference-oil controlled trial was conducted at a South African medical university. Study components included clinical, HPV type/load and lymphocyte/cytokine analyses, according to routine laboratory methods. Overall: ten children enrolled; eight completed the trial; five remained randomized; seven received CLA first; all treatments remained double-blinded. Children (4 to 12 years) received 2.5 ml p/d CLA (8 weeks) and 2.5 ml p/d HOSF (8 weeks) with a washout period (6 weeks) in-between. The one-year trial included a post-treatment period (30 weeks) and afterwards was a one-year follow-up period. Changes in numbers of surgical procedures for improved disease outcome, total/anatomical scores (staging system) for papillomatosis prevention/viral inhibition, and lymphocyte/cytokine counts for immune responses between baselines and each treatment/end of trial were measured. After each treatment all the children were in remission (no surgical procedures); after the trial two had recurrence (surgical procedures in post-treatment period); after the follow-up period three had recurrence (several surgical procedures) and five recovered (four had no surgical procedures). Effects of CLA (and HOSF to a lesser extent) were restricted to mildly/moderately aggressive papillomatosis. Children with low total scores (seven/less) and reduced infections (three/less laryngeal sub-sites) recovered after the trial. No harmful effects were observed. The number of surgical procedures during the trial (n6/available records) was significantly lower [(p 0.03) (95% CI 1.1; 0)]. Changes in scores between baselines and CLA treatments (n8) were significantly lower: total scores [(p 0.02) (95% CI -30.00; 0.00)]; anatomical scores [(p 0.008) (95% CI -33.00: -2.00)]. Immune enhancement could not be demonstrated. These preliminary case and group findings pave the way for further research on the therapeutic potential of adjuvant CLA in the treatment of HPV-induced LP.

A Double-Blind Placebo-Controlled Crossover Trial of Intravenous Magnesium Sulfate for Foscarnet-Induced Ionized Hypocalcemia and Hypomagnesemia in Patients with AIDS and Cytomegalovirus Infection

PubMed Central

Huycke, Mark M.; Naguib, M. Tarek; Stroemmel, Mathias M.; Blick, Kenneth; Monti, Katherine; Martin-Munley, Sarah; Kaufman, Chris

2000-01-01

Foscarnet (trisodium phosphonoformate hexahydrate) is an antiviral agent used to treat cytomegalovirus disease in immunocompromised patients. One common side effect is acute ionized hypocalcemia and hypomagnesemia following intravenous administration. Foscarnet-induced ionized hypomagnesemia might contribute to ionized hypocalcemia by impairing excretion of preformed parathyroid hormone (PTH) or by producing target organ resistance. Prevention of ionized hypomagnesemia following foscarnet administration could blunt the development of ionized hypocalcemia. To determine whether intravenous magnesium ameliorates the decline in ionized calcium and/or magnesium following foscarnet infusions, MgSO4 at doses of 1, 2, and 3 g was administered in a double-blind, placebo-controlled, randomized, crossover trial to 12 patients with AIDS and cytomegalovirus disease. Overall, increasing doses of MgSO4 reduced or eliminated foscarnet-induced acute ionized hypomagnesemia. Supplementation, however, had no discernible effect on foscarnet-induced ionized hypocalcemia despite significant increases in serum PTH levels. No dose-related, clinically significant adverse events were found, suggesting that intravenous supplementation with up to 3 g of MgSO4 was safe in this chronically ill population. Since parenteral MgSO4 did not alter foscarnet-induced ionized hypocalcemia or symptoms associated with foscarnet, routine intravenous supplementation for patients with normal serum magnesium levels is not recommended during treatment with foscarnet. PMID:10898688

A double blind, placebo controlled, phase II randomised cross-over trial investigating the use of duloxetine for the treatment of chemotherapy-induced peripheral neuropathy.

PubMed

Battaglini, Eva; Park, Susanna B; Barnes, Elizabeth H; Goldstein, David

2018-04-20

Chemotherapy-induced peripheral neuropathy (CIPN) is a significant side effect of cancer treatment, potentially leading to early cessation of chemotherapy, enduring symptoms and long-lasting disability. Evidence from preclinical and clinical studies suggests that duloxetine, a serotonin-noradrenaline reuptake inhibitor, may be effective in the symptomatic treatment of CIPN. This double blind, placebo controlled, phase II randomised cross-over trial aims to determine whether treatment with duloxetine results in a reduction in chronic neuropathic symptoms experienced as a result of neurotoxic chemotherapy treatment. Participants who have received neurotoxic chemotherapy and experience daily symptoms as a consequence of peripheral neuropathy will be randomly allocated to control or experimental group with a 1:1 allocation, stratified by chemotherapy type. The primary endpoint will be patient-reported CIPN symptoms, as assessed via the FACT/GOG-Ntx. As a secondary objective, the trial will investigate whether duloxetine improves neurophysiological parameters and functional status in patients who have received neurotoxic chemotherapy treatment. This trial will investigate the effectiveness of duloxetine in reducing neuropathic symptoms following chemotherapy treatment, and aims to provide insight into the mechanisms underlying the symptomatic relief that duloxetine may provide. These results will be informative in advancing clinical knowledge regarding the treatment of CIPN. Copyright © 2018 Elsevier Inc. All rights reserved.

Efficacy of naproxen with or without esomeprazole for pain and inflammation in patients after bilateral third molar extractions: A double blinded crossover study

PubMed Central

Weckwerth, Giovana M.; Simoneti, Luis F.; Zupelari-Gonçalves, Paulo; Calvo, Adriana M.; Brozoski, Daniel T.; Dionísio, Thiago J.; Torres, Elza A.; Lauris, José-Roberto P.; Faria, Flávio-Augusto C.

2017-01-01

Background Using a double-blinded randomized crossover design, this study aimed to evaluate acute postoperative pain management, swelling and trismus in 46 volunteers undergoing extractions of the two lower third molars, in similar positions, at two different appointments who consumed a tablet of either NE (naproxen 500 mg + esomepraz ole 20 mg) or only naproxen (500 mg) every 12 hours for 4 days. Material and Methods Parameters were analyzed: self-reported pain intensity using a visual analog scale (VAS) pre- and postoperative mouth opening; incidence, type and severity of adverse reactions; total quantity consumed of rescue medication; and pre- and postoperative swelling. Results Female volunteers reported significantly more postoperative pain at 1, 1.5, 2, 3 and 4hrs after surgery while also taking their first rescue medication at a time significantly earlier when consuming NE when compared to naproxen (3.7hrs and 6.7hrs). Conversely, no differences were found between each drug group in males. Conclusions In conclusion, throughout the entire study, pain was mild after using either drug in both men and women with pain scores on average well below 40mm (VAS), although in women naproxen improved acute postoperative pain management when compared to NE. Key words:Oral surgery, third molar, pain, naproxen, esomeprazole, NSAIDs. PMID:27918744

The Effect of a 12-Week Beta-hydroxy-beta-methylbutyrate (HMB) Supplementation on Highly-Trained Combat Sports Athletes: A Randomised, Double-Blind, Placebo-Controlled Crossover Study

PubMed Central

Jeszka, Jan; Podgórski, Tomasz

2017-01-01

The aim of this study was to verify the effect of beta-hydroxy-beta-methylbutyrate (HMB) supplementation on physical capacity, body composition and the value of biochemical parameters in highly-trained combat sports athletes. Forty-two males highly-trained in combat sports were subjected to 12 weeks of supplementation with HMB and a placebo in a randomized, placebo controlled, double-blind crossover manner. Over the course of the experiment, aerobic and anaerobic capacity was determined, while analyses were conducted on body composition and levels of creatine kinase, lactate dehydrogenase, testosterone, cortisol and lactate. Following HMB supplementation, fat-free mass increased (p = 0.049) with a simultaneous reduction of fat mass (p = 0.016) in comparison to placebo. In turn, after HMB supplementation, the following indicators increased significantly in comparison to the placebo: the time to reach ventilatory threshold (p < 0.0001), threshold load (p = 0.017) and the threshold HR (p < 0.0001), as well as anaerobic peak power (p = 0.005), average power (p = 0.029), maximum speed (p < 0.001) and post-exercise lactate concentrations (p < 0.0001). However, when compared to the placebo, no differences were observed in blood marker levels. The results indicate that supplying HMB promotes advantageous changes in body composition and stimulates an increase in aerobic and anaerobic capacity in combat sports athletes. PMID:28708126

The Effect of a 12-Week Beta-hydroxy-beta-methylbutyrate (HMB) Supplementation on Highly-Trained Combat Sports Athletes: A Randomised, Double-Blind, Placebo-Controlled Crossover Study.

PubMed

Durkalec-Michalski, Krzysztof; Jeszka, Jan; Podgórski, Tomasz

2017-07-14

The aim of this study was to verify the effect of beta-hydroxy-beta-methylbutyrate (HMB) supplementation on physical capacity, body composition and the value of biochemical parameters in highly-trained combat sports athletes. Forty-two males highly-trained in combat sports were subjected to 12 weeks of supplementation with HMB and a placebo in a randomized, placebo controlled, double-blind crossover manner. Over the course of the experiment, aerobic and anaerobic capacity was determined, while analyses were conducted on body composition and levels of creatine kinase, lactate dehydrogenase, testosterone, cortisol and lactate. Following HMB supplementation, fat-free mass increased ( p = 0.049) with a simultaneous reduction of fat mass ( p = 0.016) in comparison to placebo. In turn, after HMB supplementation, the following indicators increased significantly in comparison to the placebo: the time to reach ventilatory threshold ( p < 0.0001), threshold load ( p = 0.017) and the threshold HR ( p < 0.0001), as well as anaerobic peak power ( p = 0.005), average power ( p = 0.029), maximum speed ( p < 0.001) and post-exercise lactate concentrations ( p < 0.0001). However, when compared to the placebo, no differences were observed in blood marker levels. The results indicate that supplying HMB promotes advantageous changes in body composition and stimulates an increase in aerobic and anaerobic capacity in combat sports athletes.

Effect of Oral Coadministration of Ascorbic Acid with Ling Zhi Preparation on Pharmacokinetics of Ganoderic Acid A in Healthy Male Subjects: A Randomized Crossover Study

PubMed Central

Tawasri, Patcharanee; Ampasavate, Chadarat; Tharatha, Somsak

2016-01-01

The objective of this randomized, open-label, single-dose, two-phase crossover study was to determine the effect of ascorbic acid on pharmacokinetics of ganoderic acid A, an important biologically active triterpenoid compound with anticancer activities, following oral administration of water extract of fruiting bodies of Ling Zhi in 12 healthy male subjects. Each subject was randomized to receive either one of the two regimens: (1) a single dose of 3,000 mg of the Ling Zhi preparation or (2) a single dose of 3,000 mg of the Ling Zhi preparation in combination with 2,500 mg of ascorbic acid. After a washout period of at least two weeks, subjects were switched to receive the alternate regimen. Blood samples were collected in each phase immediately before dosing and at specific time points for 8 hours after dosing. Plasma ganoderic acid A concentrations were quantified using liquid chromatography-mass spectrometry (LC-MS). The pharmacokinetic parameters analyzed were maximal plasma concentration (C max), time to reach peak concentration (T max), area under the plasma concentration-time curve (AUC), and half-life (t 1/2). An oral coadministration of ascorbic acid with Ling Zhi preparation did not significantly alter the pharmacokinetic parameters of ganoderic acid A in healthy male subjects. PMID:27747224

Transcutaneous Electrical Nerve Stimulation (TENS) reduces pain, fatigue, and hyperalgesia while restoring central inhibition in primary fibromyalgia

PubMed Central

Dailey, Dana L; Rakel, Barbara A; Vance, Carol GT; Liebano, Richard E; Anand, Amrit S; Bush, Heather M; Lee, Kyoung S; Lee, Jennifer E; Sluka, Kathleen A

2014-01-01

Because TENS works by reducing central excitability and activating central inhibition pathways, we tested the hypothesis that TENS would reduce pain and fatigue and improve function and hyperalgesia in people with fibromyalgia who have enhanced central excitability and reduced inhibition. The current study used a double-blinded randomized, placebo controlled cross-over design to test effects of a single treatment of TENS in people with fibromyalgia. Three treatments were assessed in random order: active TENS, placebo TENS, no TENS. The following measures were assessed before and after each TENS treatment: pain and fatigue at rest and movement, pressure pain thresholds (PPTs), 6 minute walk test (6MWT), range of motion (ROM), five time sit to stand test (FTSTS), and single leg stance (SLS). Conditioned pain modulation (CPM) was completed at end of testing. There was a significant decrease in pain and fatigue with movement for active TENS compared to placebo and no TENS. PPTs increased at site of TENS (spine) and outside site of TENS (leg) when compared to placebo TENS or no TENS. During Active TENS CPM was significantly stronger compared to placebo TENS and no TENS. No changes in functional tasks were observed with TENS. Thus, the current study suggests TENS has short-term efficacy in relieving symptoms of fibromyalgia while the stimulator is active. Future clinical trials should examine the effects of repeated daily delivery of TENS, similar to how TENS is used clinically, on pain, fatigue, function and quality of life in individuals with fibromyalgia. PMID:23900134

The effect of fish oil supplements on blood pressure.

PubMed Central

Lofgren, R P; Wilt, T J; Nichol, K L; Crespin, L; Pluhar, R; Eckfeldt, J

1993-01-01

We conducted a double-blind, placebo-controlled crossover study to determine the effects of fish oil supplementation on blood pressure in middle-aged men. Subjects were randomly assigned to consume either 20 g of fish oil or safflower oil for 12 weeks and then consume the other oil for an additional 12 weeks after a 4-week washout period. We found no significant changes from the pretreatment value in systolic or diastolic blood pressure with the use of fish oil supplements. In addition, there were no significant differences in the posttreatment blood pressures comparing the fish and safflower oil phases of the study. PMID:8427339

Evaluation of the immediate effect of acupuncture on pain, cervical range of motion and electromyographic activity of the upper trapezius muscle in patients with nonspecific neck pain: study protocol for a randomized controlled trial.

PubMed

Calamita, Simone Aparecida Penimpedo; Biasotto-Gonzalez, Daniela Aparecida; De Melo, Nivea Cristina; dos Santos, Douglas Meira; de Lassa, Roberta; de Mendonça, Fabiana Sarilho; Oliveira, Claudia Santos; Amorim, César Ferreira; Gonzalez, Tabajara Oliveira; Fumagalli, Marco Antônio; de Gomes, Cid André Fidelis Paula; Politti, Fabiano

2015-03-19

Nonspecific neck pain can cause considerable suffering, possible disability and reductions in quality of life and productivity. The aim of the proposed study is to evaluate the immediate effect of acupuncture on pain, cervical range of motion and electromyographic activity of the upper trapezius muscle in patients with nonspecific neck pain. A total of 12 patients with nonspecific neck pain and 12 healthy subjects will be enrolled in a randomized, single-blind crossover study. Each subject will receive two forms of treatment in random order: a single session of traditional acupuncture (acupoints: triple energizer 5, 'Wai-guan' and large intestine 11, 'Qu-chi') and sham acupuncture. To eliminate carry-over treatment effects, a one-week wash-out period will be respected between sessions. Surface electromyography will be used to determine motor control in the upper trapezius muscle before and after treatment. The outcome measures in the group with neck pain will be a numerical pain rating scale (range: 0 (no pain) to 10 (maximum pain)), documentation of the pain area on a body chart and cervical range of motion. Comparisons before and after acupuncture treatment will demonstrate whether acupoints affect the activity of the upper trapezius muscle, pain and cervical range of motion. The purpose of this randomized clinical trial is to evaluate the immediate effect of acupuncture on pain, cervical range of motion and electromyographic activity of the upper trapezius muscle in patients with nonspecific neck pain. Data will be published after the study is completed. The study will support the practice of evidence-based physical therapy for individuals with nonspecific neck pain. This trial was registered with Clinicaltrials.gov (identifier: NCT0984021 ) on 7 November 2013 ( https://clinicaltrials.gov/ct2/show/NCT01984021 ).

Asperger syndrome and anxiety disorders (PAsSA) treatment trial: a study protocol of a pilot, multicentre, single-blind, randomised crossover trial of group cognitive behavioural therapy

PubMed Central

Langdon, Peter E; Murphy, Glynis H; Wilson, Edward; Shepstone, Lee; Fowler, David; Heavens, David; Malovic, Aida; Russell, Alexandra

2013-01-01

Introduction A number of studies have established that children, adolescents and adults with Asperger syndrome (AS) and high functioning autism (HFA) have significant problems with anxiety. Cognitive behavioural therapy (CBT) is an effective treatment for anxiety in a variety of clinical populations. There is a growing interest in exploring the effectiveness of CBT for people with AS who have mental health problems, but currently there are no known clinical trials involving adults with AS or HFA. Studies with children who have AS have reported some success. The current study aims to examine whether modified group CBT for clinically significant anxiety in an AS population is likely to be efficacious. Methods and analysis This study is a randomised, single-blind crossover trial. At least 36 individuals will be recruited and randomised into a treatment arm or a waiting-list control arm. During treatment, individuals will receive 3 sessions of individual CBT, followed by 21 sessions of group CBT. Primary outcome measures focus on anxiety. Secondary outcome measures focus on everyday social and psychiatric functioning, additional measures of anxiety and fear, depression, health-related quality of life and treatment cost. Assessments will be administered at pregroup and postgroup and at follow-up by researchers who are blinded to group allocation. The trial aims to find out whether or not psychological treatments for anxiety can be adapted and used to successfully treat the anxiety experienced by people with AS. Furthermore, we aim to determine whether this intervention represents good value for money. Ethics and dissemination The trial received a favourable ethical opinion from a National Health Service (NHS) Research Ethics Committee. All participants provided written informed consent. Findings will be shared with all trial participants, and the general public, as well as the scientific community. Trial Registration ISRCTN 30265294 (DOI: 10.1186/ISRCTN30265294), UKCRN 8370. PMID:23901031

Effect of pre-cooling injection site on pain perception in pediatric dentistry: “A randomized clinical trial”

PubMed Central

Ghaderi, Faezeh; Banakar, Shahin; Rostami, Shima

2013-01-01

Background: Injection of local anesthesia is one of the most important reasons for development of avoidance behavior in children. Efforts have been performed to decrease pain perception of injection. The present research evaluated the effect of cooling the injection site on pain perception before infiltration of local anesthetics. Materials and Methods: A prospective single-blind crossover clinical trial was used to investigate pain perception in 50 healthy pediatric patients who needed bilateral buccal infiltration of local anesthetics for dental treatment. They received a topical anesthetic agent (Benzocaine) on one side (control) for 1 min and topical anesthetic agent plus one minute of ice pack on the other side (trial) prior to the injection. A dentist blind to the study assessed the patients’ reaction during injection. Wilcoxon and Mann-Whitney U tests were used for statistical analysis. Statistical significance was defined at P < 0.05. Results: The means of sound, eye, and motor scales (SEM) were 4.06 ± 1.32 and 5.44 ± 1.79 for the study and control groups, respectively. The means of visual analogue scales (VAS) for the study and control groups were 42.20 ± 12.70 and 58.40 ± 16.83, respectively; with statistically significant differences between the two groups (P < 0.05). Conclusion: Cooling the injection site before infiltration of local anesthetics in the buccal mucosa for 1 min, reduced pain perceived by pediatric patients. PMID:24379869

Polarity-Dependent Misperception of Subjective Visual Vertical during and after Transcranial Direct Current Stimulation (tDCS).

PubMed

Santos-Pontelli, Taiza E G; Rimoli, Brunna P; Favoretto, Diandra B; Mazin, Suleimy C; Truong, Dennis Q; Leite, Joao P; Pontes-Neto, Octavio M; Babyar, Suzanne R; Reding, Michael; Bikson, Marom; Edwards, Dylan J

2016-01-01

Pathologic tilt of subjective visual vertical (SVV) frequently has adverse functional consequences for patients with stroke and vestibular disorders. Repetitive transcranial magnetic stimulation (rTMS) of the supramarginal gyrus can produce a transitory tilt on SVV in healthy subjects. However, the effect of transcranial direct current stimulation (tDCS) on SVV has never been systematically studied. We investigated whether bilateral tDCS over the temporal-parietal region could result in both online and offline SVV misperception in healthy subjects. In a randomized, sham-controlled, single-blind crossover pilot study, thirteen healthy subjects performed tests of SVV before, during and after the tDCS applied over the temporal-parietal region in three conditions used on different days: right anode/left cathode; right cathode/left anode; and sham. Subjects were blind to the tDCS conditions. Montage-specific current flow patterns were investigated using computational models. SVV was significantly displaced towards the anode during both active stimulation conditions when compared to sham condition. Immediately after both active conditions, there were rebound effects. Longer lasting after-effects towards the anode occurred only in the right cathode/left anode condition. Current flow models predicted the stimulation of temporal-parietal regions under the electrodes and deep clusters in the posterior limb of the internal capsule. The present findings indicate that tDCS over the temporal-parietal region can significantly alter human SVV perception. This tDCS approach may be a potential clinical tool for the treatment of SVV misperception in neurological patients.

Human Abuse Potential of an Abuse-Deterrent (AD), Extended-Release (ER) Morphine Product Candidate (Morphine-ADER Injection-Molded Tablets) versus Extended-Release Morphine Administered Orally in Nondependent Recreational Opioid Users

PubMed Central

Webster, Lynn R.; Lawler, John; Lindhardt, Karsten; Dayno, Jeffrey M.

2017-01-01

Objective. To compare the relative human abuse potential of intact and manipulated morphine abuse-deterrent, extended-release injection-molded tablets (morphine-ADER-IMT) with that of marketed morphine sulfate ER tablets Methods. This randomized, double-blind, triple-dummy, active- and placebo-controlled, 4-way crossover, single-center study included adult volunteers who were experienced, nondependent, recreational opioid users. Participants were randomized 1:1:1:1 to placebo, morphine-ADER-IMT (60 mg, intact), morphine-ADER-IMT (60 mg, manipulated), and morphine ER (60 mg, manipulated) and received 1 dose of each oral agent in crossover fashion, separated by ≥5 days. Pharmacodynamic and pharmacokinetic endpoints were assessed, including the primary endpoint of peak effect of Drug Liking (Emax) via Drug Liking Visual Analog Scale (VAS) score and the secondary endpoints of time to Emax (TEmax) and mean abuse quotient (AQ; a pharmacokinetic parameter associated with drug liking). Results. Thirty-eight participants completed the study. Median Drug Liking VAS Emax was significantly lower after treatment with manipulated morphine-ADER-IMT (67) compared with manipulated morphine ER (74; P = 0.007). TEmax was significantly shorter after treatment with manipulated morphine ER compared with intact (P < 0.0001) or manipulated (P = 0.004) morphine-ADER-IMT. Mean AQ was lower after treatment with intact (5.7) or manipulated (16.4) morphine-ADER-IMT compared with manipulated morphine ER (45.9). Conclusions. Manipulated morphine-ADER-IMT demonstrated significantly lower Drug Liking Emax compared with manipulated morphine ER when administered orally. Morphine-ADER-IMT would be an important new AD, ER morphine product with lower potential for unintentional misuse by chewing or intentional manipulation for oral abuse than currently available non-AD morphine ER products. PMID:27633773

A randomized crossover efficacy trial of oral CPAP (Oracle) compared with nasal CPAP in the management of obstructive sleep apnea.

PubMed

Anderson, Fiona E; Kingshott, Ruth N; Taylor, D Robin; Jones, David R; Kline, Lewis R; Whyte, Kenneth F

2003-09-01

To determine the therapeutic efficacy and viability of a novel oral interface for continuous positive airway pressure (CPAP) compared with conventional nasal interfaces. A randomized single-blind crossover study. Hospital-based sleep laboratory. 21 CPAP-naïve patients with obstructive sleep apnea (baseline apnea-hypopnea index, 85 +/- 36) INTERVENTIONS: Nasal CPAP and oral CPAP MEASUREMENTS AND RESULTS: Patients were each treated for two 4-week periods using nasal CPAP and oral CPAP. The CPAP titrations were undertaken at the start of each treatment arm. Outcome measures were recorded at baseline and at the end of each treatment arm. These included polysomnography variables, CPAP compliance, subjective sleepiness, obstructive sleep apnea symptom ratings, and adverse effects. There were no significant differences between oral and nasal interfaces for the on-CPAP frequency of apneas and hypopneas (mean difference, nasal-oral [95%CI] = -4.6[-10.1-1.0]/h; P = 0.06) or arousals (-3.0 [-7.8-1.8]/h; P = 0.23). There were also no statistically significant differences between interfaces for scores on the Epworth Sleepiness Scale (-0.7 [-3.1-1.7]; P = 0.20), obstructive sleep apnea symptoms (-7.7 [-17.7-2.4]; P = 0.052), CPAP compliance (0.3 [-0.5-1.1] h/night; P = 0.50), CPAP pressure (0.05 [-0.66-0.76] cmH20; P = 0.73), CPAP side effects scores (-2.0 [-5.3-1.4]; P = 0.23), or mask preference (P = 0.407). In addition, both nasal and oral interfaces significantly improved polysomnographic variables, Epworth Sleepiness Scale scores, obstructive sleep apnea symptoms, and CPAP compliance from baseline (all P < 0.05). This preliminary study indicates that oral CPAP has similar efficacy to traditionally applied nasal CPAP in treating obstructive sleep apnea. Additional large studies are required to determine the range of clinical situations where oral CPAP is indicated.

A randomized phase l pharmacokinetic study comparing SB4 and etanercept reference product (Enbrel®) in healthy subjects

PubMed Central

Shin, Donghoon; Kim, Youngdoe; Kang, Jungwon; Gauliard, Anke; Fuhr, Rainard

2016-01-01

Aims SB4 has been developed as a biosimilar of etanercept. The primary objective of the present study was to demonstrate the pharmacokinetic (PK) equivalence between SB4 and European Union ‐sourced etanercept (EU‐ETN), SB4 and United States‐sourced etanercept (US‐ETN), and EU‐ETN and US‐ETN. The safety and immunogenicity were also compared between the treatments. Methods This was a single‐blind, three‐part, crossover study in 138 healthy male subjects. In each part, 46 subjects were randomized at a 1:1 ratio to receive a single 50 mg subcutaneous dose of the treatments (part A: SB4 or EU‐ETN; part B: SB4 or US‐ETN; and part C: EU‐ETN or US‐ETN) in period 1, followed by the crossover treatment in period 2 according to their assigned sequences. PK equivalence between the treatments was determined using the standard equivalence margin of 80–125%. Results The geometric least squares means ratios of AUCinf, AUClast and Cmax were 99.04%, 98.62% and 103.71% (part A: SB4 vs. EU‐ETN); 101.09%, 100.96% and 104.36% (part B: SB4 vs. US‐ETN); and 100.51%, 101.27% and 103.29% (part C: EU‐ETN vs. US‐ETN), respectively, and the corresponding 90% confidence intervals were completely contained within the limits of 80–125 %. The incidence of treatment‐emergent adverse events was comparable, and the incidence of the antidrug antibodies was lower in SB4 compared with the reference products. Conclusions The present study demonstrated PK equivalence between SB4 and EU‐ETN, SB4 and US‐ETN, and EU‐ETN and US‐ETN in healthy male subjects. SB4 was well tolerated, with a lower immunogenicity profile and similar safety profile compared with those of the reference products. PMID:26972584

Efficacy of a Mandibular Advancement Appliance on Sleep Disordered Breathing in Children: A Study Protocol of a Crossover Randomized Controlled Trial

PubMed Central

Idris, Ghassan; Galland, Barbara; Robertson, Christopher J.; Farella, Mauro

2016-01-01

Background: Sleep-Disordered Breathing (SDB) varies from habitual snoring to partial or complete obstruction of the upper airway and can be found in up to 10% of children. SDB can significantly affect children's wellbeing, as it can cause growth disorders, educational and behavioral problems, and even life-threatening conditions, such as cardiorespiratory failure. Adenotonsillectomy represents the primary treatment for pediatric SDB where adeno-tonsillar hypertrophy is indicated. For those with craniofacial anomalies, or for whom adenotonsillectomy or other treatment modalities have failed, or surgery is contra-indicated, mandibular advancement splints (MAS) may represent a viable treatment option. Whilst the efficacy of these appliances has been consistently demonstrated in adults, there is little information about their effectiveness in children. Aims: To determine the efficacy of mandibular advancement appliances for the management of SDB and related health problems in children. Methods/design: The study will be designed as a single-blind crossover randomized controlled trial with administration of both an “Active MAS” (Twin-block) and a “Sham MAS.” Eligible participants will be children aged 8–12 years whose parents report they snore ≥3 nights per week. Sixteen children will enter the full study after confirming other inclusion criteria, particularly Skeletal class I or class II confirmed by lateral cephalometric radiograph. Each child will be randomly assigned to either a treatment sequence starting with the Active or the Sham MAS. Participants will wear the appliances for 3 weeks separated by a 2-week washout period. For each participant, home-based polysomnographic data will be collected four times; once before and once after each treatment period. The Apnea Hypopnea Index (AHI) will represent the main outcome variable. Secondary outcomes will include, snoring frequency, masseter muscle activity, sleep symptoms, quality of life, daytime sleepiness, children behavior, and nocturnal enuresis. In addition, blood samples will be collected to assess growth hormone changes. Trial registration: This study was registered in the Australian New Zealand Clinical Trials Registry (ANZCTR): [ACTRN12614001013651]. PMID:27594841

Remote Effects of Electromagnetic Millimeter Waves on Experimentally Induced Cold Pain: A Double-Blinded Crossover Investigation in Healthy Volunteers.

PubMed

Partyla, Tomasz; Hacker, Henriette; Edinger, Hardy; Leutzow, Bianca; Lange, Joern; Usichenko, Taras

2017-03-01

The hypoalgesic effect of electromagnetic millimeter waves (MW) is well studied in animal model; however, the results of human research are controversial. The aim of this study was to evaluate the effects of various frequency ranges of MW on hypoalgesia using the cold pressor test (CPT). Experimental pain was induced using standardized CPT protocols in 20 healthy male volunteers. The skin of the lower part of sternum was exposed to MW with a frequency of 42.25 GHz (active generator); MW within 50-75 GHz frequency range (noise generator); or an inactive MW device (placebo generator) in a random crossover double-blinded manner. Pain threshold, measured using the CPT, was the primary outcome. Other CPT parameters, heart rate, blood pressure, incidence of subjective sensations (paresthesia) during exposure, as well as quality of volunteers' blinding were also recorded. The end points of the condition with exposure to 42.25 GHz, were compared with baseline; exposure to noise 50-75 GHz; and placebo generators. Pain threshold increased during exposure to the 42.25 GHz generator when compared with baseline: median difference (MD), 1.97 seconds (95% confidence interval [CI], 0.35-3.73) and noise generator: MD, 1.27 seconds (95% CI, 0.05-2.33) but not compared with the placebo generator. Time to onset of cold and increasing pain sensations as well as diastolic blood pressure increased under the exposure to the 42.25 GHz generator when compared with baseline and noise generator. Other outcome measures were comparable among the study conditions. We were able to partially confirm the previously suggested hypoalgesic effects of low-intensity electromagnetic MW. However, the effect was indistinguishable from the placebo condition in our investigation.

An interactive sports video game as an intervention for rehabilitation of community-living patients with schizophrenia: A controlled, single-blind, crossover study.

PubMed

Shimizu, Nobuko; Umemura, Tomohiro; Matsunaga, Masahiro; Hirai, Takayoshi

2017-01-01

Hypofrontality is a state of decreased cerebral blood flow in the prefrontal cortex during executive function performance; it is commonly observed in patients with schizophrenia. Cognitive dysfunction, as well as the psychological symptoms of schizophrenia, influences the ability of patients to reintegrate into society. The current study investigated the effects of an interactive sports video game (IVG; Nintendo Wii™ Sports Resort) on frontal lobe function of patients with schizophrenia. A sample of eight patients (6 male and 2 female; mean age = 46.7 years, standard deviation (SD) = 13.7) engaged in an IVG every week for 3 months in a controlled, single-blind, crossover study. Before and after the intervention we examined frontal lobe blood-flow volume using functional near-infrared spectroscopy (fNIRS), and assessed functional changes using the Frontal Assessment Battery, Health-Related Quality of Life scale, and behaviorally-assessed physical function tests. fNIRS revealed that prefrontal activity during IVG performance significantly increased in the IVG period compared with the control period. Furthermore, significant correlations between cerebral blood flow changes in different channels were observed during IVG performance. In addition, we observed intervention-related improvement in health-related quality of life following IVG. IVG intervention was associated with increased prefrontal cortex activation and improved health-related quality of life performance in patients with schizophrenia. Patients with chronic schizophrenia are characterized by withdrawal and a lack of social responsiveness or interest in others. Interventions using IVG may provide a useful low-cost rehabilitation method for such patients, without the need for specialized equipment.

