The placebo effect and its determinants in fibromyalgia: meta-analysis of randomised controlled trials.

Science.gov (United States)

Chen, Xi; Zou, Kun; Abdullah, Natasya; Whiteside, Nicola; Sarmanova, Aliya; Doherty, Michael; Zhang, Weiya

2017-07-01

The aims of this study were to determine whether placebo treatment in randomised controlled trials (RCTs) is effective for fibromyalgia and to identify possible determinants of the magnitude of any such placebo effect. A systematic literature search was undertaken for RCTs in people with fibromyalgia that included a placebo and/or a no-treatment (observation only or waiting list) control group. Placebo effect size (ES) for pain and other outcomes was measured as the improvement of each outcome from baseline divided by the standard deviation of the change from baseline. This effect was compared with changes in the no-treatment control groups. Meta-analysis was undertaken to combine data from different studies. Subgroup analysis was conducted to identify possible determinants of the placebo ES. A total of 3912 studies were identified from the literature search. After scrutiny, 229 trials met the inclusion criteria. Participants who received placebo in the RCTs experienced significantly better improvements in pain, fatigue, sleep quality, physical function, and other main outcomes than those receiving no treatment. The ES of placebo for pain relief was clinically moderate (0.53, 95%CI 0.48 to 0.57). The ES increased with increasing strength of the active treatment, increasing participant age and higher baseline pain severity, but decreased in RCTS with more women and with longer duration of fibromyalgia. In addition, placebo treatment in RCTs is effective in fibromyalgia. A number of factors (expected strength of treatment, age, gender, disease duration) appear to influence the magnitude of the placebo effect in this condition.

PACE - The first placebo controlled trial of paracetamol for acute low back pain: design of a randomised controlled trial

Directory of Open Access Journals (Sweden)

Day Richard O

2010-07-01

Full Text Available Abstract Background Clinical practice guidelines recommend that the initial treatment of acute low back pain (LBP should consist of advice to stay active and regular simple analgesics such as paracetamol 4 g daily. Despite this recommendation in all international LBP guidelines there are no placebo controlled trials assessing the efficacy of paracetamol for LBP at any dose or dose regimen. This study aims to determine whether 4 g of paracetamol daily (in divided doses results in a more rapid recovery from acute LBP than placebo. A secondary aim is to determine if ingesting paracetamol in a time-contingent manner is more effective than paracetamol taken when required (PRN for recovery from acute LBP. Methods/Design The study is a randomised double dummy placebo controlled trial. 1650 care seeking people with significant acute LBP will be recruited. All participants will receive advice to stay active and will be randomised to 1 of 3 treatment groups: time-contingent paracetamol dose regimen (plus placebo PRN paracetamol, PRN paracetamol (plus placebo time-contingent paracetamol or a double placebo study arm. The primary outcome will be time (days to recovery from pain recorded in a daily pain diary. Other outcomes will be pain intensity, disability, function, global perceived effect and sleep quality, captured at baseline and at weeks 1, 2, 4 and 12 by an assessor blind to treatment allocation. An economic analysis will be conducted to determine the cost-effectiveness of treatment from the health sector and societal perspectives. Discussion The successful completion of the trial will provide the first high quality evidence on the effectiveness of the use of paracetamol, a guideline endorsed treatment for acute LBP. Trail registration ACTRN12609000966291.

Efficacy and safety of liraglutide for overweight adult patients with type 1 diabetes and insufficient glycaemic control (Lira-1)

DEFF Research Database (Denmark)

Dejgaard, Thomas Fremming; Frandsen, Christian Seerup; Hansen, Tanja Stenbæk

2016-01-01

to insulin for overweight adult patients with type 1 diabetes. Methods We did a randomised, double-blind, placebo-controlled trial at Steno Diabetes Center (Gentofte, Denmark). Patients aged 18 years or older with type 1 diabetes, insufficient glycaemic control (HbA1c >8% [64 mmol/mol]), and overweight (BMI...

Antibiotics for bronchiectasis exacerbations in children: rationale and study protocol for a randomised placebo-controlled trial

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Chang Anne B

2012-08-01

Full Text Available Abstract Background Despite bronchiectasis being increasingly recognised as an important cause of chronic respiratory morbidity in both indigenous and non-indigenous settings globally, high quality evidence to inform management is scarce. It is assumed that antibiotics are efficacious for all bronchiectasis exacerbations, but not all practitioners agree. Inadequately treated exacerbations may risk lung function deterioration. Our study tests the hypothesis that both oral azithromycin and amoxicillin-clavulanic acid are superior to placebo at improving resolution rates of respiratory exacerbations by day 14 in children with bronchiectasis unrelated to cystic fibrosis. Methods We are conducting a bronchiectasis exacerbation study (BEST, which is a multicentre, randomised, double-blind, double-dummy, placebo-controlled, parallel group trial, in five centres (Brisbane, Perth, Darwin, Melbourne, Auckland. In the component of BEST presented here, 189 children fulfilling inclusion criteria are randomised (allocation-concealed to receive amoxicillin-clavulanic acid (22.5 mg/kg twice daily with placebo-azithromycin; azithromycin (5 mg/kg daily with placebo-amoxicillin-clavulanic acid; or placebo-azithromycin with placebo-amoxicillin-clavulanic acid for 14 days. Clinical data and a paediatric cough-specific quality of life score are obtained at baseline, at the start and resolution of exacerbations, and at day 14. In most children, blood and deep nasal swabs are also collected at the same time points. The primary outcome is the proportion of children whose exacerbations have resolved at day 14. The main secondary outcome is the paediatric cough-specific quality of life score. Other outcomes are time to next exacerbation; requirement for hospitalisation; duration of exacerbation; and spirometry data. Descriptive viral and bacteriological data from nasal samples and blood markers will also be reported. Discussion Effective, evidence-based management

Reappraisal of metformin efficacy in the treatment of type 2 diabetes: a meta-analysis of randomised controlled trials.

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Rémy Boussageon

Full Text Available BACKGROUND: The UK Prospective Diabetes Study showed that metformin decreases mortality compared to diet alone in overweight patients with type 2 diabetes mellitus. Since then, it has been the first-line treatment in overweight patients with type 2 diabetes. However, metformin-sulphonylurea bitherapy may increase mortality. METHODS AND FINDINGS: This meta-analysis of randomised controlled trials evaluated metformin efficacy (in studies of metformin versus diet alone, versus placebo, and versus no treatment; metformin as an add-on therapy; and metformin withdrawal against cardiovascular morbidity or mortality in patients with type 2 diabetes. We searched Medline, Embase, and the Cochrane database. Primary end points were all-cause mortality and cardiovascular death. Secondary end points included all myocardial infarctions, all strokes, congestive heart failure, peripheral vascular disease, leg amputations, and microvascular complications. Thirteen randomised controlled trials (13,110 patients were retrieved; 9,560 patients were given metformin, and 3,550 patients were given conventional treatment or placebo. Metformin did not significantly affect the primary outcomes all-cause mortality, risk ratio (RR=0.99 (95% CI: 0.75 to 1.31, and cardiovascular mortality, RR=1.05 (95% CI: 0.67 to 1.64. The secondary outcomes were also unaffected by metformin treatment: all myocardial infarctions, RR=0.90 (95% CI: 0.74 to 1.09; all strokes, RR=0.76 (95% CI: 0.51 to 1.14; heart failure, RR=1.03 (95% CI: 0.67 to 1.59; peripheral vascular disease, RR=0.90 (95% CI: 0.46 to 1.78; leg amputations, RR=1.04 (95% CI: 0.44 to 2.44; and microvascular complications, RR=0.83 (95% CI: 0.59 to 1.17. For all-cause mortality and cardiovascular mortality, there was significant heterogeneity when including the UK Prospective Diabetes Study subgroups (I(2=41% and 59%. There was significant interaction with sulphonylurea as a concomitant treatment for myocardial infarction (p=0

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

Directory of Open Access Journals (Sweden)

Bone Kerry M

2009-06-01

Full Text Available Abstract Background Assumptions underlying placebo controlled trials include that the placebo effect impacts on all study arms equally, and that treatment effects are additional to the placebo effect. However, these assumptions have recently been challenged, and different mechanisms may potentially be operating in the placebo and treatment arms. The objective of the current study was to explore the nature of placebo versus pharmacological effects by comparing predictors of the placebo response with predictors of the treatment response in a randomised, placebo-controlled trial of a phytotherapeutic combination for the treatment of menopausal symptoms. A substantial placebo response was observed but no significant difference in efficacy between the two arms. Methods A post hoc analysis was conducted on data from 93 participants who completed this previously published study. Variables at baseline were investigated as potential predictors of the response on any of the endpoints of flushing, overall menopausal symptoms and depression. Focused tests were conducted using hierarchical linear regression analyses. Based on these findings, analyses were conducted for both groups separately. These findings are discussed in relation to existing literature on placebo effects. Results Distinct differences in predictors were observed between the placebo and active groups. A significant difference was found for study entry anxiety, and Greene Climacteric Scale (GCS scores, on all three endpoints. Attitude to menopause was found to differ significantly between the two groups for GCS scores. Examination of the individual arms found anxiety at study entry to predict placebo response on all three outcome measures individually. In contrast, low anxiety was significantly associated with improvement in the active treatment group. None of the variables found to predict the placebo response was relevant to the treatment arm. Conclusion This study was a post hoc analysis

Effect of metformin on maternal and fetal outcomes in obese pregnant women (EMPOWaR): a randomised, double-blind, placebo-controlled trial.

