Clinical evaluation of a novel herbal dental cream in plaque formation: a double-blind, randomized, controlled clinical trial

PubMed Central

Amrutesh, Sunita; Malini, J; Tandur, Prakash S; Patki, Pralhad S

2010-01-01

Background The aim of this study was to evaluate the efficacy and safety of herbal dental cream in comparison to fluoride dental cream. Objectives Clinical evaluation of a novel herbal dental cream in plaque formation: a double-blind, randomized, controlled clinical trial. Methods One hundred and two patients with established dental plaque were randomly assigned to either herbal dental group or fluoride dental group for six weeks in a double-blind design. Improvement in plaque index, oral hygiene status, bleeding index, and gingival index was evaluated in these patients along with microbiological study. Results Results indicated a significant reduction in plaque index, gingival index, oral hygiene index, and microbial growth in both groups. Difference between the groups was not significant. There was no significant change in bleeding index. No adverse events were reported and both the dental creams were well tolerated. Conclusion The finding of this preliminary study indicates that herbal dental cream is as safe and effective as fluoride dental cream, but not superior to it. PMID:27186096

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

PubMed

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

2017-09-01

The prognosis of heart failure patients with reduced ejection fraction (HFrEF) in Japan remains poor, although there is growing evidence for increasing use of evidence-based pharmacotherapies in Japanese real-world HF registries. Sacubitril/valsartan (LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor shown to reduce mortality and morbidity in the recently completed largest outcome trial in patients with HFrEF (PARADIGM-HF trial). The prospectively designed phase III PARALLEL-HF (Prospective comparison of ARNI with ACE inhibitor to determine the noveL beneficiaL trEatment vaLue in Japanese Heart Failure patients) study aims to assess the clinical efficacy and safety of LCZ696 in Japanese HFrEF patients, and show similar improvements in clinical outcomes as the PARADIGM-HF study enabling the registration of LCZ696 in Japan. This is a multicenter, randomized, double-blind, parallel-group, active controlled study of 220 Japanese HFrEF patients. Eligibility criteria include a diagnosis of chronic HF (New York Heart Association Class II-IV) and reduced ejection fraction (left ventricular ejection fraction ≤35%) and increased plasma concentrations of natriuretic peptides [N-terminal pro B-type natriuretic peptide (NT-proBNP) ≥600pg/mL, or NT-proBNP ≥400pg/mL for those who had a hospitalization for HF within the last 12 months] at the screening visit. The study consists of three phases: (i) screening, (ii) single-blind active LCZ696 run-in, and (iii) double-blind randomized treatment. Patients tolerating LCZ696 50mg bid during the treatment run-in are randomized (1:1) to receive LCZ696 100mg bid or enalapril 5mg bid for 4 weeks followed by up-titration to target doses of LCZ696 200mg bid or enalapril 10mg bid in a double-blind manner. The primary outcome is the composite of cardiovascular death or HF hospitalization and the study is an event-driven trial. The design of the PARALLEL-HF study is aligned with the PARADIGM-HF study and aims to assess the efficacy and safety of LCZ696 in Japanese HFrEF patients. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

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.

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

PubMed

Thom, E

2001-01-01

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

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...

Examining the nootropic effects of a special extract of Bacopa monniera on human cognitive functioning: 90 day double-blind placebo-controlled randomized trial.

PubMed

Stough, Con; Downey, Luke A; Lloyd, Jenny; Silber, Beata; Redman, Stephanie; Hutchison, Chris; Wesnes, Keith; Nathan, Pradeep J

2008-12-01

While Ayurvedic medicine has touted the cognitive enhancing effects of Bacopa monniera for centuries, there is a need for double-blind placebo-controlled investigations. One hundred and seven healthy participants were recruited for this double-blind placebo-controlled independent group design investigation. Sixty-two participants completed the study with 80% treatment compliance. Neuropsychological testing using the Cognitive Drug Research cognitive assessment system was conducted at baseline and after 90 days of treatment with a special extract of Bacopa monniera (2 x 150 mg KeenMind) or placebo. The Bacopa monniera product significantly improved performance on the 'Working Memory' factor, more specifically spatial working memory accuracy. The number of false-positives recorded in the Rapid visual information processing task was also reduced for the Bacopa monniera group following the treatment period. The current study provides support for the two other published studies reporting cognitive enhancing effects in healthy humans after a 90 day administration of the Bacopa monniera extract. Further studies are required to ascertain the effective dosage range, the time required to attain therapeutic levels and the effects over a longer term of administration. (c) 2008 John Wiley & Sons, Ltd.

Efficacy and safety of teneligliptin add-on to insulin monotherapy in Japanese patients with type 2 diabetes mellitus: a 16-week, randomized, double-blind, placebo-controlled trial with an open-label period.

PubMed

Kadowaki, Takashi; Kondo, Kazuoki; Sasaki, Noriyuki; Miyayama, Kyoko; Yokota, Shoko; Terata, Ryuji; Gouda, Maki

2017-09-01

To assess the efficacy and safety of teneligliptin as add-on to insulin monotherapy in patients with type 2 diabetes mellitus (T2DM). In a 16-week, double-blind period, 148 Japanese T2DM patients with inadequate glycemic control with insulin and diet/exercise therapies were randomized to placebo or teneligliptin 20 mg. In a subsequent 36-week, open-label period, all patients received teneligliptin once daily. The primary outcome measure was change in HbA1c at the end of the double-blind period. The difference between placebo and teneligliptin in change in HbA1c in the double-blind period (least squares mean ± SE) was -0.80% ± 0.11%; teneligliptin was superior (ANCOVA, P < 0.001). The HbA1c-lowering effect of teneligliptin was maintained throughout the open-label period. The incidence of adverse events was 53.5% with placebo and 44.2% with teneligliptin in the double-blind period, 66.7% in the placebo/teneligliptin group in the open-label period, and 77.9% in the teneligliptin/teneligliptin group over both double-blind/open-label periods. The incidence of hypoglycemic symptoms was 11.1% in the placebo/teneligliptin group in the open-label period and 27.3% in the teneligliptin/teneligliptin group over both double-blind/open-label periods. Teneligliptin was effective and well tolerated in Japanese T2DM patients with inadequate glycemic control. NCT02081599.

Effects of lithium carbonate on performance and biomedical functions.

DOT National Transportation Integrated Search

1977-07-01

The effects of a single 600-mg dose of lithium carbonate were evaluated in a study of 15 healthy, normal male subjects. Subjects were studied, on two occasions, by utilizing a double-blind design--once receiving the lithium carbonate and once receivi...

Investigating methotrexate toxicity within a randomized double-blinded, placebo-controlled trial: Rationale and design of the Cardiovascular Inflammation Reduction Trial-Adverse Events (CIRT-AE) Study.

PubMed

Sparks, Jeffrey A; Barbhaiya, Medha; Karlson, Elizabeth W; Ritter, Susan Y; Raychaudhuri, Soumya; Corrigan, Cassandra C; Lu, Fengxin; Selhub, Jacob; Chasman, Daniel I; Paynter, Nina P; Ridker, Paul M; Solomon, Daniel H

2017-08-01

The role of low dose methotrexate (LDM) in potential serious toxicities remains unclear despite its common use. Prior observational studies investigating LDM toxicity compared LDM to other active drugs. Prior placebo-controlled clinical trials of LDM in inflammatory conditions were not large enough to investigate toxicity. The Cardiovascular Inflammation Reduction Trial (CIRT) is an ongoing NIH-funded, randomized, double-blind, placebo-controlled trial of LDM in the secondary prevention of cardiovascular disease. We describe here the rationale and design of the CIRT-Adverse Events (CIRT-AE) ancillary study which aims to investigate adverse events within CIRT. CIRT will randomize up to 7000 participants with cardiovascular disease and no systemic rheumatic disease to either LDM (target dose: 15-20mg/week) or placebo for an average follow-up period of 3-5 years; subjects in both treatment arms receive folic acid 1mg daily for 6 days each week. The primary endpoints of CIRT include recurrent cardio vascular events, incident diabetes, and all-cause mortality, and the ancillary CIRT-AE study has been designed to adjudicate other clinically important adverse events including hepatic, gastrointestinal, respiratory, hematologic, infectious, mucocutaneous, oncologic, renal, neurologic, and musculoskeletal outcomes. Methotrexate polyglutamate levels and genome-wide single nucleotide polymorphisms will be examined for association with adverse events. CIRT-AE will comprehensively evaluate potential LDM toxicities among subjects with cardiovascular disease within the context of a large, ongoing, double-blind, placebo-controlled trial. This information may lead to a personalized approach to monitoring LDM in clinical practice. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of garlic extract on platelet aggregation: a randomized placebo-controlled double-blind study.

PubMed

Morris, J; Burke, V; Mori, T A; Vandongen, R; Beilin, L J

1995-01-01

1. Studies of the effects of garlic on platelet aggregation have produced inconsistent results possibly related to variations in study design and in the garlic preparations used. 2. The present study examined the effects on platelet aggregation and serum thromboxane and lyso-platelet activating factor, of feeding garlic extract to healthy men using a placebo-controlled, double-blind design. The effects of the same garlic preparation on platelet aggregation in vitro were also investigated. 3. There were no significant differences in platelet aggregation with adenosine diphosphate, platelet activating factor (PAF) or collagen according to treatment group. Serum thromboxane and lysoPAF also showed no change related to garlic supplements. 4. In vitro aggregation with collagen decreased linearly with increasing amounts of garlic extract, but concentrations were higher than those attainable in vivo. Gastrointestinal side effects prevented the use of higher doses of garlic which must be considered to be pharmacological as they exceed changes achievable by dietary modification.

D-camphor-crataegus berry extract combination increases blood pressure and cognitive functioning in the elderly - a randomized, placebo controlled double blind study.

PubMed

Werner, Natalie S; Duschek, Stefan; Schandry, Rainer

2009-12-01

The present study investigated whether the D-camphor-crataegus berry extract combination Korodin elevates blood pressure and enhances cognitive performance in the elderly population. Eighty women aged between 50 and 80 years were examined based on a randomized, placebo controlled double blind design. Blood pressure was measured sphygmomanometrically and through continuous noninvasive recording. Cognitive performance was assessed by means of two tests measuring general information processing capacity and visuomotor speed. The administration of the drug led to a short term increase in blood pressure as well as in cognitive performance as compared to placebo. Potential physiological mechanisms of action mediating this effect, including hemodynamic alterations, sympathetic stimulation as well as improvement of cerebral metabolism are discussed.

Management of oral lesions in HIV-positive patients.

PubMed

Baccaglini, Lorena; Atkinson, Jane C; Patton, Lauren L; Glick, Michael; Ficarra, Giuseppe; Peterson, Douglas E

2007-03-01

HIV/AIDS is currently the leading cause of death in Africa and the fourth leading cause of death worldwide. This systematic review of the literature was conducted to evaluate the evidence for treatment of the most common oral lesions associated with HIV: oral candidiasis with or without oropharyngeal involvement (OPC), oral hairy leukoplakia (OHL), recurrent aphthous-like ulcerations (RAU), oral Kaposi's sarcoma (OKS), orolabial herpes simplex infection (HSV), oral herpes zoster infection (VZV), intraoral or perioral warts (HPV), and HIV-associated periodontal diseases. Treatment of HIV-associated salivary gland disease is addressed in a different section of this World Workshop. We found the largest body of evidence for treatment of OPC in HIV patients. Future trials will be needed to test drugs currently in development for treatment of Candida strains that are resistant to existing therapies. There were no double blind, placebo-controlled randomized clinical trials (RCT) for topical treatment of OHL, and only one RCT for systemic treatment of the lesion with desciclovir. Systemic thalidomide was the only drug tested in RCT for treatment or prevention of RAU. Only 1 double-blind RCT comparing vinblastine and sodium tetradecyl sulfate was identified for localized treatment of OKS. Three drugs (famciclovir, acyclovir, and valaciclovir) were shown to be effective in randomized, double-blind trials for treatment or suppression of mucocutaneous HSV lesions in HIV patients. In all 3 trials, the effects of these medications on orolabial HSV lesions were not reported separately. There were no double-blind, placebo-controlled RCT testing topical treatments for orolabial HSV lesions in HIV patients. No trials testing treatments of oral VZV were identified. There were no double-blind, placebo-controlled RCT for treatment of HIV-associated intraoral or perioral warts or periodontal diseases. In conclusion, there is a need for well-designed RCTs to assess the safety and efficacy of topical and systemic treatments of most oral mucosal and perioral lesions in HIV patients. There is also a need to develop newer drugs for treatment of resistant fungal and viral microorganisms. Finally, standardized outcome measures should be developed for future clinical trials to allow comparisons of studies using different populations.

Therapeutic efficacy of traditional Chinese medicine, Shen-Mai San, in cancer patients undergoing chemotherapy or radiotherapy: study protocol for a randomized, double-blind, placebo-controlled trial

PubMed Central

2012-01-01

Background Cancer is one of the major health issues worldwide. An increasing number of cancer patients are offered treatment with surgery, chemotherapy and radiotherapy. Traditional Chinese medicine (TCM) is one of the most common complementary therapies offered to cancer patients in Taiwan. We designed a randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy of TCM in patients with cancer. Methods/design In this study, inclusion criteria are postoperative patients with histologically confirmed cancer within 3 years who are undergoing chemotherapy or radiotherapy, more than 18 years old, have given signed informed consent, have the ability to read Chinese, and the ability for oral intake. Exclusion criteria include being pregnant, breast feeding, having completed chemotherapy or radiotherapy, brain metastasis with Eastern Cooperative Oncology Group (ECOG) performance status of two to four, delusion or hallucinations, acute infection, and have received medications under other clinical trials. The patients were separated into an intervention group (Shen-Mai-San, SMS) and a placebo group for four weeks using a randomized, double-blind procedure. The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life questionnaire (QOL-C30) was used to evaluate the quality of life. General data, hemoglobin (Hb), hematocrit (Hct), glutamic-oxalacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), blood urea nitrogen (BUN), creatinine, carcinoembryonic antigen (CEA), TCM diagnosis data and heart rate variability (HRV) were also recorded. These data were collected at baseline, two weeks and four weeks after receiving medication. The patients were prescribed granules which contained therapeutic medicines or placebo. Paired-T test was used for statistical analysis. Discussion Shen-Mai-San is composed of processed Ginseng radis, Liriope spicata, and Schizandrae fructus. It was found to be effective for treating cancer-related fatigue and had anti-fatigue activity. In TCM theory, SMS has a synergistic effect for qi and yin deficiency and has the ability to prevent fatigue. The symptoms of qi and yin deficiency are similar to chemotherapy- or radiotherapy-induced side effects. In order to evaluate the efficacy of SMS on cancer treatment, we designed a randomized, double-blind, placebo-controlled trial. Trial registration This study is registered to Clinical Trails.gov NCT01580358 PMID:23206440

Effects on Occupants of Enhanced Particle Filtration in a non-problem office environment: A Double-Blind Crossover Intervention Study

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

Mendell, M.J.; Fisk, W.J.; Petersen, M.

1998-06-15

Workers in indoor environments often complain of symptoms, such as eye and nose irritation, headache, and fatigue, which improve away from work. Exposures causing such complaints, sometimes referred to as sick building syndrome, generally have not been identified. Evidence suggests these worker symptoms are related to chemical, microbiological, physical, and psychosocial exposures not well characterized by current methods. Most research in this area has involved cross-sectional studies, which are limited in their abilities to show causal connections. Experimental studies have also been conducted which, by changing one factor at a time to isolate its effects, can demonstrate benefits of anmore » environmental intervention even before exposures or mechanisms are understood. This study was prompted by evidence that particulate contaminants may be related to acute occupant symptoms and discomfort. The objective was to assess, with a double-blind, double crossover intervention design, whether improved removal of small airborne particles by enhanced central filtration would reduce symptoms and discomfort.« less

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

PubMed Central

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

2012-01-01

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

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

PubMed

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

2016-03-01

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

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.

ABSENCE OF SYMPTOMS WITH CARBOXYHEMOGLOBIN LEVELS OF 16-23%

EPA Science Inventory

It has been generally accepted that carboxyhemoglobin levels between 10-20% produce mild headaches, dizziness and/or nausea. Experimental double blind exposures of 18 healthy, nonsmoking young men at rest to 7,000 - 24,000 ppm, designed to elevate COHb to 15-20% in 3-5 minutes, w...

Using Functional Analysis Methodology to Evaluate Effects of an Atypical Antipsychotic on Severe Problem Behavior

ERIC Educational Resources Information Center

Danov, Stacy E.; Tervo, Raymond; Meyers, Stephanie; Symons, Frank J.

2012-01-01

The atypical antipsychotic medication aripiprazole was evaluated using a randomized AB multiple baseline, double-blind, placebo-controlled design for the treatment of severe problem behavior with 4 children with intellectual and developmental disabilities. Functional analysis (FA) was conducted concurrent with the medication evaluation to…

Monthly high dose vitamin D treatment for the prevention of functional decline: a randomized clinical trial

USDA-ARS?s Scientific Manuscript database

Importance: Vitamin D deficiency has been associated with poor physical performance. Objective: To determine the effectiveness of high dose vitamin D in lowering the risk of functional decline. Design, Setting, and Participants: One-year double-blind, randomized clinical trial conducted in Zurich,...

Effect of Piracetam on Dyslexic's Reading Ability.

ERIC Educational Resources Information Center

Wilsher, C.; And Others

1985-01-01

Forty-six dyslexic boys (aged eight to 13) were administered Piracetam or placebo in a double-blind, parallel experiment. Although, overall, there were no significant group effects, the within-subject design revealed improvements in reading speed and accuracy in Piracetam Ss. Dyslexics with higher reading ages improved significantly compared to…

Oppositional Defiant Disorder in Adults with ADHD

ERIC Educational Resources Information Center

Reimherr, Frederick W.; Marchant, Barrie K.; Olsen, John L.; Wender, Paul H.; Robison, Reid J.

2013-01-01

Objective: Oppositional defiant disorder (ODD) is the most common comorbid condition in childhood ADHD. This trial was prospectively designed to explore ODD symptoms in ADHD adults. Method: A total of 86 patients in this placebo-controlled, double-blind trial of methylphenidate transdermal system (MTS) were categorized based on the presence of ODD…

Reflexology has no immediate haemodynamic effect in patients with chronic heart failure: a double blind randomised controlled trial.

PubMed

Jones, Jenny; Thomson, Patricia; Lauder, William; Howie, Kate; Leslie, Stephen J

2013-08-01

This study measured the effects of reflexology in 12 reflexology-naive patients with chronic heart failure in a placebo-controlled, double blind randomised controlled study design. Outcomes included 'beat-to-beat' non-invasive continuous measurement of cardiovascular parameters and measurement of state of anxiety and pain/discomfort. There were no changes in any of the haemodynamic parameters measured (all p > 0.05). Perceived state of anxiety was significantly reduced post treatment in the control group only (p = 0.03). Reflexology applied to the feet of patients with chronic heart failure appears to have no immediate haemodynamic effects. While any long term treatment effect is uncertain, it would appear that reflexology is safe for use in this patient group. Copyright © 2013 Elsevier Ltd. All rights reserved.

[Treatment of cyclical mastodynia using an extract of Vitex agnus castus: results of a double-blind comparison with a placebo].

PubMed

Halaska, M; Raus, K; Bĕles, P; Martan, A; Paithner, K G

1998-10-01

The aim of study presented here was to gather the data about the tolerability and efficacy of Vitex agnus castus (VACS) extract. The study was designed as double-blind, placebo controlled in two parallel groups (each 50 patients). Treatment phase lasted 3 consequent menstrual cycles (2 x 30 drops/day = 1.8 ml of VASC) or placebo. Mastalgia during at least 5 days of the cycle before the treatment was the strict inclusion condition. For assessment of the efficacy visual analogue scale was used. Altogether 97 patients were included into the statistical analysis (VACS: n = 48, placebo: n = 49). Intensity of breast pain diminished quicker with VACS group. The tolerability was satisfactory. We found VACS to be useful in the treatment of cyclical breast pain in women.

Hyperbaric Oxygen Therapy in the Treatment of Chronic Mild-Moderate Blast-Induced Traumatic Brain Injury Post-Concussion Syndrome (PCS) and Post Traumatic Stress Disorder (PTSD)

DTIC Science & Technology

2017-10-01

a randomized sham- controlled double-blind design with the sham- control group receiving slightly pressurized air at the beginning and end of each... controlled ( non -treatment, non -sham) single-arm crossover single-blind study. The scope of the project is to recruit, enroll, test, treat, re-test and...the P.I. conducted a non - controlled pilot trial of hyperbaric oxygen therapy (HBOT 1.5 atmospheres absolute/60 minutes, twice/day, 40 treatments

Nebulized Isotonic Saline versus Water following a Laryngeal Desiccation Challenge in Classically Trained Sopranos

ERIC Educational Resources Information Center

Tanner, Kristine; Roy, Nelson; Merrill, Ray M.; Muntz, Faye; Houtz, Daniel R.; Sauder, Cara; Elstad, Mark; Wright-Costa, Julie

2010-01-01

Purpose: To examine the effects of nebulized isotonic saline (IS) versus sterile water (SW) on self-perceived phonatory effort (PPE) and phonation threshold pressure (PTP) following a surface laryngeal dehydration challenge in classically trained sopranos. Method: In a double-blind, within-subject crossover design, 34 sopranos breathed dry air…

Statin use and 25-hydroxyvitamin D blood level response to vitamin D treatment of older adults

USDA-ARS?s Scientific Manuscript database

Objectives: To determine whether statin use alters response of 25-hydroxyvitamin D (25(OH)D) level to vitamin D treatment. Design: Pooled analysis. Setting: Three double-blind randomized controlled trials that tested different doses of vitamin D. Participants: Participants of three trials (N = 646; ...

A Compound Herbal Preparation (CHP) in the Treatment of Children with ADHD: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Katz, M.; Adar Levine, A.; Kol-Degani, H.; Kav-Venaki, L.

2010-01-01

Objective: Evaluation of the efficacy of a patented, compound herbal preparation (CHP) in improving attention, cognition, and impulse control in children with ADHD. Method: Design: A randomized, double-blind, placebo-controlled trial. Setting: University-affiliated tertiary medical center. Participants: 120 children newly diagnosed with ADHD,…

A Double-Blind Atropine Trial for Active Learning of Autonomic Function

ERIC Educational Resources Information Center

Fry, Jeffrey R.; Burr, Steven A.

2011-01-01

Here, we describe a human physiology laboratory class measuring changes in autonomic function over time in response to atropine. Students use themselves as subjects, generating ownership and self-interest in the learning as well as directly experiencing the active link between physiology and pharmacology in people. The class is designed to…

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

PubMed

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

2014-06-01

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

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

Repeat dose NRPT (nicotinamide riboside and pterostilbene) increases NAD+ levels in humans safely and sustainably: a randomized, double-blind, placebo-controlled study.

PubMed

Dellinger, Ryan W; Santos, Santiago Roel; Morris, Mark; Evans, Mal; Alminana, Dan; Guarente, Leonard; Marcotulli, Eric

2017-01-01

NRPT is a combination of nicotinamide riboside (NR), a nicotinamide adenine dinucleotide (NAD +) precursor vitamin found in milk, and pterostilbene (PT), a polyphenol found in blueberries. Here, we report this first-in-humans clinical trial designed to assess the safety and efficacy of a repeat dose of NRPT (commercially known as Basis). NRPT was evaluated in a randomized, double-blind, and placebo-controlled study in a population of 120 healthy adults between the ages of 60 and 80 years. The study consisted of three treatment arms: placebo, recommended dose of NRPT (NRPT 1X), and double dose of NRPT (NRPT 2X). All subjects took their blinded supplement daily for eight weeks. Analysis of NAD + in whole blood demonstrated that NRPT significantly increases the concentration of NAD + in a dose-dependent manner. NAD + levels increased by approximately 40% in the NRPT 1X group and approximately 90% in the NRPT 2X group after 4 weeks as compared to placebo and baseline. Furthermore, this significant increase in NAD + levels was sustained throughout the entire 8-week trial. NAD + levels did not increase for the placebo group during the trial. No serious adverse events were reported in this study. This study shows that a repeat dose of NRPT is a safe and effective way to increase NAD + levels sustainably.

Randomised double-blind study comparing tropisetron alone and in combination with dexamethasone in the prevention of acute and delayed cisplatin-induced emesis.

PubMed

Garcia-del-Muro, X; Vadell, C; Pérez Manga, G; Bover, I; Rifá, J; Beltrán, M; Barros, M M; Germá, J R; Fabregat, X; Moreno, V; Salvador, A; Viladiu, P

1998-01-01

In a randomised, double-blind and parallel-design multicentre study, 282 chemotherapy-naive cancer patients received tropisetron 5 mg intravenously (i.v.) before high-dose cisplatin on day 1, and oral tropisetron 5 mg daily on days 2-6, in combination with either placebo (n = 143) or dexamethasone (n = 135), given i.v. on day 1 and orally on days 2-6. Complete protection from acute vomiting/nausea was achieved in 76.3%/79.3% of patients receiving the combination and in 55.2%/61.5% of those receiving tropisetron alone. Complete protection on days 2-6 from delayed vomiting/nausea was obtained in 60%/60% and 39.2%/40.6%, respectively. Tropisetron in combination with dexamethasone is safe and more effective than tropisetron alone in the prevention of both acute and delayed cisplatin-induced emesis.

Comparison of the Anti-Adhesion Activity of Three Different Cranberry Extracts on Uropathogenic P-fimbriated Escherichia coli: a Randomized, Double-blind, Placebo Controlled, Ex Vivo, Acute Study.

PubMed

Howell, Amy; Souza, Dan; Roller, Marc; Fromentin, Emilie

2015-07-01

Research suggests that cranberry (Vaccinium macrocarpon) helps maintain urinary tract health. Bacterial adhesion to the uroepithelium is the initial step in the progression to development of a urinary tract infection. The bacterial anti-adhesion activity of cranberry proanthocyanidins (PACs) has been demonstrated in vitro. Three different cranberry extracts were developed containing a standardized level of 36 mg of PACs. This randomized, double-blind, placebo controlled, ex vivo, acute study was designed to compare the anti-adhesion activity exhibited by human urine following consumption of three different cranberry extracts on uropathogenic P-fimbriated Escherichia coli in healthy men and women. All three cranberry extracts significantly increased anti-adhesion activity in urine. from 6 to 12 hours after intake of a single dose standardized to deliver 36 mg of PACs (as measured by the BL-DMAC method), versus placebo.

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.

The Effectiveness of Two Grammar Treatment Procedures for Children with SLI: A Randomized Clinical Trial

ERIC Educational Resources Information Center

Smith-Lock, Karen M.; Leitão, Suze; Prior, Polly; Nickels, Lyndsey

2015-01-01

Purpose: This study compared the effectiveness of two grammar treatment procedures for children with specific language impairment. Method: A double-blind superiority trial with cluster randomization was used to compare a cueing procedure, designed to elicit a correct production following an initial error, to a recasting procedure, which required…

The Explicit Learning of New Names for Known Objects Is Improved by Dexamphetamine

ERIC Educational Resources Information Center

Whiting, Emma; Chenery, Helen J.; Chalk, Jonathan; Darnell, Ross; Copland, David A.

2008-01-01

A randomised, double-blind, placebo-controlled, between subjects study design (N=37) was used to investigate the effects of dexamphetamine on explicit new name learning. Participants ingested 10 mg of dexamphetamine or placebo daily over 5 consecutive mornings before learning new names for 50 familiar objects plus fillers. The dexamphetamine group…

Effects of MPH-OROS on the Organizational, Time Management, and Planning Behaviors of Children with ADHD

ERIC Educational Resources Information Center

Abikoff, Howard; Nissley-Tsiopinis, Jenelle; Gallagher, Richard; Zambenedetti, Maurizio; Seyffert, Michael; Boorady, Roy; McCarthy, John

2009-01-01

A double-blind, placebo-controlled, crossover design study was done to evaluate the effects of methylphenidate-osmotic-release oral systems (MPH-OROS) on the organization, time management, and planning (OTMP) of children with attention deficit hyperactivity disorder (ADHD). Results show significant improvements on the OTMP of children with ADHD in…

The efficacy and safety of Baoji Tablets for treating common cold with summer-heat and dampness syndrome: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Despite the high incidence and the economic impact of the common cold, there are still no effective therapeutic options available. Although traditional Chinese medicine (TCM) is widely used in China to treat the common cold, there is still a lack of high-quality clinical trials. This article sets forth the protocol for a high-quality trial of a new TCM drug, Baoji Tablets, which is designed to treat the common cold with summer-heat and dampness syndrome (CCSDS). The trial is evaluating both the efficacy and safety of Baoji Tablets. Methods/design This study is designed as a multicenter, phase II, parallel-group, double-blind, double-dummy, randomized and placebo-controlled trial. A total of 288 patients will be recruited from four centers. The new tablets group are administered Baoji Tablets 0.9 g and dummy Baoji Pills 3.7 g. The old pills group are administered dummy Baoji Tablets 0.9 g and Baoji Pills 3.7 g. The placebo control group are administered dummy Baoji Tablets 0.9 g and dummy Baoji Pills 3.7 g. All drugs are taken three times daily for 3 days. The primary outcome is the duration of all symptoms. Secondary outcomes include the duration of primary and secondary symptoms, changes in primary and secondary symptom scores and cumulative symptom score at day 4, as well as an evaluation of treatment efficacy. Discussion This is the first multicenter, double-blind, double-dummy, randomized and placebo-controlled trial designated to treat CCSDS in an adult population from China. It will establish the basis for a scientific and objective assessment of the efficacy and safety of Baoji Tablets for treating CCSDS, and provide evidence for a phase III clinical trial. Trial registration This study is registered with the Chinese Clinical Trial Registry. The registration number is ChiCTR-TRC-13003197. PMID:24359521

Journeys in The Country of The Blind: Entanglement Theory and The Effects of Blinding on Trials of Homeopathy and Homeopathic Provings

PubMed Central

2007-01-01

The idea of quantum entanglement is borrowed from physics and developed into an algebraic argument to explain how double-blinding randomized controlled trials could lead to failure to provide unequivocal evidence for the efficacy of homeopathy, and inability to distinguish proving and placebo groups in homeopathic pathogenic trials. By analogy with the famous double-slit experiment of quantum physics, and more modern notions of quantum information processing, these failings are understood as blinding causing information loss resulting from a kind of quantum superposition between the remedy and placebo. PMID:17342236

A single dose desensitization for summer hay fever. Results of a double blind study-1988.

PubMed

Fell, P; Brostoff, J

1990-01-01

A new type of desensitising vaccine, enzyme potentiated was subjected to a double-blind randomised study during the hay fever season. The vaccine is a convenient single injection given in March and the results show good protection throughout the grass pollen season.

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

PubMed

Sorge, Jürgen; Sittl, Reinhard

2004-11-01

Buprenorphine, a potent opioid analgesic, has been available in parenteral and oral or sublingual(SL) formulations for >25 years. In 2001, the buprenorphine transdermal delivery system (TES) was introduced at 3 release rates (35, 52.5, and 70 microg/h) for the treatment of chronic cancer and noncancer pain. This study compared the analgesic efficacy and tolerability of buprenorphine TES at a release rate of 35 microg/h with those of buprenorphine SL and placebo in patients with severe or very severe chronic cancer or noncancer pain. This multicenter, double-blind, placebo-controlled, parallel-group trial was 1 of 3 Phase III studies involved in the clinical development of buprenorphine TDS. It comprised a 6-day open-label run-in phase in which patients received buprenorphine SL 0.8 to 1.6 mg/d as needed and a double-blind phase in which patients were randomized to receive 3 sequential patches containing buprenorphine TES 35 microg/h or placebo, each lasting 72 hours. Rescue analgesia consisting of buprenorphine SL 02-mg tablets was available as needed throughout the double-blind phase. The main outcome measures were (1) the number of buprenorphine SL tablets required in addition to buprenorphine TES during the double-blind phase compared with the placebo group and compared with the buprenorphine SL requirement during the run-in phase, and (2) patients' assessments of pain intensity, pain relief, and duration of sleep uninterrupted by pain in the double-blind phase compared with the run-in phase. Adverse events were documented throughout the study. One hundred thirty-seven patients were included in the double-blind phase (90 buprenorphine TES, 47 placebo). The buprenorphine TES group included 47 men and 43 women (mean [SD] age, 56.0 [12.1] years), and the placebo group included 23 men and 24 women (mean age, 55.7 [12.9] years). Forty-five patients had cancer-related pain and 92 had noncancer-related pain. The 2 treatment groups were comparable with respect to sex distribution, age, height, and body weight Patients receiving buprenorphine TES significantly reduced their consumption of buprenorphine SL tablets in the double-blind phase compared with patients receiving placebo (reduction of 0.6 [0.4] mg vs 0.4 [0.4] mg; P = 0.03). The relationship between the buprenorphine SL dose in the run-in phase and the number of buprenorphine SL tablets required in the double-blind phase was dose dependent in the active-treatment group only. Patients' assessments of pain intensity and pain relief suggested better analgesia with buprenorphine TES than with placebo, although the differences did not reach statistical significance. The proportion of patients who reported sleeping for >6 hours uninterrupted by pain in the double-blind phase compared with the run-in phase increased by 6.4% in the buprenorphine TDS group (35.6% vs 292%, respectively), compared with a decrease of 5.9% in the placebo group (40.4% vs 463%); no statistical analysis of sleep duration data was performed. Buprenorphine TDS was well tolerated, with adverse events generally similar to those associated with other opioids. The incidence of systemic adverse events in the double-blind phase was similar in the 2 treatment groups (28.9% buprenorphine TDS, 27.6% placebo), with the most common adverse events being nausea, dizziness, and vomiting. After patch removal, skin reactions (mainly mild or moderate pruritus and erythema) were seen in 35.6% of the buprenorphine TDS group and 25.5% of the placebo group. In the population studied, buprenorphine TDS provided adequate pain relief, as well as improvements in pain intensity and duration of pain-free sleep. It may be considered a therapeutic option for the treatment of moderate to severe chronic pain.

Rhodiola rosea therapy for major depressive disorder: a study protocol for a randomized, double-blind, placebo- controlled trial

PubMed Central

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

2014-01-01

Background Rhodiola rosea (R. rosea), a botanical of both western and traditional Chinese medicine, has been used as a folk remedy for improving stamina and reducing stress. However, few controlled clinical trials have examined the safety and efficacy of R. rosea for the treatment of major depressive disorder (MDD). This study seeks to evaluate the safety and efficacy of R. rosea in a 12-week, randomized, double-blind, placebo-controlled, parallel group study design. Methods / Design Subjects with MDD not receiving antidepressant therapy will be randomized to either R. rosea extract 340–1,360 mg daily; sertraline 50–200 mg daily, or placebo for 12 weeks. The primary outcome measure will be change over time in the mean 17-item Hamilton Depression Rating score. Secondary outcome measures will include safety and quality of life ratings. Statistical procedures will include mixed-effects models to assess efficacy for primary and secondary outcomes. Discussion This study will provide valuable preliminary information on the safety and efficacy data of R. rosea versus conventional antidepressant therapy of MDD. It will also inform additional hypotheses and study design of future, fully powered, phase III clinical trials with R. rosea to determine its safety and efficacy in MDD. PMID:25610752

Efficacy of kinesio taping on isokinetic quadriceps torque in knee osteoarthritis: a double blinded randomized controlled study.

PubMed

Anandkumar, Sudarshan; Sudarshan, Shobhalakshmi; Nagpal, Pratima

2014-08-01

Double blind pre-test post-test control group design. To compare the isokinetic quadriceps torque, standardized stair-climbing task (SSCT) and pain during SSCT between subjects diagnosed with knee osteoarthritis pre and post kinesio tape (KT) application with and without tension. Strength of the quadriceps and torque producing capability is frequently found to be compromised in knee osteoarthritis. The efficacy of KT in improving isokinetic quadriceps torque in knee osteoarthritis is unknown, forming the basis for this study. Forty subjects were randomly allocated to either the experimental (therapeutic KT with tension) or control group (sham KT without tension) with the allocation being concealed. Pre and post test measurements of isokinetic quadriceps torque, SSCT and pain during SSCT were carried out by a blinded assessor. A large effect size with significant improvements in the peak quadriceps torque (concentric and eccentric at angular velocities of 90° per second and 120° per second), SSCT and pain were obtained in the experimental group when compared to the control group. Application of therapeutic KT is effective in improving isokinetic quadriceps torque, SSCT and reducing pain in knee osteoarthritis.

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

PubMed

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

2016-06-01

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

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

USDA-ARS?s Scientific Manuscript database

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

High-Dose Pyridoxine and Magnesium Administration in Children with Autistic Disorder: An Absence of Salutary Effects in a Double-Blind, Placebo-Controlled Study.

ERIC Educational Resources Information Center

Findling, Robert L.; Maxwell, Kathleen; Scotese-Wojtila, Lynette; Huang, Jie; Yamashita, Toyoko; Wiznitzer, Max

1997-01-01

Evaluation of high doses of pyridoxine and magnesium in a 10-week double-blind placebo-controlled trial with 10 patients (mean age 6 years) having autism concluded that the high doses used were ineffective in ameliorating autistic behaviors. (DB)

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

ERIC Educational Resources Information Center

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

2004-01-01

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

Treatment of Menorrhagia with Tranexamic Acid. A Double-blind Trial

PubMed Central

Callender, Shei La T.; Warner, G. T.; Cope, E.

1970-01-01

In a double-blind trial tranexamic acid (Cyclokapron) 1 g. four times a day for the first four days of menstruation, significantly decreased menstrual blood loss in women with menorrhagia for which no organic cause had been found. No difference in side-effects was noted between the active and placebo treatment. PMID:4919554

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

PubMed

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

2008-04-01

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

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.

Comparison of Symptomatic versus Functional Changes in Children and Adolescents with ADHD during Randomized, Double-Blind Treatment with Psychostimulants, Atomoxetine, or Placebo

ERIC Educational Resources Information Center

Buitelaar, Jan K.; Wilens, Timothy E.; Zhang, Shuyu; Ning, Yu; Feldman, Peter D.

2009-01-01

Background: This meta-analysis was designed to determine the relationship between reduction of attention-deficit/hyperactivity disorder (ADHD) symptoms and improvement in functioning by examining short-term changes in functional and symptomatic scores in children and adolescents with ADHD. Methods: Search of atomoxetine's clinical trial database…

Educational Intervention to Modify Bottle-Feeding Behaviors among Formula-Feeding Mothers in the WIC Program: Impact on Infant Formula Intake and Weight Gain

ERIC Educational Resources Information Center

Kavanagh, Katherine F.; Cohen, Roberta J.; Heinig, M. Jane; Dewey, Kathryn G.

2008-01-01

Objective: Formula-fed infants gain weight faster than breastfed infants. This study evaluated whether encouraging formula-feeding caregivers to be sensitive to infant satiety cues would alter feeding practices and reduce infant formula intake and weight gain. Design: Double-blind, randomized educational intervention, with intake and growth…

Investigating methotrexate toxicity within a randomized double-blinded, placebo-controlled trial: rationale and design of the Cardiovascular Inflammation Reduction Trial-Adverse Events (CIRT-AE) Study

USDA-ARS?s Scientific Manuscript database

Background: The role of low dose methotrexate (LDM) in potential serious toxicities remains unclear despite its common use. Prior observational studies investigating LDM toxicity compared LDM to other active drugs. Prior placebo-controlled clinical trials of LDM in inflammatory conditions were not l...

Oxcarbazepine in migraine headache: a double-blind, randomized, placebo-controlled study.

PubMed

Silberstein, S; Saper, J; Berenson, F; Somogyi, M; McCague, K; D'Souza, J

2008-02-12

To evaluate the efficacy, safety, and tolerability of oxcarbazepine (1,200 mg/day) vs placebo as prophylactic therapy for patients with migraine headaches. This multicenter, double-blind, randomized, placebo-controlled, parallel-group trial consisted of a 4-week single-blind baseline phase and a 15-week double-blind phase consisting of a 6-week titration period, an 8-week maintenance period, and a 1-week down-titration period, after which patients could enter a 13-week open-label extension phase. During the 6-week titration period, oxcarbazepine was initiated at 150 mg/day and increased by 150 mg/day every 5 days to a maximum tolerated dose of 1,200 mg/day. The primary outcome measure was change from baseline in the number of migraine attacks during the last 28-day period of the double-blind phase. Eighty-five patients were randomized to receive oxcarbazepine and 85 to receive placebo. There was no difference between the oxcarbazepine (-1.30) and placebo groups in mean change in number of migraine attacks from baseline during the last 28 days of double-blind phase (-1.74; p = 0.2274). Adverse events were reported for 68 oxcarbazepine-treated patients (80%) and 55 placebo-treated patients (65%). The majority of adverse events were mild or moderate in severity. The most common adverse events (>or=15% of patients) in the oxcarbazepine-treated group were fatigue (20.0%), dizziness (17.6%), and nausea (16.5%); no adverse event occurred in more than 15% of the placebo-treated patients. Overall, oxcarbazepine was safe and well tolerated; however, oxcarbazepine did not show efficacy in the prophylactic treatment of migraine headaches.

New validated recipes for double-blind placebo-controlled low-dose food challenges.

PubMed

Winberg, Anna; Nordström, Lisbeth; Strinnholm, Åsa; Nylander, Annica; Jonsäll, Anette; Rönmark, Eva; West, Christina E

2013-05-01

Double-blind placebo-controlled food challenges are considered the most reliable method to diagnose or rule out food allergy. Despite this, there are few validated challenge recipes available. The present study aimed to validate new recipes for low-dose double-blind placebo-controlled food challenges in school children, by investigating whether there were any sensory differences between the active materials containing cow's milk, hen's egg, soy, wheat or cod, and the placebo materials. The challenge materials contained the same hypoallergenic amino acid-based product, with or without added food allergens. The test panels consisted of 275 school children, aged 8-10 and 14-15 yr, respectively, from five Swedish schools. Each participant tested at least one recipe. Standardized blinded triangle tests were performed to investigate whether any sensory differences could be detected between the active and placebo materials. In our final recipes, no significant differences could be detected between the active and placebo materials for any challenge food (p > 0.05). These results remained after stratification for age and gender. The taste of challenge materials was acceptable, and no unfavourable side effects related to test materials were observed. In summary, these new validated recipes for low-dose double-blinded food challenges contain common allergenic foods in childhood; cow's milk, hen's egg, soy, wheat and cod. All test materials contain the same liquid vehicle, which facilitates preparation and dosing. Our validated recipes increase the range of available recipes, and as they are easily prepared and dosed, they may facilitate the use of double-blind placebo-controlled food challenges in daily clinical practice. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

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

PubMed

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

2018-01-01

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

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

PubMed

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

2017-12-01

The aims of this study were to conduct a systematic literature review on balneotherapy about the specific therapeutic role of mineral elements and other chemical compounds of mineral waters and derivate peloids/muds and to discuss the study methods used to evaluate it (in musculoskeletal conditions). We searched Medline by PubMed using the following key words: "spa therapy" "balneotherapy" "mud" "peloid" "mud pack Therapy" in combination with "randomized controlled trial" "double blind trial." We also reviewed the reference list of articles retrieved by the Medline search. We selected the double-blind randomized clinical trials that assessed the effects of mineral water or mud treatments compared to tap water, attenuated peloid/mud therapy or similar treatments without the specific minerals or chemical compounds of the treatment group ("non-mineral"). We evaluated the internal validity and the quality of the statistical analysis of these trials. The final selection comprised 27 double-blind randomized clinical trials, 20 related to rheumatology. A total of 1118 patients with rheumatological and other musculoskeletal diseases were evaluated in these studies: 552 of knee osteoarthritis, 47 of hand osteoarthritis, 147 chronic low back pain, 308 of reumathoid arthritis, and 64 of osteoporosis; 293 of these participants were assigned to the experimental groups of knee osteoarthritis, 24 in hand osteoarthritis, 82 of low back pain, 152 with reumathoid arthritis, and 32 with osteoporosis. They were treated with mineral water baths and/or mud/peloid (with or without other forms of treatment, like physical therapy, exercise…). The rest were allocated to the control groups; they received mainly tap water and/or "non-mineral" mud/peloid treatments. Mineral water or mud treatments had better and longer improvements in pain, function, quality of life, clinical parameters, and others in some rheumatologic diseases (knee and hand osteoarthritis, chronic low back pain, rheumatoid arthritis, and osteoporosis) compared to baseline and non-mineral similar treatments. Internal validity and other limitations of the study's methodology impede causal relation of spa therapy on these improvements. Randomized clinical trials are very heterogeneous. Double-blind randomized clinical trials seem to be the key for studying the role of mineral elements and other chemical compounds, observing enough consistency to demonstrate better and longer improvements for mineral waters or derivate compared to tap water; but due to heterogeneity and gaps on study protocol and methodology, existing research is not sufficiently strong to draw firm conclusions. Well-designed studies in larger patients' population are needed to establish the role of minerals and other chemical compounds in spa therapy.

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

NASA Astrophysics Data System (ADS)

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

2017-12-01

The aims of this study were to conduct a systematic literature review on balneotherapy about the specific therapeutic role of mineral elements and other chemical compounds of mineral waters and derivate peloids/muds and to discuss the study methods used to evaluate it (in musculoskeletal conditions). We searched Medline by PubMed using the following key words: "spa therapy" "balneotherapy" "mud" "peloid" "mud pack Therapy" in combination with "randomized controlled trial" "double blind trial." We also reviewed the reference list of articles retrieved by the Medline search. We selected the double-blind randomized clinical trials that assessed the effects of mineral water or mud treatments compared to tap water, attenuated peloid/mud therapy or similar treatments without the specific minerals or chemical compounds of the treatment group ("non-mineral"). We evaluated the internal validity and the quality of the statistical analysis of these trials. The final selection comprised 27 double-blind randomized clinical trials, 20 related to rheumatology. A total of 1118 patients with rheumatological and other musculoskeletal diseases were evaluated in these studies: 552 of knee osteoarthritis, 47 of hand osteoarthritis, 147 chronic low back pain, 308 of reumathoid arthritis, and 64 of osteoporosis; 293 of these participants were assigned to the experimental groups of knee osteoarthritis, 24 in hand osteoarthritis, 82 of low back pain, 152 with reumathoid arthritis, and 32 with osteoporosis. They were treated with mineral water baths and/or mud/peloid (with or without other forms of treatment, like physical therapy, exercise…). The rest were allocated to the control groups; they received mainly tap water and/or "non-mineral" mud/peloid treatments. Mineral water or mud treatments had better and longer improvements in pain, function, quality of life, clinical parameters, and others in some rheumatologic diseases (knee and hand osteoarthritis, chronic low back pain, rheumatoid arthritis, and osteoporosis) compared to baseline and non-mineral similar treatments. Internal validity and other limitations of the study's methodology impede causal relation of spa therapy on these improvements. Randomized clinical trials are very heterogeneous. Double-blind randomized clinical trials seem to be the key for studying the role of mineral elements and other chemical compounds, observing enough consistency to demonstrate better and longer improvements for mineral waters or derivate compared to tap water; but due to heterogeneity and gaps on study protocol and methodology, existing research is not sufficiently strong to draw firm conclusions. Well-designed studies in larger patients' population are needed to establish the role of minerals and other chemical compounds in spa therapy.

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

PubMed

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

2012-01-01

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

Reporting on blinding in trial protocols and corresponding publications was often inadequate but rarely contradictory.

PubMed

Hróbjartsson, Asbjørn; Pildal, Julie; Chan, An-Wen; Haahr, Mette T; Altman, Douglas G; Gøtzsche, Peter C

2009-09-01

To compare the reporting on blinding in protocols and articles describing randomized controlled trials. We studied 73 protocols of trials approved by the scientific/ethical committees for Copenhagen and Frederiksberg, 1994 and 1995, and their corresponding publications. Three out of 73 trials (4%) reported blinding in the protocol that contradicted that in the publication (e.g., "open" vs. "double blind"). The proportion of "double-blind" trials with a clear description of the blinding of participants increased from 11 out of 58 (19%) when based on publications alone to 39 (67%) when adding the information in the protocol. The similar proportions for the blinding of health care providers were 2 (3%) and 22 (38%); and for the blinding of data collectors, they were 8 (14%) and 14 (24%). In 52 of 58 publications (90%), it was unclear whether all patients, health care providers, and data collectors had been blinded. In 4 of the 52 trials (7%), the protocols clarified that all three key trial persons had been blinded. The reporting on blinding in both trial protocols and publications is often inadequate. We suggest developing international guidelines for the reporting of trial protocols and public access to protocols.

Effect of Atomoxetine on Executive Function Impairments in Adults with ADHD

ERIC Educational Resources Information Center

Brown, Thomas E.; Holdnack, James; Saylor, Keith; Adler, Lenard; Spencer, Thomas; Williams, David W.; Padival, Anoop K.; Schuh, Kory; Trzepacz, Paula T.; Kelsey, Douglas

2011-01-01

Objective: To assess the effect of atomoxetine on ADHD-related executive functions over a 6-month period using the Brown Attention-Deficit Disorder Scale (BADDS) for Adults, a normed, 40-item, self-report scale in a randomized, double-blind, placebo-controlled clinical trial. Method: In a randomized, double-blind clinical trial, adults with ADHD…

Brief Report: Oxytocin Enhances Paternal Sensitivity to a Child with Autism--A Double-Blind Within-Subject Experiment with Intranasally Administered Oxytocin

ERIC Educational Resources Information Center

Naber, Fabienne B. A.; Poslawsky, Irina E.; van Ijzendoorn, Marinus H.; van Engeland, Herman; Bakermans-Kranenburg, Marian J.

2013-01-01

Oxytocin seems associated with parenting style, and experimental work showed positive effects of intranasally administered oxytocin on parenting style of fathers. Here, the first double-blind, placebo-controlled, within-subject experiment with intranasal oxytocin administration to fathers of children with autism spectrum disorder (ASD) is…

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

ERIC Educational Resources Information Center

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

2006-01-01

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

Choosing between NSAID and arnica for topical treatment of hand osteoarthritis in a randomised, double-blind study.

PubMed

Widrig, Reto; Suter, Andy; Saller, Reinhard; Melzer, Jörg

2007-04-01

The use of topical preparations for symptom relief is common in osteoarthritis. The effects of ibuprofen (5%) and arnica (50 g tincture/100 g, DER 1:20), as gel preparations in patients with radiologically confirmed and symptomatically active osteoarthritis of interphalangeal joints of hands, were evaluated in a randomised, double-blind study in 204 patients, to ascertain differences in pain relief and hand function after 21 days' treatment. Diagnosis was according to established criteria; primary endpoints were pain intensity and hand function; statistical design was as per current regulatory guidelines for testing topical preparations. There were no differences between the two groups in pain and hand function improvements, or in any secondary end points evaluated. Adverse events were reported by six patients (6.1%) on ibuprofen and by five patients (4.8%) on arnica. Our results confirm that this preparation of arnica is not inferior to ibuprofen when treating osteoarthritis of hands.

A Preliminary Trial: Double-Blind Comparison of Nefazodone, Bupropion-SR and Placebo in the Treatment of Cannabis Dependence

PubMed Central

Carpenter, Kenneth M.; McDowell, David; Brooks, Daniel J.; Cheng, Wendy; Levin, Frances R.

2009-01-01

The present study investigated the efficacy of nefazodone and bupropion-sustained release for treating cannabis dependence. A double blind, placebo controlled, piggy back design was employed to assess if nefazodone and bupropion-sustained release increased the probability of abstinence from cannabis and reduced the severity of cannabis dependence and cannabis withdrawal symptoms during a 13-week outpatient treatment program. One-hundred and six participants (M=32 years; Females n=25) were randomized to one of three medication conditions (nefazodone, bupropion-sustained release, or placebo) and participated in a weekly individually based coping skills therapy program. Results indicated a an increased probability of achieving abstinence over the course of treatment and a decrease in the severity of cannabis dependence and the withdrawal symptom of irritability. There were no significant effects demonstrated for nefazodone and bupropion-sustained release on cannabis use or cannabis withdrawal symptoms. The results indicate nefazodone and bupropion-sustained release may have limited efficacy in treating cannabis dependence. PMID:19219666

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

PubMed

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

2007-06-01

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

A double-blind randomized placebo-controlled feasibility study evaluating individualized homeopathy in managing pain of knee osteoarthritis.

PubMed

Koley, Munmun; Saha, Subhranil; Ghosh, Shubhamoy

2015-07-01

Few homeopathic complexes seemed to produce significant effects in osteoarthritis; still, individualized homeopathy remained untested. We evaluated the feasibility of conducting an efficacy trial of individualized homeopathy in osteoarthritis. A prospective, parallel-arm, double-blind, randomized, placebo-controlled pilot study was conducted from January to October 2014 involving 60 patients (homeopathy, n = 30; placebo, n = 30) who were suffering from acute painful episodes of knee osteoarthritis and visiting the outpatient clinic of Mahesh Bhattacharyya Homeopathic Medical College and Hospital, West Bengal, India. Statistically significant reduction was achieved in 3 visual analog scales (measuring pain, stiffness, and loss of function) and Osteoarthritis Research Society International scores in both groups over 2 weeks (P < .05); however, group differences were not significant (P > .05). Overall, homeopathy did not appear to be superior to placebo; still, further rigorous evaluation in this design involving a larger sample size seems feasible in future. Clinical Trials Registry, India (CTRI/2014/05/004589). © The Author(s) 2015.

What we know now: the Evanston Illinois field lineups.

PubMed

Steblay, Nancy K

2011-02-01

A Freedom of Information Act lawsuit secured 100 eyewitness identification reports from Evanston, Illinois, one of three cities of the Illinois Pilot Program. The files provide empirical evidence regarding three methodological aspects of the Program's comparison of non-blind simultaneous to double-blind sequential lineups. (1) A-priori differences existed between lineup conditions. For example, the simultaneous non-blind lineup condition was more likely to involve witnesses who had already identified the suspect in a previous lineup or who knew the offender (non-stranger identifications), and this condition also entailed shorter delays between event and lineup. (2) Verbatim eyewitness comments were recorded more often in double-blind sequential than in non-blind simultaneous lineup reports (83% vs. 39%). (3) Effective lineup structure was used equally in the two lineup conditions.

Double-blind trials in hyperbaric medicine: A narrative review on past experiences and considerations in designing sham hyperbaric treatment.

PubMed

Lansdorp, C A; van Hulst, Rob A

2018-06-01

Background Hyperbaric oxygen therapy, which consists of breathing 100% oxygen under a higher atmospheric pressure than normal, is utilized worldwide in the treatment of several diseases. With the growing demand for evidence-based research, hyperbaric oxygen therapy has been criticized for delivering too little high-quality research, mainly in the form of randomized controlled trials. While not always indispensable, the addition of a sham-controlled group to such a trial can contribute to the quality of the research. However, the design of a sham (hyperbaric) treatment is associated with several considerations regarding adequate blinding and the use of pressure and oxygen. This narrative review discusses information on the sham profile and the blinding and safety of double-blind trials in hyperbaric medicine, irrespective of the indication for treatment. Methods MEDLINE, Embase and CENTRAL were searched for sham-controlled trials on hyperbaric oxygen therapy. The control treatment was considered sham if patients were blinded to their allocation and treatment took place in a hyperbaric chamber, with no restrictions regarding pressurization, oxygen levels or indication. Studies involving children or only one session of hyperbaric oxygen were excluded. Information on (the choice of) treatment profile, blinding measures, patient's perception regarding allocation and safety issues was extracted from eligible studies. Results A total of 42 eligible trials were included. The main strategies for sham treatment were (1) use of a lower pressure than that of the hyperbaric oxygen group, while breathing 21% oxygen; (2) use of the same pressure as the hyperbaric oxygen group, while breathing an adjusted percentage of oxygen; and (3) use of the same pressure as the hyperbaric oxygen group, while breathing 21% oxygen. The advantages and disadvantages of each strategy are discussed using the information provided by the trials. Conclusion Based on this review, using a lower pressure than the hyperbaric oxygen group while breathing 21% oxygen best matches the inertness of the placebo. Although studies show that use of a lower pressure does allow adequate blinding, this is associated with more practical issues than with the other strategies. The choice of which sham profile to use requires careful consideration; moreover, to ensure proper performance, a clear and detailed protocol is also required.

Effects of alcohol and energy drink on mood and subjective intoxication: a double-blind, placebo-controlled, crossover study.

PubMed

Benson, Sarah; Scholey, Andrew

2014-07-01

There is concern that combining energy drinks with alcohol may 'mask' subjective intoxication leading to greater alcohol consumption. This study examines the effects of alcohol alone and combined with energy drink on objective and subjective intoxication and mood over the course of 3 h. Using a double-blind, placebo-controlled, balanced, crossover design, 24 participants (mean age 22.23 years) were administered with double placebo, 0.6 g/kg alcohol (mean peak blood alcohol content of 0.051%), 250 ml energy drink and alcohol/energy drink, according to a Latin square design, with a washout of >48 h. On each visit, they were breathalysed and rated themselves on a comprehensive battery of mood items at baseline and then at 45, 90 and 180 min post-drink. Blood alcohol and subjective intoxication were significantly increased following both alcohol alone and alcohol/energy drink. Both measures were statistically indistinguishable between alcohol conditions. In keeping with its (80 mg) caffeine content, the energy drink alone significantly increased self-rated 'alertness' and reduced 'depression-dejection' scores compared with the combined alcohol/energy drink. The alcohol/energy drink increased 'vigor' and 'contentment' at 45 min and decreased 'contentment' at 180 min. The co-ingestion of an energy drink with alcohol does not differently influence blood alcohol content recordings or subjective intoxication compared with alcohol alone, although some mood items are differentially affected. Copyright © 2014 John Wiley & Sons, Ltd.

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

PubMed Central

Goldman, Mitchel P.

2017-01-01

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

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

PubMed

Wu, Douglas C; Goldman, Mitchel P

2017-05-01

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

Double-Blind Maintenance Safety and Effectiveness Findings from the Treatment of Early-Onset Schizophrenia Spectrum (TEOSS) Study

ERIC Educational Resources Information Center

Findling, Robert L.; Johnson, Jacqueline L.; McClellan, Jon; Frazier, Jean A.; Vitiello, Benedetto; Hamer, Robert M.; Lieberman, Jeffrey A.; Ritz, Louise; McNamara, Nora K.; Lingler, Jacqui; Hlastala, Stefanie; Pierson, Leslie; Puglia, Madeline; Maloney, Ann E.; Kaufman, Emily Michael; Noyes, Nancy; Sikich, Linmarie

2010-01-01

Objective: To examine the long-term safety and efficacy of three antipsychotics in early-onset schizophrenia spectrum disorders. Method: Patients (8 to 19 years old) who had improved during an 8-week, randomized, double-blind acute trial of olanzapine, risperidone, or molindone (plus benztropine) were eligible to continue on the same medication…

Risperidone Improves Behavioral Symptoms in Children with Autism in a Randomized, Double-Blind, Placebo-Controlled Trial

ERIC Educational Resources Information Center

Pandina, Gahan J.; Bossie, Cynthia A.; Youssef, Eriene; Zhu, Young; Dunbar, Fiona

2007-01-01

Subgroup analysis of children (5-12 years) with autism enrolled in an 8-week, double-blind, placebo-controlled trial of risperidone for pervasive developmental disorders. The primary efficacy measure was the Aberrant Behavior Checklist-Irritability (ABC-I) subscale. Data were available for 55 children given risperidone (n = 27) or placebo (n =…

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

ERIC Educational Resources Information Center

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

2007-01-01

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

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

ERIC Educational Resources Information Center

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

2006-01-01

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

Randomized, Controlled Trial of Intravenous Immunoglobulin for Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections.

PubMed

Williams, Kyle A; Swedo, Susan E; Farmer, Cristan A; Grantz, Heidi; Grant, Paul J; D'Souza, Precilla; Hommer, Rebecca; Katsovich, Liliya; King, Robert A; Leckman, James F

2016-10-01

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) are hypothesized to occur as a result of cross-reactive antibodies produced in response to group A streptococcal infections. Previous research suggests that immunomodulatory therapies, such as intravenous immunoglobulin (IVIG), may lead to rapid and sustained symptom improvement in patients with PANDAS. A total of 35 children meeting criteria for PANDAS and moderate to severe obsessive-compulsive disorder (OCD) were enrolled in a randomized-entry, double-blind, placebo-controlled, 6-week trial of IVIG (1 g/kg/day on 2 consecutive days), followed by optional open-label treatment for nonresponders, with follow-up at 12 and 24 weeks. Primary outcome measures were the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) and the Clinical Global Impressions-Improvement (CGI-I) rating. "Responders" were defined, a priori, by a ≥ 30% decrease in CY-BOCS total score, and a "much" or "very much" improved rating on CGI-I. During the double-blind phase, the mean decrease in CY-BOCS score was 24% ± 31% in the IVIG group (n = 17) and 12% ± 27% in the placebo group (n = 18), with six responders in the IVIG group (35%) versus four (22%) in the placebo group; these differences were not statistically significant. Twenty-four participants met criteria for nonresponse to double-blind infusion and received open-label IVIG at week 6. Among all participants, the mean CY-BOCS improvement from baseline was 55% ± 33% at week 12 and 62% ± 33% at week 24. IVIG was safe and well tolerated. Between-group differences were smaller than anticipated, and the double-blind comparison failed to demonstrate superiority of IVIG over placebo. The observed open-label improvements indicate that future trials would benefit from larger sample sizes designed in part to aid in the identification of biomarkers predictive of a positive response to immunotherapy. Future investigations focused on the natural history of PANDAS are also warranted. Clinical trial registration information-Intravenous Immunoglobulin for PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections); http://clinicaltrials.gov/; NCT01281969ZIAMH002666. Published by Elsevier Inc.

Probiotics for fibromyalgia: study design for a pilot double-blind, randomized controlled trial.

PubMed

Roman, Pablo; Estévez, Ángeles F; Sánchez-Labraca, Nuria; Cañadas, Fernando; Miras, Alonso; Cardona, Diana

2017-10-24

Fibromyalgia syndrome (FMS) is a chronic, generalized and diffuse pain disorder accompanied by other symptoms such as emotional and cognitive deficits. The FMS patients show a high prevalence of gastrointestinal symptoms. Recently it has been found that microbes in the gut may regulate brain processes through the gut-microbiota-brain axis, modulating thus affection, motivation and higher cognitive functions. Therefore, the use of probiotics might be a new treatment that could improve the physical, psychological and cognitive state in FMS; however, no evidence about this issue is available. This paper describes the design and protocol of a double-blind, placebo-controlled and randomized pilot study. We use validated questionnaires, cognitive task through E-Prime and biological measures like urine cortisol and stool fecal samples. The trial aim is to explore the effects of eight weeks of probiotics therapy in physical (pain, impact of the FMS and quality of life), emotional (depression, and anxiety) and cognitive symptoms (attention, memory, and impulsivity) in FMS patients as compared to placebo. This pilot study is the first, to our knowledge, to evaluate the effects of probiotics in FMS. The primary hypothesis was that FMS patients will show a better performance on cognitive tasks, and an improvement in emotional and physical symptoms. These results will contribute to a better understanding in the gut-brain axis. Here we present the design and protocol of the study.

Effect of Pumpkin Seed Oil on Hair Growth in Men with Androgenetic Alopecia: A Randomized, Double-Blind, Placebo-Controlled Trial

PubMed Central

Jeong, Dong Wook; Choi, Eun Jung; Kim, Yun Jin; Lee, Jeong Gyu; Yi, Yu Hyeon; Cha, Hyeong Soo

2014-01-01

Pumpkin seed oil (PSO) has been shown to block the action of 5-alpha reductase and to have antiandrogenic effects on rats. This randomized, placebo-controlled, double-blind study was designed to investigate the efficacy and tolerability of PSO for treatment of hair growth in male patients with mild to moderate androgenetic alopecia (AGA). 76 male patients with AGA received 400 mg of PSO per day or a placebo for 24 weeks. Change over time in scalp hair growth was evaluated by four outcomes: assessment of standardized clinical photographs by a blinded investigator; patient self-assessment scores; scalp hair thickness; and scalp hair counts. Reports of adverse events were collected throughout the study. After 24 weeks of treatment, self-rated improvement score and self-rated satisfaction scores in the PSO-treated group were higher than in the placebo group (P = 0.013, 0.003). The PSO-treated group had more hair after treatment than at baseline, compared to the placebo group (P < 0.001). Mean hair count increases of 40% were observed in PSO-treated men at 24 weeks, whereas increases of 10% were observed in placebo-treated men (P < 0.001). Adverse effects were not different in the two groups. PMID:24864154

Moclobemide versus fluoxetine in the treatment of major depressive disorder in adults.

PubMed Central

Lapierre, Y D; Joffe, R; McKenna, K; Bland, R; Kennedy, S; Ingram, P; Reesal, R; Rickhi, B G; Beauclair, L; Chouinard, G; Annable, L

1997-01-01

The objective of the present study was to compare the safety and efficacy of moclobemide versus fluoxetine in adult patients with major depressive disorder. The design of the study was a multicenter, double-blind, comparative, and randomized trial. A 1- to 2-week single-blind placebo washout phase was followed by 6 weeks of double-blind treatment with moclobemide or fluoxetine. A total of 150 patients were enrolled in the study. There were 128 patients eligible to be randomized, with 66 patients receiving moclobemide and 62 patients receiving fluoxetine. At the termination of the study, patients in the moclobemide group were receiving a mean dose of 440 mg +/- 123 mg, while the mean dose in the fluoxetine group was 35 mg +/- 8 mg. No significant treatment differences were found for any of the efficacy parameters. Headache and nausea were the most frequently reported adverse events in both treatment groups. Headache and blurred vision were reported significantly more often (P < 0.05) in the fluoxetine group, whereas significantly more dry mouth was reported (P < 0.05) in the moclobemide group. These results provide supporting evidence of the comparable efficacy of moclobemide and fluoxetine and the better tolerability of moclobemide when used in the treatment of major depressive disorder. Images Figure 3 PMID:9074306

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

PubMed Central

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

2015-01-01

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

Long-Term Safety and Efficacy of Fulranumab in Patients With Moderate-to-Severe Osteoarthritis Pain: A Phase II Randomized, Double-Blind, Placebo-Controlled Extension Study.

PubMed

Sanga, Panna; Katz, Nathaniel; Polverejan, Elena; Wang, Steven; Kelly, Kathleen M; Haeussler, Juergen; Thipphawong, John

2017-04-01

To evaluate the long-term safety and efficacy of fulranumab in patients with knee or hip pain caused by moderate-to-severe chronic osteoarthritis (OA). In this phase II double-blind, placebo-controlled extension study, patients who were randomized in equal proportions to receive subcutaneous doses of either placebo or fulranumab (1 mg every 4 weeks, 3 mg every 8 weeks, 3 mg every 4 weeks, 6 mg every 8 weeks, or 10 mg every 8 weeks) in the 12-week double-blind efficacy phase and who completed this double-blind efficacy phase were eligible to continue the dosage throughout a 92-week double-blind extension phase, followed by a 24-week posttreatment follow-up period. Safety assessments included evaluation of treatment-emergent adverse events (TEAEs), pre-identified AEs of interest, and joint replacements. Efficacy assessments included changes from baseline to the end of the double-blind extension phase in scores on the patient's global assessment and the pain and physical function subscales of the Western Ontario and McMaster Universities Osteoarthritis Index. Overall, 401 of the 423 patients who completed the 12-week double-blind efficacy phase entered the extension study. Long-term sustained improvements were observed in all efficacy parameters following fulranumab treatment (1 mg every 4 weeks, 3 mg every 4 weeks, and 10 mg every 8 weeks) as compared with placebo. Similar percentages of patients in both groups experienced TEAEs (88% taking placebo and 91% taking fulranumab; all phases). Across all fulranumab groups, arthralgia (21%) and OA (18%) (e.g., exacerbation of OA pain) were the most common TEAEs. The most common serious TEAEs were the requirement for knee (10%) and hip (7%) arthroplasty, with 80% occurring during the posttreatment follow-up period. Neurologic-related TEAEs (28%; all phases) were generally mild-to-moderate. Overall, 81 joint replacements were performed in 71 patients (8 [11%] receiving placebo and 63 [89%] receiving fulranumab); 15 patients (21%) had rapid progression of OA (RPOA). All cases of RPOA occurred in fulranumab-treated patients who were concurrently receiving nonsteroidal antiinflammatory drugs and occurred in joints with preexisting OA. Long-term treatment with fulranumab was generally well-tolerated and efficacious. RPOA was observed as a safety signal. Future studies are warranted to demonstrate whether the risk of RPOA can be reduced in patients taking fulranumab. © 2016, American College of Rheumatology.