A randomised crossover placebo-controlled trial investigating the effect of brown seaweed (Ascophyllum nodosum and Fucus vesiculosus) on postchallenge plasma glucose and insulin levels in men and women.

PubMed

Paradis, Marie-Eve; Couture, Patrick; Lamarche, Benoît

2011-12-01

This study examined the impact of brown seaweed on post-load plasma glucose and insulin concentrations in men and women. Twenty-three participants (11 men, 12 women) aged 19-59 years were recruited in this double-blind, randomized, placebo-controlled crossover study. The test product consisted of a commercially available blend of brown seaweed (Ascophyllum nodosum and Fucus vesiculosus) with known inhibitory action on α-amylase and α-glucosidase activities (InSea²). Two 250 mg seaweed capsules and 2 placebo capsules were consumed on each occasion 30 min prior to the consumption of 50 g of carbohydrates from bread. Plasma glucose and insulin concentrations were measured over a period of 3 h postcarbohydrate ingestion at predetermined time points. Both treatments were separated by a 1-week washout period. Data were analysed using mixed models for repeated measures. Compared with placebo, consumption of seaweed was associated with a 12.1% reduction in the insulin incremental area under the curve (p = 0.04, adjusted for baseline) and a 7.9% increase in the Cederholm index of insulin sensitivity (p < 0.05). The single ingestion of 500 mg of brown seaweed had no significant effect on the glucose response (p = 0.24, adjusted for baseline). Glucose and insulin responses were similar between men and women. Consumption of the seaweed capsules was not associated with any adverse event. These data suggest that brown seaweed may alter the insulin homeostasis in response to carbohydrate ingestion.

Single and short-term dosing effects of levocetirizine on adenosine monophosphate bronchoprovocation in atopic asthma

PubMed Central

Lee, Daniel K C; Gray, Robert D; Wilson, Andrew M; Robb, Fiona M; Soutar, Patricia C; Lipworth, Brian J

2004-01-01

Aims Adenosine monophosphate (AMP) acts indirectly via primed airway mast cells to induce bronchial hyper-responsiveness, which in turn correlates with eosinophilic asthmatic inflammation and atopic disease expression. We evaluated single and short-term dosing effects of a modern histamine H1-receptor antagonist, levocetirizine, given at the usual clinically recommended dose, on the primary outcome of AMP bronchoprovocation. Methods Fifteen atopic asthmatics were randomized in double-blind, cross-over fashion to receive for 1 week either levocetirizine 5 mg or placebo. There was a 1-week washout period prior to each randomized treatment. The provocative concentration of AMP producing a 20% fall in FEV1 (PC20) was measured after each washout at baseline and at 4–6 h following the first and last doses of each randomized treatment. Results Baseline mean ± SEM values after washout prior to each randomized treatment comparing levocetirizine vs placebo were not significantly different for prechallenge FEV1 (% predicted) 83 ± 4 vs 82 ± 4, or AMP PC20 (mg ml−1) 45 ± 24 vs 45 ± 22, respectively. Airway calibre as prechallenge FEV1 for levocetirizine vs placebo was not significantly different following the first dose 86 ± 4 vs 82 ± 4, or the last dose 85 ± 4 vs 83 ± 4, respectively. There were significant improvements (P< 0.05) in AMP PC20 comparing levocetirizine vs placebo following the first dose 123 ± 73 vs 48 ± 24, a 1.4 doubling dilution difference (95% CI 0.8, 1.9), and the last dose 127 ± 74 vs 53 ± 29, a 1.2 doubling dilution difference (95% CI 0.5, 2.0). AMP PC20 was also improved (P< 0.05) by the first and last doses of levocetirizine but not placebo, vs respective baseline values, with there being no difference in the degree of protection between first and last doses. Conclusions Single and short-term dosing with levocetirizine conferred similar improvements in bronchial hyper-responsiveness to AMP challenge, which was unrelated to prechallenge airway calibre. Further studies are indicated to evaluate the longer-term effects of levocetirizine on asthma exacerbations. PMID:15206990

The Effect of Aromatherapy Abdominal Massage on Alleviating Menstrual Pain in Nursing Students: A Prospective Randomized Cross-Over Study

PubMed Central

Marzouk, Tyseer M. F.; El-Nemer, Amina M. R.; Baraka, Hany N.

2013-01-01

Dysmenorrhea is a common cause of sickness absenteeism from both classes and work. This study investigated the effect of aromatherapy massage on a group of nursing students who are suffering of primary dysmenorrhea. A randomized blind clinical trial of crossover design was used. In the first treatment phase, group 1 (n = 48) received aromatherapy abdominal massage once daily for seven days prior to menstruation using the essential oils (cinnamon, clove, rose, and lavender in a base of almond oil). Group 2 (n = 47) received the same intervention but with placebo oil (almond oil). In the second treatment phase, the two groups switched to alternate regimen. Level and duration of pain and the amount of menstrual bleeding were evaluated at the baseline and after each treatment phase. During both treatment phases, the level and duration of menstrual pain and the amount of menstrual bleeding were significantly lower in the aromatherapy group than in the placebo group. These results suggests that aromatherapy is effective in alleviating menstrual pain, its duration and excessive menstrual bleeding. Aromatherapy can be provided as a nonpharmacological pain relief measure and as a part of nursing care given to girls suffering of dysmenorrhea, or excessive menstrual bleeding. PMID:23662151

A single meal containing raw, crushed garlic influences expression of immunity- and cancer-related genes in whole blood of humans

USDA-ARS?s Scientific Manuscript database

Preclinical and epidemiological studies suggest that garlic intake is inversely associated with the progression of cancer and cardiovascular disease. To probe mechanisms of garlic action in humans, we conducted a randomized crossover feeding trial in which 17 volunteers consumed a garlic-containing...

An evaluation of short-term corticosteroid response in perennial allergic rhinitis using histamine and adenosine monophosphate nasal challenge

PubMed Central

Wilson, Andrew M; Sims, Erika J; Orr, Linda C; Robb, Fiona; Lipworth, Brian J

2003-01-01

Aims To evaluate the role of AMP nasal challenge as a measure of short-term treatment response in patients receiving intranasal corticosteroids. Adenosine monophosphate (AMP) challenge has been shown to be a good inflammatory surrogate in the lower airways, but it has not been properly evaluated as a nasal challenge test. Methods Fourteen patients with perennial allergic rhinitis (PAR) were randomized to receive 2 weeks treatment with placebo (PL) or 200 µg intranasal mometasone furoate (MF) once daily in a randomized single-blind crossover study. AMP (25–800 mg ml−1) and histamine (0.25–8 mg ml−1) nasal challenge testing were performed after each treatment period with 30% decrease in minimal cross-sectional area (MCA). Domiciliary symptom data were collected. Results There was a significant (P < 0.05) improvement in PC30 MCA and nasal volume with AMP but not with histamine comparing MF vs PL. This amounted to a 2.8 (95% CI 1.5, 4.0) and 0.7 (95% CI −0.5, 1.9) doubling-dose change for AMP and histamine challenges, respectively. There were significant (P < 0.05) improvements in nasal symptoms and quality of life. Conclusions AMP nasal challenge using acoustic rhinometry may be a useful test to assess short-term treatment response in patient with PAR. PMID:12680883

Coffee, hunger, and peptide YY.

PubMed

Greenberg, James A; Geliebter, Allan

2012-06-01

There is evidence from several empirical studies suggesting that coffee may help people control body weight. Our objective was to assess the effects of caffeine, caffeinated coffee, and decaffeinated coffee, both alone and in combination with 75 g of glucose, on perceived hunger and satiety and related peptides. We conducted a placebo-controlled single-blinded randomized 4-way crossover trial. Eleven healthy male volunteers (mean age, 23.5 ± 5.7 years; mean BMI, 23.6 ± 4.2 kg/m(2)) ingested 1 of 3 test beverages (caffeine in water, caffeinated coffee, or decaffeinated coffee) or placebo (water), and 60 minutes later they ingested the glucose. Eight times during each laboratory visit, hunger and satiety were assessed by visual analog scales, and blood samples were drawn to measure 3 endogenous peptides associated with hunger and satiety: ghrelin, peptide YY (PYY), and leptin. Compared to placebo, decaffeinated coffee yielded significantly lower hunger during the whole 180-minute study period and higher plasma PYY for the first 90 minutes (p < 0.05). Caffeine in water had no effects on hunger or PYY. Caffeinated coffee showed a pattern between that of decaffeinated coffee and caffeine in water. These findings suggest that one or more noncaffeine ingredients in coffee may have the potential to decrease body weight. Glucose ingestion did not change the effects of the beverages. Our randomized human trial showed that decaffeinated coffee can acutely decrease hunger and increase the satiety hormone PYY.

Effect of Intermittent Energy Restriction on Flow Mediated Dilatation, a Measure of Endothelial Function: A Short Report.

PubMed

Headland, Michelle L; Clifton, Peter M; Keogh, Jennifer B

2018-06-04

Intermittent energy restriction is a popular alternative to daily energy restriction for weight loss; however, it is unknown if endothelial function, a risk factor for cardiovascular disease, is altered by periods of severe energy restriction. The objective of the study was to determine the impact of two consecutive very low energy intake days, which is the core component of the 5:2 intermittent energy restriction diet strategy, on endothelial function compared to consecutive ad libitum eating days. The secondary objective was to explore the effects of these dietary conditions on fasting glucose concentrations. This was a 4-week randomized, single-blinded, crossover study of 35 participants. Participants consumed a very low energy diet (500 calories for women, 600 calories for men) on two consecutive days per week and 5 days of habitual eating. In weeks 3 and 4 of the trial, participants had measurements of flow mediated dilatation (FMD) and blood samples taken following either 2 habitual eating days or 2 energy restricted days in a randomized order. FMD values were not different after the two eating states (8.6% vs. 8.3%, p = 0.7). All other outcome variables were unchanged. Endothelial function, as measured by flow mediated dilatation, was not altered by two consecutive very low energy intake days. Further investigations assessing the impact in specific population groups as well as different testing conditions would be beneficial.

Low dose intranasal oxytocin delivered with Breath Powered device dampens amygdala response to emotional stimuli: A peripheral effect-controlled within-subjects randomized dose-response fMRI trial.

PubMed

Quintana, Daniel S; Westlye, Lars T; Alnæs, Dag; Rustan, Øyvind G; Kaufmann, Tobias; Smerud, Knut T; Mahmoud, Ramy A; Djupesland, Per G; Andreassen, Ole A

2016-07-01

It is unclear if and how exogenous oxytocin (OT) reaches the brain to improve social behavior and cognition and what is the optimal dose for OT response. To better understand the delivery routes of intranasal OT administration to the brain and the dose-response, we compared amygdala response to facial stimuli by means of functional magnetic resonance imaging (fMRI) in four treatment conditions, including two different doses of intranasal OT using a novel Breath Powered device, intravenous (IV) OT, which provided similar concentrations of blood plasma OT, and placebo. We adopted a randomized, double-blind, double-dummy, crossover design, with 16 healthy male adults administering a single-dose of these four treatments. We observed a treatment effect on right amygdala activation during the processing of angry and happy face stimuli, with pairwise comparisons revealing reduced activation after the 8IU low dose intranasal treatment compared to placebo. These data suggest the dampening of amygdala activity in response to emotional stimuli occurs via direct intranasal delivery pathways rather than across the blood-brain barrier via systemically circulating OT. This trial is registered at the U.S. National Institutes of Health clinical trial registry (www.clinicaltrials.gov; NCT01983514) and as EudraCT no. 2013-001608-12. Copyright © 2016 Elsevier Ltd. All rights reserved.

A "Wii" bit of fun: the effects of adding Nintendo Wii(®) Bowling to a standard exercise regimen for residents of long-term care with upper extremity dysfunction.

PubMed

Hsu, Jason K; Thibodeau, Richard; Wong, Stephanie J; Zukiwsky, Daniel; Cecile, Sara; Walton, David M

2011-04-01

The aims of this randomized, single-blind crossover trial were to investigate the effect of adding a simulated bowling video game via the Nintendo Wii(®) gaming system to the standard exercise regimen of cognitively intact residents of long-term care (LTC) with upper extremity dysfunction and to identify individual characteristics that might predict improvement. Residents (n=34) were recruited through two LTC facilities in southwestern Ontario and were randomized into a standard exercise (SG) or standard exercise plus Wii bowling (Wii) arm. After 4 weeks of intervention, the groups were crossed over to the opposite arm. Outcomes included measures of pain intensity and bothersomeness, physical activity enjoyment, and a six-item measure of functional capacity designed specifically for residents of LTC. Results suggest that subjects improved on all outcomes from pre- to postintervention but that only enjoyment of activity showed a significant difference between the SG and Wii groups. Effect sizes (Cohen's d) ranged from small (0.30 for bothersomeness) to large (1.77 for functional capacity). Responders, defined as those subjects who reported any degree of improvement following the Wii intervention, were less likely to complain of stiffness or shoulder symptoms and were more likely to complain of hand symptoms than non-responders. Limitations in interpretation and recommendations for future research are presented.

The effect of methylphenidate on decision making in patients with borderline personality disorder and attention-deficit/hyperactivity disorder.

PubMed

Gvirts, Hila Z; Lewis, Yael D; Dvora, Shira; Feffer, Kfir; Nitzan, Uriel; Carmel, Ziv; Levkovitz, Yechiel; Maoz, Hagai

2018-07-01

Impaired decision making in patients with borderline personality disorder (BPD) has been reported in several studies. Although methylphenidate (MPH) is known to ameliorate impaired decision making in patients with attention-deficit/hyperactivity disorder (ADHD), it has not yet been examined in patients with BPD. We therefore assessed the efficacy of a single dose of MPH on cognitive functions and decision making in patients with BPD. Twenty-two patients diagnosed with BPD participated in the study. The study was a randomized, double-blind placebo-controlled, random block order cross-over trial. Patients participated in two sessions and performed the Test of Variables of Attention, a digit-span test, and the computerized Iowa Gambling Task, after they had been administered either the MPH or a placebo. ADHD symptoms were assessed using the Adult ADHD Self-Report Scale-18. Lower scores on the inattention symptoms scale were associated with a greater improvement in decision making following the administration of MPH when compared with improvements in patients with higher ADHD scores [F(1,17)=5.63, P=0.030]. We conclude that MPH may improve decision making in patients with BPD, although this effect is mediated by the level of ADHD symptoms. Further studies are needed to assess whether a prolonged beneficial effect of MPH on decision making in patients with BPD might also be present in 'real life'.

Impact of a simplified in situ protocol on enamel loss after erosive challenge

PubMed Central

Buzalaf, Marília Afonso Rabelo; Oliveira, Thais Marchini; Honório, Heitor Marques; Cruvinel, Thiago

2018-01-01

This study investigated the effect of the period of use and location of intraoral appliances on enamel surface loss. This randomized, single blind in situ study was conducted in 2 crossover phases based on the period of use, in which maxillary and mandibular appliances were simultaneously worn. Bovine enamel blocks (n = 120) were randomly divided among the studied groups by surface hardness. In each phase, fifteen volunteers used one maxillary appliance and two mandibular appliances for 5 days. Erosive challenge was performed 4X/day by immersion in 0.01 M HCL for 2 minutes. In the continuous phase, the intraoral appliances were worn for 20 hours. In the intermittent phase the appliances were worn for 8 hours and 30 minutes. Enamel loss was determined profilometrically. The discomfort of use of the appliances were evaluated in a questionnaire. Data were analyzed by two-way ANOVA/Tukey’s test and chi-square test (p<0.05). The maxillary appliance promoted higher enamel loss compared to the mandibular one (p<0.001). Intermittent use of appliances resulted in similar enamel loss to the continuous one (p = 0.686). All volunteers preferred to use the maxillary appliance in an intermittent regimen. The intermittent use of maxillary appliance is a simplified reliable protocol appropriated for in situ erosion studies in enamel. PMID:29734362

A randomized clinical trial of valerian fails to improve self-reported, polysomnographic, and actigraphic sleep in older women with insomnia.

PubMed

Taibi, Diana M; Vitiello, Michael V; Barsness, Suzanne; Elmer, Gary W; Anderson, Gail D; Landis, Carol A

2009-03-01

To test the effects of nightly valerian (Valeriana officinalis) extract to improve sleep of older women with insomnia. Participants in this phase 2 randomized, double-blind, crossover controlled trial were 16 older women (mean age=69.4+/-8.1 years) with insomnia. Participants took 300 mg of concentrated valerian extract or placebo 30 min before bedtime for 2 weeks. Sleep was assessed in the laboratory by self-report and polysomnography (PSG) at baseline and again at the beginning and end of each treatment phase (total of nine nights in the laboratory) and at home by daily sleep logs and actigraphy. There were no statistically significant differences between valerian and placebo after a single dose or after 2 weeks of nightly dosing on any measure of sleep latency, wake after sleep onset (WASO), sleep efficiency, and self-rated sleep quality. In comparing each treatment to baseline in separate comparisons, WASO significantly increased (+17.7+/-25.6 min, p=.02) after 2 weeks of nightly valerian, but not after placebo (+6.8+/-26.4 min, NS). Side effects were minor and did not differ significantly between valerian and placebo. Valerian did not improve sleep in this sample of older women with insomnia. Findings from this study add to the scientific evidence that does not support use of valerian in the clinical management of insomnia.

Influence of Methylphenidate on the Frequency of Stuttering: A Randomized Controlled Trial.

PubMed

Rabaeys, Henk; Bijleveld, Henny-Annie; Devroey, Dirk

2015-10-01

Recently, a case report described a decrease in frequency of stuttering after intake of methylphenidate (MPH). This study was undertaken to investigate if this effect could again be reproduced in a population of young healthy male adult persons with developmental stuttering. A double-blind randomized crossover trial, with a 2-week washout period, including 15 Dutch-speaking young healthy persons with developmental stuttering, assessed the effects of a single dose of 20 mg MPH compared with placebo on stuttering. Dependent and 1-sample t tests were used to detect significant differences. The end point was the number of stutter moments and self-perceived improvement. MPH yielded a significant decrease in the number of stutter moments when reading and speaking (P = 0.002), which was not the case with placebo (P = 0.090). There was a significant improvement from baseline after intake of MPH as compared with placebo (P = 0.003). Self-perceived improvement with MPH was not significantly better as compared with placebo (P = 0.28). This study showed that the participants had an objective statistically significant decrease in the frequency of stuttering with MPH, and this was not the case with placebo. This was also the case for a reduction in stutter moments when reading out loud and speaking spontaneously. However, this result was not subjectively perceived by the participants. © The Author(s) 2015.

Masturbation to Orgasm Stimulates the Release of the Endocannabinoid 2-Arachidonoylglycerol in Humans.

PubMed

Fuss, Johannes; Bindila, Laura; Wiedemann, Klaus; Auer, Matthias K; Briken, Peer; Biedermann, Sarah V

2017-11-01

Endocannabinoids are critical for rewarding behaviors such as eating, physical exercise, and social interaction. The role of endocannabinoids in mammalian sexual behavior has been suggested because of the influence of cannabinoid receptor agonists and antagonists on rodent sexual activity. However, the involvement of endocannabinoids in human sexual behavior has not been studied. To investigate plasma endocannabinoid levels before and after masturbation in healthy male and female volunteers. Plasma levels of the endocannabinoids 2-arachidonoylglycerol (2-AG), anandamide, the endocannabinoid-like lipids oleoyl ethanolamide and palmitoyl ethanolamide, arachidonic acid, and cortisol before and after masturbation to orgasm. In study 1, endocannabinoid and cortisol levels were measured before and after masturbation to orgasm. In study 2, masturbation to orgasm was compared with a control condition using a single-blinded, randomized, 2-session crossover design. In study 1, masturbation to orgasm significantly increased plasma levels of the endocannabinoid 2-AG, whereas anandamide, oleoyl ethanolamide, palmitoyl ethanolamide, arachidonic acid, and cortisol levels were not altered. In study 2, only masturbation to orgasm, not the control condition, led to a significant increase in 2-AG levels. Interestingly, we also found a significant increase of oleoyl ethanolamide after masturbation to orgasm in study 2. Endocannabinoids might play an important role in the sexual response cycle, leading to possible implications for the understanding and treatment of sexual dysfunctions. We found an increase of 2-AG through masturbation to orgasm in 2 studies including a single-blinded randomized design. The exact role of endocannabinoid release as part of the sexual response cycle and the biological significance of the finding should be studied further. Cannabis and other drug use and the attainment of orgasm were self-reported in the present study. Our data indicate that the endocannabinoid 2-AG is involved in the human sexual response cycle and we hypothesize that 2-AG release plays a role in the rewarding consequences of sexual arousal and orgasm. Fuss J, Bindila L, Wiedemann K, et al. Masturbation to Orgasm Stimulates the Release of the Endocannabinoid 2-Arachidonoylglycerol in Humans. J Sex Med 2017;14:1372-1379. Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Memory strength and lineup presentation moderate effects of administrator influence on mistaken identifications.

PubMed

Zimmerman, David M; Chorn, Jacqueline Austin; Rhead, Lindsey M; Evelo, Andrew J; Kovera, Margaret Bull

2017-12-01

Administrator/witness pairs (N = 313) were randomly assigned to target-absent lineups in a 2 (Suspect/Perpetrator Similarity: High Suspect Similarity vs. Low Suspect Similarity) × 2 (Retention Interval: 30 min vs. 1 week) × 2 (Lineup Presentation: Simultaneous vs. Sequential) × 2 (Administrator Knowledge: Single-Blind vs. Double-Blind) factorial design to test whether suspect similarity and memory strength constrain interpersonal expectancy effects on eyewitness identification accuracy. Administrators who knew which lineup member was the suspect (single-blind) or who administered simultaneous lineups were more likely to emit verbal and nonverbal behaviors that suggested to the witness who the suspect was. Additionally, single-blind administrators exerted more pressure on witnesses to choose the suspect as opposed to fillers. Administrator knowledge interacted with retention interval and lineup presentation to influence mistaken identifications of innocent suspects; witnesses were more likely to mistakenly identify an innocent suspect from single-blind than double-blind lineups when witness retention intervals were long and photographs were presented simultaneously. Contrary to our predictions, suspect/perpetrator similarity did not interact with other manipulated variables to influence identification decisions. Both sequential and double-blind procedures should be used to reduce the use of suggestive behavior during lineup administration. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Single therapeutic and supratherapeutic doses of sacubitril/valsartan (LCZ696) do not affect cardiac repolarization.

PubMed

Langenickel, Thomas H; Jordaan, Pierre; Petruck, Jesika; Kode, Kiran; Pal, Parasar; Vaidya, Soniya; Chandra, Priya; Rajman, Iris

2016-08-01

Sacubitril/valsartan (LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor (ARNI) indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA class II-IV) and reduced ejection fraction. This study was aimed to evaluate the effect of single oral therapeutic (400 mg) and supratherapeutic (1200 mg) doses of LCZ696 on cardiac repolarization. This randomized double-blind crossover study in healthy male subjects compared the effect of therapeutic and supratherapeutic doses of LCZ696 with placebo and moxifloxacin 400 mg (open-label treatment) as positive control. The primary assessment was mean baseline- and placebo-corrected QTcF (∆∆QTcF; Fridericia correction). Additional assessments included the ∆∆QTcB (Bazett's correction), PR interval, QRS duration, heart rate (HR), LCZ696 pharmacokinetics, pharmacokinetic/pharmacodynamic relationships, and safety. Of the 84 subjects enrolled, 81 completed the study. The maximum upper bound of the two-sided 90 % confidence interval for ∆∆QTcF for LCZ696 400 mg and 1200 mg were <10 ms, and assay sensitivity was confirmed with moxifloxacin. No relevant treatment-emergent changes were observed in any of the ECG-derived parameters with LCZ696 or placebo, and the incidence of adverse events was comparable among the treatment groups. Single therapeutic and supratherapeutic doses of LCZ696 did not affect cardiac repolarization as defined by the E14 ICH guidelines.

Effects of Rate on Analgesia in Kilohertz Frequency Spinal Cord Stimulation: Results of the PROCO Randomized Controlled Trial

PubMed Central

Tavakkolizadeh, Moein; Love‐Jones, Sarah; Patel, Nikunj K.; Gu, Jianwen Wendy; Bains, Amarpreet; Doan, Que; Moffitt, Michael

2017-01-01

Objective The PROCO RCT is a multicenter, double‐blind, crossover, randomized controlled trial (RCT) that investigated the effects of rate on analgesia in kilohertz frequency (1–10 kHz) spinal cord stimulation (SCS). Materials and Methods Patients were implanted with SCS systems and underwent an eight‐week search to identify the best location (“sweet spot”) of stimulation at 10 kHz within the searched region (T8–T11). An electronic diary (e‐diary) prompted patients for pain scores three times per day. Patients who responded to 10 kHz per e‐diary numeric rating scale (ED‐NRS) pain scores proceeded to double‐blind rate randomization. Patients received 1, 4, 7, and 10 kHz SCS at the same sweet spot found for 10 kHz in randomized order (four weeks at each frequency). For each frequency, pulse width and amplitude were titrated to optimize therapy. Results All frequencies provided equivalent pain relief as measured by ED‐NRS (p ≤ 0.002). However, mean charge per second differed across frequencies, with 1 kHz SCS requiring 60–70% less charge than higher frequencies (p ≤ 0.0002). Conclusions The PROCO RCT provides Level I evidence for equivalent pain relief from 1 to 10 kHz with appropriate titration of pulse width and amplitude. 1 kHz required significantly less charge than higher frequencies. PMID:29220121

Efficacy of homeopathically potentized antimony on blood coagulation. A randomized placebo controlled crossover trial.

PubMed

Heusser, Peter; Berger, Sarah; Stutz, Monika; Hüsler, André; Haeberli, André; Wolf, Ursula

2009-02-01

Homeopathically potentized antimony 6x is traditionally used in anthroposophic medicine for an alleged pro-coagulatory effect in bleeding disorders. However, the scientific evidence base is yet insufficient. Results of a previous in vitro study suggested a slight increase of maximal clot firmness (MCF) and a tendency towards a shorter clotting time (CT). The objective of this study was to investigate the pro-coagulatory effects of antimony in vivo, and possible unexpected or adverse events. A randomized placebo controlled double blind crossover study was carried out in 30 healthy volunteers (15 males, 15 females). Each participant received intravenously 10 ml of antimony 6x and placebo in a randomized order at an interval of 1 month. Thrombelastography (TEG) was carried out immediately before and 30 and 60 min after the injection. Statistically significant pro-coagulatory effects were observed 30 min after injection for CT in men (p = 0.0306), and for MCF in men and women combined (p = 0.0476). The effect of antimony was significantly larger on test day 1 than on test day 2, whereas the effect of placebo was similar on both test days. No unexpected adverse or adverse events causally related to antimony were observed. This study adds evidence to the hypothesis that homeopathically potentized antimony may be efficacious in vivo. The consistency of the results with previous in vitro results indicates an effect on MCF and CT. The in vivo application of antimony 6x is safe. Copyright (c) 2009 S. Karger AG, Basel.

Comparison of antiemetic efficacy of granisetron and ondansetron in Oriental patients: a randomized crossover study.

PubMed Central

Poon, R. T.; Chow, L. W.

1998-01-01

A double-blind randomized crossover trial was performed to compare the antiemetic efficacy of two 5-HT3 receptor antagonists, granisetron and ondansetron, in Chinese patients receiving adjuvant chemotherapy (cyclophosphamide, methotrexate and 5-fluorouracil) for breast cancer. Twenty patients were randomized to receive chemotherapy with either granisetron on day 1 and ondansetron on day 8 of the first cycle followed by the reverse order in the second cycle, or vice versa. The number of vomiting episodes and the severity of nausea in the first 24 h (acute vomiting/nausea) and the following 7 days (delayed vomiting/nausea) were studied. Acute vomiting was completely prevented in 29 (72.5%) cycles with granisetron and 27 (67.5%) cycles with ondansetron, and treatment failure (>5 vomiting episodes) occurred in two (5%) cycles with each agent (P = NS). Acute nausea was completely controlled in 15 (37.5%) cycles with granisetron and 14 (35%) cycles with ondansetron, whereas severe acute nausea occurred in four (10%) cycles with each agent (P = NS). However, complete response for delayed vomiting was observed in only 21 (52.5%) cycles with granisetron and 22 (55%) cycles with ondansetron (P = NS), and delayed nausea was completely controlled in only 11 (27.5%) and ten (25%) cycles respectively (P = NS). In conclusion, both granisetron and ondansetron are effective in controlling acute nausea and vomiting in Chinese patients, with equivalent antiemetic efficacy. Control of delayed nausea and vomiting is less satisfactory. PMID:9635849

Randomized Crossover Comparison of Injection Site Pain with 40 mg/0.4 or 0.8 mL Formulations of Adalimumab in Patients with Rheumatoid Arthritis.

PubMed

Nash, Peter; Vanhoof, Johan; Hall, Stephen; Arulmani, Udayasankar; Tarzynski-Potempa, Rita; Unnebrink, Kristina; Payne, Andrew N; Cividino, Alfred

2016-12-01

Adalimumab, an anti-tumor necrosis factor antibody, is currently available in a 40 mg/0.8 mL formulation. The objective of this analysis was to evaluate injection site-related pain, safety, and tolerability of a 40 mg/0.4 mL formulation of adalimumab that had fewer excipients, a smaller volume, and a delivery presentation with a smaller gauge needle, versus the current 40 mg/0.8 mL formulation in patients with rheumatoid arthritis (RA). Two identically designed, phase 2, randomized, single-blind, two-period crossover studies were conducted in Belgium and the Czech Republic (Study 1) and Australia, Canada, and Germany (Study 2). In both studies, adults with RA [biologic-naive or current users of 40 mg/0.8 mL adalimumab with an average injection site-related pain rating ≥3 cm on a visual analog scale (VAS; 0-10 cm)] were randomized to receive 40 mg/0.8 mL or 40 mg/0.4 mL adalimumab at visit 1. After 1-2 weeks (depending on patient medication schedule), patients received the other formulation at visit 2. A pain VAS [McGill Pain Questionnaire (MPQ-SF)] and the Draize scale were evaluated immediately after injection and 15 min postinjection. The primary endpoint was immediate pain after injection. 64 and 61 patients were randomized in Studies 1 and 2, respectively. Both studies found a clinically relevant and statistically significant lower immediate pain after injection for the 40 mg/0.4 mL versus the 40 mg/0.8 mL formulation. The mean difference on the VAS for the pooled data (-2.48 cm) was also clinically relevant. Most other endpoints in both studies favored the 40 mg/0.4 mL formulation, and its tolerability and safety profile were consistent with 40 mg/0.8 mL adalimumab. A 40 mg/0.4 mL adalimumab formulation was well tolerated and associated with less injection site-related pain than the 40 mg/0.8 mL adalimumab formulation. ClinicalTrials.gov identifier, NCT01561313 and NCT01502423. AbbVie.

A randomized, double-blind, crossover, placebo-controlled clinical trial to assess effects of the single ingestion of a tablet containing lactoferrin, lactoperoxidase, and glucose oxidase on oral malodor.