Science.gov (United States)

Chiswick, Carolyn; Reynolds, Rebecca M; Denison, Fiona; Drake, Amanda J; Forbes, Shareen; Newby, David E; Walker, Brian R; Quenby, Siobhan; Wray, Susan; Weeks, Andrew; Lashen, Hany; Rodriguez, Aryelly; Murray, Gordon; Whyte, Sonia; Norman, Jane E

2015-10-01

Maternal obesity is associated with increased birthweight, and obesity and premature mortality in adult offspring. The mechanism by which maternal obesity leads to these outcomes is not well understood, but maternal hyperglycaemia and insulin resistance are both implicated. We aimed to establish whether the insulin sensitising drug metformin improves maternal and fetal outcomes in obese pregnant women without diabetes. We did this randomised, double-blind, placebo-controlled trial in antenatal clinics at 15 National Health Service hospitals in the UK. Pregnant women (aged ≥16 years) between 12 and 16 weeks' gestation who had a BMI of 30 kg/m(2) or more and normal glucose tolerance were randomly assigned (1:1), via a web-based computer-generated block randomisation procedure (block size of two to four), to receive oral metformin 500 mg (increasing to a maximum of 2500 mg) or matched placebo daily from between 12 and 16 weeks' gestation until delivery of the baby. Randomisation was stratified by study site and BMI band (30-39 vs ≥40 kg/m(2)). Participants, caregivers, and study personnel were masked to treatment assignment. The primary outcome was Z score corresponding to the gestational age, parity, and sex-standardised birthweight percentile of liveborn babies delivered at 24 weeks or more of gestation. We did analysis by modified intention to treat. This trial is registered, ISRCTN number 51279843. Between Feb 3, 2011, and Jan 16, 2014, inclusive, we randomly assigned 449 women to either placebo (n=223) or metformin (n=226), of whom 434 (97%) were included in the final modified intention-to-treat analysis. Mean birthweight at delivery was 3463 g (SD 660) in the placebo group and 3462 g (548) in the metformin group. The estimated effect size of metformin on the primary outcome was non-significant (adjusted mean difference -0·029, 95% CI -0·217 to 0·158; p=0·7597). The difference in the number of women reporting the combined adverse outcome of miscarriage

Nicotine patches in pregnant smokers: randomised, placebo controlled, multicentre trial of efficacy

Science.gov (United States)

Grangé, Gilles; Jacob, Nelly; Tanguy, Marie-Laure

2014-01-01

Objective To determine the efficacy of 16 hour nicotine patches among pregnant smokers, with the dose individually adjusted according to saliva cotinine levels (potential range 10-30 mg/day). Design Randomised, double blind, placebo controlled, parallel group, multicentre trial (Study of Nicotine Patch in Pregnancy, SNIPP) between October 2007 and January 2013. Setting 23 maternity wards in France. Participants 476 pregnant smokers aged more than 18 years and between 12 and 20 weeks’ gestation, who smoked at least five cigarettes a day. After exclusions, 402 women were randomised: 203 to nicotine patches and 199 to placebo patches. Data were available on 192 live births in each group. Interventions Nicotine and identical placebo patches were administered from quit day up to the time of delivery. Doses were adjusted to saliva cotinine levels when smoking to yield a substitution rate of 100%. Participants were assessed monthly and received behavioural smoking cessation support. Main outcome measures The primary outcomes were complete abstinence (self report confirmed by carbon monoxide level in expired air ≤8 ppm) from quit date to delivery, and birth weight. The secondary outcomes were point prevalence of abstinence, time to lapse (a few puffs) or relapse, and delivery and birth characteristics. All data were analysed on an intention to treat basis. Results Complete abstinence was achieved by 5.5% (n=11) of women in the nicotine patch group and 5.1% (n=10) in the placebo patch group (odds ratio 1.08, 95% confidence interval 0.45 to 2.60). The median time to the first cigarette smoked after target quit day was 15 days in both groups (interquartile range 13-18 in the nicotine patch group, 13-20 in the placebo patch group). The point prevalence abstinence ranged from 8% to 12.5% in the nicotine patch group and 8% to 9.5% in the placebo patch group without statistically significant differences. The nicotine substitution rate did not differ from 100%, and the self

Randomised controlled trial of homoeopathy versus placebo in perennial allergic rhinitis with overview of four trial series.

Science.gov (United States)

Taylor, M A; Reilly, D; Llewellyn-Jones, R H; McSharry, C; Aitchison, T C

To test the hypothesis that homoeopathy is a placebo by examining its effect in patients with allergic rhinitis and so contest the evidence from three previous trials in this series. Randomised, double blind, placebo controlled, parallel group, multicentre study. Four general practices and a hospital ear, nose, and throat outpatient department. 51 patients with perennial allergic rhinitis. Random assignment to an oral 30c homoeopathic preparation of principal inhalant allergen or to placebo. Changes from baseline in nasal inspiratory peak flow and symptom visual analogue scale score over third and fourth weeks after randomisation. Fifty patients completed the study. The homoeopathy group had a significant objective improvement in nasal airflow compared with the placebo group (mean difference 19.8 l/min, 95% confidence interval 10.4 to 29.1, P=0.0001). Both groups reported improvement in symptoms, with patients taking homoeopathy reporting more improvement in all but one of the centres, which had more patients with aggravations. On average no significant difference between the groups was seen on visual analogue scale scores. Initial aggravations of rhinitis symptoms were more common with homoeopathy than placebo (7 (30%) v 2 (7%), P=0.04). Addition of these results to those of three previous trials (n=253) showed a mean symptom reduction on visual analogue scores of 28% (10.9 mm) for homoeopathy compared with 3% (1.1 mm) for placebo (95% confidence interval 4.2 to 15.4, P=0.0007). The objective results reinforce earlier evidence that homoeopathic dilutions differ from placebo.

Treatment for the premenstrual syndrome with agnus castus fruit extract: prospective, randomised, placebo controlled study.

Science.gov (United States)

Schellenberg, R

2001-01-20

To compare the efficacy and tolerability of agnus castus fruit (Vitex agnus castus L extract Ze 440) with placebo for women with the premenstrual syndrome. Randomised, double blind, placebo controlled, parallel group comparison over three menstrual cycles. General medicine community clinics. 178 women were screened and 170 were evaluated (active 86; placebo 84). Mean age was 36 years, mean cycle length was 28 days, mean duration of menses was 4.5 days. Agnus castus (dry extract tablets) one tablet daily or matching placebo, given for three consecutive cycles. Main efficacy variable: change from baseline to end point (end of third cycle) in women's self assessment of irritability, mood alteration, anger, headache, breast fullness, and other menstrual symptoms including bloating. Secondary efficacy variables: changes in clinical global impression (severity of condition, global improvement, and risk or benefit) and responder rate (50% reduction in symptoms). Improvement in the main variable was greater in the active group compared with placebo group (Pagnus castus fruit is an effective and well tolerated treatment for the relief of symptoms of the premenstrual syndrome.

Ciprofloxacin DPI: a randomised, placebo-controlled, phase IIb efficacy and safety study on cystic fibrosis.

Science.gov (United States)

Dorkin, Henry L; Staab, Doris; Operschall, Elisabeth; Alder, Jeff; Criollo, Margarita

2015-01-01

Treatment of infective bronchitis involving Pseudomonas aeruginosa is a cornerstone of care in patients with cystic fibrosis (CF). This phase IIb, randomised, double-blind, placebo-controlled study assessed the efficacy and safety of ciprofloxacin dry powder for inhalation (DPI) in this population. Patients with CF, ≥12 years of age (N=286), were randomised to ciprofloxacin DPI (32.5 mg (n=93) or 48.75 mg (n=93)), or corresponding placebo (32.5 mg, n=65; 48.75 mg, n=35) twice daily for 28 days. The primary objective was the change in forced expiratory volume in 1 s (FEV1) from baseline (day 0) to end of treatment (day 29) in the intent-to-treat population for ciprofloxacin DPI compared with the corresponding placebo group. The primary effectiveness objective was not met; there were no significant differences in change in FEV1 between ciprofloxacin DPI and the corresponding placebo group for either dose (p=0.154). However, in pooled analyses, FEV1 decline from baseline to treatment end was significantly lower with ciprofloxacin DPI than with placebo (pooled data; p=0.02). Ciprofloxacin DPI showed positive effects on sputum bacterial load and quality of life, but these effects were not maintained at the 4-week follow-up. Ciprofloxacin DPI was well tolerated and there were no significant differences in type/incidence of treatment-emergent adverse events by treatment group (p=0.115). Further investigations are needed to determine the full scope of the beneficial effects of ciprofloxacin DPI for patients with CF. Clinicaltrials.gov NCT00645788; EudraCT 2008-008314-40.

Double-blind, placebo-controlled, randomised phase II trial of IH636 grape seed proanthocyanidin extract (GSPE) in patients with radiation-induced breast induration

International Nuclear Information System (INIS)

Brooker, Sonja; Martin, Susan; Pearson, Ann; Bagchi, Debasis; Earl, Judith; Gothard, Lone; Hall, Emma; Porter, Lucy; Yarnold, John

2006-01-01

Background and purpose: Tissue hardness (induration), pain and tenderness are common late adverse effects of curative radiotherapy for early breast cancer. The purpose of this study was to test the efficacy of IH636 grape seed proanthocyanidin extract (GSPE) in patients with tissue induration after high-dose radiotherapy for early breast cancer in a double-blind placebo-controlled randomised phase II trial. Patients and methods: Sixty-six eligible research volunteers with moderate or marked breast induration at a mean 10.8 years since radiotherapy for early breast cancer were randomised to active drug (n=44) or placebo (n=22). All patients were given grape seed proanthocyanidin extract (GSPE) 100 mg three times a day orally, or corresponding placebo capsules, for 6 months. The primary endpoint was percentage change in surface area (cm 2 ) of palpable breast induration measured at the skin surface 12 months after randomisation. Secondary endpoints included change in photographic breast appearance and patient self-assessment of breast hardness, pain and tenderness. Results: At 12 months post-randomisation, ≥50% reduction in surface area (cm 2 ) of breast induration was recorded in13/44 (29.5%) GSPE and 6/22 (27%) placebo group patients (NS). At 12 months post-randomisation, there was no significant difference between treatment and control groups in terms of external assessments of tissue hardness, breast appearance or patient self-assessments of breast hardness, pain or tenderness. Conclusions: The study failed to show efficacy of orally-adminstered GSPE in patients with breast induration following radiotherapy for breast cancer

The effects of resveratrol supplementation on cardiovascular risk factors in patients with non-alcoholic fatty liver disease: a randomised, double-blind, placebo-controlled study.

Science.gov (United States)

Faghihzadeh, Forouzan; Adibi, Payman; Hekmatdoost, Azita

2015-09-14

Non-alcoholic fatty liver disease (NAFLD) is usually associated with insulin resistance, central obesity, reduced glucose tolerance, type 2 diabetes mellitus and hypertriacylglycerolaemia. The beneficial effects of resveratrol on metabolic disorders have been shown previously. The aim of this study was to evaluate the effects of resveratrol supplementation on cardiovascular risk factors in patients with NAFLD. In this randomised double-blinded placebo-controlled clinical trial, fifty NAFLD patients were supplemented with either a 500-mg resveratrol capsule or a placebo capsule for 12 weeks. Both groups were advised to follow an energy-balanced diet and physical activity recommendations. resveratrol supplementation reduced alanine aminotransferase (ALT) and hepatic steatosis significantly more than placebo (P0·05). There were no significant changes in blood pressure, insulin resistance markers and TAG in either group (P>0·05). Our data have shown that 12-week supplementation of 500 mg resveratrol does not have any beneficial effect on anthropometric measurements, insulin resistance markers, lipid profile and blood pressure; however, it reduced ALT and hepatic steatosis in patients with NAFLD.

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

Science.gov (United States)

Thwaites, Guy E; Scarborough, Matthew; Szubert, Alexander; Nsutebu, Emmanuel; Tilley, Robert; Greig, Julia; Wyllie, Sarah A; Wilson, Peter; Auckland, Cressida; Cairns, Janet; Ward, Denise; Lal, Pankaj; Guleri, Achyut; Jenkins, Neil; Sutton, Julian; Wiselka, Martin; Armando, Gonzalez-Ruiz; Graham, Clive; Chadwick, Paul R; Barlow, Gavin; Gordon, N Claire; Young, Bernadette; Meisner, Sarah; McWhinney, Paul; Price, David A; Harvey, David; Nayar, Deepa; Jeyaratnam, Dakshika; Planche, Tim; Minton, Jane; Hudson, Fleur; Hopkins, Susan; Williams, John; Török, M Estee; Llewelyn, Martin J; Edgeworth, Jonathan D; Walker, A Sarah

2018-02-17

Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute

Eplerenone for early cardiomyopathy in Duchenne muscular dystrophy: a randomised, double-blind, placebo-controlled trial.