A double-blind comparison of alprazolam, diazepam and placebo in the treatment of anxious out-patients

PubMed Central

Davison, K.; Farquharson, R. G.; Khan, M. C.; Majid, A.

1985-01-01

1 In a double-blind 28-day comparison of alprazolam, diazepam and placebo, alprazolam 1.5-3 mg/day was of equivalent anxiolytic effect to 15-30 mg diazepam/day and there was some evidence of antidepressant activity by alprazolam, but not diazepam, in neurotic depression. No serious side-effects or laboratory abnormalities were encountered. PMID:2859877

Double-blind evaluation of deanol in tardive dyskinesia.

PubMed

Penovich, P; Morgan, J P; Kerzner, B; Karch, F; Goldblatt, D

1978-05-12

We administered deanol acetamidobenzoate, 2.0 g/day for four weeks, a double-blind, placebo-controlled crossover trial, to 14 patients with tardive dyskineasia. The patient population included both inpatients and outpatients. The response was evaluated by subjective clinical impression and scoring of filmed sequences. Patients' conditions improved significantly from baseline scores while receiving both deanol and placebo, but there was no distinction between the two treatments.

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

ERIC Educational Resources Information Center

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

2013-01-01

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

Double-blind randomised clinical trial of a pepsin-inhibitory pentapeptide (pepstatin) in the treatment of duodenal ulcer.

PubMed Central

Bonnevie, O; Svendsen, L B; Holst-Christensen, J; Johansen, T S; Søltoft, J; Christiansen, P M

1979-01-01

In a double-blind randomised clinical trial a specific inhibition of peptic activity with a pentapeptide, pepstatin, had no significant advantage over placebo in the ulcer healing and symptomatology of duodenal ulcer. Thus, the inhibition of pepsin in human gastric juice does not appear to have a major influence on the healing of duodenal ulcer. PMID:385457

Double-Blind Controlled Comparison of Phlebitis Produced by Cephapirin and Cephalothin

PubMed Central

Carrizosa, Jaime; Levison, Matthew E.; Kaye, Donald

1973-01-01

In a double-blind study with each patient as his own control cephapirin and cephalothin were administered to 20 patients in opposite arms for a period of 48 hr each. Neither the incidence of phlebitis nor the degree of phlebitis was significantly different with the two drugs, and there was no difference in the time of onset of pain or phlebitis. PMID:4597719

A Double-Blind, Placebo-Controlled Study of Risperidone for the Treatment of Adolescents and Young Adults with Anorexia Nervosa: A Pilot Study

ERIC Educational Resources Information Center

Hagman, Jennifer; Gralla, Jane; Sigel, Eric; Ellert, Swan; Dodge, Mindy; Gardner, Rick; O'Lonergan, Teri; Frank, Guido; Wamboldt, Marianne Z.

2011-01-01

Objective: The purpose of this double-blind, placebo-controlled exploratory pilot study was to evaluate the safety and efficacy of risperidone for the treatment of anorexia nervosa. Method: Forty female subjects 12 to 21 years of age (mean, 16 years) with primary anorexia nervosa in an eating disorders program were randomized to receive…

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

ERIC Educational Resources Information Center

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

2006-01-01

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

Translating Expertise into Effective Instruction: The Impacts of Cognitive Task Analysis (CTA) on Lab Report Quality and Student Retention in the Biological Sciences

ERIC Educational Resources Information Center

Feldon, David F.; Timmerman, Briana Crotwell; Stowe, Kirk A.; Showman, Richard

2010-01-01

Poor instruction has been cited as a primary cause of attrition from STEM majors and a major obstacle to learning for those who stay [Seymour and Hewitt [1997]. Talking about leaving: Why undergraduates leave the sciences. Boulder, CO: Westview]. Using a double-blind design, this study tests the hypothesis that the lack of explicit instructions in…

The effect of Camphor-Crataegus berry extract combination on blood pressure and mental functions in chronic hypotension--a randomized placebo controlled double blind design.

PubMed

Schandry, Rainer; Duschek, Stefan

2008-11-01

A number of studies have provided evidence for reduced cognitive performance due to chronically low blood pressure. The present studies explored whether these deficits can be reduced by pharmacological blood pressure elevation. Effects of the Camphor-Crataegus berry extract combination (Korodin(®)) were investigated in two studies with 40 and 48 hypotensive women based on a randomized, placebo controlled double blind design. The participants were presented with different tasks assessing performance in attention and cognition. Blood pressure was measured repeatedly during the experiment. The administration of the drug led to positive and differential effects on blood pressure and cognitive performance as compared to placebo. These effects were already visible within the time range of 2-5 min. A positive correlation between blood pressure increase and performance enhancement could be demonstrated for two of the four tasks. The results show that the application of Korodin(®) results in beneficial effects on resting blood pressure and cognitive performance. The positive association between the increase in blood pressure and cognitive enhancement suggests that blood pressure plays a causal role in the cognitive deficits in hypotension and underlines that they can be reduced through antihypotensive treatment.

Safety and efficacy of new glyceryl trinitrate suppository formula: first double blind placebo-controlled clinical trial.

PubMed

Emami, M H; Sayedyahossein, S; Aslani, A

2008-07-01

This study was designed to assess the safety and efficacy of 0.2 percent glyceryl trinitrate suppository form in the healing of chronic anal fissure. Thirty-four patients with symptomatic chronic anal fissures were assigned to 0.2 percent glyceryl trinitrate suppository (n = 21) or placebo (n = 13) in a double blind design. Patient's symptom scores were registered at first visit. A validated daily chart was given to assess their symptoms on a daily basis. Both groups received psyllium from the beginning of the study. They were assessed at two-week intervals for six weeks. Then, they started a washout period of one month and after that were crossed over for another six weeks. Chi-squared, t-tests, and analysis of variance were used for statistical analysis. Complete healing at six weeks was achieved in 12 of 21 patients (57 percent) in the glyceryl trinitrate group and 5 of 13 patients (38 percent) in the placebo (P < 0.05). The overall healing rates at the end of study were 15 of 21 (71 percent) vs. 11 of 13 (84 percent) in the glyceryl trinitrate and placebo groups, respectively (P > 0.05). Application of 0.2 percent glyceryl trinitrate suppository form represents a new, promising, and effective treatment for chronic anal fissure.

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

PubMed

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

2010-06-01

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

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

PubMed Central

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

2010-01-01

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

Aripiprazole long-acting injectable formulations for schizophrenia: aripiprazole monohydrate and aripiprazole lauroxil.

PubMed

Citrome, Leslie

2016-01-01

Aripiprazole monohydrate (AM) and aripiprazole lauroxil (AL) are two different long-acting injectable formulations of aripiprazole. AM 400 mg administered once monthly demonstrated efficacy in an acute, double-blind, placebo-controlled, randomized clinical trial, as well as in a double-blind, placebo-controlled, randomized-withdrawal maintenance study, and in two non-inferiority maintenance studies. AL is a prodrug of aripiprazole and available in 441 mg, 662 mg or 882 mg strengths. AL 441 mg and 882 mg administered once monthly demonstrated efficacy in an acute, double-blind, placebo-controlled, randomized clinical trial. The pharmacokinetic profile of AL also led to approval of dosing intervals of every 6 weeks for the 882 mg dose. The overall tolerability profiles of both products are consistent with what is known about oral aripiprazole.

Chorionic gonadotropin in weight control. A double-blind crossover study.

PubMed

Young, R L; Fuchs, R J; Woltjen, M J

1976-11-29

Two hundred two patients participated in a double-blind random cross-over study of the effectiveness of human chorionic gonadotropin (HCG) vs placebo in a wieght reduction program. Serial measurements were made of weight, skin-fold thickness, dropout rates, reasons for dropping out, and patient subjective response. There was no statistically significant difference between those receiving HCG vs placebo during any phase of this study (P greater than .1).

Omega 3/6 Fatty Acids for Reading in Children: A Randomized, Double-Blind, Placebo-Controlled Trial in 9-Year-Old Mainstream Schoolchildren in Sweden

ERIC Educational Resources Information Center

Johnson, Mats; Fransson, Gunnar; Östlund, Sven; Areskoug, Björn; Gillberg, Christopher

2017-01-01

Background: Previous research has shown positive effects of Omega 3/6 fatty acids in children with inattention and reading difficulties. We aimed to investigate if Omega 3/6 improved reading ability in mainstream schoolchildren. Methods: We performed a 3-month parallel, randomized, double-blind, placebo-controlled trial followed by 3-month active…

A Double-Blind, Placebo-Controlled Trial of Dexmethylphenidate Hydrochloride and D,l-Threo-Methylphenidate Hydrochloride in Children with Attention-Deficit-Hyperactivity Disorder

ERIC Educational Resources Information Center

Wigal, Sharon; Swanson, James M.; Feifel, David; Sangal, R. Bart; Elia, Josephine; Casat, Charles D.; Zeldis, Jerome B.; Conners, C. Keith

2004-01-01

Objective: To evaluate the efficacy and safety of dexmethylphenidate hydrochloride (d-MPH, Focalin[TM]) for the treatment of attention-deficit/hyperactivity disorder (ADHD) and to test an a priori hypothesis that d-MPH would have a longer duration of action than d,l-threo-methylphenidate (d,l-MPH). Method: This was a randomized, double-blind study…

Double-Blind Comparison of Phlebitis Produced by Cephalothin Infusions with Buffered and Unbuffered Diluents

PubMed Central

Carrizosa, Jaime; Levison, Matthew E.; Kaye, Donald

1974-01-01

In a double-blind study with each patient as his own control, a buffered and an unbuffered cephalothin solution was administered to 13 patients in opposite arms for a period of 48 h each. Neither the incidence of phlebitis nor the degree of phlebitis was different with the two diluents, and there was no difference in the time of onset of phlebitis. PMID:4840431

Supplementation with 1000 IU vitamin D/d leads to parathyroid hormone suppression, but not increased fractional calcium absorption, in 4-8-y-old children: A double-blind randomized controlled trial

USDA-ARS?s Scientific Manuscript database

The effects of vitamin D supplementation in healthy prepubertal children on physiologic outcomes have not been investigated. The objective was to evaluate the effects of supplementation with 1000 IU vitamin D(3)/d on calcium absorption. In a double-blind, placebo-controlled trial, we randomly assign...

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

ERIC Educational Resources Information Center

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

2012-01-01

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

100 positive double-blind studies: enough or too little?

NASA Astrophysics Data System (ADS)

Tuner, Jan; Hode, Lars

2000-06-01

A major argument among the opponents of laser therapy has been the absence of scientific documentation. This was a valid position in the 80s and partly in the 90s. But today, is this still a sound argument. There are more than 2,000 published studies in the field, including meeting abstracts and anecdotal reports. The vast majority of these papers reports positive effects of LLLT in vitro and in vivo. It is fair to argue that negative results are less prone to be published, but certainly more than 80 percent of the published studies are positive. In the field of dentistry, for instance, the positive percentage is well above 90 percent. The present literature study will look at the heart of the positive documentation: the positive double blind studies. It may come as a surprise to many critics that there are more than 100 positive double blind studies in the field laser therapy. This is a god base for a further understanding of the effects of low level laser in the clinical setting. We must, however, be as critical as the sceptics themselves in order to obtain a constructive dialogue between 'attorneys' and sceptics. In this paper, a critical review of 100 positive double blind studies will be presented.

Uniform magnetic fields and double-wrapped coil systems: improved techniques for the design of bioelectromagnetic experiments.

PubMed

Kirschvink, J L

1992-01-01

A common mistake in biomagnetic experimentation is the assumption that Helmholtz coils provide uniform magnetic fields; this is true only for a limited volume at their center. Substantial improvements on this design have been made during the past 140 years with systems of three, four, and five coils. Numerical comparisons of the field uniformity generated by these designs are made here, along with a table of construction details and recommendations for their use in experiments in which large volumes of uniform intensity magnetic exposures are needed. Double-wrapping, or systems of bifilar windings, can also help control for the non-magnetic effects of the electric coils used in many experiments. In this design, each coil is wrapped in parallel with two separate, adjacent strands of copper wire, rather than the single strand used normally. If currents are flowing in antiparallel directions, the magnetic fields generated by each strand will cancel and yield virtually no external magnetic field, whereas parallel currents will yield an external field. Both cases will produce similar non-magnetic effects of ohmic heating, and simple measures can reduce the small vibration and electric field differences. Control experiments can then be designed such that the only major difference between treated and untreated groups is the presence or absence of the magnetic field. Double-wrapped coils also facilitate the use of truly double-blind protocol, as the same apparatus can be used either for experimental or control groups.

Dexpanthenol (Ro 01-4709) in the treatment of constipation.

PubMed

Hanck, A B; Goffin, H

1982-01-01

Functional constipation is not a life-threatening disease, but as a chronic state it worries the patient and causes him discomfort and often leads him to self-medication with potentially dangerous drugs. Ro 01-4709 contains as active substance dexpanthenol, which is the alcohol of pantothenic acid, a vitamin of the B-complex. In the cells, dexpanthenol is readily oxidized to pantothenic acid, which stimulates peristalsis when administered in therapeutically effective doses. Ro 01-4709 has already proven its efficacy in the prevention and treatment of adynamic ileus. Recently, several open and two double-blind studies have been carried out, investigating the efficacy of oral Ro 01-4709 in the treatment of chronic functional constipation. The two double-blind studies showed Ro 01-4709 to be superior to placebo in all parameters measured. The studies with an open design also demonstrated a favourable effect of Ro 01-4709 in the treatment of chronic functional constipation. Owing to its physiological action-which is in a favourable contrast to that of normal laxatives. Ro 01-4709 can be recommended for the treatment of functional constipation in pregnant women, children and the elderly.

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

Moisturizers are effective in the treatment of xerosis irrespectively from their particular formulation: results from a prospective, randomized, double-blind controlled trial.

PubMed

Shim, J H; Park, J H; Lee, J H; Lee, D Y; Lee, J H; Yang, J M

2016-02-01

Many companies claim that their moisturizers are superior to others based on their ingredients. To compare the efficacy and safety of the most popular moisturizers in the field. A randomized, double-blind, controlled study was performed on 80 patients with moderate to severe xerosis. The test agents included the newly developed cream containing topical recombinant human epidermal growth factor (EGF), its vehicle without EGF and four additional therapeutic moisturizers. The study subjects applied the test agents on designated skin areas twice daily for 4 weeks. All of the clinical assessments and non-invasive objective measurements were performed at baseline, and on days 14 and 28 of the study. All of the test agents significantly improved the clinical symptoms of xerosis. The biophysical parameters similarly improved from baseline (P < 0.05). None of the test agents performed significantly better than did another. In the treatment of xerosis, consistent and regular moisturizer use is much more important than the moisturizer's particular formulation. © 2015 European Academy of Dermatology and Venereology.

The efficacy of intra-articularly administered MYC 2095, triamcinolone hexacetonide and placebo in gonarthritis. A combined double-blind clinical trial.

PubMed

Cats, A; van IJzerloo, J A; Davinova, Y; Werthauer-Rodrigues Pereira, M; Blakemore, C B; Steiner, F J

1979-01-01

We report the results of a double-blind three-centre study, employing a cross-over design, set up to compare the efficacy of intra-articular injections of Myc 2095 (20 mg), triamcinolone hexacetonide (Lederspan) (20 mg) and placebo in 40 patients with synovitis of the knee joint. Each patient included in the study contributed data on 2 of the 3 treatment variables being compared. Seven clinical parameters were assessed every 6 weeks, while the doctor's and the patient's assessments were scored. Intra articular treatment both with Myc 2095 and triamcinolone hexacetonide proved to be effective. Placebo response was also very high. After the first Myc 2095 injection, improvement in "tenderness", "pain under load" and "swelling and hydrops" was significantly superior to that following placebo treatment. The evaluation of the second injections indicated a marked carry-over effect from the first course. This was also evident from the doctor's and patient's assessments. The importance of including a placebo in the evaluation of anti-phlogistic drugs in clinical trials, emerged from this study.

The Methodology of Clinical Studies Used by the FDA for Approval of High-Risk Orthopaedic Devices.

PubMed

Barker, Jordan P; Simon, Stephen D; Dubin, Jonathan

2017-05-03

The purpose of this investigation was to examine the methodology of clinical trials used by the U.S. Food and Drug Administration (FDA) to determine the safety and effectiveness of high-risk orthopaedic devices approved between 2001 and 2015. Utilizing the FDA's online public database, this systematic review audited study design and methodological variables intended to minimize bias and confounding. An additional analysis of blinding as well as the Checklist to Evaluate a Report of a Nonpharmacological Trial (CLEAR NPT) was applied to the randomized controlled trials (RCTs). Of the 49 studies, 46 (94%) were prospective and 37 (76%) were randomized. Forty-seven (96%) of the studies were controlled in some form. Of 35 studies that reported it, blinding was utilized in 21 (60%), of which 8 (38%) were reported as single-blinded and 13 (62%) were reported as double-blinded. Of the 37 RCTs, outcome assessors were clearly blinded in 6 (16%), whereas 15 (41%) were deemed impossible to blind as implants could be readily discerned on imaging. When the CLEAR NPT was applied to the 37 RCTs, >70% of studies were deemed "unclear" in describing generation of allocation sequences, treatment allocation concealment, and adequate blinding of participants and outcome assessors. This study manifests the highly variable reporting and strength of clinical research methodology accepted by the FDA to approve high-risk orthopaedic devices.

A Double-Blind, Randomized, Placebo-Controlled Trial of Divalproex Extended-Release in the Treatment of Bipolar Disorder in Children and Adolescents

ERIC Educational Resources Information Center

Wagner, Karen Dineen; Redden, Laura; Kowatch, Robert A.; Wilens, Timothy E.; Segal, Scott; Chang, Kiki; Wozniak, Patricia; Vigna, Namita V.; Abi-Saab, Walid; Saltarelli, Mario

2009-01-01

A double-blind study that involves 150 patients aged 10-17 on the effect of divalproex extended-release in the treatment of bipolar disorder shows that the drug was similar to placebo based on adverse events and that no treatment effect was observed in the drug. The drug is not suitable for treatment of youths with bipolar I disorder, mixed or…

A Double Blind Trial of Divalproex Sodium for Affective Liability and Alcohol Use Following Traumatic Brain Injury

DTIC Science & Technology

2014-10-01

approved it in 1995 for this indication. Also, it is used in conjunction with lithium or carbamazepine to prevent recurrent manic or depressive...TITLE: A Double Blind Trial of Divalproex Sodium for Affective L ability and Alcohol Use Following Traumatic Brain Injury PRINCIPAL...NUMBER Liability and Alcohol Use Following Traumatic Brain Injury 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d

A Double Blind Trial of Divalproex Sodium for Affective Lability and Alcohol Use Following Traumatic Brain Injury

DTIC Science & Technology

2009-10-01

SUBJECT TERMS Traumatic Brain Injury, Alcohol Use , Mood , Mood Stabilization 16. SECURITY CLASSIFICATION OF: U 17. LIMITATION OF ABSTRACT 18...1995 for this indication. Also, it is used in conjunction with lithium or carbamazepine to prevent recurrent manic or depressive episodes during long...0652 TITLE: A Double Blind Trial of Divalproex Sodium for Affective Lability and Alcohol Use Following Traumatic Brain Injury PRINCIPAL

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

ERIC Educational Resources Information Center

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

2016-01-01

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

Treatment of early-onset schizophrenia spectrum disorders (TEOSS): rationale, design, and methods.

PubMed

McClellan, Jon; Sikich, Linmarie; Findling, Robert L; Frazier, Jean A; Vitiello, Benedetto; Hlastala, Stefanie A; Williams, Emily; Ambler, Denisse; Hunt-Harrison, Tyehimba; Maloney, Ann E; Ritz, Louise; Anderson, Robert; Hamer, Robert M; Lieberman, Jeffrey A

2007-08-01

The Treatment of Early Onset Schizophrenia Spectrum Disorders Study is a publicly funded clinical trial designed to compare the therapeutic benefits, safety, and tolerability of risperidone, olanzapine, and molindone in youths with early-onset schizophrenia spectrum disorders. The rationale, design, and methods of the Treatment of Early Onset Schizophrenia Spectrum Disorders Study are described. Using a randomized, double-blind, parallel-group design at four sites, youths with EOSS (ages 8-19 years) were assigned to an 8-week acute trial of risperidone (0.5-6.0 mg/day), olanzapine (2.5-20 mg/day), or molindone (10-140 mg/day). Responders continued double-blind treatment for 44 weeks. The primary outcome measure was responder status at 8 weeks, defined by a 20% reduction in baseline Positive and Negative Symptom Scale scores plus ratings of significant improvement on the Clinical Global Impressions. Secondary outcome measures included assessments of psychopathology, functional impairment, quality of life, and medication safety. An intent-to-treat analytic plan was used. From February 2002 to May 2006, 476 youths were screened, 173 were further evaluated, and 119 were randomized. Several significant study modifications were required to address safety, the use of adjunctive medications, and the termination of the olanzapine treatment arm due to weight gain. The Treatment of Early Onset Schizophrenia Spectrum Disorders Study will inform clinical practice regarding the use of antipsychotic medications for youths with early-onset schizophrenia spectrum disorders. Important safety concerns emerged during the study, including higher than anticipated rates of suicidality and problems tapering thymoleptic agents before randomization.

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

PubMed

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

2016-03-01

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

Oral challenge test with sodium metabisulfite in steroid-dependent asthmatic patients.

PubMed

Prieto, L; Juyol, M; Paricio, A; Martínez, M A; Palop, J; Castro, J

1988-01-01

Oral challenge tests were carried out with sodium metabisulfite solution doses of 0.5, 1, 10, 25, 50 mg and encapsulated doses of 100 and 200 mg, as well as with lactose-placebo, on 44 non-atopic patients with steroid-dependent bronchial asthma, without clinical evidence of intolerance to these agents. Only those patients with an acceptable and not very labile pulmonary function were tested. A single-blind challenge protocol was performed in 22 patients (sodium metabisulfite solutions at pH 2.2 to 2.6) and the positive responses were confirmed by double-blind challenge. The other 22 were tested directly in a double-blind manner (pH4). Initially, 6/44 presented a positive reaction. However, a careful analysis and the confirmation by double-blind challenge of the positive responses obtained with the single-blind test, allowed us to identify 4 false positive responses. Thus, the true prevalence of sulfite sensitivity in our population is 4.5%. A patient with intolerance to sulfite agents also suffered aspirin-induced asthma. The labile tendency of the pulmonary function of the asthmatic patients may have contributed to some false positive reactions and probably explain the very high prevalence found in some studies. It does not appear that the variations of pH decisively influence the result of the challenge test.

Rationale and design of a double-blind, placebo-controlled, randomized trial to evaluate the safety and efficacy of nimodipine in preventing cognitive impairment in ischemic cerebrovascular events (NICE)

PubMed Central

2012-01-01

Background Stroke is the second most common cause of mortality and the leading cause of neurological disability, cognitive impairment and dementia worldwide. Nimodipine is a dihydropyridinic calcium antagonist with a role in neuroprotection, making it a promising therapy for vascular cognitive impairment and dementia. Methods/design The NICE study is a multicenter, randomized, double-blind, placebo-controlled study being carried out in 23 centers in China. The study population includes patients aged 30–80 who have suffered an ischemic stroke (≤7 days). Participants are randomly allocated to nimodipine (90 mg/d) or placebo (90 mg/d). The primary efficacy is to evaluate the level of mild cognitive impairment following treatment of an ischemic stroke with nimodipine or placebo for 6 months. Safety is being assessed by observing side effects of nimodipine. Assuming a relative risk reduction of 22%, at least 656 patients are required in this study to obtain statistical power of 90%. The first patient was recruited in November 2010. Discussion Previous studies suggested that nimodipine could improve cognitive function in vascular dementia and Alzheimer’s disease dementia. It is unclear that at which time-point intervention with nimodipine should occur. Therefore, the NICE study is designed to evaluate the benefits and safety of nimodipine, which was adminstered within seven days, in preventing/treating mild cognitive impairment following ischemic stroke. PMID:22950711

Methylphenidate and emotional-motivational processing in attention-deficit/hyperactivity disorder.

PubMed

Conzelmann, Annette; Woidich, Eva; Mucha, Ronald F; Weyers, Peter; Müller, Mathias; Lesch, Klaus-Peter; Jacob, Christian P; Pauli, Paul

2016-08-01

In line with the assumption that emotional-motivational deficits are one core dysfunction in ADHD, in one of our previous studies we observed a reduced reactivity towards pleasant pictures in adult ADHD patients as compared to controls. This was indicated by a lack of attenuation of the startle reflex specifically during pleasant pictures in ADHD patients. The first choice medical agents in ADHD, methylphenidate (MPH), is discussed to normalize these dysfunctions. However, experimental evidence in the sense of double-blind placebo-controlled study designs is lacking. Therefore, we investigated 61 adult ADHD patients twice, one time with placebo and one time with MPH with the same experimental design as in our study previously and assessed emotion processing during the presentation of pleasant, neutral and unpleasant pictures. We obtained startle reflex data as well as valence and arousal ratings in association with the pictures. As previously shown, ADHD patients showed a diminished startle attenuation during pleasant pictures while startle potentiation during unpleasant pictures was normal. Valence and arousal ratings unsuspiciously increased with increasing pleasantness and arousal of the pictures, respectively. There were no significant influences of MPH. The study replicates that ADHD patients show a reduced reactivity towards pleasant stimuli. MPH did not normalize this dysfunction. Possibly, MPH only influences emotions during more complex behavioural tasks that involve executive functions in adults with ADHD. Our results emphasize the importance for the use of double-blind placebo-controlled designs in psychopharmacological research.

Long-term effects of vitamin D supplementation in vitamin D deficient obese children participating in an integrated weight-loss programme (a double-blind placebo-controlled study) - rationale for the study design.

PubMed

Szlagatys-Sidorkiewicz, Agnieszka; Brzeziński, Michał; Jankowska, Agnieszka; Metelska, Paulina; Słomińska-Frączek, Magdalena; Socha, Piotr

2017-04-04

Obesity is associated not only with an array of metabolic disorders (e.g. insulin resistance, hiperinsulinemia, impaired tolerance of glucose, lipid disorders) but also skeletal and joint abnormalities. Recently, a pleiotropic role of vitamin D has been emphasized. Obese children frequently present with vitamin D deficiency, and greater fat mass is associated with lower serum concentration of this vitamin. Although some evidence suggests that weight loss may affect vitamin D status, this issue has not been studied extensively thus far. The aim of a double-blind placebo-controlled study is to assess long-term health effects of vitamin D supplementation in vitamin D deficient obese children participating in an integrated weight-loss programme. A randomized double-blind, placebo-controlled trial analysing the effects of vitamin D3 supplementation in overweight or obese vitamin D deficient (<30 ng/ml) children participating in an integrated weight-loss programme. Children are randomized to receive either vitamin D (1200 IU) or placebo for 26 weeks. Primary endpoints include changes in BMI (body mass index), body composition and bone mineral density at the end of the study period, and secondary endpoints - the changes in laboratory parameter reflecting liver and kidney function (transaminases, creatinine) and glucose homeostasis (glucose and insulin levels during oral glucose tolerance test). The effects of vitamin D supplementation in obese individuals, especially children, subjected to a weight-loss program are still poorly understood. Considering physiological processes associated with puberty and adolescent growth, we speculate that supplementation may enhance weight reduction and prevent bone loss in obese children deficient in this vitamin. NCT 02828228 ; Trial registration date: 8 Jun 2016; Registered in: ClinicalTrials.gov. The trial was registered retrospectively.

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

PubMed Central

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

2007-01-01

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

Polyethylene glycol 3350 plus electrolytes for chronic constipation in children: a double blind, placebo controlled, crossover study

PubMed Central

Thomson, M A; Jenkins, H R; Bisset, W M; Heuschkel, R; Kalra, D S; Green, M R; Wilson, D C; Geraint, M

2007-01-01

Objectives To assess the efficacy and safety of polyethylene glycol 3350 plus electrolytes (PEG+E) for the treatment of chronic constipation in children. Design Randomised, double blind, placebo controlled crossover trial, with two 2‐week treatment periods separated by a 2‐week placebo washout. Setting Six UK paediatric departments. Participants 51 children (29 girls, 22 boys) aged 24 months to 11 years with chronic constipation (lasting ⩾3 months), defined as ⩽2 complete bowel movements per week and one of the following: pain on defaecation on 25% of days; ⩾25% of bowel movements with straining; ⩾25% of bowel movements with hard/lumpy stools. 47 children completed the double blind treatment. Main outcome measures Number of complete defaecations per week (primary efficacy variable), total number of complete and incomplete defaecations per week, pain on defaecation, straining on defaecation, faecal incontinence, stool consistency, global assessment of treatment, adverse events and physical examination. Results The mean number of complete defaecations per week was significantly higher for children on PEG+E than on placebo (3.12 (SD 2.05) v 1.45 (SD 1.20), respectively; p<0.001). Further significant differences in favour of PEG+E were observed for total number of defaecations per week (p = 0.003), pain on defaecation (p = 0.041), straining on defaecation (p<0.001), stool consistency (p<0.001) and percentage of hard stools (p = 0.001). Treatment related adverse events (all mild or moderate) occurred in similar numbers of children on PEG+E (41%) and placebo during treatment (45%). Conclusions PEG+E is significantly more effective than placebo, and appears to be safe and well tolerated in the treatment of chronic constipation in children. PMID:17626140

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

PubMed

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

2005-05-01

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

Better early functional outcome after short stem total hip arthroplasty? A prospective blinded randomised controlled multicentre trial comparing the Collum Femoris Preserving stem with a Zweymuller straight cementless stem total hip replacement for the treatment of primary osteoarthritis of the hip

PubMed Central

van Oldenrijk, Jakob; Scholtes, Vanessa A B; van Beers, Loes W A H; Geerdink, Carel H; Niers, Bob B A M; Runne, Wouter; Bhandari, Mohit; Poolman, Rudolf W

2017-01-01

Objectives Primary aim was to compare the functional results at 3 months and 2 years between short and conventional cementless stem total hip arthroplasty (THA). Secondary aim was to determine the feasibility of a double-blind implant-related trial. Design A prospective blinded randomised controlled multicentre trial in patients with osteoarthritis of the hip. All patients, research assistants, clinical assessors, investigators and data analysts were blinded to the type of prosthesis. Population: 150 patients between 18 and 70 years with osteoarthritis of the hip, 75 in the short stem and 75 in the conventional stem group. Mean age: 60 years (SD 7). Interventions: the Collum Femoris Preserving short stem versus the Zweymuller Alloclassic conventional stem. Main outcome measures The Dutch version of the Hip Disability and Osteoarthritis Outcome Score (HOOS). Secondary outcomes measures: Harris Hip Score, the Physical Component Scale of the SF12, the Timed Up and Go test, Pain and the EQ-5D. Feasibility outcomes: continued blinding, protocol adherence and follow-up success rate. Results No significant difference between the two groups. Mean HOOS total score in the short stem group increased 32.7 points from 36.6 (95% CI 32.9 to 40.2) preoperatively to 69.3 (95% CI 66.4 to 72.1) at 3 months follow-up. Mean HOOS total score in the conventional straight stem group increased 36.3 points from 37.1 (95% CI 33.9 to 40.3) preoperatively to 73.4 (95% CI 70.3 to 76.4) at 3 months follow-up. 91.2% of patients remained blinded at 2 years follow-up. Both protocol adherence and follow-up success rate were 98%. Conclusions Functional result at 3 months and 2 years after short stem THA is not superior to conventional cementless THA. There were more perioperative and postoperative complications in the short stem group. Direct comparison of two hip implants in a double-blinded randomised controlled trial is feasible. Trial registration number NTR1560. PMID:29042371

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

PubMed Central

Thase, Michael E.

2010-01-01

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

Health benefit for the child and promotion of the common good were the two most important reasons for participation in the FinIP vaccine trial.

PubMed

Nieminen, Heta; Syrjänen, Ritva K; Puumalainen, Taneli; Sirén, Päivi; Palmu, Arto A

2015-07-17

The Finnish Invasive Pneumococcal disease (FinIP) vaccine trial was a nationwide cluster-randomised double-blind trial designed to demonstrate the effectiveness of pneumococcal conjugate vaccine in vaccinated children and indirect effects in unvaccinated populations. Together with the parallel carriage/AOM trial, over 47,000 children were enrolled, 52% of the initial target. We conducted a questionnaire study to find out which factors affected parents' decision on their child's study participation. A questionnaire designed to evaluate parents' attitudes to vaccine trial participation in general and the FinIP trial in particular was mailed after the trial enrolment period had ended to parents of randomly selected children: 1484 who participated in the trial and 1485 who did not participate. Altogether 1438 parents (48%) responded to the questionnaire. The response rate was higher among FinIP participants (65%, 965/1484) than among FinIP non-participants (32%, 473/1485). The two most important reasons for giving consent to the FinIP trial were the potential benefit of immunisation against pneumococcal diseases (75% of consenters) and the promotion of the common good and public health (11%). The reasons reported as most important for declining consent were suspicions of vaccine safety (36%) and the double-blind trial design (12%). Up to 65% of the non-consenters declared that drug and vaccine trials should not be conducted in children at all. The expected health benefit for the child was by far the most important reason for consenting to the vaccine trial. Safety concern was the main reason for decline. Importance and necessity of clinical drug and vaccine trials among children and the rationale of the blinded studies should be thoroughly explained to the public. This may increase participation in future vaccine trials. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

PubMed

Hunt, Sheena; Stebbings, Simon; McNamara, Debra

2016-10-28

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

Long-term efficacy and safety of a combination of sabal and urtica extract for lower urinary tract symptoms--a placebo-controlled, double-blind, multicenter trial.

PubMed

Lopatkin, N; Sivkov, A; Walther, C; Schläfke, S; Medvedev, A; Avdeichuk, J; Golubev, G; Melnik, K; Elenberger, N; Engelmann, U

2005-06-01

The efficacy and tolerability of a fixed combination of 160 mg sabal fruit extract WS 1473 and 120 mg urtica root extract WS 1031 per capsule (PRO 160/120) was investigated in elderly, male patients suffering from lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia in a prospective multicenter trial. A total of 257 patients (129 and 128, respectively) were randomized to treatment with PRO 160/120 or placebo (127 and 126 were evaluable for efficacy). Following a single-blind placebo run-in phase of 2 weeks, the patients received 2 x 1 capsule/day of the study medication under double-blind conditions over a period of 24 weeks. Double-blind treatment was followed by an open control period of 24 weeks during which all patients were administered PRO 160/120. Outcome measures for treatment efficacy included the assessment of the patients' LUTS by means of the I-PSS self-rating questionnaire and a quality of life index as well as uroflow and sonographic parameters. Using the International Prostate Symptom Score (I-PSS), patients treated with PRO 160/120 exhibited a substantially higher total score reduction after 24 weeks of double-blind treatment than patients of the placebo group (6 points vs 4 points; P=0.003, one tailed) with a tendency in the same direction after 16 weeks. This applied to obstructive as well as to irritative symptoms, and to patients with moderate or severe symptoms at baseline. Patients randomized to placebo showed a marked improvement in LUTS (as measured by the I-PSS) after being switched to PRO 160/120 during the control period (P=0.01, one tailed, in comparison to those who had been treated with PRO 160/120 in the double-blind phase). The tolerability of PRO 160/120 was comparable to the placebo. In conclusion, PRO 160/120 was clearly superior to the placebo for the amelioration of LUTS as measured by the I-PSS. PRO 160/120 is advantageous in obstructive and irritative urinary symptoms and in patients with moderate and severe symptoms. The tolerability of the herbal extract was excellent.

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).

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

PubMed

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

2012-01-01

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

Feasibility randomised multicentre, double-blind, double-dummy controlled trial of anakinra, an interleukin-1 receptor antagonist versus intramuscular methylprednisolone for acute gout attacks in patients with chronic kidney disease (ASGARD): protocol study.

PubMed

Balasubramaniam, Gowrie; Parker, Trisha; Turner, David; Parker, Mike; Scales, Jonathan; Harnett, Patrick; Harrison, Michael; Ahmed, Khalid; Bhagat, Sweta; Marianayagam, Thiraupathy; Pitzalis, Costantino; Mallen, Christian; Roddy, Edward; Almond, Mike; Dasgupta, Bhaskar

2017-09-05

Acute gout occurs in people with chronic kidney disease, who are commonly older people with comorbidities such as hypertension, heart disease and diabetes. Potentially harmful treatments are administered to these vulnerable patients due to a lack of clear evidence. Newly available treatment that targets a key inflammatory pathway in acute gout attacks provides an opportunity to undertake the first-ever trial specifically looking treating people with kidney disease. This paper describes the protocol for a feasibility randomised controlled trial (RCT) comparing anakinra, a novel interleukin-1 antagonist versus steroids in people with chronic kidney disease (ASGARD). ASGARD is a two-parallel group double-blind, double-dummy multicentre RCT comparing anakinra 100 mg, an interleukin-1 antagonist, subcutaneous for 5 days against intramuscular methylprednisolone 120 mg. The primary objective is to assess the feasibility of the trial design and procedures for a definitive RCT. The specific aims are: (1) test recruitment and retention rates and willingness to be randomised; (2) test eligibility criteria; (3) collect and analyse outcome data to inform sample and power calculations for a trial of efficacy; (4) collect economic data to inform a future economic evaluation estimating costs of treatment and (5) assess capacity of the project to scale up to a national multicentre trial. We will also gather qualitative insights from participants. It aims to recruit 32 patients with a 1:1 randomisation. Information from this feasibility study will help design a definitive trial and provide general information in designing acute gout studies. The London-Central Ethics Committee approved the protocol. The results will be disseminated in peer-reviewed journals and at scientific conferences. EudraCT No. 2015-001787-19, NCT/Clinicalstrials.gov No. NCT02578394, pre-results, WHO Universal Trials Reference No. U1111-1175-1977. NIHR Grant PB-PG-0614-34090. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Therapeutic advances in multiple system atrophy and progressive supranuclear palsy.

PubMed

Poewe, Werner; Mahlknecht, Philipp; Krismer, Florian

2015-09-15

Multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) are relentlessly progressive neurodegenerative diseases leading to severe disability and ultimately death within less than 10 y. Despite increasing efforts in basic and clinical research, effective therapies for these atypical parkinsonian disorders are lacking. Although earlier small clinical studies in MSA and PSP mainly focused on symptomatic treatment, advances in the understanding of the molecular underpinnings of these diseases and in the search for biomarkers have paved the way for the first large and well-designed clinical trials aiming at disease modification. Targets of intervention in these trials have included α-synuclein inclusion pathology in the case of MSA and tau-related mechanisms in PSP. Since 2013, four large randomized, placebo-controlled, double-blind disease-modification trials have been completed and published, using rasagiline (MSA), rifampicin (MSA), tideglusib (PSP), or davunetide (PSP). All of these failed to demonstrate signal efficacy with regard to the primary outcome measures. In addition, two randomized, placebo-controlled, double-blind trials have studied the efficacy of droxidopa in the symptomatic treatment of neurogenic orthostatic hypotension, including patients with MSA, with positive results in one trial. This review summarizes the design and the outcomes of these and other smaller trials published since 2013 and attempts to highlight priority areas of future therapeutic research in MSA and PSP. © 2015 International Parkinson and Movement Disorder Society. © 2015 International Parkinson and Movement Disorder Society.

Ascending Single-Dose, Double-Blind, Placebo-Controlled Safety Study of Noribogaine in Opioid-Dependent Patients.

PubMed

Glue, Paul; Cape, Gavin; Tunnicliff, Donna; Lockhart, Michelle; Lam, Fred; Hung, Noelyn; Hung, C Tak; Harland, Sarah; Devane, Jane; Crockett, R S; Howes, John; Darpo, Borje; Zhou, Meijian; Weis, Holger; Friedhoff, Lawrence

2016-11-01

Ibogaine is a psychoactive substance that may reduce opioid withdrawal symptoms. This was the first clinical trial of noribogaine, ibogaine's active metabolite, in patients established on methadone opioid substitution therapy (OST). In this randomized, double-blind, placebo-controlled single ascending-dose study, we evaluated the safety, tolerability, and pharmacokinetics of noribogaine in 27 patients seeking to discontinue methadone OST who had been switched to morphine during the previous week. Noribogaine doses were 60, 120, or 180 mg (n = 6/dose level) or matching placebo (n = 3/dose level). Noribogaine was well tolerated. The most frequent treatment-emergent adverse events were noneuphoric changes in light perception ∼1 hour postdose, headache, and nausea. Noribogaine had dose-linear increases for AUC and C max and was slowly eliminated (mean t 1/2 range, 24-30 hours). There was a concentration-dependent increase in QTcI (0.17 ms/ng/mL), with the largest observed mean effect of ∼16, 28, and 42 milliseconds in the 60-, 120-, and 180-mg groups, respectively. Noribogaine showed a nonstatistically significant trend toward decreased total score in opioid withdrawal ratings, most notably at the 120-mg dose; however, the study design may have confounded evaluations of time to resumption of OST. Future exposure-controlled multiple-dose noribogaine studies are planned that will address these safety and design issues. © 2016, The American College of Clinical Pharmacology.

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

PubMed

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

2015-09-01

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

Buffered Lidocaine With Sodium Bicarbonate did not Increase Inferior Alveolar Nerve Block Success Rate in Patients Having Symptomatic Irreversible Pulpitis.

PubMed

Parirokh, Masoud

2016-03-01

Effect of buffered 4% lidocaine on the success of the inferior alveolar nerve block in patients with symptomatic irreversible pulpitis: a prospective, randomized, double-blind study. Schellenberg J, Drum M, Reader A, Nusstein J, Fowler S, Beck M. J Endod 2015;41(6):791-6. The study was supported by Meyers/Reader Graduate Endodontic Support Fund Double blinded randomized controlled trial. Copyright © 2016 Elsevier Inc. All rights reserved.

Treatment of seborrhoeic dermatitis of the scalp with ketoconazole shampoo. A double-blind study.

PubMed

Faergemann, J

1990-01-01

Thirty-six patients with seborrhoeic dermatitis of the scalp and culture positive for Pityrosporum ovale were treated in a double-blind placebo controlled study with ketoconazole shampoo twice weekly for 4 weeks. In the ketoconazole group, 16 of 18 patients (89%) became free of lesions or improved, compared with only 8 of 18 (p less than 0.01) in the placebo group. The patients found the shampoo effective, easy to use and cosmetically attractive.

[Deanol in tardive dyskinesia: a double-blind study (author's transl)].

PubMed

Bockenheimer, S; Lucius, G

1976-09-17

Tardive dyskinesia following long-term application of neuroleptics is resistant to treatment. According to the hypothesis of a relative central nervous system acetylcholine lack as the underlying mechanism 20 patients were treated with dimethylaminoethanol (Deanol) in a double-blind study. Deanol is known to be a direct precursor of intracerebral acetylcholine. For several reasons (which are discussed) the data of but 11 patients were statistically evaluated. The results suggest some therapeutic effect in some of the patients only (significant improvement of oral hyperkinesia).

A Double Blind Trial of Divalproex Sodium for Affective Lability and Alcohol Use Following Traumatic Brain Injury

DTIC Science & Technology

2013-10-01

acutely manic bipolar patients, and the FDA approved it in 1995 for this indication. Also, it is used in conjunction with lithium or carbamazepine to...0652 TITLE: A Double Blind Trial of Divalproex Sodium for Affective Lability and Alcohol Use Following Traumatic Brain Injury...and Alcohol Use Following Traumatic Brain Injury 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-08-2-0652 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR

A Double Blind Trial of Divalproex Sodium for Affective Lability and Alcohol Use Following Traumatic Brain Injury

DTIC Science & Technology

2010-10-01

comparable to lithium in treating acutely manic bipolar patients, and the FDA approved it in 1995 for this indication. Also, it is used in conjunction with...A Double Blind Trial of Divalproex Sodium for Affective Lability and Alcohol Use Following Traumatic Brain Injury PRINCIPAL INVESTIGATOR...Lability and Alcohol Use Following Traumatic Brain Injury 5b. GRANT NUMBER W81XWH-08-2-0652 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S

Double-Blind Comparison of Iodamide and Diatrizoate for Excretory Urography 1

PubMed Central

Rosenfield, Arthur T.; Putman, Charles E.; Ulreich, Sidney; Koss, Neal

1977-01-01

A double-blind comparison of meglumine iodamide and Renografin 60 (52% meglumine diatrizoate and 8% sodium diatrizoate) for bolus excretory urography was performed. Doses of 0.8 cc/kg. to a maximum of 55 cc were administered to fifty patients, twenty-five receiving each drug. There is a suggestion that iodamide may be superior to diatrizoate in pyelocalyceal opacification while being equal to diatrizoate in parenchymal opacification and in types and severity of side-effects. PMID:345632

Double-Blind Comparison of Phlebitis Produced by Cefazolin Versus Cephalothin

PubMed Central

Shemonsky, Natalie K.; Carrizosa, Jaime; Kaye, Donald; Levison, Matthew E.

1975-01-01

In a double-blind study with each patient as his own control, 1 g of cefazolin and 2 g of cephalothin were administered intravenously every 6 h to 20 patients in opposite arms for a period of 48 h each. The degree of phlebitis was significantly more severe with cephalothin than with cefazolin (P < 0.05); however, neither the incidence of phlebitis nor the time of onset of phlebitis was significantly different between the two drugs. PMID:1147583

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

PubMed

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

2014-02-01

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

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

PubMed Central

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

2014-01-01

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

Effects of laterally wedged insoles on symptoms and disease progression in medial knee osteoarthritis: a protocol for a randomised, double-blind, placebo controlled trial

PubMed Central

Bennell, Kim; Bowles, Kelly-Ann; Payne, Craig; Cicuttini, Flavia; Osborne, Richard; Harris, Anthony; Hinman, Rana

2007-01-01

Background Whilst laterally wedged insoles, worn inside the shoes, are advocated as a simple, inexpensive, non-toxic self-administered intervention for knee osteoarthritis (OA), there is currently limited evidence to support their use. The aim of this randomised, double-blind controlled trial is to determine whether laterally wedges insoles lead to greater improvements in knee pain, physical function and health-related quality of life, and slower structural disease progression as well as being more cost-effective, than control flat insoles in people with medial knee OA. Methods/Design Two hundred participants with painful radiographic medial knee OA and varus malalignment will be recruited from the community and randomly allocated to lateral wedge or control insole groups using concealed allocation. Participants will be blinded as to which insole is considered therapeutic. Blinded follow up assessment will be conducted at 12 months after randomisation. The outcome measures are valid and reliable measures recommended for OA clinical trials. Questionnaires will assess changes in pain, physical function and health-related quality-of-life. Magnetic resonance imaging will measure changes in tibial cartilage volume. To evaluate cost-effectiveness, participants will record the use of all health-related treatments in a log-book returned to the assessor on a monthly basis. To test the effect of the intervention using an intention-to-treat analysis, linear regression modelling will be applied adjusting for baseline outcome values and other demographic characteristics. Discussion Results from this trial will contribute to the evidence regarding the effectiveness of laterally wedged insoles for the management of medial knee OA. Trial registration ACTR12605000503628; NCT00415259. PMID:17892539

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

Secure entanglement distillation for double-server blind quantum computation.

PubMed

Morimae, Tomoyuki; Fujii, Keisuke

2013-07-12

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

Edoxaban for the long-term treatment of venous thromboembolism: rationale and design of the Hokusai-venous thromboembolism study--methodological implications for clinical trials.

PubMed

Raskob, G; Büller, H; Prins, M; Segers, A; Shi, M; Schwocho, L; van Kranen, R; Mercuri, M

2013-07-01

New oral anticoagulants may simplify long-term therapy by eliminating the need for laboratory monitoring. Edoxaban is an oral, direct inhibitor of factor Xa that is given in a fixed dose once daily. The Hokusai-VTE study is a randomized, double-blind trial to evaluate whether initial low molecular weight heparin (LMWH) followed by edoxaban (60 mg once daily) is non-inferior to LMWH followed by warfarin (International Normalized Ratio of 2.0-3.0) for the prevention of recurrent thromboembolism in patients with acute symptomatic venous thromboembolism (VTE). The primary efficacy outcome is symptomatic recurrent VTE during the 12-month study period. The principal safety outcome is clinically relevant bleeding (major or non-major) occurring during or within 3 days of stopping study treatment. A clinical events committee adjudicates all suspected outcome events. A unique study design feature is the flexible treatment duration of between 3 and 12 months to simulate usual clinical practice, and enabled by: (i) double-blinding to minimize bias that could occur if knowledge of the patient's treatment influenced the duration of therapy; and (ii) follow-up for 12 months of all patients and inclusion in the primary efficacy analysis, regardless of the duration of therapy received. A second innovative design feature is the strategy for achieving an appropriate time in therapeutic range in the warfarin group, with central tracking for each participating center and feedback to the investigators. The standard methods combined with innovative design features should achieve study results that are both scientifically valid and relevant to clinical practice. © 2013 International Society on Thrombosis and Haemostasis.

Granulocyte-colony stimulating factor in the prevention of postoperative infectious complications and sub-optimal recovery from operation in patients with colorectal cancer and increased preoperative risk (ASA 3 and 4). Protocol for a controlled clinical trial developed by consensus of an international study group. Part two: design of the study.

PubMed

Bauhofer, A; Lorenz, W; Stinner, B; Rothmund, M; Koller, M; Sitter, H; Celik, I; Farndon, J R; Fingerhut, A; Hay, J M; Lefering, R; Lorijn, R; Nyström, P O; Schäfer, H; Schein, M; Solomkin, J; Troidl, H; Volk, H D; Wittmann, D H; Wyatt, J

2001-04-01

Presentation of a new type of a study protocol for evaluation of the effectiveness of an immune modifier (rhG-CSF, filgrastim): prevention of postoperative infectious complications and of sub-optimal recovery from operation in patients with colorectal cancer and increased preoperative risk (ASA 3 and 4). This part describes the design of the randomised, placebo controlled, double-blinded, single-centre study performed at an university hospital (n = 40 patients for each group). The trial design includes the following elements for a prototype protocol: * The study population is restricted to patients with colorectal cancer, including a left sided resection and an increased perioperative risk (ASA 3 and 4). * Patients are allocated by random to the control or treatment group. * The double blinding strategy of the trial is assessed by psychometric indices. * An endpoint construct with quality of life (EORTC QLQ-C30) and a recovery index (modified Mc Peek index) are used as primary endpoints. Qualitative analysis of clinical relevance of the endpoints is performed by both patients and doctors. * Statistical analysis uses an area under the curve (AUC) model for improvement of quality of life on leaving hospital and two and six months after operation. A confirmatory statistical model with quality of life as the first primary endpoint in the hierarchic test procedure is used. Expectations of patients and surgeons and the negative affect are analysed by social psychological scales. This study design differs from other trials on preoperative prophylaxis and postoperative recovery, and has been developed to try a new concept and avoid previous failures.

Viewing videotaped identification procedure increases juror sensitivity to single-blind photo-array administration.

PubMed

Modjadidi, Karima; Kovera, Margaret Bull

2018-06-01

We investigated whether watching a videotaped photo array administration or expert testimony could sensitize jurors to the suggestiveness of single-blind eyewitness identification procedures. Mock jurors recruited from the community (N = 231) watched a videotaped simulation of a robbery trial in which the primary evidence against the defendant was an eyewitness identification. We varied whether the witness made an identification from a single- or double-blind photo array, the evidence included a videotape of the photo array procedure, and an expert testified about the effects of single-blind identification procedures on administrators' behaviors and witness accuracy. Watching the videotaped photo array administration sensitized mock jurors to the suggestiveness of the single-blind procedure, causing them to be less likely to convict a defendant identified through single-rather than double-blind procedures. Exposure to the videotaped procedure also decreased the favorability of mock jurors' ratings of the eyewitness, irrespective of whether the lineup was conducted by a single-blind administrator. Expert testimony did not sensitize jurors to administrator bias. Thus, videotaping identification procedures could serve as an important procedural reform that both preserves a record of whether the lineup administration was suggestive and might improve jurors' evaluations of eyewitness evidence. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

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

PubMed

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

2011-11-01

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

Study design and rationale of "Synergistic Effect of Combination Therapy with Cilostazol and ProbUcol on Plaque Stabilization and Lesion REgression (SECURE)" study: a double-blind randomised controlled multicenter clinical trial

PubMed Central

2011-01-01

Background Probucol, a cholesterol-lowering agent that paradoxically also lowers high-density lipoprotein cholesterol has been shown to prevent progression of atherosclerosis. The antiplatelet agent cilostazol, which has diverse antiatherogenic properties, has also been shown to reduce restenosis in previous clinical trials. Recent experimental studies have suggested potential synergy between probucol and cilostazol in preventing atherosclerosis, possibly by suppressing inflammatory reactions and promoting cholesterol efflux. Methods/design The Synergistic Effect of combination therapy with Cilostazol and probUcol on plaque stabilization and lesion REgression (SECURE) study is designed as a double-blind, randomised, controlled, multicenter clinical trial to investigate the effect of cilostazol and probucol combination therapy on plaque volume and composition in comparison with cilostazol monotherapy using intravascular ultrasound and Virtual Histology. The primary end point is the change in the plaque volume of index intermediate lesions between baseline and 9-month follow-up. Secondary endpoints include change in plaque composition, neointimal growth after implantation of stents at percutaneous coronary intervention target lesions, and serum levels of lipid components and biomarkers related to atherosclerosis and inflammation. A total of 118 patients will be included in the study. Discussion The SECURE study will deliver important information on the effects of combination therapy on lipid composition and biomarkers related to atherosclerosis, thereby providing insight into the mechanisms underlying the prevention of atherosclerosis progression by cilostazol and probucol. Trial registration number ClinicalTrials (NCT): NCT01031667 PMID:21226953

Implant design influences patient outcome after total knee arthroplasty: a prospective double-blind randomised controlled trial.

PubMed

Hamilton, D F; Burnett, R; Patton, J T; Howie, C R; Moran, M; Simpson, A H R W; Gaston, P

2015-01-01

Total knee arthroplasty (TKA) is an established and successful procedure. However, the design of prostheses continues to be modified in an attempt to optimise the functional outcome of the patient. The aim of this study was to determine if patient outcome after TKA was influenced by the design of the prosthesis used. A total of 212 patients (mean age 69; 43 to 92; 131 female (62%), 81 male (32%)) were enrolled in a single centre double-blind trial and randomised to receive either a Kinemax (group 1) or a Triathlon (group 2) TKA. Patients were assessed pre-operatively, at six weeks, six months, one year and three years after surgery. The outcome assessments used were the Oxford Knee Score; range of movement; pain numerical rating scales; lower limb power output; timed functional assessment battery and a satisfaction survey. Data were assessed incorporating change over all assessment time points, using repeated measures analysis of variance longitudinal mixed models. Implant group 2 showed a significantly greater range of movement (p = 0.009), greater lower limb power output (p = 0.026) and reduced report of 'worst daily pain' (p = 0.003) over the three years of follow-up. Differences in Oxford Knee Score (p = 0.09), report of 'average daily pain' (p = 0.57) and timed functional performance tasks (p = 0.23) did not reach statistical significance. Satisfaction with outcome was significantly better in group 2 (p = 0.001). These results suggest that patient outcome after TKA can be influenced by the prosthesis used. ©2015 The British Editorial Society of Bone & Joint Surgery.

Exposure of eyes to perfume: a double-blind, placebo-controlled experiment.

PubMed

Elberling, J; Duus Johansen, J; Dirksen, A; Mosbech, H

2006-08-01

Environmental perfume exposure can elicit bothersome respiratory symptoms. Symptoms are induced at exposure levels which most people find tolerable, and the mechanisms are unclear. The aim of the study was to investigate patients with eye and respiratory symptoms related to environmental perfume, by exposing the eyes to perfume in a double-blind, placebo-controlled study.Twenty-one eczema patients with respiratory symptoms elicited by perfume were compared with 21 healthy volunteers in a sex- and age-matched case-control study. The participants completed a symptom questionnaire, and underwent a double-blind, placebo-controlled exposure to perfume. Of the 42 individuals tested, 10 had more eye symptoms (irritation, itching, and tears) during perfume exposure than during placebo exposures, and eight of these individuals (P = 0.07, Fisher's exact test) belonged to the patient group. A true positive eye reaction to perfume was significantly associated with identification of perfume as an active exposure (P < 0.05). In this study, vapor of perfume elicited irritation in the eyes independently of olfaction, but the relative importance of ocular chemoperception in relation to elicitation of respiratory symptoms from common environmental exposures to perfume remains unclear. We investigated the hypothesis of an association between respiratory symptoms related to perfume and ocular perfume sensitivity by exposing the eyes to perfume in a double blind, placebo-controlled experiment. Vapors of perfume provoked symptoms in the relevant eye in some patients and healthy control persons, but under our exposure conditions, ocular chemesthesis failed to elicit respiratory symptoms.

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

Jagsi, Reshma, E-mail: rjagsi@med.umich.edu; Bennett, Katherine Egan; Griffith, Kent A.

Purpose: Peer reviewers' knowledge of author identity may influence review content, quality, and recommendations. Therefore, the International Journal of Radiation Oncology, Biology, Physics (“Red Journal”) implemented double-blinded peer review in 2011. Given the relatively small size of the specialty and the high frequency of preliminary abstract presentations, we sought to evaluate attitudes, the efficacy of blinding, and the potential impact on the disposition of submissions. Methods and Materials: In May through August 2012, all Red Journal reviewers and 1 author per manuscript completed questionnaires regarding demographics, attitudes, and perceptions of success of blinding. We also evaluated correlates of the outcomesmore » of peer review. Results: Questionnaires were received from 408 authors and 519 reviewers (100%). The majority of respondents favored double blinding; 6% of authors and 13% of reviewers disagreed that double blinding should continue in the Red Journal. In all, 50% of the reviewers did not suspect the identity of the author of the paper that they reviewed; 19% of reviewers believed that they could identify the author(s), and 31% suspected that they could. Similarly, 23% believed that they knew the institution(s) from which the paper originated, and 34% suspected that they did. Among those who at least suspected author identity, 42% indicated that prior presentations served as a clue, and 57% indicated that literature referenced did so. Of those who at least suspected origin and provided details (n=133), 13% were entirely incorrect. Rejection was more common in 2012 than 2011, and submissions from last authors with higher H-indices (>21) were more likely to survive initial review, without evidence of interactions between submission year and author gender or H-index. Conclusions: In a relatively small specialty in which preliminary research presentations are common and occur in a limited number of venues, reviewers are often familiar with research findings and suspect author identity even when manuscript review is blinded. Nevertheless, blinding appears to be effective in many cases, and support for continuing blinding was strong.« less

Behavioral and cognitive effect of theophylline: a dose-response study.

PubMed

Stein, M A; Lerner, C A

1993-02-01

The behavioral and cognitive effects of theophylline were studied in 14 asymptomatic asthmatic children. A double-blind crossover design was used with two dosage levels. Conners parent ratings suggest behavioral improvement by the second week of treatment, regardless of dosage or order of administration. No effects were found on cognitive measures. We conclude that the majority of behavior problems associated with theophylline occur during the induction phase, and that for most children behavior and attention problems rapidly return to baseline or improve.

Does EEG-neurofeedback improve neurocognitive functioning in children with attention-deficit/hyperactivity disorder? A systematic review and a double-blind placebo-controlled study.

PubMed

Vollebregt, Madelon A; van Dongen-Boomsma, Martine; Buitelaar, Jan K; Slaats-Willemse, Dorine

2014-05-01

The number of placebo-controlled randomized studies relating to EEG-neurofeedback and its effect on neurocognition in attention-deficient/hyperactivity disorder (ADHD) is limited. For this reason, a double blind, randomized, placebo-controlled study was designed to assess the effects of EEG-neurofeedback on neurocognitive functioning in children with ADHD, and a systematic review on this topic was performed. Forty-one children (8-15 years) with a DSM-IV-TR diagnosis of ADHD were randomly allocated to EEG-neurofeedback or placebo-neurofeedback treatment for 30 sessions, twice a week. Children were stratified by age, electrophysiological state of arousal, and medication use. Neurocognitive tests of attention, executive functioning, working memory, and time processing were administered before and after treatment. Researchers, teachers, children and their parents, with the exception of the neurofeedback-therapist, were all blind to treatment assignment. Outcome measures were the changes in neurocognitive performance before and after treatment. www.clinicaltrials.gov: NCT00723684. No significant treatment effect on any of the neurocognitive variables was found. A systematic review of the current literature also did not find any systematic beneficial effect of EEG-neurofeedback on neurocognitive functioning. Overall, the existing literature and this study fail to support any benefit of neurofeedback on neurocognitive functioning in ADHD, possibly due to small sample sizes and other study limitations. © 2013 The Authors. Journal of Child Psychology and Psychiatry © 2013 Association for Child and Adolescent Mental Health.

The effect of anthocyanin supplementation in modulating platelet function in sedentary population: a randomised, double-blind, placebo-controlled, cross-over trial.

PubMed

Thompson, Kiara; Hosking, Holly; Pederick, Wayne; Singh, Indu; Santhakumar, Abishek B

2017-09-01

The anti-thrombotic properties of anthocyanin (ACN) supplementation was evaluated in this randomised, double-blind, placebo (PBO) controlled, cross-over design, dietary intervention trial in sedentary population. In all, sixteen participants (three males and thirteen females) consumed ACN (320 mg/d) or PBO capsules for 28 d followed by a 2-week wash-out period. Biomarkers of thrombogenesis and platelet activation induced by ADP; platelet aggregation induced by ADP, collagen and arachidonic acid; biochemical, lipid, inflammatory and coagulation profile were evaluated before and after supplementation. ACN supplementation reduced monocyte-platelet aggregate formation by 39 %; inhibited platelet endothelial cell adhesion molecule-1 expression by 14 %; reduced platelet activation-dependant conformational change and degranulation by reducing procaspase activating compound-1 (PAC-1) (↓10 %) and P-selectin expression (↓14 %), respectively; and reduced ADP-induced whole blood platelet aggregation by 29 %. Arachidonic acid and collagen-induced platelet aggregation; biochemical, lipid, inflammatory and coagulation parameters did not change post-ACN supplementation. PBO treatment did not have an effect on the parameters tested. The findings suggest that dietary ACN supplementation has the potential to alleviate biomarkers of thrombogenesis, platelet hyperactivation and hyper-aggregation in sedentary population.

Preliminary effects of oral uridine on the ocular surface in dry eye patients.

PubMed

Chang, Ki Cheol; Oh, Joo Youn; In, Youn Seok; Kim, Mee Kum; Shin, Ki Cheul; Wee, Won Ryang; Lee, Jin Hak; Park, Myung Gyu

2009-08-01

We designed a randomized, double blinded, 3-months controlled prospective clinical study to investigate effects of oral uridine on the ocular surface in dry eye patients. Twenty-seven patients who diagnosed as dry eye with lower than 5 mm of wetting in the Schirmer strip, with corneal epithelial erosion and who completely followed-up till 3 months were enrolled. Corneal-conjunctival fluorescein staining, non-anesthetic Schirmer test, impression cytology, and Ocular Surface Disease Index (OSDI) were evaluated in the experimental and placebo groups at the baseline, 1 and 3 months after start of medication in a double blinded manner. Fluorescein stain score of the cornea was markedly decreased in oral uridine group compared to the placebo group at 3 months after medication (P=0.032, Mann-Whitney U test). The Schirmer wetting score for the oral uridine group was significantly increased (P=0.001, Wilcoxon signed rank test) at 3 months and its difference between two groups was statistically significant (P=0.030, Mann-Whitney U test). OSDI scores were significantly decreased at 1 and 3 months in treatment group. Oral uridine is effective in treatment of dry eyes.

Comparison of the effects of magnesium and ketamine on postoperative pain and morphine consumption. A double-blind randomized controlled clinical study.

PubMed

Arıkan, Müge; Aslan, Bilge; Arıkan, Osman; Horasanlı, Eyüp; But, Abdulkadir

2016-01-01

To compare the effects of magnesium sulfate and ketamine on postoperative pain and total morphine consumption in a placebo-controlled design. One hundred and twenty women scheduled for total abdominal hysterectomy were included in this prospective, randomized, double-blind study. Postoperatively, when the Numeric Pain Rating Scale (NPRS) was four or more, IV-PCA morphine was applied to all patients. The patients were randomized into three groups: Group K ketamine, Group M magnesium, and Group C saline received as infusion. Total morphine consumption for 48h, pain scores, adverse effects, and patients' satisfaction were evaluated. Total morphine consumption was significantly lower in Group K (32.6±9.2 mg) than in Group M (58.9±6.5 mg) and in Group C (65.7±8.2 mg). The satisfaction level of patients in Group K was higher than the other two groups (p<0.05). Pruritus and nausea were observed more frequently in Group C. CONCLUSİON: The addition of ketamine to IV-PCA morphine reduces the total consumption of morphine without psychotic effects; however, magnesium did not influence morphine consumption.

The effects of repeated administration of camphor-crataegus berry extract combination on blood pressure and on attentional performance - a randomized, placebo-controlled, double-blind study.

PubMed

Erfurt, L; Schandry, R; Rubenbauer, S; Braun, U

2014-09-25

The present study investigated the effects of repeated administration of Korodin(®), a combination of camphor and crataegus berry extract, on blood pressure and attentional functioning. This study was conducted based on a randomized, placebo-controlled, double-blind design. 54 persons participated (33 female, 21 male) with a mean age of 24.3 years. Blood pressure and body mass index were in the normal range. Participants received 20 drops of either Korodin(®) or a placebo for four times with interjacent time intervals of about 10 min. Blood pressure was measured sphygmomanometrically before and after each administration. Attentional performance was quantified by using two paper-and-pencil tests, the d2 Test of Attention and Digit Symbol Test. Greater increases in blood pressure occurred after the four Korodin(®) administrations in comparison to the four placebo administrations. The performance in two parameters of d2 Test of Attention was consistently superior after the intake of Korodin(®). The excellent tolerability and safety of Korodin(®), even after a total consumption of 80 drops, was confirmed. Copyright © 2014 Elsevier GmbH. All rights reserved.

Effects of lacosamide and carbamazepine on human motor cortex excitability: a double-blind, placebo-controlled transcranial magnetic stimulation study.