PubMed

Nakano, Manabu; Shimizu, Eiju; Wakabayashi, Hiroyuki; Yamauchi, Koji; Abe, Fumiaki

2016-03-22

The main components of oral malodor have been identified as volatile sulfur compounds (VSCs) including hydrogen sulfide (H2S) and methyl mercaptan (CH3SH). VSCs also play an important role in the progression of periodontal disease. The aim of the present study was to assess the effects of the single ingestion of a tablet containing 20 mg of lactoferrin, 2.6 mg of lactoperoxidase, and 2.6 mg of glucose oxidase on VSCs in the mouth. Subjects with VSCs greater than the olfactory threshold in their mouth air ingested a test or placebo tablet in two crossover phases. The concentrations of VSCs were monitored at baseline and 10 and 30 min after ingestion of the tablets using portable gas chromatography. Thirty-nine subjects were included in the efficacy analysis based on a full analysis set (FAS). The concentrations of total VSCs and H2S at 10 min were significantly lower in the test group than in the placebo group (-0.246 log ng/10 ml [95 % CI -0.395 to -0.098], P = 0.002; -0.349 log ng/10 ml; 95 % CI -0.506 to -0.192; P < 0.001, respectively). In the subgroup analysis, a significant difference in the concentration of total VSCs between the groups was also observed when subjects were fractionated by sex (male or female) and age (20-55 or 56-65 years). The reducing effect on total VSCs positively correlated with the probing pocket depth (P = 0.035). These results suggest that the ingestion of a tablet containing lactoferrin, lactoperoxidase, and glucose oxidase has suppressive effects on oral malodor. This trial was registered with the University Hospital Medical Information Network Clinical Trial Registry (number: UMIN000015140 , date of registration: 16/09/2014).

Pharmacodynamics of alfaxalone after single-dose intramuscular administration in red-eared sliders (Trachemys scripta elegans): a comparison of two different doses at two different ambient temperatures.

PubMed

Shepard, Molly K; Divers, Stephen; Braun, Christina; Hofmeister, Erik H

2013-11-01

This study compares the pharmacodynamics of two different doses of alfaxalone administered intramuscularly (IM) to red-eared sliders at two ambient temperatures. Prospective blinded crossover experimental study. Nine adult female sliders (Trachemys scripta elegans). Following a 2-week acclimation at 22-25 °C, nine sliders were randomly assigned to receive alfaxalone, 10 mg kg(-1) (W10), or 20 mg kg(-1) (W20) IM. Each turtle received each dose, with a minimum 7-day washout period. A blinded observer evaluated heart rate (HR), palpebral and corneal reflexes, muscle relaxation, handling, and response to toe pinch at the following points: pre-injection, and 5, 12, 20, 30, 45, 60, and 120 minutes post-injection. Turtles then acclimated to 18-20 °C for 63 days, and the experiment was repeated in this lower-temperature environment, with treatment groups C10 (alfaxalone 10 mg kg(-1)) and C20 (alfaxalone 20 mg kg(-1)) subjected to the same crossover design. C10 and C20 groups had significantly lower intraanesthetic HR than W10 or W20, respectively. C10 and W20 were significantly more relaxed and easier to handle than W10. No significant differences were observed in palpebral reflex, nor responsiveness to the toe pinch stimulus. None of the turtles lost corneal reflex. W20 and C20 had prolonged recoveries, compared to low-dose groups within the same temperature environment. Recovery was also longer at C20 and C10 compared to W10. Turtles given 10 mg kg(-1) were more relaxed and easier to handle in cold than warm conditions. Warm turtles were more relaxed and easier to handle when given 20 mg kg(-1) than those given 10 mg kg(-1). Cold conditions correlated with lower HR and longer recovery time for each dose category. The turtles had dose-dependent and inconsistent responses to alfaxalone. Lower ambient temperature augmented the behavioral effects of this drug. © 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

Improvement in exercise duration, lung function and well-being in G551D-cystic fibrosis patients: a double-blind, placebo-controlled, randomized, cross-over study with ivacaftor treatment.

PubMed

Edgeworth, Deirdre; Keating, Dominic; Ellis, Matthew; Button, Brenda; Williams, Elyssa; Clark, Denise; Tierney, Audrey; Heritier, Stephane; Kotsimbos, Tom; Wilson, John

2017-08-01

G551D, a mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, results in impaired chloride channel function in cystic fibrosis (CF) with multiple end-organ manifestations. The effect of ivacaftor, a CFTR-potentiator, on exercise capacity in CF is unknown. Twenty G551D-CF patients were recruited to a single-centre, double-blind, placebo-controlled, 28-day crossover study of ivacaftor. Variables measured included percentage change from baseline (%Δ) of V O 2 max (maximal oxygen consumption, primary outcome) during cardiopulmonary exercise testing (CPET), relevant other CPET physiological variables, lung function, body mass index (BMI), sweat chloride and disease-specific health related quality of life (QOL) measures (CFQ-R and Alfred Wellness (AWEscore)). %Δ V O 2 max was unchanged compared with placebo as was %Δminute ventilation. However, %Δexercise time (mean 7.3, CI 0.5-14,1, P =0.0222) significantly increased as did %ΔFEV 1 (11.7%, range 5.3-18.1, P <0·005) and %ΔBMI (1.2%, range 0.1-2.3, P =0·0393) whereas sweat chloride decreased (mean -43.4; range -55.5-18.1 mmol·l -1 , P <0·005). Total and activity based domains in both CFQ-R and AWEscore also increased. A positive treatment effect on spirometry, BMI (increased), SCT (decreased) and total and activity based CF-specific QOL measures was expected. However, the lack of discernible improvement in V O 2 max and VE despite other positive changes including spirometric lung function and exercise time with a 28-day ivacaftor intervention suggests that ventilatory parameters are not the sole driver of change in exercise capacity in this study cohort. Investigation over a more prolonged period may delineate the potential interdependencies of the observed discordances over time. ClinicalTrials.gov-NCT01937325. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Caffeine's Influence on Nicotine's Effects in Nonsmokers

PubMed Central

Blank, Melissa D.; Kleykamp, Bethea A.; Jennings, Janine M.; Eissenberg, Thomas

2011-01-01

Objective To determine if nicotine's effects are influenced by caffeine in nonsmoking, moderate-caffeine consuming individuals (N=20). Methods The first 3 sessions included one of 3 randomly ordered, double-blind caffeine doses (0, 75, or 150 mg, oral [po]) and 2 single-blind nicotine gum doses (2 and 4 mg) in ascending order. The fourth session (single blind) repeated the 0 mg caffeine condition. Results Nicotine increased heart rate and subjective ratings indicative of aversive effects, and decreased reaction times. These effects were independent of caffeine dose and reliable across sessions. Conclusions In nonsmokers, nicotine effects are not influenced by moderate caffeine doses. PMID:17555378

Satisfaction in complete denture wearers with and without adhesives: A randomized, crossover, double-blind clinical trial

PubMed Central

Torres-Sánchez, Carlos; Montoya-Salazar, Vanessa; Gutierrez-Pérez, Jose-Luis; Jimenez-Castellanos, Emilio

2018-01-01

Background The purpose of this study was to compare the satisfaction of patients regarding retention, stability and accumulation of particles with a randomized, double-blind crossed method in users with complete dentures with and without adhesive. Material and Methods Seventeen edentulous individuals were randomized and received new upper and lower complete dentures. After a period of adaptation, they participated in some masticatory tests and clinical revisions, after use the protheses with and without the use of two denture adhesives: Adhesive A (Fittydent, Fittydent International GmbH) and adhesive B (Corega, GlaxoSmithKline) at 0, 7 and 14 days. Satisfaction was measured immediately after each test through a survey using a VAS scale (0-10) and data were analyzed with McNemar’s test with Bonferroni correction. Results The results showed significant differences (p<.01) between the study groups with adhesive A - B and the group without adhesive, but no significant differences were found between the two stickers for any of the variables studied. Conclusions Complete denture adhesives significantly improved the satisfaction of patients because a better retention, stability and less accumulation of particles of the food substitute between the denture and the mucosa is obtained compared with non-use of complete denture adhesives. Key words:Complete dentures, patient satisfaction, denture adhesives, clinical trials. PMID:29946414

Intra-gastric pH following single oral administrations of rabeprazole and esomeprazole: double-blind cross-over comparison.

PubMed

Furuta, Kenji; Kohata, Yukie; Fujiwara, Yasuhiro; Sugimoto, Mitsushige; Uotani, Takahiro; Yamade, Mihoko; Sahara, Shu; Ichikawa, Hitomi; Furuta, Takahisa; Nio, Kenta; Iwakiri, Ryuichi; Inamori, Masahiko; Kawamura, Osamu; Kusano, Motoyasu; Kato, Mototsugu; Kawami, Noriyuki; Iwakiri, Katsuhiko; Takeuchi, Toshihisa; Higuchi, Kazuhide; Aimi, Masahito; Naora, Kohji; Fujimoto, Kazuma; Arakawa, Tetsuo; Kinoshita, Yoshikazu

2014-11-01

Comparisons between the acid inhibitory effects of rabeprazole and esomeprazole after single oral administration with standard doses have not been previously presented. We examined intra-gastric pH after oral administrations of these two proton pump inhibitors using 24-h pH monitoring. Fifty-four normal volunteers not infected by Helicobacter pylori were investigated. Using a cross-over design, we administered 10 mg of rabeprazole or 20 mg of esomeprazole in 27 at 30 min after supper and in the remaining 27 subjects at 15 min before supper, and performed 24-h pH monitoring. Intra-gastric pH data were nearly identical when the proton pump inhibitors were taken after meals. Even if the data were compared in different CYP2C19 genotypes, rabeprazole and esomeprazole did not show the difference. In poor metabolizer, both of the drugs showed stronger acid inhibition. When taken before meals, intra-gastric pH after esomeprazole administration was slightly but not significantly higher than that observed after rabeprazole administration not only in daytime but also in nighttime period. In conclusion, rabeprazole and esomeprazole were similarly effective when administered after a meal.

Comparative Performance in Single-Port Versus Multiport Minimally Invasive Surgery, and Small Versus Large Operative Working Spaces: A Preclinical Randomized Crossover Trial.

PubMed

Marcus, Hani J; Seneci, Carlo A; Hughes-Hallett, Archie; Cundy, Thomas P; Nandi, Dipankar; Yang, Guang-Zhong; Darzi, Ara

2016-04-01

Surgical approaches such as transanal endoscopic microsurgery, which utilize small operative working spaces, and are necessarily single-port, are particularly demanding with standard instruments and have not been widely adopted. The aim of this study was to compare simultaneously surgical performance in single-port versus multiport approaches, and small versus large working spaces. Ten novice, 4 intermediate, and 1 expert surgeons were recruited from a university hospital. A preclinical randomized crossover study design was implemented, comparing performance under the following conditions: (1) multiport approach and large working space, (2) multiport approach and intermediate working space, (3) single-port approach and large working space, (4) single-port approach and intermediate working space, and (5) single-port approach and small working space. In each case, participants performed a peg transfer and pattern cutting tasks, and each task repetition was scored. Intermediate and expert surgeons performed significantly better than novices in all conditions (P < .05). Performance in single-port surgery was significantly worse than multiport surgery (P < .01). In multiport surgery, there was a nonsignificant trend toward worsened performance in the intermediate versus large working space. In single-port surgery, there was a converse trend; performances in the intermediate and small working spaces were significantly better than in the large working space. Single-port approaches were significantly more technically challenging than multiport approaches, possibly reflecting loss of instrument triangulation. Surprisingly, in single-port approaches, in which triangulation was no longer a factor, performance in large working spaces was worse than in intermediate and small working spaces. © The Author(s) 2015.

Repeated Nitrogen Dioxide Exposures and Eosinophilic Airway Inflammation in Asthmatics: A Randomized Crossover Study

PubMed Central

Guillossou, Gaëlle; Neukirch, Catherine; Dehoux, Monique; Koscielny, Serge; Bonay, Marcel; Cabanes, Pierre-André; Samet, Jonathan M.; Mure, Patrick; Ropert, Luc; Tokarek, Sandra; Lambrozo, Jacques; Aubier, Michel

2014-01-01

Background: Nitrogen dioxide (NO2), a ubiquitous atmospheric pollutant, may enhance the asthmatic response to allergens through eosinophilic activation in the airways. However, the effect of NO2 on inflammation without allergen exposure is poorly studied. Objectives: We investigated whether repeated peaks of NO2, at various realistic concentrations, induce changes in airway inflammation in asthmatics. Methods: Nineteen nonsmokers with asthma were exposed at rest in a double-blind, crossover study, in randomized order, to 200 ppb NO2, 600 ppb NO2, or clean air once for 30 min on day 1 and twice for 30 min on day 2. The three series of exposures were separated by 2 weeks. The inflammatory response in sputum was measured 6 hr (day 1), 32 hr (day 2), and 48 hr (day 3) after the first exposure, and compared with baseline values measured twice 10–30 days before the first exposure. Results: Compared with baseline measurements, the percentage of eosinophils in sputum increased by 57% after exposure to 600 ppb NO2 (p = 0.003) but did not change significantly after exposure to 200 ppb. The slope of the association between the percentage of eosinophils and NO2 exposure level was significant (p = 0.04). Eosinophil cationic protein in sputum was highly correlated with eosinophil count and increased significantly after exposure to 600 ppb NO2 (p = 0.001). Lung function, which was assessed daily, was not affected by NO2 exposure. Conclusions: We observed that repeated peak exposures of NO2 performed without allergen exposure were associated with airway eosinophilic inflammation in asthmatics in a dose-related manner. Citation: Ezratty V, Guillossou G, Neukirch C, Dehoux M, Koscielny S, Bonay M, Cabanes PA, Samet JM, Mure P, Ropert L, Tokarek S, Lambrozo J, Aubier M. 2014. Repeated nitrogen dioxide exposures and eosinophilic airway inflammation in asthmatics: a randomized crossover study. Environ Health Perspect 122:850–855; http://dx.doi.org/10.1289/ehp.1307240 PMID:24747297

Pharmacokinetic and hemostatic properties of the recombinant plasminogen activator bm 06.022 in healthy volunteers.

PubMed

Martin, U; von Möllendorff, E; Akpan, W; Kientsch-Engel, R; Kaufmann, B; Neugebauer, G

1991-11-01

In a randomized, single-blind, placebo-controlled, cross-over Phase-I study pharmacokinetic and hemostatic properties of BM 06.022 were investigated in seven healthy, male human volunteers. The novel recombinant plasminogen activator BM 06.022 consists of the kringle 2 domain and the protease domain of human t-PA and is unglycosylated due to its expression in Escherichia coli cells. Vehicle or 6 MU (= 10.4 mg) BM 06.022 was administered as a single i.v. bolus injection of 10 ml over 2 min. BM 06.022 was well tolerated. Fibrinogen levels and clotting times remained unchanged at baseline levels after 6 MU BM 06.022; plasminogen and alpha 2-antiplasmin (collected on chloromethylketone) decreased maximally to 83 +/- 1% and 64 +/- 3%, respectively, of baseline. D-dimers and fibrinogen degradation products increased to 1,006 +/- 234 ng/ml and 555 +/- 155 ng/ml, respectively, after BM 06.022. Half-life of BM 06.022-activity was 11.2 +/- 0.4 min and of antigen was 13.9 +/- 0.7 min, followed by a terminal half-life only for antigen of 173 +/- 33 min. Plasma clearance of BM 06.022 was 371 +/- 13 ml/min for activity and 183 +/- 15 ml/min for antigen. Thus, BM 06.022 is not fibrinogenolytic at 6 MU and is a fibrinolytic agent with a longer half-life than t-PA.

Effects of befloxatone, a reversible selective monoamine oxidase-A inhibitor, on psychomotor function and memory in healthy subjects.

PubMed

Warot, D; Berlin, I; Patat, A; Durrieu, G; Zieleniuk, I; Puech, A J

1996-10-01

Befloxatone is a new reversible and selective monoamine oxidase (MAO-A) inhibitor that has been shown to have antidepressant activity in various animal models. To assess the effects of single oral doses of befloxatone (5, 10, and 20 mg) on psychomotor performance and memory, a randomized, double-blind, five-way, crossover study with both placebo and amitriptyline (50 mg) was carried out in 15 healthy male volunteers. Psychomotor and cognitive functions were evaluated using both objective measures, including Critical Flicker Frequency (CFF), Choice Reaction Time (CRT), Digit Symbol Substitution Test (DSST), and a picture memory test and subjective measures, including Visual Analog Scales (VAS) and Addiction Research Center Inventory (ARCI), before and 2, 4, and 8 hours after administration. Pupil diameter was recorded by videopupillography. Single doses of befloxatone from 5 to 20 mg did not result in any detrimental effects on skilled performance and memory. In contrast, amitriptyline significantly impaired arousal (CFF), speed of reaction (CRT), information processing (DSST) and long-term memory (delayed free recall of pictures) and produced subjective sedation from 2 to 8 hours after administration. At the doses studied amitriptyline induced miosis but befloxatone did not modify pupil diameter. There was no evidence in this study to suggest that befloxatone, at the doses studied, has any sedative or amnesic effects in healthy subjects.

Development of low erosive carbonated fruit drinks. 1. Evaluation of two experimental orange drinks in vitro and in situ.

PubMed

Hunter, M L; Hughes, J A; Parker, D M; West, N X; Newcombe, R G; Addy, M

2003-05-01

To determine the in vitro erosive potential and in situ erosive effect of two new formulation low calorie carbonated orange drinks with that of two conventional diet products and water. In the in vitro study, six specimens of deciduous and permanent enamel were randomly allocated to each of the five products and a '4h' protocol employed. In the in situ study, 15 healthy volunteers participated in a single centre, single blind, 5-phase crossover study, conducted according to Good Clinical Practice, and employing a validated model. The in vitro erosive potential of the experimental formulations was less than that of the comparators at all time points. Conversely, the observed erosive potential of both experimental formulations was greater than that of the control. Consistent statistically significant differences were found in relation to permanent enamel only. Unfortunately, the in situ study did not produce results entirely consistent with those of the in vitro study. Notably, a generally progressive loss of enamel was observed in specimens exposed to the control. The data from the in vitro study show the experimental formulations to have low comparative erosivity. However, the methodologies in vitro and in situ somewhat unusually do not correlate in ranking the erosivity of drinks. The results of this study should therefore be viewed with caution, further research being clearly warranted.

Estrogen replacement, vascular distensibility, and blood pressures in postmenopausal women.

PubMed

De Meersman, R E; Zion, A S; Giardina, E G; Weir, J P; Lieberman, J S; Downey, J A

1998-05-01

The pathogenesis of blood pressure (BP) rise in aging women remains unexplained, and one of the many incriminating factors may include abnormalities in arteriolar resistance vessels. The aim of this study was to determine the effects of unopposed estrogen on arteriolar distensibility, baroreceptor sensitivity (BRS), BP changes, and rate-pressure product (RPP). We tested the hypotheses that estrogen replacement therapy (ERT) enhances arteriolar distensibility and ameliorates BRS, which leads to decreases in BP and RPP. Postmenopausal women participated in a single-blind crossover study; the participants of this study, after baseline measurements, were randomly assigned to receive estrogen (ERT) or a drug-free treatment with a 6-wk washout period between treatments. The single-blind design was instituted because subjects become unblinded due to physiological changes (i.e., fluid shifts, weight gain, and secretory changes) associated with estrogen intake. However, investigators and technicians involved in data collection and analyses remained blind. After each treatment, subjects performed identical autonomic tests, during which electrocardiograms, beat-by-beat BPs, and respiration were recorded. The area under the dicrotic notch of the BP wave was used as an index of arteriolar distensibility. The magnitude of the reflex bradycardia after a precipitous rise in BP was used to determine BRS. Power spectral analysis of heart rate variability was used to assess autonomic activity. BPs were recorded from resistance vessels in the finger using a beat-by-beat photoplethysmographic device. RPP, a noninvasive marker of myocardial oxygen consumption, was calculated. Repeated-measures analyses of variance revealed a significantly enhanced arteriolar distensibility and BRS after ERT (P < 0.05). A trend of a lower sympathovagal balance at rest was observed after ERT, however, this trend did not reach statistical significance (P = 0.061) compared with the other treatments. The above autonomic changes produced significantly lower systolic and diastolic BP changes and RPPs (P < 0.05) at rest and during isometric exercise. We conclude that short-term unopposed ERT favorably enhances arteriolar distensibility, BRS, and hemodynamic parameters in postmenopausal women. These findings have clinical implications in the goals for treating cardiovascular risk factors in aging women.

Efficacy of 3 toothbrush treatments on plaque removal in orthodontic patients assessed with digital plaque imaging: a randomized controlled trial.

PubMed

Erbe, Christina; Klukowska, Malgorzata; Tsaknaki, Iris; Timm, Hans; Grender, Julie; Wehrbein, Heinrich

2013-06-01

Good oral hygiene is a challenge for orthodontic patients because food readily becomes trapped around the brackets and under the archwires, and appliances are an obstruction to mechanical brushing. The purpose of this study was to compare plaque removal efficacy of 3 toothbrush treatments in orthodontic subjects. This was a replicate-use, single-brushing, 3-treatment, examiner-blind, randomized, 6-period crossover study with washout periods of approximately 24 hours between visits. Forty-six adolescent and young adult patients with fixed orthodontics from a university clinic in Germany were randomized, based on computer-generated randomization, to 1 of 3 treatments: (1) oscillating-rotating electric toothbrush with a specially designed orthodontic brush head (Oral-B Triumph, OD17; Procter & Gamble, Cincinnati, Ohio); (2) the same electric toothbrush handle with a regular brush head (EB25; Procter & Gamble); and (3) a regular manual toothbrush (American Dental Association, Chicago, Ill). The primary outcome was the plaque score change from baseline, which we determined using digital plaque image analysis. Forty-five subjects completed the study. The differences in mean plaque removal (95% confidence interval) between the electric toothbrush with an orthodontic brush head (6% [4.4%-7.6%]) or a regular brush head (3.8% [2.2%-5.3%]) and the manual toothbrush were significant (P <0.001). Plaque removal with the electric toothbrush with the orthodontic brush head was superior (2.2%; P = 0.007) to the regular brush head. No adverse events were seen. The electric toothbrush, with either brush head, demonstrated significantly greater plaque removal over the manual brush. The orthodontic brush head was superior to the regular head. Copyright © 2013 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

A Prospective, Randomized, Double-Blind Comparison of 2% Lidocaine With 1 : 100,000 Epinephrine, 4% Prilocaine With 1 : 200,000 Epinephrine, and 4% Prilocaine for Maxillary Infiltrations

PubMed Central

Katz, Steven; Drum, Melissa; Reader, Al; Nusstein, John; Beck, Mike

2010-01-01

Abstract The purpose of this prospective, randomized, double-blind crossover study was to evaluate the anesthetic efficacy of 2% lidocaine with 1 : 100,000 epinephrine, 4% prilocaine with 1 : 200,000 epinephrine, and 4% prilocaine in maxillary lateral incisors and first molars. Sixty subjects randomly received, in a double-blind manner, maxillary lateral incisor and first molar infiltrations of 1.8 mL of 2% lidocaine with 1 : 100,000 epinephrine, 1.8 mL of 4% prilocaine with 1 : 200,000 epinephrine, and 1.8 mL of 4% prilocaine, at 3 separate appointments spaced at least 1 week apart. The teeth were pulp-tested in 3-minute cycles for a total of 60 minutes. Anesthetic success (ie, obtaining 2 consecutive 80 readings with the electric pulp tester) and onset of pulpal anesthesia were not significantly different between 2% lidocaine with 1 : 100,000 epinephrine, 4% prilocaine with 1 : 200,000 epinephrine, and 4% prilocaine for the lateral incisor and first molar. For both lateral incisor and first molar, 4% prilocaine with 1 : 200,000 epinephrine and 2% lidocaine with 1 : 100,000 epinephrine were equivalent for incidence of pulpal anesthesia. However, neither anesthetic agent provided an hour of pulpal anesthesia. For both lateral incisor and first molar, 4% prilocaine provided a significantly shorter duration of pulpal anesthesia compared with 2% lidocaine with 1 : 100,000 epinephrine and 4% prilocaine with 1 : 200,000 epinephrine. PMID:20553134

Aspirin-induced small bowel injuries and the preventive effect of rebamipide

PubMed Central

Mizukami, Kazuhiro; Murakami, Kazunari; Abe, Takashi; Inoue, Kunimitsu; Uchida, Masahiro; Okimoto, Tadayoshi; Kodama, Masaaki; Fujioka, Toshio

2011-01-01

AIM: To evaluate the influence of taking low-dose aspirin for 4 wk on small intestinal complications and to examine the preventive effect of rebamipide. METHODS: This study was conducted as a single-center, randomized, double-blind, cross-over, placebo-controlled study. Eleven healthy male subjects were enrolled. Each subject underwent video capsule endoscopy after 1 and 4 wk of taking aspirin and omeprazole, along with either rebamipide or placebo therapy. The primary endpoint was to evaluate small bowel damage in healthy subjects before and after taking low-dose aspirin for 4 wk. RESULTS: The number of subjects with mucosal breaks (defined as multiple erosions and/or ulcers) were 1 at 1 wk and 1 at 4 wk on the jejunum, and 6 at 1 wk (P = 0.0061) and 7 at 4 wk on the ileum (P = 0.0019). Rebamipide significantly prevented mucosal breaks on the ileum compared with the placebo group (P = 0.0173 at 1 wk and P = 0.0266 at 4 wk). CONCLUSION: Longer-term, low-dose aspirin administration induced damage in the small bowel. Rebamipide prevented this damage, and may be a candidate drug for treating aspirin-induced small bowel complications. PMID:22171147

Evaluation of multiple comparison correction procedures in drug assessment studies using LORETA maps.

PubMed

Alonso, Joan Francesc; Romero, Sergio; Mañanas, Miguel Ángel; Rojas, Mónica; Riba, Jordi; Barbanoj, Manel José

2015-10-01

The identification of the brain regions involved in the neuropharmacological action is a potential procedure for drug development. These regions are commonly determined by the voxels showing significant statistical differences after comparing placebo-induced effects with drug-elicited effects. LORETA is an electroencephalography (EEG) source imaging technique frequently used to identify brain structures affected by the drug. The aim of the present study was to evaluate different methods for the correction of multiple comparisons in the LORETA maps. These methods which have been commonly used in neuroimaging and also simulated studies have been applied on a real case of pharmaco-EEG study where the effects of increasing benzodiazepine doses on the central nervous system measured by LORETA were investigated. Data consisted of EEG recordings obtained from nine volunteers who received single oral doses of alprazolam 0.25, 0.5, and 1 mg, and placebo in a randomized crossover double-blind design. The identification of active regions was highly dependent on the selected multiple test correction procedure. The combined criteria approach known as cluster mass was useful to reveal that increasing drug doses led to higher intensity and spread of the pharmacologically induced changes in intracerebral current density.

Acute Consumption of Resistant Starch Reduces Food Intake but Has No Effect on Appetite Ratings in Healthy Subjects.

PubMed

Ble-Castillo, Jorge L; Juárez-Rojop, Isela E; Tovilla-Zárate, Carlos A; García-Vázquez, Carlos; Servin-Cruz, Magda Z; Rodríguez-Hernández, Arturo; Araiza-Saldaña, Claudia I; Nolasco-Coleman, Ana M; Díaz-Zagoya, Juan C

2017-07-04

Previous studies have shown the benefits of native banana starch (NBS) supplementation in improving glucose metabolism and reducing body weight (BW) in humans. However, the effect of this starch on appetite regulation is unknown. The aim of this study was to examine the effects of NBS rich resistant starch on subjective measurements of appetite, energy intake, and appetite hormones in healthy subjects. Postprandial glucose and insulin responses were also assessed. In a randomized, single-blind, crossover study, 28 healthy young subjects consumed a beverage containing either 40 g of NBS or 40 g of digestible corn starch (DCS) on two separate occasions. Effects on appetite were estimated using visual analogue scales (VAS) and satiety hormone responses. At the end of the intervention, participants were provided with a pre-weighed ad libitum homogeneous test meal. After a washout period of 1 week, subjects received the alternative treatment. NBS supplementation induced a reduction in food intake, glucose area under the curve (AUC)-180 min, and insulin AUC-180 min. However, there was no associated effect on the subjective appetite ratings or gut hormones. NBS supplementation may help to reduce meal size and control BW.

Heart Rate Effects of Intraosseous Injections Using Slow and Fast Rates of Anesthetic Solution Deposition

PubMed Central

Susi, Louis; Reader, Al; Nusstein, John; Beck, Mike; Weaver, Joel; Drum, Melissa

2008-01-01

The authors, using a crossover design, randomly administered, in a single-blind manner, 3 primary intraosseous injections to 61 subjects using: the Wand local anesthetic system at a deposition rate of 45 seconds (fast injection); the Wand local anesthetic system at a deposition rate of 4 minutes and 45 seconds (slow injection); a conventional syringe injection at a deposition rate of 4 minutes and 45 seconds (slow injection), in 3 separate appointments spaced at least 3 weeks apart. A pulse oximeter measured heart rate (pulse). The results demonstrated the mean maximum heart rate was statistically higher with the fast intraosseous injection (average 21 to 28 beats/min increase) than either of the 2 slow intraosseous injections (average 10 to 12 beats/min increase). There was no statistically significant difference between the 2 slow injections. We concluded that an intraosseous injection of 1.4 mL of 2% lidocaine with 1 : 100,000 epinephrine with the Wand at a 45-second rate of anesthetic deposition resulted in a significantly higher heart rate when compared with a 4-minute and 45-second anesthetic solution deposition using either the Wand or traditional syringe. PMID:18327970

Heart rate effects of intraosseous injections using slow and fast rates of anesthetic solution deposition.

PubMed

Susi, Louis; Reader, Al; Nusstein, John; Beck, Mike; Weaver, Joel; Drum, Melissa

2008-01-01

The authors, using a crossover design, randomly administered, in a single-blind manner, 3 primary intraosseous injections to 61 subjects using: the Wand local anesthetic system at a deposition rate of 45 seconds (fast injection); the Wand local anesthetic system at a deposition rate of 4 minutes and 45 seconds (slow injection); a conventional syringe injection at a deposition rate of 4 minutes and 45 seconds (slow injection), in 3 separate appointments spaced at least 3 weeks apart. A pulse oximeter measured heart rate (pulse). The results demonstrated the mean maximum heart rate was statistically higher with the fast intraosseous injection (average 21 to 28 beats/min increase) than either of the 2 slow intraosseous injections (average 10 to 12 beats/min increase). There was no statistically significant difference between the 2 slow injections. We concluded that an intraosseous injection of 1.4 mL of 2% lidocaine with 1 : 100,000 epinephrine with the Wand at a 45-second rate of anesthetic deposition resulted in a significantly higher heart rate when compared with a 4-minute and 45-second anesthetic solution deposition using either the Wand or traditional syringe.

Recombinant granulocyte colony-stimulating factor administered enterally to neonates is not absorbed.

PubMed

Calhoun, Darlene A; Maheshwari, Akhil; Christensen, Robert D

2003-08-01

Granulocyte colony-stimulating factor (G-CSF) is present in liquids swallowed by the fetus and neonate; specifically, amniotic fluid, colostrum, and human milk. The swallowed G-CSF has local effects on enteric cells, which express the G-CSF receptor. However, some portion of the G-CSF ingested by the fetus and neonate might be absorbed into the circulation and have systemic actions, such as stimulating neutrophil production. To assess this possibility we sought to determine if circulating G-CSF concentrations of neonates increase after enteral administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF). This was a single-center, prospective, blinded, randomized, 2 x 2 crossover study, with each infant receiving 1 dose of rhG-CSF (100 microg/kg) and 1 dose of placebo. Plasma G-CSF concentrations were measured at 2 and 4 hours after administration of the test solution. No significant change in plasma G-CSF concentration was observed after the enteral administration of rhG-CSF. On this basis, we conclude that orally administered rhG-CSF is not absorbed in significant quantities, and we speculate that the G-CSF swallowed by the fetus and neonate has local but not systemic effects.

Effects of intranasal insulin on endogenous glucose production in insulin-resistant men.