Science.gov (United States)

Raman, Subha V; Hor, Kan N; Mazur, Wojciech; Halnon, Nancy J; Kissel, John T; He, Xin; Tran, Tam; Smart, Suzanne; McCarthy, Beth; Taylor, Michael D; Jefferies, John L; Rafael-Fortney, Jill A; Lowe, Jeovanna; Roble, Sharon L; Cripe, Linda H

2015-02-01

Cardiomyopathy is a leading cause of death in patients with Duchenne muscular dystrophy and myocardial damage precedes decline in left ventricular systolic function. We tested the efficacy of eplerenone on top of background therapy in patients with Duchenne muscular dystrophy with early myocardial disease. In this randomised, double-blind, placebo-controlled trial, boys from three centres in the USA aged 7 years or older with Duchenne muscular dystrophy, myocardial damage by late gadolinium enhancement cardiac MRI and preserved ejection fraction received either eplerenone 25 mg or placebo orally, every other day for the first month and once daily thereafter, in addition to background clinician-directed therapy with either angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB). Computer-generated randomisation was done centrally using block sizes of four and six, and only the study statistician and the investigational pharmacy had the preset randomisation assignments. The primary outcome was change in left ventricular circumferential strain (Ecc) at 12 months, a measure of contractile dysfunction. Safety was established through serial serum potassium levels and measurement of cystatin C, a non-creatinine measure of kidney function. This trial is registered with ClinicalTrials.gov, number NCT01521546. Between Jan 26, 2012, and July 3, 2013, 188 boys were screened and 42 were enrolled. 20 were randomly assigned to receive eplerenone and 22 to receive placebo, of whom 20 in the eplerenone group and 20 in the placebo group completed baseline, 6-month, and 12-month visits. After 12 months, decline in left ventricular circumferential strain was less in those who received eplerenone than in those who received placebo (median ΔEcc 1·0 [IQR 0·3-2·2] vs 2·2 [1·3-3·1]; p=0·020). Cystatin C concentrations remained normal in both groups, and all non-haemolysed blood samples showed normal potassium concentrations. One 23-year-old patient in

Placebo response and remission rates in randomised trials of induction andmaintenance therapy for ulcerative colitis

NARCIS (Netherlands)

Jairath, Vipul; Zou, G. Y.; Parker, Claire E.; Macdonald, John K.; AlAmeel, Turki; Al Beshir, Mohammad; Almadi, Majid A.; Al-Taweel, Talal; Atkinson, Nathan S. S.; Biswas, Sujata; Chapman, Thomas; Dulai, Parambir S.; Glaire, Mark A.; Hoekman, Daniel R.; Koutsoumpas, Andreas; Minas, Elizabeth; Mosli, Mahmoud H.; Samaan, Mark; Khanna, Reena; Travis, Simon; D'Haens, Geert; Sandborn, William J.; Feagan, Brian G.

2017-01-01

Background It is important to minimize placebo rates in randomised controlled trials (RCTs) to efficiently detect treatment differences between interventions. Historically, high placebo rates have been observed in clinical trials of ulcerative colitis (UC). A better understanding of factors

Effects of empagliflozin on the urinary albumin-to-creatinine ratio in patients with type 2 diabetes and established cardiovascular disease: an exploratory analysis from the EMPA-REG OUTCOME randomised, placebo-controlled trial.

Science.gov (United States)

Cherney, David Z I; Zinman, Bernard; Inzucchi, Silvio E; Koitka-Weber, Audrey; Mattheus, Michaela; von Eynatten, Maximilian; Wanner, Christoph

2017-08-01

In a pooled analysis of short-term trials, short-term treatment with the sodium-glucose co-transporter-2 (SGLT2) inhibitor empagliflozin reduced albuminuria in patients with type 2 diabetes and prevalent albuminuria. In this exploratory analysis of the EMPA-REG OUTCOME trial, we report the short-term and long-term effects of empagliflozin on albuminuria in patients with type 2 diabetes and established cardiovascular disease, according to patients' baseline albuminuria status. In this randomised, double-blind, placebo-controlled trial at 590 sites in 42 countries, we randomly assigned patients aged 18 years and older with type 2 diabetes and established cardiovascular disease (1:1:1) to empagliflozin 10 mg, empagliflozin 25 mg, or placebo in addition to standard of care until at least 691 patients experienced an adjudicated event included in the primary outcome. We did the randomisation with a computer-generated random-sequence and interactive voice-response and web-response system, stratified by HbA 1c , BMI, region, and estimated glomerular filtration rate. Patients, investigators, and individuals involved in analysis of trial data were masked to treatment assignment. The primary and secondary efficacy and safety endpoints of this trial have been reported previously. Here, we report urinary albumin-to-creatinine ratio (UACR) data for the pooled empagliflozin group versus placebo according to albuminuria status at baseline (normoalbuminuria: UACR 300 mg/g). We did the analysis with mixed-model repeated measures including prespecified and post-hoc tests. This study is completed and registered with ClinicalTrials.gov, number NCT01131676. Between Sept 1, 2010, and April 22, 2013, we randomly assigned 7028 patients to treatment groups and 7020 patients received treatment. At baseline, we had UACR data for 6953 patients: 4171 (59% of treated patients; 1382 assigned to placebo and 2789 assigned to empagliflozin) had normoalbuminuria, 2013 (29%; 675 assigned to placebo

Evaluation of homoeopathic treatment in polycystic ovary syndrome: A single-blind, randomised, placebo-controlled pilot study

OpenAIRE

Chetna Deep Lamba; Praveen Oberai; Raj K Manchanda; Padmalaya Rath; P Hima Bindu; Maya Padmanabhan

2018-01-01

Background and Objectives: This study was conducted with the primary objective of evaluating efficacy of Homoeopathy in establishing the menstrual regularity with improvement in either ultrasonological findings or hirsutism/acne. The quality of life was also assessed using polycystic ovary syndrome questionnaire (PCOSQ). Materials and Methods: A single-blind, randomised, placebo-controlled pilot study was conducted from February 2014 to May 2015 at two research centres. The cases fulfilling t...

Impact of probiotic Saccharomyces boulardii on the gut microbiome composition in HIV-treated patients: A double-blind, randomised, placebo-controlled trial

OpenAIRE

Villar-Garc?a, Judit; G?erri-Fern?ndez, Robert; Moya, Andr?s; Gonz?lez, Alicia; Hern?ndez, Juan J.; Lerma, Elisabet; Guelar, Ana; Sorli, Luisa; Horcajada, Juan P.; Artacho, Alejandro; D?Auria, Giuseppe; Knobel, Hernando

2017-01-01

Dysbalance in gut microbiota has been linked to increased microbial translocation, leading to chronic inflammation in HIV-patients, even under effective HAART. Moreover, microbial translocation is associated with insufficient reconstitution of CD4+T cells, and contributes to the pathogenesis of immunologic non-response. In a double-blind, randomised, placebo-controlled trial, we recently showed that, compared to placebo, 12 weeks treatment with probiotic Saccharomyces boulardii significantly ...

Dulaglutide as add-on therapy to SGLT2 inhibitors in patients with inadequately controlled type 2 diabetes (AWARD-10): a 24-week, randomised, double-blind, placebo-controlled trial.

Science.gov (United States)

Ludvik, Bernhard; Frías, Juan P; Tinahones, Francisco J; Wainstein, Julio; Jiang, Honghua; Robertson, Kenneth E; García-Pérez, Luis-Emilio; Woodward, D Bradley; Milicevic, Zvonko

2018-05-01

Glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose co-transporter-2 (SGLT2) inhibitors improve glycaemic control and reduce bodyweight in patients with type 2 diabetes through different mechanisms. We assessed the safety and efficacy of the addition of the once-weekly GLP-1 receptor agonist dulaglutide to the ongoing treatment regimen in patients whose diabetes is inadequately controlled with SGLT2 inhibitors, with or without metformin. AWARD-10 was a phase 3b, double-blind, parallel-arm, placebo-controlled, 24-week study done at 40 clinical sites in Austria, Czech Republic, Germany, Hungary, Israel, Mexico, Spain, and the USA. Eligible adult patients (≥18 years) with inadequately controlled type 2 diabetes (HbA 1c concentration ≥7·0% [53 mmol/mol] and ≤9·5% [80 mmol/mol]), a BMI of 45 kg/m 2 or less, and taking stable doses (>3 months) of an SGLT2 inhibitor (with or without metformin) were randomly assigned (1:1:1) via an interactive web-response system to subcutaneous injections of either dulaglutide 1·5 mg, dulaglutide 0·75 mg, or placebo once per week for 24 weeks. Patients and investigators were masked to dulaglutide and placebo assignment, and those assessing outcomes were masked to study drug assignment. The primary objective was to test for the superiority of dulaglutide (1·5 mg or 0·75 mg) versus placebo for change in HbA 1c concentration from baseline at 24 weeks. All analyses were done in the intention-to-treat population, defined as all randomly assigned patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT02597049. Between Dec 7, 2015, and Feb 3, 2017, 424 patients were randomly assigned to dulaglutide 1·5 mg (n=142), dulaglutide 0·75 mg (n=142), and placebo (n=140). One patient in the dulaglutide 0·75 mg group was excluded from the analysis because they did not receive any dose of the study drug. The reduction in HbA 1c concentration at 24 weeks was larger

Study Protocol – Metabolic syndrome, vitamin D and bone status in South Asian women living in Auckland, New Zealand: A randomised, placebo-controlled, double-blind vitamin D intervention

Science.gov (United States)

von Hurst, Pamela R; Stonehouse, Welma; Matthys, Christophe; Conlon, Cathryn; Kruger, Marlena C; Coad, Jane

2008-01-01

Background The identification of the vitamin D receptor in the endocrine pancreas suggests a role for vitamin D in insulin secretion. There is also some limited evidence that vitamin D influences insulin resistance, and thus the early stages of the development of type 2 diabetes. Methods Eighty-four women of South Asian origin, living in Auckland, New Zealand, were randomised to receive either a supplement (4000IU 25(OH)D3 per day) or a placebo for 6 months. At baseline, all participants were vitamin D deficient (serum 25(OH)D3 1.93) and/or hyperinsulinaemic, hyperglycemic or had clinical signs of dislipidaemia. Changes in HOMA-IR, lipids, parathyroid hormone, calcium and bone markers were monitored at 3 months and 6 months. Discussion This randomised, controlled trial will be the first to investigate the effect of vitamin D supplementation on insulin resistance in non-diabetic subjects. It will subsequently contribute to the growing body of evidence about the role of vitamin D in metabolic syndrome.Registered clinical. Trial registration Registered clinical trial – Registration No. ACTRN12607000642482 PMID:18667086