PubMed

Lang, Nicolas; Rothkegel, Holger; Peckolt, Hannes; Deuschl, Günther

2013-11-01

Lacosamide (LCM) and carbamazepine (CBZ) are antiepileptic drugs both acting on neuronal voltage-gated sodium channels. Patch-clamp studies demonstrated significant differences in how LCM and CBZ affect neuronal membrane excitability. Despite valuable information patch-clamp studies provide, they also comprise some constraints. For example, little is known about effects of LCM on intracortical synaptic excitability. In contrast, transcranial magnetic stimulation (TMS) can describe drug-induced changes at the system level of the human cerebral cortex. The present study was designed to explore dose-depended effects of LCM and effects of CBZ on motor cortex excitability with TMS in a randomized, double-blind, placebo-controlled crossover trial in healthy human subjects. Subjects received 600 mg CBZ, 200 mg LCM, 400 mg LCM or placebo preceding TMS measurements. Compared to placebo, TMS motor thresholds were significantly increased after carbamazepine and lacosamide, with a trend for a dose dependent effect of lacosamide. Both, carbamazepine and lacosamide did not affect TMS parameters of intracortical synaptic excitability. TMS measurements suggest that lacosamide and carbamazepine predominantly act on neuronal membrane excitability. Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

The effect of glucose dose and fasting interval on cognitive function: a double-blind, placebo-controlled, six-way crossover study.

PubMed

Owen, Lauren; Scholey, Andrew B; Finnegan, Yvonne; Hu, Henglong; Sünram-Lea, Sandra I

2012-04-01

Previous research has identified a number of factors that appear to moderate the behavioural response to glucose administration. These include physiological state, dose, types of cognitive tasks used and level of cognitive demand. Another potential moderating factor is the length of the fasting interval prior to a glucose load. Therefore, we aimed to examine the effect of glucose dose and fasting interval on mood and cognitive function. The current study utilised a double-blind, placebo-controlled, balanced, six period crossover design to examine potential interactions between length of fasting interval (2 versus 12 hours) and optimal dose for cognition enhancement. Results demonstrated that the higher dose (60 g) increased working memory performance following an overnight fast, whereas the lower dose (25 g) enhanced working memory performance following a 2-h fast. The data suggest that optimal glucose dosage may differ under different conditions of depleted blood glucose resources. In addition, glucoregulation was observed to be a moderating factor. However, further research is needed to develop a model of the moderating and mediating factors under which glucose facilitation is best achieved.

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.

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

Double-blind trial of recombinant gamma-interferon versus placebo in the treatment of rheumatoid arthritis. 1989.

PubMed

Cannon, Grant W; Pincus, Seth H; Emkey, Ronald D; Denes, Alex; Cohen, Selwyn A; Wolfe, Frederick; Saway, P Anthony; Jaffer, Adrian M; Weaver, Arthur L; Cogen, Lewis; Schindler, John D

2008-02-01

One hundred five patients were enrolled in a 12-week, randomized, prospective, double-blind, placebo-controlled trial of recombinant human gamma-interferon (rHu gamma-IFN) for the treatment of rheumatoid arthritis. Fifty-four patients received rHu gamma-IFN and 51 received placebo. Forty-two patients in each group completed the 12-week trial. Some clinical improvement occurred in both groups of patients. Although the improvement with rHu gamma-IFN was greater than that with placebo, the differences were generally not statistically significant.

Rationale and design of the Helping Ease Renal failure with Bupi Yishen compared with the Angiotensin II Antagonist Losartan (HERBAAL) trial: a randomized controlled trial in non-diabetes stage 4 chronic kidney disease.

PubMed

Mao, Wei; Zhang, Lei; Zou, Chuan; Li, Chuang; Wu, Yifan; Su, Guobin; Guo, Xinfeng; Wu, Yuchi; Lu, Fuhua; Lin, Qizhan; Wang, Lixin; Bao, Kun; Xu, Peng; Zhao, Daixin; Peng, Yu; Liang, Hui; Lu, Zhaoyu; Gao, Yanxiang; Jie, Xina; Zhang, La; Wen, Zehuai; Liu, Xusheng

2015-09-08

Chronic kidney disease (CKD) is a global public health problem. Currently, as for advanced CKD populations, medication options limited in angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB), which were partially effective. A Chinese herbal compound, Bupi Yishen formula, has showed renal protective potential in experiments and retrospective studies. This study will evaluate the efficacy and safety of Bupi Yishen formula (BYF) in patients with CKD stage 4. In this double blind, double dummy, randomized controlled trial (RCT), there will be 554 non-diabetes stage 4 CKD patients from 16 hospitals included and randomized into two groups: Chinese medicine (CM) group or losartan group. All patients will receive basic conventional therapy. Patients in CM group will be treated with BYF daily while patients in control group will receive losartan 100 mg daily for one year. The primary outcome is the change in estimated glomerular filtration rate (eGFR) over 12 months. Secondary outcomes include the incidence of endpoint events, liver and kidney function, urinary protein creatinine ratio, cardiovascular function and quality of life. This study will be the first multi-center, double blind RCT to assess whether BYF, compared with losartan, will have beneficial effects on eGFR for non-diabetes stage 4 CKD patients. The results will help to provide evidence-based recommendations for clinicians. Chinese Clinical Trial Registry Number: ChiCTR-TRC-10001518 .

Nourkrin: objective and subjective effects and tolerability in persons with hair loss.

PubMed

Thom, E

2006-01-01

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

Randomised clinical trial: relief of upper gastrointestinal symptoms by an acid pocket-targeting alginate-antacid (Gaviscon Double Action) - a double-blind, placebo-controlled, pilot study in gastro-oesophageal reflux disease.

PubMed

Thomas, E; Wade, A; Crawford, G; Jenner, B; Levinson, N; Wilkinson, J

2014-03-01

The alginate-antacid, Gaviscon Double Action (Gaviscon DA; Reckitt Benckiser, Slough, UK) suppresses reflux after meals by creating a gel-like barrier that caps and displaces the acid pocket distal to the oesophago-gastric junction. The effect of Gaviscon DA on reflux and dyspepsia symptoms has not yet been demonstrated with a modern trial design. A pilot study to assess the efficacy and safety of Gaviscon DA compared with matched placebo for decreasing upper gastrointestinal symptoms in symptomatic gastro-oesophageal reflux disease (GERD) patients. A randomised, double-blind, parallel group study was performed in 110 patients with symptoms of GERD. Patients received Gaviscon DA or placebo tablets for 7 consecutive days. The primary endpoint compared the change in overall Reflux Disease Questionnaire (RDQ) symptom score (combined heartburn/regurgitation/dyspepsia). Secondary endpoints assessed individual dimensions, GERD dimension (heartburn and regurgitation) and overall treatment evaluation (OTE). There was a greater decrease in overall RDQ symptom score in the Gaviscon DA group compared with the placebo group (Least Squares Mean difference -0.55; P = 0.0033), and for each of the dimensions independently. Patients in the Gaviscon DA group evaluated their overall treatment response higher than patients in the placebo group [mean (standard deviation) OTE 4.1 (2.44) vs. 1.9 (3.34); P = 0.0005]. No differences in the incidence of adverse events were observed between treatment groups. Gaviscon DA decreases reflux and dyspeptic symptoms in GERD patients compared with matched placebo and has a favourable benefit-risk balance. Larger scale clinical investigations of medications targeting the acid pocket are warranted. (EudraCT, 2012-002188-84). © 2014 John Wiley & Sons Ltd.

The Efficacy and Safety of Shen Guo Lao Nian Granule for Common Cold of Qi-Deficiency Syndrome: Study Protocol for a Randomized, Double-Blind, Placebo-Controlled, Multicenter, Phase II Clinical Trial

PubMed Central

Fu, Juanjuan; Ding, Hong; Yang, Haimiao; Huang, Yuhong

2017-01-01

Background Common cold is one of the most frequently occurring illnesses in primary healthcare services and represents considerable disease burden. Common cold of Qi-deficiency syndrome (CCQDS) is an important but less addressed traditional Chinese medicine (TCM) pattern. We designed a protocol to explore the efficacy, safety, and optimal dose of Shen Guo Lao Nian Granule (SGLNG) for treating CCQDS. Methods/Design This is a multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial. A total of 240 eligible patients will be recruited from five centers. Patients are randomly assigned to high-dose group, middle-dose group, low-dose group, or control group in a 1 : 1 : 1 : 1 ratio. All drugs are required to be taken 3 times daily for 5 days with a 5-day follow-up period. Primary outcomes are duration of all symptoms, total score reduction on Jackson's scale, and TCM symptoms scale. Secondary outcomes include every single TCM symptom duration and score reduction, TCM main symptoms disappearance rate, curative effects, and comparison between Jackson's scale and TCM symptom scale. Ethics and Trial Registration This study protocol was approved by the Ethics Committee of Clinical Trials and Biomedicine of West China Hospital of Sichuan University (number IRB-2014-12) and registered with the Chinese Clinical Trial Registry (ChiCTR-IPR-15006349). PMID:29430253

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

Calcium from salmon and cod bone is well absorbed in young healthy men: a double-blinded randomised crossover design.

PubMed

Malde, Marian K; Bügel, Susanne; Kristensen, Mette; Malde, Ketil; Graff, Ingvild E; Pedersen, Jan I

2010-07-20

Calcium (Ca) - fortified foods are likely to play an important role in helping the consumer achieve an adequate Ca intake, especially for persons with a low intake of dairy products. Fish bones have a high Ca content, and huge quantities of this raw material are available as a by-product from the fish industry. Previously, emphasis has been on producing high quality products from fish by-products by use of bacterial proteases. However, documentation of the nutritional value of the enzymatically rinsed Ca-rich bone fraction remains unexplored. The objective of the present study was to assess the bioavailability of calcium in bones of Atlantic salmon (oily fish) and Atlantic cod (lean fish) in a double-blinded randomised crossover design. Ca absorption was measured in 10 healthy young men using 47Ca whole body counting after ingestion of a test meal extrinsically labelled with the 47Ca isotope. The three test meals contained 800 mg of Ca from three different calcium sources: cod bones, salmon bones and control (CaCO3). Mean Ca absorption (+/- SEE) from the three different Ca sources were 21.9 +/- 1.7%, 22.5 +/- 1.7% and 27.4 +/- 1.8% for cod bones, salmon bones, and control (CaCO3), respectively. We conclude that bones from Atlantic salmon and Atlantic cod are suitable as natural Ca sources in e.g. functional foods or as supplements.

Calcium from salmon and cod bone is well absorbed in young healthy men: a double-blinded randomised crossover design

PubMed Central

2010-01-01

Background Calcium (Ca) - fortified foods are likely to play an important role in helping the consumer achieve an adequate Ca intake, especially for persons with a low intake of dairy products. Fish bones have a high Ca content, and huge quantities of this raw material are available as a by-product from the fish industry. Previously, emphasis has been on producing high quality products from fish by-products by use of bacterial proteases. However, documentation of the nutritional value of the enzymatically rinsed Ca-rich bone fraction remains unexplored. The objective of the present study was to assess the bioavailability of calcium in bones of Atlantic salmon (oily fish) and Atlantic cod (lean fish) in a double-blinded randomised crossover design. Methods Ca absorption was measured in 10 healthy young men using 47Ca whole body counting after ingestion of a test meal extrinsically labelled with the 47Ca isotope. The three test meals contained 800 mg of Ca from three different calcium sources: cod bones, salmon bones and control (CaCO3). Results Mean Ca absorption (± SEE) from the three different Ca sources were 21.9 ± 1.7%, 22.5 ± 1.7% and 27.4 ± 1.8% for cod bones, salmon bones, and control (CaCO3), respectively. Conclusion We conclude that bones from Atlantic salmon and Atlantic cod are suitable as natural Ca sources in e.g. functional foods or as supplements. PMID:20646299

Efficacy and safety of luseogliflozin added to insulin therapy in Japanese patients with type 2 diabetes: a multicenter, 52-week, clinical study with a 16-week, double-blind period and a 36-week, open-label period.

PubMed

Seino, Yutaka; Sasaki, Takashi; Fukatsu, Atsushi; Imazeki, Hisae; Ochiai, Hidekazu; Sakai, Soichi

2018-06-01

To evaluate the efficacy and safety of luseogliflozin in Japanese patients with type 2 diabetes (T2D) inadequately controlled with insulin monotherapy. This 52-week multicenter study entailed a 16-week, double-blind period followed by a 36-week, open-label period. Patients were randomized to receive either luseogliflozin 2.5 mg (n = 159) or placebo (n = 74) during the double-blind period. All patients who entered the open-label period received luseogliflozin. Major efficacy endpoints included the changes from baseline in HbA1c, fasting plasma glucose (FPG), postprandial plasma glucose (PPG) and bodyweight. Safety assessments included adverse events, laboratory tests and vital signs. In the double-blind period, luseogliflozin significantly decreased HbA1c (-1.18%), FPG (-42.4 mg/dL), 2 hour PPG (-68.7 mg/dL) and bodyweight (-1.27 kg) compared with placebo (all p < .001); these reductions were maintained over 52 weeks. The changes from baseline at Week 52 were -1.00%, -35.1 mg/dL, -68.8 mg/dL and -1.81 kg, respectively (all p < .001). In the placebo group, favorable glycemic control and bodyweight reduction were also observed after switching to luseogliflozin. Most adverse events were mild in severity. During the double-blind period, the incidences of hypoglycemia were 20.8% and 13.5% in the luseogliflozin and placebo groups, respectively. During the 52 weeks of luseogliflozin treatment, the frequency of hypoglycemia was 33.3%, but no serious hypoglycemia occurred. The safety profile other than hypoglycemia was also acceptable. There were no new safety concerns about luseogliflozin added to insulin. Luseogliflozin added to insulin therapy significantly improved glycemic control with bodyweight reduction and was well tolerated in Japanese patients with T2D. Japan Pharmaceutical Information Center (JapicCTI-142582).

Doxycycline in early CJD: a double-blinded randomised phase II and observational study.

PubMed

Varges, Daniela; Manthey, Henrike; Heinemann, Uta; Ponto, Claudia; Schmitz, Matthias; Schulz-Schaeffer, Walter J; Krasnianski, Anna; Breithaupt, Maren; Fincke, Fabian; Kramer, Katharina; Friede, Tim; Zerr, Inga

2017-02-01

The main objective of the present study is to study the therapeutic efficiency of doxycycline in a double-blinded randomised phase II study in a cohort of patients with sporadic Creutzfeldt-Jakob disease (sCJD). From the National Reference Center of TSE Surveillance in Germany, patients with probable or definite sCJD were recruited for a double-blinded randomised study with oral doxycycline (EudraCT 2006-003934-14). In addition, we analysed the data from patients with CJD who received compassionate treatment with doxycycline in a separate group. Potential factors which influence survival such as age at onset, gender, codon 129 polymorphism and cognitive functions were evaluated. The primary outcome measure was survival. Group 1: in the double-blinded randomised phase II study, 7 patients in the treatment group were compared with 5 controls. Group 2: 55 patients with sCJD treated with oral doxycycline were analysed and compared with 33 controls by a stratified propensity score applied to a Cox proportional hazard analysis. The results of both studies were combined by means of a random-effects meta-analysis. A slight increase in survival time in the doxycycline treatment group was observed (p=0.049, HR=0.63 (95% CI 0.402 to 0.999)). On the basis of our studies, a larger trial of doxycycline should be performed in persons in the earliest stages of CJD. EudraCT 2006-003934-14; Results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Long-term efficacy and safety of certolizumab pegol in Japanese rheumatoid arthritis patients with an inadequate response to methotrexate: 52-week results from an open-label extension of the J-RAPID study

PubMed Central

Tanaka, Yoshiya; Yamamoto, Kazuhiko; Takeuchi, Tsutomu; Yamanaka, Hisashi; Ishiguro, Naoki; Eguchi, Katsumi; Watanabe, Akira; Origasa, Hideki; Shoji, Toshiharu; Miyasaka, Nobuyuki; Koike, Takao

2014-01-01

Abstract Objectives. To evaluate the long-term efficacy and safety of certolizumab pegol (CZP) plus methotrexate treatment and to assess the efficacy of two CZP maintenance dosing schedules in Japanese rheumatoid arthritis (RA) patients with an inadequate response to methotrexate. Methods. J-RAPID double-blind patients were entered into an open-label extension (OLE) study. Patients withdrawn due to lack of efficacy at 16 weeks and double-blind completers without a week-24 American College of Rheumatology (ACR) 20 response received CZP 200 mg every other week (Q2W) plus methotrexate. Double-blind completers with week-24 ACR20 responses were randomized to CZP 200 mg Q2W plus methotrexate or CZP 400 mg every 4 weeks plus methotrexate. Results. The ACR20/ACR50/ACR70 response rates of double-blind completers (n = 204) were 89.7%/67.2%/36.3% at OLE entry and 95.6%/84.8%/58.3% at 52 weeks, respectively. Other clinical, functional and radiographic outcomes were sustained with long-term CZP plus methotrexate. Long-term treatment with CZP was well-tolerated with no new unexpected adverse events observed. The efficacy and safety of CZP treatment were similar between the two dosing schedules. Conclusions. Continued CZP administration with methotrexate maintained efficacy over 52 weeks and was well-tolerated for Japanese RA patients. No obvious differences in clinical efficacy and safety were observed between the two dosing schedules, giving flexibility in maintenance administration schedules. PMID:24593170

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

PubMed

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

2017-04-01

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

Study protocol and rationale for a randomized double-blinded crossover trial of phentermine-topiramate ER versus placebo to treat binge eating disorder and bulimia nervosa.

PubMed

Dalai, Shebani Sethi; Adler, Sarah; Najarian, Thomas; Safer, Debra Lynn

2018-01-01

Bulimia nervosa (BN) and binge eating disorder (BED) are associated with severe psychological and medical consequences. Current therapies are limited, leaving up to 50% of patients symptomatic despite treatment, underscoring the need for additional treatment options. Qsymia, an FDA-approved medication for obesity, combines phentermine and topiramate ER. Topiramate has demonstrated efficacy for both BED and BN, but limited tolerability. Phentermine is FDA-approved for weight loss. A rationale for combined phentermine/topiramate for BED and BN is improved tolerability and efficacy. While a prior case series exploring Qsymia for BED showed promise, randomized studies are needed to evaluate Qsymia's safety and efficacy when re-purposed in eating disorders. We present a study protocol for a Phase I/IIa single-center, prospective, double-blinded, randomized, crossover trial examining safety and preliminary efficacy of Qsymia for BED and BN. Adults with BED (n=15) or BN (n=15) are randomized 1:1 to receive 12weeks Qsymia (phentermine/topiramate ER, 3.75mg/23mg-15mg/92mg) or placebo, followed by 2-weeks washout and 12-weeks crossover, where those on Qsymia receive placebo and vice versa. Subsequently participants receive 8weeks follow-up off study medications. The primary outcome is the number of binge days/week measured by EDE. Secondary outcomes include average number of binge episodes, percentage abstinence from binge eating, and changes in weight/vitals, eating psychopathology, and mood. To our knowledge this is the first randomized, double-blind protocol investigating the safety and efficacy of phentermine/topiramate in BED and BN. We highlight the background and rationale for this study, including the advantages of a crossover design. Clinicaltrials.gov identifier NCT02553824 registered on 9/17/2015. https://clinicaltrials.gov/ct2/show/NCT02553824. Copyright © 2017 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

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

PubMed

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

2015-02-01

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

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2016-08-01

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

A randomised, double-blind trial comparing raloxifene HCl and continuous combined hormone replacement therapy in postmenopausal women: effects on compliance and quality of life.

PubMed

Voss, Simon; Quail, Deborah; Dawson, Alison; Bäckström, Tjorbörn; Aguas, Fernanda; Erenus, Mithat; The, Hok Sien; Bonnar, John; De Geyter, Christian; Hunter, Myra; Nickelsen, Thomas

2002-08-01

To compare continuous combined hormone replacement therapy (ccHRT) and raloxifene with respect to compliance and quality of life, which were predefined secondary endpoints of a large, prospective study designed to investigate the uterine effects of both treatments. Double-blind, randomised controlled trial of six-month duration. One hundred and twenty-nine gynaecology hospital departments, clinics or practices specialised in women's healthcare, located in Europe, South Africa and Israel. Healthy postmenopausal women (n = 1008). Changes in quality of life using the Women's Health Questionnaire (WHQ) and compliance using a compliance questionnaire and pill count. Adverse event and early discontinuation rates and satisfaction with treatment using a visual analogue scale (VAS). Women taking raloxifene reported greater satisfaction with their treatment as assessed on the VAS (P = 0.004), and a lower proportion, as compared with ccHRT, reported being worried by the treatment (9.6% vs 20.2%, P < 0.01). Women taking ccHRT reported greater deterioration in scores from the WHQ for depressed mood and menstrual symptoms than those taking raloxifene (P < 0.01). For memory, vasomotor symptoms and sexual behaviour, the ccHRT group reported significantly greater mean improvements (P < 0.05). Over half (58.8%) of those taking raloxifene noticed no effect, 37.7% felt better and 3.4% felt worse as measured using the compliance questionnaire. Fifty percent of the women taking ccHRT felt better, 37.8% noticed no effect but over 10% felt worse. More women on raloxifene (94.6%) than on ccHRT (85.9%) reported that they were taking their double-blinded medication regularly (P < 0.01). A lower rate of adverse event-related discontinuations, the lack of negative effects on quality of life and a smaller proportion of women being worried by the drug treatment were associated with higher treatment satisfaction and better compliance in postmenopausal women taking ccHRT or raloxifene.

Neurogenic orthostatic hypotension: a double-blind, placebo-controlled study with midodrine

NASA Technical Reports Server (NTRS)

Jankovic, J.; Gilden, J. L.; Hiner, B. C.; Kaufmann, H.; Brown, D. C.; Coghlan, C. H.; Rubin, M.; Fouad-Tarazi, F. M.

1993-01-01

PURPOSE: To investigate the efficacy and safety of midodrine for treatment of patients with orthostatic hypotension due to autonomic failure. PATIENTS: Ninety-seven patients with orthostatic hypotension were randomized in a 4-week, double-blinded, placebo-controlled study with a 1-week placebo run-in period. Patients ranged in age from 22 to 86 years (mean: 61 years). METHODS: After a 1-week run-in phase, either placebo or midodrine at a dose of 2.5 mg, 5 mg, or 10 mg was administered three times a day for 4 weeks. Both the placebo group and the 2.5-mg midodrine group received constant doses throughout the double-blind phase. The patients receiving 5 mg or 10 mg of midodrine were given doses that were increased at weekly intervals by 2.5-mg increments until the designated dose was reached. Efficacy evaluations were based on an improvement at 1-hour postdose in standing systolic blood pressure and in symptoms of orthostatic hypotension (syncope, dizziness/lightheadedness, weakness/fatigue, and low energy level). RESULTS: Midodrine (10 mg) increased standing systolic blood pressure by 22 mm Hg (28%, p < 0.001 versus placebo). Midodrine improved (p < 0.05) the following symptoms of orthostatic hypotension compared to placebo: dizziness/lightheadedness, weakness/fatigue, syncope, low energy level, impaired ability to stand, and feelings of depression. The overall side effects were mainly mild to moderate. One or more side effects were reported by 22% of the placebo group compared with 27% of the midodrine-treated group. Scalp pruritus/tingling, which was reported by 10 of 74 (13.5%) of the midodrine-treated patients, was most frequent. Other reported side effects included supine hypertension (8%) and feelings of urinary urgency (4%). CONCLUSION: We conclude that midodrine is an effective and well-tolerated treatment for moderate-to-severe orthostatic hypotension associated with autonomic failure.

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

PubMed

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

2010-08-01

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

Yukmijihwang-tang for the treatment of xerostomia in the elderly: study protocol for a randomized, double-blind, placebo-controlled, two-center trial

PubMed Central

2013-01-01

Background Xerostomia, a subjective sense of dry mouth, is not generally regarded a disease despite its high prevalence among the elderly, and therefore continues to impair affected patients’ quality of life. In traditional Korean medicine, ‘Yin-Deficiency’ has been implicated in the pathogenesis of xerostomia among the elderly. Yukmijihwang-tang is a famous herbal prescription used to relieve ‘Yin-Deficiency’, and reportedly has antioxidant effects; therefore, it is postulated that Yukmijihwang-tang can be used to treat xerostomia in the elderly. However, to our knowledge, no clinical trial has been conducted on the effects of Yukmijihwang-tang on xerostomia. Thus, we designed a randomized clinical trial to investigate the effects and safety of Yukmijihwang-tang on xerostomia in the elderly. In addition, we will clarify the aforementioned assumption that ‘Yin-Deficiency’ is the major cause of xerostomia in the elderly by identifying a correlation between xerostomia and ‘Yin-Deficiency’. Methods/Design This randomized, double-blind, placebo-controlled trial will be carried out at two centers: Kyung Hee University Korean Medicine Hospital and Kyung Hee University Hospital at Gangdong. We will recruit 96 subjects aged 60-80 years who have experienced xerostomia for 3 months prior to participation. Subjects who present with score >40 on the visual analogue scale for xerostomia and unstimulated salivary flow rate under 0.3mL/min will be included and the randomization will be carried out by an independent statistician by using a random number creation program. The subjects and all researchers except the statistician will be blinded to the group assignment. Yukmijihwang-tang or placebo will be administered to each group for 8 weeks. The primary outcome is change in the scores for the visual analogue scale for xerostomia and the dry mouth symptom questionnaire from 0 to 8 weeks. Discussion It will be assessed whether Yukmijihwang-tang can be used as a new herbal treatment for xerostomia in the elderly by demonstrating its therapeutic effects in a well-designed clinical trial. Trial registration ClinicalTrials.gov Identifier: NCT01579877 PMID:24004451

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

PubMed

Bavestrello, L; Caimi, L; Barbera, A

1985-01-01

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

Zopiclone as a preoperative night hypnotic: a double-blind comparison with temazepam and placebo.

PubMed

Whitehead, C; Sanders, L; Appadurai, I; Power, I; Rosen, M; Robinson, J

1994-04-01

We have examined the hypnotic effects of zopiclone 7.5 mg and temazepam 20 mg compared with placebo in a double-blind, randomized, clinical study of 60 patients on the night before operation. Evaluation was both subjective (visual analogue scales and a sleep questionnaire), to measure the quality of sleep, and objective (critical flicker fusion, object recall and paired associates tasks), to measure residual impairment. We found that zopiclone was an effective single-dose hypnotic with similar residual effects to the benzodiazepine and it may therefore provide a suitable alternative to benzodiazepines.

Once-daily atenolol in hypertensive Zimbabwean blacks. A double-blind trial using two different doses.

PubMed

Abson, C P; Levy, L M; Eyherabide, G

1981-07-11

A double-blind within-patient study was carried out on Zimbabwean Blacks to investigate the effect of once-daily atenolol on hypertension in doses of 100 and 200 mg/d. Atenolol 200 mg produced significant changes in diastolic pressure readings taken in the supine and standing positions and after exercise; with atenolol 100 mg modest but non-significant changes occurred. These findings are less impressive than those previously reported in White subjects. We conclude that beta-adrenoceptor blocking agents should not be used as drugs of first choice for hypertension in our Black population.

Norepinephrine transporter blocker atomoxetine increases salivary alpha amylase.

PubMed

Warren, Christopher M; van den Brink, Ruud L; Nieuwenhuis, Sander; Bosch, Jos A

2017-04-01

It has been suggested that central norepinephrine (NE) activity may be inferred from increases in salivary alpha-amylase (SAA), but data in favor of this proposition are limited. We administered 40mg of atomoxetine, a selective NE transporter blocker that increases central NE levels, to 24 healthy adult participants in a double-blind, placebo-controlled cross-over design. Atomoxetine administration significantly increased SAA secretion and concentrations at 75-180min after treatment (more than doubling baseline levels). Consistent with evidence that elevation in central NE is a co-determinant of hypothalamic-pituitary-adrenal axis activity, salivary cortisol also approximately doubled at the same time points. Moreover, changes in salivary cortisol positively correlated with SAA (0.44

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

PubMed

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

2015-09-01

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

Intranasal oxytocin reduces social perception in women: Neural activation and individual variation.

PubMed

Hecht, Erin E; Robins, Diana L; Gautam, Pritam; King, Tricia Z

2017-02-15

Most intranasal oxytocin research to date has been carried out in men, but recent studies indicate that females' responses can differ substantially from males'. This randomized, double-blind, placebo-controlled study involved an all-female sample of 28 women not using hormonal contraception. Participants viewed animations of geometric shapes depicting either random movement or social interactions such as playing, chasing, or fighting. Probe questions asked whether any shapes were "friends" or "not friends." Social videos were preceded by cues to attend to either social relationships or physical size changes. All subjects received intranasal placebo spray at scan 1. While the experimenter was not blinded to nasal spray contents at Scan 1, the participants were. Scan 2 followed a randomized, double-blind design. At scan 2, half received a second placebo dose while the other half received 24 IU of intranasal oxytocin. We measured neural responses to these animations at baseline, as well as the change in neural activity induced by oxytocin. Oxytocin reduced activation in early visual cortex and dorsal-stream motion processing regions for the social > size contrast, indicating reduced activity related to social attention. Oxytocin also reduced endorsements that shapes were "friends" or "not friends," and this significantly correlated with reduction in neural activation. Furthermore, participants who perceived fewer social relationships at baseline were more likely to show oxytocin-induced increases in a broad network of regions involved in social perception and social cognition, suggesting that lower social processing at baseline may predict more positive neural responses to oxytocin. Copyright © 2016 Elsevier Inc. All rights reserved.

Treatment of Xerosis with a Topical Formulation Containing Glyceryl Glucoside, Natural Moisturizing Factors, and Ceramide

PubMed Central

Kausch, Martina; Rippke, Frank; Schoelermann, Andrea M.; Filbry, Alexander W.

2012-01-01

Objective: To assess the effects of Light Formulation, an oil-in-water emulsion, and Rich Formulation, a water-in-oil emulsion, for the treatment of xerosis. Design: Two double-blind, vehicle-controlled trials (both formulations); a double-blind, randomized regression study (Rich Formulation); and a single-blind tolerability study (Light Formulation). The two formulations were applied twice daily for two weeks, for five days in the regression study, and twice daily for two weeks in the tolerability study. Setting: Studies were conducted during winter in Hamburg, Germany. Participants: A total of 169 subjects were enrolled and 154 completed the studies. The majority were between 50 and 80 years of age, women, all with very dry skin. One withdrew because of an incompatibility reaction that reoccurred with the subject's own body lotion after sun exposure. Measurements: Skin hydration and skin barrier function with both formulations over two weeks, long-term moisturization effect after discontinuation of Rich Formulation, and symptom improvement and skin tolerability with Light Formulation. Results: Vehicle-controlled studies of Light and Rich Formulations demonstrated significantly improved hydration at Weeks 1 and 2 versus the untreated site and vehicles, and significantly reduced transepidermal water loss versus untreated site and basic vehicle. Both products significantly decreased visible dryness and tactile roughness. In the regression study, Rich Formulation maintained significant moisturization six days after treatment discontinuation. Light Formulation reduced symptoms of itching, burning, tightness, tingling, and feeling of dryness. Conclusion: These formulations represent a new approach for the treatment of xerosis by addressing multiple key deficiencies in skin hydration. PMID:22916312

Trial of Naltrexone and Dextromethorphan for Gulf War Veterens’ Illness

DTIC Science & Technology

2016-03-01

held by the research pharmacist . Randomization was performed by drawing a card from a box that specified the order of administration. The study...study. The pills were administered in a randomized, double- blinded fashion. The code for the blinding was held by the research pharmacist

The Effect of Caffeine on Human Dark Adaptation.

DTIC Science & Technology

1977-04-06

UO~ mg. 100 mg .< Placebo T.M. 13** 9 3** G..11 (2 te)10 S.H. 9 (1 tie) 4 13** P < .05 **p. .005 N =13 K 9 EXPERIMENT II The analysis of Experiment...caffeinated session were not included in the analysis . A double blind design was again employed. Each S received a schedule in accordance wihh which he... tannins , and sodium in coffee, tea and cocoa. Journal of the American Medical Association, 1955, 158, 1030-1031. 17. Matthias, H., 8 Erdmann, D. The

Design of the Park-in-Shape study: a phase II double blind randomized controlled trial evaluating the effects of exercise on motor and non-motor symptoms in Parkinson's disease.

PubMed

van der Kolk, Nicolien M; Overeem, Sebastiaan; de Vries, Nienke M; Kessels, Roy P C; Donders, Rogier; Brouwer, Marc; Berg, Daniela; Post, Bart; Bloem, Bas R

2015-04-16

Parkinson's disease (PD) is a neurodegenerative disorder with a wide range of motor and non-motor symptoms. Despite optimal medical management, PD still results in a high disability rate and secondary complications and many patients lead a sedentary lifestyle, which in turn is also associated with a higher co-morbidity and mortality. Exercise has been explored as a strategy to reduce secondary complications and results suggests that it not only provides general health benefits, but may also provide symptomatic relief. If this holds true exercise would be a very attractive addition to the therapeutic arsenal in PD. The supportive evidence remains incomplete. Here, we describe the design of the Park-in-Shape study, which primarily aims to evaluate whether aerobic exercise affords clinically relevant improvements in motor symptoms in sedentary PD patients. A specific new element is the introduction of gaming to optimize compliance to the exercise intervention. The Park-in-Shape study is a randomized controlled, assessor- and patient-blinded single center study. Two parallel groups will include a total of 130 patients, receiving either aerobic exercise on a home trainer equipped with gaming elements ("exergaming"), or a non-aerobic intervention (stretching, flexibility and relaxation exercises). Both groups are supported by a specifically designed motivational app that uses gaming elements to stimulate patients to exercise and rewards them after having completed the exercise. Both interventions are delivered at home at least 3 times a week for 30-45 minutes during 6 months. Eligible patients are community-dwelling, sedentary patients diagnosed with mild-moderate PD. The primary outcome is the MDS-UPDRS motor score (tested in the off state) after 6 months. Secondary outcomes include various motor and non-motor symptoms, quality of life, physical fitness, and adherence. This Park-in-Shape study is anticipated to answer the question whether high intensity aerobic exercise combined with gaming elements ("exergaming") provides symptomatic relief in PD. Strong elements include the double-blinded randomized controlled trial design, the MDS-UPDRS as valid primary outcome, the large sample size and unique combination of home-based pure aerobic exercise combined with gaming elements and motivational aspects. Dutch trial register NTR4743.

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.

Effect of homeopathic Arnica montana on bruising in face-lifts: results of a randomized, double-blind, placebo-controlled clinical trial.

PubMed

Seeley, Brook M; Denton, Andrew B; Ahn, Min S; Maas, Corey S

2006-01-01

To design a model for performing reproducible, objective analyses of skin color changes and to apply this model to evaluate the efficacy of homeopathic Arnica montana as an antiecchymotic agent when taken perioperatively. Twenty-nine patients undergoing rhytidectomy at a tertiary care center were treated perioperatively with either homeopathic A. montana or placebo in a double-blind fashion. Postoperative photographs were analyzed using a novel computer model for color changes, and subjective assessments of postoperative ecchymosis were obtained. No subjective differences were noted between the treatment group and the control group, either by the patients or by the professional staff. No objective difference in the degree of color change was found. Patients receiving homeopathic A. montana were found to have a smaller area of ecchymosis on postoperative days 1, 5, 7, and 10. These differences were statistically significant (P<.05) only on postoperative days 1 (P<.005) and 7 (P<.001). This computer model provides an efficient, objective, and reproducible means with which to assess perioperative color changes, both in terms of area and degree. Patients taking perioperative homeopathic A. montana exhibited less ecchymosis, and that difference was statistically significant (P<.05) on 2 of the 4 postoperative data points evaluated.

Double-Blind Crossover Study to Compare Pain Experience During Inferior Alveolar Nerve Block Administration Using Buffered Two Percent Lidocaine in Children.

PubMed

Chopra, Radhika; Jindal, Garima; Sachdev, Vinod; Sandhu, Meera

2016-01-01

Buffering of anesthetic solutions has been suggested to reduce pain on injection and onset of anesthesia. The purpose of this study was to assess the reduction in pain on injection during inferior alveolar nerve block administration in children. A double blind crossover study was designed where 30 six- to 12-year-old patients received two sessions of inferior alveolar nerve block scheduled one week apart. Two percent lidocaine with 1:200,000 epinephrine was given during one appointment, and a buffered solution was given during the other. Pain on injection was assessed using the sound, eye, and motor (SEM) scale, and the time to onset was assessed after gingival probing. The Heft-Parker visual analogue scale (HP-VAS) was self recorded by the patient after administration of local anesthesia. When tested using Mann-Whitney analysis, no significant differences were found between the SEM scores (P=0.71) and HP-VAS scores (P=0.93) for the two solutions used. Student's t test was used to assess the difference in the onset of anesthesia, which was also found to be statistically insignificant (P=0.824). Buffered lidocaine did not reduce the pain on injection or time to onset of anesthesia for inferior alveolar nerve block in children.

Ineffectiveness of human chorionic gonadotropin in weight reduction: a double-blind study.

PubMed

Stein, M R; Julis, R E; Peck, C C; Hinshaw, W; Sawicki, J E; Deller, J J

1976-09-01

Our investigation was designed to retest the hypothesis of the efficacy of human chorionic gonadotropin (HCG) on weight reduction in obese women in a clinic setting. We sought to duplicate the Asher-Harper study (1973) which had found that the combination of 500 cal diet and HCG had a statistically significant benefit over the diet and placebo combination as evidenced by greater weight loss and decrease in hunger. Fifty-one women between the ages of 18 and 60 participated in our 32-day prospective, randomized, double-blind comparison of HCG versus placebo. Each patient was given the same diet (the one prescribed in the Asher-Harper study), was weighed daily Monday through Saturday and was counselled by one of the investigators who administered the injections. Laboratory studies were performed at the time of initial physical examinations and at the end of the study. Twenty of 25 in the HCG and 21 of 26 patients in the placebo groups completed 28 injections. There was no statistically significant difference in the means of the two groups in number of injections received, weight loss, percent of weight loss, hip and waist circumference, weight loss per injections, or in hunger ratings. HCG does not appear to enhance the effectiveness of a rigidly imposed regimen for weight reduction.

BEMER Therapy Combined with Physiotherapy in Patients with Musculoskeletal Diseases: A Randomised, Controlled Double Blind Follow-Up Pilot Study

PubMed Central

Gyulai, Franciska; Rába, Katalin; Baranyai, Ildikó; Berkes, Enikő; Bender, Tamás

2015-01-01

Background. This study evaluates the effect of adjuvant BEMER therapy in patients with knee arthrosis and chronic low back pain in a randomized double blind design. Methods. A total of 50 patients with chronic low back pain and 50 patients with osteoarthritis of knee took part in this study and were randomized into 4 groups. Hospitalized patients received a standardized physiotherapy package for 3 weeks followed by BEMER therapy or placebo. Results. In patients with low back pain, the comparison of the results obtained at the first and second visit showed a significant improvement in resting VAS scores and Fatigue Scale scores. The Oswestry scores and Quality of Life Scale scores showed no change. In patients with knee arthrosis, the comparison of the first and second measurements showed no significant improvement in the abovementioned parameters, while the comparison of the first and third scores revealed a significant improvement in the Fatigue Scale scores and in the vitality test on the Quality of Life Scale. Conclusions. Our study showed that BEMER physical vascular therapy reduced pain and fatigue in the short term in patients with chronic low back pain, while long-term therapy appears to be beneficial in patients with osteoarthritis of knee. PMID:26078768

Static magnetic therapy does not decrease pain or opioid requirements: a randomized double-blind trial.

PubMed

Cepeda, M Soledad; Carr, Daniel B; Sarquis, Tony; Miranda, Nelcy; Garcia, Ricardo J; Zarate, Camilo

2007-02-01

A growing multibillion dollar industry markets magnetic necklaces, bracelets, bands, insoles, back braces, mattresses, etc., for pain relief, although there is little evidence for their efficacy. We sought to evaluate the effect of magnetic therapy on pain intensity and opioid requirements in patients with postoperative pain. We designed a randomized, double-blind, controlled trial. One-hundred-sixty-five patients older than 12 yr of age were randomized to magnetic (n = 81) or sham therapy (n = 84) upon reporting moderate-to-severe pain in the postanesthesia care unit. Devices were placed over the surgical incision and left in place for 2 h. Patients rated their pain intensity on a 0-10 scale every 10 min and received incremental doses of morphine until pain intensity was < or =4 of 10. Pain intensity levels were similar in both groups. The magnet group had on average 0.04 U more pain intensity (95% confidence interval, -0.4 to 0.5) than the sham group. Opioid requirements also were similar in both groups. The active magnet group required 1.5 mg more morphine (95% confidence interval, -1.8 to 4.0) than the sham magnet group. Magnetic therapy lacks efficacy in controlling acute postoperative pain intensity levels or opioid requirements and should not be recommended for pain relief in this setting.

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.

Modafinil alters decision making based on feedback history - a randomized placebo-controlled double blind study in humans.

PubMed

Bellebaum, Christian; Kuchinke, Lars; Roser, Patrik

2017-02-01

Modafinil is becoming increasingly popular as a cognitive enhancer. Research on the effects of modafinil on cognitive function have yielded mixed results, with negative findings for simple memory and attention tasks and enhancing effects for more complex tasks. In the present study we examined whether modafinil, due to its known effect on the dopamine level in the striatum, alters feedback-related choice behaviour. We applied a task that separately tests the choice of previously rewarded behaviours (approach) and avoidance of previously punished behaviours. 18 participants received a single dose of 200 mg modafinil. Their performance was compared to a group of 22 participants who received placebo in a double-blind design. Modafinil but not placebo induced a significant bias towards approach behaviour as compared to the frequency of avoidance behaviour. General attention, overall feedback-based acquisition of choice behaviour and reaction times in high vs low conflict choices were not significantly affected by modafinil. This finding suggests that modafinil has a specific effect on dopamine-mediated choice behaviour based on the history of feedback, while a contribution of noradrenaline is also conceivable. The described change in decision making cannot be considered as cognitive enhancement, but might rather have detrimental effects on decisions in everyday life.

[Prevention of migraine with flunarizine and acetylsalicylic acid. A double-blind study].

PubMed

Pothmann, R

1987-09-01

30 children between 7 and 17 years suffering from at least 2 attacks/month of common or classical migraine since more than 1 year were studied. After clinical exclusion of symptomatic headache 4 weeks were documented by means of a migraine diary. Prophylaxis with Calcium entry blocker Flunarizine (Sibelium) or Thromboxane A inhibitor Acetylsalicylic acid (ASS) was carried out in a double blind design for 3 months. Medication was given as one dosage in the evening: 2-5 mg/kg KG ASS or 5-10 mg Flunarizine. Documented attack frequency and duration were controlled at monthly physical examinations. Final results showed no differences in significant reduction of attack frequency or symptoms between both different therapeutic principals. 72.4% (ASS 73.3%; Flunarizine 71.4%) of patients were attack-free or had at least a 50% reduction. Migraine frequency of initially 7-8 was reduced to 1-2 attacks/month. Duration remained constant in both groups (1-3 h). Side effects were slight body weight gain or abdominal pain after intake, prophylaxis had not to be interrupted therefore. Longtime prognosis is not yet possible because the time of observation is too short so far. Both substances are definitely useful and have few side effects in childhood migraine. If the response to one is insufficient the other substance should be tried.

Effects of the combination of metyrapone and oxazepam on cocaine craving and cocaine taking: a double-blind, randomized, placebo-controlled pilot study.

PubMed

Kablinger, Anita S; Lindner, Marie A; Casso, Stephanie; Hefti, Franz; DeMuth, George; Fox, Barbara S; McNair, Lindsay A; McCarthy, Bruce G; Goeders, Nicholas E

2012-07-01

Although cocaine dependence affects an estimated 1.6 million people in the USA, there are currently no medications approved for the treatment of this disorder. Experiments performed in animal models have demonstrated that inhibitors of the stress response effectively reduce intravenous cocaine self-administration. This exploratory, double-blind, placebo-controlled study was designed to assess the safety and efficacy of combinations of the cortisol synthesis inhibitor metyrapone, and the benzodiazepine oxazepam, in 45 cocaine-dependent individuals. The subjects were randomized to a total daily dose of 500 mg metyrapone/20 mg oxazepam (low dose), a total daily dose of 1500 mg metyrapone/20 mg oxazepam (high dose), or placebo for 6 weeks of treatment. The outcome measures were a reduction in cocaine craving and associated cocaine use as determined by quantitative measurements of the cocaine metabolite benzoylecgonine (BE) in urine at all visits. Of the randomized subjects, 49% completed the study. The combination of metyrapone and oxazepam was well tolerated and tended to reduce cocaine craving and cocaine use, with significant reductions at several time points when controlling for baseline scores. These data suggest that further assessments of the ability of the metyrapone and oxazepam combination to support cocaine abstinence in cocaine-dependent subjects are warranted.

Lubiprostone plus PEG electrolytes versus placebo plus PEG electrolytes for outpatient colonoscopy preparation: a randomized, double-blind placebo-controlled trial.

PubMed

Sofi, Aijaz A; Nawras, Ali T; Pai, Chetan; Samuels, Qiana; Silverman, Ann L

2015-01-01

Bowel preparation using large volume of polyethylene glycol (PEG) solutions is often poorly tolerated. Therefore, there are ongoing efforts to develop an alternative bowel cleansing regimen that should be equally effective and better tolerated. The aim of this study was to assess the efficacy of lubiprostone (versus placebo) plus PEG as a bowel cleansing preparation for colonoscopy. Our study was a randomized, double-blind placebo-controlled design. Patients scheduled for screening colonoscopy were randomized 1:1 to lubiprostone (group 1) or placebo (group 2) plus 1 gallon of PEG. The primary endpoints were patient's tolerability and endoscopist's evaluation of the preparation quality. The secondary endpoint was to determine any reduction in the amount of PEG consumed in the lubiprostone group compared with the placebo group. One hundred twenty-three patients completed the study and were included in the analysis. There was no difference in overall cleanliness. The volume of PEG was similar in both the groups. The volume of PEG approached significance as a predictor of improved score for both the groups (P = 0.054). Lubiprostone plus PEG was similar to placebo plus PEG in colon cleansing and volume of PEG consumed. The volume of PEG consumed showed a trend toward improving the quality of the colon cleansing.

Randomized, double-blind, multicenter study of the immunogenicity and reactogenicity of 17DD and WHO 17D-213/77 yellow fever vaccines in children: implications for the Brazilian National Immunization Program.

PubMed

2007-04-20

Vaccines against yellow fever currently recommended by the World Health Organization contain either virus sub-strains 17D or 17DD. In adults, the 17DD vaccine demonstrated high seroconversion and similar performance to vaccines manufactured with the WHO 17D-213/77 seed-lot. In another study, 17DD vaccine showed lower seroconversion rates in children younger than 2 years. Data also suggested lower seroconversion with simultaneous application of measles vaccine. This finding in very young children is not consistent with data from studies with 17D vaccines. A multicenter, randomized, double-blind clinical trial was designed (1) to compare the immunogenicity and reactogenicity of two yellow fever vaccines: 17DD (licensed product) and 17D-213/77 (investigational product) in children aged 9-23 months; (2) to assess the effect of simultaneous administration of yellow fever and the measles-mumps-rubella vaccines; and (3) to investigate the interference of maternal antibodies in the response to yellow fever vaccination. The anticipated implications of the results are changes in vaccine sub-strains used in manufacturing YF vaccine used in several countries and changes in the yellow fever vaccination schedule recommendations in national immunization programs.

Low-level light therapy for androgenetic alopecia: a 24-week, randomized, double-blind, sham device-controlled multicenter trial.

PubMed

Kim, Hyojin; Choi, Jee Woong; Kim, Jun Young; Shin, Jung Won; Lee, Seok-Jong; Huh, Chang-Hun

2013-08-01

Androgenetic alopecia (AGA) is a common disorder affecting men and women. Finasteride and minoxidil are well-known, effective treatment methods, but patients who exhibit a poor response to these methods have no additional adequate treatment modalities. To evaluate the efficacy and safety of a low-level light therapy (LLLT) device for the treatment of AGA. This study was designed as a 24-week, randomized, double-blind, sham device-controlled trial. Forty subjects with AGA were enrolled and scheduled to receive treatment with a helmet-type, home-use LLLT device emitting wavelengths of 630, 650, and 660 nm or a sham device for 18 minutes daily. Investigator and subject performed phototrichogram assessment (hair density and thickness) and global assessment of hair regrowth for evaluation. After 24 weeks of treatment, the LLLT group showed significantly greater hair density than the sham device group. Mean hair diameter improved statistically significantly more in the LLLT group than in the sham device group. Investigator global assessment showed a significant difference between the two groups, but that of the subject did not. No serious adverse reactions were detected. LLLT could be an effective treatment for AGA. © 2013 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.

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

PubMed

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

2004-08-01

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

Efficacy and safety of rasagiline as an adjunct to levodopa treatment in Chinese patients with Parkinson's disease: a randomized, double-blind, parallel-controlled, multi-centre trial.

PubMed

Zhang, Lina; Zhang, Zhiqin; Chen, Yangmei; Qin, Xinyue; Zhou, Huadong; Zhang, Chaodong; Sun, Hongbin; Tang, Ronghua; Zheng, Jinou; Yi, Lin; Deng, Liying; Li, Jinfang

2013-08-01

Rasagiline mesylate is a highly potent, selective and irreversible monoamine oxidase type B (MAOB) inhibitor and is effective as monotherapy or adjunct to levodopa for patients with Parkinson's disease (PD). However, few studies have evaluated the efficacy and safety of rasagiline in the Chinese population. This study was designed to investigate the safety and efficacy of rasagiline as adjunctive therapy to levodopa treatment in Chinese PD patients. This was a randomized, double-blind, placebo-controlled, parallel-group, multi-centre trial conducted over a 12-wk period that enrolled 244 PD patients with motor fluctuations. Participants were randomly assigned to oral rasagiline mesylate (1 mg) or placebo, once daily. Altogether, 219 patients completed the trial. Rasagiline showed significantly greater efficacy compared with placebo. During the treatment period, the primary efficacy variable--mean adjusted total daily off time--decreased from baseline by 1.7 h in patients treated with 1.0 mg/d rasagiline compared to placebo (p < 0.05). Scores using the Unified Parkinson's Disease Rating Scale also improved during rasagiline treatment. Rasagiline was well tolerated. This study demonstrated that rasagiline mesylate is effective and well tolerated as an adjunct to levodopa treatment in Chinese PD patients with fluctuations.

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.

Prospective double-blind clinical trial evaluating the effectiveness of Bromelain in the third molar extraction postoperative period

PubMed Central

de la Barrera-Núñez, María C.; Yáñez-Vico, Rosa M.; Batista-Cruzado, Antonio; Heurtebise-Saavedra, Jean M.; Castillo-de Oyagüe, Raquel

2014-01-01

Objectives: To evaluate the anti-inflammatory and analgesic effect of Bromelain (pineapple extract) administered orally in the postoperative after extraction of impacted lower molars. Study Design: This is a prospective, placebo-controlled, unicentric, double-blind study; the sample size was 34 patients. The pre and postoperative outcomes, evaluated on the third (D3) and eighth day (D8), included inflamtion, pain and oral aperture, as well as the need for analgesics. One group received bromelain 150mg per day for three days and 100mg on days 4 to 7. The other group received placebo in the same dosage. All outcomes werrecorded quantitatively and analyzed with the Mann-Whitney U test for independent samples. Results: Although there were no statistically significant differences between the treatment groups, a trend towards less inflammation and improved oral aperture was observed in the group that received bromelain, compared to the group that received placebo. This trend can be attributed completely to random reasons, since there is no statistical difference in the results. Conclusions: Further studies are necessary to analyze different administration patterns and doses of bromelain for the use in the postoperative of impacted third molars. Key words:Tooth extraction, third molar, postoperative period, bromeline, clinical study. PMID:24316697

Does short-term exposure to mobile phone base station signals increase symptoms in individuals who report sensitivity to electromagnetic fields? A double-blind randomized provocation study.

PubMed

Eltiti, Stacy; Wallace, Denise; Ridgewell, Anna; Zougkou, Konstantina; Russo, Riccardo; Sepulveda, Francisco; Mirshekar-Syahkal, Dariush; Rasor, Paul; Deeble, Roger; Fox, Elaine

2007-11-01

Individuals with idiopathic environmental illness with attribution to electromagnetic fields (IEI-EMF) believe they suffer negative health effects when exposed to electromagnetic fields from everyday objects such as mobile phone base stations. This study used both open provocation and double-blind tests to determine if sensitive and control individuals experience more negative health effects when exposed to base station-like signals compared with sham. Fifty-six self-reported sensitive and 120 control participants were tested in an open provocation test. Of these, 12 sensitive and 6 controls withdrew after the first session. The remainder completed a series of double-blind tests. Subjective measures of well-being and symptoms as well as physiological measures of blood volume pulse, heart rate, and skin conductance were obtained. During the open provocation, sensitive individuals reported lower levels of well-being in both the global system for mobile communication (GSM) and universal mobile telecommunications system (UMTS) compared with sham exposure, whereas controls reported more symptoms during the UMTS exposure. During double-blind tests the GSM signal did not have any effect on either group. Sensitive participants did report elevated levels of arousal during the UMTS condition, whereas the number or severity of symptoms experienced did not increase. Physiological measures did not differ across the three exposure conditions for either group. Short-term exposure to a typical GSM base station-like signal did not affect well-being or physiological functions in sensitive or control individuals. Sensitive individuals reported elevated levels of arousal when exposed to a UMTS signal. Further analysis, however, indicated that this difference was likely to be due to the effect of order of exposure rather than the exposure itself.

Assessment of Allergy to Milk, Egg, Cod, and Wheat in Swedish Schoolchildren: A Population Based Cohort Study.

PubMed

Winberg, Anna; West, Christina E; Strinnholm, Åsa; Nordström, Lisbeth; Hedman, Linnea; Rönmark, Eva

2015-01-01

Knowledge about the prevalence of allergies to foods in childhood and adolescence is incomplete. The purpose of this study was to investigate the prevalence of allergies to milk, egg, cod, and wheat using reported data, clinical examinations, and double-blind placebo-controlled food challenges, and to describe the phenotypes of reported food hypersensitivity in a cohort of Swedish schoolchildren. In a population-based cohort of 12-year-old children, the parents of 2612 (96% of invited) completed a questionnaire. Specific IgE antibodies to foods were analyzed in a random sample (n=695). Children reporting complete avoidance of milk, egg, cod, or wheat due to perceived hypersensitivity and without physician-diagnosed celiac disease were invited to undergo clinical examination that included specific IgE testing, a celiac screening test, and categorization into phenotypes of food hypersensitivity according to preset criteria. Children with possible food allergy were further evaluated with double-blind challenges. In this cohort, the prevalence of reported food allergy to milk, egg, cod, or wheat was 4.8%. Food allergy was diagnosed in 1.4% of the children after clinical evaluation and in 0.6% following double-blind placebo-controlled food challenge. After clinical examination, children who completely avoided one or more essential foods due to perceived food hypersensitivity were categorized with the following phenotypes: allergy (29%), outgrown allergy (19%), lactose intolerance (40%), and unclear (12%). There was a high discrepancy in the prevalence of allergy to milk, egg, cod and wheat as assessed by reported data, clinical evaluation, and double-blind food challenges. Food hypersensitivity phenotyping according to preset criteria was helpful for identifying children with food allergy.

Does Short-Term Exposure to Mobile Phone Base Station Signals Increase Symptoms in Individuals Who Report Sensitivity to Electromagnetic Fields? A Double-Blind Randomized Provocation Study

PubMed Central

Eltiti, Stacy; Wallace, Denise; Ridgewell, Anna; Zougkou, Konstantina; Russo, Riccardo; Sepulveda, Francisco; Mirshekar-Syahkal, Dariush; Rasor, Paul; Deeble, Roger; Fox, Elaine

2007-01-01

Background Individuals with idiopathic environmental illness with attribution to electromagnetic fields (IEI-EMF) believe they suffer negative health effects when exposed to electromagnetic fields from everyday objects such as mobile phone base stations. Objectives This study used both open provocation and double-blind tests to determine if sensitive and control individuals experience more negative health effects when exposed to base station-like signals compared with sham. Methods Fifty-six self-reported sensitive and 120 control participants were tested in an open provocation test. Of these, 12 sensitive and 6 controls withdrew after the first session. The remainder completed a series of double-blind tests. Subjective measures of well-being and symptoms as well as physiological measures of blood volume pulse, heart rate, and skin conductance were obtained. Results During the open provocation, sensitive individuals reported lower levels of well-being in both the global system for mobile communication (GSM) and universal mobile telecommunications system (UMTS) compared with sham exposure, whereas controls reported more symptoms during the UMTS exposure. During double-blind tests the GSM signal did not have any effect on either group. Sensitive participants did report elevated levels of arousal during the UMTS condition, whereas the number or severity of symptoms experienced did not increase. Physiological measures did not differ across the three exposure conditions for either group. Conclusions Short-term exposure to a typical GSM base station-like signal did not affect well-being or physiological functions in sensitive or control individuals. Sensitive individuals reported elevated levels of arousal when exposed to a UMTS signal. Further analysis, however, indicated that this difference was likely to be due to the effect of order of exposure rather than the exposure itself. PMID:18007992

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

PubMed

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

2005-10-01

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

Long-term safety and efficacy of dalfampridine for walking impairment in patients with multiple sclerosis: Results of open-label extensions of two Phase 3 clinical trials

PubMed Central

Goodman, Andrew D; Bethoux, Francois; Brown, Theodore R; Schapiro, Randall T; Cohen, Ron; Marinucci, Lawrence N; Henney, Herbert R

2015-01-01

Background: In Phase 3 double-blind trials (MS-F203 and MS-F204), dalfampridine extended release tablets 10 mg twice daily (dalfampridine-ER; prolonged-release fampridine in Europe; fampridine modified or sustained release elsewhere) improved walking speed relative to placebo in patients with multiple sclerosis (MS). Objectives: Evaluation of long-term safety and efficacy of dalfampridine-ER in open-label extensions (MS-F203EXT, MS-F204EXT). Methods: Patients received dalfampridine-ER 10 mg twice daily; and had Timed 25-Foot Walk (T25FW) assessments at 2, 14 and 26 weeks, and then every 6 months. Subjects were categorized as dalfampridine-ER responders or non-responders, based on their treatment response in the double-blind parent trials that assessed T25FW. Results: We had 269 patients enter MS-F203EXT and 154 patients complete it; for a maximum exposure of 5 years. We had 214 patients enter MS-F204EXT and 146 complete it; for a maximum exposure of 3.3 years. No new safety signals emerged and dalfampridine-ER tolerability was consistent with the double-blind phase. Improvements in walking speed were lost after dalfampridine-ER was discontinued in the parent trial, but returned by the 2-week assessment after re-initiation of the drug. Throughout the extensions, mean improvement in walking speed declined, but remained improved, among the double-blind responders as compared with non-responders. Conclusions: The dalfamipridine-ER safety profile was consistent with the parent trials. Although walking speed decreased over time, dalfampridine-ER responders continued to show improved walking speed, which was sustained compared with non-responders. PMID:25583832

Assessment of Allergy to Milk, Egg, Cod, and Wheat in Swedish Schoolchildren: A Population Based Cohort Study

PubMed Central

Winberg, Anna; West, Christina E; Strinnholm, Åsa; Nordström, Lisbeth; Hedman, Linnea; Rönmark, Eva

2015-01-01

Objectives Knowledge about the prevalence of allergies to foods in childhood and adolescence is incomplete. The purpose of this study was to investigate the prevalence of allergies to milk, egg, cod, and wheat using reported data, clinical examinations, and double-blind placebo-controlled food challenges, and to describe the phenotypes of reported food hypersensitivity in a cohort of Swedish schoolchildren. Methods In a population-based cohort of 12-year-old children, the parents of 2612 (96% of invited) completed a questionnaire. Specific IgE antibodies to foods were analyzed in a random sample (n=695). Children reporting complete avoidance of milk, egg, cod, or wheat due to perceived hypersensitivity and without physician-diagnosed celiac disease were invited to undergo clinical examination that included specific IgE testing, a celiac screening test, and categorization into phenotypes of food hypersensitivity according to preset criteria. Children with possible food allergy were further evaluated with double-blind challenges. Results In this cohort, the prevalence of reported food allergy to milk, egg, cod, or wheat was 4.8%. Food allergy was diagnosed in 1.4% of the children after clinical evaluation and in 0.6% following double-blind placebo-controlled food challenge. After clinical examination, children who completely avoided one or more essential foods due to perceived food hypersensitivity were categorized with the following phenotypes: allergy (29%), outgrown allergy (19%), lactose intolerance (40%), and unclear (12%). Conclusions There was a high discrepancy in the prevalence of allergy to milk, egg, cod and wheat as assessed by reported data, clinical evaluation, and double-blind food challenges. Food hypersensitivity phenotyping according to preset criteria was helpful for identifying children with food allergy. PMID:26134827

Repeat Rifaximin for Irritable Bowel Syndrome: No Clinically Significant Changes in Stool Microbial Antibiotic Sensitivity.

PubMed

Pimentel, M; Cash, B D; Lembo, A; Wolf, R A; Israel, R J; Schoenfeld, P

2017-09-01

Rifaximin has demonstrated efficacy and safety for diarrhea-predominant irritable bowel syndrome (IBS-D). To determine the rifaximin repeat treatment effect on fecal bacterial antibiotic susceptibility. Patients with IBS in Trial 3 (TARGET 3) study who responded to open-label rifaximin 550 mg three times daily for 2 weeks, with symptom recurrence within 18 weeks, were randomized to double-blind treatment: two 2-week repeat courses of rifaximin or placebo, separated by 10 weeks. Prospective stool sample collection occurred before and after open-label rifaximin, before and after the first repeat course, and at the end of the study. Susceptibility testing was performed with 11 antibiotics, including rifaximin and rifampin, using broth microdilution or agar dilution methods. Of 103 patients receiving open-label rifaximin, 73 received double-blind rifaximin (n = 37) or placebo (n = 36). A total of 1429 bacterial and yeast isolates were identified, of which Bacteroidaceae (36.7%) and Enterobacteriaceae (33.9%) were the most common. In the double-blind phase, Clostridium difficile was highly susceptible to rifaximin [minimum inhibitory concentration (MIC) range 0.008-1 µg/mL] and rifampin (MIC range 0.004-0.25 µg/mL). Following double-blind rifaximin treatment, Staphylococcus isolates remained susceptible to rifaximin at all visits (MIC 50 range ≤0.06-32 µg/mL). Rifaximin exposure was not associated with long-term cross-resistance of Bacteroidaceae, Enterobacteriaceae, and Enterococcaceae to rifampin or nonrifamycin antibiotics tested. In this study, short-term repeat treatment with rifaximin has no apparent long-term effect on stool microbial susceptibility to rifaximin, rifampin, and nonrifamycin antibiotics. CLINICALTRIALS. NCT01543178.

Forward and inverse solutions for three-element Risley prism beam scanners.

PubMed

Li, Anhu; Liu, Xingsheng; Sun, Wansong

2017-04-03

Scan blind zone and control singularity are two adverse issues for the beam scanning performance in double-prism Risley systems. In this paper, a theoretical model which introduces a third prism is developed. The critical condition for a fully eliminated scan blind zone is determined through a geometric derivation, providing several useful formulae for three-Risley-prism system design. Moreover, inverse solutions for a three-prism system are established, based on the damped least-squares iterative refinement by a forward ray tracing method. It is shown that the efficiency of this iterative calculation of the inverse solutions can be greatly enhanced by a numerical differentiation method. In order to overcome the control singularity problem, the motion law of any one prism in a three-prism system needs to be conditioned, resulting in continuous and steady motion profiles for the other two prisms.

Misplacement of left-sided double-lumen tubes into the right mainstem bronchus: incidence, risk factors and blind repositioning techniques.

PubMed

Seo, Jeong-Hwa; Bae, Jun-Yeol; Kim, Hyun Joo; Hong, Deok Man; Jeon, Yunseok; Bahk, Jae-Hyon

2015-10-28

Double-lumen endobronchial tubes (DLTs) are commonly advanced into the mainstem bronchus either blindly or by fiberoptic bronchoscopic guidance. However, blind advancement may result in misplacement of left-sided DLTs into the right bronchus. Therefore, incidence, risk factors, and blind repositioning techniques for right bronchial misplacement of left-sided DLTs were investigated. This was an observational cohort study performed on the data depository consecutively collected from patients who underwent intubation of left-sided DLTs for 2 years. Patients' clinical and anatomical characteristics were analyzed to investigate risk factors for DLT misplacements with logistic regression analysis. Moreover, when DLTs were misplaced into the right bronchus, the bronchial tube was withdrawn into the trachea and blindly readvanced without rotation, or with 90° or 180° counterclockwise rotation while the patient's head was turned right. DLTs were inadvertently advanced into the right bronchus in 48 of 1135 (4.2 %) patients. DLT misplacements occurred more frequently in females, in patients of short stature or with narrow trachea and bronchi, and when small-sized DLTs were used. All of these factors were significantly inter-correlated each other (P < 0.001). In 40 of the 48 (83.3 %) patients, blind repositioning was successful. Smaller left-sided DLTs were more frequently misplaced into the right mainstem bronchus than larger DLTs. Moreover, we were usually able to reposition the misplaced DLTs into the left bronchus by using the blind techniques. ClinicalTrials.gov Identifier: NCT01371773.

Intraindividual comparison of 1,470 nm diode laser versus carbon dioxide laser for tonsillotomy: a prospective, randomized, double blind, controlled feasibility trial.

PubMed

Havel, Miriam; Sroka, Ronald; Englert, Elsa; Stelter, Klaus; Leunig, Andreas; Betz, Christian S

2012-09-01

The need for reduction of post-tonsillectomy hemorrhage has led to promotion of tonsillotomy techniques for tonsil tissue reduction in obstructive tonsillar hypertrophy. This trial compares ablative tissue effects using 1,470 nm diode laser and carbon dioxide laser for tonsillotomy in an intraindividual design. 21 children aged 3-13 years (mean age 6.3 years) underwent laser tonsillotomy for obstructive tonsillar hypertrophy in this double blind, prospective, randomized, clinical feasibility trial. In each of the blinded patients, tonsillotomy was performed using fiber guided 1,470 nm diode laser (contact mode, 15 W power) on the one side and carbon dioxide laser (12 W power) on the other side. An independent, blinded physician documented clinical presentation and patients' symptoms preoperatively and on Days 1, 3, 7, 14, and 21 post-operatively using standardized questionnaire including VAS for each side separately. The mean duration of operative treatment was 2.7 min using 1,470 nm laser and 4.9 min using carbon dioxide laser respectively. Intraoperative bleeding and the frequency of bipolar forceps use for intraoperative bleeding control was significantly less using 1,470 nm diode laser system. There was no difference in post-operative pain scores between the carbon dioxide laser treated and the 1,470 nm fiber guided diode laser treated side. No infections, hemorrhages or other complications occurred in the course of the 3 weeks post-operative period. A fiber-guided 1,470 nm diode laser system offers an efficient and safe method for tonsillotomy as treatment of obstructive tonsillar hypertrophy. Compared to our standard practice (carbon dioxide laser), 1,470 nm laser application provides comparable tissue ablation effects with less intraoperative bleeding and shorter operation time. Copyright © 2012 Wiley Periodicals, Inc.