PubMed

Xiao, Changting; Dash, Satya; Stahel, Priska; Lewis, Gary F

2018-03-14

The effects of intranasal insulin on the regulation of endogenous glucose production (EGP) in individuals with insulin resistance were assessed in a single-blind, crossover study. Overweight or obese insulin-resistant men (n = 7; body mass index 35.4 ± 4.4 kg/m 2 , homeostatic model assessment of insulin resistance 5.6 ± 1.6) received intranasal spray of either 40 IU insulin lispro or placebo in 2 randomized visits. Acute systemic spillover of intranasal insulin into the circulation was matched with a 30-minute intravenous infusion of insulin lispro in the nasal placebo arm. EGP was assessed under conditions of a pancreatic clamp with a primed, constant infusion of glucose tracer. Under these experimental conditions, compared with placebo, intranasal administration of insulin did not significantly affect plasma glucose concentrations, EGP or glucose disposal in overweight/obese, insulin-resistant men, in contrast to our previous study, in which an equivalent dose of intranasal insulin significantly suppressed EGP in lean, insulin-sensitive men. Insulin resistance is probably associated with impairment in centrally mediated insulin suppression of EGP. © 2018 John Wiley & Sons Ltd.

Human tolerance to a single, high dose of D-tagatose.

PubMed

Buemann, B; Toubro, S; Raben, A; Astrup, A

1999-04-01

The addition of 29 g D-tagatose added as a sweetener to a continental breakfast was tested for the appearance of gastrointestinal side effects in a double-blind randomized cross-over study with 29 g sucrose as a control treatment. The subjects reported the side effects during 72 h following the test meal on a questionnaire grading the symptoms on a five-level scale ranging from "none" to "very strong." Although "rumbling in the stomach," "distention," "nausea," "rumbling in the gut," "flatulence, " and "diarrhea" scored significantly higher with D-tagatose, the sugar otherwise was well tolerated in most of the subjects. Two cases of vomiting after D-tagatose were recorded but in one of the cases its relation to the D-tagatose intake was questionable. Only the "distention" score remained higher with D-tagatose for more than 24 h. Nausea, vomiting, and perceived distension may be due to an osmotic effect in the small intestine of unabsorbed D-tagatose. The increased flatus is caused by D-tagatose being fermented in the large intestine. Diarrhea may be explained by osmotic effects in the colon from nondegraded D-tagatose or nonabsorbed short-chain fatty acids produced by the increased fermentation. Copyright 1999 Academic Press.

Acute Consumption of Resistant Starch Reduces Food Intake but Has No Effect on Appetite Ratings in Healthy Subjects

PubMed Central

Ble-Castillo, Jorge L.; Juárez-Rojop, Isela E.; Tovilla-Zárate, Carlos A.; García-Vázquez, Carlos; Servin-Cruz, Magda Z.; Rodríguez-Hernández, Arturo; Araiza-Saldaña, Claudia I.; Nolasco-Coleman, Ana M.

2017-01-01

Previous studies have shown the benefits of native banana starch (NBS) supplementation in improving glucose metabolism and reducing body weight (BW) in humans. However, the effect of this starch on appetite regulation is unknown. The aim of this study was to examine the effects of NBS rich resistant starch on subjective measurements of appetite, energy intake, and appetite hormones in healthy subjects. Postprandial glucose and insulin responses were also assessed. In a randomized, single-blind, crossover study, 28 healthy young subjects consumed a beverage containing either 40 g of NBS or 40 g of digestible corn starch (DCS) on two separate occasions. Effects on appetite were estimated using visual analogue scales (VAS) and satiety hormone responses. At the end of the intervention, participants were provided with a pre-weighed ad libitum homogeneous test meal. After a washout period of 1 week, subjects received the alternative treatment. NBS supplementation induced a reduction in food intake, glucose area under the curve (AUC)-180 min, and insulin AUC-180 min. However, there was no associated effect on the subjective appetite ratings or gut hormones. NBS supplementation may help to reduce meal size and control BW. PMID:28677623

Effects of dopaminergic modulation on electrophysiological brain response to affective stimuli.

PubMed

Franken, Ingmar H A; Nijs, Ilse; Pepplinkhuizen, Lolke

2008-01-01

Several theoretical accounts of the role of dopamine suggest that dopamine has an influence on the processing of affective stimuli. There is some indirect evidence for this from studies showing an association between the treatment with dopaminergic agents and self-reported affect. We addressed this issue directly by examining the electrophysiological correlates of affective picture processing during a single-dose treatment with a dopamine D2 agonist (bromocriptine), a dopamine D2 antagonist (haloperidol), and a placebo. We compared early and late event-related brain potentials (ERPs) that have been associated with affective processing in the three medication treatment conditions in a randomized double-blind crossover design amongst healthy males. In each treatment condition, subjects attentively watched neutral, pleasant, and unpleasant pictures while ERPs were recorded. Results indicate that neither bromocriptine nor haloperidol has a selective effect on electrophysiological indices of affective processing. In concordance with this, no effects of dopaminergic modulation on self-reported positive or negative affect was observed. In contrast, bromocriptine decreased overall processing of all stimulus categories regardless of their affective content. The results indicate that dopaminergic D2 receptors do not seem to play a crucial role in the selective processing of affective visual stimuli.

High Amylose White Rice Reduces Post-Prandial Glycemic Response but Not Appetite in Humans

PubMed Central

Zenel, Alison M.; Stewart, Maria L.

2015-01-01

The present study compared the effects of three rice cultivars on postprandial glycemic control and appetite. A single-blind, randomized, crossover clinical trial was performed with 18 healthy subjects, nine males and nine females. Three treatments were administered at three separate study visits: commercially available conventional white rice (short grain), specialty high amylose white rice 1 (Dixiebelle), and specialty high amylose white rice 2 (Rondo). Postprandial capillary blood glucose, venous blood glucose and insulin measurements, and appetite visual analog scale (VAS) surveys were done over the course of two hours. The capillary blood glucose concentrations were significantly lower for Rondo compared to short grain rice at 30 min, and for Dixiebelle and Rondo compared to short grain rice at 45, 60, and 120 min. Capillary blood glucose area under the curve (AUC) was significantly lower for Dixiebelle and Rondo compared to short grain rice. Subjects were significantly more hungry at 30 min after Dixiebelle intake than Rondo intake, but there were no other significant effects in appetite ratings. The present study determined that intake of high amylose rice with resistant starch (RS) can attenuate postprandial blood glucose and insulin response in comparison to short grain rice. PMID:26147654

Repetitive electric brain stimulation reduces food intake in humans.

PubMed

Jauch-Chara, Kamila; Kistenmacher, Alina; Herzog, Nina; Schwarz, Marianka; Schweiger, Ulrich; Oltmanns, Kerstin M

2014-10-01

The dorsolateral prefrontal cortex (DLPFC) plays an important role in appetite and food intake regulation. Because previous data revealed that transcranial direct current stimulation (tDCS) of the DLPFC reduces food cravings, we hypothesized that repetitive electric stimulation of the right DLPFC would lower food intake behavior in humans. In a single-blind, code-based, placebo-controlled, counterbalanced, randomized crossover experiment, 14 healthy young men with body mass index (in kg/m(2)) from 20 to 25 were examined during 8 d of daily tDCS or a sham stimulation. After tDCS or sham stimulation on the first and the last day of both experimental conditions, participants consumed food ad libitum from a standardized test buffet. One week of daily anodal tDCS reduced overall caloric intake by 14% in comparison with sham stimulation. Moreover, repetitive tDCS diminished self-reported appetite scores. Our study implies that the application of anodal direct currents to the right DLPFC represents a promising option for reducing both caloric intake and appetite in humans. This trial was registered at the German Clinical Trials Register (www.germanctr.de) as DRKS00005811. © 2014 American Society for Nutrition.

Double-blind, placebo-controlled study of vigabatrin (gamma-vinyl GABA) in drug-resistant epilepsy.

PubMed

Loiseau, P; Hardenberg, J P; Pestre, M; Guyot, M; Schechter, P J; Tell, G P

1986-01-01

Vigabatrin (GVG) (3 g/day) and placebo were compared as an add-on to standard therapy in therapy-resistant epileptic patients using a double-blind crossover design with randomized treatment allocation. Twenty-three patients entered the trial, with four dropping out due to either increased seizure frequency following the cross-over from GVG to placebo (n = 1), intolerance to GVG therapy (n = 2), or poor seizure record (n = 1). Of the 19 patients who completed the study, 17 had partial seizures, eight of whom had secondary generalization and two who had primary generalized seizures. Compared with placebo, GVG was associated with a significant reduction in seizure frequency (p less than 0.01), with 11 of 19 patients experiencing greater than 50% reduction in weekly seizure occurrence, two showing a 25-50% reduction, four unchanged, and two showing an increase in seizures. Global efficacy ratings were greater in the GVG period for 15 patients (p less than 0.05) compared with one in whom there was no period difference and two in whom ratings were higher in the placebo period. Fourteen of the 19 patients indicated a preference for the GVG period. Adverse effects observed during GVG treatment were generally mild and consisted of drowsiness, confusion, nausea, irritability, and constipation. No clinically significant alterations in laboratory test results were observed. No treatment-related changes in plasma concentrations of concomitant antiepileptic drugs were noted. These results confirm the antiepileptic efficacy of oral GVG in refractory epileptics.

L-theanine and caffeine improve task switching but not intersensory attention or subjective alertness.

PubMed

Einöther, Suzanne J L; Martens, Vanessa E G; Rycroft, Jane A; De Bruin, Eveline A

2010-04-01

Tea ingredients L-theanine and caffeine have repeatedly been shown to deliver unique cognitive benefits when consumed in combination. The current randomized, placebo-controlled, double-blind, cross-over study compared a combination of L-theanine (97 mg) and caffeine (40 mg) to a placebo on two attention tasks and a self-report questionnaire before, and 10 and 60 min after consumption. The combination of L-theanine and caffeine significantly improved attention on a switch task as compared to the placebo, while subjective alertness and intersensory attention were not improved significantly. The results support previous evidence that L-theanine and caffeine in combination can improve attention. Copyright 2010 Elsevier Ltd. All rights reserved.

Inhibition of platelet function by low-dose plain and micro-encapsulated acetylsalicylic acid.

PubMed

Waldemar, G; Petersen, P; Boysen, G; Knudsen, J B

1988-04-15

The effect of two acetylsalicylic acid (ASA) formulations, plain (Magnyl) and micro-encapsulated (Globentyl), on platelet aggregation, thromboxane formation, and bleeding time was studied in 12 healthy volunteers in a randomized double-blind cross-over study. All subjects were treated with Magnyl and Globentyl (75 mg daily) in periods of 2 weeks, separated by a wash-out period of 2 weeks. Both drugs significantly depressed platelet aggregation and thromboxane formation and prolonged bleeding time without difference in mode of action of the drugs. It is concluded that significant inhibition of platelet activity may be achieved by low-dose ASA treatment with micro-encapsulated as well as with plain formulations.

Endoscopic evaluation of the comparative effects of acetylsalicylic acid and choline magnesium trisalicylate on human gastric and duodenal mucosa.

PubMed

Kilander, A; Dotevall, G

1983-02-01

A new salicylate product, choline magnesium trisalicylate (Trilisate tablets), and acetylsalicylic acid were compared for their local effects in equipotent doses on the gastroduodenal mucosa in a randomized, double-blind, cross-over study, using 10 healthy volunteers. After five-day periods of administration, gastroduodenoscopy was performed and photographs were obtained. All subjects given acetylsalicylic acid developed multiple mucosal lesions, but in only four subjects given choline magnesium trisalicylate were slight mucosal changes noted. Mean serum salicylate levels were similar in the two groups. Our data suggest that the risk of developing mucosal lesions is much less during treatment with choline magnesium trisalicylate than with acetylsalicylic acid.

Effects of Weighted Vests on Classroom Behavior for Children with Autism and Cognitive Impairments

ERIC Educational Resources Information Center

Hodgetts, Sandra; Magill-Evans, Joyce; Misiaszek, John

2011-01-01

This randomized controlled single-case study investigated the effects of weighted vests for 10 children with autism in a classroom setting. Blinded observers rated targeted behaviors through video taken during structured table-top activities typically part of the classroom routine. Blinded teachers rated each child's behavior with the Conners'…

Randomized Prospective Double-Blind Studies to Evaluate the Cognitive Effects of Inositol-Stabilized Arginine Silicate in Healthy Physically Active Adults

PubMed Central

Kalman, Douglas; Harvey, Philip D.; Perez Ojalvo, Sara; Komorowski, James

2016-01-01

Inositol-stabilized arginine silicate (ASI; Nitrosigine®) has been validated to increase levels of arginine, silicon and nitric oxide production. To evaluate potential enhancement of mental focus and clarity, ASI (1500 mg/day) was tested in two double-blind placebo-controlled crossover (DBPC-X) studies using the Trail Making Test (TMT, Parts A and B). In the two studies, healthy males took ASI for 14 and 3 days, respectively. In the first study, after 14 days of dosing, TMT B time decreased significantly from baseline (28% improvement, p = 0.045). In the second study evaluating shorter-term effects, TMT B time decreased significantly compared to placebo (33% improvement, p = 0.024) in a 10-min period. After 3 days of dosing, TMT B time significantly decreased from baseline scores (35% improvement, p < 0.001). These findings show that ASI significantly improved the ability to perform complex cognitive tests requiring mental flexibility, processing speed and executive functioning. PMID:27869715

Crossover ensembles of random matrices and skew-orthogonal polynomials

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

Kumar, Santosh, E-mail: skumar.physics@gmail.com; Pandey, Akhilesh, E-mail: ap0700@mail.jnu.ac.in

2011-08-15

Highlights: > We study crossover ensembles of Jacobi family of random matrices. > We consider correlations for orthogonal-unitary and symplectic-unitary crossovers. > We use the method of skew-orthogonal polynomials and quaternion determinants. > We prove universality of spectral correlations in crossover ensembles. > We discuss applications to quantum conductance and communication theory problems. - Abstract: In a recent paper (S. Kumar, A. Pandey, Phys. Rev. E, 79, 2009, p. 026211) we considered Jacobi family (including Laguerre and Gaussian cases) of random matrix ensembles and reported exact solutions of crossover problems involving time-reversal symmetry breaking. In the present paper we givemore » details of the work. We start with Dyson's Brownian motion description of random matrix ensembles and obtain universal hierarchic relations among the unfolded correlation functions. For arbitrary dimensions we derive the joint probability density (jpd) of eigenvalues for all transitions leading to unitary ensembles as equilibrium ensembles. We focus on the orthogonal-unitary and symplectic-unitary crossovers and give generic expressions for jpd of eigenvalues, two-point kernels and n-level correlation functions. This involves generalization of the theory of skew-orthogonal polynomials to crossover ensembles. We also consider crossovers in the circular ensembles to show the generality of our method. In the large dimensionality limit, correlations in spectra with arbitrary initial density are shown to be universal when expressed in terms of a rescaled symmetry breaking parameter. Applications of our crossover results to communication theory and quantum conductance problems are also briefly discussed.« less

Two Randomized Clinical Studies to Confirm Differential Plaque Removal by Sodium Bicarbonate Dentifrices in a Single Timed Brushing Model.

PubMed

Mason, Stephen; Karwal, Ritu; Bosma, Mary Lynn

2017-09-01

This study evaluated and compared plaque removal efficacy of commercially available dentifrices containing sodium bicarbonate (NaHCO3) to those without NaHCO3 in a single timed brushing clinical study model. Two randomized, examiner-blind, three-period, three-treatment, crossover studies were performed in adults with a mean Turesky modification of the Quigley-Hein Plaque Index (TPI) score of = 2.00. In Study 1, 60 subjects were randomized to commercially available dentifrices containing: (i) 67% NaHCO3 plus 1425 ppm fluoride (F) as sodium fluoride (NaF); (ii) 45% NaHCO3 plus 1425 ppm F as NaF; or (iii) 0% NaHCO3 plus silica and 1450 ppm F as NaF. In Study 2, 55 subjects were randomized to commercially available dentifrices containing: (i) 67% NaHCO3 plus 1425 ppm F as NaF; (ii) 0% NaHCO3 plus silica and 1400 ppm F as amine F/stannous F; or (iii) 0% NaHCO3 plus chlorhexidine/aluminum lactate and silica with 1360 ppm F as aluminum F. In both studies, subjects brushed their teeth for one timed minute under supervised conditions. Plaque was assessed pre- and post-brushing according to a six-site modification of the TPI. Mean TPI score was analyzed using an analysis of covariance model with treatment and study period as fixed effects, subject as a random variable, and pre-brushing score as a covariate. In both studies, mean TPI score decreased in all groups post-brushing compared with pre-brushing. In Study 1, statistically significant improvements in mean TPI score were reported with the 67% and 45% NaHCO3 dentifrices compared with the 0% NaHCO3 dentifrice (p = 0.0003 and p = 0.0005, respectively). In Study 2, improvements in mean TPI score were statistically significantly greater with the 67% NaHCO3 dentifrice compared with both 0% NaHCO3 dentifrices (p < 0.0001 for both comparisons). All dentifrices were generally well tolerated. A single timed brushing with commercially available dentifrices containing 67% or 45% NaHCO3 exerted a significantly greater effect on plaque removal than commercially available dentifrices without NaHCO3.

Symptoms in Response to Controlled Diesel Exhaust More Closely Reflect Exposure Perception Than True Exposure

PubMed Central

Carlsten, Chris; Oron, Assaf P.; Curtiss, Heidi; Jarvis, Sara; Daniell, William; Kaufman, Joel D.

2013-01-01

Background Diesel exhaust (DE) exposures are very common, yet exposure-related symptoms haven’t been rigorously examined. Objective Describe symptomatic responses to freshly generated and diluted DE and filtered air (FA) in a controlled human exposure setting; assess whether such responses are altered by perception of exposure. Methods 43 subjects participated within three double-blind crossover experiments to order-randomized DE exposure levels (FA and DE calibrated at 100 and/or 200 micrograms/m3 particulate matter of diameter less than 2.5 microns), and completed questionnaires regarding symptoms and dose perception. Results For a given symptom cluster, the majority of those exposed to moderate concentrations of diesel exhaust do not report such symptoms. The most commonly reported symptom cluster was of the nose (29%). Blinding to exposure is generally effective. Perceived exposure, rather than true exposure, is the dominant modifier of symptom reporting. Conclusion Controlled human exposure to moderate-dose diesel exhaust is associated with a range of mild symptoms, though the majority of individuals will not experience any given symptom. Blinding to DE exposure is generally effective. Perceived DE exposure, rather than true DE exposure, is the dominant modifier of symptom reporting. PMID:24358296

Pharmacokinetics and Safety of Intravenous Murepavadin Infusion in Healthy Adult Subjects Administered Single and Multiple Ascending Doses.

PubMed

Wach, Achim; Dembowsky, Klaus; Dale, Glenn E

2018-04-01

Murepavadin is the first in class of the outer membrane protein-targeting antibiotics (OMPTA) and a pathogen-specific peptidomimetic antibacterial with a novel, nonlytic mechanism of action targeting Pseudomonas aeruginosa Murepavadin is being developed for the treatment of hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP). The pharmacokinetics (PK) and safety of single and multiple doses of murepavadin were investigated in healthy male subjects. Part A of the study was a double-blind, randomized, placebo-controlled, single-ascending-dose investigation in 10 sequential cohorts where each cohort comprised 6 healthy male subjects; 4 subjects were randomized to murepavadin, and 2 subjects were randomized to placebo. Part B was a double-blind, randomized, placebo-controlled, multiple-ascending-dose investigation in 3 sequential cohorts. After a single dose of murepavadin, the geometric mean half-life (2.52 to 5.30 h), the total clearance (80.1 to 114 ml/h/kg), and the volume of distribution (415 to 724 ml/kg) were consistent across dose levels. The pharmacokinetics of the dosing regimens evaluated were dose proportional and linear. Murepavadin was well tolerated, adverse events were transient and generally mild, and no dose-limiting toxicity was identified. Copyright © 2018 American Society for Microbiology.

Crossover Control Study of the Effect of Personal Care Products Containing Triclosan on the Microbiome

PubMed Central

Poole, Angela C.; Pischel, Lauren; Ley, Catherine; Suh, Gina; Goodrich, Julia K.; Haggerty, Thomas D.; Ley, Ruth E.

2016-01-01

ABSTRACT Commonly prescribed antibiotics are known to alter human microbiota. We hypothesized that triclosan and triclocarban, components of many household and personal care products (HPCPs), may alter the oral and gut microbiota, with potential consequences for metabolic function and weight. In a double-blind, randomized, crossover study, participants were given triclosan- and triclocarban (TCS)-containing or non-triclosan/triclocarban (nTCS)-containing HPCPs for 4 months and then switched to the other products for an additional 4 months. Blood, stool, gingival plaque, and urine samples and weight data were obtained at baseline and at regular intervals throughout the study period. Blood samples were analyzed for metabolic and endocrine markers and urine samples for triclosan. The microbiome in stool and oral samples was then analyzed. Although there was a significant difference in the amount of triclosan in the urine between the TCS and nTCS phases, no differences were found in microbiome composition, metabolic or endocrine markers, or weight. Though this study was limited by the small sample size and imprecise administration of HPCPs, triclosan at physiologic levels from exposure to HPCPs does not appear to have a significant or important impact on human oral or gut microbiome structure or on a panel of metabolic markers. IMPORTANCE Triclosan and triclocarban are commonly used commercial microbicides found in toothpastes and soaps. It is unknown what effects these chemicals have on the human microbiome or on endocrine function. From this randomized crossover study, it appears that routine personal care use of triclosan and triclocarban neither exerts a major influence on microbial communities in the gut and mouth nor alters markers of endocrine function in humans. PMID:27303746

Comparison between single-diode low-level laser therapy (LLLT) and LED multi-diode (cluster) therapy (LEDT) applications before high-intensity exercise.

PubMed

Leal Junior, Ernesto Cesar Pinto; Lopes-Martins, Rodrigo Alvaro Brandão; Baroni, Bruno Manfredini; De Marchi, Thiago; Rossi, Rafael Paolo; Grosselli, Douglas; Generosi, Rafael Abeche; de Godoi, Vanessa; Basso, Maira; Mancalossi, José Luis; Bjordal, Jan Magnus

2009-08-01

There is anecdotal evidence that low-level laser therapy (LLLT) may affect the development of muscular fatigue, minor muscle damage, and recovery after heavy exercises. Although manufacturers claim that cluster probes (LEDT) maybe more effective than single-diode lasers in clinical settings, there is a lack of head-to-head comparisons in controlled trials. This study was designed to compare the effect of single-diode LLLT and cluster LEDT before heavy exercise. This was a randomized, placebo-controlled, double-blind cross-over study. Young male volleyball players (n = 8) were enrolled and asked to perform three Wingate cycle tests after 4 x 30 sec LLLT or LEDT pretreatment of the rectus femoris muscle with either (1) an active LEDT cluster-probe (660/850 nm, 10/30 mW), (2) a placebo cluster-probe with no output, and (3) a single-diode 810-nm 200-mW laser. The active LEDT group had significantly decreased post-exercise creatine kinase (CK) levels (-18.88 +/- 41.48 U/L), compared to the placebo cluster group (26.88 +/- 15.18 U/L) (p < 0.05) and the active single-diode laser group (43.38 +/- 32.90 U/L) (p < 0.01). None of the pre-exercise LLLT or LEDT protocols enhanced performance on the Wingate tests or reduced post-exercise blood lactate levels. However, a non-significant tendency toward lower post-exercise blood lactate levels in the treated groups should be explored further. In this experimental set-up, only the active LEDT probe decreased post-exercise CK levels after the Wingate cycle test. Neither performance nor blood lactate levels were significantly affected by this protocol of pre-exercise LEDT or LLLT.

Transcutaneous electrical nerve stimulation reduces pain, fatigue and hyperalgesia while restoring central inhibition in primary fibromyalgia.

PubMed

Dailey, Dana L; Rakel, Barbara A; Vance, Carol G T; Liebano, Richard E; Amrit, Anand S; Bush, Heather M; Lee, Kyoung S; Lee, Jennifer E; Sluka, Kathleen A

2013-11-01

Because transcutaneous electrical nerve stimulation (TENS) works by reducing central excitability and activating central inhibition pathways, we tested the hypothesis that TENS would reduce pain and fatigue and improve function and hyperalgesia in people with fibromyalgia who have enhanced central excitability and reduced inhibition. The current study used a double-blinded randomized, placebo-controlled cross-over design to test the effects of a single treatment of TENS with people with fibromyalgia. Three treatments were assessed in random order: active TENS, placebo TENS and no TENS. The following measures were assessed before and after each TENS treatment: pain and fatigue at rest and in movement; pressure pain thresholds, 6-m walk test, range of motion; 5-time sit-to-stand test, and single-leg stance. Conditioned pain modulation was completed at the end of testing. There was a significant decrease in pain and fatigue with movement for active TENS compared to placebo and no TENS. Pressure pain thresholds increased at the site of TENS (spine) and outside the site of TENS (leg) when compared to placebo TENS or no TENS. During active TENS, conditioned pain modulation was significantly stronger compared to placebo TENS and no TENS. No changes in functional tasks were observed with TENS. Thus, the current study suggests TENS has short-term efficacy in relieving symptoms of fibromyalgia while the stimulator is active. Future clinical trials should examine the effects of repeated daily delivery of TENS, similar to the way in which TENS is used clinically on pain, fatigue, function, and quality of life in individuals with fibromyalgia. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Mucuna pruriens in Parkinson disease: A double-blind, randomized, controlled, crossover study.

PubMed

Cilia, Roberto; Laguna, Janeth; Cassani, Erica; Cereda, Emanuele; Pozzi, Nicolò G; Isaias, Ioannis U; Contin, Manuela; Barichella, Michela; Pezzoli, Gianni

2017-08-01

To investigate whether Mucuna pruriens (MP), a levodopa-containing leguminous plant growing in all tropical areas worldwide, may be used as alternative source of levodopa for indigent individuals with Parkinson disease (PD) who cannot afford long-term therapy with marketed levodopa preparations. We investigated efficacy and safety of single-dose intake of MP powder from roasted seeds obtained without any pharmacologic processing. Eighteen patients with advanced PD received the following treatments, whose sequence was randomized: (1) dispersible levodopa at 3.5 mg/kg combined with the dopa-decarboxylase inhibitor benserazide (LD+DDCI; the reference treatment); (2) high-dose MP (MP-Hd; 17.5 mg/kg); (3) low-dose MP (MP-Ld; 12.5 mg/kg); (4) pharmaceutical preparation of LD without DDCI (LD-DDCI; 17.5 mg/kg); (5) MP plus benserazide (MP+DDCI; 3.5 mg/kg); (6) placebo. Efficacy outcomes were the change in motor response at 90 and 180 minutes and the duration of on state. Safety measures included any adverse event (AE), changes in blood pressure and heart rate, and the severity of dyskinesias. When compared to LD+DDCI, MP-Ld showed similar motor response with fewer dyskinesias and AEs, while MP-Hd induced greater motor improvement at 90 and 180 minutes, longer ON duration, and fewer dyskinesias. MP-Hd induced less AEs than LD+DDCI and LD-DDCI. No differences in cardiovascular response were recorded. Single-dose MP intake met all noninferiority efficacy and safety outcome measures in comparison to dispersible levodopa/benserazide. Clinical effects of high-dose MP were similar to levodopa alone at the same dose, with a more favorable tolerability profile. NCT02680977. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Anticaries Potential of a Sodium Monofluorophosphate Dentifrice Containing Calcium Sodium Phosphosilicate: Exploratory in situ Randomized Trial.

PubMed

Parkinson, Charles R; Siddiqi, Muhammad; Mason, Stephen; Lippert, Frank; Hara, Anderson T; Zero, Domenick T

2017-01-01

Calcium sodium phosphosilicate (CSPS) is a bioactive glass material that alleviates dentin hypersensitivity and is postulated to confer remineralization of caries lesions. This single-centre, randomized, single (investigator)-blind, placebo-controlled, crossover, in situ study explored whether the addition of 5% CSPS to a nonaqueous fluoride (F) such as sodium monofluorophosphate (SMFP)-containing dentifrice affects its cariostatic ability. Seventy-seven subjects wore 4 gauze-covered enamel specimens with preformed lesions (2 surface-softened and 2 subsurface) placed buccally on their mandibular bilateral dentures for up to 4 weeks. Subjects brushed twice daily with 1 of the 5 study dentifrices: 927 ppm F/5% CSPS, 927 ppm F/0% CSPS, 250 ppm F/0% CSPS, 0 ppm F/5% CSPS, or 0 ppm F/0% CSPS. Specimens were retrieved after either 21 (surface-softened lesions; analyzed by Knoop surface microhardness [SMH]) or 28 days (subsurface lesions; analyzed by transverse microradiography). The enamel fluoride uptake was determined for all specimens using a microbiopsy technique. The concentrations of fluoride and calcium in gauze-retrieved plaque were also evaluated. Higher dentifrice fluoride concentrations led to greater remineralization and fluoridation of both lesion types and increased plaque fluoride concentrations. CSPS did not improve the cariostatic properties of SMFP; there were no statistically significant differences between 927 ppm F/5% CSPS and 927 ppm F/0% CSPS in percent SMH recovery (p = 0.6788), change in integrated mineral loss (p = 0.5908), or lesion depth (p = 0.6622). Likewise, 0 ppm F/5% CSPS did not provide any benefits in comparison to 0 ppm F/0% CSPS. In conclusion, CSPS does not negatively impact nor does it improve the ability of an SMFP dentifrice to affect remineralization of caries lesions. © 2017 S. Karger AG, Basel.

Effects of a Gentle, Self-Administered Stimulation of Perineal Skin for Nocturia in Elderly Women: A Randomized, Placebo-Controlled, Double-Blind Crossover Trial

PubMed Central

Iimura, Kaori; Watanabe, Nobuhiro; Masunaga, Koichi; Miyazaki, Shogo; Hotta, Harumi; Kim, Hunkyung; Hisajima, Tatsuya; Takahashi, Hidenori; Kasuya, Yutaka

2016-01-01

Background Somatic afferent nerve stimuli are used for treating an overactive bladder (OAB), a major cause of nocturia in the elderly. Clinical evidence for this treatment is insufficient because of the lack of appropriate control stimuli. Recent studies on anesthetized animals show that gentle stimuli applied to perineal skin with a roller could inhibit micturition contractions depending on the roller’s surface material. We examined the efficacy of gentle skin stimuli for treating nocturia. Methods The study was a cross-over, placebo-controlled, double-blind randomized clinical study using two rollers with different effects on micturition contractions. Participants were elderly women (79–89 years) with nocturia. Active (soft elastomer roller) or placebo (hard polystyrene roller) stimuli were applied to perineal skin by participants for 1 min at bedtime. A 3-day baseline assessment period was followed by 3-day stimulation and 4-day resting periods, after which the participants were subjected to other stimuli for another 3 days. The primary outcome was change in the frequency of nighttime urination, for which charts were maintained during each 3-day period. Results Twenty-four participants were randomized, of which 22 completed all study protocols. One participant discontinued treatment because of an adverse event (abdominal discomfort). In participants with OAB (n = 9), change from baseline in the mean frequency of urination per night during the active stimuli period (mean ± standard deviation, −0.74 ± 0.7 times) was significantly greater than that during placebo stimuli periods (−0.15 ± 0.8 times [p < 0.05]). In contrast, this difference was not observed in participants without OAB (n = 13). Conclusions These results suggest that gentle perineal stimulation with an elastomer roller is effective for treating OAB-associated nocturia in elderly women. Here the limitation was a study period too short to assess changes in the quality of sleep and life. Trial Registration UMIN Clinical Trial Registry (CTR) UMIN000015809 PMID:27003163

Isoflavone supplement composition and equol producer status affect gene expression in adipose tissue: a double-blind, randomized, placebo-controlled crossover trial in postmenopausal women.