Evaluation of homoeopathic treatment in polycystic ovary syndrome: A single-blind, randomised, placebo-controlled pilot study

Directory of Open Access Journals (Sweden)

Chetna Deep Lamba

2018-01-01

Full Text Available Background and Objectives: This study was conducted with the primary objective of evaluating efficacy of Homoeopathy in establishing the menstrual regularity with improvement in either ultrasonological findings or hirsutism/acne. The quality of life was also assessed using polycystic ovary syndrome questionnaire (PCOSQ. Materials and Methods: A single-blind, randomised, placebo-controlled pilot study was conducted from February 2014 to May 2015 at two research centres. The cases fulfilling the eligibility criteria were enrolled (n = 60 and randomised to either the homoeopathic intervention (HI (n = 30 or identical placebo (P (n = 30 with uniform lifestyle modification (LSM for 6 months. Results: The menstrual regularity with improvement in other signs/symptoms was observed in 60% of the cases (n = 18 in HI + LSM group and none (n = 0 in control group (P = 0.001. Statistically significant difference (P = 0.016 was observed in reduction of intermenstrual duration (from 76.1 ± 37.7 to 46.6 ± 38.7 days in HI + LSM in comparison to placebo + LSM group (from 93.0 ± 65.2 to 93.9 ± 96.2 days. In PCOSQ, also, significant improvement was observed in HI group in domains of weight, fertility, emotions and menstrual problems (P < 0.05 with no difference in body hair (P = 0.708. No change was observed in respect of improvement in the ultrasound findings. Pulsatilla was the most frequently indicated medicine (n = 12, 40%. Conclusion: HI along with LSM has shown promising outcome; further comparative study with standard conventional treatment on adequate sample size is desirable.

Early pregnancy probiotic supplementation with Lactobacillus rhamnosus HN001 may reduce the prevalence of gestational diabetes mellitus: a randomised controlled trial.

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Wickens, Kristin L; Barthow, Christine A; Murphy, Rinki; Abels, Peter R; Maude, Robyn M; Stone, Peter R; Mitchell, Edwin A; Stanley, Thorsten V; Purdie, Gordon L; Kang, Janice M; Hood, Fiona E; Rowden, Judy L; Barnes, Phillipa K; Fitzharris, Penny F; Crane, Julian

2017-03-01

The study aims to assess whether supplementation with the probiotic Lactobacillus rhamnosus HN001 (HN001) can reduce the prevalence of gestational diabetes mellitus (GDM). A double-blind, randomised, placebo-controlled parallel trial was conducted in New Zealand (NZ) (Wellington and Auckland). Pregnant women with a personal or partner history of atopic disease were randomised at 14-16 weeks' gestation to receive HN001 (6×109 colony-forming units) (n 212) or placebo (n 211) daily. GDM at 24-30 weeks was assessed using the definition of the International Association of Diabetes and Pregnancy Study Groups (IADPSG) (fasting plasma glucose ≥5·1 mmol/l, or 1 h post 75 g glucose level at ≥10 mmol/l or at 2 h ≥8·5 mmol/l) and NZ definition (fasting plasma glucose ≥5·5 mmol/l or 2 h post 75 g glucose at ≥9 mmol/l). All analyses were intention-to-treat. A total of 184 (87 %) women took HN001 and 189 (90 %) women took placebo. There was a trend towards lower relative rates (RR) of GDM (IADPSG definition) in the HN001 group, 0·59 (95 % CI 0·32, 1·08) (P=0·08). HN001 was associated with lower rates of GDM in women aged ≥35 years (RR 0·31; 95 % CI 0·12, 0·81, P=0·009) and women with a history of GDM (RR 0·00; 95 % CI 0·00, 0·66, P=0·004). These rates did not differ significantly from those of women without these characteristics. Using the NZ definition, GDM prevalence was significantly lower in the HN001 group, 2·1 % (95 % CI 0·6, 5·2), v. 6·5 % (95 % CI 3·5, 10·9) in the placebo group (P=0·03). HN001 supplementation from 14 to 16 weeks' gestation may reduce GDM prevalence, particularly among older women and those with previous GDM.

Efficacy of Intravenous Haloperidol on the duration of Delirium and Coma in Critically Ill Patients (Hope-ICU): a Randomised, Placebo-Controlled Trial

Science.gov (United States)

Page, Valerie J; Ely, E Wesley; Gates, Simon; Zhao, Xiao Bei; Alce, Timothy; Shintani, Ayumi; Jackson, Jim; Perkins, Gavin D; McAuley, Daniel F

2016-01-01

Background Delirium is frequently diagnosed in critically ill patients and is associated with poor clinical outcomes. Haloperidol is the most commonly used drug for delirium despite little evidence of its effectiveness. The aim of this study was to establish whether early treatment with haloperidol would decrease the time that survivors of critical illness spent in delirium or in coma. Methods We did this double-blind, placebo-controlled randomised trial in a general adult intensive care unit (ICU). Critically ill patients (≥18 years) needing mechanical ventilation within 72 of admission were enrolled. Patients were randomised (by an independent nurse, in 1:1 ratio, with permuted block size of four and six, using a centralised, secure web-based randomisation service) to receive haloperidol 2·5mgs or 0·9% saline placebo intravenously every 8 h irrespective of coma or delirium status. Study drug was discontinued on ICU discharge, once delirium-free and coma-free for 2 consecutive days, or after a maximum of 14 days treatment, which ever came first. Delirium was assessed using the confusion assessment method - for the ICU (CAM-ICU). The primary outcome was delirium-free and coma-free days, defined as the number of days in the first 14 days after randomisation during which the patient was alive without delirium and not in coma from any cause. Patients who died within the 14-day study period were recorded as having 0 days free of delirium and coma. ICU clinical and research staff and patients were masked to treatment throughout the study. Analyses were by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial Registry, number ISRCTN83567338. Findings 142 patients were randomised, 141 were included in the final analysis (71 haloperidol, 70 placebo). Patients in the haloperidol group spent about the same number of days alive, without delirium, and without coma as did patients in the placebo group (median 5 days [IQR 0

Effects of tonabersat on migraine with aura: a randomised, double-blind, placebo-controlled crossover study

DEFF Research Database (Denmark)

Hauge, Anne W; Asghar, Mohammed S; Schytz, Henrik W

2009-01-01

BACKGROUND: Migraine with aura is thought likely to be caused by cortical spreading depression (CSD). Tonabersat inhibits CSD, and we therefore investigated whether tonabersat has a preventive effect in migraine with aura. METHODS: In this randomised, double-blind, placebo-controlled crossover......, of whom 31 were included in the statistical analysis of efficacy. Median (IQR) attacks of aura were reduced from 3.2 (1.0-5.0) per 12 weeks on placebo to 1.0 (0-3.0) on tonabersat (p=0.01), whereas the other primary outcome measure, median migraine headache days with or without aura, was not significantly...... inhibitory effect on CSD. The results support the theory that auras are caused by CSD and that this phenomenon is not involved in attacks without aura. FUNDING: Minster Pharmaceuticals; Lundbeck Foundation....

3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes

DEFF Research Database (Denmark)

le Roux, Carel W; Astrup, Arne; Fujioka, Ken

2017-01-01

BACKGROUND: Liraglutide 3·0 mg was shown to reduce bodyweight and improve glucose metabolism after the 56-week period of this trial, one of four trials in the SCALE programme. In the 3-year assessment of the SCALE Obesity and Prediabetes trial we aimed to evaluate the proportion of individuals...... with prediabetes who were diagnosed with type 2 diabetes. METHODS: In this randomised, double-blind, placebo-controlled trial, adults with prediabetes and a body-mass index of at least 30 kg/m(2), or at least 27 kg/m(2) with comorbidities, were randomised 2:1, using a telephone or web-based system, to once...... that withdrawn individuals were not followed up after discontinuation. Liraglutide 3·0 mg might provide health benefits in terms of reduced risk of diabetes in individuals with obesity and prediabetes. FUNDING: Novo Nordisk, Denmark....

Prevention of preterm delivery with vaginal progesterone in women with preterm labour (4P): randomised double-blind placebo-controlled trial

NARCIS (Netherlands)

Martinez de Tejada, B.; Karolinski, A.; Ocampo, M. C.; Laterra, C.; Hösli, I.; Fernández, D.; Surbek, D.; Huespe, M.; Drack, G.; Bunader, A.; Rouillier, S.; López de Degani, G.; Seidenstein, E.; Prentl, E.; Antón, J.; Krähenmann, F.; Nowacki, D.; Poncelas, M.; Nassif, J. C.; Papera, R.; Tuma, C.; Espoile, R.; Tiberio, O.; Breccia, G.; Messina, A.; Peker, B.; Schinner, E.; Mol, B. W.; Kanterewicz, L.; Wainer, V.; Boulvain, M.; Othenin-Girard, V.; Bertolino, M. V.; Irion, O.; Tellenbach, M.; Vögele, E.; Azbar, R.; Raggi, A.; Birkenmaier, A.; Kann, S.; Scheibner, K.; Huguelet, M.; Amann, E.; Baumann, M.; Jakob, E.; Biedermann, K.; Hodel, M.; Fischer, T.; Pfau, K.; Estermann, K.