Improvement in health-related quality of life after therapy with omeprazole in patients with coronary artery disease and recurrent angina-like chest pain. A double-blind, placebo-controlled trial of the SF-36 survey

PubMed Central

2011-01-01

Background Many patients with coronary artery disease (CAD) have overlapping gastroenterological causes of recurrent chest pain, mainly due to gastroesophageal reflux (GER) and aspirin-induced gastrointestinal tract damage. These symptoms can be alleviated by proton pump inhibitors (PPIs). The study addressed whether omeprazole treatment also affects general health-related quality of life (HRQL) in patients with CAD. Study 48 patients with more than 50% narrowing of the coronary arteries on angiography without clinically overt gastrointestinal symptoms were studied. In a double-blind, placebo-controlled, cross-over study design, patients were randomized to take omeprazole 20 mg bid or a placebo for two weeks, and then crossed over to the other study arm. The SF-36 questionnaire was completed before treatment and again after two weeks of therapy. Results Patients treated with omeprazole in comparison to the subjects taking the placebo had significantly greater values for the SF-36 survey (which relates to both physical and mental health), as well as for bodily pain, general health perception, and physical health. In comparison to the baseline values, therapy with omeprazole led to a significant increase in the three summarized health components: total SF-36; physical and mental health; and in the following detailed health concept scores: physical functioning, limitations due to physical health problems, bodily pain and emotional well-being. Conclusions A double dose of omeprazole improved the general HRQL in patients with CAD without severe gastrointestinal symptoms more effectively than the placebo. PMID:21939510

Ticagrelor with aspirin or alone in high-risk patients after coronary intervention: Rationale and design of the TWILIGHT study.

PubMed

Baber, Usman; Dangas, George; Cohen, David J; Gibson, C Michael; Mehta, Shamir R; Angiolillo, Dominick J; Pocock, Stuart J; Krucoff, Mitchell W; Kastrati, Adnan; Ohman, E Magnus; Steg, Philippe Gabriel; Badimon, Juan; Zafar, M Urooj; Chandrasekhar, Jaya; Sartori, Samantha; Aquino, Melissa; Mehran, Roxana

2016-12-01

Dual antiplatelet therapy (DAPT) is necessary to prevent thrombosis yet increases bleeding after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). Antiplatelet monotherapy with a potent P2Y 12 receptor antagonist may reduce bleeding while maintaining anti thrombotic efficacy compared with conventional DAPT. TWILIGHT is a randomized, double-blind placebo-controlled trial evaluating the comparative efficacy and safety of antiplatelet monotherapy versus DAPT in up to 9000 high-risk patients undergoing PCI with DES. Upon enrollment after successful PCI, all patients will be treated with open label low-dose aspirin (81-100 mg daily) plus ticagrelor (90 mg twice daily) for 3 months. Event-free patients will then be randomized in a double-blind fashion to low-dose aspirin versus matching placebo with continuation of open-label ticagrelor for an additional 12 months. The primary hypothesis is that a strategy of ticagrelor monotherapy will be superior with respect to the primary endpoint of bleeding academic research consortium type 2, 3 or 5, while maintaining non-inferiority for ischemic events compared with ticagrelor plus ASA. TWILIGHT is the largest study to date that is specifically designed and powered to demonstrate reductions in bleeding with ticagrelor monotherapy versus ticagrelor plus ASA beyond 3 months post-procedure in a high-risk PCI population treated with DES. The trial will provide novel insights with respect to the potential role of ticagrelor monotherapy as an alternative for long-term platelet inhibition in a broad population of patients undergoing PCI with DES. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

Warfarin versus aspirin in patients with reduced cardiac ejection fraction (WARCEF): rationale, objectives, and design.

PubMed

Pullicino, Patrick; Thompson, John L P; Barton, Bruce; Levin, Bruce; Graham, Susan; Freudenberger, Ronald S

2006-02-01

Warfarin is widely prescribed for patients with heart failure without level 1 evidence, and an adequately powered randomized study is needed. The Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction study is a National Institutes of Health-funded, randomized, double-blind clinical trial with a target enrollment of 2860 patients. It is designed to test with 90% power the 2-sided primary null hypothesis of no difference between warfarin (International Normalized Ratio 2.5-3) and aspirin (325 mg) in 3- to 5-year event-free survival for the composite endpoint of death, or stroke (ischemic or hemorrhagic) among patients with cardiac ejection fraction < or =35% who do not have atrial fibrillation or mechanical prosthetic heart valves. Secondary analyses will compare warfarin and aspirin for reduction of all-cause mortality, ischemic stroke, and myocardial infarction (MI), balanced against the risk of intracerebral hemorrhage, among women and African Americans; and compare warfarin and aspirin for prevention of stroke alone. Randomization is stratified by site, New York Heart Association (NYHA) heart class (I vs II-IV), and stroke or transient ischemic attack (TIA) within 1 year before randomization versus no stroke or TIA in that period. NYHA class I patients will not exceed 20%, and the study has a target of 20% (or more) patients with stroke or TIA within 12 months. Randomized patients receive active warfarin plus placebo or active aspirin plus placebo, double-blind. The results should help guide the selection of optimum antithrombotic therapy for patients with left ventricular dysfunction.

Study protocol of Prednisone in episodic Cluster Headache (PredCH): a randomized, double-blind, placebo-controlled parallel group trial to evaluate the efficacy and safety of oral prednisone as an add-on therapy in the prophylactic treatment of episodic cluster headache with verapamil

PubMed Central

2013-01-01

Background Episodic cluster headache (ECH) is a primary headache disorder that severely impairs patient’s quality of life. First-line therapy in the initiation of a prophylactic treatment is verapamil. Due to its delayed onset of efficacy and the necessary slow titration of dosage for tolerability reasons prednisone is frequently added by clinicians to the initial prophylactic treatment of a cluster episode. This treatment strategy is thought to effectively reduce the number and intensity of cluster attacks in the beginning of a cluster episode (before verapamil is effective). This study will assess the efficacy and safety of oral prednisone as an add-on therapy to verapamil and compare it to a monotherapy with verapamil in the initial prophylactic treatment of a cluster episode. Methods and design PredCH is a prospective, randomized, double-blind, placebo-controlled trial with parallel study arms. Eligible patients with episodic cluster headache will be randomized to a treatment intervention with prednisone or a placebo arm. The multi-center trial will be conducted in eight German headache clinics that specialize in the treatment of ECH. Discussion PredCH is designed to assess whether oral prednisone added to first-line agent verapamil helps reduce the number and intensity of cluster attacks in the beginning of a cluster episode as compared to monotherapy with verapamil. Trial registration German Clinical Trials Register DRKS00004716 PMID:23889923

The effectiveness of dopamine agonists for treatment of neuropsychiatric symptoms post brain injury and stroke.

PubMed

Sami, Musa Basseer; Faruqui, Rafey

2015-12-01

Traumatic brain injury and stroke are among the leading causes of neurological disability worldwide. Although dopaminergic agents have long been associated with improvement of neuropsychiatric outcomes, to date much of the evidence to date has been in case reports and case series or open label trials. We undertook a systematic review of double-blinded randomised controlled trials (RCT) to determine the effect of dopaminergic agents on pre-defined outcomes of (a) apathy; (b) psychomotor retardation; (c) behavioural management and (d) cognitive function. Databases searched were: Medline, EMBASE, and PsychInfo for human studies. The Cochrane Clinical Trials Database and the TRIP Medical database were also searched. All identified studies, were further hand-searched. We identified six studies providing data on 227 participants, 150 of whom received dopaminergic therapy. Trials were compromised by cross-over design, inadequate wash out period, small numbers and heterogeneous outcome measures. However one good quality RCT demonstrates the efficacy of amantadine in behavioural management. One further RCT shows methylphenidate-levodopa is efficacious for mood post-stroke. One study shows rotigotine to improve hemi-inattention caused by prefrontal damage. Our systematic review demonstrates an evolving evidence base to suggest some benefits in agitation and aggression, mood and attentional deficits. However, there are key limitations of the studies undertaken to date involving small numbers of participants, heterogeneous outcome measures, and variable study designs. There is a need for on-going large prospective double-blind RCTs in these medications using standardised criteria and outcomes to fully understand their effectiveness in this patient group.

Double Blind Test For Bio-Stimulation Effects On Pain Relief By Diode Laser

NASA Astrophysics Data System (ADS)

Saeki, Norio; Sembokuya, Iwajiro; Arakawa, Kazuo; Fujimasa, Iwao; Mabuchi, Kunihiko; Abe, Yuusuke; Atsumi, Kazuhiko

1989-09-01

The bio-stimulation effect of semiconductor laser on therapeutic pain relief was investigated by conducting a double blind test performed on more than one hundred patient subjects suffering from various neualgia. A compact laser therapeutic equipment with two laser probes each having 60 mW power was developed and utilized for the experiment. Each probe was driven by either the active or the dummy source selected randomly, and its results were stored in the memory for statistical processing. The therapeutic treatments including active and dummy treatments were performed on 102 subjects. The pain relief effects were confirmed for 85.5% of the subjects.

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

PubMed

Bounds, W; Vessey, M; Wiggins, P

1979-04-01

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

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

PubMed Central

Vischer, T L

1988-01-01

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

A randomized, 14-day, double-blind study evaluating conversion from hydrocodone/acetaminophen (Vicodin) to buprenorphine transdermal system 10 μg/h or 20 μg/h in patients with osteoarthritis pain.

PubMed

Ripa, Steven R; McCarberg, Bill H; Munera, Catherine; Wen, Warren; Landau, Craig J

2012-06-01

The objective of this study was to evaluate continued pain control and tolerability of converting patients from Vicodin (hydrocodone/acetaminophen; HCD/APAP) to the buprenorphine transdermal system (BTDS). Adult patients with pain from osteoarthritis receiving a stable dosage of HCD/APAP (i.e., 15 - 30 mg hydrocodone/day) were switched to an equivalent or near-equivalent dosage of open-label Vicodin for 7 days. Patients maintaining acceptable analgesia were stratified based on their Vicodin dosage and randomized to receive either titratable BTDS 10 μg/h or fixed-dose BTDS 20 μg/h. The primary efficacy variable was completion of the 14-day double-blind phase. Tolerability was assessed. A total of 84.3% of patients met the primary end point, completion of the 14-day double-blind phase (167/198 patients, 95% CI 79.3 - 89.4). Adverse events were consistent with those associated with the use of opioid analgesics and transdermal patches. There was a similar analgesic and tolerability profile when patients treated with Vicodin for osteoarthritis pain were switched to 7-day BTDS treatment.

Clinical effectiveness of garlic (Allium sativum).

PubMed

Pittler, Max H; Ernst, Edzard

2007-11-01

The objective of this review is to update and assess the clinical evidence based on rigorous trials of the effectiveness of garlic (A. sativum). Systematic searches were carried out in Medline, Embase, Amed, the Cochrane Database of Systematic Reviews, Natural Standard, and the Natural Medicines Comprehensive Database (search date December 2006). Our own files, the bibliographies of relevant papers and the contents pages of all issues of the review journal FACT were searched for further studies. No language restrictions were imposed. To be included, trials were required to state that they were randomized and double blind. Systematic reviews and meta-analyses of garlic were included if based on the results of randomized, double-blind trials. The literature searches identified six relevant systematic reviews and meta-analysis and double-blind randomized trials (RCT) that were published subsequently. These relate to cancer, common cold, hypercholesterolemia, hypertension, peripheral arterial disease and pre-eclampsia. The evidence based on rigorous clinical trials of garlic is not convincing. For hypercholesterolemia, the reported effects are small and may therefore not be of clinical relevance. For reducing blood pressure, few studies are available and the reported effects are too small to be clinically meaningful. For all other conditions not enough data are available for clinical recommendations.

Effects of an oral contraceptive (norgestimate/ethinyl estradiol) on bone mineral density in women with hypothalamic amenorrhea and osteopenia: an open-label extension of a double-blind, placebo-controlled study.

PubMed

Warren, Michelle P; Miller, K K; Olson, W H; Grinspoon, S K; Friedman, A J

2005-09-01

The effects of long-term triphasic oral contraceptive administration on bone mineral density (BMD) were investigated in premenopausal women with hypothalamic amenorrhea (HA) and osteopenia. After completing three 28-day cycles in the double-blind phase of a placebo-controlled trial, women (mean age, 26.7 years) who received norgestimate 180-250 microg/ethinyl estradiol 35 microg (NGM/EE, n = 15) or placebo (n = 12) in the double-blind phase were to receive open-label NGM/EE for 10 additional cycles. For subjects completing > or =10 NGM/EE treatment cycles, mean posteroanterior total lumbar spine BMD (L1-L4) increased from 0.881+/-0.0624 g/cm2 at baseline (last visit prior to NGM/EE) to 0.894+/-0.0654 g/cm2 at final visit (p = .043); no significant changes in hip BMD occurred. Decreases in N-telopeptide, osteocalcin, procollagen type I propeptide and bone-specific alkaline phosphatase levels indicated effects on bone metabolism. Long-term administration of triphasic NGM/EE to osteopenic women with HA may increase total lumbar spine BMD.

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

Double-blinded, placebo-controlled study to evaluate an antipruritic shampoo for dogs with allergic pruritus.

PubMed

Schilling, J; Mueller, R S

2012-07-28

Shampoo therapy is frequently used on pruritic dogs. However, there are few double-blinded, placebo-controlled studies of this form of therapy. This randomised, double-blinded, placebo-controlled study evaluated the efficacy of a commercial medicated shampoo (DermaTopic; Almapharm) containing chlorhexidine, lactoferrin, piroctone olamine, chitosan and essential fatty acids in 27 dogs with mild to moderate allergic pruritus without secondary skin infections. All dogs received shampoo therapy with either DermaTopic or a shampoo vehicle as placebo twice weekly for four weeks. The extent of pruritus was evaluated before the study and then on a daily basis by the owners using a visual analogue scale. Before beginning the treatment and after four weeks, the skin lesions were evaluated by an experienced clinician with a validated lesion score (Canine Atopic Dermatitis Extent and Severity Index - CADESI). The pruritus was reduced significantly by both DermaTopic and placebo. However, there was no significant difference between both groups. There was no statistically significant difference in the CADESI scores pre- and post-treatment in either group or between the two types of treatment. This study provides further evidence of the benefit of shampoo therapy for pruritic dogs.

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

PubMed

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

2014-02-01

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

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

PubMed

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

2016-06-02

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

Key considerations for the experimental training and evaluation of cancer odour detection dogs: lessons learnt from a double-blind, controlled trial of prostate cancer detection

PubMed Central

2014-01-01

Background Cancer detection using sniffer dogs is a potential technology for clinical use and research. Our study sought to determine whether dogs could be trained to discriminate the odour of urine from men with prostate cancer from controls, using rigorous testing procedures and well-defined samples from a major research hospital. Methods We attempted to train ten dogs by initially rewarding them for finding and indicating individual prostate cancer urine samples (Stage 1). If dogs were successful in Stage 1, we then attempted to train them to discriminate prostate cancer samples from controls (Stage 2). The number of samples used to train each dog varied depending on their individual progress. Overall, 50 unique prostate cancer and 67 controls were collected and used during training. Dogs that passed Stage 2 were tested for their ability to discriminate 15 (Test 1) or 16 (Tests 2 and 3) unfamiliar prostate cancer samples from 45 (Test 1) or 48 (Tests 2 and 3) unfamiliar controls under double-blind conditions. Results Three dogs reached training Stage 2 and two of these learnt to discriminate potentially familiar prostate cancer samples from controls. However, during double-blind tests using new samples the two dogs did not indicate prostate cancer samples more frequently than expected by chance (Dog A sensitivity 0.13, specificity 0.71, Dog B sensitivity 0.25, specificity 0.75). The other dogs did not progress past Stage 1 as they did not have optimal temperaments for the sensitive odour discrimination training. Conclusions Although two dogs appeared to have learnt to select prostate cancer samples during training, they did not generalise on a prostate cancer odour during robust double-blind tests involving new samples. Our study illustrates that these rigorous tests are vital to avoid drawing misleading conclusions about the abilities of dogs to indicate certain odours. Dogs may memorise the individual odours of large numbers of training samples rather than generalise on a common odour. The results do not exclude the possibility that dogs could be trained to detect prostate cancer. We recommend that canine olfactory memory is carefully considered in all future studies and rigorous double-blind methods used to avoid confounding effects. PMID:24575737

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

PubMed Central

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

2013-01-01

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

Homeopathy for Perennial Asthma in Adolescents: Pilot Feasibility Study Testing a Randomised Withdrawal Design.

PubMed

Mitchiguian Hotta, Livia; Cardinalli Adler, Ubiratan; de Toledo Cesar, Amarilys; Martinez, Edson Zangiacomi; Demarzo, Marcelo Marcos Piva

2018-05-01

 Previous findings from a pragmatic trial suggest that usual care compared with usual care plus individualised homeopathy is not a feasible design to address homeopathic interventions for asthma.  The main purpose of this article was to investigate the feasibility of the randomised withdrawal design as a strategy to assess the effectiveness of a standardised clinical-pharmaceutical homeopathic protocol ( Organon.modus ) on perennial asthma in adolescents.  Randomised withdrawal, double-blind, parallel, placebo-controlled, 12-week study. 12 to 17 years old adolescents, with the diagnosis of perennial asthma, using inhalatory beclomethasone (plus fenoterol for wheezing episodes), who achieved 3 months of well-controlled asthma, after a variable period of individualised homeopathic treatment according to Organon.modus protocol. a secondary care medical specialist centre. continuation with the individualised homeopathic medicine or with indistinguishable placebo during 12 weeks of beclomethasone step-down. number of days of well-controlled asthma. Secondary measures: number of days of fenoterol use, number of visits to an emergency service (without hospitalisation) and percentage of patients excluded due to an exacerbation characterising a partly controlled asthma. Tolerability was assessed by Adverse Events, registered at every visit.  Nineteen patients were randomised to continue treatment with homeopathy and 21 with placebo. Effectiveness measures for the homeopathy and placebo groups respectively were median number of days of good clinical control: 84 versus 30 ( p  = 0.18); median number of days of fenoterol use per patient: 3 versus 5 ( p  = 0.41); visits to an emergency room: 1 versus 6 ( p  = 0.35); percentage of exclusion due to partly controlled asthma: 36.8% versus 71.4% ( p  = 0.05). Few Adverse Events were reported.  This pilot study supports the feasibility of the double-blind randomised withdrawal design in studies investigating homeopathy on teenage asthma, when performed by specialists following a standardised clinical-pharmaceutical homeopathic protocol.  RBR-6XTS8Z. The Faculty of Homeopathy.

Design and Rationale of the LAPLACE-TIMI 57 Trial: A Phase II, Double-Blind, Placebo-Controlled Study of the Efficacy and Tolerability of a Monoclonal Antibody Inhibitor of PCSK9 in Subjects With Hypercholesterolemia on Background Statin Therapy

PubMed Central

Kohli, Payal; Desai, Nihar R.; Giugliano, Robert P.; Kim, Jae B.; Somaratne, Ransi; Huang, Fannie; Knusel, Beat; McDonald, Shannon; Abrahamsen, Timothy; Wasserman, Scott M.; Scott, Robert; Sabatine, Marc S.

2013-01-01

Lowering low-density lipoprotein cholesterol (LDL-C) is a cornerstone for the prevention of atherosclerotic heart disease, improving clinical outcomes and reducing vascular mortality in patients with hypercholesterolemia. The clinical benefits of LDL-C reduction appear to extend even to patients starting with LDL-C as low as 60–80 mg/dL prior to initiating therapy. Statins are the first-line agents for treating hypercholesterolemia and are effective in reducing LDL-C, but many patients are unable to achieve their optimal lipid targets despite intensive statin therapy. Therefore, there has been a strong impetus for the development of novel pharmacologic agents designed to lower LDL-C further in patients already on statin therapy. Genetic mutations resulting in altered cholesterol homeostasis provide valuable information regarding novel approaches for treating hypercholesterolemia. To that end, mutations in proprotein convertase subtilisin/kexin type 9 (PCSK9) were linked to altered levels of LDL-C, illustrating this protein’s role in lipid metabolism. PCSK9 promotes degradation of the LDL receptor, preventing its transport back to the cell surface and thereby increasing circulating LDL-C. Conversely, inhibition of PCSK9 can profoundly decrease circulating LDL-C, and thus is an attractive new target for LDL-C–lowering therapy. AMG 145 is a fully human monoclonal immunoglobulin G2 antibody that binds specifically to human PCSK9 and inhibits its interaction with the low-density lipoprotein receptor. In this manuscript, we describe the rationale and design of LDL-C Assessment with PCSK9 Monoclonal Antibody Inhibition Combined With Statin Therapy–Thrombolysis In Myocardial Infarction 57 (LAPLACE-TIMI 57; NCT01380730), a 12-week, randomized, double-blind, dose-ranging, placebo-controlled study designed to assess the safety and efficacy of AMG 145 when added to statin therapy in patients with hypercholesterolemia. PMID:22714699

Opicapone as Adjunct to Levodopa Therapy in Patients With Parkinson Disease and Motor Fluctuations: A Randomized Clinical Trial.

PubMed

Lees, Andrew J; Ferreira, Joaquim; Rascol, Olivier; Poewe, Werner; Rocha, José-Francisco; McCrory, Michelle; Soares-da-Silva, Patricio

2017-02-01

Catechol O-methyltransferase (COMT) inhibitors are an established treatment for end-of-dose motor fluctuations associated with levodopa therapy in patients with Parkinson disease (PD). Current COMT inhibitors carry a high risk for toxic effects to hepatic cells or show moderate improvement. Opicapone was designed to be effective without the adverse effects. To evaluate the efficacy and safety of 25- and 50-mg/d dosages of opicapone compared with placebo as adjunct to levodopa therapy in patients with PD experiencing end-of-dose motor fluctuations. This phase 3 international, multicenter outpatient study evaluated a 25- and a 50-mg/d dosage of opicapone in a randomized, double-blind, 14- to 15-week, placebo-controlled clinical trial, followed by a 1-year open-label phase during which all patients received active treatment with opicapone. Patients with PD who experienced signs of end-of-dose deterioration and had a mean total awake off-time (state of akinesia or decreased mobility) of at least 1.5 hours, not including morning akinesia, were enrolled. Data were collected from March 18, 2011, through June 25, 2013. Data from the evaluable population were analyzed from July 31, 2013, to July 31, 2014. The primary efficacy outcome of the double-blind phase was the change from baseline in absolute off-time vs placebo based on patient diaries. The open-label phase focused on maintenance of treatment effect in off-time. A total of 427 patients (258 men [60.4%] and 169 women [39.6%]; mean [SD] age, 63.1 [8.8] years) were randomized to a 25-mg/d (n = 129) or a 50-mg/d (n = 154) dosage of opicapone or to placebo (n = 144). Of these, 376 patients completed the double-blind phase and entered the open-label phase, of whom 286 completed 1 year of open-label treatment. At the end of the double-blind phase, the least squares mean change (SE) in off-time was -64.5 (14.4) minutes for the placebo group, -101.7 (14.9) minutes for the 25-mg/d opicapone group, and -118.8 (13.8) minutes for the 50-mg/d opicapone group. The adjusted treatment difference vs placebo was significant for the 50-mg/d opicapone group (treatment effect, -54.3 [95% CI, -96.2 to -12.4] minutes; P = .008), but not for the 25-mg/d opicapone group (treatment effect, -37.2 [95% CI, -80.8 to 6.4] minutes; P = .11). The off-time reduction was sustained throughout the open-label phase (-126.3 minutes at 1-year open-label end point). The most common adverse events in the opicapone vs placebo groups were dyskinesia, constipation, and dry mouth. Fifty-one patients (11.9%) discontinued from the study during the double-blind phase. Treatment with a 50-mg once-daily dose of opicapone was associated with a significant reduction in mean daily off-time in levodopa-treated patients with PD and motor fluctuations, and this effect is maintained for at least 1 year. Opicapone was safe and well tolerated. clinicaltrials.gov Identifier: NCT01227655.

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

PubMed

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

2018-03-01

Gastroesophageal reflux disease (GERD) is one of the most common gastrointestinal complaints. GERD, caused by the reflux of stomach contents into the esophagus, leads to troublesome symptoms such as heartburn and regurgitation. It is classified into two types: erosive esophagitis, characterized by visible esophageal mucosa erosion in endoscopy, and non-erosive reflux disease (NERD). GERD is a chronic and recurrent disease that impairs the quality of life and imposes socioeconomic and therapeutic burdens to both patients and society. Due to the failure of the conventional treatments for GERD and to the traditional use of Amla (Phyllanthus emblica L.), in addition to beneficial effects shown in recent studies, we evaluated the safety and efficacy of Amla tablet for improvement of symptoms of patients with NERD. We designed a double-arm, randomized, double-blind, placebo-controlled clinical trial. Sixty-eight patients who had classic symptoms of GERD (heartburn, regurgitation and epigastralgia) for at least three months before the start of the trial were randomized in two parallel groups. Patients in the Amla group received two 500 mg Amla tablets twice a day, after meals, for 4 weeks. In the control group, patients received placebo tablets similar to the Amla prescription. The patients were visited at baseline, and at the end of the 2nd and 4th weeks of intervention; their symptoms were measured on a frequency and severity scale for the symptoms of NERD, according to the quality of life in reflux-associated disease questionnaire. Frequencies of heartburn and regurgitation in both groups of the study were significantly reduced after intervention (P < 0.001). Repeated measures logistic regression analysis showed that, in the Amla group, there was a more significant reduction in regurgitation frequency, heartburn frequency, regurgitation severity and heartburn severity during the study period, compared with the placebo group (P < 0.001). This randomized double-blind, placebo-controlled clinical trial demonstrated that Amla could reduce frequencies of heartburn and regurgitation and improve heartburn and regurgitation severity in patients with NERD. Iranian Registry of Clinical Trials IRCT2016061428469N1. Copyright © 2018 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.

Effect of double dose oseltamivir on clinical and virological outcomes in children and adults admitted to hospital with severe influenza: double blind randomised controlled trial

PubMed Central

2013-01-01

Objective To investigate the validity of recommendations in treatment guidelines to use higher than approved doses of oseltamivir in patients with severe influenza. Design Double blind randomised trial. Setting Thirteen hospitals in Indonesia, Singapore, Thailand, and Vietnam. Participants Patients aged ≥1 year admitted to hospital with confirmed severe influenza. Interventions Oral oseltamivir at double dose (150 mg twice a day/paediatric equivalent) versus standard dose (75 mg twice a day/paediatric equivalent). Main outcome measure Viral status according to reverse transcriptase polymerase chain reaction (RT-PCR) for influenza RNA in nasal and throat swabs on day five. Results Of 326 patients (including 246 (75.5%) children aged <15), 165 and 161 were randomised to double or standard dose oseltamivir, respectively. Of these, 260 (79.8%) were infected with influenza virus A (133 (40.8%) with A/H3N2, 72 (22.1%) with A/H1N1-pdm09, 38 (11.7%) with seasonal A/H1N1, 17 (5.2%) with A/H5N1) and 53 (16.2%) with influenza virus B. A further 3.9% (13) were false positive by rapid antigen test (negative by RT-PCR and no rise in convalescent haemagglutination inhibition titers). Similar proportions of patients were negative for RT-PCR on day five of treatment: 115/159 (72.3%, 95% confidence interval 64.9% to 78.7%) double dose recipients versus 105/154 (68.2%, 60.5% to 75.0%) standard dose recipients; difference 4.2% (−5.9 to 14.2); P=0.42. No differences were found in clearance of virus in subgroup analyses by virus type/subtype, age, and duration of illness before randomisation. Mortality was similar: 12/165 (7.3%, 4.2% to 12.3%) in double dose recipients versus 9/161 (5.6%, 3.0% to 10.3%) in standard dose recipients. No differences were found between double and standard dose arms in median days on supplemental oxygen (3 (interquartile range 2-5) v 3.5 (2-7)), in intensive care (4.5 (3-6) v 5 (2-11), and on mechanical ventilation (2.5 (1-16) v 8 (1-16)), respectively. No important differences in tolerability were found. Conclusions There were no virological or clinical advantages with double dose oseltamivir compared with standard dose in patients with severe influenza admitted to hospital. Registration Clinical Trials NCT00298233 PMID:23723457

Blindness, Diabetes, and Amputation: Alleviation of Depression and Pain through Thermal Biofeedback Therapy.

ERIC Educational Resources Information Center

Needham, W. E.; And Others

1993-01-01

A 39-year-old man who was blind, diabetic, and had a double amputation with chronic renal failure and peripheral vascular disease was treated with thermal biofeedback to reduce his depression through increased self-control, to minimize pain, and to facilitate healing of a pregangrenous hand. On treatment discharge, his mental and physical states…

Deterministic entanglement distillation for secure double-server blind quantum computation.

PubMed

Sheng, Yu-Bo; Zhou, Lan

2015-01-15

Blind quantum computation (BQC) provides an efficient method for the client who does not have enough sophisticated technology and knowledge to perform universal quantum computation. The single-server BQC protocol requires the client to have some minimum quantum ability, while the double-server BQC protocol makes the client's device completely classical, resorting to the pure and clean Bell state shared by two servers. Here, we provide a deterministic entanglement distillation protocol in a practical noisy environment for the double-server BQC protocol. This protocol can get the pure maximally entangled Bell state. The success probability can reach 100% in principle. The distilled maximally entangled states can be remaind to perform the BQC protocol subsequently. The parties who perform the distillation protocol do not need to exchange the classical information and they learn nothing from the client. It makes this protocol unconditionally secure and suitable for the future BQC protocol.

Deterministic entanglement distillation for secure double-server blind quantum computation

PubMed Central

Sheng, Yu-Bo; Zhou, Lan

2015-01-01

Blind quantum computation (BQC) provides an efficient method for the client who does not have enough sophisticated technology and knowledge to perform universal quantum computation. The single-server BQC protocol requires the client to have some minimum quantum ability, while the double-server BQC protocol makes the client's device completely classical, resorting to the pure and clean Bell state shared by two servers. Here, we provide a deterministic entanglement distillation protocol in a practical noisy environment for the double-server BQC protocol. This protocol can get the pure maximally entangled Bell state. The success probability can reach 100% in principle. The distilled maximally entangled states can be remaind to perform the BQC protocol subsequently. The parties who perform the distillation protocol do not need to exchange the classical information and they learn nothing from the client. It makes this protocol unconditionally secure and suitable for the future BQC protocol. PMID:25588565

Neurofeedback ineffective in paediatric brain tumour survivors: Results of a double-blind randomised placebo-controlled trial.

PubMed

de Ruiter, Marieke Anna; Oosterlaan, Jaap; Schouten-van Meeteren, Antoinette Yvonne Narda; Maurice-Stam, Heleen; van Vuurden, Dannis Gilbert; Gidding, Corrie; Beek, Laura Rachel; Granzen, Bernd; Caron, Huib N; Grootenhuis, Martha Alexandra

2016-09-01

Many paediatric brain tumour survivors (PBTS) suffer from neurocognitive impairments. Promising effects of neurofeedback (NF) on neurocognitive functioning have been reported, however research into NF for PBTS has not been conducted. We investigated the effects of NF on neurocognitive functioning in PBTS using a double-blind randomised placebo-controlled trial with a parallel-group design (Pediatric Research on Improving Speed, Memory, and Attention; the PRISMA study). Eligible for inclusion were PBTS with neurocognitive complaints, aged 8-18 years, >2 years post-treatment. They were recruited from five medical centres in the Netherlands. A randomisation table assigned participants to 30 sessions (two per week) of either NF or placebo feedback (PF) (ratio 1:1). Participants, parents, trainers, and researchers handling the data were blinded to group assignment. Participants were assessed pre-, post- and 6 months post-training to determine whether NF training would lead to improved functioning as compared with PF training. Primary outcome measures were attention, processing speed, memory, executive functioning, visuomotor integration, and intelligence. Linear mixed models analyses were used to test differences between NF and PF training over time. A total of 82 children were enrolled (mean age 13.9 years, standard deviation = 3.2, 49% males); 80 participants were randomised (NF: n = 40, PF n = 40); 71 participants completed the training (NF: n = 34, PF: n = 37); 68 participants completed training and 6 months post-training assessment (NF: n = 33, PF: n = 35). Similar improvements were found over time for the two treatment groups on the primary outcomes (all p's > 0.15). Results indicated no specific treatment-effects of NF on neurocognitive functioning of PBTS. Copyright © 2016 Elsevier Ltd. All rights reserved.

Angioedema in heart failure patients treated with sacubitril/valsartan (LCZ696) or enalapril in the PARADIGM-HF study.

PubMed

Shi, Victor; Senni, Michele; Streefkerk, Hendrik; Modgill, Vikas; Zhou, Wenchun; Kaplan, Allen

2018-08-01

PARADIGM-HF demonstrated significant clinical benefits for sacubitril/valsartan (LCZ696, an angiotensin receptor neprilysin inhibitor) versus the angiotensin-converting enzyme inhibitor (ACEI) enalapril in patients with heart failure with reduced ejection fraction. As inhibition of ACE, and co-inhibition of ACE and neprilysin, may increase the risk of angioedema, this was an adverse event of special interest. Following sequential enalapril and sacubitril/valsartan run-ins, patients were randomized to twice-daily sacubitril/valsartan 200 mg or enalapril 10 mg. The study design incorporated two wash-out periods (~36 h each) to minimize any potential risk of angioedema due to overlapping ACE and neprilysin inhibition. Suspected cases of angioedema were reported to, and blindly adjudicated by, an independent angioedema adjudication committee (AAC). Of the 10,513 patients entering the enalapril run-in, 9419 entered the sacubitril/valsartan run-in and 8432 received double-blind treatment. Overall, 148 suspected angioedema events occurring in 144 patients were reported to AAC, with one event reported during screening period. Of the remaining 147 events, 54 were confirmed as angioedema by AAC. A confirmed event was experienced by 15 (0.14%) and 10 (0.11%) patients, during the enalapril and sacubitril/valsartan run-ins, respectively, and by 10 (0.24%) and 19 (0.45%) patients in the corresponding randomized arms during the double-blind phase. The frequency of confirmed angioedema was higher in black patients. Most events were mild. Only five patients required hospitalization and none required mechanical airway support. The number of confirmed angioedema events in PARADIGM-HF was low and there was no-marked excess risk of angioedema with sacubitril/valsartan versus enalapril. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Effectiveness of green tea mouthwash in postoperative pain control following surgical removal of impacted third molars: double blind randomized clinical trial

PubMed Central

2013-01-01

Background Pain following surgical removal of impacted molars has remained an important concern among practitioners. Various protocols have been proposed to reduce postoperative pain. However, each one has special side effects and limitations. As green tea possesses anti-inflammatory and antibacterial properties, the aim of the current study was to evaluate the effectiveness of green tea mouthwash in controlling postoperative pain. Materials and methods In a study with split-mouth and double blind design, 44 patients in need of bilateral removal of impacted third molars underwent randomized surgical extraction; following one surgery patients rinsed with a green tea mouthwash from the first to seventh postoperative day and after other extraction rinsed with placebo mouthwash in the same duration. Both patients and surgeon were blinded to the type of mouthwash. The predictor variable was type of mouthwash and primary outcome variable was postoperative pain measured by visual analogue scale (VAS) during first week after surgery. In addition, number of analgesics patients used after surgery recorded. To measure the effect of green tea mouthwash, repeated measures test with confidence interval of 95% was performed. Results Total of 43 patients with mean age of 24 years underwent total of 86 surgeries. VAS value had no statistically difference prior rinsing among groups (P-value > 0.05). However, the mean value of VAS following rinsing with green tea was statistically lower than placebo in postoperative days of 3–7 (P-value < 0.05). In addition, while rinsing with green tea, patients took significantly lower number of analgesics after surgery (P-value < 0.05). No side effects reported. Conclusion Green tea mouthwash could be an appropriate and safe choice to control postoperative pain after third molar surgery. PMID:23866761

Randomized controlled trial of zonisamide for the treatment of refractory partial-onset seizures.

PubMed

Faught, E; Ayala, R; Montouris, G G; Leppik, I E

2001-11-27

Zonisamide is a sulfonamide antiepilepsy drug with sodium and calcium channel-blocking actions. Experience in Japan and a previous European double-blind study have demonstrated its efficacy against partial-onset seizures. A randomized, double-blind, placebo-controlled trial enrolling 203 patients was conducted at 20 United States sites to assess zonisamide efficacy and dose response as adjunctive therapy for refractory partial-onset seizures. Zonisamide dosages were elevated by 100 mg/d each week. The study design allowed parallel comparisons with placebo for three dosages and a final crossover to 400 mg/d of zonisamide for all patients. The primary efficacy comparison was change in seizure frequency from a 4-week placebo baseline to weeks 8 through 12 on blinded therapy. At 400 mg/d, zonisamide reduced the median frequency of all seizures by 40.5% from baseline, compared with a 9% reduction (p = 0.0009) with placebo treatment, and produced a > or =50% seizure reduction (responder rate) in 42% of patients. A dosage of 100 mg/d produced a 20.5% reduction in median seizure frequency (p = 0.038 compared with placebo) and a dosage of 200 mg/d produced a 24.7% reduction in median seizure frequency (p = 0.004 compared with placebo). Dropouts from adverse events (10%) did not differ from placebo (8.2%, NS). The only adverse event differing significantly from placebo was weight loss, though somnolence, anorexia, and ataxia were slightly more common with zonisamide treatment. Serum zonisamide concentrations rose with increasing dose. Zonisamide is effective and well tolerated as an adjunctive agent for refractory partial-onset seizures. The minimal effective dosage was 100 mg/d, but 400 mg/d was the most effective dosage.

Effects of naltrexone on electrocutaneous pain in patients with hypertension compared to normotensive individuals

PubMed Central

Ring, Christopher; France, Christopher R.; al'Absi, Mustafa; Edwards, Louisa; McIntyre, David; Carroll, Douglas; Martin, Una

2008-01-01

An opioid mechanism may help explain hypertensive hypoalgesia. A double-blind placebo-controlled design compared the effects of opioid blockade (naltrexone) and placebo on electrocutaneous pain threshold, pain tolerance, and retrospective McGill Pain Questionnaire ratings in 35 unmedicated patients with essential hypertension and 28 normotensive individuals. The hypertensives experienced less pain than normotensives during the assessment of their pain tolerance; however, this manifestation of hypertensive hypoalgesia was not moderated by naltrexone. These findings fail to support the hypothesis that essential hypertension is characterised by relative opioid insensitivity. PMID:18031920

Therapeutic touch: is there a scientific basis for the practice?

PubMed

Clark, P E; Clark, M J

1984-01-01

The research-related literature on the topic of therapeutic touch is critically reviewed. The purpose of the review is to explore the current scientific basis for the teaching and practice of therapeutic touch as a treatment modality. An examination of published research literature indicates that empirical support for the practice of therapeutic touch is, at best, weak. The results of well-designed, double-blind studies have been transient, of no significance, or are in need of independent replication. Current practice of therapeutic touch is empirically little more than practice of placebo. Considerations for further nursing research are also presented.

Influence of inhomogeneous static magnetic field-exposure on patients with erosive gastritis: a randomized, self- and placebo-controlled, double-blind, single centre, pilot study

PubMed Central

Juhász, Márk; Nagy, Viktor L.; Székely, Hajnal; Kocsis, Dorottya; Tulassay, Zsolt; László, János F.

2014-01-01

This pilot study was devoted to the effect of static magnetic field (SMF)-exposure on erosive gastritis. The randomized, self- and placebo-controlled, double-blind, pilot study included 16 patients of the 2nd Department of Internal Medicine, Semmelweis University diagnosed with erosive gastritis. The instrumental analysis followed a qualitative (pre-intervention) assessment of the symptoms by the patient: lower heartburn (in the ventricle), upper heartburn (in the oesophagus), epigastric pain, regurgitation, bloating and dry cough. Medical diagnosis included a double-line upper panendoscopy followed by 30 min local inhomogeneous SMF-exposure intervention at the lower sternal region over the stomach with peak-to-peak magnetic induction of 3 mT and 30 mT m−1 gradient at the target site. A qualitative (post-intervention) assessment of the same symptoms closed the examination. Sham- or SMF-exposure was used in a double-blind manner. The authors succeeded in justifying the clinically and statistically significant beneficial effect of the SMF- over sham-exposure on the symptoms of erosive gastritis, the average effect of inhibition was 56% by p = 0.001, n = 42 + 96. This pilot study was aimed to encourage gastroenterologists to test local, inhomogeneous SMF-exposure on erosive gastritis patients, so this intervention may become an evidence-based alternative or complementary method in the clinical use especially in cases when conventional therapy options are contraindicated. PMID:25008086

Influence of inhomogeneous static magnetic field-exposure on patients with erosive gastritis: a randomized, self- and placebo-controlled, double-blind, single centre, pilot study.

PubMed

Juhász, Márk; Nagy, Viktor L; Székely, Hajnal; Kocsis, Dorottya; Tulassay, Zsolt; László, János F

2014-09-06

This pilot study was devoted to the effect of static magnetic field (SMF)-exposure on erosive gastritis. The randomized, self- and placebo-controlled, double-blind, pilot study included 16 patients of the 2nd Department of Internal Medicine, Semmelweis University diagnosed with erosive gastritis. The instrumental analysis followed a qualitative (pre-intervention) assessment of the symptoms by the patient: lower heartburn (in the ventricle), upper heartburn (in the oesophagus), epigastric pain, regurgitation, bloating and dry cough. Medical diagnosis included a double-line upper panendoscopy followed by 30 min local inhomogeneous SMF-exposure intervention at the lower sternal region over the stomach with peak-to-peak magnetic induction of 3 mT and 30 mT m(-1) gradient at the target site. A qualitative (post-intervention) assessment of the same symptoms closed the examination. Sham- or SMF-exposure was used in a double-blind manner. The authors succeeded in justifying the clinically and statistically significant beneficial effect of the SMF- over sham-exposure on the symptoms of erosive gastritis, the average effect of inhibition was 56% by p = 0.001, n = 42 + 96. This pilot study was aimed to encourage gastroenterologists to test local, inhomogeneous SMF-exposure on erosive gastritis patients, so this intervention may become an evidence-based alternative or complementary method in the clinical use especially in cases when conventional therapy options are contraindicated. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Corneal wound healing after superficial foreign body injury: vitamin A and dexpanthenol versus a calf blood extract. A randomized double-blind study.

PubMed

Egger, S F; Huber-Spitzy, V; Alzner, E; Scholda, C; Vecsei, V P

1999-01-01

A prospective randomized double-blind clinical study was performed to investigate corneal wound healing after treatment either with an eye gel containing calf blood extract or an eye ointment containing vitamin A and dexpanthenol. A total of 54 outpatients were included in this study, all treated for corneal foreign body injury. The size of the corneal lesions was measured by planimetry on days 0, 1, and on the following days until complete epithelial healing occurred. Results showed the calf blood extract eye gel to be statistically more effective in promoting corneal wound healing, especially in patients with wound areas larger than 6 mm(2).

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.

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

PubMed

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

2002-04-01

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

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

PubMed

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

2017-07-01

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

Implications of clinical trial design on sample size requirements.

PubMed

Leon, Andrew C

2008-07-01

The primary goal in designing a randomized controlled clinical trial (RCT) is to minimize bias in the estimate of treatment effect. Randomized group assignment, double-blinded assessments, and control or comparison groups reduce the risk of bias. The design must also provide sufficient statistical power to detect a clinically meaningful treatment effect and maintain a nominal level of type I error. An attempt to integrate neurocognitive science into an RCT poses additional challenges. Two particularly relevant aspects of such a design often receive insufficient attention in an RCT. Multiple outcomes inflate type I error, and an unreliable assessment process introduces bias and reduces statistical power. Here we describe how both unreliability and multiple outcomes can increase the study costs and duration and reduce the feasibility of the study. The objective of this article is to consider strategies that overcome the problems of unreliability and multiplicity.

Case Studies of Effects of Artificial Food Colors on Hyperactivity.

ERIC Educational Resources Information Center

Spring, Carl; And Others

1981-01-01

A double blind, double crossover study with six hyperactive boys (8 to 13 years old) tested B. Feingold's hypothesis that synthetic food colors cause hyperactivity in some children. All Ss were on the Feingold diet, eliminating artificial colors and flavors. The authors conclude that evidence for Feingold's hypothesis is weak. (Author)

Chinese herbal medicine (Ma Zi Ren Wan) for functional constipation: study protocol for a prospective, double-blinded, double-dummy, randomized controlled trial

PubMed Central

2013-01-01

Background Functional constipation is a common clinical complaint. Although the effectiveness of Ma Zi Ren Wan for alleviating functional constipation symptoms has been proven in a previous randomized placebo-controlled study, further evidence is needed to make clinical recommendations about Chinese herbal medicine. In particular, a comparison with conventional western medicine for functional constipation patients is needed. Methods/Design This is a prospective, double-blinded, double dummy, randomized, controlled trial. After a 2-week run-in period, eligible patients (Rome III) with excessive traditional Chinese medicine syndrome will randomly be assigned to the Chinese medicine arm (Ma Zi Ren Wan and western medicine placebo), western medicine arm (senna and Chinese medicine placebo) or placebo arm (Chinese medicine placebo and western medicine placebo). Patients will undergo an 8-week treatment and an 8-week follow-up. The primary outcome is the responder rate for complete spontaneous bowel movement (CSBM) during treatment. Patients with a mean increase of CSBM ≧1/week in comparison with their baselines are defined as responders. The secondary outcomes include responder rate during follow-up, changes of colonic transit as measured with radio-opaque markers, individual and global symptom assessments, and reported adverse effects. Discussion This study is the first study to compare a Chinese Herbal Medicine (Ma Zi Ren Wan) with a laxative that is commonly used in the clinical practice of western medicine, and with a placebo. This study will complete the investigation of Ma Zi Ren Wan for functional constipation, and should, therefore, suggest recommendations for clinical practice. Furthermore, the process of first conducting a systematic review, then implementing a dose determination study followed by a placebo-control trial, and finally, comparing traditional Chinese medicine with an active conventional medicine in a controlled trial can be a reference to other researches on Chinese medicine interventions in the future. Trial registration NCT01695850 PMID:24180235

Low-Dose Adrenaline, Promethazine, and Hydrocortisone in the Prevention of Acute Adverse Reactions to Antivenom following Snakebite: A Randomised, Double-Blind, Placebo-Controlled Trial

PubMed Central

de Silva, H. Asita; Pathmeswaran, Arunasalam; Ranasinha, Channa D.; Jayamanne, Shaluka; Samarakoon, Senarath B.; Hittharage, Ariyasena; Kalupahana, Ranjith; Ratnatilaka, G. Asoka; Uluwatthage, Wimalasiri; Aronson, Jeffrey K.; Armitage, Jane M.; Lalloo, David G.; de Silva, H. Janaka

2011-01-01

Background Envenoming from snakebites is most effectively treated by antivenom. However, the antivenom available in South Asian countries commonly causes acute allergic reactions, anaphylactic reactions being particularly serious. We investigated whether adrenaline, promethazine, and hydrocortisone prevent such reactions in secondary referral hospitals in Sri Lanka by conducting a randomised, double-blind placebo-controlled trial. Methods and Findings In total, 1,007 patients were randomized, using a 2×2×2 factorial design, in a double-blind, placebo-controlled trial of adrenaline (0.25 ml of a 1∶1,000 solution subcutaneously), promethazine (25 mg intravenously), and hydrocortisone (200 mg intravenously), each alone and in all possible combinations. The interventions, or matching placebo, were given immediately before infusion of antivenom. Patients were monitored for mild, moderate, or severe adverse reactions for at least 96 h. The prespecified primary end point was the effect of the interventions on the incidence of severe reactions up to and including 48 h after antivenom administration. In total, 752 (75%) patients had acute reactions to antivenom: 9% mild, 48% moderate, and 43% severe; 89% of the reactions occurred within 1 h; and 40% of all patients were given rescue medication (adrenaline, promethazine, and hydrocortisone) during the first hour. Compared with placebo, adrenaline significantly reduced severe reactions to antivenom by 43% (95% CI 25–67) at 1 h and by 38% (95% CI 26–49) up to and including 48 h after antivenom administration; hydrocortisone and promethazine did not. Adding hydrocortisone negated the benefit of adrenaline. Conclusions Pretreatment with low-dose adrenaline was safe and reduced the risk of acute severe reactions to snake antivenom. This may be of particular importance in countries where adverse reactions to antivenom are common, although the need to improve the quality of available antivenom cannot be overemphasized. Trial registration www.ClinicalTrials.gov NCT00270777 Please see later in the article for the Editors' Summary PMID:21572992

A Randomized, Double-Blind, Placebo-Controlled Trial of Eszopiclone for the Treatment of Insomnia in Patients with Chronic Low Back Pain

PubMed Central

Goforth, Harold W.; Preud'homme, Xavier A.; Krystal, Andrew D.

2014-01-01

Study Objectives: Insomnia, which is very common in patients with chronic low back pain (LBP), has long been viewed as a pain symptom that did not merit specific treatment. Recent data suggest that adding insomnia therapy to pain-targeted treatment should improve outcome; however, this has not been empirically tested in LBP or in any pain condition treated with a standardized pain medication regimen. We sought to test the hypothesis that adding insomnia therapy to pain-targeted treatment might improve sleep and pain in LBP. Design: Double-blind, placebo-controlled, parallel-group, 1-mo trial. Setting: Duke University Medical Center Outpatient Sleep Clinic. Patients: Fifty-two adult volunteers with LBP of at least 3 mo duration who met diagnostic criteria for insomnia (mean age: 42.5 y; 63% females). Interventions: Subjects were randomized to eszopiclone (ESZ) 3 mg plus naproxen 500 mg BID or matching placebo plus naproxen 500 mg twice a day. Measurements and Results: ESZ significantly improved total sleep time (mean increase: ESZ, 95 min; placebo, 9 min) (primary outcome) and nearly all sleep measures as well as visual analog scale pain (mean decrease: ESZ, 17 mm; placebo, 2 mm) (primary pain outcome), and depression (mean Hamilton Depression Rating Scale improvement ESZ, 3.8; placebo, 0.4) compared with placebo. Changes in pain ratings were significantly correlated with changes in sleep. Conclusions: The addition of insomnia-specific therapy to a standardized naproxen pain regimen significantly improves sleep, pain, and depression in patients with chronic low back pain (LBP). The findings indicate the importance of administering both sleep and pain-directed therapies to patients with LBP in clinical practice and provide strong evidence that improving sleep disturbance may improve pain. Trial Registration: clinicaltrials.gov identifier: NCT00365976 Citation: Goforth HW, Preud'homme XA, Krystal AD. A randomized, double-blind, placebo-controlled trial of eszopiclone for the treatment of insomnia in patients with chronic low back pain. SLEEP 2014;37(6):1053-1060. PMID:24882900

Oral Aripiprazole as Maintenance Treatment in Adolescent Schizophrenia: Results From a 52-Week, Randomized, Placebo-Controlled Withdrawal Study.

PubMed

Correll, Christoph U; Kohegyi, Eva; Zhao, Cathy; Baker, Ross A; McQuade, Robert; Salzman, Phyllis M; Sanchez, Raymond; Nyilas, Margaretta; Carson, William

2017-09-01

To evaluate the efficacy, safety, and tolerability of aripiprazole, a dopamine D 2 receptor partial agonist, as maintenance treatment in adolescent outpatients with schizophrenia. This was a multicenter, double-blind, placebo-controlled, randomized withdrawal design trial. Participants 13 to 17 years of age with a diagnosis of schizophrenia (DSM-IV-TR) were first cross-titrated from their other oral antipsychotic(s) (4-6 weeks), then stabilized (7-21 weeks) on oral aripiprazole 10 to 30 mg/d, and finally randomized 2:1 to continuation of oral aripiprazole or to placebo in a double-blind maintenance phase (≤52 weeks). The primary endpoint was time from randomization to exacerbation of psychotic symptoms/impending relapse. Safety and tolerability were assessed. Of 201 enrolled participants, 146 were randomized to aripiprazole (n = 98) or placebo (n = 48) in the double-blind maintenance phase. Treatment with aripiprazole was associated with a significantly longer time to exacerbation of psychotic symptoms/impending relapse compared with placebo (hazard ratio, 0.46 [95% CI = 0.24-0.88]; p = .016). Aripiprazole was associated with lower rates of serious treatment-emergent adverse events (TEAEs) versus placebo (3.1% versus 12.5%; p = .059) and severe TEAEs (2.0% versus 10.4%; p = .039). The rate of discontinuation due to TEAEs was lower with aripiprazole versus placebo (20.4% versus 39.6%, p = .014; number-needed-to-harm = 5.1). The incidences of extrapyramidal symptoms, weight gain, and somnolence were similar or lower with aripiprazole than with placebo, and no TEAEs related to elevated serum prolactin were reported. Based on Tanner staging, 27.6% of participants treated with aripiprazole and 16.7% of those who received placebo progressed one or two stages from baseline. Aripiprazole was observed to be safe and effective for the maintenance treatment of adolescents with schizophrenia. Efficacy and Safety Study of Oral Aripiprazole in Adolescents With Schizophrenia; http://clinicaltrials.gov/; NCT01149655. Copyright © 2017 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Pacing as a Treatment for Reflex-Mediated (Vasovagal, Situational, or Carotid Sinus Hypersensitivity) Syncope: A Systematic Review for the 2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society.

PubMed

Varosy, Paul D; Chen, Lin Y; Miller, Amy L; Noseworthy, Peter A; Slotwiner, David J; Thiruganasambandamoorthy, Venkatesh

2017-08-01

To determine, using systematic review of the biomedical literature, whether pacing reduces risk of recurrent syncope and relevant clinical outcomes among adult patients with reflex-mediated syncope. MEDLINE (through PubMed), EMBASE, and the Cochrane Central Register of Controlled Trials (through October 7, 2015) were searched for randomized trials and observational studies examining pacing and syncope, and the bibliographies of known systematic reviews were also examined. Studies were rejected for poor-quality study methods and for the lack of the population, intervention, comparator, or outcome(s) of interest. Of 3,188 citations reviewed, 10 studies met the inclusion criteria for systematic review, including a total of 676 patients. These included 9 randomized trials and 1 observational study. Of the 10 studies, 4 addressed patients with carotid sinus hypersensitivity, and the remaining 6 addressed vasovagal syncope. Among the 6 open-label (unblinded) studies, we found that pacing was associated with a 70% reduction in recurrent syncope (relative risk [RR]: 0.30; 95% confidence interval [CI]: 0.15-0.60). When the 2 analyzable studies with double-blinded methodology were considered separately, there was no clear benefit (RR: 0.73; 95% CI: 0.25-2.1), but confidence intervals were wide. The strongest evidence was from the randomized, double-blinded ISSUE-3 (Third International Study on Syncope of Uncertain Etiology) trial, which demonstrated a benefit of pacing among patients with recurrent syncope and asystole documented by implantable loop recorder. There are limited data with substantive evidence of outcome ascertainment bias, and only 2 studies with a double-blinded study design have been conducted. The evidence does not support the use of pacing for reflex-mediated syncope beyond patients with recurrent vasovagal syncope and asystole documented by implantable loop recorder. Copyright © 2017 American College of Cardiology Foundation, American Heart Association, Inc., and Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Pacing as a treatment for reflex-mediated (vasovagal, situational, or carotid sinus hypersensitivity) syncope: A systematic review for the 2017 ACC/AHA/HRS guideline for the evaluation and management of patients with syncope: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society.

PubMed

Varosy, Paul D; Chen, Lin Y; Miller, Amy L; Noseworthy, Peter A; Slotwiner, David J; Thiruganasambandamoorthy, Venkatesh

2017-08-01

To determine, using systematic review of the biomedical literature, whether pacing reduces risk of recurrent syncope and relevant clinical outcomes among adult patients with reflex-mediated syncope. MEDLINE (through PubMed), EMBASE, and the Cochrane Central Register of Controlled Trials (through October 7, 2015) were searched for randomized trials and observational studies examining pacing and syncope, and the bibliographies of known systematic reviews were also examined. Studies were rejected for poor-quality study methods and for the lack of the population, intervention, comparator, or outcome(s) of interest. Of 3,188 citations reviewed, 10 studies met the inclusion criteria for systematic review, including a total of 676 patients. These included 9 randomized trials and 1 observational study. Of the 10 studies, 4 addressed patients with carotid sinus hypersensitivity, and the remaining 6 addressed vasovagal syncope. Among the 6 open-label (unblinded) studies, we found that pacing was associated with a 70% reduction in recurrent syncope (relative risk [RR]: 0.30; 95% confidence interval [CI]: 0.15-0.60). When the 2 analyzable studies with double-blinded methodology were considered separately, there was no clear benefit (RR: 0.73; 95% CI: 0.25-2.1), but confidence intervals were wide. The strongest evidence was from the randomized, double-blinded ISSUE-3 (Third International Study on Syncope of Uncertain Etiology) trial, which demonstrated a benefit of pacing among patients with recurrent syncope and asystole documented by implantable loop recorder. There are limited data with substantive evidence of outcome ascertainment bias, and only 2 studies with a double-blinded study design have been conducted. The evidence does not support the use of pacing for reflex-mediated syncope beyond patients with recurrent vasovagal syncope and asystole documented by implantable loop recorder. Copyright © 2017 American College of Cardiology Foundation, American Heart Association, Inc., and Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Pacing as a Treatment for Reflex-Mediated (Vasovagal, Situational, or Carotid Sinus Hypersensitivity) Syncope: A Systematic Review for the 2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society.

PubMed

Varosy, Paul D; Chen, Lin Y; Miller, Amy L; Noseworthy, Peter A; Slotwiner, David J; Thiruganasambandamoorthy, Venkatesh

2017-08-01

To determine, using systematic review of the biomedical literature, whether pacing reduces risk of recurrent syncope and relevant clinical outcomes among adult patients with reflex-mediated syncope. MEDLINE (through PubMed), EMBASE, and the Cochrane Central Register of Controlled Trials (through October 7, 2015) were searched for randomized trials and observational studies examining pacing and syncope, and the bibliographies of known systematic reviews were also examined. Studies were rejected for poor-quality study methods and for the lack of the population, intervention, comparator, or outcome(s) of interest. Of 3188 citations reviewed, 10 studies met the inclusion criteria for systematic review, including a total of 676 patients. These included 9 randomized trials and 1 observational study. Of the 10 studies, 4 addressed patients with carotid sinus hypersensitivity, and the remaining 6 addressed vasovagal syncope. Among the 6 open-label (unblinded) studies, we found that pacing was associated with a 70% reduction in recurrent syncope (relative risk [RR]: 0.30; 95% confidence interval [CI]: 0.15-0.60). When the 2 analyzable studies with double-blinded methodology were considered separately, there was no clear benefit (RR: 0.73; 95% CI: 0.25-2.1), but confidence intervals were wide. The strongest evidence was from the randomized, double-blinded ISSUE-3 (Third International Study on Syncope of Uncertain Etiology) trial, which demonstrated a benefit of pacing among patients with recurrent syncope and asystole documented by implantable loop recorder. There are limited data with substantive evidence of outcome ascertainment bias, and only 2 studies with a double-blinded study design have been conducted. The evidence does not support the use of pacing for reflex-mediated syncope beyond patients with recurrent vasovagal syncope and asystole documented by implantable loop recorder. © 2017 by the American College of Cardiology Foundation, the American Heart Association, Inc., and the Heart Rhythm Society.

Efficacy and safety of Postoperative Intravenous Parecoxib sodium Followed by ORal CElecoxib (PIPFORCE) post-total knee arthroplasty in patients with osteoarthritis: a study protocol for a multicentre, double-blind, parallel-group trial

PubMed Central

Zhuang, Qianyu; Bian, Yanyan; Wang, Wei; Jiang, Jingmei; Feng, Bin; Sun, Tiezheng; Lin, Jianhao; Zhang, Miaofeng; Yan, Shigui; Shen, Bin; Pei, Fuxing; Weng, Xisheng

2016-01-01

Introduction Total knee arthroplasty (TKA) has been regarded as a most painful orthopaedic surgery. Although many surgeons sequentially use parecoxib and celecoxib as a routine strategy for postoperative pain control after TKA, high quality evidence is still lacking to prove the effect of this sequential regimen, especially at the medium-term follow-up. The purpose of this study, therefore, is to evaluate efficacy and safety of postoperative intravenous parecoxib sodium followed by oral celecoxib in patients with osteoarthritis (OA) undergoing TKA. The hypothesis is that compared to placebo with opioids as rescue treatment, sequential use of parecoxib and celecoxib can achieve less morphine consumption over the postoperative 2 weeks, as well as better pain control, quicker functional recovery in the postoperative 6 weeks and less opioid-related adverse events during the 12-week recovery phase. Methods and analysis This study is designed as a multicentre, randomised, double-blind, parallel-group and placebo-controlled trial. The target sample size is 246. All participants who meet the study inclusion and exclusion criteria will be randomly assigned in a 1:1 ratio to either the parecoxib/celecoxib group or placebo group. The randomisation and allocation will be study site based. The study will consist of three phases: an initial screening phase; a 6-week double-blind treatment phase; and a 6-week follow-up phase. The primary end point is cumulative opioid consumption during 2 weeks postoperation. Secondary end points consist of the postoperative visual analogue scale score, knee joint function, quality of life, local skin temperature, erythrocyte sedimentation rate, C reactive protein, cytokines and blood coagulation parameters. Safety end points will be monitored too. Ethics and dissemination Ethics approval for this study has been obtained from the Ethics Committee, Peking Union Medical College Hospital, China (Protocol number: S-572) Study results will be available as published manuscripts and presentations at national and international meetings. Trial registration number NCT02198924. PMID:27609846

Efficacy and safety of Postoperative Intravenous Parecoxib sodium Followed by ORal CElecoxib (PIPFORCE) post-total knee arthroplasty in patients with osteoarthritis: a study protocol for a multicentre, double-blind, parallel-group trial.

PubMed

Zhuang, Qianyu; Bian, Yanyan; Wang, Wei; Jiang, Jingmei; Feng, Bin; Sun, Tiezheng; Lin, Jianhao; Zhang, Miaofeng; Yan, Shigui; Shen, Bin; Pei, Fuxing; Weng, Xisheng

2016-09-08

Total knee arthroplasty (TKA) has been regarded as a most painful orthopaedic surgery. Although many surgeons sequentially use parecoxib and celecoxib as a routine strategy for postoperative pain control after TKA, high quality evidence is still lacking to prove the effect of this sequential regimen, especially at the medium-term follow-up. The purpose of this study, therefore, is to evaluate efficacy and safety of postoperative intravenous parecoxib sodium followed by oral celecoxib in patients with osteoarthritis (OA) undergoing TKA. The hypothesis is that compared to placebo with opioids as rescue treatment, sequential use of parecoxib and celecoxib can achieve less morphine consumption over the postoperative 2 weeks, as well as better pain control, quicker functional recovery in the postoperative 6 weeks and less opioid-related adverse events during the 12-week recovery phase. This study is designed as a multicentre, randomised, double-blind, parallel-group and placebo-controlled trial. The target sample size is 246. All participants who meet the study inclusion and exclusion criteria will be randomly assigned in a 1:1 ratio to either the parecoxib/celecoxib group or placebo group. The randomisation and allocation will be study site based. The study will consist of three phases: an initial screening phase; a 6-week double-blind treatment phase; and a 6-week follow-up phase. The primary end point is cumulative opioid consumption during 2 weeks postoperation. Secondary end points consist of the postoperative visual analogue scale score, knee joint function, quality of life, local skin temperature, erythrocyte sedimentation rate, C reactive protein, cytokines and blood coagulation parameters. Safety end points will be monitored too. Ethics approval for this study has been obtained from the Ethics Committee, Peking Union Medical College Hospital, China (Protocol number: S-572) Study results will be available as published manuscripts and presentations at national and international meetings. NCT02198924. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Low-dose budesonide for maintenance of clinical remission in collagenous colitis: a randomised, placebo-controlled, 12-month trial

PubMed Central

Münch, Andreas; Bohr, Johan; Miehlke, Stephan; Benoni, Cecilia; Olesen, Martin; Öst, Åke; Strandberg, Lars; Hellström, Per M; Hertervig, Erik; Armerding, Peter; Stehlik, Jiri; Lindberg, Greger; Björk, Jan; Lapidus, Annika; Löfberg, Robert; Bonderup, Ole; Avnström, Sören; Rössle, Martin; Dilger, Karin; Mueller, Ralph; Greinwald, Roland; Tysk, Curt; Ström, Magnus

2016-01-01

Objective This 1-year study aimed to assess low-dose budesonide therapy for maintenance of clinical remission in patients with collagenous colitis. Design A prospective, randomised, placebo-controlled study beginning with an 8-week open-label induction phase in which patients with histologically confirmed active collagenous colitis received budesonide (Budenofalk, 9 mg/day initially, tapered to 4.5 mg/day), after which 92 patients in clinical remission were randomised to budesonide (mean dose 4.5 mg/day; Budenofalk 3 mg capsules, two or one capsule on alternate days) or placebo in a 12-month double-blind phase with 6 months treatment-free follow-up. Primary endpoint was clinical remission throughout the double-blind phase. Results Clinical remission during open-label treatment was achieved by 84.5% (93/110 patients). The median time to remission was 10.5 days (95% CI (9.0 to 14.0 days)). The maintenance of clinical remission at 1 year was achieved by 61.4% (27/44 patients) in the budesonide group versus 16.7% (8/48 patients) receiving placebo (treatment difference 44.5% in favour of budesonide; 95% CI (26.9% to 62.7%), p<0.001). Health-related quality of life was maintained during the 12-month double-blind phase in budesonide-treated patients. During treatment-free follow-up, 82.1% (23/28 patients) formerly receiving budesonide relapsed after study drug discontinuation. Low-dose budesonide over 1 year resulted in few suspected adverse drug reactions (7/44 patients), all non-serious. Conclusions Budesonide at a mean dose of 4.5 mg/day maintained clinical remission for at least 1 year in the majority of patients with collagenous colitis and preserved health-related quality of life without safety concerns. Treatment extension with low-dose budesonide beyond 1 year may be beneficial given the high relapse rate after budesonide discontinuation. Trial registration numbers http://www.clinicaltrials.gov (NCT01278082) and http://www.clinicaltrialsregister.eu (EudraCT: 2007-001315-31). PMID:25425655

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

PubMed

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

2016-04-01

Type 2 diabetes mellitus (T2DM) is associated with endothelial dysfunction, characterized by a reduction of nitric oxide (NO)-mediated relaxation. Phosphodiesterase type 5 inhibitors (PDE5i) improve NO levels. The aim of the study was to investigate whether long-term, chronic treatment with the PDE5i vardenafil improves systemic endothelial function in diabetic men. A prospective, investigator-initiated, randomized, placebo-controlled, double-blind, clinical trial was conducted. In total, 54 male patients affected by T2DM, diagnosed within the last 5 years, and erectile dysfunction were enrolled, regardless of testosterone levels. In all, 26 and 28 patients were assigned to verum and placebo groups respectively. The study consisted of an enrollment phase, a treatment phase (24 weeks) (vardenafil/placebo 10  mg twice in a day) and a follow-up phase (24 weeks). Parameters evaluated were as follows: International Index of Erectile Function 15 (IIEF-15), flow-mediated dilation (FMD), serum interleukin 6 (IL6), endothelin 1 (ET-1), gonadotropins and testosterone (measured by liquid chromatography/tandem mass spectrometry). IIEF-15 erectile function improved during the treatment (P<0.001). At the end of the treatment both FMD (P=0.040) and IL6 (P=0.019) significantly improved. FMD correlated with serum testosterone levels (R(2)=0.299; P<0.001). Testosterone increased significantly under vardenafil treatment and returned in the eugonadal range only in hypogonadal men (n=13), without changes in gonadotropins. Chronic vardenafil treatment did not result in relevant side effects. This is the first double-blind, placebo-controlled clinical trial designed to evaluate the effects of chronic treatment of vardenafil on endothelial health-related parameters and sexual hormones in patients affected by a chronic disease. Chronically administered vardenafil is effective and improves endothelial parameters in T2DM patient. Moreover, chronic vardenafil therapy improves hypogonadism in diabetic, hypogonadal men. © 2016 European Society of Endocrinology.