PubMed

van der Velpen, Vera; Geelen, Anouk; Hollman, Peter C H; Schouten, Evert G; van 't Veer, Pieter; Afman, Lydia A

2014-11-01

Isoflavone supplements, consumed by women experiencing menopausal symptoms, are suggested to have positive effects on menopause-related adiposity and cardiovascular disease risk profile, but discussions about their safety are still ongoing. The objective was to study the effects of an 8-wk consumption of 2 different isoflavone supplements compared with placebo on whole-genome gene expression in the adipose tissue of postmenopausal women. This double-blind, randomized, placebo-controlled crossover intervention consisted of 2 substudies, one with a low-genistein (LG) supplement (56% daidzein + daidzin, 16% genistein + genistin, and 28% glycitein + glycitin) and the other with a high-genistein (HG) supplement (49% daidzein + daidzin, 41% genistein + genistin, and 10% glycitein + glycitin). Both supplements provided ∼ 100 mg isoflavones/d (aglycone equivalents). After the 8-wk isoflavone and placebo period, whole-genome arrays were performed in subcutaneous adipose tissue of postmenopausal women (n = 26 after LG, n = 31 after HG). Participants were randomized by equol-producing phenotype, and data analysis was performed per substudy for equol producers and nonproducers separately. Gene set enrichment analysis showed downregulation of expression of energy metabolism-related genes after LG supplementation (n = 24) in both equol-producing phenotypes and oppositely regulated expression for equol producers (down) and nonproducers (up) after HG supplementation (n = 31). Expression of inflammation-related genes was upregulated in equol producers but downregulated in nonproducers, independent of supplement type. Only 4.4-7.0% of the genes with significantly changed expression were estrogen responsive. Body weight, adipocyte size, and plasma lipid profile were not affected by isoflavone supplementation. Effects of isoflavones on adipose tissue gene expression were influenced by supplement composition and equol-producing phenotype, whereas estrogen-responsive effects were lacking. LG isoflavone supplementation resulted in a caloric restriction-like gene expression profile for both producer phenotypes and pointed toward a potential beneficial effect, whereas both supplements induced anti-inflammatory gene expression in equol producers. The study was registered at clinicaltrials.gov as NCT01556737. © 2014 American Society for Nutrition.

A randomized, double-blind, placebo-controlled crossover study of the effects of levetiracetam on cognition, mood, and balance in healthy older adults.

PubMed

Schoenberg, Mike R; Rum, Ruba S; Osborn, Katie E; Werz, Mary Ann

2017-09-01

The cognitive and mood effects of levetiracetam (LEV) in older adults are not known. This study compared the cognitive and mood effects of LEV to placebo in healthy older adults. Cognitive, mood, and balance variables were compared between LEV and placebo using a randomized, double-blind, placebo-controlled crossover study with two 5-week treatment periods. Healthy volunteers (n = 20) aged 65-80 (mean age 72.4) received either LEV or placebo in which the LEV target dose was 1,000 mg/day. Volunteers, aged 65-80, were without epilepsy to limit potentially confounding the impact of seizures and/or underlying neuropathology on outcomes. LEV was initiated at 250 mg twice a day for 2 weeks, then increased to 500 mg twice a day for 2 weeks, and then tapered to 250 mg twice a day for 1 week. This was randomized with placebo for the two treatment arms. Measures included standardized neuropsychological, mood, and balance tests yielding 32 variables. Balance was assessed using subjective report (e.g., A-B neurotoxicity scale) and objective data (e.g., Berg Balance Scale). Average LEV serum concentration was 16.9 (standard deviation [SD} 7.7). Repeated-measures analysis of variance (ANOVA) found no differences between LEV and placebo phases for 29 (90.6%) of 32 variables including no change in balance. Performance on LEV was better than placebo on a visual memory (MCG Complex Figure Recall; p = 0.007) and two attention tests (Trail Making Test, Part A, p = 0.009; Stroop Interference, p = 0.004). There was a trend for greater irritability and fatigue (POMS Anger and Fatigue) during the LEV phase (p = 0.029, p = 0.035). Effect-size changes were generally small (Cohen d < 0.5). LEV was well tolerated in this elderly population in terms of cognition, mood, and balance. When anticonvulsant medication is indicated for older adults, LEV has pharmacokinetic advantages, and these data indicate no adverse impact on cognition or balance. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

The effect of chronic progressive-dose sodium bicarbonate ingestion on CrossFit-like performance: A double-blind, randomized cross-over trial.

PubMed

Durkalec-Michalski, Krzysztof; Zawieja, Emilia E; Podgórski, Tomasz; Łoniewski, Igor; Zawieja, Bogna E; Warzybok, Marta; Jeszka, Jan

2018-01-01

Sodium bicarbonate (SB) has been proposed as an ergogenic aid, as it improves high-intensity and resistance exercise performance. However, no studies have yet investigated SB application in CrossFit. This study examined the effects of chronic, progressive-dose SB ingestion on CrossFit-like performance and aerobic capacity. In a randomized, double-blind, cross-over trial, 21 CrossFit-trained participants were randomly allocated to 2 groups and underwent 2 trials separated by a 14-day washout period. Participants ingested either up to 150 mg∙kg-1 of SB in a progressive-dose regimen or placebo for 10 days. Before and after each trial, Fight Gone Bad (FGB) and incremental cycling (ICT) tests were performed. In order to examine biochemical responses, blood samples were obtained prior to and 3 min after completing each exercise test. No gastrointestinal (GI) side effects were reported during the entire protocol. The overall FGB performance improved under SB by ~6.1% (p<0.001) and it was ~3.1% higher compared to post placebo (PLApost) (p = 0.040). The number of repetitions completed in each round also improved under SB (mean from baseline: +5.8% to +6.4%). Moreover, in ICT, the time to ventilatory threshold (VT) (~8:25 min SBpost vs. ~8:00 min PLApost, p = 0.020), workload at VT (~218 W SBpost vs. ~208 W PLApost, p = 0.037) and heart rate at VT (~165 bpm SBpost vs. ~161 bpm PLApost, p = 0.030) showed higher SBpost than PLApost. Furthermore, the maximum carbon dioxide production increased under SB by ~4.8% (from ~3604 mL∙min-1 to ~3776 mL∙min-1, p = 0.049). Pyruvate concentration and creatine kinase activity before ICT showed higher SBpost than PLApost (~0.32 mmol∙L-1 vs. ~0.26 mmol∙L-1, p = 0.001; ~275 U∙L-1 vs. ~250 U∙L-1, p = 0.010, respectively). However, the small sample size limits the wide-application of our results. Progressive-dose SB ingestion regimen eliminated GI side effects and improved CrossFit-like performance, as well as delayed ventilatory threshold occurrence.

Effects of the pure flavonoids epicatechin and quercetin on vascular function and cardiometabolic health: a randomized, double-blind, placebo-controlled, crossover trial.

PubMed

Dower, James I; Geleijnse, Johanna M; Gijsbers, Lieke; Zock, Peter L; Kromhout, Daan; Hollman, Peter C H

2015-05-01

Prospective cohort studies showed inverse associations between the intake of flavonoid-rich foods (cocoa and tea) and cardiovascular disease (CVD). Intervention studies showed protective effects on intermediate markers of CVD. This may be due to the protective effects of the flavonoids epicatechin (in cocoa and tea) and quercetin (in tea). We investigated the effects of supplementation of pure epicatechin and quercetin on vascular function and cardiometabolic health. Thirty-seven apparently healthy men and women aged 40-80 y with a systolic blood pressure (BP) between 125 and 160 mm Hg at screening were enrolled in a randomized, double-blind, placebo-controlled, crossover trial. CVD risk factors were measured before and after 4 wk of daily flavonoid supplementation. Participants received (-)-epicatechin (100 mg/d), quercetin-3-glucoside (160 mg/d), or placebo capsules for 4 wk in random order. The primary outcome was the change in flow-mediated dilation from pre- to postintervention. Secondary outcomes included other markers of CVD risk and vascular function. Epicatechin supplementation did not change flow-mediated dilation significantly (1.1% absolute; 95% CI: -0.1%, 2.3%; P = 0.07). Epicatechin supplementation improved fasting plasma insulin (Δ insulin: -1.46 mU/L; 95% CI: -2.74, -0.18 mU/L; P = 0.03) and insulin resistance (Δ homeostasis model assessment of insulin resistance: -0.38; 95% CI: -0.74, -0.01; P = 0.04) and had no effect on fasting plasma glucose. Epicatechin did not change BP (office BP and 24-h ambulatory BP), arterial stiffness, nitric oxide, endothelin 1, or blood lipid profile. Quercetin-3-glucoside supplementation had no effect on flow-mediated dilation, insulin resistance, or other CVD risk factors. Our results suggest that epicatechin may in part contribute to the cardioprotective effects of cocoa and tea by improving insulin resistance. It is unlikely that quercetin plays an important role in the cardioprotective effects of tea. This study was registered at clinicaltrials.gov as NCT01691404. © 2015 American Society for Nutrition.

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

PubMed Central

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

2016-01-01

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

Deanol, lithium and placebo in the treatment of tardive dyskinesia. A double-blind crossover study.

PubMed

Jus, A; Villeneuve, A; Gautier, J; Jus, K; Villeneuve, C; Pires, P; Villeneuve, R

1978-01-01

A double-blind crossover study on the effects of deanol and lithium carbonate was conducted on a sample of 29 chronic schizophrenic patients with tardive dyskinesia. In addition to his usual treatment with different neuroleptics, each patient received during an 8-week period either deanol, lithium carbonate or placebo. A 4-week wash-out period was inserted between each of the 8-week periods of experimental treatment of the tardive dyskinesia. The administration of either deanol, lithium carbonate or placebo added to the neuroleptic treatment did not produce a statistically significant improvement of tardive dyskinesia in our patient population as a whole. Favorable and unfavorable responses are discussed.

Palonosetron and Hydroxyzine Pre-treatment Reduces the Objective Signs of Experimentally-Induced Acute Opioid Withdrawal in Humans: A Double-Blinded, Randomized, Placebo-Controlled Crossover Study

PubMed Central

Erlendson, Matthew; D'Arcy, Nicole; Encisco, Ellen; Yu, Jeff; Rincon-Cruz, Lorena; Peltz, Gary; Clark, J. David

2017-01-01

Background Treatments for reducing opioid withdrawal are limited and prone to problematic side effects. Laboratory studies, clinical observations, and limited human trial data suggest 5-HT3-receptor antagonists and antihistamines may be effective. Objectives This double-blind, crossover, placebo-controlled study employing an acute physical dependence model evaluated whether (i) treatment with a 5-HT3-receptor antagonist (palonosetron) would reduce opioid withdrawal symptoms, and (ii) co-administration of an antihistamine (hydroxyzine) would enhance any treatment effect. Methods At timepoint T=0, healthy (non-opioid dependent, non-substance abuser) male volunteers (N=10) were pre-treated with either a) placebo, b) palonosetron IV (0.75 mg), or c) palonosetron IV (0.75 mg) and hydroxyzine PO (100 mg) in a crossover study design. This was followed at T=30 by intravenous morphine (10mg/70kg). At T=165, 10mg/70kg naloxone IV was given to precipitate opioid withdrawal. The objective opioid withdrawal score (OOWS) and subjective opioid withdrawal score (SOWS) were determined 5 and 15 minutes after naloxone administration (T=170, 180, respectively). Baseline measurements were recorded at T=-30 and T=-15. Results Comparison of average baseline OOWS scores with OOWS scores obtained fifteen minutes after naloxone was significant (p=0.0001). Scores from fifteen minutes post-naloxone infusion showed significant differences in OOWS scores between treatment groups: placebo, 3.7 ± 2.4; palonosetron, 1.5± 0.97; and palonosetron with hydroxyzine, 0.2 ± .1333. Conclusions Pretreatment with palonosetron significantly reduced many signs of experimental-induced opioid withdrawal. Co-administration with hydroxyzine further reduced opioid withdrawal severity. These results suggest that 5-HT3 receptor antagonists, alone or in combination with an antihistamine, may be useful in the treatment of opioid withdrawal. PMID:27712113

Impact of cooked functional meat enriched with omega-3 fatty acids and rosemary extract on inflammatory and oxidative status; a randomised, double-blind, crossover study.

PubMed

Bermejo, L M; López-Plaza, B; Weber, T K; Palma-Milla, S; Iglesias, C; Reglero, G; Gómez-Candela, C

2014-11-01

n-3 fatty acid intake has been associated with inflammatory benefits in cardiovascular disease (CVD). Functionalising meat may be of great interest. The aim of the present study was to assess the effect of functional meat containing n-3 and rosemary extract on inflammatory and oxidative status markers in subjects with risk for CVD. A randomised, double-blind, cross-over study was undertaken to compare the effects on the above markers of consuming functional or control meat products. 43 volunteers with at least two lipid profile variables showing risk for CVD were randomly assigned to receive functional meat (FM) or control meat (CM) over 12-weeks with a 4-week wash-out interval before crossover. Functional effects were assessed by examining lipid profile, CRP, PAI-1, TNF-alpha, IL-6, fibrinogen (inflammatory markers), and TBARS, FRAP and 8-iso-PGF2 (oxidative status markers). 33 subjects (24 women) aged 50.7±8.8 years completed the study. In FM treatment, PAI-1, fibrinogen and 8-iso-PGF2 decreased significantly after 12 weeks, while FRAP significantly increased. In contrast, in CM treatment, a significant increase was seen in PAI-1, while FRAP significantly declined. Significant differences were also seen between the FM and CM treatments after 12 weeks in terms of the change observed in PAI-1, FRAP and 8-iso-PGF2 values. No significant differences were seen in anthropometric variables nor were adverse effects reported. The consumption of FM containing n-3 and rosemary extract improved oxidative and inflammatory status of people with at least two lipid profile variables showing risk for CVD. The inclusion of such functional meat in a balanced diet might be a healthy lifestyle option. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Pediatric functional constipation treatment with Bifidobacterium-containing yogurt: a crossover, double-blind, controlled trial.

PubMed

Guerra, Paula V P; Lima, Luiza N; Souza, Tassia C; Mazochi, Vanessa; Penna, Francisco J; Silva, Andreia M; Nicoli, Jacques R; Guimarães, Elizabet V

2011-09-14

To evaluate the treatment of pediatric functional chronic intestinal constipation (FCIC) with a probiotic goat yogurt. A crossover double-blind formula-controlled trial was carried out on 59 students (age range: 5-15 years) of a public school in Belo Horizonte, MG, Brazil, presenting a FCIC diagnostic, according to Roma III criteria. The students were randomized in two groups to receive a goat yogurt supplemented with 10(9) colony forming unit/mL Bifidobacterium longum (B. longum) (probiotic) daily or only the yogurt for a period of 5 wk (formula). Afterwards, the groups were intercrossed for another 5 wk. Defecation frequency, stool consistency and abdominal and defecation pain were assessed. Both treatment groups demonstrated improvement in defecation frequency compared to baseline. However, the group treated with probiotic showed most significant improvement in the first phase of the study. An inversion was observed after crossing over, resulting in a reduction in stool frequency when this group was treated by formula. Probiotic and formula improved stool consistency in the first phase of treatment, but the improvement obtained with probiotic was significantly higher (P = 0.03). In the second phase of treatment, the group initially treated with probiotic showed worsening stool consistency when using formula. However, the difference was not significant. A significant improvement in abdominal pain and defecation pain was observed with both probiotic and formula in the first phase of treatment, but again the improvement was more significant for the group treated with B. longum during phase I (P < 0.05). When all data of the crossover study were analyzed, significant differences were observed between probiotic yogurt and yogurt only for defecation frequency (P = 0.012), defecation pain (P = 0.046) and abdominal pain (P = 0.015). An improvement in defecation frequency and abdominal pain was observed using both supplemented and non-supplemented yogurt, but an additional improvement with B. longum supplementation was obtained.

Effects of repetitive transcranial magnetic stimulation and trans-spinal direct current stimulation associated with treadmill exercise in spinal cord and cortical excitability of healthy subjects: A triple-blind, randomized and sham-controlled study

PubMed Central

Albuquerque, Plínio Luna; Campêlo, Mayara; Mendonça, Thyciane; Fontes, Luís Augusto Mendes; Brito, Rodrigo de Mattos

2018-01-01

Repetitive transcranial magnetic stimulation (rTMS) over motor cortex and trans-spinal direct current stimulation (tsDCS) modulate corticospinal circuits in healthy and injured subjects. However, their associated effects with physical exercise is still not defined. This study aimed to investigate the effect of three different settings of rTMS and tsDCS combined with treadmill exercise on spinal cord and cortical excitability of healthy subjects. We performed a triple blind, randomized, sham-controlled crossover study with 12 healthy volunteers who underwent single sessions of rTMS (1Hz, 20Hz and Sham) and tsDCS (anodal, cathodal and Sham) associated with 20 minutes of treadmill walking. Cortical excitability was assessed by motor evoked potential (MEP) and spinal cord excitability by the Hoffmann reflex (Hr), nociceptive flexion reflex (NFR) and homosynaptic depression (HD). All measures were assessed before, immediately, 30 and 60 minutes after the experimental procedures. Our results demonstrated that anodal tsDCS/treadmill exercise reduced MEP’s amplitude and NFR’s area compared to sham condition, conversely, cathodal tsDCS/treadmill exercise increased NFR’s area. High-frequency rTMS increased MEP’s amplitude and NFR’s area compared to sham condition. Anodal tsDCS/treadmill exercise and 20Hz rTMS/treadmill exercise reduced Hr amplitude up to 30 minutes after stimulation offset and no changes were observed in HD measures. We demonstrated that tsDCS and rTMS combined with treadmill exercise modulated cortical and spinal cord excitability through different mechanisms. tsDCS modulated spinal reflexes in a polarity-dependent way acting at local spinal circuits while rTMS probably promoted changes in the presynaptic inhibition of spinal motoneurons. In addition, the association of two neuromodulatory techniques induced long-lasting changes. PMID:29596524

Effects of repetitive transcranial magnetic stimulation and trans-spinal direct current stimulation associated with treadmill exercise in spinal cord and cortical excitability of healthy subjects: A triple-blind, randomized and sham-controlled study.

PubMed

Albuquerque, Plínio Luna; Campêlo, Mayara; Mendonça, Thyciane; Fontes, Luís Augusto Mendes; Brito, Rodrigo de Mattos; Monte-Silva, Katia

2018-01-01

Repetitive transcranial magnetic stimulation (rTMS) over motor cortex and trans-spinal direct current stimulation (tsDCS) modulate corticospinal circuits in healthy and injured subjects. However, their associated effects with physical exercise is still not defined. This study aimed to investigate the effect of three different settings of rTMS and tsDCS combined with treadmill exercise on spinal cord and cortical excitability of healthy subjects. We performed a triple blind, randomized, sham-controlled crossover study with 12 healthy volunteers who underwent single sessions of rTMS (1Hz, 20Hz and Sham) and tsDCS (anodal, cathodal and Sham) associated with 20 minutes of treadmill walking. Cortical excitability was assessed by motor evoked potential (MEP) and spinal cord excitability by the Hoffmann reflex (Hr), nociceptive flexion reflex (NFR) and homosynaptic depression (HD). All measures were assessed before, immediately, 30 and 60 minutes after the experimental procedures. Our results demonstrated that anodal tsDCS/treadmill exercise reduced MEP's amplitude and NFR's area compared to sham condition, conversely, cathodal tsDCS/treadmill exercise increased NFR's area. High-frequency rTMS increased MEP's amplitude and NFR's area compared to sham condition. Anodal tsDCS/treadmill exercise and 20Hz rTMS/treadmill exercise reduced Hr amplitude up to 30 minutes after stimulation offset and no changes were observed in HD measures. We demonstrated that tsDCS and rTMS combined with treadmill exercise modulated cortical and spinal cord excitability through different mechanisms. tsDCS modulated spinal reflexes in a polarity-dependent way acting at local spinal circuits while rTMS probably promoted changes in the presynaptic inhibition of spinal motoneurons. In addition, the association of two neuromodulatory techniques induced long-lasting changes.

Effects of conjugated linoleic acid and high oleic acid safflower oil in the treatment of children with HPV-induced laryngeal papillomatosis: a randomized, double-blinded and crossover preliminary study

PubMed Central

2012-01-01

Background Surgery is the mainstay therapy for HPV-induced laryngeal papillomatosis (LP) and adjuvant therapies are palliative at best. Research revealed that conjugated-linoleic acid (CLA) may improve the outcome of virally-induced diseases. The effects of Clarinol™ G-80 (CLA) and high oleic safflower oil (HOSF) on children with LP (concomitant with surgery) were evaluated. Design A randomized, double-blinded, crossover and reference-oil controlled trial was conducted at a South African medical university. Study components included clinical, HPV type/load and lymphocyte/cytokine analyses, according to routine laboratory methods. Participants Overall: ten children enrolled; eight completed the trial; five remained randomized; seven received CLA first; all treatments remained double-blinded. Intervention Children (4 to 12 years) received 2.5 ml p/d CLA (8 weeks) and 2.5 ml p/d HOSF (8 weeks) with a washout period (6 weeks) in-between. The one-year trial included a post-treatment period (30 weeks) and afterwards was a one-year follow-up period. Main outcome measures Changes in numbers of surgical procedures for improved disease outcome, total/anatomical scores (staging system) for papillomatosis prevention/viral inhibition, and lymphocyte/cytokine counts for immune responses between baselines and each treatment/end of trial were measured. Findings After each treatment all the children were in remission (no surgical procedures); after the trial two had recurrence (surgical procedures in post-treatment period); after the follow-up period three had recurrence (several surgical procedures) and five recovered (four had no surgical procedures). Effects of CLA (and HOSF to a lesser extent) were restricted to mildly/moderately aggressive papillomatosis. Children with low total scores (seven/less) and reduced infections (three/less laryngeal sub-sites) recovered after the trial. No harmful effects were observed. The number of surgical procedures during the trial (n6/available records) was significantly lower [(p 0.03) (95% CI 1.1; 0)]. Changes in scores between baselines and CLA treatments (n8) were significantly lower: total scores [(p 0.02) (95% CI −30.00; 0.00)]; anatomical scores [(p 0.008) (95% CI −33.00: -2.00)]. Immune enhancement could not be demonstrated. Conclusions These preliminary case and group findings pave the way for further research on the therapeutic potential of adjuvant CLA in the treatment of HPV-induced LP. PMID:23061633

Handwashing with soap or alcoholic solutions? A randomized clinical trial of its effectiveness.

PubMed

Zaragoza, M; Sallés, M; Gomez, J; Bayas, J M; Trilla, A

1999-06-01

The effectiveness of an alcoholic solution compared with the standard hygienic handwashing procedure during regular work in clinical wards and intensive care units of a large public university hospital in Barcelona was assessed. A prospective, randomized clinical trial with crossover design, paired data, and blind evaluation was done. Eligible health care workers (HCWs) included permanent and temporary HCWs of wards and intensive care units. From each category, a random sample of persons was selected. HCWs were randomly assigned to regular handwashing (liquid soap and water) or handwashing with the alcoholic solution by using a crossover design. The number of colony-forming units on agar plates from hands printing in 3 different samples was counted. A total of 47 HCWs were included. The average reduction in the number of colony-forming units from samples before handwashing to samples after handwashing was 49.6% for soap and water and 88.2% for the alcoholic solution. When both methods were compared, the average number of colony-forming units recovered after the procedure showed a statistically significant difference in favor of the alcoholic solution (P <.001). The alcoholic solution was well tolerated by HCWs. Overall acceptance rate was classified as "good" by 72% of HCWs after 2 weeks use. Of all HCWs included, 9.3% stated that the use of the alcoholic solution worsened minor pre-existing skin conditions. Although the regular use of hygienic soap and water handwashing procedures is the gold standard, the use of alcoholic solutions is effective and safe and deserves more attention, especially in situations in which the handwashing compliance rate is hampered by architectural problems (lack of sinks) or nursing work overload.

Intravenous immunoglobulin treatment of the complex regional pain syndrome: a randomized trial.

PubMed

Goebel, Andreas; Baranowski, Andrew; Maurer, Konrad; Ghiai, Artemis; McCabe, Candy; Ambler, Gareth

2010-02-02

Treatment of long-standing complex regional pain syndrome (CRPS) is empirical and often of limited efficacy. Preliminary data suggest that the immune system is involved in sustaining this condition and that treatment with low-dose intravenous immunoglobulin (IVIG) may substantially reduce pain in some patients. To evaluate the efficacy of IVIG in patients with longstanding CRPS under randomized, controlled conditions. A randomized, double-blind, placebo-controlled crossover trial. (National Research Registry number: N0263177713; International Standard Randomised Controlled Trial Number Registry: 63918259) University College London Hospitals Pain Management Centre. Persons who had pain intensity greater than 4 on an 11-point (0 to 10) numerical rating scale and had CRPS for 6 to 30 months that was refractory to standard treatment. IVIG, 0.5 g/kg, and normal saline in separate treatments, divided by a washout period of at least 28 days. The primary outcome was pain intensity 6 to 19 days after the initial treatment and the crossover treatment. 13 eligible participants were randomly assigned between November 2005 and May 2008; 12 completed the trial. The average pain intensity was 1.55 units lower after IVIG treatment than after saline (95% CI, 1.29 to 1.82; P < 0.001). In 3 patients, pain intensity after IVIG was less than after saline by 50% or more. No serious adverse reactions were reported. The trial was small, and recruitment bias and chance variation could have influenced results and their interpretation. IVIG, 0.5 g/kg, can reduce pain in refractory CRPS. Studies are required to determine the best immunoglobulin dose, the duration of effect, and when repeated treatments are needed. Association of Anaesthetists of Great Britain and Ireland, University College London Hospitals Charity, and CSL-Behring.

A Randomized Dose-Ranging Study of Neuropeptide Y in Patients with Posttraumatic Stress Disorder.

PubMed

Sayed, Sehrish; Van Dam, Nicholas T; Horn, Sarah R; Kautz, Marin M; Parides, Michael; Costi, Sara; Collins, Katherine A; Iacoviello, Brian; Iosifescu, Dan V; Mathé, Aleksander A; Southwick, Steven M; Feder, Adriana; Charney, Dennis S; Murrough, James W

2018-01-01

Anxiety and trauma-related disorders are among the most prevalent and disabling medical conditions in the United States, and posttraumatic stress disorder in particular exacts a tremendous public health toll. We examined the tolerability and anxiolytic efficacy of neuropeptide Y administered via an intranasal route in patients with posttraumatic stress disorder. Twenty-six individuals were randomized in a cross-over, single ascending dose study into 1 of 5 cohorts: 1.4 mg (n=3), 2.8 mg (n=6), 4.6 mg (n=5), 6.8 mg (n=6), and 9.6 mg (n=6). Each individual was dosed with neuropeptide Y or placebo on separate treatment days 1 week apart in random order under double-blind conditions. Assessments were conducted at baseline and following a trauma script symptom provocation procedure subsequent to dosing. Occurrence of adverse events represented the primary tolerability outcome. The difference between treatment conditions on anxiety as measured by the Beck Anxiety Inventory and the State-Trait Anxiety Inventory immediately following the trauma script represented efficacy outcomes. Twenty-four individuals completed both treatment days. Neuropeptide Y was well tolerated up to and including the highest dose. There was a significant interaction between treatment and dose; higher doses of neuropeptide Y were associated with a greater treatment effect, favoring neuropeptide Y over placebo on Beck Anxiety Inventory score (F1,20=4.95, P=.038). There was no significant interaction for State-Trait Anxiety Inventory score. Our study suggests that a single dose of neuropeptide Y is well tolerated up to 9.6 mg and may be associated with anxiolytic effects. Future studies exploring the safety and efficacy of neuropeptide Y in stress-related disorders are warranted. The reported study is registered at: http://clinicaltrials.gov (ID: NCT01533519). © The Author(s) 2017. Published by Oxford University Press on behalf of CINP.

Reduced Sodium Transport With Nasal Administration of the Prostasin Inhibitor Camostat in Subjects With Cystic Fibrosis

PubMed Central

Reeves, Ginger; Hathorne, Heather; Solomon, G. Martin; Abbi, Smita; Renard, Didier; Lock, Ruth; Zhou, Ping; Danahay, Henry; Clancy, John P.; Waltz, David A.

2013-01-01

Background: Prostasin, a trypsin-like serine protease, is a channel-activating protease and major regulator of epithelial sodium channel-mediated sodium absorption. Its direct inhibition by camostat represents a potential approach to inhibiting sodium transport in cystic fibrosis (CF). Methods: To determine whether a topical formulation of camostat represents an efficacious and tolerable approach to reducing Na+ transport in the CF airway, we conducted a two-part randomized, double-blind, placebo-controlled, crossover, ascending single-dose study to evaluate the pharmacodynamics, safety, and pharmacokinetics of camostat administered through a nasal spray pump in subjects with CF. Nasal potential difference (PD) was measured before and after treatment, and safety and pharmacokinetics were assessed by a standardized approach. Results: In part 1, nine subjects were enrolled, and six completed crossover dosing at the maximally tolerated dose. The change in maximal (most polarizing) basal PD 2 h following administration of camostat was +13.1 mV (1.6-mg dose group) compared with −8.6 mV following placebo (P < .005). Intrasubject change in Ringer and amiloride-sensitive PDs exhibited similar and consistent responses. Bayesian analysis in an additional six subjects in part 2 estimated a dose of 18 μg/mL to provide 50% of the maximum effect. There was no significant change in chloride transport or total nasal symptom score, nasal examination rating, and laboratory parameters. Conclusions: This study establishes the proof of concept that a reduction in sodium transport in the human CF airway can be achieved through inhibition of prostasin activity, identifying a potential therapeutic target in the disease. Trial registration: ClinicalTrials.gov; No.: NCT00506792; URL: www.clinicaltrials.gov PMID:23412700

Transvertebral direct current stimulation paired with locomotor training in chronic spinal cord injury: A case study.

PubMed

Powell, Elizabeth Salmon; Carrico, Cheryl; Raithatha, Ravi; Salyers, Emily; Ward, Andrea; Sawaki, Lumy

2016-01-01

This double-blind, sham-controlled, crossover case study combined transvertebral direct current stimulation (tvDCS) and locomotor training on a robot-assisted gait orthosis (LT-RGO). Determine whether cathodal tvDCS paired with LT-RGO leads to greater changes in function and neuroplasticity than sham tvDCS paired with LT-RGO. University of Kentucky (UK) HealthCare Stroke and Spinal Cord Neurorehabilitation Research at HealthSouth Cardinal Hill Hospital. A single subject with motor incomplete spinal cord injury (SCI) participated in 24 sessions of sham tvDCS paired with LT-RGO before crossover to 24 sessions of cathodal tvDCS paired with LT-RGO. Functional outcomes were measured with 10 Meter Walk Test (10MWT), 6 Minute Walk Test (6MWT), Spinal Cord Independence Measure-III (SCIM-III) mobility component, lower extremity manual muscle test (MMT), and Berg Balance Scale (BBS). Corticospinal changes were assessed using transcranial magnetic stimulation. Improvement in 10MWT speed, SCIM-III mobility component, and BBS occurred with both conditions. 6MWT worsened after sham tvDCS and improved after cathodal tvDCS. MMT scores for both lower extremities improved following sham tvDCS but decreased following cathodal tvDCS. Corticospinal excitability increased following cathodal tvDCS but not sham tvDCS. These results suggest that combining cathodal tvDCS and LT-RGO may improve functional outcomes, increase corticospinal excitability, and possibly decrease spasticity. Randomized controlled trials are needed to confirm these conclusions. This publication was supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant UL1TR000117, and the HealthSouth Cardinal Hill Stroke and Spinal Cord Endowment (1215375670).

Actual driving performance and psychomotor function in healthy subjects after acute and subchronic treatment with escitalopram, mirtazapine, and placebo: a crossover trial.