2015-01-01

To evaluate the effectiveness of 200 mg of daily vaginal natural progesterone to prevent preterm birth in women with preterm labour. Multicentre, randomised, double-blind, placebo-controlled trial. Twenty-nine centres in Switzerland and Argentina. A total of 385 women with preterm labour (24(0/7) to

Bronchodilator Efficacy of Single Doses of Indacaterol in Japanese Patients with COPD: A Randomised, Double-Blind, Placebo-Controlled Trial

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Motokazu Kato

Full Text Available ABSTRACT: Background: Indacaterol is an investigational, novel, inhaled once-daily ultra-long-acting beta-2 agonist for the treatment of chronic obstructive pulmonary disease (COPD. This study evaluated the 24-h bronchodilatory efficacy and safety of indacaterol in Japanese patients with COPD. Methods: This Phase-II, randomised, placebo-controlled, crossover study comprised four double-blind, single-dose treatment periods (washout between periods: 14-28 days. Japanese patients aged 40-75 years with moderate-to-severe COPD were randomised to receive single doses of indacaterol (150, 300, or 600 μg or placebo via a single-dose dry-powder inhaler. Efficacy (primary endpoint: standardised FEV1AUC22-24h and safety were assessed for 24 h post-dose in each treatment period. Results: Of the 50 patients randomised (92% male; mean age, 67.2 years, 45 completed the study. Standardised FEV1AUC22-24h was significantly higher for all indacaterol doses as compared with placebo, with clinically relevant differences of 130, 160, and 170 mL for 150, 300, and 600 μg, respectively (P < 0.001. The improvement in FEV1 was seen as early as 5 min post-dose with indacaterol and sustained for 24 h (P < 0.001 vs placebo at all time points. All indacaterol doses were well tolerated and showed no clinically meaningful effect on pulse rate, blood pressure, QTc interval, and laboratory parameters when compared with placebo. Conclusions: In the Japanese COPD population studied, single doses of indacaterol (150, 300, and 600 μg provided sustained 24-h bronchodilation, with onset of action within 5 min post-dose. All doses were well tolerated. These results are consistent with data from Caucasian populations. KEY WORDS: beta2-agonists, bronchodilator, COPD, efficacy, indacaterol

Intra-articular bupivacaine after joint arthroplasty: a systematic review and meta-analysis of randomised placebo-controlled studies

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Cui, Yang; Yang, Tuo; Zeng, Chao; Wei, Jie; Xie, Xi; Li, Liangjun; Ding, Xiang; Zhang, Yi; Lei, Guanghua

2016-01-01

Objectives To evaluate the efficacy and safety of intra-articular (IA) bupivacaine administered for pain relief after joint arthroplasty. Design Meta-analysis. Methods A systematic review was conducted to identify the randomised controlled trials using IA bupivacaine for postoperative pain relief from MEDLINE, Cochrane Library and EMBASE databases (up to October 2015). The standardised mean difference (SMD), the relative risk (RR) and their corresponding 95% CIs were calculated using the RevMan statistical software. Results A total of 11 randomised controlled trials were included. Statistically significant differences between IA bupivacaine and placebo were observed for the mean visual analogue scale (VAS) values (SMD −0.55; 95% CI −0.89 to −0.22; pbupivacaine after joint arthroplasty is effective for pain relief without increasing adverse effects. PMID:27406643

The gait and balance of patients with diabetes can be improved: a randomised controlled trial.

NARCIS (Netherlands)

Allet, L.; Armand, S.; Bie, R.A. de; Golay, A.; Monnin, D.; Aminian, K.; Staal, J.B.; Bruin, E.D. de

2010-01-01

AIMS/HYPOTHESIS: Gait characteristics and balance are altered in diabetic patients. Little is known about possible treatment strategies. This study evaluates the effect of a specific training programme on gait and balance of diabetic patients. METHODS: This was a randomised controlled trial (n=71)

Antidepressant Controlled Trial For Negative Symptoms In Schizophrenia (ACTIONS): a double-blind, placebo-controlled, randomised clinical trial.

Science.gov (United States)

Barnes, Thomas R E; Leeson, Verity C; Paton, Carol; Costelloe, Céire; Simon, Judit; Kiss, Noemi; Osborn, David; Killaspy, Helen; Craig, Tom K J; Lewis, Shôn; Keown, Patrick; Ismail, Shajahan; Crawford, Mike; Baldwin, David; Lewis, Glyn; Geddes, John; Kumar, Manoj; Pathak, Rudresh; Taylor, Simon

2016-04-01

Negative symptoms of schizophrenia represent deficiencies in emotional responsiveness, motivation, socialisation, speech and movement. When persistent, they are held to account for much of the poor functional outcomes associated with schizophrenia. There are currently no approved pharmacological treatments. While the available evidence suggests that a combination of antipsychotic and antidepressant medication may be effective in treating negative symptoms, it is too limited to allow any firm conclusions. To establish the clinical effectiveness and cost-effectiveness of augmentation of antipsychotic medication with the antidepressant citalopram for the management of negative symptoms in schizophrenia. A multicentre, double-blind, individually randomised, placebo-controlled trial with 12-month follow-up. Adult psychiatric services, treating people with schizophrenia. Inpatients or outpatients with schizophrenia, on continuing, stable antipsychotic medication, with persistent negative symptoms at a criterion level of severity. Eligible participants were randomised 1 : 1 to treatment with either placebo (one capsule) or 20 mg of citalopram per day for 48 weeks, with the clinical option at 4 weeks to increase the daily dosage to 40 mg of citalopram or two placebo capsules for the remainder of the study. The primary outcomes were quality of life measured at 12 and 48 weeks assessed using the Heinrich's Quality of Life Scale, and negative symptoms at 12 weeks measured on the negative symptom subscale of the Positive and Negative Syndrome Scale. No therapeutic benefit in terms of improvement in quality of life or negative symptoms was detected for citalopram over 12 weeks or at 48 weeks, but secondary analysis suggested modest improvement in the negative symptom domain, avolition/amotivation, at 12 weeks (mean difference -1.3, 95% confidence interval -2.5 to -0.09). There were no statistically significant differences between the two treatment arms over 48-week

Effect of candesartan on progression and regression of retinopathy in type 2 diabetes (DIRECT-Protect 2): a randomised placebo-controlled trial

DEFF Research Database (Denmark)

Sjolie, A.K.; Klein, R.; Porta, M.

2008-01-01

-group, placebo-controlled trial in 309 centres worldwide. We recruited normoalbuminuric, normotensive, or treated hypertensive people with type 2 diabetes with mild to moderately severe retinopathy and assigned them to candesartan 16 mg once a day or placebo. After a month, the dose was doubled to 32 mg once per...... day. Investigators and patients were unaware of the treatment allocation status. Progression of retinopathy was the primary endpoint, and regression was a secondary endpoint. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00252694. FINDINGS: 1905...... or changes in blood pressure during the trial. An overall change towards less severe retinopathy by the end of the trial was observed in the candesartan group (odds 1.17, 95% CI 1.05-1.30, p=0.003). Adverse events did not differ between the treatment groups. INTERPRETATION: Treatment with candesartan in type...

MD1003 (high-dose biotin) for the treatment of progressive multiple sclerosis: A randomised, double-blind, placebo-controlled study.

Science.gov (United States)

Tourbah, Ayman; Lebrun-Frenay, Christine; Edan, Gilles; Clanet, Michel; Papeix, Caroline; Vukusic, Sandra; De Sèze, Jerome; Debouverie, Marc; Gout, Olivier; Clavelou, Pierre; Defer, Gilles; Laplaud, David-Axel; Moreau, Thibault; Labauge, Pierre; Brochet, Bruno; Sedel, Frédéric; Pelletier, Jean

2016-11-01

Treatment with MD1003 (high-dose biotin) showed promising results in progressive multiple sclerosis (MS) in a pilot open-label study. To confirm the efficacy and safety of MD1003 in progressive MS in a double-blind, placebo-controlled study. Patients (n = 154) with a baseline Expanded Disability Status Scale (EDSS) score of 4.5-7 and evidence of disease worsening within the previous 2 years were randomised to 12-month MD1003 (100 mg biotin) or placebo thrice daily, followed by 12-month MD1003 for all patients. The primary endpoint was the proportion of patients with disability reversal at month 9, confirmed at month 12, defined as an EDSS decrease of ⩾1 point (⩾0.5 for EDSS 6-7) or a ⩾20% decrease in timed 25-foot walk time compared with the best baseline among screening or randomisation visits. A total of 13 (12.6%) MD1003-treated patients achieved the primary endpoint versus none of the placebo-treated patients (p = 0.005). MD1003 treatment also reduced EDSS progression and improved clinical impression of change compared with placebo. Efficacy was maintained over follow-up, and the safety profile of MD1003 was similar to that of placebo. MD1003 achieves sustained reversal of MS-related disability in a subset of patients with progressive MS and is well tolerated. © The Author(s), 2016.

RESPIRE 1: a phase III placebo-controlled randomised trial of ciprofloxacin dry powder for inhalation in non-cystic fibrosis bronchiectasis.

Science.gov (United States)

De Soyza, Anthony; Aksamit, Timothy; Bandel, Tiemo-Joerg; Criollo, Margarita; Elborn, J Stuart; Operschall, Elisabeth; Polverino, Eva; Roth, Katrin; Winthrop, Kevin L; Wilson, Robert

2018-01-01

We evaluated the efficacy and safety of ciprofloxacin dry powder for inhalation (DPI) in patients with non-cystic fibrosis bronchiectasis, two or more exacerbations in the previous year and pre-defined bacteria in sputum.In this phase III, double-blind, placebo-controlled trial, patients were randomised 2:1 to twice-daily ciprofloxacin DPI 32.5 mg or placebo in two treatment regimens consisting of on/off treatment cycles of 14 or 28 days for 48 weeks. The primary end-points were time to first exacerbation and frequency of exacerbations.A total of 416 patients were randomised to the 14-day on/off regimen (ciprofloxacin DPI (n=137) and placebo (n=68)) or the 28-day on/off regimen (ciprofloxacin DPI (n=141) and placebo (n=70)). Ciprofloxacin DPI 14 days on/off significantly prolonged time to first exacerbation versus pooled placebo (median time >336 versus 186 days; hazard ratio 0.53, 97.5% CI 0.36-0.80; p=0.0005) and reduced the frequency of exacerbations compared with matching placebo by 39% (mean number of exacerbations 0.6 versus 1.0; incidence rate ratio 0.61, 97.5% CI 0.40-0.91; p=0.0061). Outcomes for ciprofloxacin DPI 28 days on/off were not statistically significantly different from placebo. The safety profile of ciprofloxacin DPI was favourable.Ciprofloxacin DPI was well tolerated and has the potential to be an effective treatment option in non-cystic fibrosis bronchiectasis. Copyright ©ERS 2018.

Cophenylcaine spray vs. placebo in flexible nasendoscopy: a prospective double-blind randomised controlled trial

NARCIS (Netherlands)

Georgalas, C.; Sandhu, G.; Frosh, A.; Xenellis, J.

2005-01-01

Practices vary across the UK on the use of topical preparation prior to flexible fibreoptic nasendoscopy. In this double-blind study, we randomised 98 patients to receive cophenylcaine or placebo nasal spray before flexible nasendoscopy. A visual analogue scale (1-100) was used to record pain,

Novel glucose-sensing technology and hypoglycaemia in type 1 diabetes: a multicentre, non-masked, randomised controlled trial.

Science.gov (United States)

Bolinder, Jan; Antuna, Ramiro; Geelhoed-Duijvestijn, Petronella; Kröger, Jens; Weitgasser, Raimund

2016-11-05

Tight control of blood glucose in type 1 diabetes delays onset of macrovascular and microvascular diabetic complications; however, glucose levels need to be closely monitored to prevent hypoglycaemia. We aimed to assess whether a factory-calibrated, sensor-based, flash glucose-monitoring system compared with self-monitored glucose testing reduced exposure to hypoglycaemia in patients with type 1 diabetes. In this multicentre, prospective, non-masked, randomised controlled trial, we enrolled adult patients with well controlled type 1 diabetes (HbA 1c ≤58 mmol/mol [7·5%]) from 23 European diabetes centres. After 2 weeks of all participants wearing the blinded sensor, those with readings for at least 50% of the period were randomly assigned (1:1) to flash sensor-based glucose monitoring (intervention group) or to self-monitoring of blood glucose with capillary strips (control group). Randomisation was done centrally using the biased-coin minimisation method dependent on study centre and type of insulin administration. Participants, investigators, and study staff were not masked to group allocation. The primary outcome was change in time in hypoglycaemia (diabetes spent in hypoglycaemia. Future studies are needed to assess the effectiveness of this technology in patients with less well controlled diabetes and in younger age groups. Abbott Diabetes Care. Copyright © 2016 Elsevier Ltd. All rights reserved.