Validation of novel recipes for double-blind, placebo-controlled food challenges in children and adults.

PubMed

Vlieg-Boerstra, B J; Herpertz, I; Pasker, L; van der Heide, S; Kukler, J; Jansink, C; Vaessen, W; Beusekamp, B J; Dubois, A E J

2011-07-01

In double-blind, placebo-controlled food challenges (DBPCFCs), the use of challenge materials in which blinding is validated is a prerequisite for obtaining true blinded conditions during the test procedure. Therefore, the aim of this study was to enlarge the available range of validated recipes for DBPCFCs to facilitate oral challenge tests in all age groups, including young children, while maximizing the top dose in an acceptable volume. Recipes were developed and subsequently validated by a panel recruited by a matching sensory test. The best 30% of candidates were selected to participate in sensory testing using the paired comparison test. For young children, three recipes with cow's milk and one recipe with peanut could be validated which may be utilized in DBPCFCs. For children older than 4 years and adults, one recipe with egg, two with peanut, one with hazelnut, and one with cashew nut were validated for use in DBPCFCs. All recipes contained larger amounts of allergenic foods than previously validated. These recipes increase the range of validated recipes for use in DBPCFCs in adults and children. © 2011 John Wiley & Sons A/S.

Placebo controlled, prospectively randomized, double-blinded study for the investigation of the effectiveness and safety of the acoustic wave therapy (AWT(®)) for cellulite treatment.

PubMed

Russe-Wilflingseder, Katharina; Russe-Wilfingsleder, Katharina; Russe, Elisabeth; Vester, Johannes C; Haller, Gerd; Novak, Pavel; Krotz, Alexander

2013-06-01

Placebo controlled double-blinded, prospectively randomized clinical trial with 17 patients (11 verum, 5 placebo) for evaluation of cellulite treatment with Acoustic Wave Therapy, (AWT(®)) was performed. The patients were treated once a week for 7 weeks, a total of 8 treatments with the D-ACTOR(®) 200 by Storz Medical AG. Data were collected at baseline, before 8th treatment, at 1 month (follow-up 1) and at 3 months (follow-up 2) after the last treatment with a patients' questionnaire, weight control, measurement of circumference and standardized photography. Treatment progress was further documented using a specially designed 3D imaging system (SkinSCAN(3D), 3D-Shape GmbH) providing an objective measure of cellulite (primary efficacy criteria). Patient's questionnaire in the verum group revealed an improvement in number and depth of dimples, skin firmness and texture, in shape and in reduction of circumference. The overall result (of skin waviness, Sq and Sz, surface and volume of depressions and elevations, Vvv and Vmp) at two follow-up visits indicates a more than medium sized superiority (MW = 0.6706) and is statistically significant (pWei-Lachin = 0.0106). The placebo group revealed no statistical significance. No side effects were seen. This indicates the efficacy and safety of AWT(®) for patients with cellulite.

Effects of propranolol on conversational reciprocity in autism spectrum disorder: a pilot, double-blind, single-dose psychopharmacological challenge study.

PubMed

Zamzow, Rachel M; Ferguson, Bradley J; Stichter, Janine P; Porges, Eric C; Ragsdale, Alexandra S; Lewis, Morgan L; Beversdorf, David Q

2016-04-01

Pharmacological intervention for autism spectrum disorder (ASD) is an important addition to treatment, yet currently available agents target co-morbid psychiatric concerns, such as aggression and irritability. Propranolol, a beta-adrenergic antagonist with anxiolytic effects, has been shown to improve verbal fluency and working memory in adults and adolescents with ASD in single-dose challenges. The present pilot study explores the acute effects of propranolol on a measure of conversational reciprocity in this population. We also examined whether autonomic activity and anxiety moderate or mediate response to the drug, given relationships between these variables and ASD, as well as the drug's effects. In a within-subject crossover design, 20 individuals with ASD received a single dose of propranolol or placebo during two sessions in a double-blinded, counterbalanced manner. After drug administration, participants performed a conversational reciprocity task by engaging in a short conversation with the researcher. Measurements of autonomic activity and anxiety were obtained before and after drug administration. Propranolol significantly improved performance on the conversational reciprocity task total [d = 0.40] and nonverbal communication domain scores when compared to the placebo condition. However, neither autonomic activity nor anxiety was significantly associated with drug response. Acute propranolol administration improved conversational reciprocity in ASD. Further exploration of these preliminary findings, as well as other potential treatment response predictors, with serial doses is warranted.

Randomised, double blind, placebo controlled trial of intravenous antioxidant (n‐acetylcysteine, selenium, vitamin C) therapy in severe acute pancreatitis

PubMed Central

Siriwardena, Ajith K; Mason, James M; Balachandra, Srinivasan; Bagul, Anil; Galloway, Simon; Formela, Laura; Hardman, Jonathan G; Jamdar, Saurabh

2007-01-01

Background Based on equivocal clinical data, intravenous antioxidant therapy has been used for the treatment of severe acute pancreatitis. To date there is no randomised comparison of this therapy in severe acute pancreatitis. Methods We conducted a randomised, double blind, placebo controlled trial of intravenous antioxidant (n‐acetylcysteine, selenium, vitamin C) therapy in patients with predicted severe acute pancreatitis. Forty‐three patients were enrolled from three hospitals in the Manchester (UK) area over the period June 2001 to November 2004. Randomisation stratified for APACHE‐II score and hospital site, and delivered groups that were similar at baseline. Results Relative serum levels of antioxidants rose while markers of oxidative stress fell in the active treatment group during the course of the trial. However, at 7 days, there was no statistically significant difference in the primary end point, organ dysfunction (antioxidant vs placebo: 32% vs 17%, p = 0.33) or any secondary end point of organ dysfunction or patient outcome. Conclusions This study provides no evidence to justify continued use of n‐acetylcysteine, selenium, vitamin C based antioxidant therapy in severe acute pancreatitis. In the context of any future trial design, careful consideration must be given to the risks raised by the greater trend towards adverse outcome in patients in the treatment arm of this study. PMID:17356040

Evaluation of a Standardized Extract from Morus alba against α-Glucosidase Inhibitory Effect and Postprandial Antihyperglycemic in Patients with Impaired Glucose Tolerance: A Randomized Double-Blind Clinical Trial

PubMed Central

Hwang, Seung Hwan; Li, Hong Mei; Wang, Zhiqiang

2016-01-01

To evaluate the antihyperglycemic effect of a standardized extract of the leaves of Morus alba (SEMA), the present study was designed to investigate the α-glucosidase inhibitory effect and acute single oral toxicity as well as evaluate blood glucose reduction in animals and in patients with impaired glucose tolerance in a randomized double-blind clinical trial. SEMA was found to inhibit α-glucosidase at a fourfold higher level than the positive control (acarbose), in a concentration-dependent manner. Moreover, blood glucose concentration was suppressed by SEMA in vivo. Clinical signs and weight changes were observed when conducting an evaluation of the acute toxicity of SEMA through a single-time administration, with clinical observation conducted more than once each day. After administration of the SEMA, observation was for 14 days; all of the animals did not die and did not show any abnormal symptoms. In addition, the inhibitory effects of rice coated with SEMA were evaluated in a group of impaired glucose tolerance patients on postprandial glucose and a group of normal persons, and results showed that SEMA had a clear inhibitory effect on postprandial hyperglycemia in both groups. Overall, SEMA showed excellent potential in the present study as a material for improving postprandial hyperglycemia. PMID:27974904

Tribulus terrestris for treatment of sexual dysfunction in women: randomized double-blind placebo - controlled study.

PubMed

Akhtari, Elham; Raisi, Firoozeh; Keshavarz, Mansoor; Hosseini, Hamed; Sohrabvand, Farnaz; Bioos, Soodabeh; Kamalinejad, Mohammad; Ghobadi, Ali

2014-04-28

Tribulus terrestris as a herbal remedy has shown beneficial aphrodisiac effects in a number of animal and human experiments. This study was designed as a randomized double-blind placebo-controlled trial to assess the safety and efficacy of Tribulus terrestris in women with hypoactive sexual desire disorder during their fertile years. Sixty seven women with hypoactive sexual desire disorder were randomly assigned to Tribulus terrestris extract (7.5 mg/day) or placebo for 4 weeks. Desire, arousal, lubrication, orgasm, satisfaction, and pain were measured at baseline and after 4 weeks after the end of the treatment by using the Female Sexual Function Index (FSFI). Two groups were compared by repeated measurement ANOVA test. Thirty women in placebo group and thirty women in drug group completed the study. At the end of the fourth week, patients in the Tribulus terrestris group had experienced significant improvement in their total FSFI (p < 0.001), desire (p < 0.001), arousal (p = 0.037), lubrication (p < 0.001), satisfaction (p < 0.001) and pain (p = 0.041) domains of FSFI. Frequency of side effects was similar between the two groups. Tribulus terrestris may safely and effectively improve desire in women with hypoactive sexual desire disorder. Further investigation of Tribulus terrestris in women is warranted.

Tribulus terrestris for treatment of sexual dysfunction in women: randomized double-blind placebo - controlled study

PubMed Central

2014-01-01

Background Tribulus terrestris as a herbal remedy has shown beneficial aphrodisiac effects in a number of animal and human experiments. This study was designed as a randomized double-blind placebo-controlled trial to assess the safety and efficacy of Tribulus terrestris in women with hypoactive sexual desire disorder during their fertile years. Sixty seven women with hypoactive sexual desire disorder were randomly assigned to Tribulus terrestris extract (7.5 mg/day) or placebo for 4 weeks. Desire, arousal, lubrication, orgasm, satisfaction, and pain were measured at baseline and after 4 weeks after the end of the treatment by using the Female Sexual Function Index (FSFI). Two groups were compared by repeated measurement ANOVA test. Results Thirty women in placebo group and thirty women in drug group completed the study. At the end of the fourth week, patients in the Tribulus terrestris group had experienced significant improvement in their total FSFI (p < 0.001), desire (p < 0.001), arousal (p = 0.037), lubrication (p < 0.001), satisfaction (p < 0.001) and pain (p = 0.041) domains of FSFI. Frequency of side effects was similar between the two groups. Conclusions Tribulus terrestris may safely and effectively improve desire in women with hypoactive sexual desire disorder. Further investigation of Tribulus terrestris in women is warranted. PMID:24773615

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.

(S)-citalopram influences amygdala modulation in healthy subjects: a randomized placebo-controlled double-blind fMRI study using dynamic causal modeling.

PubMed

Sladky, Ronald; Spies, Marie; Hoffmann, Andre; Kranz, Georg; Hummer, Allan; Gryglewski, Gregor; Lanzenberger, Rupert; Windischberger, Christian; Kasper, Siegfried

2015-03-01

Citalopram and Escitalopram are gold standard pharmaceutical treatment options for affective, anxiety, and other psychiatric disorders. However, their neurophysiologic function on cortico-limbic circuits is incompletely characterized. Here we studied the neuropharmacological influence of Citalopram and Escitalopram on cortico-limbic regulatory processes by assessing the effective connectivity between orbitofrontal cortex (OFC) and amygdala using dynamic causal modeling (DCM) applied to functional MRI data. We investigated a cohort of 15 healthy subjects in a randomized, crossover, double-blind design after 10days of Escitalopram (10mg/d (S)-citalopram), Citalopram (10mg/d (S)-citalopram and 10mg/d (R)-citalopram), or placebo. Subjects performed an emotional face discrimination task, while undergoing functional magnetic resonance imaging (fMRI) scanning at 3 Tesla. As hypothesized, the OFC, in the context of the emotional face discrimination task, exhibited a down-regulatory effect on amygdala activation. This modulatory effect was significantly increased by (S)-citalopram, but not (R)-citalopram. For the first time, this study shows that (1) the differential effects of the two enantiomers (S)- and (R)-citalopram on cortico-limbic connections can be demonstrated by modeling effective connectivity methods, and (2) one of their mechanisms can be linked to an increased inhibition of amygdala activation by the orbitofrontal cortex. Copyright © 2014 Elsevier Inc. All rights reserved.

A prospective, randomized, double-blinded single-site control study comparing blood loss prevention of tranexamic acid (TXA) to epsilon aminocaproic acid (EACA) for corrective spinal surgery

PubMed Central

2010-01-01

Background Multilevel spinal fusion surgery has typically been associated with significant blood loss. To limit both the need for transfusions and co-morbidities associated with blood loss, the use of anti-fibrinolytic agents has been proposed. While there is some literature comparing the effectiveness of tranexamic acid (TXA) to epsilon aminocaproic acid (EACA) in cardiac procedures, there is currently no literature directly comparing TXA to EACA in orthopedic surgery. Methods/Design Here we propose a prospective, randomized, double-blinded control study evaluating the effects of TXA, EACA, and placebo for treatment of adolescent idiopathic scoliosis (AIS), neuromuscular scoliosis (NMS), and adult deformity (AD) via corrective spinal surgery. Efficacy will be determined by intraoperative and postoperative blood loss. Other clinical outcomes that will be compared include transfusion rates, preoperative and postoperative hemodynamic values, and length of hospital stay after the procedure. Discussion The primary goal of the study is to determine perioperative blood loss as a measure of the efficacy of TXA, EACA, and placebo. Based on current literature and the mechanism by which the medications act, we hypothesize that TXA will be more effective at reducing blood loss than EACA or placebo and result in improved patient outcomes. Trial Registration ClinicalTrials.gov ID: NCT00958581 PMID:20370916

Antioxidant supplementation for the prevention of kwashiorkor in Malawian children: randomised, double blind, placebo controlled trial

PubMed Central

Ciliberto, Heather; Ciliberto, Michael; Briend, Andreé; Ashorn, Per; Bier, Dennis; Manary, Mark

2005-01-01

Objective To evaluate the efficacy of antioxidant supplementation in preventing kwashiorkor in a population of Malawian children at high risk of developing kwashiorkor. Design Prospective, double blind, placebo controlled trial randomised by household. Setting 8 villages in rural southern Malawi. Participants 2372 children in 2156 households aged 1-4 years were enrolled; 2332 completed the trial. Intervention Daily supplementation with an antioxidant powder containing riboflavin, vitamin E, selenium, and N-acetylcysteine in a dose that provided about three times the recommended dietary allowance of each nutrient or placebo for 20 weeks. Main outcome measures The primary outcome was the incidence of oedema. Secondary outcomes were the rates of change for weight and length and the number of days of infectious symptoms. Results 62 children developed kwashiorkor (defined by the presence of oedema); 39/1184 (3.3%) were in the antioxidant group and 23/1188 (1.9%) were in the placebo group (relative risk 1.70, 95% confidence interval 0.98 to 2.42). The two groups did not differ in rates of weight or height gain. Children who received antioxidant supplementation did not experience less fever, cough, or diarrhoea. Conclusions Antioxidant supplementation at the dose provided did not prevent the onset of kwashiorkor. This finding does not support the hypothesis that depletion of vitamin E, selenium, cysteine, or riboflavin has a role in the development of kwashiorkor. PMID:15851401

Double-blind, Placebo-controlled Study Assessing the Effect of Chocolate Consumption in Subjects with a History of Acne Vulgaris

PubMed Central

Caperton, Caroline; Block, Samantha; Viera, Martha; Keri, Jonette

2014-01-01

Objective: To assess the effect of chocolate on acne exacerbation in males between the ages of 18 and 35 with a history of acne vulgaris. Design: Double-blind, placebo-controlled, randomized, controlled trial. Setting: Single-site, outpatient, research, clinical facility at an academic research institution. Participants: Fourteen men between the ages of 18 and 35 were assigned to swallow capsules filled with either unsweetened 100-percent cocoa, hydrolyzed gelatin powder, or a combination of the two, at baseline. Measurements: Lesions were assessed and photographs were taken at baseline, Day 4, and Day 7. Results: Of the 14 subjects, 13 completed this Institutional Review Board approved study. A statistically significant increase in the mean number of total acneiform lesions (comedones, papules, pustules, nodules) was detected on both Day 4 (p=0.006) and Day 7 (p=0.043) compared to baseline. A small-strength positive Pearson’s correlation coefficient existed between the amount of chocolate each subject consumed and the number of lesions each subject developed between baseline and Day 4 (r=0.250), while a medium-strength positive correlation existed between baseline and Day 7 (r=0.314). No serious adverse events occurred. Conclusion: It appears that in acne-prone, male individuals, the consumption of chocolate correlates to an increase in the exacerbation of acne. PMID:24847404

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

L-Dopa Modulates Functional Connectivity in Striatal Cognitive and Motor Networks: A Double-Blind Placebo-Controlled Study

PubMed Central

Kelly, Clare; de Zubicaray, Greig; Di Martino, Adriana; Copland, David A.; Reiss, Philip T.; Klein, Donald F.; Castellanos, F. Xavier; Milham, Michael P.; McMahon, Katie

2010-01-01

Functional connectivity (FC) analyses of resting-state fMRI data allow for the mapping of large-scale functional networks, and provide a novel means of examining the impact of dopaminergic challenge. Here, using a double-blind, placebo-controlled design, we examined the effect of L-dopa, a dopamine precursor, on striatal resting-state FC in 19 healthy young adults. We examined the FC of 6 striatal regions-of-interest previously shown to elicit networks known to be associated with motivational, cognitive and motor subdivisions of the caudate and putamen (Di Martino et al., Cerebral Cortex, 2008). In addition to replicating the previously demonstrated patterns of striatal FC, we observed robust effects of L-dopa. Specifically, L-dopa increased FC in motor pathways connecting the putamen ROIs with the cerebellum and brainstem. While L-dopa also increased FC between the inferior ventral striatum and ventrolateral prefrontal cortex, it disrupted ventral striatal and dorsal caudate FC with the default mode network. These alterations in FC are consistent with studies that have demonstrated dopaminergic modulation of cognitive and motor striatal networks in healthy participants. Recent studies have demonstrated altered resting state FC in several conditions believed to be characterized by abnormal dopaminergic neurotransmission. Our findings suggest that the application of similar experimental pharmacological manipulations in such populations may further our understanding of the role of dopaminergic neurotransmission in those conditions. PMID:19494158

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.

Prospective, double-blinded, randomised controlled trial assessing the effect of an Octenidine-based hydrogel on bacterial colonisation and epithelialization of skin graft wounds in burn patients.

PubMed

W, Eisenbeiß; F, Siemers; G, Amtsberg; P, Hinz; B, Hartmann; T, Kohlmann; A, Ekkernkamp; U, Albrecht; O, Assadian; A, Kramer

2012-01-01

Moist wound treatment improves healing of skin graft donor site wounds. Microbial colonised wounds represent an increased risk of wound infection; while antimicrobially active, topical antiseptics may impair epithelialization. The aim of this prospective randomised controlled clinical trial was to examine the influence of an Octenidine-dihydrochloride (OCT) hydrogel on bacterial colonisation and epithelialization of skin graft donor sites. The study was designed as a randomised, double-blinded, controlled clinical trial. Skin graft donor sites from a total of 61 patients were covered either with 0.05% OCT (n=31) or an OCT-free placebo wound hydrogel (n=30). Potential interaction with wound healing was assessed by measuring the time until 100% re-epithelialization. In addition, microbial wound colonisation was quantitatively determined in all skin graft donor sites. There was no statistically significant difference in the time for complete epithelialization of skin graft donor sites in the OCT and the placebo group (7.3±0.2 vs. 6.9±0.2 days; p=0.236). Microbial wound colonisation was significantly lower in the OCT group than in the placebo group (p=0.014). The OCT-based hydrogel showed no delay in wound epithelialization and demonstrated a significantly lower bacterial colonisation of skin graft donor site wounds.

Prospective, double-blinded, randomised controlled trial assessing the effect of an Octenidine-based hydrogel on bacterial colonisation and epithelialization of skin graft wounds in burn patients

PubMed Central

W, Eisenbeiß; F, Siemers; G, Amtsberg; P, Hinz; B, Hartmann; T, Kohlmann; A, Ekkernkamp; U, Albrecht; O, Assadian; A, Kramer

2012-01-01

Background: Moist wound treatment improves healing of skin graft donor site wounds. Microbial colonised wounds represent an increased risk of wound infection; while antimicrobially active, topical antiseptics may impair epithelialization. Objectives: The aim of this prospective randomised controlled clinical trial was to examine the influence of an Octenidine-dihydrochloride (OCT) hydrogel on bacterial colonisation and epithelialization of skin graft donor sites. Methods: The study was designed as a randomised, double-blinded, controlled clinical trial. Skin graft donor sites from a total of 61 patients were covered either with 0.05% OCT (n=31) or an OCT-free placebo wound hydrogel (n=30). Potential interaction with wound healing was assessed by measuring the time until 100% re-epithelialization. In addition, microbial wound colonisation was quantitatively determined in all skin graft donor sites. Results: There was no statistically significant difference in the time for complete epithelialization of skin graft donor sites in the OCT and the placebo group (7.3±0.2 vs. 6.9±0.2 days; p=0.236). Microbial wound colonisation was significantly lower in the OCT group than in the placebo group (p=0.014). Conclusions: The OCT-based hydrogel showed no delay in wound epithelialization and demonstrated a significantly lower bacterial colonisation of skin graft donor site wounds. PMID:23071904

Effect of caffeine on SPECT myocardial perfusion imaging during regadenoson pharmacologic stress: rationale and design of a prospective, randomized, multicenter study.

PubMed

Tejani, Furqan H; Thompson, Randall C; Iskandrian, Ami E; McNutt, Bruce E; Franks, Billy

2011-02-01

Caffeine attenuates the coronary hyperemic response to adenosine by competitive A₂(A) receptor blockade. This study aims to determine whether oral caffeine administration compromises diagnostic accuracy in patients undergoing vasodilator stress myocardial perfusion imaging (MPI) with regadenoson, a selective adenosine A(2A) agonist. This multicenter, randomized, double-blind, placebo-controlled, parallel-group study includes patients with suspected coronary artery disease who regularly consume caffeine. Each participant undergoes three SPECT MPI studies: a rest study on day 1 (MPI-1); a regadenoson stress study on day 3 (MPI-2), and a regadenoson stress study on day 5 with double-blind administration of oral caffeine 200 or 400 mg or placebo capsules (MPI-3; n = 90 per arm). Only participants with ≥ 1 reversible defect on the second MPI study undergo the subsequent stress MPI test. The primary endpoint is the difference in the number of reversible defects on the two stress tests using a 17-segment model. Pharmacokinetic/pharmacodynamic analyses will evaluate the effect of caffeine on the regadenoson exposure-response relationship. Safety will also be assessed. The results of this study will show whether the consumption of caffeine equivalent to 2-4 cups of coffee prior to an MPI study with regadenoson affects the diagnostic validity of stress testing (ClinicalTrials.gov number, NCT00826280).

Antipyretic effect of ibuprofen in Gabonese children with uncomplicated falciparum malaria: a randomized, double-blind, placebo-controlled trial

PubMed Central

Matsiégui, Pierre-Blaise; Missinou, Michel A; Necek, Magdalena; Mavoungou, Elie; Issifou, Saadou; Lell, Bertrand; Kremsner, Peter G

2008-01-01

Background Antipyretic drugs are widely used in children with fever, though there is a controversy about the benefit of reducing fever in children with malaria. In order to assess the effect of ibuprofen on fever compared to placebo in children with uncomplicated Plasmodium falciparum malaria in Gabon, a randomized double blind placebo controlled trial, was designed. Methods Fifty children between two and seven years of age with uncomplicated malaria were included in the study. For the treatment of fever, all patients "received" mechanical treatment when the temperature rose above 37.5°C. In addition to the mechanical treatment, continuous fanning and cooling blanket, patients were assigned randomly to receive ibuprofen (7 mg/kg body weight, every eight hours) or placebo. Results The fever clearance time using a fever threshold of 37.5°C was similar in children receiving ibuprofen compared to those receiving placebo. The difference was also not statistically significant using a fever threshold of 37.8°C or 38.0°C. However, the fever time and the area under the fever curve were significantly smaller in the ibuprofen group compared to the placebo group. Conclusion Ibuprofen is effective in reducing the time with fever. The effect on fever clearance is less obvious and depends on definition of the fever threshold. Trial registration The trial registration number is: NCT00167713 PMID:18503714

The effect of EarthPulse on learning of declarative knowledge

NASA Astrophysics Data System (ADS)

McKinney, Heather E.

The purpose of this double-blind, bio-medical research study was to investigate the effect of EarthPulse, a brainwave entrainment and pulsed electromagnetic field (PEMF) device, on learning of declarative knowledge. Currently, PEMF research explores physiological and psychological effects but a gap exists in the potential effects of PEMF on learning. The study explored whether a relationship existed between receiving a thirty minute EarthPulse treatment on the "Entrain Up" setting and learning of declarative knowledge; whether the relationship remained over time; whether EarthPulse had an effect on sleep; and whether EarthPulse had an effect on attrition. Ninety-eight, randomly assigned, undergraduate students participated in this double-blind, experimental design study, of which 87 remained after attrition. After receiving a thirty minute EarthPulse or placebo treatment, experimental and control groups read identical passages and completed identical instruments to test learning and retention of declarative knowledge. Participants completed the same test in two intervals: an immediate (learning) and delayed (retention) posttest. Assumptions for normality and reliability were met. One-way ANOVA revealed no statistically significant effects on learning or retention at the 0.05 level. However, Chi square analysis revealed those who received the EarthPulse treatment were significantly less likely to fall asleep than those who received the control treatment (p=0.022) and very closely approached significance for attrition (p=0.051).

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

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

PubMed

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

2012-12-06

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

Enzyme potentiated desensitisation in treatment of seasonal allergic rhinitis: double blind randomised controlled study

PubMed Central

Radcliffe, Michael J; Lewith, George T; Turner, Richard G; Prescott, Philip; Church, Martin K; Holgate, Stephen T

2003-01-01

Objective To assess the efficacy of enzyme potentiated desensitisation in the treatment of severe summer hay fever poorly controlled by pharmacotherapy. Design Double blind randomised placebo controlled parallel group study. Setting Hospital in Hampshire. Participants 183 participants aged between 18 and 64 with a history of severe summer hay fever for at least two years; all were skin prick test positive to timothy grass pollen. 90 randomised to active treatment; 93 randomised to placebo. Interventions Active treatment: two injections of enzyme potentiated desensitisation, given between eight and 11 weeks apart, each comprising 200 Fishman units of β glucuronidase, 50 pg 1,3-cyclohexanediol, 50 ng protamine sulphate, and a mixed inhaled allergen extract (pollen mixes for trees, grasses, and weeds; allergenic fungal spores; cat and dog danders; dust and storage mites) in a total volume of 0.05 ml of buffered saline. Placebo: two injections of 0.05 ml buffered saline solution. Main outcome measures Proportion of problem-free days; global rhinoconjunctivitis quality of life scores assessed weekly during pollen season. Results The active treatment group and the placebo group did not differ in the proportion of problem-free days, quality of life scores, symptom severity scores, change in quantitative skin prick provocation threshold, or change in conjunctival provocation threshold. No clinically significant adverse reactions occurred. Conclusions Enzyme potentiated desensitisation showed no treatment effect in this study. PMID:12896934

The Bipolar Depression Electrical Treatment Trial (BETTER): Design, Rationale, and Objectives of a Randomized, Sham-Controlled Trial and Data from the Pilot Study Phase

PubMed Central

Pereira Junior, Bernardo de Sampaio; Nunes, Paula; Benseñor, Isabela Martins; Lotufo, Paulo Andrade; Machado-Vieira, Rodrigo; Brunoni, André R.

2015-01-01

Background. Bipolar depression (BD) is a prevalent condition, with poor therapeutic options and a high degree of refractoriness. This justifies the development of novel treatment strategies, such as transcranial direct current stimulation (tDCS) that showed promising results in unipolar depression. Methods. We describe a randomized, sham-controlled, double-blinded trial using tDCS for refractory, acutely symptomatic BD (the bipolar depression electrical treatment trial, BETTER). Sixty patients will be enrolled and assessed with clinical and neuropsychological tests. The primary outcome is change (over time and across groups) in the scores of the Hamilton Depression Rating Scale (17 items). Biological markers such as blood neurotrophins and interleukins, genetic polymorphisms, heart rate variability, and motor cortical excitability will be assessed. Twelve anodal-left/cathodal-right 2 mA tDCS sessions over the dorsolateral prefrontal cortex will be performed in 6 weeks. Results. In the pilot phase, five patients received active tDCS and were double-blindly assessed, two presenting clinical response. TDCS was well-tolerated, with no changes in cognitive scores. Conclusion. This upcoming clinical trial will address the efficacy of tDCS for BD on different degrees of refractoriness. The evaluation of biological markers will also help in understanding the pathophysiology of BD and the mechanisms of action of tDCS. PMID:25878904

The TRACTISS Protocol: a randomised double blind placebo controlled clinical TRial of Anti-B-Cell Therapy In patients with primary Sjögren’s Syndrome

PubMed Central

2014-01-01

Background Primary Sjögren’s Syndrome (PSS) mainly affects women (9:1 female:male ratio) and is one of the commonest autoimmune diseases with a prevalence of 0.1 – 0.6% of adult women. For patients with PSS there is currently no effective therapy that can alter the progression of the disease. The aim of the TRACTISS study is to establish whether in patients with PSS, treatment with rituximab improves clinical outcomes. Methods/design TRACTISS is a UK multi-centre, double-blind, randomised, controlled, parallel group trial of 110 patients with PSS. Patients will be randomised on a 1:1 basis to receive two courses of either rituximab or placebo infusion in addition to standard therapy, and will be followed up for up to 48 weeks. The primary objective is to assess the extent to which rituximab improves symptoms of fatigue and oral dryness. Secondary outcomes include ocular dryness, salivary flow rates, lacrimal flow, patient quality of life, measures of disease damage and disease activity, serological and peripheral blood biomarkers, and glandular histology and composition. Discussion The TRACTISS trial will provide direct evidence as to whether rituximab in patients with PSS leads to an improvement in patient symptoms and a reduction in disease damage and activity. Trial registration UKCRN Portfolio ID: 9809 ISRCTN65360827. PMID:24438039

Suspected Nonceliac Gluten Sensitivity Confirmed in Few Patients After Gluten Challenge in Double-Blind, Placebo-Controlled Trials.

PubMed

Molina-Infante, Javier; Carroccio, Antonio

2017-03-01

A double-blind, placebo-controlled, gluten challenge has been proposed to confirm a diagnosis of nonceliac gluten sensitivity (NCGS) in patients without celiac disease who respond to a gluten-free diet. To determine the accuracy of this approach, we analyzed data from 10 double-blind, placebo-controlled, gluten-challenge trials, comprising 1312 adults. The studies varied in the duration of the challenge (range, 1 d to 6 wk), daily doses for the gluten challenge (range, 2-52 g; 3 studies administered <8 g/d), and composition of the placebo (gluten-free products, xylose, whey protein, rice, or corn starch containing fermentable carbohydrates). Most of the studies found gluten challenge to significantly increase symptom scores compared with placebo. However, only 38 of 231 NCGS patients (16%) showed gluten-specific symptoms. Furthermore, 40% of these subjects had a nocebo response (similar or increased symptoms in response to placebo). These findings reveal heterogeneity and potential methodology flaws among studies of gluten challenge, cast doubt on gluten as the culprit food component in most patients with presumptive NCGS, and highlight the importance of the nocebo effect in these types of studies. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Efficacy and safety of pioglitazone added to alogliptin in Japanese patients with type 2 diabetes mellitus: a multicentre, randomized, double-blind, parallel-group, comparative study.

PubMed

Kaku, K; Katou, M; Igeta, M; Ohira, T; Sano, H

2015-12-01

A phase IV, multicentre, randomized, double-blind, parallel-group, comparative study was conducted in Japanese subjects with type 2 diabetes mellitus (T2DM) who had inadequate glycaemic control, despite treatment with alogliptin in addition to diet and/or exercise therapy. Subjects with glycated haemoglobin (HbA1c) concentrations of 6.9-10.5% were randomized to receive 16 weeks' double-blind treatment with pioglitazone 15 mg, 30 mg once daily or placebo added to alogliptin 25 mg once daily. The primary endpoint was the change in HbA1c from baseline at the end of treatment period (week 16). Both pioglitazone 15 and 30 mg combination therapy resulted in a significantly greater reduction in HbA1c than alogliptin monotherapy [-0.80 and -0.90% vs 0.00% (the least squares mean using analysis of covariance model); p < 0.0001, respectively]. The overall incidence rates of treatment-emergent adverse events were similar among the treatment groups. Pioglitazone/alogliptin combination therapy was effective and generally well tolerated in Japanese subjects with T2DM and is considered to be useful in clinical settings. © 2015 John Wiley & Sons Ltd.

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

PubMed

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

2018-06-08

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

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

PubMed

Lueangarun, Suparuj; Sermsilp, Chairat; Tempark, Therdpong

2018-04-13

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

A double-blind atropine trial for active learning of autonomic function.

PubMed

Fry, Jeffrey R; Burr, Steven A

2011-12-01

Here, we describe a human physiology laboratory class measuring changes in autonomic function over time in response to atropine. Students use themselves as subjects, generating ownership and self-interest in the learning as well as directly experiencing the active link between physiology and pharmacology in people. The class is designed to concomitantly convey the importance of bias in experimentation by adopting a double-blind placebo-controlled approach. We have used this class effectively in various forms with ∼600 students receiving atropine over the last 16 yr. This class has received favorable feedback from staff and students of medicine, pharmacy, and neuroscience, and we recommend it for such undergraduates. The learning objectives that students are expected to achieve are to be able to 1) know the ethical, safety, and hygiene requirements for using human volunteers as subjects; 2) implement and explain a double-blind placebo-controlled trial; 3) design, agree, and execute a protocol for making (and accurately recording) precise reproducible measurements of pulse rate, pupil diameter, and salivary flow; 4) evaluate the importance of predose periods and measurement consistency to detect effects (including any reversibility) after an intervention; 5) experience direct cause-and-effect relationships integrating physiology with pharmacology in people; 6) calculate appropriate summary statistics to describe the data and determine the data's statistical significance; 7) recognize normal variability both within and between subjects in baseline physiological parameters and also recognize normal variability in response to pharmacological treatment; 8) infer the distribution and role of muscarinic receptors in the autonomic nervous system with respect to the heart, eye, and mouth; 9) identify and explain the clinical significance of differences in effect due to the route and formulation of atropine; 10) produce and deliver a concise oral presentation of experimental findings; and 11) produce a written report in the form of a short scientific research article. The results of a typical study are presented, which demonstrate that the administration of atropine by a subcutaneous injection elicited a significant increase in pulse rate and pupil diameter and a significant decrease in salivary flow, whereas administration of atropine in an oral liquid elicited significant effects on pulse rate and salivary flow, and an oral solid format elicited a significant alteration in salivary flow alone. More detailed analysis of the salivary flow data demonstrated clear differences between the routes of administration and formulation in the onset and magnitude of action of atropine.

Recent advances in the management of neuropsychiatric symptoms in dementia.

PubMed

Forlenza, Orestes V; Loureiro, Júlia Cunha; Pais, Marcos Vasconcelos; Stella, Florindo

2017-03-01

The present article addresses intriguing questions related to the clinical intervention in distinct neuropsychiatric syndromes of patients with dementia. We reviewed 154 articles published between 2015 and 2016 targeting psychopharmacological and nonpharmacological interventions, and safety-tolerability concerns. We selected 115 articles addressing the purpose of this study. Of these, 33 were chosen because they were dedicated to subtopics: agitation (42), depression (33), apathy (18), sleep disorders/anxiety (8), and psychosis (4). Clinical studies using both pharmacological (70) and nonpharmacological (37) interventions were considered; others were included for theoretical support. Regarding the methodological design, we found double-blind RCTs (17), single-blinded RCTs (4), open-label studies (18), case reports (5), cross-sectional or cohort studies (25), epidemiological papers (2), and expert reviews (44). This observation raises concerns about the overall methodological adequacy of a substantial proportion of studies in this field, which limits the potential of generalization of the findings. Finally, 18 studies were designed to determine safety-tolerability issues of psychotropic medications (6 were discussed). Effective and well tolerated treatment of neuropsychiatric syndromes in dementia remains a critically unsolved challenge. We understand that this is an extremely important area of research, and critically required to guide clinical decisions in geriatric neuropsychiatry.

Lansoprazole for secondary prevention of gastric or duodenal ulcers associated with long-term non-steroidal anti-inflammatory drug (NSAID) therapy: results of a prospective, multicenter, double-blind, randomized, double-dummy, active-controlled trial.

PubMed

Sugano, Kentaro; Kontani, Teiji; Katsuo, Shinichi; Takei, Yoshinori; Sakaki, Nobuhiro; Ashida, Kiyoshi; Mizokami, Yuji; Asaka, Masahiro; Matsui, Shigeyuki; Kanto, Tatsuya; Soen, Satoshi; Takeuchi, Tsutomu; Hiraishi, Hideyuki; Hiramatsu, Naoki

2012-05-01

Low-dose lansoprazole has not been intensively evaluated for its efficacy in the prevention of recurrent gastric or duodenal ulcers in patients receiving long-term non-steroidal anti-inflammatory drug (NSAID) therapy for pain relief in such diseases as rheumatoid arthritis, osteoarthritis, and low back pain. This multi-center, prospective, double-blind, randomized, active-controlled study involving 99 sites in Japan was designed to compare the efficacy of lansoprazole (15 mg daily) with gefarnate (50 mg twice daily). Patients with a history of gastric or duodenal ulcers who required long-term NSAID therapy were randomized to receive lansoprazole 15 mg daily (n = 185) or gefarnate 50 mg twice daily (n = 181) and followed up for 12 months or longer prospectively. The cumulative incidence of gastric or duodenal ulcer at days 91, 181, and 361 from the start of the study was calculated by the Kaplan-Meier method as 3.3, 5.9, and 12.7%, respectively, in the lansoprazole group versus 18.7, 28.5, and 36.9%, respectively, in the gefarnate group. The risk for ulcer development was significantly (log-rank test, P < 0.0001) lower in the lansoprazole group than in the gefarnate group, with the hazard ratio being 0.2510 (95% CI 0.1400-0.4499). A long-term follow-up study showed an acceptable safety profile for low-dose lansoprazole therapy, with diarrhea as the most frequent adverse event. Lansoprazole was superior to gefarnate in reducing the risk of gastric or duodenal ulcer recurrence in patients with a definite history of gastric or duodenal ulcers who required long-term NSAID therapy.

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

PubMed

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

1997-01-01

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

Multicentre Double-Blind Placebo-Controlled Food Challenge Study in Children Sensitised to Cashew Nut.

PubMed

van der Valk, Johanna P M; Gerth van Wijk, Roy; Dubois, Anthony E J; de Groot, Hans; Reitsma, Marit; Vlieg-Boerstra, Berber; Savelkoul, Huub F J; Wichers, Harry J; de Jong, Nicolette W

2016-01-01

Few studies with a limited number of patients have provided indications that cashew-allergic patients may experience severe allergic reactions to minimal amounts of cashew nut. The objectives of this multicentre study were to assess the clinical relevance of cashew nut sensitisation, to study the clinical reaction patterns in double-blind placebo-controlled food challenge tests and to establish the amount of cashew nuts that can elicit an allergic reaction. A total of 179 children were included (median age 9.0 years; range 2-17 years) with cashew nut sensitisation and a clinical history of reactions to cashew nuts or unknown exposure. Sensitised children who could tolerate cashew nuts were excluded. The study included three clinical visits and a telephone consultation. During the first visit, the medical history was evaluated, physical examinations were conducted, blood samples were drawn and skin prick tests were performed. The children underwent a double-blind placebo-controlled food challenge test with cashew nut during the second and third visits. The study showed that 137 (76.5%) of the sensitised children suspected of allergy to cashew nut had a positive double-blind placebo-controlled food challenge test, with 46% (63) manifesting subjective symptoms to the lowest dose of 1 mg cashew nut protein and 11% (15) developing objective symptoms to the lowest dose. Children most frequently had gastro-intestinal symptoms, followed by oral allergy and skin symptoms. A total of 36% (49/137) of the children experienced an anaphylactic reaction and 6% (8/137) of the children were treated with epinephrine. This prospective study demonstrated a strikingly high percentage of clinical reactions to cashew nut in this third line population. Severe allergic reactions, including anaphylaxis requiring epinephrine, were observed. These reactions were to minimal amounts of cashew nut, demonstrated the high potency of this allergens. www.ncbi.nlm.nih.gov/pubmed NTR3572.

Multicentre Double-Blind Placebo-Controlled Food Challenge Study in Children Sensitised to Cashew Nut

PubMed Central

van der Valk, Johanna P. M.; Gerth van Wijk, Roy; Dubois, Anthony E. J.; de Groot, Hans; Reitsma, Marit; Vlieg-Boerstra, Berber; Savelkoul, Huub F. J.; Wichers, Harry J.; de Jong, Nicolette W.

2016-01-01

Background Few studies with a limited number of patients have provided indications that cashew-allergic patients may experience severe allergic reactions to minimal amounts of cashew nut. The objectives of this multicentre study were to assess the clinical relevance of cashew nut sensitisation, to study the clinical reaction patterns in double-blind placebo-controlled food challenge tests and to establish the amount of cashew nuts that can elicit an allergic reaction. Methods and Findings A total of 179 children were included (median age 9.0 years; range 2–17 years) with cashew nut sensitisation and a clinical history of reactions to cashew nuts or unknown exposure. Sensitised children who could tolerate cashew nuts were excluded. The study included three clinical visits and a telephone consultation. During the first visit, the medical history was evaluated, physical examinations were conducted, blood samples were drawn and skin prick tests were performed. The children underwent a double-blind placebo-controlled food challenge test with cashew nut during the second and third visits. The study showed that 137 (76.5%) of the sensitised children suspected of allergy to cashew nut had a positive double-blind placebo-controlled food challenge test, with 46% (63) manifesting subjective symptoms to the lowest dose of 1 mg cashew nut protein and 11% (15) developing objective symptoms to the lowest dose. Children most frequently had gastro-intestinal symptoms, followed by oral allergy and skin symptoms. A total of 36% (49/137) of the children experienced an anaphylactic reaction and 6% (8/137) of the children were treated with epinephrine. Conclusion This prospective study demonstrated a strikingly high percentage of clinical reactions to cashew nut in this third line population. Severe allergic reactions, including anaphylaxis requiring epinephrine, were observed. These reactions were to minimal amounts of cashew nut, demonstrated the high potency of this allergens. Trial Registration www.ncbi.nlm.nih.gov/pubmed NTR3572 PMID:26967158

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

PubMed

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

2016-07-01

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

Analysis of opioid-mediated analgesia in Phase III studies of methylnaltrexone for opioid-induced constipation in patients with chronic noncancer pain

PubMed Central

Webster, Lynn R; Brenner, Darren M; Barrett, Andrew C; Paterson, Craig; Bortey, Enoch; Forbes, William P

2015-01-01

Background Subcutaneous methylnaltrexone is efficacious and well tolerated for opioid-induced constipation (OIC) but may theoretically disrupt opioid-mediated analgesia. Methods Opioid use, pain intensity, and opioid withdrawal (Objective Opioid Withdrawal Scale [OOWS] and Subjective Opiate Withdrawal Scale [SOWS] scores) were reported in a randomized, double-blind trial with an open-label extension (RCT) and an open-label trial (OLT) evaluating safety in adults with chronic noncancer pain. In the RCT, patients taking ≥50 mg of oral morphine equivalents daily with <3 rescue-free bowel movements weekly received methyl naltrexone 12 mg once daily (n=150), every other day (n=148), or placebo (n=162) for 4 weeks, followed by open-label methylnaltrexone 12 mg (as needed [prn]; n=364) for 8 weeks. In the OLT, patients (n=1,034) on stable opioid doses with OIC received methylnaltrexone 12 mg prn for up to 48 weeks. Results Minimal fluctuations of median morphine equivalent dose from baseline (BL) were observed in the RCT double-blind period (BL, 154.8–161.0 mg/d; range, 137.1–168.0 mg/d), RCT open-label period (BL, 156.3–174.6; range, 144.0–180.0) and OLT (BL, 120 mg/d; range, 117.3–121.1 mg/d). No significant change from BL in pain intensity score occurred in any group at weeks 2 or 4 (both P≥0.1) of the RCT double-blind period, and scores remained stable during the open-label period and in the OLT (mean change, −0.2 to 0.1). Changes from BL in OOWS and SOWS scores during the double-blind period were not significantly impacted by methylnaltrexone exposure at weeks 2 or 4 (P>0.05 for all). Conclusion Methylnaltrexone did not affect opioid-mediated analgesia in patients with chronic noncancer pain and OIC. PMID:26586963

Cardiovascular Profile of Valbenazine: Analysis of Pooled Data from Three Randomized, Double-Blind, Placebo-Controlled Trials.

PubMed

Thai-Cuarto, Dao; O'Brien, Christopher F; Jimenez, Roland; Liang, Grace S; Burke, Joshua

2018-04-01

Valbenazine is a novel vesicular monoamine transporter 2 inhibitor approved for the treatment of tardive dyskinesia in adults. Using data from double-blind, placebo-controlled trials, analyses were conducted to evaluate the cardiovascular effects of once-daily valbenazine in patients with a psychiatric disorder who developed tardive dyskinesia after exposure to a dopamine-blocking medication. Data were pooled from three 6-week, double-blind, placebo-controlled trials: KINECT (NCT01688037), KINECT 2 (NCT01733121), and KINECT 3 (NCT02274558). Data from the 42-week valbenazine extension period of KINECT 3 were also analyzed. Outcomes of interest included cardiovascular-related treatment-emergent adverse events, vital sign measurements, and electrocardiogram parameters. The pooled safety population included 400 participants (placebo, n = 178; valbenazine 40 mg/day, n = 110; valbenazine 80 mg/day, n = 112). A history of cardiac disorders was present in 11.8% of participants, and 74.3% were taking a concomitant medication with known potential for QT prolongation. Mean changes from baseline to week 6 in supine vital signs and QTcF (Fridericia correction) were as follows for placebo, valbenazine 40 mg/day, and valbenazine 80 mg/day, respectively: systolic blood pressure (0.2, - 2.1, - 1.8 mmHg), diastolic blood pressure (- 0.1, - 1.6, - 1.2 mmHg), heart rate (- 1.7, - 2.2, - 1.7 bpm), QTcF interval (1.2, 1.1, 2.1 ms); all p > 0.05 for valbenazine vs. placebo. No statistically significant differences were observed between placebo and valbenazine in cardiovascular-related, treatment-emergent adverse events. No notable additional effects on cardiovascular outcomes were found with up to 48 weeks of valbenazine treatment. Results from double-blind, placebo-controlled trials showed no apparent difference between valbenazine and placebo on cardiovascular outcomes. No additional cardiovascular risk was detected during a longer extension study with valbenazine.

Comparative safety of intravenous Ferumoxytol versus Ferric Carboxymaltose for the Treatment of Iron Deficiency Anemia: rationale and study design of a randomized double-blind study with a focus on acute hypersensitivity reactions.

PubMed

Adkinson, N Franklin; Strauss, William E; Bernard, Kristine; Kaper, Robert F; Macdougall, Iain C; Krop, Julie S

2017-01-01

Intravenous (IV) iron is often used to treat iron deficiency anemia in patients who are unable to tolerate or are inadequately managed with oral iron. However, IV iron treatment has been associated with acute hypersensitivity reactions. The comparative risk of adverse events (AEs) with IV iron preparations has been assessed by a few randomized controlled trials, which are most often limited by small patient numbers, which lack statistical power to identify differences in low-frequency AE such as hypersensitivity reactions. Ferumoxytol versus Ferric Carboxymaltose for the Treatment of Iron Deficiency Anemia (FIRM) is a randomized, double-blind, international, multicenter, Phase III study designed to compare the safety of ferumoxytol and ferric carboxymaltose (FCM). The study includes adults with hemoglobin <12.0 g/dL (females) or <14.0 g/dL (males), transferrin saturation ≤20% or ferritin ≤100 ng/mL within 60 days of dosing, and a history of unsatisfactory or nontolerated oral iron therapy or in whom oral iron therapy is inappropriate. Patients are randomized (1:1) to ferumoxytol 510 mg or FCM 750 mg, each given intravenously on days 1 and 8. Primary end points are the incidence of moderate-to-severe hypersensitivity reactions, including anaphylaxis, and moderate-to-severe hypotension. All potential hypersensitivity and hypotensive reactions will be adjudicated by a blinded, independent Clinical Events Committee. A secondary safety end point is the composite frequency of moderate-to-severe hypersensitivity reactions, including anaphylaxis, serious cardiovascular events, and death. Secondary efficacy end points include mean change in hemoglobin and mean change in hemoglobin per milligram of iron administered from baseline to week 5. Urinary excretion of phosphorus and the occurrence of hypophosphatemia after IV iron administration will be examined as well as the mechanisms of such hypophosphatemia in a substudy. FIRM will provide data on the comparative safety of ferumoxytol and FCM, two IV iron preparations with similar dosing schedules, focusing on moderate-to-severe hypersensitivity reactions, including anaphylaxis, and moderate-to-severe hypotension. The study plans to enroll 2000 patients and is expected to complete in 2017.

Yukmijihwang-tang for the treatment of xerostomia in the elderly: study protocol for a randomized, double-blind, placebo-controlled, two-center trial.

PubMed

Han, Gajin; Park, Jae-Woo; Ko, Seok-Jae; Son, Jihee; Seon, Jongki; Kim, Juyeon; Kim, Seulki; Yeo, Inkwon; Ryu, Bongha; Kim, Jinsung

2013-09-03

Xerostomia, a subjective sense of dry mouth, is not generally regarded a disease despite its high prevalence among the elderly, and therefore continues to impair affected patients' quality of life. In traditional Korean medicine, 'Yin-Deficiency' has been implicated in the pathogenesis of xerostomia among the elderly. Yukmijihwang-tang is a famous herbal prescription used to relieve 'Yin-Deficiency', and reportedly has antioxidant effects; therefore, it is postulated that Yukmijihwang-tang can be used to treat xerostomia in the elderly. However, to our knowledge, no clinical trial has been conducted on the effects of Yukmijihwang-tang on xerostomia. Thus, we designed a randomized clinical trial to investigate the effects and safety of Yukmijihwang-tang on xerostomia in the elderly. In addition, we will clarify the aforementioned assumption that 'Yin-Deficiency' is the major cause of xerostomia in the elderly by identifying a correlation between xerostomia and 'Yin-Deficiency'. This randomized, double-blind, placebo-controlled trial will be carried out at two centers: Kyung Hee University Korean Medicine Hospital and Kyung Hee University Hospital at Gangdong. We will recruit 96 subjects aged 60-80 years who have experienced xerostomia for 3 months prior to participation. Subjects who present with score >40 on the visual analogue scale for xerostomia and unstimulated salivary flow rate under 0.3mL/min will be included and the randomization will be carried out by an independent statistician by using a random number creation program. The subjects and all researchers except the statistician will be blinded to the group assignment. Yukmijihwang-tang or placebo will be administered to each group for 8 weeks. The primary outcome is change in the scores for the visual analogue scale for xerostomia and the dry mouth symptom questionnaire from 0 to 8 weeks. It will be assessed whether Yukmijihwang-tang can be used as a new herbal treatment for xerostomia in the elderly by demonstrating its therapeutic effects in a well-designed clinical trial. ClinicalTrials.gov Identifier: NCT01579877.

Efficacy of individualized homeopathic treatment and fluoxetine for moderate to severe depression in peri- and postmenopausal women (HOMDEP-MENOP): study protocol for a randomized, double-dummy, double-blind, placebo-controlled trial

PubMed Central

2013-01-01

Background The perimenopausal period refers to the interval when women’s menstrual cycles become irregular and is characterized by an increased risk of depressive symptoms. Use of homeopathy to treat depression is widespread but there is a lack of clinical trials about its efficacy in depression in peri- and postmenopausal women. Previous trials suggest that individualized homeopathic treatments improve depression. In classical homeopathy, an individually selected homeopathic remedy is prescribed after a complete case history of the patient. The aim of this study is to assess the efficacy and safety of the homeopathic individualized treatment versus placebo or fluoxetine in peri- and postmenopausal women with moderate to severe depression. Methods/design A randomized, placebo-controlled, double-blind, double-dummy, three-arm trial with a six-week follow-up study was designed. The study will be conducted in a public research hospital in Mexico City (Juárez de México Hospital) in the outpatient service of homeopathy. One hundred eighty nine peri- and postmenopausal women diagnosed with major depression according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (moderate to severe intensity) will be included. The primary outcome is change in the mean total score among groups on the 17-item Hamilton Rating Scale for Depression after the fourth and sixth week of treatment. Secondary outcomes are: Beck Depression Inventory change in mean score, Greene’s Scale change in mean score, response and remission rates and safety. Efficacy data will be analyzed in the intention-to-treat population. To determine differences in the primary and secondary outcomes among groups at baseline and weeks four and six, data will be analyzed by analysis of variance for independent measures with the Bonferroni post-hoc test. Discussion This study is the first trial of classical homeopathy that will evaluate the efficacy of homeopathic individualized treatment using C-potencies versus placebo or fluoxetine in peri- and postmenopausal women with moderate to severe depression. It is an attempt to deal with the obstacles of homeopathic research due to the need for individual prescriptions in one of the most common psychiatric diseases. Trial registration ClinicalTrials.gov Identifier: NCT01635218. PMID:23782520

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.

Probiotic administration among free-living older adults: a double blinded, randomized, placebo-controlled clinical trial.

PubMed

Östlund-Lagerström, Lina; Kihlgren, Annica; Repsilber, Dirk; Björkstén, Bengt; Brummer, Robert J; Schoultz, Ida

2016-09-10

Diseases of the digestive system have been found to contribute to a higher symptom burden in older adults. Thus, therapeutic strategies able to treat gastrointestinal discomfort might impact the overall health status and help older adults to increase their overall health status and optimal functionality. The aim of this double-blinded, randomized, placebo-controlled clinical trial was to evaluate the effect of the probiotic strain Lactobacillus reuteri on digestive health and wellbeing in older adults. The study enrolled general older adults (>65 years). After eligibility screening qualified subjects (n = 290) participated in a 2-arm study design, with each arm consisting of 12 weeks of intervention of either active or placebo product. Primary outcome measure was set to changes in gastrointestinal symptoms and secondary outcome measures were changes in level of wellbeing, anxiety and stress. Follow up was performed at 8 and 12 weeks. No persistent significant effects were observed on the primary or secondary outcome parameters of the study. A modest effect was observed in the probiotic arm, were levels of stress decreased at week 8 and 12. Similarly, we found that subjects suffering from indigestion and abdominal pain, respectively, showed a significant decrease of anxiety at week 8 after probiotic treatment, but not at week 12. The RCT failed to show any improvement in digestive health after daily intake of a probiotic supplement containing L. reuteri. Neither was any significant improvement in wellbeing, stress or anxiety observed. Even though the RCT had a negative outcome, the study highlights issues important to take into consideration when designing trials among older adults. Clinicaltrials.gov/ NCT01837940 .

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

PubMed

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

2014-04-22

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

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.

Design and methods for the Better Resiliency Among Veterans and non-Veterans with Omega-3's (BRAVO) study: A double blind, placebo-controlled trial of omega-3 fatty acid supplementation among adult individuals at risk of suicide.

PubMed

Marriott, Bernadette P; Hibbeln, Joseph R; Killeen, Therese K; Magruder, Kathryn M; Holes-Lewis, Kelly; Tolliver, Bryan K; Turner, Travis H

2016-03-01

Suicide remains the 10th leading cause of death among adults in the United States (U.S.). Annually, approximately 30 per 100,000 U.S. military Veterans commit suicide, compared to 14 per 100,000 U.S. civilians. Symptoms associated with suicidality can be treatment resistant and proven-effective pharmaceuticals may have adverse side-effects. Thus, a critical need remains to identify effective approaches for building psychological resiliency in at-risk individuals. Omega-3 highly unsaturated fatty acids (n-3 HUFAs) are essential nutrients, which must be consumed in the diet. N-3 HUFAs have been demonstrated to reduce symptoms of depression, anxiety, and impulsivity - which are associated with suicide risk. Here we present the design and methods for the Better Resiliency Among Veterans and non-Veterans with Omega-3's (BRAVO) study, which is a double blind, randomized, controlled trial among individuals at risk of suicide of an n-3 HUFA versus placebo supplementation in the form of all natural fruit juice beverages. The BRAVO study seeks to determine if dietary supplementation with n-3 HUFAs reduces the risk for serious suicidal behaviors, suicidal thinking, negative emotions, and symptoms associated with suicide risk. Sub-analyses will evaluate efficacy in reducing depressive symptoms, alcohol, and nicotine use. A sub-study utilizes functional magnetic resonance imaging (fMRI) to evaluate the neuropsychological and neurophysiological effects of n-3 HUFAs. We also outline selection of appropriate proxy outcome measures for detecting response to treatment and collection of ancillary data, such as diet and substance use, that are critical for interpretation of results. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

The Infant Fish Oil Supplementation Study (IFOS): design and research protocol of a double-blind, randomised controlled n--3 LCPUFA intervention trial in term infants.

PubMed

Meldrum, S J; D'Vaz, N; Dunstan, J; Mori, T A; Prescott, S L

2011-09-01

The Infant Fish Oil Supplementation Study is a double-blind randomised controlled trial investigating whether the incidence of allergic disease can be reduced and developmental outcomes enhanced through supplementation with omega-3 fatty acids. Infants at high risk of developing allergic disease will be randomised to receive either fish oil or olive oil supplements until 6 months of age and followed up at six postnatal clinic visits to assess allergy outcomes and infant neurodevelopment. Study groups to consist of a treatment group allocated to receive 650 mg of fish oil daily (250-280 mg docosahexaenoic acid and at least 60 mg eicosapentaenoic acid and a placebo group (olive oil) from birth to 6 months of age. Allergy outcomes will be assessed by clinical history, clinical assessments and allergen skin prick tests at the 12, 30 and 60 month visits. Neurodevelopmental assessments to be conducted at 18 months, and language questionnaires at 12, 18 and 30 months. Samples will be collected from mothers antenatally, from infants at birth, and at clinic visits from 6 months onwards for immunological assessments. Fatty acid composition to be measured in erythrocytes and plasma (at birth and after the supplementation period) to assess the effect of the intervention on fatty acid status. Information on medical history, diet and other lifestyle factors at an antenatal clinic visit and postnatal clinic visits will also be collected. This study is designed to examine clinically relevant effects of a novel, non-invasive and potentially low cost approach to reduce the incidence of allergic disease and facilitate neurodevelopment during early childhood. Copyright © 2011 Elsevier Inc. All rights reserved.

Freeze-dried Lactobacillus plantarum 299v increases iron absorption in young females—Double isotope sequential single-blind studies in menstruating women

PubMed Central

Önning, Gunilla; Hulthén, Lena

2017-01-01

Background The probiotic strain Lactobacillus plantarum 299v has earlier been shown to increase iron absorption when added to foods. However, it is not known if the same probiotic strain in a freeze-dried format included in a capsule increases the iron absorption. Objective The aim of this study was to test the hypotheses that non-heme iron absorption from a light meal is promoted by a simultaneous intake of freeze-dried Lactobacillus plantarum 299v (Lp299v, DSM 9843). Study design With a single blinded placebo controlled sequential design, iron absorption from a light breakfast meal administered with or without capsules containing 1010 cfu freeze-dried Lp299v was studied in healthy female volunteers of fertile age. The methodology used was a double isotope technique (59Fe and 55Fe). Two studies were performed using the same protocol. Results In study 1, the absorption of iron from a meal without Lp299v was found to be 17.4 ± 13.4%, and from an identical meal with Lp299v was found to be 22.4 ± 17.3% (mean ± SD). This difference was statistically significant (p = 0.040, n = 14). In study 2, the absorption of iron from a meal without Lp299v was found to be 20.9 ± 13.1%, and from an identical meal with Lp299v found to be 24.5 ± 12.0% (mean ± SD, n = 28), which again was statistically significant (p = 0.003). Conclusion Freeze-dried Lp299v enhances the absorption of iron when administered together with a meal with a high iron bioavailability. Trial registration ClinicalTrials.gov Identifier: NCT02131870 PMID:29236734

Rationale and design of a community-based double-blind randomized clinical trial of an HPV 16 and 18 vaccine in Guanacaste, Costa Rica

PubMed Central

Herrero, Rolando; Hildesheim, Allan; Rodríguez, Ana C; Wacholder, Sholom; Bratti, Concepción; Solomon, Diane; González, Paula; Porras, Carolina; Jiménez, Silvia; Guillen, Diego; Morales, Jorge; Alfaro, Mario; Cyr, Jean; Morrisey, Kerrygrace; Estrada, Yenory; Cortés, Bernal; Morera, Lidia Ana; Freer, Enrique; Schussler, John; Schiller, John; Lowy, Douglas; Schiffman, Mark

2008-01-01

We report the rationale, design, methods and details of participation of a community-based, double blind, randomized clinical trial of an HPV 16 and 18 vaccine conducted in two provinces of Costa Rica to investigate the efficacy and population impact of the vaccine in the prevention of cervical cancer precursors. More than 24,000 women between 18 and 25 years of age were invited to participate and pre-screened for eligibility, with recruitment of 7,466 women (30% of those prescreened, 59% of those eligible) who were randomized to receive 3 doses of the HPV vaccine or hepatitis A vaccine as control. A complex protocol of data and specimen collection was applied, including an interview, pelvic exam for sexually active women, blood for serology and cell-mediated immunity, cervical secretions for local immunity and cells for HPV, Chlamydia trachomatis and Gonorrhea testing. Eighty percent of the women received 3 doses, 12.4% two doses and 7.4% one dose. At visits, compliance with data and specimen collection was close to 100%. Baseline characteristics and age-specific prevalence of HPV and cervical neoplasia are reported. Overall prevalence of HPV was high (50%), with 8.3% of women having HPV 16 and 3.2% HPV 18. LSIL was detected in 12.7% of women at baseline and HSIL in 1.9%. Prevalence of Chlamydia was 14.2%. There was very good agreement in HPV detection between clinician-collected and self-collected specimens (89.4% agreement for all types, kappa 0.59). Follow up will continue with yearly or more frequent examinations for at least 4 years for each participant. PMID:18640170

Probiotic prophylaxis in patients with predicted severe acute pancreatitis (PROPATRIA): design and rationale of a double-blind, placebo-controlled randomised multicenter trial [ISRCTN38327949

PubMed Central

Besselink, Marc GH; Timmerman, Harro M; Buskens, Erik; Nieuwenhuijs, Vincent B; Akkermans, Louis MA; Gooszen, Hein G

2004-01-01

Background Infectious complications are the major cause of death in acute pancreatitis. Small bowel bacterial overgrowth and subsequent bacterial translocation are held responsible for the vast majority of these infections. Goal of this study is to determine whether selected probiotics are capable of preventing infectious complications without the disadvantages of antibiotic prophylaxis; antibiotic resistance and fungal overgrowth. Methods/design PROPATRIA is a double-blind, placebo-controlled randomised multicenter trial in which 200 patients will be randomly allocated to a multispecies probiotic preparation (Ecologic 641) or placebo. The study is performed in all 8 Dutch University Hospitals and 7 non-University hospitals. The study-product is administered twice daily through a nasojejunal tube for 28 days or until discharge. Patients eligible for randomisation are adult patients with a first onset of predicted severe acute pancreatitis: Imrie criteria 3 or more, CRP 150 mg/L or more, APACHE II score 8 or more. Exclusion criteria are post-ERCP pancreatitis, malignancy, infection/sepsis caused by a second disease, intra-operative diagnosis of pancreatitis and use of probiotics during the study. Administration of the study product is started within 72 hours after onset of abdominal pain. The primary endpoint is the total number of infectious complications. Secondary endpoints are mortality, necrosectomy, antibiotic resistance, hospital stay and adverse events. To demonstrate that probiotic prophylaxis reduces the proportion of patients with infectious complications from 50% to 30%, with alpha 0,05 and power 80%, a total sample size of 200 patients was calculated. Conclusion The PROPATRIA study is aimed to show a reduction in infectious complications due to early enteral use of multispecies probiotics in severe acute pancreatitis. PMID:15456517

Effect of a new treatment protocol called Functional Chewing Training on chewing function in children with cerebral palsy: a double-blind randomised controlled trial.

PubMed

Serel Arslan, S; Demir, N; Karaduman, A A

2017-01-01

Cerebral palsy (CP) is a group of permanent sensorimotor impairments. Children with CP have various feeding difficulties including chewing disorder, which may affect their nutritional status. Functional Chewing Training (FuCT) was designed as a holistic approach to improve chewing function by providing postural alignment, sensory and motor training, and food and environmental adjustments. This study aimed to investigate the effect of FuCT on chewing function in children with CP. This study was designed as a double-blind, randomised controlled trial. Eighty CP children with chewing disorder were randomised and split between the FuCT group (31 males, 19 females; mean age 3·5 ± 1·9 years) and the control group (16 males, 14 females; 3·4 ± 2·3 years) receiving traditional oral motor exercises. Each group received the training programme for 12 weeks with weekly follow-up and with two evaluations at baseline and end of 12 weeks. Chewing function was evaluated by analysing video recordings and scored with the Karaduman Chewing Performance Scale (KCPS). The Behavioral Pediatrics Feeding Assessment Scale (BPFAS) was used to evaluate feeding behaviours of children. A significant improvement was observed in KCPS scores at 12 weeks after training in the FuCT group (P < 0·001), but no change was found in the control group (P = 0·07). A significant improvement was detected in all parameters of BPFAS at 12 weeks after training in the FuCT group (P < 0·001) and in four parameters of BPFAS in the control group (P = 0·02, P = 0·02). FuCT is an effective method to improve chewing function compared with traditional oral motor exercises. © 2016 John Wiley & Sons Ltd.

The efficacy and safety of Fufangdanshen tablets (Radix Salviae miltiorrhizae formula tablets) for mild to moderate vascular dementia: a study protocol for a randomized controlled trial.

PubMed

Tian, Jinzhou; Shi, Jing; Wei, Mingqing; Qin, Renan; Ni, Jingnian; Zhang, Xuekai; Li, Ting; Wang, Yongyan

2016-06-08

Vascular dementia (VaD) is the second most common subtype of dementia after Alzheimer's disease (AD). Currently, there are no medications approved for treating patients with VaD. Fufangdanshen (FFDS) tablets (Radix Salviae miltiorrhizae formula tablets) are a traditional Chinese medicine that has been reported to improve memory. However, the existing evidence for FFDS tablets in clinical practice derives from methodologically flawed studies. To further investigate the safety, tolerability, and efficacy of FFDS tables in the treatment of mild to moderate VaD, we designed and reported the methodology for a 24-week randomized, double-blind, parallel, multicenter study. This ongoing study is a double-blind, randomized, parallel placebo-controlled trial. A total of 240 patients with mild to moderate VaD will be enrolled. After a 2-week run-in period, the eligible patients will be randomized to receive either three FFDS or placebo tablets three times per day for 24 weeks, with a follow-up 12 weeks after the last treatment. The primary efficacy measurement will be the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and the Clinician Interview-Based Impression of Change (CIBIC-plus). The secondary efficacy measurements will include the Mini Mental State Examination (MMSE) and activities of daily living (ADL). Adverse events will also be reported. This randomized trial will be the first rigorous study on the efficacy and safety of FFDS tablets for treating cognitive symptoms in patients with VaD using a rational design. ClinicalTrials.gov: NCT01761227 . Registered on 2 January 2013.

Calcium phosphate supplementation increases faecal Lactobacillus spp. in a randomised trial of young adults.