PubMed

Wingen, Marleen; Bothmer, John; Langer, Stefan; Ramaekers, Johannes G

2005-04-01

The effects of escitalopram 10 to 20 mg/day and mirtazapine 30 to 45 mg/day on actual driving and psychomotor performance of 18 healthy subjects were determined in a randomized, double-blind, placebo-controlled, multiple-dose, 3-way crossover trial. Each treatment period lasted for 15 days and was separated from the next period by a washout period of at least 13 days. Subjects received an evening dose of escitalopram 10 mg, mirtazapine 30 mg, or placebo from days 1 to 7 and an evening dose of escitalopram 20 mg, mirtazapine 45 mg, or placebo from days 8 to 15. On days 2, 9, and 16, reflecting acute period, dose increase, and steady state, respectively, the Road Tracking Test was performed. The main parameter was standard deviation of lateral position. Psychomotor performance was also assessed on days 2, 9, and 16 by laboratory computer tasks. Subjective sleep quality was measured with the Groninger Sleep Quality Scale, and mood was measured by visual analogue scales. Treatment differences were apparent during the acute treatment period, in which subjects treated with mirtazapine 30 mg performed less well on the driving test as compared to placebo. The Divided Attention Task results also revealed a significant increase in tracking error after a single dose of mirtazapine 30 mg as compared to placebo. Mirtazapine decreased feelings of alertness and contentedness. Mirtazapine did not affect performance on days 9 and 16 of treatment. Escitalopram did not affect driving, psychomotor performance, or subjective mood throughout treatment. Driving performance, as well as psychomotor functioning, was not affected by escitalopram treatment in healthy subjects. Driving performance was significantly impaired after ingestion of mirtazapine 30 mg during the acute treatment period.

The Toronto outcome measure for craniofacial prosthetics: reliability and validity of a condition-specific quality-of-life instrument.

PubMed

Anderson, James D; Johnston, Dennis A; Haugh, Gil S; Kiat-Amnuay, Sudarat; Gettleman, Lawrence

2013-01-01

The purpose of this study was to refine the Toronto Outcome Measure for Craniofacial Prosthetics (TOMCP), present evidence for its reliability and validity, and use the instrument to explore differences in quality of life between prostheses made with chlorinated polyethylene (CPE) (experimental) and silicone (control). As part of a multicenter prospective controlled randomized double-blind single-crossover clinical trial of the two materials, the TOMCP was administered at the start and end of two 4-month study arms, during which 42 patients wore prostheses made from one material then the other. Reliability was assessed at the crossover. To determine validity of the TOMCP, the Linear Analogue Self-Assessment (LASA-12) and the Short-Form 8 (SF-8) were also administered with the TOMCP. The TOMCP was reduced by removing items that were unreliable, had poorly distributed answers, showed increased internal consistency after their removal, or were too highly correlated with more than one other item. The tests of reliability and validity were then repeated. Finally, the reduced instrument was used to test for differences in quality of life between prostheses made of the two materials. The item reduction tactics pared the 52-item instrument down to 27 items. The correlations of both TOMCP versions with the LASA-12 and the SF-8 were found to be statistically significant, providing evidence of the validity of the TOMCP. The instrument revealed significantly better quality of life with silicone rather than CPE prostheses. Both versions of the TOMCP were found to be reliable and valid. The instrument was able to show differences in quality of life between two materials.

Oligofructose promotes satiety in healthy human: a pilot study.

PubMed

Cani, P D; Joly, E; Horsmans, Y; Delzenne, N M

2006-05-01

The administration of a fermentable dietary fibre (oligofructose) in rats increases satietogenic gut peptides and lowered spontaneous energy intake. The aim of the study was to assess the relevance of those effects of oligofructose on satiety and energy intake in humans. Single-blinded, crossover, placebo-controlled design, pilot study. Volunteers included five men and five women aged 21-39 years, BMI ranging from 18.5 to 27.4 kg/m(2), were randomly assigned as described below. Subjects were included in two 2-week experimental phases during which they received either fibre (oligofructose (OFS)) or placebo (dextrine maltose (DM)); a 2-week washout period was included between crossover phases. In total, 8 g OFS or 8 g DM were ingested twice daily (16 g/day in total). Energy intake, hunger, satiety, fullness and prospective food consumption were assessed with analogue scales at the end of each experimental phase. During breakfast, OFS significantly increases the satiety (P=0.04) without any difference on other sensations as compared to DM treatment periods. After lunch, no significant differences are observed between treatment period. At dinner, OFS significantly increases satiety (P=0.04), reduces hunger (P=0.04) and prospective food consumption (P=0.05). The energy intake at breakfast and lunch are significantly lower (P=0.01, 0.03, respectively) after OFS treatment than after DM treatment. Total energy intake per day is 5% lower during OFS than in DM period. Oligofructose treatment increases satiety following breakfast and dinner, reduces hunger and prospective food consumption following dinner. This pilot study presents a rationale to propose oligofructose supplements in the management of food intake in overweight and obese patients.

Polarity-Dependent Misperception of Subjective Visual Vertical during and after Transcranial Direct Current Stimulation (tDCS)

PubMed Central

Santos-Pontelli, Taiza E. G.; Rimoli, Brunna P.; Favoretto, Diandra B.; Mazin, Suleimy C.; Truong, Dennis Q.; Leite, Joao P.; Pontes-Neto, Octavio M.; Babyar, Suzanne R.; Reding, Michael; Bikson, Marom; Edwards, Dylan J.

2016-01-01

Pathologic tilt of subjective visual vertical (SVV) frequently has adverse functional consequences for patients with stroke and vestibular disorders. Repetitive transcranial magnetic stimulation (rTMS) of the supramarginal gyrus can produce a transitory tilt on SVV in healthy subjects. However, the effect of transcranial direct current stimulation (tDCS) on SVV has never been systematically studied. We investigated whether bilateral tDCS over the temporal-parietal region could result in both online and offline SVV misperception in healthy subjects. In a randomized, sham-controlled, single-blind crossover pilot study, thirteen healthy subjects performed tests of SVV before, during and after the tDCS applied over the temporal-parietal region in three conditions used on different days: right anode/left cathode; right cathode/left anode; and sham. Subjects were blind to the tDCS conditions. Montage-specific current flow patterns were investigated using computational models. SVV was significantly displaced towards the anode during both active stimulation conditions when compared to sham condition. Immediately after both active conditions, there were rebound effects. Longer lasting after-effects towards the anode occurred only in the right cathode/left anode condition. Current flow models predicted the stimulation of temporal-parietal regions under the electrodes and deep clusters in the posterior limb of the internal capsule. The present findings indicate that tDCS over the temporal-parietal region can significantly alter human SVV perception. This tDCS approach may be a potential clinical tool for the treatment of SVV misperception in neurological patients. PMID:27031726

Vision restoration through extrastriate stimulation in patients with visual field defects: a double-blind and randomized experimental study.

PubMed

Jobke, Sandra; Kasten, Erich; Sabel, Bernhard A

2009-01-01

. Vision restoration therapy (VRT) to treat visual field defects used single-point visual stimulation in areas of residual vision up to now. The question arises if the efficiency of restoration can be increased when the entire region of blindness is trained by a visual stimulus aimed at activating extrastriate pathways (extrastriate VRT). . In this crossover study, 18 patients with visual field defects with prior VRT experience were treated with 2 training paradigms. Group 1 (n = 8) first used extrastriate VRT followed by conventional standard VRT. Group 2 (n = 10) trained in reverse order. Visual field size was assessed with computer-based perimetry and subjective vision with the National Eye Institute Visual Function Questionnaire (NEI-VFQ). . In group 1, stimulus detection in high-resolution perimetry (HRP) improved by 5.9% (P < .01) after extrastriate VRT. After the second training period (standard VRT), detection further improved by 1.8% (P = .093). In group 2, detection performance improved after standard VRT by 2.9% (P < .05) and after extrastriate VRT by 2.9% (P < .05). Detection performance increased twice as much after extrastriate VRT (4.2%) than after standard VRT (2.4%; P < .05). All changes in fixation performance were unrelated to detection improvements. NEI-VFQ did not show any significant changes. . Greater improvement after extrastriate VRT is interpreted as an activation of extrastriate pathways by massive "spiral-like" stimulation. These pathways bypass the damaged visual cortex, stimulating extrastriate cortical regions, and are thought to be involved in blindsight.

Do randomized clinical trials with inadequate blinding report enhanced placebo effects for intervention groups and nocebo effects for placebo groups? A protocol for a meta-epidemiological study of PDE-5 inhibitors

PubMed Central

2012-01-01

Background Patients’ expectations of treatment effects may contribute to positive (placebo) and negative (nocebo) outcomes. The effect of patient expectations may be pronounced in subjectively assessed conditions, such as male erectile dysfunction. The aim of this project is to examine the magnitude of expectancy in trials of phosphodiesterase-5 inhibitors. We hypothesize that randomized controlled trials with inadequate blinding will report enhanced placebo effects for intervention groups and nocebo effects for placebo groups, compared with adequately blinded studies. Methods/design We will quantify the magnitude of expectancy by comparing the effect estimates of trials with inadequate and adequate blinding. Blinding will be assessed using four domains from the Cochrane ‘risk-of-bias’ tool: allocation concealment; blinding of patient; caregiver; and outcome assessor. Our secondary aim is to identify factors that can modify expectations, such as prior experience with the intervention and drug side effects. We will perform an electronic search using a combination of controlled vocabulary and free text words in the following databases: MEDLINE, EMBASE, CENTRAL, and a clinical trials register. We will include randomized controlled trials, with either parallel or crossover design, that compare one phosphodiesterase-5 inhibitor with a placebo. The study’s primary aim should be to investigate the efficacy of phosphodiesterase-5 inhibitors for treating male erectile dysfunction. Screening will take place at two levels: abstracts and titles, followed by full text reports. Two reviewers will independently extract data on the primary outcome and assess risk of bias. We will meta-analyze treatment effects, if appropriate, to assess the magnitude of enhanced placebo effects and nocebo effects in intervention and placebo groups, respectively. We will explore possible mediators of placebo and nocebo effects with subgroup and meta-regression analyses. Discussion Treatments may confer significant costs and risk of adverse effects; it is important, therefore, to determine whether the effects of treatments are larger than expectancy alone. If treatment expectations can be used in a non-deceptive way to produce clinically advantageous outcomes, then it may be possible to incorporate such mechanisms into evidence-based healthcare decision-making. PMID:23151403

Effect of long-term intranasal oxytocin on sexual dysfunction in premenopausal and postmenopausal women: a randomized trial.

PubMed

Muin, Dana A; Wolzt, Michael; Marculescu, Rodrig; Sheikh Rezaei, Safoura; Salama, Mohamed; Fuchs, Carola; Luger, Anton; Bragagna, Elia; Litschauer, Brigitte; Bayerle-Eder, Michaela

2015-09-01

To assess the effect of on-demand intranasal oxytocin administration on female sexual function and activity. Randomized, prospective, double-blind, placebo-controlled, crossover trial with duration of 22 weeks. Academic medical center. Thirty pre-and postmenopausal women with sexual dysfunction. Over 8 weeks, intranasal oxytocin (32 IU) or placebo self-administered by women within 50 minutes before sexual intercourse; after a washout period of 2 weeks, crossover with patients switched to the alternate group for another 8 weeks. Primary outcome parameter: Female Sexual Function Index (FSFI); secondary outcome parameters: Female Sexual Distress Scale (FSDS), Sexual Quality of Life-Female (SQOL-F), Sexual Interest and Desire Inventory-Female (SIDI-F), and Hamilton depression scale (HDS). After oxytocin and placebo, the FSFI score increased by 26% and 31%, SQOL-F score by 144% and 125%, and SIDI-F score by 29% and 23%, respectively (repeated measures analysis of variance between groups). After oxytocin and placebo, the FSDS score decreased by 36% and 45%, respectively (repeated measures analysis of variance between groups). There was no statistically significant treatment, sequence (placebo first/second), or interaction effect. Long-term intranasal oxytocin and placebo administration both improved sexual function and symptoms of depression in women over time with no treatment, sequence (placebo first/second), or interaction effect. NCT02229721. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

The effects of alprazolam on tinnitus: a cross-over randomized clinical trial.

PubMed

Jalali, Mir Mohammad; Kousha, Abdorrahim; Naghavi, Sayed Ebrahim; Soleimani, Robabeh; Banan, Rozbeh

2009-11-01

Tinnitus remains a phenomenon with an unknown pathophysiology and for which few therapeutic measures are available. To date there has been insufficient evidence to support the use of alprazolam in the treatment of tinnitus. We sought to evaluate the efficacy of alprazolam for relief of tinnitus. Thirty-six tinnitus sufferers participated in this cross-over, randomized, triple-blind, placebo-controlled trial. Inclusion criteria included patients between ages 21 and 65, with a complaint of non-pulsatile tinnitus of more than 1 year duration. Patients with depressive or anxiety disorders were excluded, as were those using hearing aids. Participants received alprazolam 1.5 mg daily versus placebo in each period. Primary outcome variables included the Tinnitus Handicap Inventory (THI), a Visual Analog Scale (VAS), and tinnitus loudness. Thirty patients completed the study. The average age of patients was 47.58+/-7.65 years. Alprazolam in comparison with placebo did not result in statistically significantly greater relief in THI score and tinnitus loudness. There was a significant improvement in VAS score in the alprazolam group compared with the placebo group (p<0.001). These results suggest that although alprazolam did not improve the THI score or sensation level of loudness significantly, it has a desirable effect on VAS. Further work is needed to determine the beneficial effects of alprazolam in distressed or depressed patients.

Using acupressure and Montessori-based activities to decrease agitation for residents with dementia: a cross-over trial.

PubMed

Lin, Li-Chan; Yang, Man-Hua; Kao, Chieh-Chun; Wu, Shiao-Chi; Tang, Sai-Hung; Lin, Jaung-Geng

2009-06-01

To explore the effectiveness of acupressure and Montessori-based activities in decreasing the agitated behaviors of residents with dementia. A double-blinded, randomized (two treatments and one control; three time periods) cross-over design was used. Six special care units for residents with dementia in long-term care facilities in Taiwan were the sites for the study. One hundred thirty-three institutionalized residents with dementia. Subjects were randomized into three treatment sequences: acupressure-presence-Montessori methods, Montessori methods-acupressure-presence and presence-Montessori methods-acupressure. All treatments were done once a day, 6 days per week, for a 4-week period. The Cohen-Mansfield Agitation Inventory, Ease-of-Care, and the Apparent Affect Rating Scale. After receiving the intervention, the acupressure and Montessori-based-activities groups saw a significant decrease in agitated behaviors, aggressive behaviors, and physically nonaggressive behaviors than the presence group. Additionally, the ease-of-care ratings for the acupressure and Montessori-based-activities groups were significantly better than for the presence group. In terms of apparent affect, positive affect in the Montessori-based-activities group was significantly better than in the presence group. This study confirms that a blending of traditional Chinese medicine and a Western activities program would be useful in elderly care and that in-service training for formal caregivers in the use of these interventions would be beneficial for patients

Soluble corn fiber increases bone calcium retention in postmenopausal women in a dose-dependent manner: a randomized crossover trial.

PubMed

Jakeman, Steven A; Henry, Courtney N; Martin, Berdine R; McCabe, George P; McCabe, Linda D; Jackson, George S; Peacock, Munro; Weaver, Connie M

2016-09-01

Dietary soluble corn fiber (SCF) significantly improves calcium absorption in adolescents and the bone strength and architecture in rodent models. In this study, we aimed to determine the skeletal benefits of SCF in postmenopausal women. We used our novel technology of determining bone calcium retention by following the urinary appearance of (41)Ca, a rare long-lived radioisotope, from prelabeled bone to rapidly and sensitively evaluate the effectiveness of SCF in reducing bone loss. A randomized-order, crossover, double-blinded trial was performed in 14 healthy postmenopausal women to compare doses of 0, 10, and 20 g fiber from SCF/d for 50 d. A dose-response effect was shown with 10 and 20 g fiber from SCF/d, whereby bone calcium retention was improved by 4.8% (P < 0.05) and 7% (P < 0.04), respectively. The bone turnover biomarkers N-terminal telopeptide and osteocalcin were not changed by the interventions; however, a significant increase in bone-specific alkaline phosphatase, which is a bone-formation marker, was detected between 0 and 20 g fiber from SCF/d (8%; P = 0.035). Daily SCF consumption significantly increased bone calcium retention in postmenopausal women, which improved the bone calcium balance by an estimated 50 mg/d. This study was registered at clinicaltrials.gov as NCT02416947. © 2016 American Society for Nutrition.

Effect of amiloride on experimental acid-induced heartburn in non-erosive reflux disease.

PubMed

Bulsiewicz, William J; Shaheen, Nicholas J; Hansen, Mark B; Pruitt, Amy; Orlando, Roy C

2013-07-01

Acid-sensing ion channels (ASICs) are esophageal nociceptors that are candidates to mediate heartburn in non-erosive reflux disease (NERD). Amiloride, a diuretic, is known to inhibit ASICs. For this reason, we sought a role for ASICs in mediating heartburn by determining whether amiloride could block heartburn in NERD induced by esophageal acid perfusion. In a randomized double-blind crossover study, we perfused the esophagus with amiloride or (saline) placebo prior to eliciting acid-induced heartburn in patients with a history of proton pump inhibitor-responsive NERD. Those with NERD and positive modified Bernstein test were randomized to perfusion with amiloride, 1 mmol/l, or placebo for 5 min, followed by repeat acid-perfusion. Heartburn severity and time to onset was measured and the process repeated following crossover to the alternative agent. 14 subjects completed the study. Amiloride did not reduce the frequency (100 vs. 100 %) or severity of acid-induced heartburn (Mean 2.50 ± SEM 0.33 vs. 2.64 ± 0.45), respectively. There was a trend towards longer time to onset of heartburn for amiloride versus placebo (Mean 2.93 ± SEM 0.3 vs. 2.36 ± 0.29 min, respectively), though these differences did not reach statistical significance (p > 0.05). Amiloride had no significant effect on acid-induced heartburn frequency or severity in NERD, although there was a trend towards prolonged time to onset of symptoms.

Randomized Controlled Trial of Strain-Specific Probiotic Formulation (Renadyl) in Dialysis Patients

PubMed Central

Natarajan, Ranganathan; Mallappallil, Mary C.; Norin, Allen J.; Friedman, Eli A.; Saggi, Subodh J.

2014-01-01

Background. Primary goal of this randomized, double-blind, placebo-controlled crossover study of Renadyl in end-stage renal disease patients was to assess the safety and efficacy of Renadyl measured through improvement in quality of life or reduction in levels of known uremic toxins. Secondary goal was to investigate the effects on several biomarkers of inflammation and oxidative stress. Methods. Two 2-month treatment periods separated by 2-month washout and crossover, with physical examinations, venous blood testing, and quality of life questionnaires completed at each visit. Data were analyzed with SAS V9.2. Results. 22 subjects (79%) completed the study. Observed trends were as follows (none reaching statistical significance): decline in WBC count (−0.51 × 109/L, P = 0.057) and reductions in levels of C-reactive protein (−8.61 mg/L, P = 0.071) and total indoxyl glucuronide (−0.11 mg%, P = 0.058). No statistically significant changes were observed in other uremic toxin levels or measures of QOL. Conclusions. Renadyl appeared to be safe to administer to ESRD patients on hemodialysis. Stability in QOL assessment is an encouraging result for a patient cohort in such advanced stage of kidney disease. Efficacy could not be confirmed definitively, primarily due to small sample size and low statistical power—further studies are warranted. PMID:25147806

Language-specific strategy for programming hearing aids - A double-blind randomized controlled crossover study.

PubMed

Matsumoto, Nozomu; Suzuki, Nobuyoshi; Iwasaki, Satoshi; Ishikawa, Kazuha; Tsukiji, Hiroki; Higashino, Yoshie; Tabuki, Tomoko; Nakagawa, Takashi

2018-08-01

Voice-aligned compression (VAC) is a method used in Oticon's hearing aids to provide more comfortable hearing without sacrificing speech discrimination. The complex, non-linear compression curve for the VAC strategy is designed based on the frequency profile of certain spoken Western languages. We hypothesized that hearing aids could be further customized for Japanese-speaking users by modifying the compression curve using the frequency profile of spoken Japanese. A double-blind randomized controlled crossover study was performed to determine whether or not Oticon's modified amplification strategy (VAC-J) provides subjectively preferable hearing aids for Japanese-speaking hearing aid users compared to the same company's original amplification strategy (VAC). The participants were randomized to two groups. The VAC-first group received a pair of hearing aids programmed using the VAC strategy and wore them for three weeks, and then received a pair of hearing aids programmed using VAC-J strategy and wore them for three weeks. The VAC-J-first group underwent the same study, but they received hearing aids in the reverse sequence. A Speech, Spatial and Qualities (SSQ) questionnaire was administered before beginning to use the hearing aids, at the end of using the first pair of hearing aids, and at the end of using the second pair of hearing aids. Twenty-five participants that met the inclusion/exclusion criteria from January 1 to October 31, 2016, were randomized to two groups. Twenty-two participants completed the study. There were no statistically significant differences in the increment of SSQ scores between the participants when using the VAC- or the VAC-J-programmed hearing aids. However, participants preferred the VAC-J strategy to the VAC strategy at the end of the study, and this difference was statistically significant. Japanese-speaking hearing aid users preferred using hearing aids that were fitted with the VAC-J strategy. Our results show that the VAC strategy can be adjusted to the frequency profile of different languages and that participants expressed their subjective preference more clearly than was reflected in the SSQ scores. A similar language-specific strategy may improve user's satisfaction while using hearing devices, and this concept may be extended to implantable hearing devices. R000023191. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparison of the efficacy and safety of 2% lidocaine HCl with different epinephrine concentration for local anesthesia in participants undergoing surgical extraction of impacted mandibular third molars: A multicenter, randomized, double-blind, crossover, phase IV trial.

PubMed

Karm, Myong-Hwan; Park, Fiona Daye; Kang, Moonkyu; Kim, Hyun Jeong; Kang, Jeong Wan; Kim, Seungoh; Kim, Yong-Deok; Kim, Cheul-Hong; Seo, Kwang-Suk; Kwon, Kyung-Hwan; Kim, Chul-Hwan; Lee, Jung-Woo; Hong, Sung-Woon; Lim, Mi Hyoung; Nam, Seung Kwan; Cho, Jae Min

2017-05-01

The most commonly impacted tooth is the third molar. An impacted third molar can ultimately cause acute pain, infection, tumors, cysts, caries, periodontal disease, and loss of adjacent teeth. Local anesthesia is employed for removing the third molar. This study aimed to evaluate the efficacy and safety of 2% lidocaine with 1:80,000 or 1:200,000 epinephrine for surgical extraction of bilateral impacted mandibular third molars. Sixty-five healthy participants underwent surgical extraction of bilateral impacted mandibular third molars in 2 separate visits while under local anesthesia with 2% lidocaine with different epinephrine concentration (1:80,000 or 1:200,000) in a double-blind, randomized, crossover trial. Visual analog scale pain scores obtained immediately after surgical extraction were primarily evaluated for the 2 groups receiving different epinephrine concentrations. Visual analog scale pain scores were obtained 2, 4, and 6 hours after administering an anesthetic. Onset and duration of analgesia, onset of pain, intraoperative bleeding, operator's and participant's overall satisfaction, drug dosage, and hemodynamic parameters were evaluated for the 2 groups. There were no statistically significant differences between the 2 groups in any measurements except hemodynamic factors (P >.05). Changes in systolic blood pressure and heart rate following anesthetic administration were significantly greater in the group receiving 1:80,000 epinephrine than in that receiving 1:200,000 epinephrine (P ≤.01). The difference in epinephrine concentration between 1:80,000 and 1:200,000 in 2% lidocaine liquid does not affect the medical efficacy of the anesthetic. Furthermore, 2% lidocaine with 1:200,000 epinephrine has better safety with regard to hemodynamic parameters than 2% lidocaine with 1:80,000 epinephrine. Therefore, we suggest using 2% lidocaine with 1:200,000 epinephrine rather than 2% lidocaine with 1:80,000 epinephrine for surgical extraction of impacted mandibular third molars in hemodynamically unstable patients.

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.

Articaine and mepivacaine buccal infiltration in securing mandibular first molar pulp anesthesia following mepivacaine inferior alveolar nerve block: A randomized, double-blind crossover study

PubMed Central

Gazal, Giath; Alharbi, Abdullah Muteb; Al-Samadani, Khalid HidayatAllah; Kanaa, Mohammad Dib

2015-01-01

Aims: A crossover double-blind, randomized study was designed to explore the efficacy of 2% mepivacaine with 1:100,000 adrenaline buccal infiltration and 4% articaine with 1:100,000 adrenaline buccal infiltration following 2% mepivacaine with 1:100,000 adrenaline inferior alveolar nerve block (IANB) for testing pulp anesthesia of mandibular first molar teeth in adult volunteers. Materials and Methods: A total of 23 healthy adult volunteers received two regimens with at least 1-week apart; one with 4% articaine buccal infiltration and 2% mepivacaine IANB (articaine regimen) and another with 2% mepivacaine buccal infiltration supplemented to 2% mepivacaine IANB (mepivacaine regimen). Pulp testing of first molar tooth was electronically measured twice at baseline, then at intervals of 2 min for the first 10 min, then every 5 min until 45 min postinjection. Anesthetic success was considered when two consecutive maximal stimulation on pulp testing readings without sensation were obtained within 10 min and continuously sustained for 45 min postinjection. Results: In total, the number of no sensations to maximum pulp testing for first molar teeth were significantly higher after articaine regimen than mepivacaine during 45 min postinjection (267 vs. 250 episodes, respectively, P < 0.001), however, both articaine and mepivacaine buccal infiltrations are equally effective in securing anesthetic success for first molar pulp anesthesia when supplemented to mepivacaine IANB injections (P > 0.05). Interestingly, volunteers in the articaine regimen provided faster onset and longer duration (means 2.78 min, 42.22 min, respectively) than mepivacaine regimen (means 4.26 min, 40.74 min, respectively) for first molar pulp anesthesia (P < 0.001). Conclusions: Supplementary mepivacaine and articaine buccal infiltrations produced similar successful first molar pulp anesthesia following mepivacaine IANB injections in volunteers. Articaine buccal infiltration produced faster onset and longer duration than mepivacaine buccal infiltration following mepivacaine IANB injections. PMID:26543456

Effects of ultrafine particles on the allergic inflammation in the lung of asthmatics: results of a double-blinded randomized cross-over clinical pilot study

PubMed Central

2014-01-01

Background Epidemiological and experimental studies suggest that exposure to ultrafine particles (UFP) might aggravate the allergic inflammation of the lung in asthmatics. Methods We exposed 12 allergic asthmatics in two subgroups in a double-blinded randomized cross-over design, first to freshly generated ultrafine carbon particles (64 μg/m3; 6.1 ± 0.4 × 105 particles/cm3 for 2 h) and then to filtered air or vice versa with a 28-day recovery period in-between. Eighteen hours after each exposure, grass pollen was instilled into a lung lobe via bronchoscopy. Another 24 hours later, inflammatory cells were collected by means of bronchoalveolar lavage (BAL). (Trial registration: NCT00527462) Results For the entire study group, inhalation of UFP by itself had no significant effect on the allergen induced inflammatory response measured with total cell count as compared to exposure with filtered air (p = 0.188). However, the subgroup of subjects, which inhaled UFP during the first exposure, exhibited a significant increase in total BAL cells (p = 0.021), eosinophils (p = 0.031) and monocytes (p = 0.013) after filtered air exposure and subsequent allergen challenge 28 days later. Additionally, the potential of BAL cells to generate oxidant radicals was significantly elevated at that time point. The subgroup that was exposed first to filtered air and 28 days later to UFP did not reveal differences between sessions. Conclusions Our data demonstrate that pre-allergen exposure to UFP had no acute effect on the allergic inflammation. However, the subgroup analysis lead to the speculation that inhaled UFP particles might have a long-term effect on the inflammatory course in asthmatic patients. This should be reconfirmed in further studies with an appropriate study design and sufficient number of subjects. PMID:25204642

Articaine and mepivacaine buccal infiltration in securing mandibular first molar pulp anesthesia following mepivacaine inferior alveolar nerve block: A randomized, double-blind crossover study.

PubMed

Gazal, Giath; Alharbi, Abdullah Muteb; Al-Samadani, Khalid HidayatAllah; Kanaa, Mohammad Dib

2015-01-01

A crossover double-blind, randomized study was designed to explore the efficacy of 2% mepivacaine with 1:100,000 adrenaline buccal infiltration and 4% articaine with 1:100,000 adrenaline buccal infiltration following 2% mepivacaine with 1:100,000 adrenaline inferior alveolar nerve block (IANB) for testing pulp anesthesia of mandibular first molar teeth in adult volunteers. A total of 23 healthy adult volunteers received two regimens with at least 1-week apart; one with 4% articaine buccal infiltration and 2% mepivacaine IANB (articaine regimen) and another with 2% mepivacaine buccal infiltration supplemented to 2% mepivacaine IANB (mepivacaine regimen). Pulp testing of first molar tooth was electronically measured twice at baseline, then at intervals of 2 min for the first 10 min, then every 5 min until 45 min postinjection. Anesthetic success was considered when two consecutive maximal stimulation on pulp testing readings without sensation were obtained within 10 min and continuously sustained for 45 min postinjection. In total, the number of no sensations to maximum pulp testing for first molar teeth were significantly higher after articaine regimen than mepivacaine during 45 min postinjection (267 vs. 250 episodes, respectively, P < 0.001), however, both articaine and mepivacaine buccal infiltrations are equally effective in securing anesthetic success for first molar pulp anesthesia when supplemented to mepivacaine IANB injections (P > 0.05). Interestingly, volunteers in the articaine regimen provided faster onset and longer duration (means 2.78 min, 42.22 min, respectively) than mepivacaine regimen (means 4.26 min, 40.74 min, respectively) for first molar pulp anesthesia (P < 0.001). Supplementary mepivacaine and articaine buccal infiltrations produced similar successful first molar pulp anesthesia following mepivacaine IANB injections in volunteers. Articaine buccal infiltration produced faster onset and longer duration than mepivacaine buccal infiltration following mepivacaine IANB injections.

Metabolic effects of liothyronine therapy in hypothyroidism: a randomized, double-blind, crossover trial of liothyronine versus levothyroxine.

PubMed

Celi, Francesco S; Zemskova, Marina; Linderman, Joyce D; Smith, Sheila; Drinkard, Bart; Sachdev, Vandana; Skarulis, Monica C; Kozlosky, Merel; Csako, Gyorgy; Costello, Rene; Pucino, Frank

2011-11-01

Levothyroxine (L-T(4)) therapy is based on the assumption that the conversion of T(4) into T(3) provides adequate amounts of active hormone at target tissues. However, in rodents, L-T(4) alone does not restore a euthyroid state in all tissues. Previous combination L-T(4)/liothyronine (L-T(3)) therapy trials focused on quality-of-life endpoints, and limited information is available on the effects on other measures of thyroid hormone action. Our objective was to evaluate the efficacy of thyroid hormone replacement with L-T(4) or L-T(3) at doses producing equivalent normalization of TSH. Fourteen hypothyroid patients participated in this randomized, double-blind, crossover intervention at the National Institutes of Health Clinical Center. L-T(3) or L-T(4) were administered thrice daily to achieve a target TSH from 0.5-1.5 mU/liter. Volunteers were studied as inpatients after 6 wk on a stable dose and at the target TSH. Serum thyroid hormones, lipid parameters, and indices of glucose metabolism were evaluated. No difference was observed in TSH between L-T(3) and L-T(4) treatments. L-T(3) resulted in significant weight loss [L-T(4), 70.6 ± 12.5, vs. L-T(3), 68.5 ± 11.9 kg (P = 0.009)] and in a 10.9 ± 10.0% decrease in total cholesterol (P = 0.002), 13.3 ± 12.1% decrease in low-density lipoprotein-cholesterol (P = 0.002), and an 18.3 ± 28.6% decrease in apolipoprotein B (P = 0.018). No significant differences were observed in high-density lipoprotein-cholesterol, heart rate, blood pressure, exercise tolerance, or insulin sensitivity. The substitution of L-T(3) for L-T(4) at equivalent doses (relative to the pituitary) reduced body weight and resulted in greater thyroid hormone action on the lipid metabolism, without detected differences in cardiovascular function or insulin sensitivity.

A randomized, controlled, double-blind crossover study on the effects of 1-L infusions of 6% hydroxyethyl starch suspended in 0.9% saline (voluven) and a balanced solution (Plasma Volume Redibag) on blood volume, renal blood flow velocity, and renal cortical tissue perfusion in healthy volunteers.