Veterinary homeopathy: meta-analysis of randomised placebo-controlled trials.

Science.gov (United States)

Mathie, Robert T; Clausen, Jürgen

2015-01-01

Meta-analysis of randomised controlled trials (RCTs) of veterinary homeopathy has not previously been undertaken. For all medical conditions and species collectively, we tested the hypothesis that the outcome of homeopathic intervention (treatment and/or prophylaxis, individualised and/or non-individualised) is distinguishable from corresponding intervention using placebos. All facets of the review, including literature search strategy, study eligibility, data extraction and assessment of risk of bias, were described in an earlier paper. A trial was judged to comprise reliable evidence if its risk of bias was low or was unclear in specific domains of assessment. Effect size was reported as odds ratio (OR). A trial was judged free of vested interest if it was not funded by a homeopathic pharmacy. Meta-analysis was conducted using the random-effects model, with hypothesis-driven sensitivity analysis based on risk of bias. Nine of 15 trials with extractable data displayed high risk of bias; low or unclear risk of bias was attributed to each of the remaining six trials, only two of which comprised reliable evidence without overt vested interest. For all N = 15 trials, pooled OR = 1.69 [95% confidence interval (CI), 1.12 to 2.56]; P = 0.01. For the N = 2 trials with suitably reliable evidence, pooled OR = 2.62 [95% CI, 1.13 to 6.05]; P = 0.02). Meta-analysis provides some very limited evidence that clinical intervention in animals using homeopathic medicines is distinguishable from corresponding intervention using placebos. The low number and quality of the trials hinders a more decisive conclusion. Copyright © 2014 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

Design and rationale of the WELCOME trial: A randomised, placebo controlled study to test the efficacy of purified long chainomega-3 fatty acid treatment in non-alcoholic fatty liver disease [corrected].

Science.gov (United States)

Scorletti, E; Bhatia, L; McCormick, K G; Clough, G F; Nash, K; Calder, P C; Byrne, C D

2014-03-01

Non-alcoholic fatty liver disease (NAFLD) represents a range of liver conditions from simple fatty liver to progressive end stage liver disease requiring liver transplantation. NAFLD is common in the population and in certain sub groups (e.g. type 2 diabetes) up to 70% of patients may be affected. NAFLD is not only a cause of end stage liver disease and hepatocellular carcinoma, but is also an independent risk factor for type 2 diabetes and cardiovascular disease. Consequently, effective treatments for NAFLD are urgently needed. The WELCOME study is testing the hypothesis that treatment with high dose purified long chain omega-3 fatty acids will have a beneficial effect on a) liver fat percentage and b) two histologically validated algorithmically-derived biomarker scores for liver fibrosis. In a randomised double blind placebo controlled trial, 103 participants with NAFLD were randomised to 15-18months treatment with either 4g/day purified long chain omega-3 fatty acids (Omacor) or 4g/day olive oil as placebo. Erythrocyte percentage DHA and EPA enrichment (a validated proxy for hepatic enrichment) was determined by gas chromatography. Liver fat percentage was measured in three discrete liver zones by magnetic resonance spectroscopy (MRS). We also measured body fat distribution, physical activity and a range of cardiometabolic risk factors. Recruitment started in January 2010 and ended in June 2011. We identified 178 potential participants, and randomised 103 participants who met the inclusion criteria. The WELCOME study was approved by the local ethics committee (REC: 08/H0502/165; www.clinicalTrials.gov registration number NCT00760513). Copyright © 2014 Elsevier Inc. All rights reserved.

A randomised, blinded, placebo-controlled trial in dementia patients continuing or stopping neuroleptics (the DART-AD trial.

Directory of Open Access Journals (Sweden)

Clive Ballard

2008-04-01

Full Text Available BACKGROUND: There have been increasing concerns regarding the safety and efficacy of neuroleptics in people with dementia, but there are very few long-term trials to inform clinical practice. The aim of this study was to determine the impact of long-term treatment with neuroleptic agents upon global cognitive decline and neuropsychiatric symptoms in patients with Alzheimer disease. METHODS AND FINDINGS: DESIGN: Randomised, blinded, placebo-controlled parallel two-group treatment discontinuation trial. SETTING: Oxfordshire, Newcastle and Gateshead, London and Edinburgh, United Kingdom. PARTICIPANTS: Patients currently prescribed the neuroleptics thioridazine, chlorpromazine, haloperidol trifluoperazine or risperidone for behavioural or psychiatric disturbance in dementia for at least 3 mo. INTERVENTIONS: Continue neuroleptic treatment for 12 mo or switch to an identical placebo. OUTCOME MEASURES: Primary outcome was total Severe Impairment Battery (SIB score. Neuropsychiatric symptoms were evaluated with the Neuropsychiatric Inventory (NPI. RESULTS: 165 patients were randomised (83 to continue treatment and 82 to placebo, i.e., discontinue treatment, of whom 128 (78% commenced treatment (64 continue/64 placebo. Of those, 26 were lost to follow-up (13 per arm, resulting in 51 patients per arm analysed for the primary outcome. There was no significant difference between the continue treatment and placebo groups in the estimated mean change in SIB scores between baseline and 6 mo; estimated mean difference in deterioration (favouring placebo -0.4 (95% confidence interval [CI] -6.4 to 5.5, adjusted for baseline value (p = 0.9. For neuropsychiatric symptoms, there was no significant difference between the continue treatment and placebo groups (n = 56 and 53, respectively in the estimated mean change in NPI scores between baseline and 6 mo; estimated mean difference in deterioration (favouring continue treatment -2.4 (95% CI -8.2 to 3.5, adjusted for

Single-dose intra-articular bupivacaine plus morphine after knee arthroscopic surgery: a meta-analysis of randomised placebo-controlled studies

Science.gov (United States)

Wang, Yi-lun; Zeng, Chao; Xie, Dong-xing; Yang, Ye; Wei, Jie; Yang, Tuo; Li, Hui; Lei, Guang-hua

2015-01-01

Objectives To evaluate the efficacy and safety of single-dose intra-articular bupivacaine plus morphine after knee arthroscopic surgery. Design Meta-analysis. Data sources and study eligibility criteria A comprehensive literature search, using Medline (1966–2014), the Cochrane Central Register of Controlled Trials and Embase databases, was conducted to identify randomised placebo-controlled trials that used a combination of single-dose intra-articular bupivacaine and morphine for postoperative pain relief. Results 12 articles were included in this meta-analysis. The mean visual analogue scale (VAS) scores of the bupivacaine plus morphine group were significantly lower than those of the placebo group (weighted mean difference (WMD) −1.75; 95% CI −2.16 to −1.33; pbupivacaine plus morphine group were also significantly lower than those of the placebo group (WMD −1.46; 95% CI −1.63 to −1.29; pbupivacaine plus morphine after knee arthroscopic surgery is effective for pain relief, and its short-term side effects remain similar to saline placebo. PMID:26078306

Effect of intravenous haloperidol on the duration of delirium and coma in critically ill patients (Hope-ICU): a randomised, double-blind, placebo-controlled trial.

Science.gov (United States)

Page, Valerie J; Ely, E Wesley; Gates, Simon; Zhao, Xiao Bei; Alce, Timothy; Shintani, Ayumi; Jackson, Jim; Perkins, Gavin D; McAuley, Daniel F

2013-09-01

Delirium is frequently diagnosed in critically ill patients and is associated with poor clinical outcomes. Haloperidol is the most commonly used drug for delirium despite little evidence of its effectiveness. The aim of this study was to establish whether early treatment with haloperidol would decrease the time that survivors of critical illness spent in delirium or coma. We did this double-blind, placebo-controlled randomised trial in a general adult intensive care unit (ICU). Critically ill patients (≥18 years) needing mechanical ventilation within 72 h of admission were enrolled. Patients were randomised (by an independent nurse, in 1:1 ratio, with permuted block size of four and six, using a centralised, secure web-based randomisation service) to receive haloperidol 2.5 mg or 0.9% saline placebo intravenously every 8 h, irrespective of coma or delirium status. Study drug was discontinued on ICU discharge, once delirium-free and coma-free for 2 consecutive days, or after a maximum of 14 days of treatment, whichever came first. Delirium was assessed using the confusion assessment method for the ICU (CAM-ICU). The primary outcome was delirium-free and coma-free days, defined as the number of days in the first 14 days after randomisation during which the patient was alive without delirium and not in coma from any cause. Patients who died within the 14 day study period were recorded as having 0 days free of delirium and coma. ICU clinical and research staff and patients were masked to treatment throughout the study. Analyses were by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial Registry, number ISRCTN83567338. 142 patients were randomised, 141 were included in the final analysis (71 haloperidol, 70 placebo). Patients in the haloperidol group spent about the same number of days alive, without delirium, and without coma as did patients in the placebo group (median 5 days [IQR 0-10] vs 6 days [0-11] days; p=0

The gait and balance of patients with diabetes can be improved: a randomised controlled trial

OpenAIRE

Allet, L.; Armand, S.; de Bie, R. A.; Golay, A.; Monnin, D.; Aminian, K.; Staal, J. B.; de Bruin, E. D.

2009-01-01

Aims/hypothesis Gait characteristics and balance are altered in diabetic patients. Little is known about possible treatment strategies. This study evaluates the effect of a specific training programme on gait and balance of diabetic patients. Methods This was a randomised controlled trial (n?=?71) with an intervention (n?=?35) and control group (n?=?36). The intervention consisted of physiotherapeutic group training including gait and balance exercises with function-orientated strengthening (...

A randomised, double blind, placebo-controlled, multi-centric parallel arm trial to assess the effects of homoeopathic medicines on chronic rhinosinusitis

Directory of Open Access Journals (Sweden)

Raj K Manchanda

2014-01-01

Full Text Available Background: Chronic rhinosinusitis (CRS is one of the most common illnesses interfering with patient′s quality of life and work. Observational studies conducted by the Council indicate positive outcome. This protocol has been developed to ascertain the usefulness of homoeopathic intervention in comparison with control group in a randomised control setting. Objectives: Primary objective is to evaluate the changes in TSS (Total Symptoms Score and SNOT-22 (Sino-nasal Outcome Test-22 within the two groups of the study (Homoeopathy + Placebo. Secondary objective is to evaluate changes in SNOT-22 at end of the trial, changes in Lund and Mackay staging of CT scan, rhinoscopy grading, absolute eosinophil count, global assessment by investigator and patient, and number of acute exacerbations of CRS (for frequency, duration and intensity as per TSS scale compared to placebo. Methods/Design: This is a randomised double blind, placebo-controlled, multi-centric parallel arm trial of 6 months (three months treatment and three months observation period with 14 days run-in period. The primary outcome is a composite of the changes in the TSS and SNOT-22 over 3 months from baseline with area under the curve and changes over 3 months in the Sinus Nasal Outcome Test 22 (SNOT-22 from baseline. Prescription shall be made as per the homoeopathic principles. Efficacy data will be analysed in the intention-to-treat population. Discussion: This trial will help to evaluate the efficacy of homoeopathic individualised treatment using LM-potencies versus placebo in patients suffering from CRS as per the homoeopathic dictum.