PubMed

Dahl, W J; Ford, A L; Coppola, J A; Lopez, D; Combs, W; Rohani, A; Ukhanova, M; Culpepper, T; Tompkins, T A; Christman, M; Mai, V

2016-02-01

The aim of the studies was to determine the effects of calcium carbonate and calcium phosphate supplementation on faecal Lactobacillus spp., with and without a probiotic supplement, in healthy adults. Study 1 comprised of a randomised, double-blind, crossover design; participants (n=15) received 2 capsules/d of 250 mg elemental calcium as calcium carbonate (Ca1) and calcium phosphate (Ca2) each for 2-week periods, with 2-week baseline and washout periods. Study 2 was a randomised, double-blind, crossover design; participants (n=17) received 2 capsules/d of Lactobacillus helveticus R0052 and Lactobacillus rhamnosus R0011 (probiotic) alone, the probiotic with 2 capsules/d of Ca1, and probiotic with 2 capsules/d of Ca2 each for 2-week periods with 2-week baseline and washout periods. In both studies, stools were collected during the baseline, intervention and washout periods for Lactobacillus spp. quantification and qPCR analyses. Participants completed daily questionnaires of stool frequency and compliance. In Study 1, neither calcium supplement influenced viable counts of resident Lactobacillus spp., genome equivalents of lactic acid bacteria or stool frequency. In Study 2, faecal Lactobacillus spp. counts were significantly enhanced from baseline when the probiotic was administered with Ca2 (4.83±0.30, 5.79±0.31) (P=0.02), but not with Ca1 (4.98±0.31) or with the probiotic alone (5.36±0.31, 5.55±0.29) (not significant). Detection of L. helveticus R0052 and L. rhamnosus R0011 was significantly increased with all treatments, but did not differ among treatments. There were no changes in weekly stool frequency. Calcium phosphate co-administration may increase gastrointestinal survival of orally-administered Lactobacillus spp.

Towards evidence-based vitamin D supplementation in infants: vitamin D intervention in infants (VIDI) - study design and methods of a randomised controlled double-blinded intervention study.

PubMed

Helve, Otto; Viljakainen, Heli; Holmlund-Suila, Elisa; Rosendahl, Jenni; Hauta-Alus, Helena; Enlund-Cerullo, Maria; Valkama, Saara; Heinonen, Kati; Räikkönen, Katri; Hytinantti, Timo; Mäkitie, Outi; Andersson, Sture

2017-03-29

Vitamin D is important for bone mass accrual during growth. Additionally, it is considered a requirement for a multitude of processes associated with, for example, the development of immunity. Many countries apply vitamin D supplementation strategies in infants, but the guidelines are not based on scientific evidence and aim at prevention of rickets. It remains unclear whether the recommended doses are sufficient for the wide array of other effects of vitamin D. The VIDI trial performed in Finland is the first large randomised controlled study for evaluation of the effects of different vitamin D supplemental doses in infancy on: 1. bone strength 2. infections and immunity 3. allergy, atopy and asthma 4. cognitive development 5. genetic regulation of mineral homeostasis METHODS/DESIGN: VIDI, a randomised controlled double-blinded single-centre intervention study is conducted in infants from the age of 2 weeks to 24 months. Participants, recruited at Helsinki Maternity Hospital, are randomised to receive daily either 10 μg (400 IU) or 30 μg (1 200 IU) of vitamin D3 supplementation. Both groups are assessed at 6 months of age for calcium homeostasis, and at 12 and 24 months of age for parameters associated with bone strength, growth, developmental milestones, infections, immunity, atopy-related diseases, and genetic factors involved in these functions. The study enables evaluation of short and long term effects of supplemental vitamin D on growth, immune functions and skeletal and developmental parameters in infants, and the effects of genetic factors therein. The results enable institution of evidence-based guidelines for vitamin D supplementation in infancy. ClinicalTrials.gov, NCT01723852 , registration date 6.11.2012.

Design and conduct of 'Xtreme Alps': a double-blind, randomised controlled study of the effects of dietary nitrate supplementation on acclimatisation to high altitude.

PubMed

Martin, Daniel S; Gilbert-Kawai, Edward T; Meale, Paula M; Fernandez, Bernadette O; Cobb, Alexandra; Khosravi, Maryam; Mitchell, Kay; Grocott, Michael P W; Levett, Denny Z H; Mythen, Michael G; Feelisch, Martin

2013-11-01

The study of healthy human volunteers ascending to high altitude provides a robust model of the complex physiological interplay that emulates human adaptation to hypoxaemia in clinical conditions. Nitric oxide (NO) metabolism may play an important role in both adaptation to high altitude and response to hypoxaemia during critical illness at sea level. Circulating nitrate and nitrite concentrations can be augmented by dietary supplementation and this is associated with improved exercise performance and mitochondrial efficiency. We hypothesised that the administration of a dietary substance (beetroot juice) rich in nitrate would improve oxygen efficiency during exercise at high altitude by enhancing tissue microcirculatory blood flow and oxygenation. Furthermore, nitrate supplementation would lead to measurable increases in NO bioactivity throughout the body. This methodological manuscript describes the design and conduct of the 'Xtreme Alps' expedition, a double-blind randomised controlled trial investigating the effects of dietary nitrate supplementation on acclimatisation to hypobaric hypoxia at high altitude in healthy human volunteers. The primary outcome measure was the change in oxygen efficiency during exercise at high altitude between participants allocated to receive nitrate supplementation and those receiving a placebo. A number of secondary measures were recorded, including exercise capacity, peripheral and microcirculatory blood flow and tissue oxygenation. Results from this study will further elucidate the role of NO in adaption to hypoxaemia and guide clinical trials in critically ill patients. Improved understanding of hypoxaemia in critical illness may provide new therapeutic avenues for interventions that will improve survival in critically ill patients. © 2013. Published by Elsevier Inc. All rights reserved.

[Treatment-resistant anxiety disorders: A literature review of drug therapy strategies].

PubMed

Ammar, G; Naja, W J; Pelissolo, A

2015-06-01

Anxiety disorders are widespread psychiatric conditions with significant social and professional disability, poor quality of life, an increased risk of suicide, and frequent attendance of medical services. Serotonin reuptake inhibitors (SRI) and serotonin and norepinephrine reuptake inhibitors (SNRI) have demonstrated a rather robust efficacy for the treatment of most of anxiety disorders. Nevertheless a substantial number of patients are resistant or still suffer from residual symptoms despite this first line treatment. The objective of our paper is to review relevant studies for the pharmacologic management of anxiety disorders resistant to the first line treatment. For this purpose, we conducted a pubmed/medline search for double-blind placebo-controlled trials of treatment-resistant anxiety disorders. An adequate trial for a SRI in the treatment of obsessive-compulsive disorder (OCD) should continue for at least 12 weeks. Special considerations of the comorbidities and symptom profile could help in the choice of an appropriate pharmacotherapy. Several trials have highlighted the efficacy of antipsychotics as an add-on to SRI in treatment-resistant OCD such as haloperidol more so when comorbid with a tic disorder, or risperidone that can reduce OCD as well as depressive symptoms. Aripiprazole has been shown efficacious in two placebo-controlled double-blind trials, while the efficacy of quetiapine and olanzapine remains controversial. Other trials showed some efficacy of anticonvulsants (lamotrigine, topiramate), pindolol, memantin and N-acetylcystein as an adjunctive treatment to SRI for resistant OCD. Few trials have investigated selective serotonin reuptake inhibitors (SSRI) or SNRI resistant generalized anxiety disorder showing a failure of adjunctive therapy with olanzapine, quetiapine, ziprasidone and risperidone. These studies were underpowered and very limited in number. Adjunctive risperidone for resistant post-traumatic stress disorder (PTSD) showed benefit in some but not all trials. Olanzapine was beneficial for the reduction of the CAPS score in addition to the improvement of sleep disturbances. Furthermore, prazosin was efficacious by reducing PTSD symptoms, sleep disturbances, nightmares, and psychological distress. One double-blind placebo-controlled study was conducted to investigate treatment-resistant social phobia showing no benefit of pindolol add-on paroxetine. Our results demonstrate that the pharmacological management of treatment-resistant anxiety disorders is not sufficiently investigated in double-blind placebo-controlled trials, despite a growing evidence in favor of antipsychotics and some other pharmacological agents in resistant OCD and, to a lesser extent, PTSD. Hence, there is a crucial need for larger double-blind placebo-controlled trials for resistant anxiety disorders. Finally, being out of the scope of our review, we omitted studies of non-pharmacologic therapies. Copyright © 2014. Published by Elsevier Masson SAS.

Patient-reported health-related quality of life, work productivity, and activity impairment during treatment with ALO-02 (extended-release oxycodone and sequestered naltrexone) for moderate-to-severe chronic low back pain.

PubMed

Weil, Arnold J; Masters, Elizabeth T; Barsdorf, Alexandra I; Bass, Almasa; Pixton, Glenn; Wilson, Jacquelyn G; Wolfram, Gernot

2017-10-17

The efficacy of ALO-02, an abuse-deterrent formulation containing extended-release oxycodone and sequestered naltrexone, in the treatment of chronic low back pain (CLBP) was studied in a 12-week randomized controlled trial. Primary efficacy endpoint results have been published previously (Rauck et al., 2015). The current paper focuses on patient-reported outcomes for health-related quality of life (HRQL), work productivity, and activity impairment that were assessed during this study. This was a double-blind, placebo-controlled, randomized withdrawal study in patients with moderate-to-severe CLBP. After a screening period (≤2 weeks), patients entered an open-label titration period (4-6 weeks). Treatment responders were then randomized to a double-blind placebo-controlled treatment period (12 weeks). HRQL was assessed using changes in the Short Form-36 v2 Health Survey (SF-36v2) and the EuroQol-5 Dimensions Health Questionnaire 3-Level version (EQ-5D-3L). Work productivity and regular activities were evaluated using the Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP). A total of 410 patients received ALO-02 during the open-label titration period, of which 280 (intent-to-treat (ITT) population) were treated during the double-blind placebo-controlled treatment period (placebo, n = 134; ALO-02, n = 146). Significant improvement was observed for all SF-36v2 subscales and component scores (p < 0.005) and the EQ-5D-3L summary index and visual analog scale (p < 0.0001) during the titration period. Improvement was also significant (p < 0.0001) for all WPAI:SHP outcomes except 'work time missed due to CLBP' for the titration period. Significant differences favoring ALO-02 compared with placebo were only observed for the SF-36v2 Bodily Pain subscale (p ≤ 0.0232; ITT population) during the double-blind treatment period and the overall study period (screening to the end of the double-blind treatment period). The percentage change in activity impairment due to low back pain subscale of the WPAI:SHP significantly favored ALO-02 compared with placebo for the ITT population when considering the overall study period (p = 0.0040). HRQL, work productivity, and activity impairment may be improved with ALO-02 treatment. ClinicalTrials.gov NCT01571362 , registered April 3, 2012.

Effects of amphetamine and/or L-dopa and physiotherapy after stroke - a blinded randomized study.

PubMed

Sonde, L; Lökk, J

2007-01-01

Major therapeutic advances in the rehabilitation of subacute stroke are lacking. A promising approach is treatment with facilitating drugs like amphetamine or levodopa in combination with physiotherapy. In a randomized, double-blind, placebo-controlled clinical trail, the effect of 10 sessions with either 20 mg of D-amphetamine, 100 mg of L-dopa or 10 mg of D-amphetamine + 50 mg of L-dopa combined with physiotherapy during a 2-week period was investigated in 25 patients admitted to a stroke rehabilitation unit. Motor function (Fugl-Meyer score) and activities of daily living (Barthel's index) were assessed. All patients improved significantly over the intervention period. Drug-treated patients did not show any additional increase in motor function or ADL. It is feasible and safe to perform larger clinical trials with this type of four-arm design. However, the lack of significant effects could be because of type, dosage, and time of drugs as well as the physical intervention strategy.

Rationale and design of the 'F.I.R.E.' study. A multicenter, double-blind, randomized, placebo-controlled study to measure the effect of FX06 (a fibrin-derived peptide Bbeta(15-42)) on ischemia-reperfusion injury in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention.

PubMed

Atar, Dan; Huber, Kurt; Rupprecht, Hans-Jürgen; Kopecky, Stephen L; Schwitter, Jürg; Theek, Carmen; Brandl, Katherine; Henning, Rainer; Geudelin, Bernard

2007-01-01

Immediate reopening of acutely occluded coronary arteries via primary percutaneous coronary intervention (PCI) is the treatment of choice to salvage the ischemic myocardium in the setting of ST-segment elevation myocardial infarction (STEMI). However, the sudden re-initiation of blood flow achieved with PCI can lead to a local acute inflammatory response with further endothelial and myocardial damage. This phenomenon, described as 'reperfusion injury', has been recognized for several decades, yet no pharmacologic intervention has so far succeeded in reducing myocardial damage linked to reperfusion. FX06 is a naturally occurring peptide derived from the neo-N-terminus of fibrin (Bbeta(15-42)). It prevents leukocyte migration through the gap junctions of endothelial cells. Experimental studies have shown that FX06 inhibits the binding of the proinflammatory fibrin E1 fragment to VE-cadherin expressed in the adherence junction. It represents a novel approach to reducing local and systemic inflammation, including myocardial reperfusion injury, in the adherens junction. The present multicenter, double-blind, randomized, placebo-controlled study is designed to test the hypothesis that FX06 injection during and immediately after primary PCI can reduce infarct size in patients with STEMI. The primary outcome measure of efficacy in this study is the degree of myocardial salvage calculated as the difference between the perfusion defect before and after PCI, determined by myocardial perfusion scintigraphy during rest. Further, infarct size at the end of the index hospitalization, as well as at 4 months, will be measured by cardiac magnetic resonance imaging. The present position paper describes the rationale, design and the methods utilized in this trial. 2007 S. Karger AG, Basel

Investigator-reported efficacy of azelaic acid foam 15% in patients with papulopustular rosacea: secondary efficacy outcomes from a randomized, controlled, double-blind, phase 3 trial.

PubMed

Solomon, James A; Tyring, Stephen; Staedtler, Gerald; Sand, Meike; Nkulikiyinka, Richard; Shakery, Kaweh

2016-09-01

Papulopustular rosacea (PPR) is characterized by centrofacial papules and pustules commonly associated with erythema. To compare investigator-reported efficacy outcomes for azelaic acid (AzA) foam 15% versus vehicle foam in PPR, a randomized, vehicle-controlled, double-blind phase 3 clinical trial was conducted at 48 US sites. Participants received AzA foam or vehicle foam for 12 weeks. Secondary efficacy outcomes included change in inflammatory lesion count (ILC), therapeutic response rate according to investigator global assessment (IGA), and change in erythema rating. This study was comprised of 961 participants with PPR. The results support the therapeutic superiority of AzA foam over vehicle foam.

A comparative double blind study of amoxycillin/clavulanate vs placebo in the prevention of infection after animal bites.

PubMed Central

Brakenbury, P H; Muwanga, C

1989-01-01

The value of prophylactic antibiotics in the treatment of animal bites is uncertain. A prospective double blind stratified trial was performed comparing a broad spectrum antibiotic amoxycillin/clavulanate with placebo in full thickness animal bite wounds in a series of 185 consecutive patients. In wounds less than 9 h old, no significant benefit was found with the antibiotic. In older wounds, presenting 9-24 h after injury, the infection rate was reduced significantly (P = 0.023), although the numbers were small. We recommend the use of such an antibiotic on wounds 9-24 h old and query its use in more recent injuries, unless tendons or joints are likely to be involved. PMID:2692580

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

PubMed Central

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

2002-01-01

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

Design and Methodology of the Trial to Assess Chelation Therapy (TACT)

PubMed Central

Lamas, Gervasio A.; Goertz, Christine; Boineau, Robin; Mark, Daniel B.; Rozema, Theodore; Nahin, Richard L.; Drisko, Jeanne A.; Lee, Kerry L.

2011-01-01

The Trial to Assess Chelation Therapy (TACT) is an NIH-sponsored, randomized, double blind, placebo-controlled, 2×2 factorial clinical trial testing the benefits and risks of 40 infusions of a multi-component Na2EDTA-chelation solution compared with placebo, and of an oral, high-dose multivitamin and mineral supplement. TACT has randomized and will follow 1708 patients for an average of approximately 4 years. The primary endpoint is a composite of all cause mortality, myocardial infarction, stroke, coronary revascularization, and hospitalization for angina. A 900 patient substudy will examine quality of life outcomes. The trial is designed to have >85% power to detect a 25% relative reduction in the primary endpoint for each treatment factor. Enrollment began in September 2003 and completed in October 2010. PMID:22172430

Herlyn-Werner-Wunderlich syndrome (uterus didelphys, blind hemivagina and ipsilateral renal agenesis) - a case report

PubMed Central

Arıkan, İlker İnan; Harma, Müge; Harma, Mehmet İbrahim; Bayar, Ülkü; Barut, Aykut

2010-01-01

Uterovaginal duplication with obstructed hemivagina and ipsilateral renal agenesis is referred to as the Herlyn-Werner-Wunderlich (HWW) syndrome. A 17 year old woman presented with right pelvic pain and dysmenorrhea, present since menarche at 13 and worsening over the past year. Ultrasound examination revealed a right pelvic mass (5×5 cm), double endometrial echoes, and hematocolpos. A right pelvic mass, agenesis of the right kidney, double uterus, and blind hemivagina with hematocolpos were detected by magnetic resonance imaging and intravenous pyelography. A right tubo-ovarian abscess with dense adhesions and a double uterus were observed on diagnostic laparoscopy. Adhesiolysis was carried out and purulent material irrigated. After a course of antibiotics, a vaginal septum resection was performed and the pyocolpos drained. She remained symptom free after four months of follow-up. Prompt and accurate diagnosis and treatment of this syndrome can significantly improve the lives of sufferers and prevent future complications. PMID:24591910

Visual Impairment and Blindness in Adults in the United States: Demographic and Geographic Variations from 2015 to 2050

PubMed Central

Varma, Rohit; Vajaranant, Thasarat S.; Burkemper, Bruce; Wu, Shuang; Torres, Mina; Hsu, Chunyi; Choudhury, Farzana; McKean-Cowdin, Roberta

2016-01-01

Importance This paper describes the current and projected prevalence of visual impairment (VI) (visual acuity worse than 20/40, but better than 20/200) and blindness (visual acuity 20/200 or worse) in the United States. Objective To determine the demographic and geographic variations in VI and blindness in adults in the US population in 2015 and to estimate the projected prevalence through 2050 Design Descriptive Setting Population-based cross-sectional Participants Pooled data from adults, 40 years and older, from six major population-based studies on VI and blindness in the US. Prevalence of VI and blindness were reported by age, sex, race/ethnicity, and per capita prevalence by state, using the US census projections (2015 – 2050). Main Outcome and Measures Prevalence of VI and blindness Results In 2015, 1.02 million people were blind, and approximately 3.22 million people in the US had VI (best-corrected VA in the better-seeing eye), while up to 8.2 million people had VI due to uncorrected refractive error. By 2050, the number of these conditions are projected to double to approximately 2.01 million people with blindness, 6.95 million people with VI, and 16.4 million with VI due to uncorrected refractive error. The highest numbers of these conditions are predicted among non-Hispanic whites, women, and older adults, however African Americans are projected to experience the highest prevalence of blindness. By 2050, the highest prevalence of VI among minorities will shift from African Americans to Hispanics. From 2015-2050, the states projected to have the highest per-capita prevalence of VI are Florida and Hawaii and highest projected per-capita prevalence of blindness are Mississippi, Louisiana, and Florida. Conclusion & Relevance These data suggest that vision screening for refractive error and early eye disease may reduce or prevent a high proportion of individuals from experiencing unnecessary vision loss and blindness, decrease associated costs to the US economy for medical services and lost productivity, and contribute to better quality of life. Targeted education and screening programs for non-Hispanic white women and minorities should become increasingly important due to the projected growth of these populations and their relative contribution to the overall numbers of these conditions. PMID:27197072

Tranexamic acid therapy in ulcerative colitis

PubMed Central

Hollanders, D.; Thomson, Jean M.; Schofield, Phillip F.

1982-01-01

The antifibrinolytic drug tranexamic acid was assessed in controlling bleeding in 12 patients with left-sided proctocolitis. The study was designed as a double-blind cross-over trial employing a dose of 4·5 g of tranexamic acid/day together with identical placebo. A statistically significant reduction in rectal bleeding was achieved in 50% of cases with a minimum of side effects. Sigmoidoscopic grading of rectal mucosal appearances was improved. Frequency of diarrhoea and stool consistency were not altered. Tranexamic acid may have a part to play in the management of selected patients with ulcerative colitis in whom bleeding is difficult to control with orthodox treatment. PMID:6980404

The Current Indication for Pacemaker in Patients with Cardioinhibitory Vasovagal Syncope

PubMed Central

da Silva, Rose Mary Ferreira Lisboa

2016-01-01

The most frequent cause of syncope is vasovagal reflex. It is associated with worse quality of life, depression, fatigue and physical injury. Recurrence of vasovagal syncope is an aggravating, reaching the rate of 69%. Initial step and pharmacological treatment may not work, especially in patients with recurrent syncope without prodrome. These patients can present cardioinhibitory response with asystole. Studies were designed to analyses the effectiveness of pacemaker for prevention of syncope. In this review, nonrandomized clinical trials, open-label randomized, double-blind randomized, placebo-controlled, and studies based on tilt test or Implantable Loop Recorder findings will be discussed. PMID:27651841

Music therapy as a non-pharmacological treatment for epilepsy.

PubMed

Liao, Huan; Jiang, Guohui; Wang, Xuefeng

2015-01-01

Epilepsy is one of the most common neurological diseases. Currently, the primary methods of treatment include pharmacological and surgical treatment. However, approximately one-third of patients exhibit refractory epilepsy. Therefore, a novel approach to epilepsy treatment is necessary. Several studies have confirmed that music therapy can be effective at reducing seizures and epileptiform discharges, thus providing a new option for clinicians in the treatment of epilepsy. Although the underlying mechanism of music therapy is unknown, it may be related to resonance, mirror neurons, dopamine pathways and parasympathetic activation. Large sample, multicenter, randomized double-blind and more effectively designed studies are needed for future music therapy studies.

Quantitative research.

PubMed

Watson, Roger

2015-04-01

This article describes the basic tenets of quantitative research. The concepts of dependent and independent variables are addressed and the concept of measurement and its associated issues, such as error, reliability and validity, are explored. Experiments and surveys – the principal research designs in quantitative research – are described and key features explained. The importance of the double-blind randomised controlled trial is emphasised, alongside the importance of longitudinal surveys, as opposed to cross-sectional surveys. Essential features of data storage are covered, with an emphasis on safe, anonymous storage. Finally, the article explores the analysis of quantitative data, considering what may be analysed and the main uses of statistics in analysis.

A Double-Blind, Placebo-Controlled Safety and Efficacy Study of NA-831

ClinicalTrials.gov

2018-05-25

Mild Cognitive Impairment; Alzheimer Disease; Alzheimer Dementia; Dementia, Vascular; Dementia With Lewy Bodies; Cognitive Impairment; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Cognitive Disorder

Unlinkable Serial Transactions

DTIC Science & Technology

1997-01-01

the result of blinding X, for use with the appropriate signature key. 3.3 Registration Message 1 C ! V : fPayment ;Kaudit;CreditAuth;KCV gV ; [Request...anonymous e-cash as presented by Chaum et al. [6], is characterized by several requirements [13]: independent of physical requirements, unforgeable and...penalties can then be applied that make double spending not cost e ective. Chaum’s notion of blinding [5] is a fundamental technique used in

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

PubMed

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

2015-11-01

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

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

PubMed

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

1994-10-01

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

Aggregated data from two double-blind base station provocation studies comparing individuals with idiopathic environmental intolerance with attribution to electromagnetic fields and controls.

PubMed

Eltiti, Stacy; Wallace, Denise; Russo, Riccardo; Fox, Elaine

2015-02-01

Data from two previous studies were aggregated to provide a statistically powerful test of whether exposure to electromagnetic fields (EMFs) produced by telecommunication base stations negatively affects well-being in individuals who report idiopathic environmental illness with attribution to electromagnetic fields (IEI-EMF) and control participants. A total of 102 IEI-EMF and 237 controls participated in open provocation trials and 88 IEI-EMF and 231 controls went on to complete double-blind trials in which they were exposed to EMFs from a base station emitting either a Global System for Mobile Communication and Universal Mobile Telecommunications System or a Terrestrial Trunked Radio Telecommunications System signal. Both experiments included a comparison sham condition. Visual analog and symptom scales measured subjective well-being. Results showed that IEI-EMF participants reported lower levels of well-being during real compared to sham exposure during open provocation, but not during double-blind trials. Additionally, participants reported lower levels of well-being during high compared to low load trials and this did not interact with radiofrequency-EMF exposure. These findings are consistent with a growing body of literature indicating there is no causal relationship between short-term exposure to EMFs and subjective well-being in members of the public whether or not they report perceived sensitivity to EMFs. © 2015 Wiley Periodicals, Inc.

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

PubMed

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

2013-12-01

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

Augmentation in the treatment of restless legs syndrome with transdermal rotigotine.

PubMed

Beneš, Heike; García-Borreguero, Diego; Ferini-Strambi, Luigi; Schollmayer, Erwin; Fichtner, Andreas; Kohnen, Ralf

2012-06-01

To assess the risk of augmentation under treatment with the transdermally delivered dopamine agonist rotigotine for restless legs syndrome (RLS). Experts in RLS augmentation retrospectively reviewed data from two double-blind, placebo-controlled 6-month trials (745 rotigotine and 214 placebo subjects, NCT00136045 and NCT00135993) and from two open-label 1-year trials (620 rotigotine subjects, NCT00498108 and NCT00263068). All study visits were systematically evaluated applying the Max Planck Institute (MPI) criteria for the diagnosis of both augmentation and clinically relevant augmentation. MPI criteria for augmentation were met on at least one visit by 8.2% of all subjects in the double-blind trials with 12 subjects meeting the criteria for clinically relevant augmentation: 11 under rotigotine (1.5%) and one under placebo treatment. In the open-label trials, 9.7% of all subjects met the MPI criteria for augmentation and 2.9% met the criteria for clinically relevant augmentation. None of the patients treated with rotigotine for up to 1.5 years (double-blind plus open-label trial) discontinued prematurely owing to augmentation. Neither could dose-dependency or a time pattern for clinically relevant augmentation episodes be detected. Our analyses suggest that the risk for clinically relevant augmentation for the duration of up to 18 months of rotigotine treatment is low. Copyright © 2012 Elsevier B.V. All rights reserved.

Narcolepsy: current treatment options and future approaches

PubMed Central

Billiard, Michel

2008-01-01

The management of narcolepsy is presently at a turning point. Three main avenues are considered in this review: 1) Two tendencies characterize the conventional treatment of narcolepsy. Modafinil has replaced methylphenidate and amphetamine as the first-line treatment of excessive daytime sleepiness (EDS) and sleep attacks, based on randomized, double blind, placebo-controlled clinical trials of modafinil, but on no direct comparison of modafinil versus traditional stimulants. For cataplexy, sleep paralysis, and hypnagogic hallucinations, new antidepressants tend to replace tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) in spite of a lack of randomized, double blind, placebo-controlled clinical trials of these compounds; 2) The conventional treatment of narcolepsy is now challenged by sodium oxybate, the sodium salt of gammahydroxybutyrate, based on a series of randomized, double-blind, placebo-controlled clinical trials and a long-term open label study. This treatment has a fairly good efficacy and is active on all symptoms of narcolepsy. Careful titration up to an adequate level is essential both to obtain positive results and avoid adverse effects; 3) A series of new treatments are currently being tested, either in animal models or in humans, They include novel stimulant and anticataplectic drugs, endocrine therapy, and, more attractively, totally new approaches based on the present state of knowledge of the pathophysiology of narcolepsy with cataplexy, hypocretine-based therapies, and immunotherapy. PMID:18830438

Triple-server blind quantum computation using entanglement swapping

NASA Astrophysics Data System (ADS)

Li, Qin; Chan, Wai Hong; Wu, Chunhui; Wen, Zhonghua

2014-04-01

Blind quantum computation allows a client who does not have enough quantum resources or technologies to achieve quantum computation on a remote quantum server such that the client's input, output, and algorithm remain unknown to the server. Up to now, single- and double-server blind quantum computation have been considered. In this work, we propose a triple-server blind computation protocol where the client can delegate quantum computation to three quantum servers by the use of entanglement swapping. Furthermore, the three quantum servers can communicate with each other and the client is almost classical since one does not require any quantum computational power, quantum memory, and the ability to prepare any quantum states and only needs to be capable of getting access to quantum channels.

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.

The impact of helminths on the response to immunization and on the incidence of infection and disease in childhood in Uganda: design of a randomized, double-blind, placebo-controlled, factorial trial of deworming interventions delivered in pregnancy and early childhood [ISRCTN32849447

PubMed Central

Kizza, Moses; Quigley, Maria A; Ndibazza, Juliet; Nampijja, Margaret; Muhangi, Lawrence; Morison, Linda; Namujju, Proscovia B; Muwanga, Moses; Kabatereine, Narcis; Whitworth, James AG

2007-01-01

Background Helminths have profound effects on the immune response, allowing long-term survival of parasites with minimal damage to the host. Some of these effects "spill-over", altering responses to non-helminth antigens or allergens. It is suggested that this may lead to impaired responses to immunizations and infections, while conferring benefits against inflammatory responses in allergic and autoimmune disease. These effects might develop in utero, through exposure to maternal helminth infections, or through direct exposure in later life. Purpose To determine the effects of helminths and their treatment in pregnancy and in young children on immunological and disease outcomes in childhood. Methods The trial has three randomized, double-blind, placebo-controlled interventions at two times, in two people: a pregnant woman and her child. Pregnant women are randomized to albendazole or placebo and praziquantel or placebo. At age 15 months their children are randomized to three-monthly albendazole or placebo, to continue to age five years. The proposed designation for this sequence of interventions is a 2 X 2(x2) factorial design. Children are immunized with BCG and against polio, Diphtheria, tetanus, Pertussis, Haemophilus, hepatitis B and measles. Primary immunological outcomes are responses to BCG antigens and tetanus toxoid in whole blood cytokine assays and antibody assays at one, three and five years of age. Primary disease outcomes are incidence of malaria, pneumonia, diarrhoea, tuberculosis, measles, vertical HIV transmission, and atopic disease episodes, measured at clinic visits and twice-monthly home visits. Effects on anaemia, growth and intellectual development are also assessed. Conclusion This trial, with a novel design comprising related interventions in pregnant women and their offspring, is the first to examine effects of helminths and their treatment in pregnancy and early childhood on immunological, infectious disease and allergic disease outcomes. The results will enhance understanding of both detrimental and beneficial effects of helminth infection and inform policy. Clinical Trials 2007; 4: 42–57. http://ctj.sagepub.com PMID:17327245

A double-blind placebo controlled trial of medroxyprogesterone acetate and cyproterone acetate with seven pedophiles.

PubMed

Cooper, A J; Sandhu, S; Losztyn, S; Cernovsky, Z

1992-12-01

Seven of ten pedophiles in hospital completed a double-blind, placebo-controlled two-dose comparison of medroxyprogesterone acetate and cyproterone acetate. Sequential measures during the 28 week study were: patient self-reports, nurses' observations, phallometry, hormone levels and side-effects. The drugs, which performed equivalently, reduced sexual thoughts and fantasies, the frequency of early morning erections on awakening, the frequency and pleasure of masturbation, and level of sexual frustration. Penile responses were also reduced but to a lesser degree and were more variable. Serum testosterone FSH and LH all declined during drug administration, but by the end of the final placebo phase had essentially returned to (or exceeded) pre-drug values. Our experience suggests that only a minority of pedophiles are likely to accept libido-reducing drugs.

Functional census of mutation sequence spaces: The example of p53 cancer rescue mutants

PubMed Central

Danziger, Samuel A.; Swamidass, S. Joshua; Zeng, Jue; Dearth, Lawrence R.; Lu, Qiang; Chen, Jonathan H.; Cheng, Jainlin; Hoang, Vinh P.; Saigo, Hiroto; Luo, Ray; Baldi, Pierre; Brachmann, Rainer K.; Lathrop, Richard H.

2009-01-01

Many biomedical problems relate to mutant functional properties across a sequence space of interest, e.g., flu, cancer, and HIV. Detailed knowledge of mutant properties and function improves medical treatment and prevention. A functional census of p53 cancer rescue mutants would aid the search for cancer treatments from p53 rescue. We devised a general methodology for conducting a functional census of a mutation sequence space, and conducted a double-blind predictive test on the functional rescue property of 71 novel putative p53 cancer rescue mutants iteratively predicted in sets of 3. Double-blind predictive accuracy (15-point moving window) rose from 47% to 86% over the trial (r = 0.74). Code and data are available upon request1. PMID:17048398

Sildenafil citrate for the management of antidepressant-associated erectile dysfunction.

PubMed

Nurnberg, H George; Hensley, Paula L

2003-01-01

Sexual side effects of serotonin reuptake inhibitors, such as antidepressant-associated erectile dysfunction, are common and negatively impact treatment compliance. Current management approaches have important limitations, and most lack clear and meaningful efficacy in double-blind, placebo-controlled trials. A MEDLINE search (English language, 1966-2003) was performed using the terms antidepressive agents, erectile dysfunction, and sildenafil. Emphasis was placed on studies that used specific sexual function measurements and were placebo controlled. Sildenafil citrate, a selective and competitive inhibitor of phosphodiesterase type 5, enhances the cyclic guanosine monophosphate-mediated relaxation of cavernosal smooth muscles in response to sexual stimulation, permitting vascular engorgement and penile erection. The efficacy and tolerability of sildenafil in the treatment of antidepressant-associated erectile dysfunction have been confirmed in double-blind, placebo-controlled trials.

Lactobacillus plantarum 299v for the treatment of recurrent Clostridium difficile-associated diarrhoea: a double-blind, placebo-controlled trial.

PubMed

Wullt, Marlene; Hagslätt, Marie-Louise Johansson; Odenholt, Inga

2003-01-01

A double-blind, placebo-controlled trial was performed to analyse the ability of Lactobacillus plantarum 299v to prevent further recurrent episodes of Clostridium difficile-associated diarrhoea (RCDAD). Recurrence of clinical symptoms (main outcome) was seen in 4 of 11 patients who received metronidazole in combination with L. plantarum 299v and in 6 of 9 treated with metronidazole in combination with placebo. The lactobacilli treatment had no side-effects. Although the small sample size does not allow any conclusion to be drawn concerning the efficacy of L. plantarum in patients with RCDAD, these results may contribute to the ongoing discussion about the benefits of probiotics in patients with RCDAD and encourage the performance of larger multicentre studies.

Treatment of acute cerebral infarction with a choline precursor in a multicenter double-blind placebo-controlled study.

PubMed

Tazaki, Y; Sakai, F; Otomo, E; Kutsuzawa, T; Kameyama, M; Omae, T; Fujishima, M; Sakuma, A

1988-02-01

A multicenter double-blind placebo-controlled study of cytidine 5'-diphosphocholine (CDP-choline) was conducted to evaluate possible clinical benefits of the drug in patients with acute, moderate to severe cerebral infarction. The patients included also suffered from moderate to mild disturbances of consciousness, and all were admitted within 14 days of the ictus. Patients were allocated randomly to treatment with either CDP-choline (1,000 mg/day i.v. once daily for 14 days) or with placebo (physiological saline). One hundred thirty-three patients received CDP-choline treatment, and 139 received placebo. The group treated with CDP-choline showed significant improvements in level of consciousness compared with the placebo-treated group, and CDP-choline was an entirely safe treatment.

Double-blind comparative trial of indoprofen and acetylsalicylic acid in osteoarthritis.

PubMed

Katona, G

1981-01-01

The effectiveness, safety and acceptability of indoprofen (IP) and acetylsalicylic acid (ASA) were assessed in patients with osteoarthritis, in a double-blind comparative trial. Each patient received IP 600 mg/day or ASA 2100 mg/day for a four-week period; after a one-week wash-out period, the same drug was given at a higher dosage (IP 800 or ASA 2800 mg/day) for another four weeks. Seventeen patients on indoprofen and 14 on SAS completed the trial. A significant improvement was obtained with indoprofen in the different parameters measuring pain, from the first treatment period; results were similar at the end of the second period. Results with ASA, at both dosages, appeared less impressive. Two patients on indoprofen and five on ASA complained of side effects.

Quetiapine versus aripiprazole in children and adolescents with psychosis - protocol for the randomised, blinded clinical Tolerability and Efficacy of Antipsychotics (TEA) trial

PubMed Central

2014-01-01

Background The evidence for choices between antipsychotics for children and adolescents with schizophrenia and other psychotic disorders is limited. The main objective of the Tolerability and Efficacy of Antipsychotics (TEA) trial is to compare the benefits and harms of quetiapine versus aripiprazole in children and adolescents with psychosis in order to inform rational, effective and safe treatment selections. Methods/Design The TEA trial is a Danish investigator-initiated, independently funded, multi-centre, randomised, blinded clinical trial. Based on sample size estimation, 112 patients aged 12-17 years with psychosis, antipsychotic-naïve or treated for a limited period are, 1:1 randomised to a 12- week, double-blind intervention with quetiapine versus aripiprazole. Effects on psychopathology, cognition, health-related quality of life, and adverse events are assessed 2, 4, and 12 weeks after randomisation. The primary outcome is change in the positive symptom score of the Positive and Negative Syndrome Scale. The recruitment period is 2010-2014. Discussion Antipsychotics are currently the only available pharmacologic treatments for psychotic disorders. However, information about head-to-head differences in efficacy and tolerability of antipsychotics are scarce in children and adolescents. The TEA trial aims at expanding the evidence base for the use of antipsychotics in early onset psychosis in order to inform more rational treatment decisions in this vulnerable population. Here, we account for the trial design, address methodological challenges, and discuss the estimation of sample size. Trial registration ClinicalTrials.gov: NCT01119014 PMID:25015535

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

PubMed

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

2017-02-01

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

Probiotics for standard triple Helicobacter pylori eradication: a randomized, double-blind, placebo-controlled trial.

PubMed

Hauser, Goran; Salkic, Nermin; Vukelic, Karina; JajacKnez, Alenka; Stimac, Davor

2015-05-01

The primary objective in the study is determination of efficacy of probiotic preparation as a supportive therapy in eradication of Helicobacter pylori.The study was multicenter, prospective, randomized, placebo controlled, and double-blind. The subjects first filled out a specially designed questionnaire to assess the severity of the 10 symptoms, which can be related to eradication therapy to be monitored during the trial. Each subject then received 28 capsules of probiotic preparation or matching placebo capsules, which they were supposed to take over the following 14 days, twice a day, at least 2 hours prior to or after the antibiotic therapy administration.A total of 804 patients were enrolled in the trial, of which 650 (80.85%) were included in the analysis. The results show a significantly larger share of cured subjects in the probiotic arm versus the placebo arm (87.38% vs 72.55%; P < 0.001). Additionally, presence and intensity of epigastric pain, bloating, flatulence, taste disturbance, loss of appetite, nausea, vomiting, heartburn, rash, and diarrhea were monitored over the study period. At 15 days postinclusion, probiotic treatment was found superior to placebo in 7 of 10 mentioned symptoms. Average intensity for symptoms potentially related to antibiotic therapy was significantly higher in the placebo group, 0.76 vs 0.55 (P < 0.001).Adding probiotics to the standard triple therapy for H pylori eradication significantly contributes to treatment efficacy and distinctly decreases the adverse effects of therapy and the symptoms of the underlying disease.

Effect of Bupropion Treatment on Brain Activation Induced by Cigarette-Related Cues in Smokers

PubMed Central

Culbertson, Christopher S.; Bramen, Jennifer; Cohen, Mark S.; London, Edythe D.; Olmstead, Richard E.; Gan, Joanna J.; Costello, Matthew R.; Shulenberger, Stephanie; Mandelkern, Mark A.; Brody, Arthur L.

2011-01-01

Context Nicotine-dependent smokers exhibit craving and brain activation in the prefrontal and limbic regions when presented with cigarette-related cues. Bupropion hydrochloride treatment reduces cue-induced craving in cigarette smokers; however, the mechanism by which bupropion exerts this effect has not yet been described. Objective To assess changes in regional brain activation in response to cigarette-related cues from before to after treatment with bupropion (vs placebo). Design Randomized, double-blind, before-after controlled trial. Setting Academic brain imaging center. Participants Thirty nicotine-dependent smokers (paid volunteers). Interventions Participants were randomly assigned to receive 8 weeks of treatment with either bupropion or a matching placebo pill (double-blind). Main Outcome Measures Subjective cigarette craving ratings and regional brain activations (blood oxygen level-dependent response) in response to viewing cue videos. Results Bupropion-treated participants reported less craving and exhibited reduced activation in the left ventral striatum, right medial orbitofrontal cortex, and bilateral anterior cingulate cortex from before to after treatment when actively resisting craving compared with placebo-treated participants. When resisting craving, reduction in self-reported craving correlated with reduced regional brain activation in the bilateral medial orbitofrontal and left anterior cingulate cortices in all participants. Conclusions Treatment with bupropion is associated with improved ability to resist cue-induced craving and a reduction in cue-induced activation of limbic and prefrontal brain regions, while a reduction in craving, regardless of treatment type, is associated with reduced activation in prefrontal brain regions. PMID:21199957

Effectiveness of Cranberry Capsules to Prevent Urinary Tract Infections in Vulnerable Older Persons: A Double-Blind Randomized Placebo-Controlled Trial in Long-Term Care Facilities

PubMed Central

Caljouw, Monique A A; van den Hout, Wilbert B; Putter, Hein; Achterberg, Wilco P; Cools, Herman J M; Gussekloo, Jacobijn

2014-01-01

Objectives To determine whether cranberry capsules prevent urinary tract infection (UTI) in long-term care facility (LTCF) residents. Design Double-blind randomized placebo-controlled multicenter trial. Setting Long-term care facilities (LTCFs). Participants LTCF residents (N = 928; 703 women, median age 84). Measurements Cranberry and placebo capsules were taken twice daily for 12 months. Participants were stratified according to UTI risk (risk factors included long-term catheterization, diabetes mellitus, ≥1 UTI in preceding year). Main outcomes were incidence of UTI according to a clinical definition and a strict definition. Results In participants with high UTI risk at baseline (n = 516), the incidence of clinically defined UTI was lower with cranberry capsules than with placebo (62.8 vs 84.8 per 100 person-years at risk, P = .04); the treatment effect was 0.74 (95% confidence interval (CI) = 0.57–0.97). For the strict definition, the treatment effect was 1.02 (95% CI = 0.68–1.55). No difference in UTI incidence between cranberry and placebo was found in participants with low UTI risk (n = 412). Conclusion In LTCF residents with high UTI risk at baseline, taking cranberry capsules twice daily reduces the incidence of clinically defined UTI, although it does not reduce the incidence of strictly defined UTI. No difference in incidence of UTI was found in residents with low UTI risk. PMID:25180378

Effect of omega-3 and ascorbic acid on inflammation markers in depressed shift workers in Shahid Tondgoyan Oil Refinery, Iran: a randomized double-blind placebo-controlled study

PubMed Central

Khajehnasiri, Farahnaz; Mortazavi, Seyed Bagher; Allameh, Abdolamir; Akhondzadeh, Shahin

2013-01-01

The present study aimed to assess the effect of supplementation of omega-3 and/or vitamin C on serum interleukin-6 and high sensitivity C-reactive protein concentration and depression scores among shift workers in Shahid Tondgoyan oil refinery. The study design was randomized, double-blind, placebo-controlled, parallel trial. Totally 136 shift workers with a depression score ≥10 in 21-item Beck Depression Rating Scale were randomly assigned to receive omega-3 (180 mg eicosapentaenoate acid and 120 mg docosahexaenoic acid) or/and vitamin C 250 mg or placebo twice daily (with the same taste and shape as omega-3 and vitamin C) for 60 days in four groups. Depression score, interleukin-6 and high sensitivity C-reactive protein were measured at baseline and after 60 days. This study showed that supplementation of omega-3 plus vitamin C is associated with a decrease in depression score (p<0.05). Supplementation of omega-3 without vitamin C, is associated with a reduction in depression score (p<0.0001) and high sensitivity C-reactive protein concentration (p<0.01). Therefore omega-3 supplementation showed a better effect on reducing depression score and high sensitivity C-reactive protein, but supplementation of vitamin C along with omega-3 did not have significant effect on change in C-reactive protein level compared to omega-3 alone. (Registration number: IRCT201202189056N1) PMID:23874068

Transcutaneous Electrical Nerve Stimulation in Children with Monosymptomatic Nocturnal Enuresis: A Randomized, Double-Blind, Placebo Controlled Study.

PubMed

Jørgensen, Cecilie Siggaard; Kamperis, Konstantinos; Borch, Luise; Borg, Britt; Rittig, Søren

2017-09-01

In a third of all children with monosymptomatic nocturnal enuresis their condition is refractory to first line treatments. Transcutaneous electrical nerve stimulation has been documented to be efficacious in children with daytime incontinence. We investigated the effect of transcutaneous electrical nerve stimulation in children with monosymptomatic nocturnal enuresis without nocturnal polyuria. Children with monosymptomatic nocturnal enuresis (3 or more wet nights per week) and no nocturnal polyuria were randomized to treatment with active or sham transcutaneous electrical nerve stimulation involving 1-hour sessions twice daily for 10 weeks in a double-blind design. Of the 52 children with monosymptomatic nocturnal enuresis included in the study 47 completed treatment (mean age 9.5 ± 2.1 years, 38 males). None of the children experienced a full response with complete remission of enuresis. Treatment with transcutaneous electrical nerve stimulation did not lead to significant changes in number of wet nights, nocturnal urine production on wet or dry nights, maximum voided volume with and without first morning voided volume, or voiding frequency when comparing parameters before and after treatment. The present study demonstrates no anti-enuretic effect of transcutaneous electrical nerve stimulation in children with monosymptomatic nocturnal enuresis without nocturnal polyuria. Nocturnal urine production and bladder capacity remained unchanged during and after treatment with transcutaneous electrical nerve stimulation. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

The benefit of lithium carbonate adjunct in refractory depression--fact or fiction?

PubMed

Kantor, D; McNevin, S; Leichner, P; Harper, D; Krenn, M

1986-06-01

Our group attempted to validate previous claims of rapid success with lithium carbonate adjunct therapy in antidepressant-resistant depression. Seven depressed patients volunteered for a study of placebo controlled, double-blind design. During their treatment on general hospital psychiatric wards, these patients received antidepressant medication for a period of at least 21 days. While continuing to receive antidepressant medication after the 21 day period, four of the patients then received lithium carbonate, and three received placebo. This combination pharmacological therapy continued for a 48 hour period. After this time, six of the seven patients showed no significant improvement. The remaining patient, who had received lithium carbonate, improved markedly over the 48 hour period. However, this patient relapsed within one week. A review of the two most extensive studies claiming significant results with the lithium carbonate adjunct therapy was performed. We feel that they, as presented, leave serious doubt as to the validity of their conclusions. We conclude that on the basis of our work up to this point in time and the analysis of previous reports claiming otherwise, no valid evidence exists for a consistent therapeutic effect of lithium carbonate adjunct in antidepressant-resistant depression. It was also found that methodologic contamination necessitated the exclusion of an additional six patients from the double-blind trial. We conclude that in order to objectively examine the rapidly expanding field of biological psychiatry, teaching of clinical staff in basic research procedure should be stressed as a part of routine ward orientation.

Efficacy and safety of topical diclofenac/menthol gel for ankle sprain: A randomized, double-blind, placebo- and active-controlled trial

PubMed Central

Collaku, Agron; Reed, Kenneth

2017-01-01

Purpose This study was performed to evaluate topical 1% diclofenac/3% menthol gel in treating ankle sprain. Design In this randomized, double-blind, placebo-controlled trial, adolescents and adults with acute ankle sprain (N = 385) applied 4 g of gel containing 1% diclofenac/3% menthol (n = 117), 1% diclofenac (n = 112), 3% menthol (n = 77), or placebo (n = 75) four times daily. The primary outcome was the area under the curve of pain intensity (PI) on movement [0 (no pain) to 10 (extreme pain)] from 24 to 72 hours post-application (AUC1–3 days). Secondary outcomes included pain relief (PR); PI; time to onset of PR, meaningful PR, cooling, and complete recovery; PI difference; sum of PI difference; total PR; reduction in ankle swelling; and the patient’s global assessment of response to treatment. Results There were no statistically significant differences in AUC1–3 between 1% diclofenac/3% menthol and placebo, diclofenac, or menthol gels and no meaningful advantages of 1% diclofenac/3% menthol for any secondary outcome. There was a higher incidence of skin and application-site events with 1% diclofenac/3% menthol than with placebo or 1% diclofenac. Conclusion No significant improvement was observed with topical 1% diclofenac/3% menthol gel compared with placebo, 1% diclofenac, or 3% menthol gel in treating pain from ankle sprain. ClinicalTrials.Gov Identifier: NCT02100670 PMID:28345425

Rationale and design of a randomized double-blind clinical trial in breast cancer: dextromethorphan in chemotherapy-induced peripheral neuropathy.

PubMed

Martin, Elodie; Morel, Véronique; Joly, Dominique; Villatte, Christine; Delage, Noémie; Dubray, Claude; Pereira, Bruno; Pickering, Gisèle

2015-03-01

Anti-cancer chemotherapy often induces peripheral neuropathy and consequent cognitive and quality of life impairment. Guidelines recommend antiepileptics or antidepressants but their efficacy is limited.Dextromethorphan, a N-methyl-D-aspartate receptor antagonist, has shown its efficacy in painful diabetic neuropathy and in post-operative pain but has not been studied in chemotherapy-induced peripheral neuropathy. This clinical trial evaluates the effect of dextromethorphan on pain, cognition and quality of life in patients who suffer from neuropathic pain induced by chemotherapy for breast cancer. It also assesses the impact of dextromethorphan genetic polymorphism on analgesia. This trial is a randomized, placebo-controlled, double-blind clinical study in two parallel groups (NCT02271893). It includes 40 breast cancer patients suffering from chemotherapy-induced peripheral neuropathy. They are randomly allocated to dextromethorphan (maximal dose 90 mg/day) or placebo for 4 weeks. The primary endpoint is pain intensity measured after 4 weeks of treatment on a (0-10) Numeric Pain Rating Scale. Secondary outcomes include assessment of neuropathic pain, cognitive function, anxiety/depression, sleep and quality of life. Data analysis is performed using mixed models and the tests are two-sided, with a type I error set at α=0.05. Considering the poor efficacy of available drugs in chemotherapy-induced neuropathic pain, dextromethorphan may be a valuable therapeutic option. Pharmacogenetics may provide predictive factors of dextromethorphan response in patients suffering from breast cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

A randomized controlled trial of levosimendan to reduce mortality in high-risk cardiac surgery patients (CHEETAH): Rationale and design.

PubMed

Zangrillo, Alberto; Alvaro, Gabriele; Pisano, Antonio; Guarracino, Fabio; Lobreglio, Rosetta; Bradic, Nikola; Lembo, Rosalba; Gianni, Stefano; Calabrò, Maria Grazia; Likhvantsev, Valery; Grigoryev, Evgeny; Buscaglia, Giuseppe; Pala, Giovanni; Auci, Elisabetta; Amantea, Bruno; Monaco, Fabrizio; De Vuono, Giovanni; Corcione, Antonio; Galdieri, Nicola; Cariello, Claudia; Bove, Tiziana; Fominskiy, Evgeny; Auriemma, Stefano; Baiocchi, Massimo; Bianchi, Alessandro; Frontini, Mario; Paternoster, Gianluca; Sangalli, Fabio; Wang, Chew-Yin; Zucchetti, Maria Chiara; Biondi-Zoccai, Giuseppe; Gemma, Marco; Lipinski, Michael J; Lomivorotov, Vladimir V; Landoni, Giovanni

2016-07-01

Patients undergoing cardiac surgery are at risk of perioperative low cardiac output syndrome due to postoperative myocardial dysfunction. Myocardial dysfunction in patients undergoing cardiac surgery is a potential indication for the use of levosimendan, a calcium sensitizer with 3 beneficial cardiovascular effects (inotropic, vasodilatory, and anti-inflammatory), which appears effective in improving clinically relevant outcomes. Double-blind, placebo-controlled, multicenter randomized trial. Tertiary care hospitals. Cardiac surgery patients (n = 1,000) with postoperative myocardial dysfunction (defined as patients with intraaortic balloon pump and/or high-dose standard inotropic support) will be randomized to receive a continuous infusion of either levosimendan (0.05-0.2 μg/[kg min]) or placebo for 24-48 hours. The primary end point will be 30-day mortality. Secondary end points will be mortality at 1 year, time on mechanical ventilation, acute kidney injury, decision to stop the study drug due to adverse events or to start open-label levosimendan, and length of intensive care unit and hospital stay. We will test the hypothesis that levosimendan reduces 30-day mortality in cardiac surgery patients with postoperative myocardial dysfunction. This trial is planned to determine whether levosimendan could improve survival in patients with postoperative low cardiac output syndrome. The results of this double-blind, placebo-controlled randomized trial may provide important insights into the management of low cardiac output in cardiac surgery. Copyright © 2016 Elsevier Inc. All rights reserved.

A Randomized, Double-blind, Vehicle-controlled Trial of Luliconazole Cream 1% in the Treatment of Interdigital Tinea Pedis

PubMed Central

Vlahovic, Tracey C.; Gold, Michael H.; Parish, Lawrence Charles; Korotzer, Andrew

2014-01-01

Objective: To evaluate the efficacy and safety of luliconazole cream 1% applied once daily for 14 days in patients with interdigital tinea pedis. Design: Multicenter, randomized, double-blind, parallel-group, vehicle-controlled study. Setting: Private dermatology clinics and clinical research centers in the United States and Central America. Participants: Three hundred twenty-two male and female patients ≥12 years of age diagnosed with interdigital tinea pedis. Measurements: Complete clearance (i.e., clinical and mycological cure), effective treatment, and fungal culture and susceptibility. Results: At study Day 42, complete clearance was obtained by a larger percentage (14.0% [15/107] vs. 2.8% [3/107]; p<0.001) of patients treated with luliconazole cream 1% compared with vehicle. Also at Day 42, more luliconazole-treated patients compared with vehicle-treated patients obtained effective treatment (32.7% vs. 15.0%), clinical cure (15.0% vs. 3.7%), and mycologic cure (56.1% vs. 27.1%). Erythema, scaling, and pruritus scores were lower for the luliconazole cream 1% group compared with vehicle on Day 14, Day 28, and Day 42. For all species and the same isolates, the MIC50/90 for luliconazole cream 1% was 6- to 12-fold lower than for other agents tested. No patients discontinued treatment because of a treatment-emergent adverse event. Conclusion: Luliconazole cream 1% was safe and well-tolerated and demonstrated significantly greater efficacy than vehicle cream in patients with interdigital tinea pedis. PMID:25371767

Pulpal response following photo-biomodulation with a 904-nm diode laser: a double-blind clinical study.

PubMed

Liang, Ryan; George, Roy; Walsh, Laurence J

2016-12-01

The aim of this study was to evaluate pulpal responses in healthy human teeth to photo-biomodulation therapy (PBMT) with 904-nm GaAs diode laser. The study followed a double-blind split mouth design, with a randomly selected maxillary first premolar acting as a sham-irradiated control tooth, and the contralateral tooth receiving active laser treatment. Two coded but otherwise identical laser probes (Irradia™, SpectraMedics Ltd., NC, USA) were used to deliver the sham (placebo) and laser radiation, with both the operator and patient unaware of each probe's identity. The selection of teeth for sham or laser irradiation was randomised for each treatment. Pulpal responses were assessed using electric pulp testing (EPT), 2 min prior to exposure, and immediately after laser irradiation (60 s, 30 mW average power, 25 Hz pulse frequency, 3.6 J/cm 2 ). Treatment effects were analysed using the Wilcoxon-signed rank test. A total of 30 participants provided written informed consent. Majority of the participants (66.7 %) demonstrated an analgesic effect following PBMT (elevated EPT scores); however, nine participants (30 %) reported the lower EPT scores than the control. Both the treatment effects (stimulation and analgesia) were significant compared to the placebo. In most individuals, PBMT of healthy teeth with a 904-nm GaAs diode laser can induce analgesia, as witnessed by elevated EPT scores. A converse effect can occur in a minority of subjects.

Saturated fat -a never ending story?

PubMed

Svendsen, Karianne; Arnesen, Erik; Retterstøl, Kjetil

2017-01-01

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

Development and validation of challenge materials for double-blind, placebo-controlled food challenges in children.

PubMed

Vlieg-Boerstra, Berber J; Bijleveld, Charles M A; van der Heide, Sicco; Beusekamp, Berta J; Wolt-Plompen, Saskia A A; Kukler, Jeanet; Brinkman, Joep; Duiverman, Eric J; Dubois, Anthony E J

2004-02-01

The use of double-blind, placebo-controlled food challenges (DBPCFCs) is considered the gold standard for the diagnosis of food allergy. Despite this, materials and methods used in DBPCFCs have not been standardized. The purpose of this study was to develop and validate recipes for use in DBPCFCs in children by using allergenic foods, preferably in their usual edible form. Recipes containing milk, soy, cooked egg, raw whole egg, peanut, hazelnut, and wheat were developed. For each food, placebo and active test food recipes were developed that met the requirements of acceptable taste, allowance of a challenge dose high enough to elicit reactions in an acceptable volume, optimal matrix ingredients, and good matching of sensory properties of placebo and active test food recipes. Validation was conducted on the basis of sensory tests for difference by using the triangle test and the paired comparison test. Recipes were first tested by volunteers from the hospital staff and subsequently by a professional panel of food tasters in a food laboratory designed for sensory testing. Recipes were considered to be validated if no statistically significant differences were found. Twenty-seven recipes were developed and found to be valid by the volunteer panel. Of these 27 recipes, 17 could be validated by the professional panel. Sensory testing with appropriate statistical analysis allows for objective validation of challenge materials. We recommend the use of professional tasters in the setting of a food laboratory for best results.

Effect of pulsed electromagnetic field therapy on experimental pain: A double-blind, randomized study in healthy young adults.

PubMed

Beaulieu, Karen; Beland, Patricia; Pinard, Marilee; Handfield, Guilène; Handfield, Nicole; Goffaux, Philippe; Corriveau, Hélène; Léonard, Guillaume

2016-01-01

Previous studies suggested that pulsed electromagnetic field (PEMF) therapy can decrease pain. To date, however, it remains difficult to determine whether the analgesic effect observed in patients are attributable to a direct effect of PEMF on pain or to an indirect effect of PEMF on inflammation and healing. In the present study, we used an experimental pain paradigm to evaluate the direct effect of PEMF on pain intensity, pain unpleasantness, and temporal summation of pain. Twenty-four healthy subjects (mean age 22 ± 2 years; 9 males) participated in the experiment. Both real and sham PEMF were administered to every participant using a randomized, double-blind, cross-over design. For each visit, PEMF was applied for 10 minutes on the right forearm using a portable device. Experimental pain was evoked before (baseline) and after PEMF with a 9 cm(2) Pelletier-type thermode, applied on the right forearm (120 s stimulation; temperature individually adjusted to produce moderate baseline pain). Pain intensity and unpleasantness were evaluated using a 0-100 numerical pain rating scale. Temporal summation was evaluated by comparing pain intensity ratings obtained at the end of tonic nociceptive stimulation (120 s) with pain intensity ratings obtained after 60 s of stimulation. When compared to baseline, there was no change in pain intensity and unpleasantness following the application of real or sham PEMF. PEMF did not affect temporal summation. The present observations suggest that PEMF does not directly influence heat pain perception in healthy individuals.

Efficacy of a Standardized Extract of Prunus mume in Liver Protection and Redox Homeostasis: A Randomized, Double-Blind, Placebo-Controlled Study.

PubMed

Beretta, Alberto; Accinni, Roberto; Dellanoce, Cinzia; Tonini, Annamaria; Cardot, Jean-Michel; Bussière, Anthony

2016-06-01

The antioxidant, anti-inflammatory and hepatoprotective effects of Prunus mume (PM) have previously been demonstrated. This double-blind, placebo-controlled study was designed to evaluate the influence of two doses of a food supplement, made of 150 mg of a standardized PM extract on liver transaminases, lipid profile, glycemia, neopterin and reduced and oxidized thiols in plasma and erythrocytes, during a 3-month treatment period, in healthy subjects with transaminases levels between 20 and 40 UI/L. Forty-five subjects (56.0 ± 11.6 years) were enrolled. The results showed a beneficial and statistically significant effect versus placebo of PM extract on liver function, with a decrease versus baseline in alanine aminotransferase (47%), aspartate aminotransferase (7%), gamma-glutamyl transpeptidase (15%) and glycemia (11%). The lipid profile modification was also positive with an increase versus baseline in HDL cholesterol (13%), and a decrease in LDL/HDL ratio (12%) and triglycerides (8%). The antioxidant action of PM translated into a decrease in oxidized glutathione, reduced/oxidized cysteine-glycine, oxidized cysteine (intracellular pro-oxidant) and neopterin (inflammation biomarker), was associated with an increase in reduced glutathione. These results are in favor of the use of a standardized extract of P. mume for the support of liver health and prevention of common metabolic and inflammation-based diseases. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Treatment of the organic brain syndrome in the elderly. A double-blind comparison on the effects of a neurotropic drug and placebo.

PubMed

Noël, G; Jeanmart, M; Reinhardt, B

1983-01-01

100 inpatients of both sexes, most of them older than 65 years and suffering from symptoms of the organic brain syndrome (OBS), primarily associated with aging were included in a 6-week double-blind study. Patients were randomly assigned to two treatment groups of 50 patients each and received either a neurotropic drug (3 X 200 mg EMD 21657) or placebo coated tablets of identical appearance. Patients were evaluated at the beginning of the study and after 6 weeks of treatment using a physician's symptom rating, the Nurses' Observation Scale for Inpatient Evaluation ( NOSIE ), EEG, and a psychometric test battery to assess level of mental and memory functioning ( Rey test, Benton visual retention test, block design test by Kohs ). At the final assessment global response and overall tolerance were rated by the physician. The therapeutic effects of EMD 21657 were shown to be statistically significant compared to placebo in global response (p less than or equal to 0.05), in the factor 'cognitive disturbances' (p less than or equal to 0.05 doctor's symptom rating) and in the negative factors of the NOSIE (p less than or equal to 0.05). In the other parameters of the scales, the EEG and the mental ability tests no statistically significant changes could be demonstrated in the two groups after 6 weeks of treatment. The drugs were well tolerated. EMD 21657 treatment was interrupted because of side effects (increased aggressiveness, rash) in 2 cases.

Double-Blind Randomized Placebo Controlled Trial Demonstrating Serum Cholesterol Lowering Efficacy of a Smoothie Drink with Added Plant Stanol Esters in an Indonesian Population

PubMed Central

Lestiani, Lanny; Ambarwati, Fransisca Diah

2018-01-01

Indonesians have a high intake of saturated fats, a key contributing dietary factor to elevated blood cholesterol concentrations. We investigated the cholesterol lowering efficacy of a smoothie drink with 2 grams of plant stanols as esters to lower serum total and LDL-cholesterol concentrations in hypercholesterolemic Indonesian adults. The double-blind randomized placebo controlled parallel design study involved 99 subjects. Fifty subjects received control drink and dietary advice, and 49 subjects received intervention drink (Nutrive Benecol®) and dietary advice. Baseline, midline (week 2), and endline (week 4) assessments were undertaken for clinical, anthropometric, and biochemical variables. Compared to control, the smoothie drink with plant stanols reduced serum LDL-cholesterol concentration by 7.6% (p < 0.05) and 9.0% (p < 0.05) in two and four weeks, respectively. Serum total cholesterol was reduced by 5.7% (p < 0.05 compared to control) in two weeks, and no further reduction was detected after four weeks (5.6%). Compared to baseline habitual diet, LDL-cholesterol was reduced by 9.3% (p < 0.05) and 9.8% (p < 0.05) in the plant stanol ester group in two and four weeks, respectively. We conclude that consumption of smoothie drink with added plant stanol esters effectively reduces serum total and LDL-cholesterol of hypercholesterolemic Indonesian subjects already in two weeks. Trial is registered as NCT02316808. PMID:29535869

Panax ginseng and Salvia miltiorrhiza supplementation during eccentric resistance training in middle-aged and older adults: A double-blind randomized control trial.

PubMed

Lin, Hsin-Fu; Chou, Chun-Chung; Chao, Hsiao-Han; Tanaka, Hirofumi

2016-12-01

Muscle damage induced by an acute bout of eccentric exercise results in transient arterial stiffening. In this study, we sought to determine the effects of progressive eccentric resistance exercise training on vascular functions, and whether herb supplementation would enhance training adaptation by ameliorating the arterial stiffening effects. By using a double-blinded randomized placebo-controlled design, older adults were randomly assigned to either the Panax ginseng and Salvia miltiorrhiza supplementation group (N=12) or the placebo group (N=11). After pre-training testing, all subjects underwent 12 weeks of unilateral eccentric-only exercise training on knee extensor. Maximal leg strength and muscle quality increased in both groups (P<0.05). Relative increases in muscle mass were significantly greater in the placebo group than in the herb supplement group. Eccentric exercise training did not elicit any significant changes in muscle damage, oxidative and inflammatory biomarkers. There were no significant changes in blood pressure or endothelium-dependent vasodilation. None of the measures of arterial stiffness changed significantly with eccentric resistance training in both groups. These results suggest that Chinese herb supplementation does not appear to modulate vascular, and inflammatory adaptations to eccentric exercise training in middle-aged and older adults. However, Chinese herb supplementation abolished the increase in muscle mass induced by eccentric resistance training. (Trial registration: ClinicalTrials.gov: NCT02007304. Registered Dec. 5, 2013). Copyright © 2016 Elsevier Ltd. All rights reserved.

An acute, double-blind, placebo-controlled crossover study of 320 mg and 640 mg doses of a special extract of Bacopa monnieri (CDRI 08) on sustained cognitive performance.

PubMed

Downey, Luke A; Kean, James; Nemeh, Fiona; Lau, Angela; Poll, Alex; Gregory, Rebecca; Murray, Margaret; Rourke, Johanna; Patak, Brigit; Pase, Matthew P; Zangara, Andrea; Lomas, Justine; Scholey, Andrew; Stough, Con

2013-09-01

Standardized extracts of the traditional Ayurvedic medicine Bacopa monnieri (BM) (Brahmi) have been recently shown to have cognitive enhancing effects in chronic administration studies. Pre-clinical work has also identified a number of acute anxiolytic, nootropic, and cardiovascular effects of BM. There has, however, been little research on the acute effects of BM on cognitive function. The current study aimed to assess the acute effects of a specific extract of BM (KeenMind®-CDRI 08) in a double-blind, placebo-controlled study in normal healthy participants who completed a cognitively demanding series of tests. Twenty-four healthy volunteers completed six repetitions of the Cognitive Demand Battery (CDB) after consuming a placebo, 320 mg BM or 640 mg of BM in a cross-over design and provided cardiovascular and mood assessments before and after treatment. Change from baseline scores indicated that the 320 mg dose of BM improved performance at the first, second, and fourth repetition post-dosing on the CDB, and the treatments had no effect upon cardiovascular activity or in attenuating task-induced ratings of stress and fatigue. It was concluded that assessment of an earlier pharmacological window and use of less memory-specific cognitive tests together with more temporally sensitive measures of brain activity may improve our understanding of the acute neurocognitive properties of BM. Copyright © 2012 John Wiley & Sons, Ltd.