PubMed

Chowdhury, Abeed H; Cox, Eleanor F; Francis, Susan T; Lobo, Dileep N

2014-05-01

We compared the effects of intravenous administration of 6% hydroxyethyl starch (maize-derived) in 0.9% saline (Voluven; Fresenius Kabi, Runcorn, United Kingdom) and a "balanced" preparation of 6% hydroxyethyl starch (potato-derived) [Plasma Volume Redibag (PVR); Baxter Healthcare, Thetford, United Kingdom] on renal blood flow velocity and renal cortical tissue perfusion in humans using magnetic resonance imaging. Hyperchloremia resulting from 0.9% saline infusion may adversely affect renal hemodynamics when compared with balanced crystalloids. This phenomenon has not been studied with colloids. Twelve healthy adult male subjects received 1-L intravenous infusions of Voluven or PVR over 30 minutes in a randomized, double-blind manner, with crossover studies 7 to 10 days later. Magnetic resonance imaging proceeded for 60 minutes after commencement of infusion to measure renal artery blood flow velocity and renal cortical perfusion. Blood was sampled, and weight was recorded at 0, 30, 60, 120, 180, and 240 minutes. Mean peak serum chloride concentrations were 108 and 106 mmol/L, respectively, after Voluven and PVR infusion (P = 0.032). Changes in blood volume (P = 0.867), strong ion difference (P = 0.219), and mean renal artery flow velocity (P = 0.319) were similar. However, there was a significant increase in mean renal cortical tissue perfusion after PVR when compared with Voluven (P = 0.033). There was no difference in urinary neutrophil gelatinase-associated liopcalin to creatinine ratios after the infusion (P = 0.164). There was no difference in the blood volume-expanding properties of the 2 preparations of 6% hydroxyethyl starch. The balanced starch produced an increase in renal cortical tissue perfusion, a phenomenon not seen with starch in 0.9% saline.

Effects of a hops (Humulus lupulus L.) dry extract supplement on self-reported depression, anxiety and stress levels in apparently healthy young adults: a randomized, placebo-controlled, double-blind, crossover pilot study.

PubMed

Kyrou, Ioannis; Christou, Aimilia; Panagiotakos, Demosthenes; Stefanaki, Charikleia; Skenderi, Katerina; Katsana, Konstantina; Tsigos, Constantine

2017-04-01

The Humulus lupulus L. plant (hops) is used as a herbal medicinal product for anxiety/mood disorders. Our aim was to study the effects of a hops dry extract on self-reported depression, anxiety and stress levels in young adults. Apparently healthy young adults from our university completed the Depression Anxiety Stress Scale-21 (DASS-21) and those reporting at least mild depression, anxiety and stress were invited to complete the study intervention. This followed a randomized (1:1), placebo-controlled, double-blind, crossover design with two 4-week intervention periods (Melcalin hops or placebo; two 0.2 gr capsules once daily) separated by a 2-week wash-out. Anthropometric measurements, DASS-21 assessments and measurements of morning cortisol plasma levels were performed at the beginning and the end of the 4-week treatment periods. 36 participants (Females/Males: 31/5; age: 24.7±0.5 years) completed the study intervention (attrition: 6/42). No significant changes in body weight and composition or morning circulating cortisol were noted with the hops or placebo. Significantly decreased DASS-21 anxiety, depression and stress scores were documented with hops (9.2±7.3 vs. 5.1±5.9, 11.9±7.9 vs. 9.2±7.4, and 19.1±8.1 vs. 11.6±8.1; all p values <0.05), which were significantly greater compared to those caused by the placebo (all p values <0.05). In otherwise healthy young adults reporting at least mild depression, anxietyand stress symptoms, daily supplementation with a hops dry extract can significantly improve all these symptoms over a 4-week period. These beneficial effects agree with the indication of hops for anxiety/mood disorders and restlessness, as approved by the German Commission E.

Interaction of clopidogrel and statins in secondary prevention after cerebral ischaemia – a randomized, double-blind, double-dummy crossover study

PubMed Central

Siepmann, Timo; Heinke, Denise; Kepplinger, Jessica; Barlinn, Kristian; Gehrisch, Siegmund; Grählert, Xina; Schwanebeck, Uta; Reichmann, Heinz; Puetz, Volker; Bodechtel, Ulf; Gahn, Georg

2014-01-01

Aims Variability in responsiveness to clopidogrel is a clinical problem in secondary prevention after cerebral ischaemia which has been suggested to be linked to competitive metabolization of clopidogrel and cytochrome P450 (CYP) 3A4-oxidated statins such as simvastatin. We assessed the hypothesis that simvastatin, in contrast to CYP 2C9-metabolized fluvastatin, reduces clopidogrel-mediated platelet inhibition. Methods We performed a randomized, double-blind, double-dummy, two period crossover study in 13 patients with cerebral ischaemia (8F, 5 M), aged 64.1 ± 8.0 years (mean ± SD). After a 14 day period in which all patients received 75 mg clopidogrel day−1, patients additionally received either 20 mg simvastatin day−1 or 80 mg fluvastatin day−1 for 14 days. Regimens were crossed over after a 14 day wash-out period and switched regimens were continued for another 14 days. Platelet aggregation, clopidogrel active metabolite (CAM) plasma concentrations and routine laboratory parameters including prothrombin time (PT) Quick percent value were assessed at baseline and following each treatment phase. Results Clopidogrel reduced platelet aggregation in all patients as expected. Platelet aggregation and CAM plasma concentrations were unaltered when simvastatin or fluvastatin was added to clopidogrel. Simvastatin decreased PT Quick percent value (decrease from 109 ± 10.5% to 103 ± 11%, P < 0.05) when combined with clopidogrel but there was no such change following treatment with fluvastatin and clopidogrel. Conclusions Our data indicate that treatment with CYP 3A4-metabolized simvastatin does not jeopardize clopidogrel-mediated inhibition of platelet aggregation. After co-administration of simvastatin and clopidogrel we observed a decrease in the PT Quick percent value which could be due to simvastatin-induced reduction of activity of prothrombin fragment 1 + 2. PMID:24803100

Efficacy, safety and tolerability of an orally administered cannabis extract in the treatment of spasticity in patients with multiple sclerosis: a randomized, double-blind, placebo-controlled, crossover study.

PubMed

Vaney, C; Heinzel-Gutenbrunner, M; Jobin, P; Tschopp, F; Gattlen, B; Hagen, U; Schnelle, M; Reif, M

2004-08-01

Cannabis may alleviate some symptoms associated with multiple sclerosis (MS). This study investigated the effect of an orally administered standardized Cannabis sativa plant extract in MS patients with poorly controlled spasticity. During their inpatient rehabilitation programme, 57 patients were enrolled in a prospective, randomized, double-blind, placebo-controlled crossover study of cannabis-extract capsules standardized to 2.5 mg tetrahydrocannabinol (THC) and 0.9 mg cannabidiol (CBD) each. Patients in group A started with a drug escalation phase from 15 to maximally 30 mg THC by 5 mg per day if well tolerated, being on active medication for 14 days before starting placebo. Patients in group B started with placebo for seven days, crossed to the active period (14 days) and closed with a three-day placebo period (active drug dose escalation and placebo sham escalation as in group A). Measures used included daily self-report of spasm frequency and symptoms, Ashworth Scale, Rivermead Mobility Index, 10-m timed walk, nine-hole peg test, paced auditory serial addition test (PASAT), and the digit span test. In the 50 patients included into the intention-to-treat analysis set, there were no statistically significant differences associated with active treatment compared to placebo, but trends in favour of active treatment were seen for spasm frequency, mobility and getting to sleep. In the 37 patients (per-protocol set) who received at least 90% of their prescribed dose, improvements in spasm frequency (P = 0.013) and mobility after excluding a patient who fell and stopped walking were seen (P = 0.01). Minor adverse events were slightly more frequent and severe during active treatment, and toxicity symptoms, which were generally mild, were more pronounced in the active phase. A standardized Cannabis sativa plant extract might lower spasm frequency and increase mobility with tolerable side effects in MS patients with persistent spasticity not responding to other drugs.

Comparison of speed of action and injection discomfort of 4% articaine and 2% mepivacaine for pulpal anesthesia in mandibular teeth: A randomized, double-blind cross-over trial

PubMed Central

Gazal, Giath

2015-01-01

Objective: To compare the injection pain and speed of local anesthetic effect induced by tissue infiltration of mepivacaine 2% with epinephrine 1:100,000 versus articaine 4% with epinephrine 1:100,000 in securing mandibular first molar pulp anesthesia. Materials and Methods: Totally, 25 patients were recruited in a crossover, randomized, double-blind study. Each subject received injections of mepivacaine 2% with epinephrine 1:100,000 as inferior alveolar nerve block (IANB) supplemented with either articaine 4% with epinephrine 1:100,000 (septocaine) or mepivacaine 2% buccal infiltration (BI) injection on two visits. The time of first numbness to associated lip, tongue and tooth was recorded by asking the participant directly and using electrical pulp tester. Anesthetic success was considered when two consecutive maximal stimulation on pulp testing readings without sensation. The patients rated the pain of infiltration using a 100 mm visual analog scale immediately after receiving each injection. The pain scores were compared using the paired t-test. Results: There were significant differences in the meantime of first numbness to associated lip and tooth of volunteers between mepivacaine and articaine BI groups P = 0.03 and 0.002. Volunteers in articaine group recorded earlier lip and teeth numbness than those in mepivacaine group. There were significant differences between the mean pain scores for volunteers in the post IANB and postbuccal injection groups (t-test: P <0.001). Mepivacaine IANB injection was significantly more painful than articaine/mepivacaine buccal injection. Conclusions: About 4% articaine was faster than 2% mepivacaine (both with 1:100,000 adrenaline) in anesthetizing the pulps of lower molar teeth after BIs. Earlier lip and teeth numbness were recorded in articaine group. Articaine and mepivacaine BIs were more comfortable than mepivacaine IANB injections. PMID:26038650

Effects of Pycnogenol on endothelial function in patients with stable coronary artery disease: a double-blind, randomized, placebo-controlled, cross-over study.

PubMed

Enseleit, Frank; Sudano, Isabella; Périat, Daniel; Winnik, Stephan; Wolfrum, Mathias; Flammer, Andreas J; Fröhlich, Georg M; Kaiser, Priska; Hirt, Astrid; Haile, Sarah R; Krasniqi, Nazmi; Matter, Christian M; Uhlenhut, Klaus; Högger, Petra; Neidhart, Michel; Lüscher, Thomas F; Ruschitzka, Frank; Noll, Georg

2012-07-01

Extracts from pine tree bark containing a variety of flavonoids have been used in traditional medicine. Pycnogenol is a proprietary bark extract of the French maritime pine tree (Pinus pinaster ssp. atlantica) that exerts antioxidative, anti-inflammatory, and anti-platelet effects. However, the effects of Pycnogenol on endothelial dysfunction, a precursor of atherosclerosis and cardiovascular events, remain still elusive. Twenty-three patients with coronary artery disease (CAD) completed this randomized, double-blind, placebo-controlled cross-over study. Patients received Pycnogenol (200 mg/day) for 8 weeks followed by placebo or vice versa on top of standard cardiovascular therapy. Between the two treatment periods, a 2-week washout period was scheduled. At baseline and after each treatment period, endothelial function, non-invasively assessed by flow-mediated dilatation (FMD) of the brachial artery using high-resolution ultrasound, biomarkers of oxidative stress and inflammation, platelet adhesion, and 24 h blood pressure monitoring were evaluated. In CAD patients, Pycnogenol treatment was associated with an improvement of FMD from 5.3 ± 2.6 to 7.0 ± 3.1 (P < 0.0001), while no change was observed with placebo (5.4 ± 2.4 to 4.7 ± 2.0; P = 0.051). This difference between study groups was significant [estimated treatment effect 2.75; 95% confidence interval (CI): 1.75, 3.75, P < 0.0001]. 15-F(2t)-Isoprostane, an index of oxidative stress, significantly decreased from 0.71 ± 0.09 to 0.66 ± 0.13 after Pycnogenol treatment, while no change was observed in the placebo group (mean difference 0.06 pg/mL with an associated 95% CI (0.01, 0.11), P = 0.012]. Inflammation markers, platelet adhesion, and blood pressure did not change after treatment with Pycnogenol or placebo. This study provides the first evidence that the antioxidant Pycnogenol improves endothelial function in patients with CAD by reducing oxidative stress.

Efficacy and safety of 400 and 800 mg etodolac vs. 1,000 mg paracetamol in acute treatment of migraine: a randomized, double-blind, crossover, multicenter, phase III clinical trial.

PubMed

Öztürk, Vesile; Ertaş, Mustafa; Baykan, Betül; Sirin, Hadiye; Özge, Aynur

2013-03-01

We aimed to determine the efficacy and safety of etodolac, in acute migraine attacks in comparison with paracetamol (acetaminophen). We designed a randomized, double-blind, crossover phase III clinical trial for patients diagnosed with migraine for at least 1 year, according to ICHD-II criteria. Two hundred and twenty-nine adult patients having 2 to 8 attacks monthly from 17 centers were included. The patients were instructed to use 3 attack treatment packages consisting of 1,000 mg paracetamol, 400 mg etodolac, and 800 mg etodolac on 3 migraine attacks of moderate-severe intensity each in a 3-month treatment period, interchangeably. Any pain medication was used in 1,570 migraine attacks while study treatments were used in 1,047 attacks. The results for 1,000 mg paracetamol, 400 mg etodolac, and 800 mg etodolac were as follows: response of headache at 2 hours 44.9%, 48.3% and 46.1%; pain-free at 2 hours 19.2%, 19.3% and 24.1%; sustained pain-free from 2 to 24 hours 34.3%, 38.3% and 41.1%; relapse rates in 2 to 24 hours 7.3%, 14.3% and 9.7%. There were no statistically significant differences between the groups regarding the headache response, pain-free, sustained pain-free, and relapse rates. Nausea, vomiting, phonophobia, or photophobia decreased similarly in all groups within 24 hours of treatment administration. Drug-related adverse events were noted in 8 patients with 1,000 mg paracetamol, in 9 patients with 400 mg etodolac and in 9 patients for 800 mg etodolac during the study. Our study showed that etodolac is a safe and effective alternative in acute migraine treatment and showed comparable efficacy to paracetamol 1,000 mg. Etodolac may be considered as an alternative option for acute treatment of migraine. © 2012 The Authors. Pain Practice © 2012 World Institute of Pain.

Effects of smartphone use with and without blue light at night in healthy adults: A randomized, double-blind, cross-over, placebo-controlled comparison.

PubMed

Heo, Jung-Yoon; Kim, Kiwon; Fava, Maurizio; Mischoulon, David; Papakostas, George I; Kim, Min-Ji; Kim, Dong Jun; Chang, Kyung-Ah Judy; Oh, Yunhye; Yu, Bum-Hee; Jeon, Hong Jin

2017-04-01

Smartphones deliver light to users through Light Emitting Diode (LED) displays. Blue light is the most potent wavelength for sleep and mood. This study investigated the immediate effects of smartphone blue light LED on humans at night. We investigated changes in serum melatonin levels, cortisol levels, body temperature, and psychiatric measures with a randomized, double-blind, cross-over, placebo-controlled design of two 3-day admissions. Each subject played smartphone games with either conventional LED or suppressed blue light from 7:30 to 10:00PM (150 min). Then, they were readmitted and conducted the same procedure with the other type of smartphone. Serum melatonin levels were measured in 60-min intervals before, during and after use of the smartphones. Serum cortisol levels and body temperature were monitored every 120 min. The Profile of Mood States (POMS), Epworth Sleepiness Scale (ESS), Fatigue Severity Scale (FSS), and auditory and visual Continuous Performance Tests (CPTs) were administered. Among the 22 participants who were each admitted twice, use of blue light smartphones was associated with significantly decreased sleepiness (Cohen's d = 0.49, Z = 43.50, p = 0.04) and confusion-bewilderment (Cohen's d = 0.53, Z = 39.00, p = 0.02), and increased commission error (Cohen's d = -0.59, t = -2.64, p = 0.02). Also, users of blue light smartphones experienced a longer time to reach dim light melatonin onset 50% (2.94 vs. 2.70 h) and had increases in body temperature, serum melatonin levels, and cortisol levels, although these changes were not statistically significant. Use of blue light LED smartphones at night may negatively influence sleep and commission errors, while it may not be enough to lead to significant changes in serum melatonin and cortisol levels. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of Mangifera indica (Careless) on Microcirculation and Glucose Metabolism in Healthy Volunteers.

PubMed

Buchwald-Werner, Sybille; Schön, Christiane; Frank, Sonja; Reule, Claudia

2017-07-01

A commercial Mangifera indica fruit powder (Careless) showed beneficial acute effects on microcirculation in a randomized, double-blind, crossover pilot study. Here, long-term effects on microcirculation and glucose metabolism were investigated in a double-blind, randomized, placebo-controlled, 3-arm parallel-design study in healthy individuals. A daily dose of 100 mg or 300 mg of the fruit powder was compared to placebo after supplementation for 4 weeks. Microcirculation and endothelial function were assessed by the Oxygen-to-see System and pulse amplitude tonometry, respectively. Glucose metabolism was assessed under fasting and postprandial conditions by capillary glucose and HbA1c values.Microcirculatory reactive hyperemia flow increased, especially in the 100 mg group (p = 0.025). The 300 mg of the M. indica fruit preparation reduced postprandial glucose levels by trend if compared to placebo (p = 0.0535) accompanied by significantly lower HbA1c values compared to baseline. Furthermore, 300 mg intake significantly improved postprandial endothelial function in individuals with decreased endothelial function after high-dose glucose intake (p = 0.0408; n = 11).In conclusion, the study suggests moderate beneficial effects of M. indica fruit preparation on microcirculation, endothelial function, and glucose metabolism. Georg Thieme Verlag KG Stuttgart · New York.

Pharmacokinetics of lacosamide and omeprazole coadministration in healthy volunteers: results from a phase I, randomized, crossover trial.

PubMed

Cawello, Willi; Mueller-Voessing, Christa; Fichtner, Andreas

2014-05-01

The antiepileptic drug lacosamide has a low potential for drug-drug interactions, but is a substrate and moderate inhibitor of the cytochrome P450 (CYP) enzyme CYP2C19. This phase I, randomized, open-label, two-way crossover trial evaluated the pharmacokinetic effects of lacosamide and omeprazole coadministration. Healthy, White, male volunteers (n = 36) who were not poor metabolizers of CYP2C19 were randomized to treatment A (single-dose 40 mg omeprazole on days 1 and 8 together with 6 days of multiple-dose lacosamide [200-600 mg/day] on days 3-8) and treatment B (single doses of 300 mg lacosamide on days 1 and 8 with 7 days of 40 mg/day omeprazole on days 3-9) in pseudorandom order, separated by a ≥ 7-day washout period. Area under the concentration-time curve (AUC) and peak concentration (C(max)) were the primary pharmacokinetic parameters measured for lacosamide or omeprazole administered alone (reference) or in combination (test). Bioequivalence was determined if the 90 % confidence interval (CI) of the ratio (test/reference) fell within the acceptance range of 0.8-1.25. The point estimates (90 % CI) of the ratio of omeprazole + lacosamide coadministered versus omeprazole alone for AUC (1.098 [0.996-1.209]) and C(max) (1.105 [0.979-1.247]) fell within the acceptance range for bioequivalence. The point estimates (90 % CI) of the ratio of lacosamide + omeprazole coadministration versus lacosamide alone also fell within the acceptance range for bioequivalence (AUC 1.133 [1.102-1.165]); C(max) 0.996 (0.947-1.047). Steady-state lacosamide did not influence omeprazole single-dose pharmacokinetics, and multiple-dose omeprazole did not influence lacosamide single-dose pharmacokinetics.

Spinal Muscular Atrophy Biomarker Measurements from Blood Samples in a Clinical Trial of Valproic Acid in Ambulatory Adults

PubMed Central

Renusch, Samantha R.; Harshman, Sean; Pi, Hongyang; Workman, Eileen; Wehr, Allison; Li, Xiaobai; Prior, Thomas W.; Elsheikh, Bakri H.; Swoboda, Kathryn J.; Simard, Louise R.; Kissel, John T.; Battle, Daniel; Parthun, Mark R.; Freitas, Michael A.; Kolb, Stephen J.

2015-01-01

Abstract Background: Clinical trials of therapies for spinal muscular atrophy (SMA) that are designed to increase the expression the SMN protein ideally include careful assessment of relevant SMN biomarkers. Objective: In the SMA VALIANT trial, a recent double-blind placebo-controlled crossover study of valproic acid (VPA) in ambulatory adult subjects with SMA, we investigated relevant pharmacodynamic biomarkers in blood samples from SMA subjects by direct longitudinal measurement of histone acetylation and SMN mRNA and protein levels in the presence and absence of VPA treatment. Methods: Thirty-three subjects were randomized to either VPA or placebo for the first 6 months followed by crossover to the opposite arm for an additional 6 months. Outcome measures were compared between the two treatments (VPA and placebo) using a standard crossover analysis. Results: A significant increase in histone H4 acetylation was observed with VPA treatment (p = 0.005). There was insufficient evidence to suggest a treatment effect with either full length or truncated SMN mRNA transcript levels or SMN protein levels. Conclusions: These measures were consistent with the observed lack of change in the primary clinical outcome measure in the VALIANT trial. These results also highlight the added benefit of molecular and pharmacodynamic biomarker measurements in the interpretation of clinical trial outcomes. PMID:27858735

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

PubMed

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

2014-05-01

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

A RANDOMIZED CLINICAL TRIAL OF VALERIAN FAILS TO IMPROVE SELF-REPORT, POLYSOMNOGRAPHIC, AND ACTIGRAPHIC SLEEP IN OLDER WOMEN WITH INSOMNIA

PubMed Central

Taibi, Diana M.; Vitiello, Michael V.; Barsness, Suzanne; Elmer, Gary W.; Anderson, Gail D.; Landis, Carol A.

2009-01-01

Objective To test the effects of nightly valerian (Valeriana officinalis) extract to improve sleep of older women with insomnia. Methods Participants in this phase 2 randomized, double-blind, cross-over controlled trial were 16 older women (mean age = 69.4 ± 8.1 years) with insomnia. Participants took 300 mg of concentrated valerian extract or placebo 30 minutes before bedtime for two weeks. Sleep was assessed in the laboratory by self-report and polysomnography (PSG) at baseline and again at the beginning and end of each treatment phase (total of 9 nights in the laboratory) and at home by daily sleep logs and actigraphy. Results There were no statistically significant differences between valerian and placebo after a single dose or after two weeks of nightly dosing on any measure of sleep latency, wake after sleep onset (WASO), sleep efficiency, and self-rated sleep quality. In comparing each treatment to baseline in separate comparisons, WASO significantly increased (+17.7 ± 25.6 min, p=.02) after two weeks of nightly valerian, but not after placebo (+6.8 ± 26.4 min, NS). Side effects were minor and did not differ significantly between valerian and placebo. Conclusion Valerian did not improve sleep in this sample of older women with insomnia. Findings from this study add to the scientific evidence that does not support use of valerian in the clinical management of insomnia. PMID:18482867

The Norwegian Cervical Arthroplasty Trial (NORCAT): 2-year clinical outcome after single-level cervical arthroplasty versus fusion-a prospective, single-blinded, randomized, controlled multicenter study.

PubMed

Sundseth, Jarle; Fredriksli, Oddrun Anita; Kolstad, Frode; Johnsen, Lars Gunnar; Pripp, Are Hugo; Andresen, Hege; Myrseth, Erling; Müller, Kay; Nygaard, Øystein P; Zwart, John-Anker

2017-04-01

Standard surgical treatment for symptomatic cervical disc disease has been discectomy and fusion, but the use of arthroplasty, designed to preserve motion, has increased, and most studies report clinical outcome in its favor. Few of these trials, however, blinded the patients. We, therefore, conducted the Norwegian Cervical Arthroplasty Trial, and present 2-year clinical outcome after arthroplasty or fusion. This multicenter trial included 136 patients with single-level cervical disc disease. The patients were randomized to arthroplasty or fusion, and blinded to the treatment modality. The surgical team was blinded to randomization until nerve root decompression was completed. Primary outcome was the self-rated Neck Disability Index. Secondary outcomes were the numeric rating scale for pain and quality of life questionnaires Short Form-36 and EuroQol-5Dimension-3 Level. There was a significant improvement in the primary and all secondary outcomes from baseline to 2-year follow-up for both arthroplasty and fusion (P < 0.001), and no observed significant between-group differences at any follow-up times. However, linear mixed model analyses, correcting for baseline values, dropouts and missing data, revealed a difference in Neck Disability Index (P = 0.049), and arm pain (P = 0.027) in favor of fusion at 2 years. The duration of surgery was longer (P < 0.001), and the frequency of reoperations higher (P = 0.029) with arthroplasty. The present study showed excellent clinical results and no significant difference between treatments at any scheduled follow-up. However, the rate of index level reoperations was higher and the duration of surgery longer with arthroplasty. http://www.clinicaltrials.gov NCT 00735176.19.

Rational dosages of nutrients have a prolonged effect on learning disabilities.

PubMed

Carlton, R M; Ente, G; Blum, L; Heyman, N; Davis, W; Ambrosino, S

2000-05-01

Reports that administration of nutrients has increased the academic performance of learning-disabled children exist in the literature. To document the effects of nutrients on learning-disabled children in a controlled study. A randomized, double-blind, placebo-controlled crossover trial, which followed 1 year of open-label nutrients. Children who improved in the open-label trial were eligible to enter the controlled phase of the study. Subjects were enrolled from the general community through advertisements. Twenty children met the criteria for being learning disabled. Each child was tried out on some (but not necessarily all) of the B vitamins and minerals used in this study. These were administered semi-blinded for the first year; double-blinded in crossover rotations during the second year; and open-label in the ensuing years. At various time points, school-certified psychologists administered psychoeducational tests. School report cards were evaluated at baseline and for all subsequent periods. Twenty learning-disabled children entered the study, but 1 dropped out because of nausea. The remaining 19 children showed significant academic and behavioral improvements within a few weeks or months of open-label treatment with nutrient supplements. Some children gained 3 to 5 years in reading comprehension within the first year of treatment; and all children in special education classes became mainstreamed, and their grades rose significantly. Twelve of the children completed the 1-year double-blind phase, after which approximately half of the children chose to remain on the nutrients for at least 2 additional years. For those who discontinued, it took at least 1 year to begin to see the first indications of decline in academic performance, and another year for their grades to drop significantly. In contrast, for children who remained on nutrients, the gains continued the upward trend; at the end of year 4, the difference in scores between the 2 groups had reached statistical significance (P < .01). The overall results of this study tentatively support the concept that learning disabilities may in some cases be a nutrient-responsive disorder.

A Single Dose of LSD Does Not Alter Gene Expression of the Serotonin 2A Receptor Gene (HTR2A) or Early Growth Response Genes (EGR1-3) in Healthy Subjects

PubMed Central

Dolder, Patrick C.; Grünblatt, Edna; Müller, Felix; Borgwardt, Stefan J.; Liechti, Matthias E.

2017-01-01

Rationale: Renewed interest has been seen in the use of lysergic acid diethylamide (LSD) in psychiatric research and practice. The repeated use of LSD leads to tolerance that is believed to result from serotonin (5-HT) 5-HT2A receptor downregulation. In rats, daily LSD administration for 4 days decreased frontal cortex 5-HT2A receptor binding. Additionally, a single dose of LSD acutely increased expression of the early growth response genes EGR1 and EGR2 in rat and mouse brains through 5-HT2A receptor stimulation. No human data on the effects of LSD on gene expression has been reported. Therefore, we investigated the effects of single-dose LSD administration on the expression of the 5-HT2A receptor gene (HTR2A) and EGR1-3 genes. Methods: mRNA expression levels were analyzed in whole blood as a peripheral biomarker in 15 healthy subjects before and 1.5 and 24 h after the administration of LSD (100 μg) and placebo in a randomized, double-blind, placebo-controlled, cross-over study. Results: LSD did not alter the expression of the HTR2A or EGR1-3 genes 1.5 and 24 h after administration compared with placebo. Conclusion: No changes were observed in the gene expression of LSD’s primary target receptor gene or genes that are implicated in its downstream effects. Remaining unclear is whether chronic LSD administration alters gene expression in humans. PMID:28701958

DDD versus VVIR pacing in patients, ages 70 and over, with complete heart block.

PubMed

Ouali, Sana; Neffeti, Elyes; Ghoul, Karima; Hammas, Sami; Kacem, Slim; Gribaa, Rim; Remedi, Fahmi; Boughzela, Essia

2010-05-01

Dual-chamber pacing is believed to have an advantage over single-chamber ventricular pacing. The aim of the study was to determine whether elderly patients with implanted pacemaker for complete atrioventricular block gain significant benefit from dual-chamber (DDD) compared with single-chamber ventricular demand (VVIR). The study was designed as a double-blind randomized two-period crossover study-each pacing mode was maintained for 3 months. Thirty patients (eight men, mean age 76.5 +/- 4.3 years) with implanted PM were submitted to a standard protocol, which included an interview, functional class assessment, quality of life (QoL) questionnaires, 6-minute walk test, and transthoracic echocardiographic examinations. QoL was measured by the SF-36. All these parameters were obtained on DDD mode pacing and VVIR mode pacing. Paired data were compared. QoL was significantly different between the two groups and showed the best values in DDD. Overall, no patient preferred VVIR mode, 18 preferred DDD mode, and 12 expressed no preference. No differences in mean walking distances were observed between patients with single-chamber and dual-chamber pacing. VVI pacing elicited marked decrease in left ventricle ejection fraction and significant enlargement of the left atrium. DDD pacing resulted in significant increase of the peak systolic velocities in lateral mitral annulus and septal mitral annulus. Early diastolic velocities on both sides of mitral annulus did not change. In active elderly patients with complete heart block, DDD pacing is associated with improved quality of life and systolic ventricular function compared with VVI pacing.

Valeriana officinalis Root Extract Modulates Cortical Excitatory Circuits in Humans.

PubMed

Mineo, Ludovico; Concerto, Carmen; Patel, Dhaval; Mayorga, Tyrone; Paula, Michael; Chusid, Eileen; Aguglia, Eugenio; Battaglia, Fortunato

2017-01-01

Valeriana officinalis extract (VE) is a popular herbal medicine used for the treatment of anxiety and sleep disorders. Although the anxiolytic and sedative effects are mainly attributed to the modulation of GABA-ergic transmission, the mechanism of action has not been fully investigated in humans. Noninvasive brain stimulation protocols can be used to elucidate the mechanisms of action of psychoactive substances at the cortical level in humans. In this study, we investigated the effects of a single dose of VE on cortical excitability as assessed with transcranial magnetic stimulation (TMS). Fifteen healthy volunteers participated in a double-blind, randomized, cross-over, placebo-controlled study. Subjects were required to take either 900 mg of VE (valerenic acid 0.8%) or placebo (an equal dose of vitamin E). Motor cortex excitability was studied by single and paired TMS before and at 1 h and 6 h after the oral administration. Cortical excitability was assessed using different TMS parameters: resting motor threshold, motor-evoked potential amplitude, cortical silent period, short-interval intracortical inhibition, and intracortical facilitation. Furthermore, we assessed sensorimotor integration by short-latency and long-latency afferent inhibition. We found a significant reduction in ICF, without any significant changes in other TMS measures of motor cortex excitability. The amount of ICF returned to baseline value 6 h after the intake of the VE. A single oral dose of VE modulates intracortical facilitatory circuits. Our results in healthy subjects could be predictive markers of treatment response in patients and further support the use of pharmaco-TMS to investigate the neuropsychiatric effects of herbal therapies in humans. © 2017 S. Karger AG, Basel.

Comparative study of dihydroartemisinin and artesunate safety in healthy Thai volunteers.