Increasing work-place healthiness with the probiotic Lactobacillus reuteri: A randomised, double-blind placebo-controlled study

Directory of Open Access Journals (Sweden)

Stan Vlaicu

2005-11-01

Full Text Available Abstract Background Short term illnesses, usually caused by respiratory or gastrointestinal diseases are disruptive to productivity and there is relatively little focus on preventative measures. This study examined the effect of the probiotic Lactobacillus reuteri protectis (ATCC55730 on its ability to improve work-place healthiness by reducing short term sick-leave caused by respiratory or gastrointestinal infections. Methods 262 employees at TetraPak in Sweden (day-workers and three-shift-workers that were healthy at study start were randomised in a double-blind fashion to receive either a daily dose of 108 Colony Forming Units of L. reuteri or placebo for 80 days. The study products were administered with a drinking straw. 181 subjects complied with the study protocol, 94 were randomised to receive L. reuteri and 87 received placebo. Results In the placebo group 26.4% reported sick-leave for the defined causes during the study as compared with 10.6% in the L. reuteri group (p L. reuteri group (p L. reuteri group(p

Angiotensin receptor blockade in acute stroke. The Scandinavian Candesartan Acute Stroke Trial: rationale, methods and design of a multicentre, randomised- and placebo-controlled clinical trial (NCT00120003)

DEFF Research Database (Denmark)

Sandset, Else Charlotte; Murray, Gordon; Boysen, Gudrun Margrethe

2010-01-01

AND DESIGN: The Scandinavian Candesartan Acute Stroke Trial is an international randomised, placebo-controlled, double-blind trial of candesartan in acute stroke. We plan to recruit 2500 patients presenting within 30 h of stroke (ischaemic or haemorrhagic) and with systolic blood pressure =140 mm......Hg. The recruited patients are randomly assigned to candesartan or placebo for 7-days (doses increasing from 4 to 16 mg once daily). Randomisation is performed centrally via a secure web interface. The follow-up period is 6-months. Patients are included from the following nine North-European countries: Norway...

The efficacy of Femal in women with premenstrual syndrome: a randomised, double-blind, parallel-group, placebo-controlled, multicentre study

DEFF Research Database (Denmark)

Gerhardsen, G.; Hansen, A.V.; Killi, M.

2008-01-01

Introduction: A double-blind, placebo-controlled, randomised, parallel-group, multicentre study was conducted to evaluate the effect of a pollen-based herbal medicinal product, Femal (R) (Sea-Band Ltd, Leicestershire, UK), on premenstrual sleep disturbances (PSD) in women with premenstrual syndrome...... as the main symptom cluster makes this herbal medicinal product a promising addition to the therapeutic arsenal for women with PMS Udgivelsesdato: 2008/6...

Efficacy of rasagiline in patients with the parkinsonian variant of multiple system atrophy: a randomised, placebo-controlled trial.

Science.gov (United States)

Poewe, Werner; Seppi, Klaus; Fitzer-Attas, Cheryl J; Wenning, Gregor K; Gilman, Sid; Low, Phillip A; Giladi, Nir; Barone, Paolo; Sampaio, Cristina; Eyal, Eli; Rascol, Olivier

2015-02-01

Multiple system atrophy is a complex neurodegenerative disorder for which no effective treatment exists. We aimed to assess the effect of rasagiline on symptoms and progression of the parkinsonian variant of multiple system atrophy. We did this randomised, double-blind, placebo-controlled trial between Dec 15, 2009, and Oct 20, 2011, at 40 academic sites specialised in the care of patients with multiple systemic atrophy across 12 countries. Eligible participants aged 30 years or older with possible or probable parkinsonian variant multiple system atrophy were randomly assigned (1:1), via computer-generated block randomisation (block size of four), to receive either rasagiline 1 mg per day or placebo. Randomisation was stratified by study centre. The investigators, study funder, and personnel involved in patient assessment, monitoring, analysis and data management were masked to group assignment. The primary endpoint was change from baseline to study end in total Unified Multiple System Atrophy Rating Scale (UMSARS) score (parts I and II). Analysis was by modified intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00977665. We randomly assigned 174 participants to the rasagiline group (n=84) or the placebo group (n=90); 21 (25%) patients in the rasagiline group and 15 (17%) in the placebo group withdrew from the study early. At week 48, patients in the rasagiline group had progressed by an adjusted mean of 7·2 (SE 1·2) total UMSARS units versus 7·8 (1·1) units in those in the placebo group. This treatment difference of -0·60 (95% CI -3·68 to 2·47; p=0·70) was not significant. 68 (81%) patients in the rasagiline group and 67 (74%) patients in the placebo group reported adverse events, and we recorded serious adverse events in 29 (35%) versus 23 (26%) patients. The most common adverse events in the rasagiline group were dizziness (n=10 [12%]), peripheral oedema (n=9 [11%]), urinary tract infections (n=9 [11%]), and orthostatic

Effect of adrenaline on survival in out-of-hospital cardiac arrest: A randomised double-blind placebo-controlled trial.

Science.gov (United States)

Jacobs, Ian G; Finn, Judith C; Jelinek, George A; Oxer, Harry F; Thompson, Peter L

2011-09-01

There is little evidence from clinical trials that the use of adrenaline (epinephrine) in treating cardiac arrest improves survival, despite adrenaline being considered standard of care for many decades. The aim of our study was to determine the effect of adrenaline on patient survival to hospital discharge in out of hospital cardiac arrest. We conducted a double blind randomised placebo-controlled trial of adrenaline in out-of-hospital cardiac arrest. Identical study vials containing either adrenaline 1:1000 or placebo (sodium chloride 0.9%) were prepared. Patients were randomly allocated to receive 1 ml aliquots of the trial drug according to current advanced life support guidelines. Outcomes assessed included survival to hospital discharge (primary outcome), pre-hospital return of spontaneous circulation (ROSC) and neurological outcome (Cerebral Performance Category Score - CPC). A total of 4103 cardiac arrests were screened during the study period of which 601 underwent randomisation. Documentation was available for a total of 534 patients: 262 in the placebo group and 272 in the adrenaline group. Groups were well matched for baseline characteristics including age, gender and receiving bystander CPR. ROSC occurred in 22 (8.4%) of patients receiving placebo and 64 (23.5%) who received adrenaline (OR=3.4; 95% CI 2.0-5.6). Survival to hospital discharge occurred in 5 (1.9%) and 11 (4.0%) patients receiving placebo or adrenaline respectively (OR=2.2; 95% CI 0.7-6.3). All but two patients (both in the adrenaline group) had a CPC score of 1-2. Patients receiving adrenaline during cardiac arrest had no statistically significant improvement in the primary outcome of survival to hospital discharge although there was a significantly improved likelihood of achieving ROSC. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Erythropoietin in amyotrophic lateral sclerosis: a multicentre, randomised, double blind, placebo controlled, phase III study.

Science.gov (United States)

Lauria, Giuseppe; Dalla Bella, Eleonora; Antonini, Giovanni; Borghero, Giuseppe; Capasso, Margherita; Caponnetto, Claudia; Chiò, Adriano; Corbo, Massimo; Eleopra, Roberto; Fazio, Raffaella; Filosto, Massimiliano; Giannini, Fabio; Granieri, Enrico; La Bella, Vincenzo; Logroscino, Giancarlo; Mandrioli, Jessica; Mazzini, Letizia; Monsurrò, Maria Rosaria; Mora, Gabriele; Pietrini, Vladimiro; Quatrale, Rocco; Rizzi, Romana; Salvi, Fabrizio; Siciliano, Gabriele; Sorarù, Gianni; Volanti, Paolo; Tramacere, Irene; Filippini, Graziella

2015-08-01

To assess the efficacy of recombinant human erythropoietin (rhEPO) in amyotrophic lateral sclerosis (ALS). Patients with probable laboratory-supported, probable or definite ALS were enrolled by 25 Italian centres and randomly assigned (1:1) to receive intravenous rhEPO 40,000 IU or placebo fortnightly as add-on treatment to riluzole 100 mg daily for 12 months. The primary composite outcome was survival, tracheotomy or >23 h non-invasive ventilation (NIV). Secondary outcomes were ALSFRS-R, slow vital capacity (sVC) and quality of life (ALSAQ-40) decline. Tolerability was evaluated analysing adverse events (AEs) causing withdrawal. The randomisation sequence was computer-generated by blocks, stratified by centre, disease severity (ALSFRS-R cut-off score of 33) and onset (spinal or bulbar). The main outcome analysis was performed in all randomised patients and by intention-to-treat for the entire population and patients stratified by severity and onset. The study is registered, EudraCT 2009-016066-91. We randomly assigned 208 patients, of whom 5 (1 rhEPO and 4 placebo) withdrew consent and 3 (placebo) became ineligible (retinal thrombosis, respiratory insufficiency, SOD1 mutation) before receiving treatment; 103 receiving rhEPO and 97 placebo were eligible for analysis. At 12 months, the annualised rate of death (rhEPO 0.11, 95% CI 0.06 to 0.20; placebo: 0.08, CI 0.04 to 0.17), tracheotomy or >23 h NIV (rhEPO 0.16, CI 0.10 to 0.27; placebo 0.18, CI 0.11 to 0.30) did not differ between groups, also after stratification by onset and ALSFRS-R at baseline. Withdrawal due to AE was 16.5% in rhEPO and 8.3% in placebo. No differences were found for secondary outcomes. RhEPO 40,000 IU fortnightly did not change the course of ALS. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Randomised, double-blinded, placebo-controlled, clinical trial of ozone therapy as treatment of sudden sensorineural hearing loss.

Science.gov (United States)

Ragab, A; Shreef, E; Behiry, E; Zalat, S; Noaman, M

2009-01-01

To investigate the safety and efficacy of ozone therapy in adult patients with sudden sensorineural hearing loss. Prospective, randomised, double-blinded, placebo-controlled, parallel group, clinical trial. Forty-five adult patients presented with sudden sensorineural hearing loss, and were randomly allocated to receive either placebo (15 patients) or ozone therapy (auto-haemotherapy; 30 patients). For the latter treatment, 100 ml of the patient's blood was treated immediately with a 1:1 volume, gaseous mixture of oxygen and ozone (from an ozone generator) and re-injected into the patient by intravenous infusion. Treatments were administered twice weekly for 10 sessions. The following data were recorded: pre- and post-treatment mean hearing gains; air and bone pure tone averages; speech reception thresholds; speech discrimination scores; and subjective recovery rates. Significant recovery was observed in 23 patients (77 per cent) receiving ozone treatment, compared with six (40 per cent) patients receiving placebo (p < 0.05). Mean hearing gains, pure tone averages, speech reception thresholds and subjective recovery rates were significantly better in ozone-treated patients compared with placebo-treated patients (p < 0.05). Ozone therapy is a significant modality for treatment of sudden sensorineural hearing loss; no complications were observed.