Efficacy and safety of teneligliptin, a novel dipeptidyl peptidase-4 inhibitor, in Korean patients with type 2 diabetes mellitus: a 24-week multicentre, randomized, double-blind, placebo-controlled phase III trial.

PubMed

Hong, S; Park, C-Y; Han, K A; Chung, C H; Ku, B J; Jang, H C; Ahn, C W; Lee, M-K; Moon, M K; Son, H S; Lee, C B; Cho, Y-W; Park, S-W

2016-05-01

We assessed the 24-week efficacy and safety of teneligliptin, a novel dipeptidyl peptidase-4 inhibitor, in Korean patients with type 2 diabetes mellitus (T2DM) that was inadequately controlled with diet and exercise. The present study was designed as a multicentre, randomized, double-blind, placebo-controlled, parallel-group, phase III study. Patients (n = 142) were randomized 2 : 1 into two different treatment groups as follows: 99 received teneligliptin (20 mg) and 43 received placebo. The primary endpoint was change in glycated haemoglobin (HbA1c) level from baseline to week 24. Teneligliptin significantly reduced the HbA1c level from baseline compared with placebo after 24 weeks. At week 24, the differences between changes in HbA1c and fasting plasma glucose (FBG) in the teneligliptin and placebo groups were -0.94% [least-squares (LS) mean -1.22, -0.65] and -1.21 mmol/l (-1.72, -0.70), respectively (all p < 0.001). The incidence of hypoglycaemia and adverse events were not significantly different between the two groups. This phase III, randomized, placebo-controlled study provides evidence of the safety and efficacy of 24 weeks of treatment with teneligliptin as a monotherapy in Korean patients with T2DM. © 2016 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

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

PubMed Central

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

2017-01-01

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

Schizotypal Traits are Linked to Dopamine-Induced Striato-Cortical Decoupling: A Randomized Double-Blind Placebo-Controlled Study.

PubMed

Rössler, Julian; Unterassner, Lui; Wyss, Thomas; Haker, Helene; Brugger, Peter; Rössler, Wulf; Wotruba, Diana

2018-06-07

The dopamine hypothesis of schizophrenia implies that alterations in the dopamine system cause functional abnormalities in the brain that may converge to aberrant salience attribution and eventually lead to psychosis. Indeed, widespread brain disconnectivity across the psychotic spectrum has been revealed by resting-state functional magnetic resonance imaging (rs-fMRI). However, the dopaminergic involvement in intrinsic functional connectivity (iFC) and its putative relationship to the development of psychotic spectrum disorders remains partly unclear-in particular at the low-end of the psychosis continuum. Therefore, we investigated dopamine-induced changes in striatal iFC and their modulation by psychometrically assessed schizotypy. Our randomized, double-blind placebo-controlled study design included 54 healthy, right-handed male participants. Each participant was assessed with the Schizotypal Personality Questionnaire (SPQ) and underwent 10 minutes of rs-fMRI scanning. Participants then received either a placebo or 200 mg of L-DOPA, a dopamine precursor. We analyzed iFC of 6 striatal seeds that are known to evoke modulation of dopamine-related networks. The main effect of L-DOPA was a significant functional decoupling from the right ventral caudate to both occipital fusiform gyri. This dopamine-induced decoupling emerged primarily in participants with low SPQ scores, while participants with high positive SPQ scores showed decoupling indifferently of the L-DOPA challenge. Taken together, these findings demonstrate that schizotypal traits may be the result of dopamine-induced striato-occipital decoupling.

D-cycloserine does not improve but might slightly speed up the outcome of in-vivo exposure therapy in patients with severe agoraphobia and panic disorder in a randomized double blind clinical trial.

PubMed

Siegmund, Anja; Golfels, Fabian; Finck, Claudia; Halisch, Anna; Räth, Daniela; Plag, Jens; Ströhle, Andreas

2011-08-01

D-cycloserine (DCS)-augmented exposure therapy has proven efficacy in the treatment of acrophobia, social phobia, panic disorder and OCD. Here we studied whether DCS can also improve the effect of cognitive behavioral therapy (CBT) in patients with agoraphobia and panic disorder. To this end, 39 patients with the diagnoses of agoraphobia and panic disorder were treated with 11 sessions of CBT including three individual in-vivo exposure sessions (flooding), augmented with either 50mg of DCS (N=20) or placebo (N=19) in a randomized double blind design. Primary outcome was the total score of the panic and agoraphobia scale. Both groups profited considerably from therapy and DCS did not significantly improve this outcome (p=0.475; η(2)p = 0.01). However, there was a statistical trend (p=0.075; η(2)p = 0.17) in the more severely ill patients that DCS accelerated symptom reduction in the primary outcome at post-therapy. No serious adverse effects occurred during the trial. We conclude that in patients with agoraphobia and panic disorder, DCS seems to lack an additional benefit to efficient cbt, probably due to a floor effect. Nonetheless, the acceleration of symptom reduction in severely ill patients might represent a valuable treatment option deserving further investigation. Copyright © 2011 Elsevier Ltd. All rights reserved.

Lysine clonixinate in minor dental surgery: double-blind randomized parallel study versus paracetamol.

PubMed

Martí, M L; De los Santos, A R; Di Girolamo, G; Gil, M; Manero, E O; Fraga, C

1993-01-01

Lysine clonixinate (LC), an effective and well tolerated non-morphinic analgesic whose mechanism of action is basically due to the inhibition of cyclo-oxygenase, was assessed with a double-blind randomized dummy design versus paracetamol (P) on 200 patients suffering from pain after minor dental surgery. Patients received according to their needs 1 or 2 tablets of 125 mg lysine clonixinate or 500 mg paracetamol every 8 h during 48 h or until pain relief. Both groups, each composed of 100 patients, were comparable in terms of demographic conditions (t test), initial symptoms (chi-square test), characteristics of the extracted dental pieces, surgical complications and wound treatment (chi-square test). Pain intensity scores and daily average intake of tablets (3.4/day) documented in the patients' diary revealed no statistically significant differences between the two treatments (chi-square test). It was found that spontaneous pain measured using a visual analogue scale (VAS) decreased significantly in both treatment groups at the 24-h control examination. The following values were observed in the LC group: baseline 4.38 +/- 1.7; 24-h * 1.20 +/- 1.4; 48-h * 0.36 +/- 1.2. In the P group the values were: baseline 4.28 +/- 1.6; 24-h * 1.11 +/- 1.4; 48-h * 0.30 +/- 0.7 (*p < 0.05). Other variables like facial swelling and night pain, evaluated on a score from 0 to 4 and symptom presence or absence respectively, showed a similar response.(ABSTRACT TRUNCATED AT 250 WORDS)

Intravenous Nicotine Self-Administration in Smokers: Dose-Response Function and Sex Differences.

PubMed

Jensen, Kevin P; DeVito, Elise E; Valentine, Gerald; Gueorguieva, Ralitza; Sofuoglu, Mehmet

2016-07-01

Sex differences in the sensitivity to nicotine may influence vulnerability to tobacco dependence. The goal of this study was to investigate the dose-response function for the reinforcing and subjective effects of intravenous nicotine in male and female smokers. Tobacco-dependent subjects (12 male and 14 female) participated in four experimental sessions in which they received sample infusions of saline and nicotine (0.1, 0.2, 0.3, or 0.4 mg doses) in a randomized double-blind crossover design. During each session, subjects first received the sample infusions, and heart rate (HR), blood pressure, and subjective stimulatory, pleasurable and aversive responses were monitored. Immediately following the sample infusions, subjects self-administered either nicotine or saline in six double-blind forced-choice trials. A sex by dose interaction was observed in the nicotine choice paradigm. Nicotine self-administration rate was negatively correlated with nicotine dose in males (males displayed choice preference for low doses of nicotine over high doses of nicotine), but no significant relationship between dose and choice preference was evident in females. Relative to placebo, sample doses of nicotine increased heart rate and blood pressure, and induced stimulatory, pleasurable, and aversive subjective effects. Diastolic blood pressure increased dose dependently in males, but not in females. These findings, which demonstrate sex differences in nicotine self-administration for doses that are near to the reinforcement threshold, suggest that male and female smokers may respond differently to the changes in nicotine doses available for self-administration.

Diathermy vs. scalpel skin incisions in general surgery: double-blind, randomized, clinical trial.

PubMed

Shamim, Muhammad

2009-08-01

This prospective, double-blind, randomized, controlled trial was designed to compare the outcome of diathermy incisions versus scalpel incisions in general surgery. A total of 369 patients who underwent diathermy incision (group A: 185 patients) or scalpel incision (group B: 184 patients) were analyzed. Variables analyzed were: surgical wound classification, length and depth of incision, incision time, duration of operation, incisional blood loss, postoperative pain, duration of hospital stay, duration of healing, and postoperative complications. The inclusion criteria were all patients who underwent elective or emergency general surgery. The exclusion criteria were only cases with incomplete patients' data and patients who were lost to follow-up. This study was conducted at Fatima Hospital-Baqai Medical University and Shamsi Hospital (Karachi), from January 2006 to December 2007. Incision time was significantly longer for patients in group B (p = 0.001). Incisional blood loss also was more for patients in group B (p = 0.000). Pain perception was found to be markedly reduced during the first 48 h in group A (p = 0.000). Total period of hospital stay (p = 0.129) and time for complete wound healing (p = 0.683) were almost the same for both groups. Postoperative complication rate by wound classification did not differ markedly between the two groups (p = 0.002 vs. p = 0.000). Diathermy incision has significant advantages compared with the scalpel because of reduced incision time, less blood loss, & reduced early postoperative pain.

Are Luxury Brand Labels and “Green” Labels Costly Signals of Social Status? An Extended Replication

PubMed Central

2017-01-01

Costly signaling theory provides an explanation for why humans are willing to a pay a premium for conspicuous products such as luxury brand-labeled clothing or conspicuous environmentally friendly cars. According to the theory, the extra cost of such products is a signal of social status and wealth and leads to advantages in social interactions for the signaler. A previous study found positive evidence for the case of luxury brand labels. However, an issue of this study was that some of the experiments were not conducted in a perfectly double-blind manner. I resolved this by replicating variations of the original design in a double-blind procedure. Additionally, besides the luxury label condition, I introduced a “green” label condition. Thus, the hypothesis that signaling theory is able to explain pro-environmental behavior was tested for the first time in a natural field setting. Further, I conducted experiments in both average and below-average socioeconomic neighborhoods, where, according to signaling theory, the effects of luxury signals should be even stronger. In contrast to the original study, I did not find positive effects of the luxury brand label in any of the five experiments. Nor did I find evidence for a green-signaling effect. Moreover, in poor neighborhoods a negative tendency of the luxury label actually became evident. This suggests that a signaling theory explanation of costly labels must take into account the characteristics of the observers, e.g. their social status. PMID:28170399

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.

Influence of the antiseptic agents polyhexanide and octenidine on FL cells and on healing of experimental superficial aseptic wounds in piglets. A double-blind, randomised, stratified, controlled, parallel-group study.

PubMed

Kramer, A; Roth, B; Müller, G; Rudolph, P; Klöcker, N

2004-01-01

The main target of the combination of octenidine with phenoxyethanol (Octenisept) is the antisepsis of acute wounds, whereas polyhexanide combined with polyethylene glycol in Ringer solution (Lavasept) is the agent of choice for antisepsis of chronic wounds and burns. Because comparative data for both agents on the effects on wound healing are lacking, we investigated the influence of preparations based on polyhexanide and octenidine versus placebo (Ringer solution) in experimental superficial aseptic skin wounds (n = 108) of 20 mm diameter, using a double-blind, randomised, stratified, controlled, parallel-group design in piglets. Computerised planimetry and histopathological methods were used for the assessment of wound healing. Histologically, no significant differences could be verified at any time between the 3 groups. However, in the early phase (day 9 after wounding), the octenidine-based product retarded wound contraction to a significantly greater extent than placebo and polyhexanide, whereas in the later phase (days 18 and 28), polyhexanide promoted contraction significantly more than did placebo and octenidine. The consequence is complete wound closure after 22.9 days using polyhexanide, in comparison to the placebo after 24.1 days (p < 0.05) and octenidine after 28.3 days (no statistical difference to placebo). This may be explained by the better tolerance of polyhexanide in vitro, which was demonstrated with dose and time dependence in cytotoxicity tests on human amnion cells. Copyright 2004 S. Karger AG, Basel

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.

Oral Administration of Lactobacillus plantarum 299v Reduces Cortisol Levels in Human Saliva during Examination Induced Stress: A Randomized, Double-Blind Controlled Trial.

PubMed

Andersson, Hannah; Tullberg, Cecilia; Ahrné, Siv; Hamberg, Kristina; Lazou Ahrén, Irini; Molin, Göran; Sonesson, Mikael; Håkansson, Åsa

2016-01-01

Objective . To clarify the effect of Lactobacillus plantarum 299v on the salivary cortisol and salivary IgA levels in young adults under examination stress. Design . Forty-one students with an upcoming academic exam were included in a randomized double-blind, placebo-controlled study. The probiotic bacteria or the placebo product was administered in capsules once a day during 14 days. Saliva was collected and a perceived stress test was filled out at each sampling occasion. Saliva was collected for cortisol analysis by Electrochemiluminescence Immunoassay (ECLI) and salivary IgA was analysed by Enzyme-Linked Immunosorbent Assay (ELISA). Abundance of lactobacilli was evaluated by cultivation of saliva on selective medium and identification of L. plantarum 299v was done on randomly selected colonies by a random amplification of polymorphic DNA (RAPD) typing. Results . A significant difference in cortisol levels was found between the treatment group and the placebo group ( P < 0.05), together with a significant increase in levels of lactobacilli in the treatment group compared with the placebo group ( P < 0.001). No significant changes were found for salivary IgA. Conclusion . A probiotic bacterium with ability to reduce symptoms of irritable bowel syndrome (IBS) prohibited increased levels of the stress marker cortisol during the examination period. The registration number of the study is NCT02974894, and the study is registered at ClinicalTrials.gov.

Oral Administration of Lactobacillus plantarum 299v Reduces Cortisol Levels in Human Saliva during Examination Induced Stress: A Randomized, Double-Blind Controlled Trial

PubMed Central

Andersson, Hannah; Tullberg, Cecilia; Ahrné, Siv; Hamberg, Kristina; Lazou Ahrén, Irini; Molin, Göran; Sonesson, Mikael

2016-01-01

Objective. To clarify the effect of Lactobacillus plantarum 299v on the salivary cortisol and salivary IgA levels in young adults under examination stress. Design. Forty-one students with an upcoming academic exam were included in a randomized double-blind, placebo-controlled study. The probiotic bacteria or the placebo product was administered in capsules once a day during 14 days. Saliva was collected and a perceived stress test was filled out at each sampling occasion. Saliva was collected for cortisol analysis by Electrochemiluminescence Immunoassay (ECLI) and salivary IgA was analysed by Enzyme-Linked Immunosorbent Assay (ELISA). Abundance of lactobacilli was evaluated by cultivation of saliva on selective medium and identification of L. plantarum 299v was done on randomly selected colonies by a random amplification of polymorphic DNA (RAPD) typing. Results. A significant difference in cortisol levels was found between the treatment group and the placebo group (P < 0.05), together with a significant increase in levels of lactobacilli in the treatment group compared with the placebo group (P < 0.001). No significant changes were found for salivary IgA. Conclusion. A probiotic bacterium with ability to reduce symptoms of irritable bowel syndrome (IBS) prohibited increased levels of the stress marker cortisol during the examination period. The registration number of the study is NCT02974894, and the study is registered at ClinicalTrials.gov. PMID:28101105

Effects of Multivitamin, Multimineral and Phytonutrient Supplementation on Nutrient Status and Biomarkers of Heart Health Risk in a Russian Population: A Randomized, Double Blind, Placebo Controlled Study.

PubMed

Isakov, Vasily A; Bogdanova, Alexandra A; Bessonov, Vladimir V; Sentsova, Tatiana B; Tutelyan, Victor A; Lin, Yumei; Kazlova, Valentina; Hong, Jina; Velliquette, Rodney A

2018-01-25

The primary objective of this clinical study was to evaluate the effect of a dietary multivitamin, multimineral and phytonutrient (VMP) supplement on blood nutrient status and biomarkers of heart health risk in a Russian population. One hundred twenty healthy adults (40-70 years) were recruited for a 56-day (eight-week) randomized, double blind, placebo controlled study with parallel design. Subjects were divided into two groups and received either a VMP or a placebo (PLA) supplement. Blood nutrient levels of β-carotene, α-tocopherol, vitamin C, B6, B12, red blood cell (RBC) folate, Zinc and Selenium were measured at baseline and on Days 28 and 56, and quercetin was measured at baseline and on Day 56. Blood biomarkers of heart health, i.e. homocysteine (Hcy), high-sensitivity C-reactive protein (hs-CRP), oxidized LDL (ox-LDL), gamma-glutamyl transferase (GGT), uric acid and blood lipid profile, were measured at baseline and Day 56. Dietary VMP supplementation for 56 days significantly increased circulating levels of quercetin, vitamin C, RBC folate and partially prevented the decline in vitamin B6 and B12 status. Both serum Hcy and GGT were significantly reduced (-3.97 ± 10.09 µmol/L; -1.68 ± 14.53 U/L, respectively) after VMP supplementation compared to baseline. Dietary VMP supplementation improved the nutrient status and reduced biomarkers of heart health risk in a Russian population.

Effects of Multivitamin, Multimineral and Phytonutrient Supplementation on Nutrient Status and Biomarkers of Heart Health Risk in a Russian Population: A Randomized, Double Blind, Placebo Controlled Study

PubMed Central

Bogdanova, Alexandra A.; Bessonov, Vladimir V.; Sentsova, Tatiana B.; Tutelyan, Victor A.; Lin, Yumei; Kazlova, Valentina; Velliquette, Rodney A.

2018-01-01

The primary objective of this clinical study was to evaluate the effect of a dietary multivitamin, multimineral and phytonutrient (VMP) supplement on blood nutrient status and biomarkers of heart health risk in a Russian population. One hundred twenty healthy adults (40–70 years) were recruited for a 56-day (eight-week) randomized, double blind, placebo controlled study with parallel design. Subjects were divided into two groups and received either a VMP or a placebo (PLA) supplement. Blood nutrient levels of β-carotene, α-tocopherol, vitamin C, B6, B12, red blood cell (RBC) folate, Zinc and Selenium were measured at baseline and on Days 28 and 56, and quercetin was measured at baseline and on Day 56. Blood biomarkers of heart health, i.e. homocysteine (Hcy), high-sensitivity C-reactive protein (hs-CRP), oxidized LDL (ox-LDL), gamma-glutamyl transferase (GGT), uric acid and blood lipid profile, were measured at baseline and Day 56. Dietary VMP supplementation for 56 days significantly increased circulating levels of quercetin, vitamin C, RBC folate and partially prevented the decline in vitamin B6 and B12 status. Both serum Hcy and GGT were significantly reduced (−3.97 ± 10.09 µmol/L; −1.68 ± 14.53 U/L, respectively) after VMP supplementation compared to baseline. Dietary VMP supplementation improved the nutrient status and reduced biomarkers of heart health risk in a Russian population. PMID:29370120

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

PubMed Central

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

2013-01-01

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

Are Luxury Brand Labels and "Green" Labels Costly Signals of Social Status? An Extended Replication.

PubMed

Berger, Joël

2017-01-01

Costly signaling theory provides an explanation for why humans are willing to a pay a premium for conspicuous products such as luxury brand-labeled clothing or conspicuous environmentally friendly cars. According to the theory, the extra cost of such products is a signal of social status and wealth and leads to advantages in social interactions for the signaler. A previous study found positive evidence for the case of luxury brand labels. However, an issue of this study was that some of the experiments were not conducted in a perfectly double-blind manner. I resolved this by replicating variations of the original design in a double-blind procedure. Additionally, besides the luxury label condition, I introduced a "green" label condition. Thus, the hypothesis that signaling theory is able to explain pro-environmental behavior was tested for the first time in a natural field setting. Further, I conducted experiments in both average and below-average socioeconomic neighborhoods, where, according to signaling theory, the effects of luxury signals should be even stronger. In contrast to the original study, I did not find positive effects of the luxury brand label in any of the five experiments. Nor did I find evidence for a green-signaling effect. Moreover, in poor neighborhoods a negative tendency of the luxury label actually became evident. This suggests that a signaling theory explanation of costly labels must take into account the characteristics of the observers, e.g. their social status.

HT1001, a proprietary North American ginseng extract, improves working memory in schizophrenia: a double-blind, placebo-controlled study.

PubMed

Chen, Eric Y H; Hui, Christy L M

2012-08-01

Evidence suggests that HT1001™, a proprietary North American ginseng extract containing known levels of active ginsenosides, may improve cognitive function. Importantly, individuals with schizophrenia show marked deficits in working memory, which are believed to be predictive of functional outcome in this population. The present study aimed to characterize the effect of HT1001 on working memory in a group of stable individuals with schizophrenia. In a double-blind, placebo-controlled study design, a total of 64 individuals satisfying DSM-IV criteria for schizophrenia were randomly assigned to receive either HT100 or placebo for 4 weeks. Verbal working memory and visual working memory were assessed at baseline and again at the end of the treatment phase using the Letter-Number Span Test and Visual Pattern Test, respectively. Symptoms and medication side effects were also measured at baseline and post-treatment. Visual working memory was significantly improved in the HT1001 group, but not in the placebo group. Furthermore, extrapyramidal symptoms were significantly reduced after 4 weeks treatment with HT1001, whereas no difference in extrapyramidal effects was observed in the placebo group. These results provide a solid foundation for the further investigation of HT1001 as an adjunct therapy in schizophrenia, as an improvement in working memory and a reduction in medication-related side effects has considerable potential to improve functional outcome in this population. Copyright © 2011 John Wiley & Sons, Ltd.

Double-blind randomised controlled trial of the independent and synergistic effect of Spirulina maxima with exercise (ISESE) on general fitness, lipid profile and redox status in overweight and obese subjects: study protocol

PubMed Central

Hernández-Lepe, Marco Antonio; López-Díaz, José Alberto; de la Rosa, Laura Alejandra; Hernández-Torres, Rosa Patricia; Wall-Medrano, Abraham; Juarez-Oropeza, Marco Antonio; Pedraza-Chaverri, José; Urquidez-Romero, Rene; Ramos-Jiménez, Arnulfo

2017-01-01

Introduction In order to reduce cardiovascular disease risk factors, a healthy diet must include dietary antioxidants from different sources (eg, Spirulina maxima) and regular practice of exercise should be promoted. There is some evidence from animal studies that S. maxima and exercise decrease cardiovascular disease risks factors. However, very few studies have proved the independent or synergistic effect of S. maxima plus exercise in humans. This study attempts to address the independent and synergistic effects in overweight and obese subjects participating in a systematic physical exercise programme at moderate intensity on general fitness, plasma lipid profile and antioxidant capacity. Methods and analysis Using a randomised, double-blind, placebo-controlled, counterbalanced crossover study design, 80 healthy overweight and obese subjects will be evaluated during a 12-week isoenergetic diet accompanied by 4.5 g/day S. maxima intake and/or a physical systematic exercise programme at moderate intensity. Body composition, oxygen uptake, heart rate, capillary blood lactate, plasma concentrations of triacylglycerols, total, low-density and high-density lipoprotein cholesterol, antioxidant status, lipid oxidation, protein carbonyls, superoxide dismutase, catalase, glutathione, glutathione peroxidase, glutathione reductase and paraoxonase will be assessed. Ethics and dissemination This study and all the procedures have been approved by the Universidad Autonoma de Ciudad Juarez Bioethics Committee. Findings will be disseminated through peer-reviewed journals, national and international conferences. Trial registration number ClinicalTrials.gov: NCT02837666. PMID:28645949

Efficacy of Dragon's blood cream on wound healing: A randomized, double-blind, placebo-controlled clinical trial

PubMed Central

Namjoyan, Foroogh; Kiashi, Fatemeh; Moosavi, Zahra Beigom; Saffari, Fatemeh; Makhmalzadeh, Behzad Sharif

2015-01-01

The blood-red sap of Dragon's blood has been used in folk medicine for fractures, wounds, inflammation, gastrointestinal disorders, rheumatism, blood circulation dysfunctions, and cancer. Existing in vitro and in vivo bioactivity of this herb on different mechanisms of healing shows strong potential of this sap in wound healing. This clinical trial study was designated to evaluate the wound healing effect of Dragon's blood on human wounds. Sixty patients, between the ages of 14–65 years, who were referred to remove their skin tag, were assigned to this double-blind, placebo-controlled, randomized clinical trial and received either Dragon's blood or a placebo cream. They were visited on the 3rd, 5th, 7th, 10th, 14th, and 20th day of the trial to check the process of healing and to measure the wound's surface. At the end of trial, there was a significant difference in the mean duration of wound healing between the two groups (p = 0.0001). The phenolic compounds and the alkaloid taspine, which exist in Dragon's-blood resin, are probably the main reasons for the wound healing property of this plant. Being natural accessible, safe, and affordable makes Dragon's blood cream, a good choice for addition to the wound healing armamentarium. Further studies on wounds with different causes and among larger populations are suggested to ensure the effectiveness and safety of Dragon's blood. PMID:26870678

Efficacy of Dragon's blood cream on wound healing: A randomized, double-blind, placebo-controlled clinical trial.

PubMed

Namjoyan, Foroogh; Kiashi, Fatemeh; Moosavi, Zahra Beigom; Saffari, Fatemeh; Makhmalzadeh, Behzad Sharif

2016-01-01

The blood-red sap of Dragon's blood has been used in folk medicine for fractures, wounds, inflammation, gastrointestinal disorders, rheumatism, blood circulation dysfunctions, and cancer. Existing in vitro and in vivo bioactivity of this herb on different mechanisms of healing shows strong potential of this sap in wound healing. This clinical trial study was designated to evaluate the wound healing effect of Dragon's blood on human wounds. Sixty patients, between the ages of 14-65 years, who were referred to remove their skin tag, were assigned to this double-blind, placebo-controlled, randomized clinical trial and received either Dragon's blood or a placebo cream. They were visited on the 3rd, 5th, 7th, 10th, 14th, and 20th day of the trial to check the process of healing and to measure the wound's surface. At the end of trial, there was a significant difference in the mean duration of wound healing between the two groups (p = 0.0001). The phenolic compounds and the alkaloid taspine, which exist in Dragon's-blood resin, are probably the main reasons for the wound healing property of this plant. Being natural accessible, safe, and affordable makes Dragon's blood cream, a good choice for addition to the wound healing armamentarium. Further studies on wounds with different causes and among larger populations are suggested to ensure the effectiveness and safety of Dragon's blood.

Efficacy trial of bioresonance in children with atopic dermatitis.

PubMed

Schöni, M H; Nikolaizik, W H; Schöni-Affolter, F

1997-03-01

Single case reports and uncontrolled studies claim significant improvements in patients with atopic diseases treated with bioresonance therapy, also called biophysical information therapy (BIT). To assess the efficacy of this alternative method of treatment, we performed a conventional double-blind parallel group study in children hospitalized for long-lasting atopic dermatitis. Over a period of 1.5 year, 32 children with atopic dermatitis, age range 1.5-16.8 years and hospitalized for 4-6 weeks at the Alpine Children's Hospital Davos, Switzerland, were randomized according to sex, age and severity of the skin disease to receive conventional inpatient therapy and either a putatively active or a sham (placebo) BIT treatment. Short- and long-term outcome within 1 year were assessed by skin symptom scores, sleep and itch scores, blood cell activation markers of allergy, and a questionnaire. Hospitalization and conventional therapy in a high altitude climate resulted in immediate and sustained amelioration of the disease state in both the BIT-treated and sham-treated groups. BIT had no significant additive measurable effect on the outcome variables determined in this study. The statement by protagonists of this alternative form of therapy that BIT can considerably influence or even cure atopic dermatitis was not confirmed using for the first time a conventional double-blind study design. Considering the high costs and false promises caused by the promotors of this kind of therapy, it is concluded that BIT has no place in the treatment of children with atopic dermatitis.

Abuse potential of carbohydrates for overweight carbohydrate cravers

PubMed Central

Spring, Bonnie; Schneider, Kristin; Smith, Malaina; Kendzor, Darla; Appelhans, Bradley; Hedeker, Donald; Pagoto, Sherry

2010-01-01

Rationale The long-rejected construct of food addiction is undergoing re-examination. Objectives . To evaluate whether a novel carbohydrate food shows abuse potential for rigorously defined carbohydrate cravers, as evidenced by selective self-administration and mood enhancement during double-blind discrimination testing. Methods Discrete trials choice testing was performed with 61 overweight (BMI m=27.64, SD=2.59) women (ages 18–45; 19.70% African American) whose diet records showed >4 weekly afternoon/evening emotional eating episodes confined to snacks with carbohydrate:protein ≥ 6:1. After being induced into a sad mood, participants were exposed, double-blind and in counterbalanced order, to taste-matched carbohydrate and protein beverages. They were asked to choose and self-administer the drink that made them feel better. Results Women overwhelmingly chose the carbohydrate beverage, even though blinded. Mixed-effects regression modeling, controlling for beverage order, revealed greater liking and greater reduction in dysphoria following the carbohydrate beverage compared to the protein beverage, but no differential effect on vigor. Conclusion For women who crave them, carbohydrates appear to display abuse potential, plausibly contributing to overconsumption and overweight. PMID:18273603

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

PubMed

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

2006-01-01

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

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

PubMed

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

2008-08-02

Some children with juvenile idiopathic arthritis either do not respond, or are intolerant to, treatment with disease-modifying antirheumatic drugs, including anti-tumour necrosis factor (TNF) drugs. We aimed to assess the safety and efficacy of abatacept, a selective T-cell costimulation modulator, in children with juvenile idiopathic arthritis who had failed previous treatments. We did a double-blind, randomised controlled withdrawal trial between February, 2004, and June, 2006. We enrolled 190 patients aged 6-17 years, from 45 centres, who had a history of active juvenile idiopathic arthritis; at least five active joints; and an inadequate response to, or intolerance to, at least one disease-modifying antirheumatic drug. All 190 patients were given 10 mg/kg of abatacept intravenously in the open-label period of 4 months. Of the 170 patients who completed this lead-in course, 47 did not respond to the treatment according to predefined American College of Rheumatology (ACR) paediatric criteria and were excluded. Of the patients who did respond to abatacept, 60 were randomly assigned to receive 10 mg/kg of abatacept at 28-day intervals for 6 months, or until a flare of the arthritis, and 62 were randomly assigned to receive placebo at the same dose and timing. The primary endpoint was time to flare of arthritis. Flare was defined as worsening of 30% or more in at least three of six core variables, with at least 30% improvement in no more than one variable. We analysed all patients who were treated as per protocol. This trial is registered, number NCT00095173. Flares of arthritis occurred in 33 of 62 (53%) patients who were given placebo and 12 of 60 (20%) abatacept patients during the double-blind treatment (p=0.0003). Median time to flare of arthritis was 6 months for patients given placebo (insufficient events to calculate IQR); insufficient events had occurred in the abatacept group for median time to flare to be assessed (p=0.0002). The risk of flare in patients who continued abatacept was less than a third of that for controls during that double-blind period (hazard ratio 0.31, 95% CI 0.16-0.95). During the double-blind period, the frequency of adverse events did not differ in the two treatment groups. Adverse events were recorded in 37 abatacept recipients (62%) and 34 (55%) placebo recipients (p=0.47); only two serious adverse events were reported, both in controls (p=0.50). Selective modulation of T-cell costimulation with abatacept is a rational alternative treatment for children with juvenile idiopathic arthritis. Bristol-Myers Squibb.

Turmeric

MedlinePlus

... irritation that often occurs after radiation treatments for breast cancer. Other preliminary studies in people have looked at ... double-blind, placebo-controlled clinical trial of thirty breast cancer patients . Radiation Research. 2013;180(1):34-43. ...

Correct titration of non-drugs and some other methodological issues.

PubMed

Beneke, M; Rasmus, W; Rød, I S; Fritze, J

1994-01-01

Doctors' prescription and dosing behaviour was investigated using data from 9 clinical trials in 550 patients treated with psychotropics. 7 trials were conducted under double- and 2 under single-blind conditions. In 3 of these trials, oral and i.m. preparations were used demanding a double-dummy design. All patients were evaluated on a weekly or 2-week basis using psychopathological rating scales (i.e. Hamilton Anxiety Scale, Hamilton Depression Scale, Clinical Global Impressions, Simpson and Angus EPS). It was found that (a) oral-medication titration was 3- to 4-fold more broad-ranging than i.m. medication titration, (b) oral placebo was titrated to the same extent as the oral investigational drugs, and (c) the titration schedule did not follow protocol requirements. Moreover, the average doses in all drug and placebo groups were the same. Concomitant medication like sleep inducers was found to be more closely related to doctors' habits than to actual medical need. Independent of trial and investigational drug, 10-33% of all patients received additional sleep inducers.

Exploratory Decision-Tree Modeling of Data from the Randomized REACTT Trial of Tadalafil Versus Placebo to Predict Recovery of Erectile Function After Bilateral Nerve-Sparing Radical Prostatectomy

PubMed Central

Montorsi, Francesco; Oelke, Matthias; Henneges, Carsten; Brock, Gerald; Salonia, Andrea; d’Anzeo, Gianluca; Rossi, Andrea; Mulhall, John P.; Büttner, Hartwig

2017-01-01

Background Understanding predictors for the recovery of erectile function (EF) after nerve-sparing radical prostatectomy (nsRP) might help clinicians and patients in preoperative counseling and expectation management of EF rehabilitation strategies. Objective To describe the effect of potential predictors on EF recovery after nsRP by post hoc decision-tree modeling of data from A Study of Tadalafil After Radical Prostatectomy (REACTT). Design, setting, and participants Randomized double-blind double-dummy placebo-controlled trial in 423 men aged <68 yr with adenocarcinoma of the prostate (Gleason ≤7, normal preoperative EF) who underwent nsRP at 50 centers from nine European countries and Canada. Intervention Postsurgery 1:1:1 randomization to 9-mo double-blind treatment with tadalafil 5 mg once a day (OaD), tadalafil 20 mg on demand, or placebo, followed by a 6-wk drug-free-washout, and a 3-mo open-label tadalafil OaD treatment. Outcome measurements and statistical analysis Three decision-tree models, using the International Index of Erectile Function-Erectile Function (IIEF-EF) domain score at the end of double-blind treatment, washout, and open-label treatment as response variable. Each model evaluated the association between potential predictors: presurgery IIEF domain and IIEF single-item scores, surgical approach, nerve-sparing score (NSS), and postsurgery randomized treatment group. Results and limitations The first decision-tree model (n = 422, intention-to-treat population) identified high presurgery sexual desire (IIEF item 12: ≥3.5 and <3.5) as the key predictor for IIEF-EF at the end of double-blind treatment (mean IIEF-EF: 14.9 and 11.1), followed by high confidence to get and maintain an erection (IIEF item 15: ≥3.5 and <3.5; IIEF-EF: 15.4 and 7.1). For patients meeting these criteria, additional non-IIEF–related predictors included robot-assisted laparoscopic surgery (yes or no; IIEF-EF: 19.3 and 12.6), quality of nerve sparing (NSS: <2.5 and ≥2.5; IIEF-EF: 14.3 and 10.5), and treatment with tadalafil OaD (yes and no; IIEF-EF: 17.6 and 14.3). Additional analyses after washout and open-label treatment identified high presurgery intercourse satisfaction as the key predictor. Conclusions Exploratory decision-tree analyses identified high presurgery sexual desire, confidence, and intercourse satisfaction as key predictors for EF recovery. Patients meeting these criteria might benefit the most from conserving surgery and early postsurgery EF rehabilitation. Strategies for improving EF after surgery should be discussed preoperatively with all patients; this information may support expectation management for functional recovery on an individual patient level. Patient summary Understanding how patient characteristics and different treatment options affect the recovery of erectile function (EF) after radical surgery for prostate cancer might help physicians select the optimal treatment for their patients. This analysis of data from a clinical trial suggested that high presurgery sexual desire, sexual confidence, and intercourse satisfaction are key factors predicting EF recovery. Patients meeting these criteria might benefit the most from conserving surgery (robot-assisted surgery, perfect nerve sparing) and postsurgery medical rehabilitation of EF. Trial registration ClinicalTrials.gov, NCT01026818 PMID:26947602

Effect of beta2-adrenergic receptor polymorphism on response to longacting beta2 agonist in asthma (LARGE trial): a genotype-stratified, randomised, placebo-controlled, crossover trial.

PubMed

Wechsler, Michael E; Kunselman, Susan J; Chinchilli, Vernon M; Bleecker, Eugene; Boushey, Homer A; Calhoun, William J; Ameredes, Bill T; Castro, Mario; Craig, Timothy J; Denlinger, Loren; Fahy, John V; Jarjour, Nizar; Kazani, Shamsah; Kim, Sophia; Kraft, Monica; Lazarus, Stephen C; Lemanske, Robert F; Markezich, Amy; Martin, Richard J; Permaul, Perdita; Peters, Stephen P; Ramsdell, Joe; Sorkness, Christine A; Sutherland, E Rand; Szefler, Stanley J; Walter, Michael J; Wasserman, Stephen I; Israel, Elliot

2009-11-21

Some studies suggest that patients with asthma who are homozygous for arginine at the 16th amino acid position of the beta2-adrenergic receptor (B16 Arg/Arg) benefit less from treatment with longacting beta2 agonists and inhaled corticosteroids than do those homozygous for glycine (B16 Gly/Gly). We investigated whether there is a genotype-specific response to treatment with a longacting beta2 agonist in combination with inhaled corticosteroid. In this multicentre, randomised, double-blind, placebo-controlled trial, adult patients with moderate asthma were enrolled in pairs matched for forced expiratory volume in 1 s and ethnic origin, according to whether they had the B16 Arg/Arg (n=42) or B16 Gly/Gly (n=45) genotype. Individuals in a matched pair were randomly assigned by computer-generated randomisation sequence to receive inhaled longacting beta2 agonist (salmeterol 50 microg twice a day) or placebo given in a double-blind, crossover design for two 18-week periods. Open-label inhaled corticosteroid (hydrofluoroalkane beclometasone 240 microg twice a day) was given to all participants during the treatment periods. The primary endpoint was morning peak expiratory flow (PEF). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00200967. After 18 weeks of treatment, mean morning PEF in Arg/Arg participants was 21.4 L/min (95% CI 11.8-31.1) higher when participants were assigned to receive salmeterol than when assigned to receive placebo (p<0.0001). In Gly/Gly participants, morning PEF was 21.5 L/min (11.0-32.1) higher when participants were assigned to receive salmeterol than when assigned to receive placebo (p<0.0001). The improvement in PEF did not differ between genotypes (difference [Arg/Arg-Gly/Gly] -0.1, -14.4 to 14.2; p=0.99). In Gly/Gly participants, methacholine PC20 (20% reduction in forced expiratory volume in 1 s; a prespecified secondary outcome) was 2.4 times higher when participants were assigned to salmeterol than when assigned to placebo (p<0.0001). Responsiveness to methacholine did not differ between salmeterol and placebo in Arg/Arg participants (p=0.87). The 2.5 times higher genotype-specific difference in responsiveness to methacholine was significant (1.32 doubling dose difference between genotypes, 0.43-2.21, p=0.0038). Seven Arg/Arg participants (placebo, n=5; salmeterol, n=2) and six Gly/Gly participants (placebo, n=3; salmeterol, n=3) had an asthma exacerbation. Five serious adverse events were reported, one each during the pre-match and run-in phases on open-label inhaled corticosteroid, two during double-blind treatment with salmeterol/inhaled corticosteroid, and one during double-blind treatment with placebo/inhaled corticosteroid. None of the serious events was asthma-related or related to study drugs or procedures. In asthma patients with B16 Arg/Arg and B16 Gly/Gly genotypes, combination treatment with salmeterol and inhaled corticosteroid improved airway function when compared with inhaled corticosteroid therapy alone. These findings suggest that patients should continue to be treated with longacting beta2 agonists plus moderate-dose inhaled corticosteroids irrespective of B16 genotype. Further investigation is needed to establish the importance of the genotype-specific difference in responsiveness to methacholine. National Institutes of Health.

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.

Subcallosal cingulate deep brain stimulation for treatment-resistant depression: a multisite, randomised, sham-controlled trial.

PubMed

Holtzheimer, Paul E; Husain, Mustafa M; Lisanby, Sarah H; Taylor, Stephan F; Whitworth, Louis A; McClintock, Shawn; Slavin, Konstantin V; Berman, Joshua; McKhann, Guy M; Patil, Parag G; Rittberg, Barry R; Abosch, Aviva; Pandurangi, Ananda K; Holloway, Kathryn L; Lam, Raymond W; Honey, Christopher R; Neimat, Joseph S; Henderson, Jaimie M; DeBattista, Charles; Rothschild, Anthony J; Pilitsis, Julie G; Espinoza, Randall T; Petrides, Georgios; Mogilner, Alon Y; Matthews, Keith; Peichel, DeLea; Gross, Robert E; Hamani, Clement; Lozano, Andres M; Mayberg, Helen S

2017-11-01

Deep brain stimulation (DBS) of the subcallosal cingulate white matter has shown promise as an intervention for patients with chronic, unremitting depression. To test the safety and efficacy of DBS for treatment-resistant depression, a prospective, randomised, sham-controlled trial was conducted. Participants with treatment-resistant depression were implanted with a DBS system targeting bilateral subcallosal cingulate white matter and randomised to 6 months of active or sham DBS, followed by 6 months of open-label subcallosal cingulate DBS. Randomisation was computer generated with a block size of three at each site before the site started the study. The primary outcome was frequency of response (defined as a 40% or greater reduction in depression severity from baseline) averaged over months 4-6 of the double-blind phase. A futility analysis was performed when approximately half of the proposed sample received DBS implantation and completed the double-blind phase. At the conclusion of the 12-month study, a subset of patients were followed up for up to 24 months. The study is registered at ClinicalTrials.gov, number NCT00617162. Before the futility analysis, 90 participants were randomly assigned to active (n=60) or sham (n=30) stimulation between April 10, 2008, and Nov 21, 2012. Both groups showed improvement, but there was no statistically significant difference in response during the double-blind, sham-controlled phase (12 [20%] patients in the stimulation group vs five [17%] patients in the control group). 28 patients experienced 40 serious adverse events; eight of these (in seven patients) were deemed to be related to the study device or surgery. This study confirmed the safety and feasibility of subcallosal cingulate DBS as a treatment for treatment-resistant depression but did not show statistically significant antidepressant efficacy in a 6-month double-blind, sham-controlled trial. Future studies are needed to investigate factors such as clinical features or electrode placement that might improve efficacy. Abbott (previously St Jude Medical). Copyright © 2017 Elsevier Ltd. All rights reserved.

Real-time dose adjustment using point-of-care platelet reactivity testing in a double-blind study of prasugrel in children with sickle cell anaemia.

PubMed

Jakubowski, Joseph A; Hoppe, Carolyn C; Zhou, Chunmei; Smith, Brendan E; Brown, Patricia B; Heath, Lori E; Inusa, Baba; Rees, David C; Small, David S; Gupta, Neehar; Yao, Suqin; Heeney, Matthew; Kanter, Julie

2017-02-28

Patients with sickle cell anaemia (SCA) have vaso-occlusive crises resulting from occlusive hypoxic-ischaemic injury. Prasugrel inhibits platelet activation and aggregation involved in SCA pathophysiology. Determining Effects of Platelet Inhibition on Vaso-Occlusive Events (DOVE) was a phase 3, double-blind, randomised, placebo-controlled trial assessing prasugrel efficacy. DOVE sought to bring patients' P2Y12 reaction unit (PRU) value within a targeted range via prasugrel dose adjustments using encrypted VerifyNow P2Y12 ® (VN-P2Y12) point-of-care testing and an interactive voice-response system (IVRS). After PRU determination, randomised patients received 0.08 mg/kg/day prasugrel or placebo. Encrypted PRUs and IVRS provided double-blind dose adjustments to achieve a defined PRU target range of 136-231; placebo patients had mock titrations. Of 341 randomised patients, 166 placebo and 160 prasugrel patients reached the fully titrated dose (FTD). Most prasugrel patients (n=104, 65 %) remained on the initial 0.08 mg/kg dose; doses escalations occurred in 23 % of patients (n=36). Mean PRUs for the pharmacodynamic population at baseline were similar in the prasugrel (273 ± 44.9) and placebo groups (273 ± 51.7), with significant reductions in PRU (p<0.001) for prasugrel patients at the FTD and at 9 months. Concomitant use of hydroxyurea did not affect platelet reactivity at any time. The majority of prasugrel patients (n=135, 84.4 %) at the FTD were within the target range of 136-231 PRUs. Mean VN-P2Y12 percentage inhibition at baseline was similar in the prasugrel (2.8  ± 5.4 %) and placebo groups (2.0 ± 4.7 %); prasugrel patients had significant increases in inhibition (p<0.001) at FTD and at 9 months. Patients with higher PRU values at baseline required higher prasugrel doses to bring PRU within the prespecified range. DOVE is the first study to successfully employ double-blind, real-time, encrypted, point-of-care platelet testing and IVRS to dose-adjust antiplatelet therapy to a targeted range of platelet inhibition.

Aripiprazole for the maintenance treatment of bipolar I disorder: A review.

PubMed

McIntyre, Roger S

2010-01-01

Bipolar disorder is a chronic neuropsychiatric syndrome associated with substantial rates of recurrence, interepisodic dysfunction, comorbidity, and premature mortality. Metabolic comorbidity (eg, overweight, obesity, metabolic syndrome) differentially affects individuals with bipolar disorder and contributes to increased illness-associated morbidity and mortality (ie, cardiovascular disease). Few pharmacologic agents have been approved by the US Food and Drug Administration for the maintenance treatment of bipolar disorder. This paper discusses the metabolic profile of aripiprazole and reviews pivotal registration trials of aripiprazole for the maintenance treatment of adults with bipolar I disorder. MEDLINE was searched for English-language articles published between January 1995 and November 2009. The key search term was aripiprazole, combined with bipolar disorder and maintenance treatment. The review was limited to randomized, controlled registration trials, supplemented by poster presentations involving the registration-trial data sets. Three studies of the efficacy and tolerability of aripiprazole monotherapy in the maintenance treatment of bipolar I disorder were identified by the literature search: a 26-week, randomized, double-blind study and its 74-week extension phase (for a total of 100 weeks of double-blind treatment), and a randomized, double-blind comparison of aripiprazole with placebo and lithium (internal comparator) for up to 12 weeks. After 100 weeks of double-blind treatment, aripiprazole had a minimal effect on body composition and did not disrupt metabolic parameters compared with placebo. The mean (SD) weight change was 0.4 (0.8) kg with aripiprazole and -1.9 (0.8) kg with placebo (P = NS). A clinically significant (> or =7%) increase in weight occurred in 20% of the aripiprazole group and 5% of the placebo group (P = 0.01). Extrapyramidal symptoms were reported in 22% of the aripiprazole group and 15% of the placebo group. The identified trials of aripiprazole primarily enrolled patients during a manic state; no maintenance trials of combination therapy or trials enrolling individuals presenting with an acute depressive episode were identified. The available evidence supports the efficacy and tolerability of aripiprazole in the maintenance treatment of bipolar disorder. The placebo-subtracted differences in body composition and metabolic parameters suggest utility for aripiprazole in the long-term treatment of bipolar disorder. 2010 Excerpta Medica Inc. All rights reserved.

Neurological adverse events of new generation sodium blocker antiepileptic drugs. Meta-analysis of randomized, double-blinded studies with eslicarbazepine acetate, lacosamide and oxcarbazepine.

PubMed

Zaccara, Gaetano; Giovannelli, Fabio; Maratea, Dario; Fadda, Valeria; Verrotti, Alberto

2013-09-01

Analysis of overall tolerability and neurological adverse effects (AEs) of eslicarbazepine acetate (ESL), lacosamide (LCM) and oxcarbazepine (OXC) from double-blind, placebo-controlled trials. Indirect comparisons of patients withdrawing because of AEs, and the incidence of some vestibulocerebellar AEs between these three antiepileptic dugs (AEDs). We searched MEDLINE for all randomized, double-blind, placebo-controlled trials investigating therapeutic effects of fixed oral doses of ESL, LCM and OXC in patients with drug resistant epilepsy. Withdrawal rate due to AEs, percentages of patients with serious AEs, and the proportion of patients experiencing any neurological AE, nausea and vomiting were assessed for their association with the experimental drug. Analyses were performed between recommended daily doses of each AED according to the approved summary of product characteristics (SPC). Risk differences were used to evaluate the association of any AE [99% confidence intervals (CIs)] or study withdrawals because of AEs (95% CIs) with the experimental drug. Indirect comparisons between withdrawal rate and AEs dizziness, coordination abnormal/ataxia and diplopia were estimated according to network meta-analysis (Net-MA). Eight randomized, placebo-controlled, double-blind trials (4 with ESL, 3 with LCM, and 1 with OXC) were included in our analysis. At high doses (OXC 1200mg, ESL 1200mg and LCM 400mg) there was an increased risk of AE-related study withdrawals compared to placebo for all drugs. Several AEs were associated with the experimental drug. Both number and frequency of AEs were dose-related. At high recommended doses, patients treated with OXC withdrew from the experimental treatment significantly more frequently than patients treated with ESL and LCM. Furthermore, the AEs coordination abnormal/ataxia and diplopia were significantly more frequently observed in patients treated with OXC compared to patients treated with LCM and ESL. The overall tolerability of AEDs and the incidence of several neurological AEs were clearly dose-dependent. Indirect comparisons between these AEDs, taking into account dose-effect, showed that OXC may be associated with more frequent neurological AEs than LCM and ESL. Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

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

PubMed

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

2017-09-26

Urinary tract infections (UTI) are among the most prevalent microbial diseases and their financial burden on society is substantial. The continuing increase of antibiotic resistance worldwide is alarming. Thus, well-tolerated, highly effective therapeutic alternatives are urgently needed. Although there is evidence indicating that bacteriophage therapy may be effective and safe for treating UTIs, the number of investigated patients is low and there is a lack of randomized controlled trials. This study is the first randomized, placebo-controlled, double-blind trial investigating bacteriophages in UTI treatment. Patients planned for transurethral resection of the prostate are screened for UTIs and enrolled if in urine culture eligible microorganisms ≥10 4 colony forming units/mL are found. Patients are randomized in a double-blind fashion to the 3 study treatment arms in a 1:1:1 ratio to receive either: a) bacteriophage (i.e. commercially available Pyo bacteriophage) solution, b) placebo solution, or c) antibiotic treatment according to the antibiotic sensitivity pattern. All treatments are intended for 7 days. No antibiotic prophylaxes will be given to the double-blinded treatment arms a) and b). As common practice, the Pyo bacteriophage cocktail is subjected to periodic adaptation cycles during the study. Urinalysis, urine culture, bladder and pain diary, and IPSS questionnaire will be completed prior to and at the end of treatment (i.e. after 7 days) or at withdrawal/drop out from the study. Patients with persistent UTIs will undergo antibiotic treatment according to antibiotic sensitivity pattern. Based on the high lytic activity and the potential of resistance optimization by direct adaptation of bacteriophages, and considering the continuing increase of antibiotic resistance worldwide, bacteriophage therapy is a very promising treatment option for UTIs. Thus, our randomized controlled trial investigating bacteriophages for treating UTIs will provide essential insights into this potentially revolutionizing treatment option. This study has been registered at clinicaltrials.gov ( www.clinicaltrials.gov/ct2/show/NCT03140085 ). April 27, 2017.

Benzodiazepine temazepam suppresses the transient auditory 40-Hz response amplitude in humans.

PubMed

Jääskeläinen, I P; Hirvonen, J; Saher, M; Pekkonen, E; Sillanaukee, P; Näätänen, R; Tiitinen, H

1999-06-18

To discern the role of the GABA(A) receptors in the generation and attentive modulation of the transient auditory 40-Hz response, the effects of the benzodiazepine temazepam (10 mg) were studied in 10 healthy social drinkers, using a double-blind placebo-controlled design. Three hundred Hertz standard and 330 Hz rare deviant tones were presented to the left, and 1000 Hz standards and 1100 Hz deviants to the right ear of the subjects. Subjects attended to a designated ear and were to detect deviants therein while ignoring tones to the other. Temazepam significantly suppressed the amplitude of the 40-Hz response, the effect being equal for attended and non-attended tone responses. This suggests involvement of GABA(A) receptors in transient auditory 40-Hz response generation, however, not in the attentive modulation of the 40-Hz response.

Overview of somatization: diagnosis, epidemiology, and management.

PubMed

Escobar, J I

1996-01-01

This article outlines critical issues in the psychiatric assessment of patients presenting with medically unexplained physical symptoms that form the core of the somatoform disorders in current nosologies. The prevalence of these disorders in communities and clinical settings emphasizes that a majority of these patients are primary care service users rather than mental health clients. A brief review of previous studies on the pharmacological management of these syndromes with antidepressants highlights unique features of these disorders that are relevant to the design of double-blind studies. The promising results emerging from some of these studies bring new excitement to the field that may help counter the prevailing therapeutic nihilism, thus attracting new investigators to this area. Finally, several caveats are provided on issues of research design and interpretation for the benefit of those entering this field of research.

Unintended Consequences of Sensor, Signal, and Imaging Informatics: New Problems and New Solutions.

PubMed

Hughes, C; Voros, S; Moreau-Gaudry, A

2016-11-10

This synopsis presents a selection for the IMIA (International Medical Informatics Association) Yearbook 2016 of excellent research in the broad field of Sensor, Signal and Imaging Informatics published in the year 2015, with a focus on Unintended consequences: new problems and new solutions. We performed a systematic initial selection and a double blind peer review process to find the best papers in this domain published in 2015, from the PubMed and Web of Science databases. The set of MesH keywords used was provided by experts. The constant advances in medical technology allow ever more relevant diagnostic and therapeutic approaches to be designed. Nevertheless, there is a need to acquire expert knowledge of these innovations in order to identify precociously new associated problems for which new solutions need to be designed and developed.

Study protocol for the G-SPIRIT trial: a randomised, placebo-controlled, double-blinded phase III trial of granulocyte colony-stimulating factor-mediated neuroprotection for acute spinal cord injury

PubMed Central

Koda, Masao; Hanaoka, Hideki; Sato, Takatoshi; Fujii, Yasuhisa; Hanawa, Michiko; Takahashi, Sho; Furuya, Takeo; Ijima, Yasushi; Saito, Junya; Kitamura, Mitsuhiro; Ohtori, Seiji; Matsumoto, Yukei; Abe, Tetsuya; Watanabe, Kei; Hirano, Toru; Ohashi, Masayuki; Shoji, Hirokazu; Mizouchi, Tatsuki; Takahashi, Ikuko; Kawahara, Norio; Kawaguchi, Masahito; Orita, Yugo; Sasamoto, Takeshi; Yoshioka, Masahito; Fujii, Masafumi; Yonezawa, Katsutaka; Soma, Daisuke; Taneichi, Hiroshi; Takeuchi, Daisaku; Inami, Satoshi; Moridaira, Hiroshi; Ueda, Haruki; Asano, Futoshi; Shibao, Yosuke; Aita, Ikuo; Takeuchi, Yosuke; Mimura, Masaya; Shimbo, Jun; Someya, Yukio; Ikenoue, Sumio; Sameda, Hiroaki; Takase, Kan; Ikeda, Yoshikazu; Nakajima, Fumitake; Hashimoto, Mitsuhiro; Ozawa, Tomoyuki; Hasue, Fumio; Fujiyoshi, Takayuki; Kamiya, Koshiro; Watanabe, Masahiko; Katoh, Hiroyuki; Matsuyama, Yukihiro; Yamamoto, Yu; Togawa, Daisuke; Hasegawa, Tomohiko; Kobayashi, Sho; Yoshida, Go; Oe, Shin; Banno, Tomohiro; Arima, Hideyuki; Akeda, Koji; Kawamoto, Eiji; Imai, Hiroshi; Sakakibara, Toshihiko; Sudo, Akihiro; Ito, Yasuo; Kikuchi, Tsuyoshi; Osaki, Shuhei; Tanaka, Nobuhiro; Nakanishi, Kazuyoshi; Kamei, Naosuke; Kotaka, Shinji; Baba, Hideo; Okudaira, Tsuyoshi; Konishi, Hiroaki; Yamaguchi, Takayuki; Ito, Keigo; Katayama, Yoshito; Matsumoto, Taro; Matsumoto, Tomohiro; Idota, Masaru; Kanno, Haruo; Aizawa, Toshimi; Hashimoto, Ko; Eto, Toshimitsu; Sugaya, Takehiro; Matsuda, Michiharu; Fushimi, Kazunari; Nozawa, Satoshi; Iwai, Chizuo; Taguchi, Toshihiko; Kanchiku, Tsukasa; Suzuki, Hidenori; Nishida, Norihiro; Funaba, Masahiro; Yamazaki, Masashi

2018-01-01

Introduction Granulocyte colony-stimulating factor (G-CSF) is generally used for neutropaenia. Previous experimental studies revealed that G-CSF promoted neurological recovery after spinal cord injury (SCI). Next, we moved to early phase of clinical trials. In a phase I/IIa trial, no adverse events were observed. Next, we conducted a non-randomised, non-blinded, comparative trial, which suggested the efficacy of G-CSF for promoting neurological recovery. Based on those results, we are now performing a phase III trial. Methods and analysis The objective of this study is to evaluate the efficacy of G-CSF for acute SCI. The study design is a prospective, multicentre, randomised, double-blinded, placebo-controlled comparative study. The current trial includes cervical SCI (severity of American Spinal Injury Association (ASIA) Impairment Scale B/C) within 48 hours after injury. Patients are randomly assigned to G-CSF and placebo groups. The G-CSF group is administered 400 µg/m2/day×5 days of G-CSF in normal saline via intravenous infusion for 5 consecutive days. The placebo group is similarly administered a placebo. Our primary endpoint is changes in ASIA motor scores from baseline to 3 months. Each group includes 44 patients (88 total patients). Ethics and dissemination The study will be conducted according to the principles of the World Medical Association Declaration of Helsinki and in accordance with the Japanese Medical Research Involving Human Subjects Act and other guidelines, regulations and Acts. Results of the clinical study will be submitted to the head of the respective clinical study site as a report after conclusion of the clinical study by the sponsor-investigator. Even if the results are not favourable despite conducting the clinical study properly, the data will be published as a paper. Trial registration number UMIN000018752. PMID:29730616

The use of tenoxicam to prevent symptoms of discomfort induced by vagotonia during uterus manipulation in cesarean sections

PubMed Central

Chen, Shih-Hong; Chen, Shiou-Sheng; Chang, Ching-Tao; Huang, Chi-Hsiang; Fan, Shou-Zen; Chen, Li-Kuei

2017-01-01

Abstract Purpose: Symptoms such as nausea, vomiting, tightness of the chest, bradycardia, and shoulder or abdominal discomfort, caused by vagotonia occurring during uterus manipulation, have concerned healthcare professionals for some time. Patients sometimes report these symptoms when undergoing spinal anesthesia for cesarean sections (CSs). We designed a prospective, double-blind study to investigate the effectiveness of tenoxicam in preventing these symptoms of discomfort. Methods: A total of 105 American Society of Anesthesiologists (ASA) class I-II nulliparous pregnant women, who were scheduled for a CS, were enrolled into this prospective, double-blind study. Spinal anesthesia was conducted to reach a peak dermatome level of no more than T3. The 100 patients were randomly divided into 2 groups having completed study course: Group T (N = 50) received a 20 mg dose of tenoxicam in 5 mL of normal saline (NS) immediately after skin incision and Group N (N = 50) only received 5 mL NS. The incidence and severity of the symptoms experienced by the patients were recorded by a nurse anesthetist who was blinded to the injection regimen the patients were receiving. A chi-square test was used for statistical analysis t test and P < .05 was defined as significant. Results: The incidence and degree of severity of nausea and vomiting were same in both the groups. The incidence and degree of severity of bradycardia, nausea, vomiting, tightness of the chest, shoulder discomfort, and abdominal discomfort were lower in Group T than in Group N. Conclusion: Tenoxicam might theoretically block the parasympathetic vagus pathway and decrease the visceral pain or visceral-specific symptoms, alleviating the symptoms caused by vagotonia. However, the prophylactic effect of tenoxicam in reducing the incidence and severity of nausea and vomiting was not statistically significant. This could be because nausea and vomiting are not solely caused by vagotonia, but also by other mechanisms. PMID:28746222

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

PubMed Central

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

2011-01-01

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

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

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

PubMed

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

2017-01-01

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

COMPARE CPM-RMI Trial: Intramyocardial Transplantation of Autologous Bone Marrow-Derived CD133+ Cells and MNCs during CABG in Patients with Recent MI: A Phase II/III, Multicenter, Placebo-Controlled, Randomized, Double-Blind Clinical Trial.

PubMed

Naseri, Mohammad Hassan; Madani, Hoda; Ahmadi Tafti, Seyed Hossein; Moshkani Farahani, Maryam; Kazemi Saleh, Davood; Hosseinnejad, Hossein; Hosseini, Saeid; Hekmat, Sepideh; Hossein Ahmadi, Zargham; Dehghani, Majid; Saadat, Alireza; Mardpour, Soura; Hosseini, Seyedeh Esmat; Esmaeilzadeh, Maryam; Sadeghian, Hakimeh; Bahoush, Gholamreza; Bassi, Ali; Amin, Ahmad; Fazeli, Roghayeh; Sharafi, Yaser; Arab, Leila; Movahhed, Mansour; Davaran, Saeid; Ramezanzadeh, Narges; Kouhkan, Azam; Hezavehei, Ali; Namiri, Mehrnaz; Kashfi, Fahimeh; Akhlaghi, Ali; Sotoodehnejadnematalahi, Fattah; Vosough Dizaji, Ahmad; Gourabi, Hamid; Syedi, Naeema; Shahverdi, Abdol Hosein; Baharvand, Hossein; Aghdami, Nasser

2018-07-01

The regenerative potential of bone marrow-derived mononuclear cells (MNCs) and CD133+ stem cells in the heart varies in terms of their pro-angiogenic effects. This phase II/III, multicenter and double-blind trial is designed to compare the functional effects of intramyocardial autologous transplantation of both cell types and placebo in patients with recent myocardial infarction (RMI) post-coronary artery bypass graft. This was a phase II/III, randomized, double-blind, placebo-controlled trial COMPARE CPM-RMI (CD133, Placebo, MNCs - recent myocardial infarction) conducted in accordance with the Declaration of Helsinki that assessed the safety and efficacy of CD133 and MNCs compared to placebo in patients with RMI. We randomly assigned 77 eligible RMI patients selected from 5 hospitals to receive CD133+ cells, MNC, or a placebo. Patients underwent gated single photon emission computed tomography assessments at 6 and 18 months post-intramyocardial transplantation. We tested the normally distributed efficacy outcomes with a mixed analysis of variance model that used the entire data set of baseline and between-group comparisons as well as within subject (time) and group×time interaction terms. There were no related serious adverse events reported. The intramyocardial transplantation of both cell types increased left ventricular ejection fraction by 9% [95% confidence intervals (CI): 2.14% to 15.78%, P=0.01] and improved decreased systolic wall thickening by -3.7 (95% CI: -7.07 to -0.42, P=0.03). The CD133 group showed significantly decreased non-viable segments by 75% (P=0.001) compared to the placebo and 60% (P=0.01) compared to the MNC group. We observed this improvement at both the 6- and 18-month time points. Intramyocardial injections of CD133+ cells or MNCs appeared to be safe and efficient with superiority of CD133+ cells for patients with RMI. Although the sample size precluded a definitive statement about clinical outcomes, these results have provided the basis for larger studies to confirm definitive evidence about the efficacy of these cell types (Registration Number: NCT01167751). Copyright© by Royan Institute. All rights reserved.

Working memory training in children with neuropsychiatric disorders and mild to borderline intellectual functioning, the role of coaching; a double-blind randomized controlled trial.

PubMed

Roording-Ragetlie, Sammy; Klip, Helen; Buitelaar, Jan; Slaats-Willemse, Dorine

2017-03-28

Working memory training (WMT) has been shown to offer therapeutic benefits to both patients with Attention-Deficit Hyperactivity Disorder (ADHD) and patients with mild to borderline Intellectual Disabilities (MBID; 60 < IQ < 85). However, robust evidence for transfer effects and treatment benefits of WMT over placebo training are lacking. Owing to the nature of double-blind research designs in RCTs, children have received non-specific coaching not based on their actual training performance. Active coaching based on individual training results (such as in clinical practice) might enhance the efficacy of Cogmed WMT. Furthermore, clinical experience and the general treatment approach to these vulnerable children has shown that the intensity and duration of WMT is often too stressful. This study therefore investigated the efficacy of a less intensive, but more prolonged Cogmed WMT (including active personalized coaching and feedback) in reducing behavioral symptoms and improving neurocognitive functioning and academic achievements in children with MBID and neuropsychiatric disorders. A double-blind RCT with children (age 10.0-13.11) with neuropsychiatric disorders (ADHD and/or autism spectrum disorder (ASD)) and MBID (IQ: 60 < IQ < 85). Two groups (each n = 26) will receive Cogmed WMT (version R/M) at home or at school for 8 weeks, 4 days a week, at 30 min a day. One group will receive active personalized coaching and feedback based on their actual individual performance during Cogmed training. The other group will only receive general non-personalized coaching (i.e. no receive personalized coaching and feedback). Both groups will undergo a neurocognitive assessment (working memory, executive functioning, academic achievements) before and after training and complete several questionnaires (behavioral problems, parenting style) with a 6 months follow-up. This study will add to the literature since the role of coaching in Cogmed WMT has not been studied before. It will also provide opportunities to investigate an alternative version of WMT in a large group of vulnerable children, for whom few evidence-based treatments are available. Ultimately, this will allow us to advise mental health care professionals and special education schools about the use of this type of intervention for children with MBID and neuropsychiatric disorders. Dutch Trial Register. NTR5223 . Registration date 06-09-2015.

An open-label study to evaluate the long-term safety and efficacy of lanadelumab for prevention of attacks in hereditary angioedema: design of the HELP study extension.

PubMed

Riedl, Marc A; Bernstein, Jonathan A; Craig, Timothy; Banerji, Aleena; Magerl, Markus; Cicardi, Marco; Longhurst, Hilary J; Shennak, Mustafa M; Yang, William H; Schranz, Jennifer; Baptista, Jovanna; Busse, Paula J

2017-01-01

Hereditary angioedema (HAE) is characterized by recurrent attacks of subcutaneous or submucosal edema. Attacks are unpredictable, debilitating, and have a significant impact on quality of life. Patients may be prescribed prophylactic therapy to prevent angioedema attacks. Current prophylactic treatments may be difficult to administer (i.e., intravenously), require frequent administrations or are not well tolerated, and breakthrough attacks may still occur frequently. Lanadelumab is a subcutaneously-administered monoclonal antibody inhibitor of plasma kallikrein in clinical development for prophylaxis of hereditary angioedema attacks. A Phase 1b study supported its efficacy in preventing attacks. A Phase 3, randomized, double-blind, placebo-controlled, parallel-arm study has been completed and an open-label extension is currently ongoing. The primary objective of the open-label extension is to evaluate the long-term safety of repeated subcutaneous administrations of lanadelumab in patients with type I/II HAE. Secondary objectives include evaluation of efficacy and time to first angioedema attack to determine outer bounds of the dosing interval. The study will also evaluate immunogenicity, pharmacokinetics/pharmacodynamics, quality of life, characteristics of breakthrough attacks, ease of self-administration, and safety/efficacy in patients who switch to lanadelumab from another prophylactic therapy. The open-label extension will enroll patients who completed the double-blind study ("rollover patients") and those who did not participate in the double-blind study ("non-rollover patients"), which includes patients who may or may not be currently using another prophylactic therapy. Rollover patients will receive a single 300 mg dose of lanadelumab on Day 0 and the second dose after the patient's first confirmed angioedema attack. Thereafter, lanadelumab will be administered every 2 weeks. Non-rollover patients will receive 300 mg lanadelumab every 2 weeks regardless of the first attack. All patients will receive their last dose on Day 350 (maximum of 26 doses), and will then undergo a 4-week follow-up. Prevention of attacks can reduce the burden of illness associated with HAE. Prophylactic therapy requires extended, repeated dosing and the results of this study will provide important data on the long-term safety and efficacy of lanadelumab, a monoclonal antibody inhibitor of plasma kallikrein for subcutaneous administration for the treatment of HAE. Trial registration NCT02741596.