PubMed

Kongpatanakul, S; Chatsiricharoenkul, S; Khuhapinant, A; Atipas, S; Kaewkungwal, J

2009-09-01

As part of new drug development initiatives in Thailand, a new tablet formulation of dihydroartemisinin (DHA, an antimalarial drug) has been developed. Our previous bioequivalence study indicated that the new and reference DHA formulations were well tolerated; however, a significant decrease in hemoglobin was detected after a single 200-mg oral dose. To explore further, a clinical study with an emphasis on hematological parameters was conducted. A single-center, randomized, single-blind, cross-over clinical study was conducted in 18 healthy volunteers with a dosage of 300 mg daily for 2 days. Artesunate was used as a comparator. Adverse events were monitored and laboratory parameters on study Days 0, 2, 5, and 7 post drug administrations were analyzed. Eighteen volunteers completed both rounds of the study. Both drugs were well tolerated. All adverse events were mild. Significant decrease in hemoglobin compared to baseline was detected for both drugs 7 days after administration (DHA: 0.48 g/dl, p = 0.007; artesunate 0.38 g/dl, p = 0.001). Transient bone marrow suppression was evidenced by reduction of reticulocytes with a lowest number on study Day 5 (artesunate 75% reduction in reticulocyte count; DHA 47%, p < 0.001 for both drugs compared to baseline). The present study confirmed our previous finding on significant decrease in hemoglobin. Artesunate appeared to have more negative effects on the numbers of reticulocytes and white blood cells than DHA. Systemic laboratory and toxicity profiles presented in this study may be used as a framework for future clinical studies of artemisinin and its derivatives.

Acute and Chronic Noradrenergic Effects on Cortical Excitability in Healthy Humans

PubMed Central

Kuo, Hsiao-I; Paulus, Walter; Batsikadze, Giorgi; Jamil, Asif; Kuo, Min-Fang

2017-01-01

Abstract Background Noradrenaline is a major neuromodulator in the central nervous system, and it is involved in the pathophysiology of diverse neuropsychiatric diseases. Previous transcranial magnetic stimulation studies suggested that acute application of selective noradrenaline reuptake inhibitors enhances cortical excitability in the human brain. However, other, such like clinical effects, usually require prolonged noradrenaline reuptake inhibitor treatment, which might go along with different physiological effects. Methods The purpose of this study was to investigate the acute and chronic effects of the selective noradrenaline reuptake inhibitor reboxetine on cortical excitability in healthy humans in a double-blind, placebo-controlled, randomized crossover study. Sixteen subjects were assessed with different transcranial magnetic stimulation measurements: motor thresholds, input-output curve, short-latency intracortical inhibition and intracortical facilitation, I-wave facilitation, and short-interval afferent inhibition before and after placebo or reboxetine (8 mg) single-dose administration. Afterwards, the same subjects took reboxetine (8 mg/d) consecutively for 21 days. During this period (subjects underwent 2 experimental sessions with identical transcranial magnetic stimulation measures under placebo or reboxetine), transcranial magnetic stimulation measurements were assessed before and after drug intake. Results Both single-dose and chronic administration of reboxetine increased cortical excitability; increased the slope of the input-output curve, intracortical facilitation, and I-wave facilitation; but decreased short-latency intracortical inhibition and short-interval afferent inhibition. Moreover, chronic reboxetine showed a larger enhancement of intracortical facilitation and I-wave facilitation compared with single-dose application. Conclusions The results show physiological mechanisms of noradrenergic enhancement possibly underlying the functional effects of reboxetine regarding acute and chronic application. PMID:28430976

The effect of cannabis on tremor in patients with multiple sclerosis.

PubMed

Fox, P; Bain, P G; Glickman, S; Carroll, C; Zajicek, J

2004-04-13

Disabling tremor is common in patients with multiple sclerosis (MS). Data from animal model experiments and subjective and small objective studies involving patients suggest that cannabis may be an effective treatment for tremor associated with MS. To our knowledge, there are no published double-blind randomized controlled trials of cannabis as a treatment for tremor in MS patients. The authors conducted a randomized double-blind placebo-controlled crossover trial to examine the effect of oral cannador (cannabis extract) on 14 patients with MS with upper limb tremors. There were eight women and six men, with a mean age of 45 years and mean Expanded Disability Status Scale score of 6.25. Patients were randomly assigned to receive each treatment and the doses escalated over a 2-week period before each assessment. The primary outcome was change on a tremor index, measured using a validated tremor rating scale. The study was powered to detect a functionally significant 50% improvement in the tremor index. Secondary outcomes included accelerometry, an ataxia scale, spiral drawing, finger tapping, and nine-hole pegboard test performance. Analysis of the data showed no significant improvement in any of the objective measures of upper limb tremor with cannabis extract compared to placebo. Finger tapping was faster on placebo compared to cannabis extract (p < 0.02). However, there was a nonsignificant trend for patients to experience more subjective relief from their tremors while on cannabis extract compared to placebo. Cannabis extract does not produce a functionally significant improvement in MS-associated tremor.

Effect of structured physical activity on prevention of serious fall injuries in adults aged 70-89: randomized clinical trial (LIFE Study)

USDA-ARS?s Scientific Manuscript database

OBJECTIVE: To test whether a long term, structured physical activity program compared with a health education program reduces the risk of serious fall injuries among sedentary older people with functional limitations. DESIGN: Multicenter, single blinded randomized trial (Lifestyle Interventions and ...

Influence of menthol on caffeine disposition and pharmacodynamics in healthy female volunteers.

PubMed

Gelal, Ayse; Guven, Hulya; Balkan, Dilara; Artok, Levent; Benowitz, Neal L

2003-09-01

The present study was undertaken to determine whether a single oral dose of menthol affects the metabolism of caffeine, a cytochrome P(450) 1A2 (CYP1A2) substrate, and pharmacological responses to caffeine in people. Eleven healthy female subjects participated in a randomized, double-blind, two-way crossover study, comparing the kinetics and effects of a single oral dose of caffeine (200 mg) in coffee taken together with a single oral dose of menthol (100 mg) or placebo capsules. Serum caffeine concentrations and cardiovascular and subjective parameters were measured throughout the study. Co-administration of menthol resulted in an increase of caffeine t(max) values from 43.6+/-20.6 min (mean+/-SD) to 76.4+/-28.0 min ( P<0.05). The C(max) values of caffeine were lower in the menthol phase than in the placebo phase, but this effect was not statistically significant ( P=0.06). (AUC)(0-24), (AUC)(0- infinity ), terminal half-life and oral clearance were not affected by menthol. Only nine subjects' cardiovascular data were included in the analysis because of technical problems during the measurements. After caffeine, heart rate decreased in both treatment phases. The maximum decrease in heart rate was less in the menthol phase (-8.9+/-3.9 beats/min) than in the placebo phase (-13.1+/-2.1 beats/min) ( P=0.024). There were no statistically significant differences in systolic and diastolic blood pressures between the two treatments. We conclude that a single oral dose of pure menthol (100 mg) delays caffeine absorption and blunts the heart-rate slowing effect of caffeine, but does not affect caffeine metabolism. The possibility that menthol slows the absorption of other drugs should be considered.

The study protocol of a blinded randomised-controlled cross-over trial of lavender oil as a treatment of behavioural symptoms in dementia

PubMed Central

2010-01-01

Background The agitated behaviours that accompany dementia (e.g. pacing, aggression, calling out) are stressful to both nursing home residents and their carers and are difficult to treat. Increasingly more attention is being paid to alternative interventions that are associated with fewer risks than pharmacology. Lavandula angustifolia (lavender) has been thought, for centuries, to have soothing properties, but the existing evidence is limited and shows mixed results. The aim of the current study is to test the effectiveness of topically applied pure lavender oil in reducing actual counts of challenging behaviours in nursing home residents. Methods/Design We will use a blinded repeated measures design with random cross-over between lavender oil and placebo oil. Persons with moderate to severe dementia and associated behavioural problems living in aged care facilities will be included in the study. Consented, willing participants will be assigned in random order to lavender or placebo blocks for one week then switched to the other condition for the following week. In each week the oils will be applied on three days with at least a two-day wash out period between conditions. Trained observers will note presence of target behaviours and predominant type of affect displayed during the 30 minutes before and the 60 minutes after application of the oil. Nursing staff will apply 1 ml of 30% high strength essential lavender oil to reduce the risk of missing a true effect through under-dosing. The placebo will comprise of jojoba oil only. The oils will be identical in appearance and texture, but can easily be identified by smell. For blinding purposes, all staff involved in applying the oil or observing the resident will apply a masking cream containing a mixture of lavender and other essential oils to their upper lip. In addition, nursing staff will wear a nose clip during the few minutes it takes to massage the oil to the resident's forearms. Discussion If our results show that the use of lavender oil is effective in reducing challenging behaviours in individuals with dementia, it will potentially provide a safer intervention rather than reliance on pharmacology alone. The study's findings will translate easily to other countries and cultures. Trial Registration Australian New Zealand Clinical Trials Registry - ACTRN 12609000569202 PMID:20649945

Effect of simethicone on lactulose-induced H2 production and gastrointestinal symptoms.

PubMed

Friis, H; Bodé, S; Rumessen, J J; Gudmand-Høyer, E

1991-01-01

The results of studies of the effect of simethicone on abdominal gas-related symptoms have been contradictory. In a randomized, double-blind cross-over study, 10 healthy volunteers were given 30 g lactulose and 600 mg simethicone or placebo. End-expiratory breath samples were collected and analyzed for H2 and gastrointestinal symptoms registered. There were no differences in biochemical parameters or symptom score between simethicone and placebo. In contrast to previous studies, we used a sufficiently large dose of lactulose to produce gastrointestinal symptoms, a higher dose of simethicone and placebo tablets containing the same additives as the simethicone tablets. There was no demonstrable effect of simethicone on symptoms or intestinal gas production caused by carbohydrate malabsorption.

Selective adrenergic beta-2-receptor blocking drug, ICI-118.551, is effective in essential tremor.

PubMed

Teräväinen, H; Huttunen, J; Larsen, T A

1986-07-01

Eighteen patients with essential tremor were treated for 2 days with a non-selective adrenergic beta-blocking drug (dl-propranolol, 80 mg X 3), a beta-2-selective blocker (ICI-118.551, 50 mg X 3) and placebo (X 3) in a randomized double blind cross-over study. Postural hand tremor was recorded with an accelerometer before administration of the drugs and at the end of each treatment period. Compared with placebo, both the beta-blocking drugs caused a statistically significant decrease in tremor intensity and they possessed approximately similar antitremor potency. Subjective benefit was reported by 12 of the 18 patients receiving ICI-118.551, 13 when on propranolol and 3 when on placebo.

Reducing dosing frequency of carbidopa/levodopa: double-blind crossover study comparing twice-daily bilayer formulation of carbidopa/levodopa (IPX054) versus 4 daily doses of standard carbidopa/levodopa in stable Parkinson disease patients.

PubMed

Hinson, Vanessa K; Goetz, Christopher G; Leurgans, Sue; Fan, Wenqing; Nguyen, Tiffany; Hsu, Ann

2009-01-01

We compared IPX054, a bilayer tablet of immediate- and extended-release carbidopa/levodopa (CD/LD) given twice daily to standard CD/LD given 4 times daily in patients with stable Parkinson disease (PD). Twelve PD patients with no or mild fluctuations on CD/LD 25/100 mg 4 times daily were randomized to a double-blind crossover comparison with IPX054 (50/200 mg) twice daily. At the end of each 2-week treatment, patients were video recorded while performing a modified Unified Parkinson's Disease Rating Scale motor examination and Rush Dyskinesia Rating Scale at 30-minute intervals over 8.5 hours. The primary outcome measure was the number of videotape epochs rated as "ON" without troublesome dyskinesia by a blinded observer (Wilcoxon signed rank tests). The 9 men and 3 women had a mean age of 69 years and mean PD duration of 6 years. IPX054 and CD/LD showed no significant differences in the primary outcome measure (mean number of video epochs rated as ON without troublesome dyskinesia; P = 0.14). The mean time to ON was improved with IPX054 (P = 0.014), and the mean modified Unified Parkinson's Disease Rating Scale scores slightly favored IPX054 (14.4 vs 16.9; P = 0.052). Mean Rush Dyskinesia Rating Scale scores were not significantly different between IPX054 and CD/LD (0.45 vs 0.69; P = 0.25). No patient developed troublesome dyskinesias. In stable PD patients, no difference was detected between twice-daily treatment with IPX054 and CD/LD given 4 times daily. In this group, substitution with IPX054 reduced dosing frequency while maintaining CD/LD efficacy. In clinical practice, this ease of administration may offer improved treatment compliance.

Efficacy and tolerability of ramelteon in a double-blind, placebo-controlled, crossover study in Japanese patients with chronic primary insomnia.

PubMed

Kohsaka, Masako; Kanemura, Takashi; Taniguchi, Mitsutaka; Kuwahara, Hiroo; Mikami, Akira; Kamikawa, Kunihisa; Uno, Hideki; Ogawa, Atsushi; Murasaki, Mitsukuni; Sugita, Yoshiro

2011-10-01

The aim of this study was to evaluate the efficacy and safety of ramelteon 4, 8, 16 or 32 mg and placebo in Japanese patients with chronic insomnia using a randomized, double-blind, five-period crossover design. A total of 65 Japanese patients with chronic primary insomnia received ramelteon or placebo for two nights each in sleep laboratories. Changes in sleep parameters were assessed objectively by polysomnography and subjectively by postsleep questionnaires. Safety and tolerability was evaluated by assessment of the occurrence of adverse events, next-day residual effects and laboratory and ECG investigations. Ramelteon 8 and 32 mg significantly shortened the mean latency to persistent sleep in comparison with placebo, and there was a statistically significant trend for linear dose-response for this sleep parameter. Overall changes in sleep architecture were modest (<3% changes vs placebo), with increases in stage 1 and decreases in stage 3/4. Ramelteon was well tolerated, the most common adverse effect being somnolence, which was similar to placebo at doses up to 8 mg, but increased with higher doses. Next-day residual effects occurred no more frequently with ramelteon at any dose than with placebo. When compared with sleep latency data from a similarly-designed US study, there was no evidence of any ethnic differences in the efficacy of ramelteon between Japanese and US patients. Overall, ramelteon 8 mg showed the most favorable balance between sleep-promoting effects and tolerability. The unique efficacy profile of ramelteon, promoting sleep initiation without affecting other sleep parameters, may be due to its circadian shifting effect.

Melatonin versus Placebo in Children with Autism Spectrum Conditions and Severe Sleep Problems Not Amenable to Behaviour Management Strategies: A Randomised Controlled Crossover Trial

ERIC Educational Resources Information Center

Wright, Barry; Sims, David; Smart, Siobhan; Alwazeer, Ahmed; Alderson-Day, Ben; Allgar, Victoria; Whitton, Clare; Tomlinson, Heather; Bennett, Sophie; Jardine, Jenni; McCaffrey, Nicola; Leyland, Charlotte; Jakeman, Christine; Miles, Jeremy

2011-01-01

Twenty-two children with autism spectrum disorders who had not responded to supported behaviour management strategies for severe dysomnias entered a double blind, randomised, controlled crossover trial involving 3 months of placebo versus 3 months of melatonin to a maximum dose of 10 mg. 17 children completed the study. There were no significant…

The effect of atomoxetine on random and directed exploration in humans.

PubMed

Warren, Christopher M; Wilson, Robert C; van der Wee, Nic J; Giltay, Eric J; van Noorden, Martijn S; Cohen, Jonathan D; Nieuwenhuis, Sander

2017-01-01

The adaptive regulation of the trade-off between pursuing a known reward (exploitation) and sampling lesser-known options in search of something better (exploration) is critical for optimal performance. Theory and recent empirical work suggest that humans use at least two strategies for solving this dilemma: a directed strategy in which choices are explicitly biased toward information seeking, and a random strategy in which decision noise leads to exploration by chance. Here we examined the hypothesis that random exploration is governed by the neuromodulatory locus coeruleus-norepinephrine system. We administered atomoxetine, a norepinephrine transporter blocker that increases extracellular levels of norepinephrine throughout the cortex, to 22 healthy human participants in a double-blind crossover design. We examined the effect of treatment on performance in a gambling task designed to produce distinct measures of directed exploration and random exploration. In line with our hypothesis we found an effect of atomoxetine on random, but not directed exploration. However, contrary to expectation, atomoxetine reduced rather than increased random exploration. We offer three potential explanations of our findings, involving the non-linear relationship between tonic NE and cognitive performance, the interaction of atomoxetine with other neuromodulators, and the possibility that atomoxetine affected phasic norepinephrine activity more so than tonic norepinephrine activity.

Retention of blinding at follow-up in a randomized clinical study using a sham-control cervical manipulation procedure for neck pain: secondary analyses from a randomized clinical study.

PubMed

Vernon, Howard; Triano, John T; Soave, David; Dinulos, Maricelle; Ross, Kim; Tran, Steven

2013-10-01

Participants in clinical trials of spinal manipulation have not been rigorously blinded to group assignment. This study reports on secondary analyses of the retention of participant blinding beyond the immediate posttreatment time frame following a single-session, randomized clinical study. A novel control cervical manipulation procedure that has previously been shown to be therapeutically inert was contrasted with a typical manipulation procedure. A randomized clinical study of a single session of typical vs sham-control manipulation in patients with chronic neck pain was conducted. Findings of self-reported group registration at 24 to 48 hours posttreatment were computed. The Blinding Index (BI) of Bang et al was then applied to both the immediate and post-24- to 48-hour results. Twenty-four to 48 hours after treatment, 94% and 22% of participants in the typical and control groups, respectively, correctly identified their group assignment. When analyzed with the BI of Bang et al, the immediate posttreatment BI for the group receiving a typical manipulation was 0.22 (95% confidence interval [CI], -0.03 to 0.47); for the group receiving a control manipulation, it was 0.19 (95% CI, -0.06 to 0.43). The BI at post-24 hours was as follows: typical = 0.75 (95% CI, 0.59-0.91) and control = -0.34 (95% CI, -0.58 to -0.11). This study found that the novel sham-control cervical manipulation procedure may be effective in blinding sham group allocation up to 48 hours posttreatment. It appears that, at 48 hours posttreatment, the modified form of the typical cervical manipulation was not. The sham-control procedure appears to be a promising procedure for future clinical trials. © 2013. Published by National University of Health Sciences All rights reserved.

Nifedipine vs Placebo for Treatment of Chronic Chilblains: A Randomized Controlled Trial

PubMed Central

Souwer, Ibo H.; Bor, Jacobus H. J.; Smits, Paul; Lagro-Janssen, Antoine L. M.

2016-01-01

PURPOSE Nifedipine is commonly prescribed for the treatment of chilblains (pernio, perniosis) on the basis of observational studies and a single small, older clinical trial. We aimed to confirm the proposed superiority of oral nifedipine 60 mg per day over placebo for treatment of chronic chilblains in primary care. METHODS We performed a randomized, placebo-controlled, double-blind, crossover trial, closely following the design of the older trial. A total of 32 patients with chronic chilblains were randomly assigned to nifedipine (30 mg controlled release twice a day) or placebo. The primary outcome was patient-reported complaints; the secondary outcome was patient-reported disability. Both were assessed from daily ratings on 100-mm visual analogue scales recorded in a diary. We took ambient temperatures into account and checked for a carry-over effect, and monitored for adverse effects. RESULTS After 6 weeks of treatment, mean scores on the visual analogue scale on complaints showed a nonsignificant difference of 1.84 mm (95% CI, −6.67 to 2.99 mm) in favor of nifedipine (P = .44). Mean scores on the visual analogue scale on disability showed a nonsignificant difference of 0.56 mm (95% CI, −2.97 to 4.09 mm) in favor of placebo (P = .75). There was no carry-over effect of prior study treatment. Nifedipine was associated with significantly lower systolic blood pressure and a significantly higher incidence of edema. CONCLUSIONS In our study, nifedipine was not superior to placebo for treating chronic chilblains. These findings contrast with those of the older study and do not support routine use of nifedipine for this condition. PMID:27621162

Acute Effects of Mecamylamine and Varenicline on Cognitive Performance in Non-smokers With and Without Schizophrenia

PubMed Central

Roh, Sungwon; Hoeppner, Susanne S.; Schoenfeld, David; Fullerton, Catherine A.; Stoeckel, Luke E.; Evins, A. Eden

2013-01-01

Rationale Nicotinic acetylcholine receptors (nAChRs) have been implicated in the pathophysiology of cognitive deficits in the domains of attention and memory in schizophrenia. While nicotinic agonists and antagonists have been proposed as smoking cessation aids, few comparisons have been made of these agents on cognitive performance in individuals with schizophrenia. Objectives This study investigated the acute effects of a nAChR antagonist, mecamylamine, and partial agonist, varenicline, on cognitive function in non-smokers with and without schizophrenia. Methods Single oral doses of mecamylamine, 10 mg, varenicline, 1 mg, and placebo were administered, one week apart, in random order to adults with schizophrenia (n=30) and to healthy volunteers (n=41) in a double-blind, crossover design. The primary outcome of interest was sustained attention as assessed with hit reaction time variability (HRT-SD) on the identical pairs continuous performance test (CPT-IP). Results Mecamylamine worsened performance on CPT-IP HRT-SD, a measure of attention, compared to varenicline in both groups. Performance on mecamylamine was worse than performance on both placebo and varenicline on several additional measures of attention, including CPT-IP hit reaction time (HRT) and random errors at various levels of task difficulty. There was a treatment by diagnosis interaction, such that mecamylamine worsened performance on CPT-IP 2-digit HRT, 3-digit random errors, and 4-digit hit rate compared to placebo and varenicline in participants with schizophrenia, effects not observed in controls. Conclusions These findings support a role for nAChR’s in attention and suggest that those with schizophrenia may be particularly sensitive to nAChR blockade. PMID:24114425

Percutaneous electrical nerve stimulation for low back pain: a randomized crossover study.

PubMed

Ghoname, E A; Craig, W F; White, P F; Ahmed, H E; Hamza, M A; Henderson, B N; Gajraj, N M; Huber, P J; Gatchel, R J

1999-03-03

Low back pain (LBP) contributes to considerable disability and lost wages in the United States. Commonly used opioid and nonopioid analgesic drugs produce adverse effects and are of limited long-term benefit in the management of this patient population. To compare the effectiveness of a novel nonpharmacologic pain therapy, percutaneous electrical nerve stimulation (PENS), with transcutaneous electrical nerve stimulation (TENS) and flexion-extension exercise therapies in patients with long-term LBP. A randomized, single-blinded, sham-controlled, crossover study from March 1997 to December 1997. An ambulatory pain management center at a university medical center. Twenty-nine men and 31 women with LBP secondary to degenerative disk disease. Four therapeutic modalities (sham-PENS, PENS, TENS, and exercise therapies) were each administered for a period of 30 minutes 3 times a week for 3 weeks. Pretreatment and posttreatment visual analog scale (VAS) scores for pain, physical activity, and quality of sleep; daily analgesic medication usage; a global patient assessment questionnaire; and Health Status Survey Short Form (SF-36). PENS was significantly more effective in decreasing VAS pain scores after each treatment than sham-PENS, TENS, and exercise therapies (after-treatment mean +/- SD VAS for pain, 3.4+/-1.4 cm, 5.5+/-1.9 cm, 5.6+/-1.9 cm, and 6.4+/-1.9 cm, respectively). The average +/- SD daily oral intake of nonopioid analgesics (2.6+/-1.4 pills per day) was decreased to 1.3+/-1.0 pills per day with PENS (P<.008) compared with 2.5+/-1.1, 2.2+/-1.0, and 2.6+/-1.2 pills per day with sham-PENS, TENS, and exercise, respectively. Compared with the other 3 modalities, 91 % of the patients reported that PENS was the most effective in decreasing their LBP. The PENS therapy was also significantly more effective in improving physical activity, quality of sleep, and sense of well-being (P<.05 for each). The SF-36 survey confirmed that PENS improved posttreatment function more than sham-PENS, TENS, and exercise. In this sham-controlled study, PENS was more effective than TENS or exercise therapy in providing short-term pain relief and improved physical function in patients with long-term LBP.

Comparison of soft toothbrush and new ultra-soft cleaner in ability to remove plaque from teeth.

PubMed

Stewart, William J; Gratzel, Kristen; Gearity, Erin J; Akerman, Meredith; Hill, Jennifer M

2014-11-01

In this single-blind, crossover study, the difference between a brushless tooth cleaner and a soft toothbrush was studied to compare plaque removal efficiency. The sample was composed of 15 human subjects who were categorized into two groups. Group 1 was composed of subjects randomly assigned to the brushless tooth cleaner for the first two weeks. Group 2 was composed of those randomly assigned to begin the study using the soft toothbrush. After two weeks of brushing with their assigned device, subjects returned to their normal modality to brush their teeth for one week. For the last two weeks of the study, subjects were told to brush with the opposite device they were originally assigned to at the beginning of the trial. Investigators recorded the subjects' gingival indices (based on probe depths) and Quigley scores (based on plaque indices using disclosing solution) at the beginning of week one, the end of week two, the end of week three and the end of week five. The main outcomes in this study were the Silness Loe Index (SLI) and the Quigley Hein Index (QHI). The SLI was assessed on the buccal, lingual, mesial and distal surfaces of six teeth, for a total of 24 surfaces. The QHI was assessed on the buccal and lingual surfaces of six teeth, for a total of 12 surfaces. Each index was measured at each visit by the sum total score divided by the total number of surfaces. The data were analyzed separately using a mixed-effects repeated measures analysis of variance (RMANOVA) for crossover designs. Results indicate that, according to the SLI, there is no significant difference between the two treatments after the first or second weeks. However, based on the QHI, statistically significant differences existed between the two treatments after week one and two. After week one, the soft toothbrush use had a higher QHI than the brushless tooth cleaner. After week two, the brushless tooth cleaner had a higher QHI than the soft toothbrush.

Effect of breathing oxygen-enriched air on exercise performance in patients with precapillary pulmonary hypertension: randomized, sham-controlled cross-over trial.

PubMed

Ulrich, Silvia; Hasler, Elisabeth D; Saxer, Stéphanie; Furian, Michael; Müller-Mottet, Séverine; Keusch, Stephan; Bloch, Konrad E

2017-04-14

The purpose of the current trial was to test the hypothesis that breathing oxygen-enriched air increases exercise performance of patients with pulmonary arterial or chronic thrombo-embolic pulmonary hypertension (PAH/CTEPH) and to investigate involved mechanisms. Twenty-two patients with PAH/CTEPH, eight women, means ± SD 61 ± 14 years, resting mPAP 35 ± 9mmHg, PaO2 ambient air >7.3 kPa, underwent four bicycle ergospirometries to exhaustion on different days, while breathing oxygen-enriched (FiO2 0.50, hyperoxia) or ambient air (FiO2 0.21, normoxia) using progressively increased or constant load protocols (with 75% maximal work rate under FiO2 0.21), according to a randomized, sham-controlled, single-blind, cross-over design. ECG, pulmonary gas-exchange, arterial blood gases, cerebral and quadriceps muscle tissue oxygenation (CTO and QMTO) by near-infrared spectroscopy were measured. In ramp exercise, maximal work rate increased from 113 ± 38 W with normoxia to 132 ± 48 W with hyperoxia, mean difference 19.7 (95% CI 10.5-28.9) W, P < 0.001. Constant load exercise endurance increased from 571 ± 443 to 1242 ± 514 s, mean difference 671 (95% CI 392-951) s, P < 0.001. At end-exercise with hyperoxia PaO2, CTO, QMTO, and PaCO2 were increased, and ventilatory equivalents for CO2 were reduced while the physiological dead space/tidal volume ratio remained unchanged. In patients with PAH/CTEPH, breathing oxygen-enriched air provides major increases in exercise performance. This is related to an improved arterial oxygenation that promotes oxygen availability in muscles and brain and to a reduction of the excessive ventilatory response to exercise thereby enhancing ventilatory efficiency. Patients with PAH/CTEPH may therefore benefit from oxygen therapy during daily physical activities and training. clinicaltrials.gov Identifier: NCT01748474. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Pharmacokinetic Comparison of a Single Oral Dose of Polymorph Form I versus Form V Capsules of the Antiorthopoxvirus Compound ST-246 in Human Volunteers

PubMed Central

Chinsangaram, Jarasvech; Honeychurch, Kady M.; Tyavanagimatt, Shanthakumar R.; Bolken, Tove' C.; Jordan, Robert; Jones, Kevin F.; Marbury, Thomas; Lichtenstein, Israel; Pickens, Margaret; Corrado, Michael; Landis, Patrick; Clarke, Jean M.; Frimm, Annie M.

2012-01-01

ST-246, a novel compound that inhibits egress of orthopoxvirus from mammalian cells, is being tested as a treatment for pathogenic orthopoxvirus infections in humans. This phase I, double-blind, randomized, crossover, exploratory study was conducted to compare the pharmacokinetics (PK) of a single daily 400-mg oral dose of ST-246 polymorph form I versus polymorph form V administered to fed, healthy human volunteers. Both forms appeared to be well tolerated, with no serious adverse events. The order of administration of the two forms had no effect on the results of the PK analyses. Form I and form V both exhibited comparable plasma concentration versus time profiles, but complete bioequivalence between the two forms was not found. Maximum drug concentration (Cmax) met the bioequivalence criteria, as the 90% confidence interval (CI) was 80.6 to 96.9%. However, the area under the concentration-time curve from time zero to time t (AUC0-t) and AUC0-∞ did not meet the bioequivalence criteria (CIs of 67.8 to 91.0% and 73.9 to 104.7%, respectively). The extent of absorption of form I, as defined by AUC0-∞, was 11.7% lower than that of form V. Since ST-246 form I is more thermostable than form V, form I was selected for further development and use in all future studies. PMID:22526314

Impact of escitalopram on vagally mediated cardiovascular function in healthy participants: implications for understanding differential age-related, treatment emergent effects.

PubMed

Kemp, Andrew H; Outhred, Tim; Saunders, Sasha; Brunoni, Andre R; Nathan, Pradeep J; Malhi, Gin S

2014-06-01

Black box warnings for young adults under the age of 25 years indicate that antidepressants may increase risk of suicide. While underlying mechanisms for age-related treatment effects remain unclear, vagally mediated cardiovascular function may play a key role. Decreased heart rate (HR) and an increase in its variability (HRV) improve one's capacity to adapt to environmental stress and attenuate risk for suicide. Using a double blind, randomized, placebo-controlled, crossover, experimental study, we examine whether a single dose of escitalopram (20 mg) attenuates cardiovascular responses to stress under experimental conditions and determine whether age moderates these effects. Forty-four healthy females received a single dose of escitalopram (20 mg) and placebo treatment separated by a 1-week interval (>5 half-lives). HR and high frequency HRV (HF HRV normalized units; 0.15-0.40 Hz) were measured during resting state and stress. While escitalopram attenuated the increase in HR and increased HF HRV, these moderate to large effects were only significant in participants over 25 years of age. No beneficial cardiovascular effects of escitalopram were observed in those under the age of 25. Maturational differences in the development of the prefrontal cortex--a critical region in the central network of autonomic control--may underpin these differential findings. This study provides a theoretical framework on which future research on treatment-emergent suicidality in clinical populations could be based.

The effect of methylphenidate on postural stability under single and dual task conditions in children with attention deficit hyperactivity disorder - a double blind randomized control trial.

PubMed

Jacobi-Polishook, Talia; Shorer, Zamir; Melzer, Itshak

2009-05-15

To investigate the effects of Methylphenidate (MPH) on postural stability in attention deficit hyperactivity disorder (ADHD) children in single and dual task conditions. A randomized controlled double-blind study analyzing postural stability in 24 ADHD children before and after MPH vs. placebo treatments, in three task conditions: (1) Single task, standing still; (2) dual task, standing still performing a memory-attention demanding task; (3) standing still listening to music. MPH resulted in a significant improvement in postural stability during the dual task condition and while listening to music, with no equivalent improvement in placebo controls. MPH improves postural stability in ADHD, especially when an additional task is performed. This is probably due to enhanced attention abilities, thus contributing to improved balance control during performance of tasks that require attention. MPH remains to be studied as a potential drug treatment to improve balance control and physical functioning in other clinical populations.