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

PubMed Central

2011-01-01

Background The scaphoid bone is the most commonly fractured of the carpal bones. In the Netherlands 90% of all carpal fractures is a fracture of the scaphoid bone. The scaphoid has an essential role in functionality of the wrist, acting as a pivot. Complications in healing can result in poor functional outcome. The scaphoid fracture is a troublesome fracture and failure of treatment can result in avascular necrosis (up to 40%), non-union (5-21%) and early osteo-arthritis (up to 32%) which may seriously impair wrist function. Impaired consolidation of scaphoid fractures results in longer immobilization and more days lost at work with significant psychosocial and financial consequences. Initially Pulsed Electromagnetic Fields was used in the treatment of tibial pseudoarthrosis and non-union. More recently there is evidence that physical forces can also be used in the treatment of fresh fractures, showing accelerated healing by 30% and 71% reduction in nonunion within 12 weeks after initiation of therapy. Until now no double blind randomized, placebo controlled trial has been conducted to investigate the effect of this treatment on the healing of fresh fractures of the scaphoid. Methods/Design This is a multi center, prospective, double blind, placebo controlled, randomized trial. Study population consists of all patients with unilateral acute scaphoid fracture. Pregnant women, patients having a life supporting implanted electronic device, patients with additional fractures of wrist, carpal or metacarpal bones and pre-existing impairment in wrist function are excluded. The scaphoid fracture is diagnosed by a combination of physical and radiographic examination (CT-scanning). Proven scaphoid fractures are treated with cast immobilization and a small Pulsed Electromagnetic Fields bone growth stimulating device placed on the cast. Half of the devices will be disabled at random in the factory. Study parameters are clinical consolidation, radiological consolidation evaluated by CT-scanning, functional status of the wrist, including assessment by means of the patient rated wrist evaluation (PRWE) questionnaire and quality of life using SF-36 health survey questionnaire. Primary endpoint is number of scaphoid unions at six weeks, secondary endpoints are time interval to clinical and radiological consolidation, number of non-unions, functional status at 52 weeks and non-adherence to the treatment protocol. Trial registration Netherlands Trial Register (NTR): NTR2064 PMID:21548951

Clinical Comparison of Haloperidol with Chlorpromazine in Mentally Retarded Children

ERIC Educational Resources Information Center

LeVann, Leonard J.

1971-01-01

In an 8-week double-blind comparison, haloperidol reduced the severity of the target symptoms impulsiveness, hostility, and aggressiveness in significantly more mentally retarded children than did chlorpromazine. (Author)

Fairness in peer review

NASA Astrophysics Data System (ADS)

Adams, Bob

2014-06-01

In reply to Penny Gowland's article “Turning a double-blind eye” (Forum, May p17), which argued that a paper's authors, as well as its reviewers, should be anonymous during the peer-review process.

Individualized Homeopathic Treatment and Fluoxetine for Moderate to Severe Depression in Peri- and Postmenopausal Women (HOMDEP-MENOP Study): A Randomized, Double-Dummy, Double-Blind, Placebo-Controlled Trial

PubMed Central

Macías-Cortés, Emma del Carmen; Llanes-González, Lidia; Aguilar-Faisal, Leopoldo; Asbun-Bojalil, Juan

2015-01-01

Background Perimenopausal period refers to the interval when women's menstrual cycles become irregular and is characterized by an increased risk of depression. Use of homeopathy to treat depression is widespread but there is a lack of clinical trials about its efficacy in depression in peri- and postmenopausal women. The aim of this study was to assess efficacy and safety of individualized homeopathic treatment versus placebo and fluoxetine versus placebo in peri- and postmenopausal women with moderate to severe depression. Methods/Design A randomized, placebo-controlled, double-blind, double-dummy, superiority, three-arm trial with a 6 week follow-up study was conducted. The study was performed in a public research hospital in Mexico City in the outpatient service of homeopathy. One hundred thirty-three peri- and postmenopausal women diagnosed with major depression according to DSM-IV (moderate to severe intensity) were included. The outcomes were: change in the mean total score among groups on the 17-item Hamilton Rating Scale for Depression, Beck Depression Inventory and Greene Scale, after 6 weeks of treatment, response and remission rates, and safety. Efficacy data were analyzed in the intention-to-treat population (ANOVA with Bonferroni post-hoc test). Results After a 6-week treatment, homeopathic group was more effective than placebo by 5 points in Hamilton Scale. Response rate was 54.5% and remission rate, 15.9%. There was a significant difference among groups in response rate definition only, but not in remission rate. Fluoxetine-placebo difference was 3.2 points. No differences were observed among groups in the Beck Depression Inventory. Homeopathic group was superior to placebo in Greene Climacteric Scale (8.6 points). Fluoxetine was not different from placebo in Greene Climacteric Scale. Conclusion Homeopathy and fluoxetine are effective and safe antidepressants for climacteric women. Homeopathy and fluoxetine were significantly different from placebo in response definition only. Homeopathy, but not fluoxetine, improves menopausal symptoms scored by Greene Climacteric Scale. Trial Registration ClinicalTrials.gov NCT01635218 Protocol Publication http://www.trialsjournal.com/content/14/1/105. PMID:25768800

Bupropion and Naltrexone for Smoking Cessation: A Double-Blind Randomized Placebo-Controlled Clinical Trial

PubMed Central

Mooney, Marc E.; Schmitz, Joy M.; Allen, Sharon; Grabowski, John; Pentel, Paul; Oliver, Andrew; Hatsukami, Dorothy K.

2016-01-01

Combination of non-nicotine pharmacotherapies has been under-examined for cigarette smoking cessation. A randomized, double-blind, parallel-group double-dummy study evaluated two medications, bupropion (BUP) and naltrexone (NTX), in treatment-seeking cigarette smokers (N = 121) over a 7-week treatment intervention with 6-month follow-up. Smokers were randomized to either BUP (300 mg/day) + Placebo (PBO) or BUP (300 mg/day) + NTX (50 mg/day). The primary outcome was biochemically-verified (saliva cotinine, carbon monoxide) 7-day, point-prevalence abstinence. BUP+NTX was associated with significantly higher point-prevalence abstinence rates after 7-weeks of treatment (BUP+NTX, 54.1%; BUP+PBO, 33.3%), p = 0.0210, but not at 6-month follow-up (BUP+NTX, 27.9%; BUP+PBO, 15.0%), p = 0.09. Continuous abstinence rates did not differ, p = 0.0740 (BUP+NTX, 26.2%; BUP+PBO, 13.3%). Those receiving BUP+NTX reported reduced nicotine withdrawal, p = 0.0364. The BUP+NTX combination was associated with elevated rates of some side effects, but with no significant difference in retention between the groups. PMID:27213949

A Model for Pharmacological Research-Treatment of Cocaine Dependence

PubMed Central

Montoya, Ivan D.; Hess, Judith M.; Preston, Kenzie L.; Gorelick, David A.

2008-01-01

Major problems for research on pharmacological treatments for cocaine dependence are lack of comparability of results from different treatment research programs and poor validity and/or reliability of results. Double-blind, placebo-controlled, random assignment, experimental designs, using standard intake and assessment procedures help to reduce these problems. Cessation or reduction of drug use and/or craving, retention in treatment, and medical and psychosocial improvement are some of the outcome variables collected in treatment research programs. A model to be followed across different outpatient clinical trials for pharmacological treatment of cocaine dependence is presented here. This model represents an effort to standardize data collection to make results more valid and comparable. PMID:8749725

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

Negres, Raluca A.; Stolz, Christopher J.; Thomas, Michael D.

Here, this competition aimed to survey state-of-the-art UV high reflectors. The requirements of the coatings are a minimum reflection of 99.5% at 45 degrees incidence angle for P-polarized light at 355-nm. The choice of coating materials, design, and deposition method were left to the participants. Laser damage testing was performed at a single testing facility using the raster scan method with a 5-ns pulse length laser system operating at 10 Hz in a single longitudinal mode. A double blind test assured sample and submitter anonymity. Finally, in addition to the laser damage resistance results, details of the deposition processes, cleaningmore » method, coating materials and layer count are also shared.« less

355-nm, nanosecond laser mirror thin film damage competition

NASA Astrophysics Data System (ADS)

Negres, Raluca A.; Stolz, Christopher J.; Thomas, Michael D.; Caputo, Mark

2017-11-01

This competition aimed to survey state-of-the-art UV high reflectors. The requirements of the coatings are a minimum reflection of 99.5% at 45 degrees incidence angle for P-polarized light at 355-nm. The choice of coating materials, design, and deposition method were left to the participants. Laser damage testing was performed at a single testing facility using the raster scan method with a 5-ns pulse length laser system operating at 10 Hz in a single longitudinal mode. A double blind test assured sample and submitter anonymity. In addition to the laser damage resistance results, details of the deposition processes, cleaning method, coating materials and layer count are also shared.

Cannabidiol as potential treatment in refractory pediatric epilepsy.

PubMed

Paolino, Maria Chiara; Ferretti, Alessandro; Papetti, Laura; Villa, Maria Pia; Parisi, Pasquale

2016-01-01

In recent years there has been great scientific and public interest focused on the therapeutic potential of compounds derived from cannabis for the treatment of refractory epilepsy in children. From in vitro and in vivo studies on animal models, cannabidiol (CBD) appears to be a promising anticonvulsant drug with a favorable side-effect profile. In humans, CBD efficacy and safety is not supported by well-designed trials and its use has been described by anecdotal reports. It will be necessary to investigate CBD safety, pharmacokinetics and interaction with other anti-epileptic drugs (AEDs) alongside performing double-blinded placebo-controlled trials in order to obtain conclusive data on its efficacy and safety in children.

Nivolumab-Based Treatments for Advanced Melanoma

Cancer.gov

A summary of results from an international, double-blind, randomized phase III trial testing the combination of nivolumab (Opdivo®) and ipilimumab (Yervoy®) against nivolumab alone and ipilimumab alone in patients with advanced melanoma.

Double-blind whitening Night-Guard study using ten percent carbamide peroxide.

PubMed

Ouellet, D; Los, S; Case, H; Healy, R

1992-01-01

The conservative technique of professionally dispensed and supervised, home-administered vital bleaching is now a routine treatment in the dental profession. This double-blind study evaluated the Rembrandt Lightening Gel and Whitening Toothpaste for shade change, colorimeter shade change. As well, it evaluated soft tissue health by periodontal probing, plaque index, and bleeding index. A patient questionnaire evaluated perception of whitening, perception of oral hygiene, average hours per day, and average days per week. Bleaching trays were worn over a 4-week period. The bleaching system showed definitive whitening effects as evaluated with the Vita shade guide and the colorimeter. The bleaching system had no deleterious effects on the soft tissue. The Rembrandt toothpaste alone demonstrated two-shade lightening. This vital bleaching system shows definitive whitening of the teeth in short periods of time with no adverse effects.

EFFECT OF A DENTIFRICE CONTAINING ALOE VERA ON PLAQUE AND GINGIVITIS CONTROL. A DOUBLE-BLIND CLINICAL STUDY IN HUMANS

PubMed Central

de Oliveira, Sílvia Morgana Araújo; Torres, Ticiana Carneiro; Pereira, Sérgio Luís da Silva; Mota, Olívia Morais de Lima; Carlos, Márlio Ximenes

2008-01-01

The effect of Aloe vera on the reduction of plaque and gingivitis was evaluated in a randomized, parallel and double-blind clinical trial. Subjects were randomly allocated to the test group (n=15) – dentifrice containing Aloe vera - or the control group (n=15) – fluoridated dentifrice. Plaque index (PI) and gingival bleeding index (GBI) were assessed at days 0 and 30. Subjects were asked to brush their teeth with the control or test dentifrice, three times a day, during a 30-day period. There was a significant reduction on plaque and gingivitis in both groups, but no statistically significant difference was observed among them (p>0.01). The dentifrice containing Aloe vera did not show any additional effect on plaque and gingivitis control compared to the fluoridated dentifrice. PMID:19089263

A randomized, double-blind, dose-finding Phase II study to evaluate immunogenicity and safety of the third generation smallpox vaccine candidate IMVAMUNE®

PubMed Central

von Krempelhuber, Alfred; Vollmar, Jens; Pokorny, Rolf; Rapp, Petra; Wulff, Niels; Petzold, Barbara; Handley, Amanda; Mateo, Lyn; Siersbol, Henriette; Kollaritsch, Herwig; Chaplin, Paul

2009-01-01

IMVAMUNE® is a Modified Vaccinia Ankara-based virus that is being developed as a safer 3rd generation smallpox vaccine. In order to determine the optimal dose for further development, a double-blind, randomized Phase II trial was performed testing three different doses of IMVAMUNE® in 164 healthy volunteers. All three IMVAMUNE® doses displayed a favourable safety profile, with local reactions as the most frequent observation. The 1×108 TCID50 IMVAMUNE® dose induced a total antibody response in 94% of the subjects following the first vaccination and the highest peak seroconversion rates by ELISA (100%) and PRNT (71%). This IMVAMUNE® dose was considered to be optimal for the further clinical development of this highly attenuated poxvirus as a safer smallpox vaccine. PMID:19944151

Randomised double-blind trial of acyclovir (Zovirax) and adenine arabinoside in herpes simplex amoeboid corneal ulceration.

PubMed

Collum, L M; Logan, P; McAuliffe-Curtin, D; Hung, S O; Patterson, A; Rees, P J

1985-11-01

Fifty-one patients were treated in a dual-centre, double-blind comparison of acyclovir and adenine arabinoside in herpetic amoeboid (geographic) corneal ulceration. Twenty-four of the 25 patients receiving acyclovir healed in a mean time of 12.2 days, while 24 of the 26 patients treated with adenine arabinoside healed in a mean time of 11.0 days. There was no statistically significant difference between the two groups in terms of healing. A second analysis, excluding any patients who had received antiviral treatment immediately prior to entry into the study, showed that 18 of the 19 who received acyclovir healed in an average of 11.7 days and 18 of the 19 recipients of adenine arabinoside healed in a mean time of 11.2 days. Again the difference was not statistically significant.

Effect of a dentifrice containing Aloe vera on plaque and gingivitis control. A double-blind clinical study in humans.

PubMed

de Oliveira, Sílvia Morgana Araújo; Torres, Ticiana Carneiro; Pereira, Sérgio Luís da Silva; Mota, Olívia Morais de Lima; Carlos, Márlio Ximenes

2008-01-01

The effect of Aloe vera on the reduction of plaque and gingivitis was evaluated in a randomized, parallel and double-blind clinical trial. Subjects were randomly allocated to the test group (n=15) - dentifrice containing Aloe vera - or the control group (n=15) - fluoridated dentifrice. Plaque index (PI) and gingival bleeding index (GBI) were assessed at days 0 and 30. Subjects were asked to brush their teeth with the control or test dentifrice, three times a day, during a 30-day period. There was a significant reduction on plaque and gingivitis in both groups, but no statistically significant difference was observed among them (p>0.01). The dentifrice containing Aloe vera did not show any additional effect on plaque and gingivitis control compared to the fluoridated dentifrice.

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

PubMed

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

2016-01-01

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

Evaluation of bendectin embryotoxicity in nonhuman primates: II. Double-blind study in term cynomolgus monkeys.

PubMed

Hendrickx, A G; Cukierski, M; Prahalada, S; Janos, G; Booher, S; Nyland, T

1985-10-01

The embryotoxic and teratogenic potential of Bendectin was assessed in this double-blind study in the cynomolgus monkey (Macaca fascicularis). Bendectin was administered orally at doses approximately two, five, and 20 times the human dose equivalent from 22 +/- 2 through 50 days of gestation. Fetuses were delivered by cesarean section near term and examined for malformations. There was no maternal toxicity as evidenced by maternal weights and physical signs. There was no correlation between dosage and the number of prenatal deaths. No significant abnormalities related to treatment were observed in postdelivery physical examinations, placental evaluations, external and internal gross examinations, or from radiographs of the neonates. Under the conditions of this study the treatment of pregnant cynomolgus monkeys with Bendectin produced no evidence of teratogenicity or embryo-, or fetal-, or maternal toxicity.

Phlebitis induced by parenteral treatment with flucloxacillin and cloxacillin: a double-blind study.

PubMed Central

Svedhem, A; Alestig, K; Jertborn, M

1980-01-01

Two studies were performed on a total of 54 patients with staphylococcal infections. Study I compares with phlebitogenic properties of flucloxacillin after intravenous infusions when either saline or sterile water was used as a solvent. No difference was observed between the two solvents, and the frequency of phlebitis for the total material without respect to solvents was 5% after 1 day of treatment and 13% after 2 days. Study II was a double-blind comparison of phlebitis caused by intravenous infusions of either flucloxacillin or cloxacillin. The frequencies of phlebitis were found to be 18 and 13%, respectively. After 2 days of treatment the frequency of phlebitis increased dramatically for both drugs. All infusions were given through a plastic cannula of 5-cm length and 1.2-mm diameter. PMID:7447412

Antihypertensive effect of Iranian Crataegus curvisepala Lind.: a randomized, double-blind study.

PubMed

Asgary, S; Naderi, G H; Sadeghi, M; Kelishadi, R; Amiri, M

2004-01-01

The aim of the present study was to investigate the potential antihypertensive effects of extracts of the flavonoid-rich Iranian flower, Crataegus curvisepala Lind., a member of the Rosaceae family. The hydroalcoholic extract of the leaves and flowers were studied in a double-blind, placebo-controlled clinical trial to determine its effects. A total of 92 men and women with primary mild hypertension, aged 40-60 years, were selected and divided randomly into two groups, receiving either hydroalcoholic extract of C. curvisepala Lind. or placebo three times daily for more than 4 months. Blood pressure (BP) was measured each month. Statistical analysis was carried out using Student's t-test. The results obtained showed a significant decrease in both systolic and diastolic BP after 3 months (p < 0.05). C. curvisepala has a time-dependent antihypertensive effect.

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

Cognitive and physiological responses in humans exposed to a TETRA base station signal in relation to perceived electromagnetic hypersensitivity.

PubMed

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

2012-01-01

Terrestrial Trunked Radio (TETRA) technology ("Airwave") has led to public concern because of its potential interference with electrical activity in the brain. The present study is the first to examine whether acute exposure to a TETRA base station signal has an impact on cognitive functioning and physiological responses. Participants were exposed to a 420 MHz TETRA signal at a power flux density of 10 mW/m(2) as well as sham (no signal) under double-blind conditions. Fifty-one people who reported a perceived sensitivity to electromagnetic fields as well as 132 controls participated in a double-blind provocation study. Forty-eight sensitive and 132 control participants completed all three sessions. Measures of short-term memory, working memory, and attention were administered while physiological responses (blood volume pulse, heart rate, skin conductance) were monitored. After applying exclusion criteria based on task performance for each aforementioned cognitive measure, data were analyzed for 36, 43, and 48 sensitive participants for these respective tasks and, likewise, 107,125, and 129 controls. We observed no differences in cognitive performance between sham and TETRA exposure in either group; physiological response also did not differ between the exposure conditions. These findings are similar to previous double-blind studies with other mobile phone signals (900-2100 MHz), which could not establish any clear evidence that mobile phone signals affect health or cognitive function. Copyright © 2011 Wiley Periodicals, Inc.

Effect of preoperative acetaminophen/hydrocodone on the efficacy of the inferior alveolar nerve block in patients with symptomatic irreversible pulpitis: a prospective, randomized, double-blind, placebo-controlled study.

PubMed

Fullmer, Spencer; Drum, Melissa; Reader, Al; Nusstein, John; Beck, Mike

2014-01-01

The purpose of this prospective, randomized, double-blind, placebo-controlled study was to determine the effect of the administration of the combination acetaminophen/hydrocodone on the anesthetic success of mandibular posterior teeth in patients experiencing symptomatic irreversible pulpitis. One hundred emergency patients in moderate to severe pain diagnosed with symptomatic irreversible pulpitis of a mandibular posterior tooth randomly received, in a double-blind manner, identical capsules of either a combination dose of 1000 mg acetaminophen/10 mg hydrocodone or placebo 60 minutes before the administration of a conventional inferior alveolar nerve (IAN) block. Endodontic access was begun 15 minutes after completion of the block, and all patients used for data analysis had profound lip numbness. Success was defined as no or mild pain (visual analog scale recordings) on pulpal access or instrumentation. The success rate for the IAN block was 32% for the combination dose of 1000 mg acetaminophen/10 hydrocodone and 28% for the placebo dose, with no statistically significant difference between the 2 groups (P = .662). A combination dose of 1000 mg acetaminophen/10 mg hydrocodone given 60 minutes before the administration of the IAN block did not result in a statistically significant increase in anesthetic success for mandibular posterior teeth in patients experiencing symptomatic irreversible pulpitis. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Efficacy and safety of saxagliptin in combination with insulin in Japanese patients with type 2 diabetes mellitus: a 16-week double-blind randomized controlled trial with a 36-week open-label extension.

PubMed

Kadowaki, Takashi; Muto, Satsuki; Ouchi, Yoshiumi; Shimazaki, Ryutaro; Seino, Yutaka

2017-12-01

We examined the efficacy and safety of saxagliptin as an add-on to insulin in Japanese patients with type 2 diabetes mellitus. We randomized 240 patients with type 2 diabetes mellitus on insulin monotherapy to 5-mg saxagliptin or placebo as add-on therapy for a 16-week, double-blind period. All patients received 5-mg saxagliptin and insulin for an additional 36 weeks (open-label extension). Change in hemoglobin A1c (HbA1c) at Week 16 was the main endpoint. At Week 16, the adjusted change in HbA1c from baseline increased by 0.51% with placebo and decreased by 0.40% with saxagliptin (difference -0.92% [95% confidence interval -1.07%, -0.76%; p < 0.001]). In patients receiving saxagliptin, reductions in HbA1c at Week 16 were maintained to Week 52, while switching from placebo to saxagliptin resulted in a similar reduction in HbA1c. The incidence of hypoglycemia was not markedly increased with saxagliptin versus placebo in the double-blind period and did not increase substantially during the open-label extension period. The efficacy and safety of saxagliptin was similar between the elderly and non-elderly patient groups. Adding saxagliptin to ongoing insulin therapy improved glycemic control and was well tolerated in Japanese patients with type 2 diabetes.

Soy germ extract alleviates menopausal hot flushes: placebo-controlled double-blind trial.

PubMed

Imhof, Martin; Gocan, Anca; Imhof, Marianne; Schmidt, Mathias

2018-05-30

A double-blind, placebo-controlled study was performed to assess the potency of a soy germ preparation for the alleviation of menopausal hot flushes. Caucasian women with at least seven hot flushes daily were treated with soy germ extract (100 mg isoflavone glycosides) daily or with placebo for 12 weeks, followed by 12 weeks of open treatment with soy. Outcome parameters were the number of hot flushes and the evaluation of the Greene Climacteric Scale. A total of 192 women were included. As the hot flush diaries from one study centre were lost, the assessment of hot flushes was based on 136 participants (soy: 54 women; placebo: 82 women). After 12 weeks, 180 women were available for the analysis of Greene Scale and safety (soy and placebo: each 90 women). Hot flushes were reduced by 43.3% (-3.5 hot flushes) with soy and by 30.8% with placebo (-2.6; p < 0.001). After the open treatment phase with soy, both original groups showed a reduction of 68% of hot flushes. A subgroup analysis showed better effects for soy when symptoms were classified as "severe" at baseline. After 12 weeks of double-blind treatment, there was an improvement from baseline values of 71 and 78% with soy with the items "hot flushes" and "sweating", compared with 24% for both items with placebo. Hormonal safety parameters remained uninfluenced. Soy germ extract with 100 mg of isoflavone glycosides was shown to modestly, but significantly reduce menopausal hot flushes.

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

PubMed

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

2010-11-01

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

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

PubMed

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

2012-08-14

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

Bright light therapy decreases winter binge frequency in women with bulimia nervosa: a double-blind, placebo-controlled study.

PubMed

Braun, D L; Sunday, S R; Fornari, V M; Halmi, K A

1999-01-01

The study objective was to determine the effect of winter bright light therapy on binge and purge frequencies and depressive symptoms in subjects with bulimia nervosa. Thirty-four female bulimic outpatients were treated with either 10,000 lux bright white light or 50 lux dim red light (placebo control) during the winter months. In this double-blind study, the placebo group (n = 18) and the bright light group (n = 16) were matched for age, degree of seasonality (measured by the Seasonal Patterns Assessment Questionnaire [SPAQ]), and concurrent depression (measured by Structured Clinical Interview for DSM-IV [SCID]). Three weeks of baseline data collection were followed by 3 weeks of half-hour daily morning light treatment and 2 weeks of follow-up evaluation. There was a significant light-treatment by time interaction (Wilks' lambda = .81, F(2,28) = 3.31, P = .05). The mean binge frequency decreased significantly more from baseline to the end of treatment for the bright light group (F(1,29) = 6.41, P = .017) than for the placebo group. The level of depression (measured by daily Beck Depression Inventory [BDI] scores) did not significantly differ between the groups during any phase, and neither depression nor seasonality affected the response to light treatment. In this double-blind study, bulimic women who received 3 weeks of winter bright light treatment reported a reduced binge frequency between baseline and the active treatment period in comparison to subjects receiving dim red light.

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

PubMed

Moore, Nicholas; Verdoux, Hélène; Fantino, Bruno

2005-05-01

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

Double-blind maintenance safety and effectiveness findings from the Treatment of Early-Onset Schizophrenia Spectrum Study (TEOSS)

PubMed Central

Findling, Robert L; Johnson, Jacqueline L; McClellan, Jon; Frazier, Jean A; Vitiello, Benedetto; Hamer, Robert M; Lieberman, Jeffrey A; Ritz, Louise; McNamara, Nora K; Lingler, Jacqui; Hlastala, Stefanie; Pierson, Leslie; Puglia, Madeline; Maloney, Ann E; Kaufman, Emily Michael; Noyes, Nancy; Sikich, Linmarie

2010-01-01

OBJECTIVE To examine the long-term safety and efficacy of three antipsychotics in early-onset schizophrenia spectrum disorders (EOSS). METHOD Patients (age 8–19 years) who had improved during an 8-week, randomized double-blind acute trial of olanzapine, risperidone, or molindone (plus benztropine) were eligible to continue on the same medication for up to 44 additional weeks under double-blind conditions. Adjunctive medications were allowed following defined algorithms. Standardized symptom, safety, and functional assessments were conducted every 4 weeks. RESULTS Of the 116 youth randomized in the acute trial, 54 entered maintenance treatment (molindone, N=20; olanzapine, N=13; risperidone, N=21). Fourteen (26%) completed 44 weeks of treatment. Adverse effects (N=15), inadequate efficacy (N=14), or study non-adherence (N=8) were the most common reasons for discontinuation. The three treatment arms did not significantly differ in symptom reduction or time to discontinuation. Akathisia was more common with molindone and elevated prolactin concentrations more common with risperidone. Although weight gain and metabolic adverse events had occurred more often with olanzapine and risperidone during the acute trial, no significant between-drug differences emerged in most of these parameters during maintenance treatment. CONCLUSIONS Only 12 % of youth with EOSS continued on their originally randomized treatment at 52 weeks. No agent demonstrated superior efficacy, and all were associated with side effects, including weight gain. Improved treatments are needed for EOSS. PMID:20494268

A double-blind, placebo-controlled study of risperidone in adults with autistic disorder and other pervasive developmental disorders.

PubMed

McDougle, C J; Holmes, J P; Carlson, D C; Pelton, G H; Cohen, D J; Price, L H

1998-07-01

Neurobiological research has implicated the dopamine and serotonin systems in the pathogenesis of autism. Open-label reports suggest that the serotonin2A-dopamine D2 antagonist risperidone may be safe and effective in reducing the interfering symptoms of patients with autism. Thirty-one adults (age [mean+/-SD], 28.1+/-7.3 years) with autistic disorder (n=17) or pervasive developmental disorder not otherwise specified (n=14) participated in a 12-week double-blind, placebo-controlled trial of risperidone. Patients treated with placebo subsequently received a 12-week open-label trial of risperidone. For persons completing the study, 8 (57%) of 14 patients treated with risperidone were categorized as responders (daily dose [mean+/-SD], 2.9+/-1.4 mg) compared with none of 16 in the placebo group (P<.002). Risperidone was superior to placebo in reducing repetitive behavior (P<.001), aggression (P<.001), anxiety or nervousness (P<.02), depression (P<.03), irritability (P<.01), and the overall behavioral symptoms of autism (P<.02). Objective, measurable change in social behavior and language did not occur. Nine (60%) of 15 patients who received treatment with open-label risperidone following the double-blind placebo phase responded. Other than mild, transient sedation, risperidone was well tolerated, with no evidence of extrapyramidal effects, cardiac events, or seizures. Risperidone is more effective than placebo in the short-term treatment of symptoms of autism in adults.

Reduction of fatigue in Sjögren syndrome with rituximab: results of a randomised, double-blind, placebo-controlled pilot study.

PubMed

Dass, S; Bowman, S J; Vital, E M; Ikeda, K; Pease, C T; Hamburger, J; Richards, A; Rauz, S; Emery, P

2008-11-01

Primary Sjögren syndrome (pSS) causes significant systemic symptoms including fatigue as well as glandular dysfunction. There are currently no effective systemic therapies; however, open label series have suggested that rituximab may be beneficial for systemic and glandular manifestations. Therefore, we performed a double blind, placebo-controlled, randomised pilot study of the efficacy of rituximab in reducing fatigue in pSS. A total of 17 patients with pSS and a score on fatigue visual analogue scale (VAS) >50 were randomised to receive either 2 infusions of rituximab 1 g or placebo; patients also received oral and intravenous steroids. Outcome measures included: the proportion of patients with >20% reduction in fatigue VAS, changes in pSS related symptoms, health related quality of life and immunological parameters of pSS. These were measured 6 months after therapy. There was significant improvement from baseline in fatigue VAS in the rituximab group (p<0.001) in contrast to the placebo group (p = 0.147). There was a significant difference between the groups at 6 months in the social functioning score of SF-36 (p = 0.01) and a trend to significant difference in the mental health domain score of SF-36 (p = 0.06). There was one episode of serum sickness in the rituximab treated group. This is the first double blind study of rituximab in pSS to show benefit; further studies are justified.

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

PubMed

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

2018-04-20

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

Long-term safety and tolerability of once-daily mesalamine granules in the maintenance of remission of ulcerative colitis.

PubMed

Lichtenstein, Gary R; Barrett, Andrew C; Bortey, Enoch; Paterson, Craig; Forbes, William P

2014-08-01

Ulcerative colitis (UC), a chronic, relapsing, and remitting inflammatory bowel disease, requires long-term treatment to maintain remission. In this study, the long-term safety and tolerability of mesalamine granules (MG) therapy was evaluated in the maintenance of UC remission. Previous prospective studies evaluating different oral mesalamine formulations have not exceeded a duration of 14 months. A phase 3, multicenter, 24-month, open-label extension study evaluating MG 1.5 g once daily in patients who achieved previous remission from mild to moderate UC was performed. Eligible patients had successfully participated in 1 of 2 previous 6-month double-blind, placebo-controlled trials or were new patients in remission. Safety assessments included monitoring of adverse events (AEs) and clinical laboratory tests. Risk of UC recurrence was assessed by the occurrence of UC-related AEs. Of the 393 patients enrolled (280 from the double-blind studies; 113 new patients), 388 were included in the safety population. The most common AEs included nasopharyngitis (13.9%), headache (11.6%), and diarrhea (10.8%), and the incidence of these events was generally lower in the MG group versus historical placebo group from the double-blind studies. Pancreatic, renal, and hepatic AEs occurred in 23 patients (5.9%). The risk of UC-related AEs was low and was maintained for 24 months during the open-label study. Once-daily MG has a favorable safety profile for the maintenance of remission for up to 2 years in patients with UC.

Zonisamide and renal calculi in patients with epilepsy: how big an issue?

PubMed

Wroe, Stephen

2007-08-01

To determine the prevalence of renal calculi in patients treated with zonisamide during randomized, controlled and open-label clinical trials, and from post-marketing surveillance data. Reports of renal calculi from four placebo-controlled double-blind trials of zonisamide, their long-term open-label treatment extension phases, and the US/European zonisamide clinical trial programme were reviewed. One double-blind study and its extension included routine ultrasound screening to identify asymptomatic calculi. Post-marketing surveillance data were also investigated, as was concomitant treatment with topiramate. No symptomatic renal calculi were reported during four randomized double-blind, placebo-controlled trials involving 848 subjects (including 498 zonisamide recipients) treated for up to 3 months. In long-term extension studies with treatment for up to 24 months, symptomatic renal calculi were reported in 9/626 (1.4%) patients. Pooled safety data from all US/European clinical trials identified 15/1296 (1.2%) patients with symptomatic renal calculi during treatment for up to 8.7 years. Post-marketing surveillance revealed nine cases from 59 667 patient-years of exposure in the USA, and 14 from 709 294 patient-years of exposure in Japan; only one case occurred during concomitant topiramate and zonisamide treatment. No imbalance in electrolyte levels was found from 35 patients receiving such co-treatment in clinical trials. The available data suggest that the risk of developing renal calculi during zonisamide treatment is low. Data are insufficient to determine whether concomitant treatment with topiramate increases the risk of renal stones.

Development of a Novel Six-Month Nutrition Intervention for a Randomized Trial in Older Men with Mobility Limitations.

PubMed

Apovian, C M; Singer, M R; Campbell, W W; Bhasin, S; McCarthy, A C; Shah, M; Basaria, S; Moore, L L

2017-01-01

Nutrition impacts the development of sarcopenia and protein intake is an important modulator of skeletal muscle mass loss in older people. The Optimizing Protein Intake in Older Men with Mobility Limitation (OPTIMEN) Trial was designed to assess the independent and combined effects of higher protein intake and a promyogenic agent, testosterone, on lean body mass, muscle strength and physical function in older men with mobility disability. The purpose of this paper is to describe the experimental design and nutrition intervention, including techniques used by research dietitians to develop and deliver energy and protein-specific meals to the homes of community-dwelling participants. Strategies to enhance long-term dietary compliance are detailed. Randomized, double-blind, placebo-controlled six-month intervention trial. Participants were recruited from Boston MA USA and surrounding communities. Older men who were mobility-limited (Short Physical Performance Battery (SPPB) 3-10) and consuming less protein (<0.83 g/kg/day) were recruited for this study. Here we report the successful implementation of a double-blind, placebo-controlled, parallel group, randomized controlled trial with a 6-month intervention period among community-living men, age 65 years and older with a mobility limitation. A controlled feeding plan was used to deliver required energy intakes and prescribed protein quantities of 0.8 or 1.3 grams/kilogram/day (g/kg/d) in three meals plus snacks and supplements. A 2x2 factorial design was used to assess the effects of protein level alone and in combination with testosterone (vs. placebo) on changes in lean body mass (primary outcome), muscle strength, and physical function. A total of 154 men met the eligibility criteria; 112 completed a 2-week run-in period designed to evaluate compliance with the nutrition intervention. Of these, 92 subjects met compliance eligibility criteria and agreed to be randomized; 85% completed the full trial. The study successfully delivered three meals per day to subjects, with a high degree of compliance and subject satisfaction. Overall self-reported compliance rates were 80% and 93% for the meals and supplements, respectively. Details of compliance strategies are discussed. This community-based study design may serve as a model for longer-term nutritional interventions requiring monitoring of dietary compliance in a home-based feeding and supplementation trial.

A novel dual‐wavelength, Nd:YAG, picosecond‐domain laser safely and effectively removes multicolor tattoos

PubMed Central

Schomacker, Kevin T.; Basilavecchio, Lisa D.; Plugis, Jessica M.; Bhawalkar, Jayant D.

2015-01-01

Background and Objectives Although nanosecond‐domain lasers have been the mainstay of laser tattoo removal for decades, recent disruptive innovations in laser design have introduced a new class of commercial Q‐switched lasers that generate picosecond‐domain pulses. Study A picosecond‐domain, Nd:YAG laser with a KTP frequency‐doubling crystal was used to treat 31 decorative tattoos in 21 subjects. Safety and effectiveness were determined by blinded evaluation of digital images in this prospective clinical study. Results The average clearance overall as evaluated by blinded observers evaluating randomized digital photographs was 79 ± 0.9% (mean ± sem) after an average of 6.5 treatments. Of the 31 tattoos completing treatment, 6 had evidence of mild hyper‐ or hypo‐pigmentation by evaluation of photographs. Conclusion The 350 picosecond, 532 nm, and 450 picosecond 1,064 nm Nd:YAG laser is safe and effective for removing decorative tattoos. Lasers Surg. Med. 47:542–548, 2015. © 2015 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc. PMID:26175187

Assisting persons with multiple disabilities to move through simple occupational activities with automatic prompting.

PubMed

Lancioni, Giulio E; Singh, Nirbhay N; O'Reilly, Mark F; Sigafoos, Jeff; Oliva, Doretta; Campodonico, Francesca; Groeneweg, Jop

2008-01-01

The present study assessed the possibility of assisting four persons with multiple disabilities to move through and perform simple occupational activities arranged within a room with the help of automatic prompting. The study involved two multiple probe designs across participants. The first multiple probe concerned the two participants with blindness or minimal vision and deafness, who received air blowing as a prompt. The second multiple probe concerned the two participants with blindness and typical hearing who received a voice calling as a prompt. Initially, all participants had baseline sessions. Then intervention started with the first participant of each dyad. When their performance was consolidated, new baseline and intervention occurred with the second participant of each dyad. Finally, all four participants were exposed to a second intervention phase, in which the number of activities per session doubled (i.e., from 8 to 16). Data showed that all four participants: (a) learned to move across and perform the activities available with the help of automatic prompting and (b) remained highly successful through the second intervention phase when the sessions were extended. Implications of the findings are discussed.

Maternal Opioid Treatment: Human Experimental Research (MOTHER) – Approach, Issues, and Lessons Learned

PubMed Central

Jones, Hendrée E.; Fischer, Gabriele; Heil, Sarah H.; Kaltenbach, Karol; Martin, Peter R.; Coyle, Mara G.; Selby, Peter; Stine, Susan M.; O’Grady, Kevin E.; Arria, Amelia M.

2015-01-01

Aims The Maternal Opioid Treatment: Human Experimental Research (MOTHER) project, an eight-site randomized, double-blind, double-dummy, flexible-dosing, parallel-group clinical trial is described. This study is the most current – and single most comprehensive – research effort to investigate the safety and efficacy of maternal and prenatal exposure to methadone and buprenorphine. Methods The MOTHER study design is outlined, and its basic features are presented. Conclusions At least seven important lessons have been learned from the MOTHER study: (1) an interdisciplinary focus improves the design and methods of a randomized clinical trial; (2) multiple sites in a clinical trial present continuing challenges to the investigative team due to variations in recruitment goals, patient populations, and hospital practices that in turn differentially impact recruitment rates, treatment compliance, and attrition; (3) study design and protocols must be flexible in order to meet the unforeseen demands of both research and clinical management; (4) staff turnover needs to be addressed with a proactive focus on both hiring and training; (5) the implementation of a protocol for the treatment of a particular disorder may identify important ancillary clinical issues worthy of investigation; (6) timely tracking of data in a multi-site trial is both demanding and unforgiving; and, (7) complex multi-site trials pose unanticipated challenges that complicate the choice of statistical methods, thereby placing added demands on investigators to effectively communicate their results. PMID:23106924

Exenatide and the treatment of patients with Parkinson’s disease

PubMed Central

Aviles-Olmos, Iciar; Dickson, John; Kefalopoulou, Zinovia; Djamshidian, Atbin; Ell, Peter; Soderlund, Therese; Whitton, Peter; Wyse, Richard; Isaacs, Tom; Lees, Andrew; Limousin, Patricia; Foltynie, Thomas

2013-01-01

Background. There is increasing interest in methods to more rapidly and cost-efficiently investigate drugs that are approved for clinical use in the treatment of another condition. Exenatide is a type 2 diabetes treatment that has been shown to have neuroprotective/neurorestorative properties in preclinical models of neurodegeneration. Methods. As a proof of concept, using a single-blind trial design, we evaluated the progress of 45 patients with moderate Parkinson’s disease (PD), randomly assigned to receive subcutaneous exenatide injection for 12 months or to act as controls. Their PD was compared after overnight withdrawal of conventional PD medication using blinded video assessment of the Movement Disorders Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), together with several nonmotor tests, at baseline, 6 months, and 12 months and after a further 2-month washout period (14 months). Results. Exenatide was well tolerated, although weight loss was common and l-dopa dose failures occurred in a single patient. Single-blinded rating of the exenatide group suggested clinically relevant improvements in PD across motor and cognitive measures compared with the control group. Exenatide-treated patients had a mean improvement at 12 months on the MDS-UPDRS of 2.7 points, compared with mean decline of 2.2 points in control patients (P = 0.037). Conclusion. These results demonstrate a potential cost-efficient approach through which preliminary clinical data of possible biological effects are obtainable, prior to undertaking the major investment required for double-blind trials of a potential disease-modifying drug in PD. Trial registration. Clinicaltrials.gov NCT01174810. Funding. Cure Parkinson’s Trust. PMID:23728174

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

PubMed

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

2013-03-28

Non-invasive electrotherapy is commonly used for treatment of chronic low back pain. Evidence for efficacy of most electrotherapy modalities is weak or lacking. This study aims to execute a high-quality, double-blinded randomized controlled clinical trial comparing 1) H-Wave(®) Device stimulation plus usual care with 2) transcutaneous electrical nerve stimulation (TENS) plus usual care, and 3) Sham electrotherapy plus usual care to determine comparative efficacy for treatment of chronic non-specific low back pain patients. Chronic non-specific low back pain patients between ages of 18-65 years, with pain of at least 3 months duration and minimal current 5/10 VAS pain. Patients will have no significant signs or symptoms of lumbosacral nerve impingement, malignancy, spinal stenosis, or mood disorders. Double blind RCT with 3 arms and 38 subjects per arm. Randomization by permuted blocks of random length, stratified by Workers Compensation claim (yes vs. no), and use of opioids. The null hypothesis of this study is that there are no statistically significant differences in functional improvement between treatment types during and at the end of a 12-week week treatment period. Subjective data will be collected using Filemaker Pro™ database management collection tools. Objective data will be obtained through functional assessments. Data will be collected at enrollment and at 1, 4, 8, and 12 weeks for each participant by a blinded assessor. H-Wave(®) device stimulation (Intervention A) plus usual care, transcutaneous electrical nerve stimulation (TENS) (Intervention B) plus usual care, and sham electrotherapy plus usual care (control). Each treatment arm will have identical numbers of visits (4) and researcher contact time (approximately 15 hours). Oswestry Disability Index. Secondary measures include: Rowland Morris Instrument, VAS pain score, functional evaluation including strength when pushing and pulling, pain free range of motion in flexion and extension. Outcome measures assessed at baseline, 1, 4, 8, and 12 weeks. Treatment failure will be defined if patient terminates assigned treatment arm for non-efficacy or undergoes invasive procedure or other excluded cointerventions. Data will be analyzed using intention-to-treat analysis and adjusted for covariates related to LBP (e.g. age) as needed. Study strengths include complex randomization, treatment group allocation concealment, double blinding, controlling for co-interventions, rigorous inclusion criteria, assessment of compliance, plans for limiting dropout, identical assessment methods and timing for each treatment arm, and planned intention-to-treat analyses.

A randomised, double-blind trial comparing budesonide formulations and dosages for short-term treatment of eosinophilic oesophagitis

PubMed Central

Miehlke, Stephan; Hruz, Petr; Vieth, Michael; Bussmann, Christian; von Arnim, Ulrike; Bajbouj, Monther; Schlag, Christoph; Madisch, Ahmed; Fibbe, Christiane; Wittenburg, Henning; Allescher, Hans Dieter; Reinshagen, Max; Schubert, Stefan; Tack, Jan; Müller, Michaela; Krummenerl, Patrick; Arts, Joris; Mueller, Ralph; Dilger, Karin; Greinwald, Roland; Straumann, Alex

2016-01-01

Objective To investigate the efficacy and safety of two different budesonide formulations (effervescent tablet for orodispersible use (BET) and viscous suspension (BVS)) with different daily dosages for short-term treatment of eosinophilic oesophagitis (EoE). Design Adults with active EoE (n=76) randomly received 14 days’ treatment with either BET 2×1 mg/day (BET1, n=19) or BET 2×2 mg/day (BET2, n=19), or BVS 2×5 mL (0.4 mg/mL)/day (BVS, n=19) or placebo (n=19) in a double-blind, double-dummy fashion, with a 2-week follow-up. Primary end point was histological remission (mean of <16 eosinophils/mm2 hpf). Secondary end points included endoscopy score, dysphagia score, drug safety and patient's preference for drug formulation. Results Histological remission occurred in 100%, 94.7% and 94.7% of budesonide (BET1, BET2, BVS, respectively) and in 0% of placebo recipients (p<0.0001). The improvement in total endoscopic intensity score was significantly higher in the three budesonide groups compared with placebo. Dysphagia improved in all groups at the end of treatment; however, improvement of dysphagia persisted only in those treated with BET1 (p=0.0196 vs placebo). There were no serious adverse events. Local fungal infection (stained fungi) occurred in two patients of each budesonide group (10.5%). The effervescent tablet was preferred by 80% of patients. Conclusions BET or BVS was highly effective and safe for short-term treatment of EoE. The 1 mg (twice daily) dosage was equally effective as the 2 mg twice daily dosage. The majority of patients preferred the effervescent tablet formulation. ClinicalTrials.gov number NCT02280616; EudraCT number, 2009-016692-29. PMID:25792708

2-dimethylaminoethanol (Deanol) in Huntington's chorea.

PubMed

Caraceni, T A; Girotti, F; Celano, I; Parati, E; Balboni, L

1978-12-01

A double-blind crossover trial with 2-dimethylaminoethanol (Deanol), a possible precursor of brain acetylcholine, was carried out in nine patients with Huntington's chorea. It was found to be ineffective in inducing any alteration in hyperkinesia.

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

Antidepressant Efficacy of the Antimuscarinic Drug Scopolamine

PubMed Central

Furey, Maura L.; Drevets, Wayne C.

2010-01-01

Context The need for improved therapeutic agents that more quickly and effectively treat depression is critical. In a pilot study we evaluated the role of the cholinergic system in cognitive symptoms of depression and unexpectedly observed rapid reductions in depression severity following the administration of the antimuscarinic drug scopolamine hydrobromide (4 μg/kg intravenously) compared with placebo (P=.002). Subsequently a clinical trial was designed to assess more specifically the antidepressant efficacy of scopolamine. Objective To evaluate scopolamine as a potential antidepressant agent. Design Two studies were conducted: a double-blind, placebo-controlled, dose-finding study followed by a double-blind, placebo-controlled, crossover clinical trial. Setting The National Institute of Mental Health. Patients Currently depressed outpatients aged 18 to 50 years meeting DSM-IV criteria for recurrent major depressive disorder or bipolar disorder. Of 39 eligible patients, 19 were randomized and 18 completed the trial. Interventions Multiple sessions including intravenous infusions of placebo or scopolamine hydrobromide (4 μg/kg). Individuals were randomized to a placebo/ scopolamine or scopolamine/placebo sequence (series of 3 placebo sessions and series of 3 scopolamine sessions). Sessions occurred 3 to 5 days apart. Main Outcome Measures Psychiatric evaluations using the Montgomery-Asberg Depression Rating Scale and the Hamilton Anxiety Rating Scale were performed to assess antidepressant and antianxiety responses to scopolamine. Results The placebo/scopolamine group showed no significant change during placebo infusion vs baseline; reductions in depression and anxiety rating scale scores (P<.001 for both) were observed after the administration of scopolamine compared with placebo. The scopolamine/placebo group also showed reductions in depression and anxiety rating scale scores (P<.001 for both) after the administration of scopolamine, relative to baseline, and these effects persisted as they received placebo. In both groups, improvement was significant at the first evaluation after scopolamine administration (P≤.002). Conclusion Rapid, robust antidepressant responses to the antimuscarinic scopolamine occurred in currently depressed patients who predominantly had poor prognoses. PMID:17015814

Probiotic strain Lactobacillus plantarum 299v increases iron absorption from an iron-supplemented fruit drink: a double-isotope cross-over single-blind study in women of reproductive age.

PubMed

Hoppe, Michael; Önning, Gunilla; Berggren, Anna; Hulthén, Lena

2015-10-28

Iron deficiency is common, especially among young women. Adding probiotics to foods could be one way to increase iron absorption. The aim of this study was to test the hypothesis that non-haem iron absorption from a fruit drink is improved by adding Lactobacillus plantarum 299v (Lp299v). Iron absorption was studied in healthy women of reproductive age using a single-blind cross-over design in two trials applying the double-isotope (55Fe and 59Fe) technique. In Trial 1, iron absorption from a fruit drink containing 109 colony-forming units (CFU) Lp299v was compared with that from a control drink without Lp299v. Trial 2 had the same design but 1010 CFU were used. The test and control drinks contained approximately 5 mg of iron as ferrous lactate and were labelled with 59Fe (B) and 55Fe (A), respectively, and consumed on 4 consecutive days in the order AABB. Retention of the isotopes was measured with whole-body counting and in blood. Mean iron absorption from the drink containing 109 CFU Lp299v (28·6(sd 12·5) %) was significantly higher than from the control drink (18·5(sd 5·8) %), n 10, P<0·028). The fruit drink with 1010 CFU Lp299v gave a mean iron absorption of 29·1(sd 17·0) %, whereas the control drink gave an absorption of (20·1(sd 6·4) %) (n 11, P<0·080). The difference in iron absorption between the 109 CFU Lp299v and the 1010 CFU Lp299v drinks was not significant (P=0·941). In conclusion, intake of probiotics can increase iron absorption by approximately 50 % from a fruit drink having an already relatively high iron bioavailability.

Quantity and source of dietary protein influence metabolite production by gut microbiota and rectal mucosa gene expression: a randomized, parallel, double-blind trial in overweight humans.

PubMed

Beaumont, Martin; Portune, Kevin Joseph; Steuer, Nils; Lan, Annaïg; Cerrudo, Victor; Audebert, Marc; Dumont, Florent; Mancano, Giulia; Khodorova, Nadezda; Andriamihaja, Mireille; Airinei, Gheorghe; Tomé, Daniel; Benamouzig, Robert; Davila, Anne-Marie; Claus, Sandrine Paule; Sanz, Yolanda; Blachier, François

2017-10-01

Background: Although high-protein diets (HPDs) are frequently consumed for body-weight control, little is known about the consequences for gut microbiota composition and metabolic activity and for large intestine mucosal homeostasis. Moreover, the effects of HPDs according to the source of protein need to be considered in this context. Objective: The objective of this study was to evaluate the effects of the quantity and source of dietary protein on microbiota composition, bacterial metabolite production, and consequences for the large intestinal mucosa in humans. Design: A randomized, double-blind, parallel-design trial was conducted in 38 overweight individuals who received a 3-wk isocaloric supplementation with casein, soy protein, or maltodextrin as a control. Fecal and rectal biopsy-associated microbiota composition was analyzed by 16S ribosomal DNA sequencing. Fecal, urinary, and plasma metabolomes were assessed by 1 H-nuclear magnetic resonance. Mucosal transcriptome in rectal biopsies was determined with the use of microarrays. Results: HPDs did not alter the microbiota composition, but induced a shift in bacterial metabolism toward amino acid degradation with different metabolite profiles according to the protein source. Correlation analysis identified new potential bacterial taxa involved in amino acid degradation. Fecal water cytotoxicity was not modified by HPDs, but was associated with a specific microbiota and bacterial metabolite profile. Casein and soy protein HPDs did not induce inflammation, but differentially modified the expression of genes playing key roles in homeostatic processes in rectal mucosa, such as cell cycle or cell death. Conclusions: This human intervention study shows that the quantity and source of dietary proteins act as regulators of gut microbiota metabolite production and host gene expression in the rectal mucosa, raising new questions on the impact of HPDs on the large intestine mucosa homeostasis. This trial was registered at clinicaltrials.gov as NCT02351297. © 2017 American Society for Nutrition.

Rationale and Design of a Clinical Trial to Evaluate the Safety and Efficacy of Intracoronary Infusion of Allogeneic Human Cardiac Stem Cells in Patients With Acute Myocardial Infarction and Left Ventricular Dysfunction: The Randomized Multicenter Double-Blind Controlled CAREMI Trial (Cardiac Stem Cells in Patients With Acute Myocardial Infarction).

PubMed

Sanz-Ruiz, Ricardo; Casado Plasencia, Ana; Borlado, Luis R; Fernández-Santos, María Eugenia; Al-Daccak, Reem; Claus, Piet; Palacios, Itziar; Sádaba, Rafael; Charron, Dominique; Bogaert, Jan; Mulet, Miguel; Yotti, Raquel; Gilaberte, Immaculada; Bernad, Antonio; Bermejo, Javier; Janssens, Stefan; Fernández-Avilés, Franciso

2017-06-23

Stem cell therapy has increased the therapeutic armamentarium in the fight against ischemic heart disease and heart failure. The administration of exogenous stem cells has been investigated in patients suffering an acute myocardial infarction, with the final aim of salvaging jeopardized myocardium and preventing left ventricular adverse remodeling and functional deterioration. However, phase I and II clinical trials with autologous and first-generation stem cells have yielded inconsistent benefits and mixed results. In the search for new and more efficient cellular regenerative products, interesting cardioprotective, immunoregulatory, and cardioregenerative properties have been demonstrated for human cardiac stem cells. On the other hand, allogeneic cells show several advantages over autologous sources: they can be produced in large quantities, easily administered off-the-shelf early after an acute myocardial infarction, comply with stringent criteria for product homogeneity, potency, and quality control, and may exhibit a distinctive immunologic behavior. With a promising preclinical background, CAREMI (Cardiac Stem Cells in Patients With Acute Myocardial Infarction) has been designed as a double-blind, 2:1 randomized, controlled, and multicenter clinical trial that will evaluate the safety, feasibility, and efficacy of intracoronary delivery of allogeneic human cardiac stem cell in 55 patients with large acute myocardial infarction, left ventricular dysfunction, and at high risk of developing heart failure. This phase I/II clinical trial represents a novel experience in humans with allogeneic cardiac stem cell in a rigorously imaging-based selected group of acute myocardial infarction patients, with detailed safety immunologic assessments and magnetic resonance imaging-based efficacy end points. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02439398. © 2017 American Heart Association, Inc.

Apixaban for reduction in stroke and other ThromboemboLic events in atrial fibrillation (ARISTOTLE) trial: design and rationale.

PubMed

Lopes, Renato D; Alexander, John H; Al-Khatib, Sana M; Ansell, Jack; Diaz, Raphael; Easton, J Donald; Gersh, Bernard J; Granger, Christopher B; Hanna, Michael; Horowitz, John; Hylek, Elaine M; McMurray, John J V; Verheugt, Freek W A; Wallentin, Lars

2010-03-01

Atrial fibrillation (AF) is associated with increased risk of stroke that can be attenuated with vitamin K antagonists (VKAs). Vitamin K antagonist use is limited, in part, by the high incidence of complications when patients' international normalized ratios (INRs) deviate from the target range. The primary objective of ARISTOTLE is to determine if the factor Xa inhibitor, apixaban, is noninferior to warfarin at reducing the combined endpoint of stroke (ischemic or hemorrhagic) and systemic embolism in patients with AF and at least 1 additional risk factor for stroke. We have randomized 18,206 patients from over 1,000 centers in 40 countries. Patients were randomly assigned in a 1:1 ratio to receive apixaban or warfarin using a double-blind, double-dummy design. International normalized ratios are monitored and warfarin (or placebo) is adjusted aiming for a target INR range of 2 to 3 using a blinded, encrypted point-of-care device. Minimum treatment is 12 months, and maximum expected exposure is 4 years. Time to accrual of at least 448 primary efficacy events will determine treatment duration. The key secondary objectives are to determine if apixaban is superior to warfarin for the combined endpoint of stroke (ischemic or hemorrhagic) and systemic embolism, and for all-cause death. These will be tested after the primary objective using a closed test procedure. The noninferiority boundary is 1.38; apixaban will be declared noninferior if the 95% CI excludes the possibility that the primary outcome rate with apixaban is >1.38 times higher than with warfarin. ARISTOTLE will determine whether apixaban is noninferior or superior to warfarin in preventing stroke and systemic embolism; whether apixaban has particular benefits in the warfarin-naïve population; whether it reduces the combined rate of stroke, systemic embolism, and death; and whether it impacts bleeding.

Rationale and design of a randomized, double-blind, parallel-group study of terutroban 30 mg/day versus aspirin 100 mg/day in stroke patients: the prevention of cerebrovascular and cardiovascular events of ischemic origin with terutroban in patients with a history of ischemic stroke or transient ischemic attack (PERFORM) study.

PubMed

Bousser, M G; Amarenco, P; Chamorro, A; Fisher, M; Ford, I; Fox, K; Hennerici, M G; Mattle, H P; Rothwell, P M

2009-01-01

Ischemic stroke is the leading cause of mortality worldwide and a major contributor to neurological disability and dementia. Terutroban is a specific TP receptor antagonist with antithrombotic, antivasoconstrictive, and antiatherosclerotic properties, which may be of interest for the secondary prevention of ischemic stroke. This article describes the rationale and design of the Prevention of cerebrovascular and cardiovascular Events of ischemic origin with teRutroban in patients with a history oF ischemic strOke or tRansient ischeMic Attack (PERFORM) Study, which aims to demonstrate the superiority of the efficacy of terutroban versus aspirin in secondary prevention of cerebrovascular and cardiovascular events. The PERFORM Study is a multicenter, randomized, double-blind, parallel-group study being carried out in 802 centers in 46 countries. The study population includes patients aged > or =55 years, having suffered an ischemic stroke (< or =3 months) or a transient ischemic attack (< or =8 days). Participants are randomly allocated to terutroban (30 mg/day) or aspirin (100 mg/day). The primary efficacy endpoint is a composite of ischemic stroke (fatal or nonfatal), myocardial infarction (fatal or nonfatal), or other vascular death (excluding hemorrhagic death of any origin). Safety is being evaluated by assessing hemorrhagic events. Follow-up is expected to last for 2-4 years. Assuming a relative risk reduction of 13%, the expected number of primary events is 2,340. To obtain statistical power of 90%, this requires inclusion of at least 18,000 patients in this event-driven trial. The first patient was randomized in February 2006. The PERFORM Study will explore the benefits and safety of terutroban in secondary cardiovascular prevention after a cerebral ischemic event. Copyright 2009 S. Karger AG, Basel.

EFFECT of daily antiseptic body wash with octenidine on nosocomial primary bacteraemia and nosocomial multidrug-resistant organisms in intensive care units: design of a multicentre, cluster-randomised, double-blind, cross-over study

PubMed Central

Meißner, Anne; Hasenclever, Dirk; Brosteanu, Oana; Chaberny, Iris Freya

2017-01-01

Introduction Nosocomial infections are serious complications that increase morbidity, mortality and costs and could potentially be avoidable. Antiseptic body wash is an approach to reduce dermal micro-organisms as potential pathogens on the skin. Large-scale trials with chlorhexidine as the antiseptic agent suggest a reduction of nosocomial infection rates. Octenidine is a promising alternative agent which could be more effective against Gram-negative organisms. We hypothesise that daily antiseptic body wash with octenidine reduces the risk of intensive care unit (ICU)-acquired primary bacteraemia and ICU-acquired multidrug-resistant organisms (MDRO) in a standard care setting. Methods and analysis EFFECT is a controlled, cluster-randomised, double-blind study. The experimental intervention consists in using octenidine-impregnated wash mitts for the daily routine washing procedure of the patients. This will be compared with using placebo wash mitts. Replacing existing washing methods is the only interference into clinical routine. Participating ICUs are randomised in an AB/BA cross-over design. There are two 15-month periods, each consisting of a 3-month wash-out period followed by a 12-month intervention and observation period. Randomisation determines only the sequence in which octenidine-impregnated or placebo wash mitts are used. ICUs are left unaware of what mitts packages they are using. The two coprimary endpoints are ICU-acquired primary bacteraemia and ICU-acquired MDRO. Endpoints are defined based on individual ward-movement history and microbiological test results taken from the hospital information systems without need for extra documentation. Data on clinical symptoms of infection are not collected. EFFECT aims at recruiting about 45 ICUs with about 225 000 patient-days per year. Ethics and dissemination The study was approved by the ethics committee of the University of Leipzig (number 340/16-ek) in November 2016. Findings will be published in peer-reviewed journals. Trial registration number DRKS-ID: DRKS00011282. PMID:29122787

Pain Management after Laparoscopic Cholecystectomy-A Randomized Prospective Trial of Low Pressure and Standard Pressure Pneumoperitoneum

PubMed Central

Singla, Sanjeev; Mittal, Geeta; Raghav; Mittal, Rajinder K

2014-01-01

Background: Abdominal pain and shoulder tip pain after laparoscopic cholecystectomy are distressing for the patient. Various causes of this pain are peritoneal stretching and diaphragmatic irritation by high intra-abdominal pressure caused by pneumoperitoneum . We designed a study to compare the post operative pain after laparoscopic cholecystectomy at low pressure (7-8 mm of Hg) and standard pressure technique (12-14 mm of Hg). Aim : To compare the effect of low pressure and standard pressure pneumoperitoneum in post laparoscopic cholecystectomy pain . Further to study the safety of low pressure pneumoperitoneum in laparoscopic cholecystectomy. Settings and Design: A prospective randomised double blind study. Materials and Methods: A prospective randomised double blind study was done in 100 ASA grade I & II patients. They were divided into two groups -50 each. Group A patients underwent laparoscopic cholecystectomy with low pressure pneumoperitoneum (7-8 mm Hg) while group B underwent laparoscopic cholecystectomy with standard pressure pneumoperitoneum (12-13 mm Hg). Both the groups were compared for pain intensity, analgesic requirement and complications. Statistical Analysis: Demographic data and intraoperative complications were analysed using chi-square test. Frequency of pain, intensity of pain and analgesics consumption was compared by applying ANOVA test. Results: Post-operative pain score was significantly less in low pressure group as compared to standard pressure group. Number of patients requiring rescue analgesic doses was more in standard pressure group . This was statistically significant. Also total analgesic consumption was more in standard pressure group. There was no difference in intraoperative complications. Conclusion: This study demonstrates the use of simple expedient of reducing the pressure of pneumoperitoneum to 8 mm results in reduction in both intensity and frequency of post-operative pain and hence early recovery and better outcome.This study also shows that low pressure technique is safe with comparable rate of intraoperative complications. PMID:24701492

Dexmedetomidine as an adjuvant to bupivacaine in caudal analgesia in children

PubMed Central

Goyal, Vigya; Kubre, Jyotsna; Radhakrishnan, Krishnaprabha

2016-01-01

Context: Postoperative pain management is becoming an integral part of anesthesia care. Various techniques of pediatric pain relief have been designed among which the most commonly practiced is caudal epidural block. Several adjuvants have been used to prolong the duration of caudal analgesia such as clonidine, neostigmine, ketamine, opioids, and ephedrine. We have designed the study using dexmedetomidine as an adjuvant to assess analgesic efficacy, duration of postoperative analgesia, hemodynamic stability, postoperative sedation, and any adverse effects in children. Aims: The aim is to study the effects of dexmedetomidine as an adjuvant to bupivacaine in caudal analgesia in pediatric patients posted for infraumbilical surgeries. Settings and Design: This is a randomized, double-blind study in which effect of dexmedetomidine is studied when added to bupivacaine in the caudal epidural block. The observations are made intraoperatively for hemodynamic stability and postoperatively for the duration of analgesia. Subjects and Methods: This study was conducted in 100 children of American Society of Anesthesiologists physical status I and II, aged 2–10 years, undergoing elective infraumbilical surgeries. They were divided into two groups as follows: Group A: (0.25%) bupivacaine 1 ml/kg + normal saline (NS) 1 ml. Group B: (0.25%) bupivacaine 1 ml/kg + 1 μg/kg dexmedetomidine in 1 ml NS. As this study was double-blind, patients were randomly assigned to receive either (bupivacaine + saline) or (bupivacaine + dexmedetomidine) in each group. The patients were observed for hemodynamic stability, respiratory depression, and postoperative pain using face, legs, activity, cry, consolability (FLACC) pain scale for 24 h postoperatively. Statistical Analysis Used: Unpaired Student's t-test. Results: The mean duration of effective analgesia in Group A patients was 4.33 ± 0.98 h versus 9.88 ± 0.90 h in Group B patients. Likewise, the difference in mean FLACC score of both the groups was also statistically significant, 7.21 ± 0.76 and 6.49 ± 1.72 in Group A and Group B, respectively. Conclusion: Dexmedetomidine as adjuvant to Bupivacaine increases duration of caudal analgesia and improves hemodynamic stability without an increase in adverse effects in children undergoing infraumbilical surgeries. PMID:27212752

Methylphenidate, modafinil, and caffeine for cognitive enhancement in chess: A double-blind, randomised controlled trial.

PubMed

Franke, Andreas G; Gränsmark, Patrik; Agricola, Alexandra; Schühle, Kai; Rommel, Thilo; Sebastian, Alexandra; Balló, Harald E; Gorbulev, Stanislav; Gerdes, Christer; Frank, Björn; Ruckes, Christian; Tüscher, Oliver; Lieb, Klaus

2017-03-01

Stimulants and caffeine have been proposed for cognitive enhancement by healthy subjects. This study investigated whether performance in chess - a competitive mind game requiring highly complex cognitive skills - can be enhanced by methylphenidate, modafinil or caffeine. In a phase IV, randomized, double-blind, placebo-controlled trial, 39 male chess players received 2×200mg modafinil, 2×20mg methylphenidate, and 2×200mg caffeine or placebo in a 4×4 crossover design. They played twenty 15-minute games during two sessions against a chess program (Fritz 12; adapted to players' strength) and completed several neuropsychological tests. Marked substance effects were observed since all three substances significantly increased average reflection time per game compared to placebo resulting in a significantly increased number of games lost on time with all three treatments. Treatment effects on chess performance were not seen if all games (n=3059) were analysed. Only when controlling for game duration as well as when excluding those games lost on time, both modafinil and methylphenidate enhanced chess performance as demonstrated by significantly higher scores in the remaining 2876 games compared to placebo. In conjunction with results from neuropsychological testing we conclude that modifying effects of stimulants on complex cognitive tasks may in particular result from more reflective decision making processes. When not under time pressure, such effects may result in enhanced performance. Yet, under time constraints more reflective decision making may not improve or even have detrimental effects on complex task performance. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.