Multidisciplinary diabetes care with and without bariatric surgery in overweight people: a randomised controlled trial.

Science.gov (United States)

Wentworth, John M; Playfair, Julie; Laurie, Cheryl; Ritchie, Matthew E; Brown, Wendy A; Burton, Paul; Shaw, Jonathan E; O'Brien, Paul E

2014-07-01

Bariatric surgery improves glycaemia in obese people with type 2 diabetes, but its effects are uncertain in overweight people with this disease. We aimed to identify whether laparoscopic adjustable gastric band surgery can improve glucose control in people with type 2 diabetes who were overweight but not obese. We did an open-label, parallel-group, randomised controlled trial between Nov 1, 2009, and June 30, 2013, at one centre in Melbourne, Australia. Patients aged 18-65 years with type 2 diabetes and a BMI between 25 and 30 kg/m2 were randomly assigned (1:1), by computer-generated random sequence, to receive either multidisciplinary diabetes care plus laparoscopic adjustable gastric band surgery or multidisciplinary diabetes care alone. The primary outcome was diabetes remission 2 years after randomisation, defined as glucose concentrations of less than 7.0 mmol/L when fasting and less than 11.1 mmol/L 2 h after 75 g oral glucose, at least two days after stopping glucose-lowering drugs. Analysis was by intention to treat. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12609000286246. 51 patients were randomised to the multidisciplinary care plus gastric band group (n=25) or the multidisciplinary care only group (n=26), of whom 23 participants and 25 participants, respectively, completed follow-up to 2 years. 12 (52%) participants in the multidisciplinary care plus gastric band group and two (8%) participants in the multidisciplinary care only group achieved diabetes remission (difference in proportions 0.44, 95% CI 0.17-0.71; p=0.0012). One (4%) participant in the gastric band group needed revisional surgery and four others (17%) had a total of five episodes of food intolerance due to excessive adjustment of the band. When added to multidisciplinary care, laparoscopic adjustable gastric band surgery for overweight people with type 2 diabetes improves glycaemic control with an acceptable adverse event profile

Itopride in functional dyspepsia: results of two phase III multicentre, randomised, double-blind, placebo-controlled trials.

Science.gov (United States)

Talley, N J; Tack, J; Ptak, T; Gupta, R; Giguère, M

2008-06-01

Functional dyspepsia (FD) is a common disorder but there is currently little efficacious drug therapy. Itopride, a prokinetic approved in several countries, showed promising efficacy in FD in a phase IIb trial. The aim of this study was to test the efficacy and safety of this drug in FD. Two similar placebo-controlled clinical trials were conducted (International and North America). Males and females, 18-65 years old, with a diagnosis of FD (Rome II) and the absence (by upper endoscopy) of any relevant structural disease were recruited. All were negative for Helicobacter pylori and, if present, heartburn could not exceed one episode per week. Following screening, patients were randomised to itopride 100 mg three times daily or identical placebo. The co-primary end points were: (1) global patient assessment (GPA) of efficacy; and (2) Leeds Dyspepsia Questionnaire (LDQ). Symptoms were evaluated at weeks 2, 4 and 8. Secondary measures of efficacy included Nepean Dyspepsia Index (NDI) quality of life. The GPA responder rates at week 8 on itopride versus placebo were similar in both trials (45.2% vs 45.6% and 37.8 vs 35.4%, respectively; p = NS). A significant benefit of itopride over placebo was observed for the LDQ responders in the International (62% vs 52.7%, p = 0.04) but not the North American trial (46.9% vs 44.8%). The safety and tolerability profile were comparable with placebo, with the exception of prolactin elevations, which occurred more frequently on itopride (18/579) than placebo (1/591). In this population with FD, itopride did not show a difference in symptom response from placebo.

Minocycline as an adjunct for treatment-resistant depressive symptoms: A pilot randomised placebo-controlled trial.

Science.gov (United States)

Husain, Muhammad I; Chaudhry, Imran B; Husain, Nusrat; Khoso, Ameer B; Rahman, Raza R; Hamirani, Munir M; Hodsoll, John; Qurashi, Inti; Deakin, John Fw; Young, Allan H

2017-09-01

Evidence suggests that anti-inflammatory medication may be effective in the treatment of depressive symptoms. In this study, we aimed to investigate whether minocycline added to treatment as usual (TAU) for 3 months in patients with treatment-resistant depression will lead to an improvement in depressive symptoms. Multi-site, 12-week, double-blind, placebo-controlled, pilot trial of minocycline added to TAU for patients suffering from DSM-5 major depressive disorder, whose current episode has failed to respond to at least two antidepressants. The primary outcome measure was mean change in Hamilton Depression Rating Scale (HAMD-17) scores from baseline to week 12. Secondary measures were the Clinical Global Impression scale (CGI), Patient Health Questionnaire-9 (PHQ-9), the Generalised Anxiety Disorder scale (GAD-7) and EuroQoL (EQ-5D) quality-of-life questionnaire. Side-effect checklists were also used. Minocycline was started at 100 mg once daily (OD) and increased to 200 mg after 2 weeks. A total of 41 participants were randomised, with 21 in the minocycline group and 20 in the placebo group. A large decrease in HAMD scores was observed in the minocycline group compared to the placebo group (standardised effect size (ES) -1.21, p minocycline group also showed a large improvement compared with placebo (odds ratio (OR): 17.6, p minocycline leads to improvement in symptoms of treatment-resistant depression. However, our findings require replication in a larger sample. ClinicalTrials.gov identifier: NCT02263872, registered October 2014.

Penicillin for acute sore throat : randomised double blind trial of seven days versus three days treatment or placebo in adults

NARCIS (Netherlands)

Zwart, S; Sachs, APE; Ruijs, GJHM; Gubbels, JW; Hoes, AW; de Melker, RA

2000-01-01

Objective To assess whether treatment with penicillin for three days and the traditional treatment for seven days were equally as effective at accelerating resolution of symptoms in patients with sore throat compared with placebo. Design Randomised double blind placebo controlled trial. Setting 43

Efficacy of physiotherapy management of knee joint osteoarthritis: a randomised, double blind, placebo controlled trial

Science.gov (United States)

Bennell, K; Hinman, R; Metcalf, B; Buchbinder, R; McConnell, J; McColl, G; Green, S; Crossley, K

2005-01-01

Objective: To determine whether a multimodal physiotherapy programme including taping, exercises, and massage is effective for knee osteoarthritis, and if benefits can be maintained with self management. Methods: Randomised, double blind, placebo controlled trial; 140 community volunteers with knee osteoarthritis participated and 119 completed the trial. Physiotherapy and placebo interventions were applied by 10 physiotherapists in private practices for 12 weeks. Physiotherapy included exercise, massage, taping, and mobilisation, followed by 12 weeks of self management. Placebo was sham ultrasound and light application of a non-therapeutic gel, followed by no treatment. Primary outcomes were pain measured by visual analogue scale and patient global change. Secondary measures included WOMAC, knee pain scale, SF-36, assessment of quality of life index, quadriceps strength, and balance test. Results: Using an intention to treat analysis, physiotherapy and placebo groups showed similar pain reductions at 12 weeks: –2.2 cm (95% CI, –2.6 to –1.7) and –2.0 cm (–2.5 to –1.5), respectively. At 24 weeks, pain remained reduced from baseline in both groups: –2.1 (–2.6 to –1.6) and –1.6 (–2.2 to –1.0), respectively. Global improvement was reported by 70% of physiotherapy participants (51/73) at 12 weeks and by 59% (43/73) at 24 weeks. Similarly, global improvement was reported by 72% of placebo participants (48/67) at 12 weeks and by 49% (33/67) at 24 weeks (all p>0.05). Conclusions: The physiotherapy programme tested in this trial was no more effective than regular contact with a therapist at reducing pain and disability. PMID:15897310

Niacin therapy and the risk of new-onset diabetes: a meta-analysis of randomised controlled trials.

Science.gov (United States)

Goldie, Christina; Taylor, Allen J; Nguyen, Peter; McCoy, Cody; Zhao, Xue-Qiao; Preiss, David

2016-02-01

Previous studies have suggested that niacin treatment raises glucose levels in patients with diabetes and may increase the risk of developing diabetes. We undertook a meta-analysis of published and unpublished data from randomised trials to confirm whether an association exists between niacin and new-onset diabetes. We searched Medline, EMBASE and the Cochrane Central Register of Controlled Trials, from 1975 to 2014, for randomised controlled trials of niacin primarily designed to assess its effects on cardiovascular endpoints and cardiovascular surrogate markers. We included trials with ≥50 non-diabetic participants and average follow-up of ≥24 weeks. Published data were tabulated and unpublished data sought from investigators. We calculated risk ratios (RR) for new-onset diabetes with random-effects meta-analysis. Heterogeneity between trials was assessed using the I(2) statistic. In 11 trials with 26 340 non-diabetic participants, 1371 (725/13 121 assigned niacin; 646/13 219 assigned control) were diagnosed with diabetes during a weighted mean follow-up of 3.6 years. Niacin therapy was associated with a RR of 1.34 (95% CIs 1.21 to 1.49) for new-onset diabetes, with limited heterogeneity between trials (I(2)=0.0%, p=0.87). This equates to one additional case of diabetes per 43 (95% CI 30 to 70) initially non-diabetic individuals who are treated with niacin for 5 years. Results were consistent regardless of whether participants received background statin therapy (p for interaction=0.88) or combined therapy with laropiprant (p for interaction=0.52). Niacin therapy is associated with a moderately increased risk of developing diabetes regardless of background statin or combination laropiprant therapy. 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/

Theobromine for the treatment of persistent cough: a randomised, multicentre, double-blind, placebo-controlled clinical trial.

Science.gov (United States)

Morice, Alyn H; McGarvey, Lorcan; Pavord, Ian D; Higgins, Bernard; Chung, Kian Fan; Birring, Surinder S

2017-07-01

To investigate the effect of BC1036 on health-related quality of life (QOL) in subjects with persistent cough. The secondary objective was to investigate the effect of BC1036 on subjective cough severity. This was a randomised, multicentre, double-blind, placebo-controlled, parallel-group study in 289 subjects with persistent cough. Subjects received BC1036 or placebo twice daily for 14 days. The primary endpoint comprised cough-related QOL assessed using the validated Leicester Cough Questionnaire (LCQ) at Day 14. Secondary endpoints comprised the LCQ scores at Day 7 and Day 28, cough severity VAS scores at each visit and pulmonary function tests. At baseline, mean total LCQ score in the BC1036 group was lower (i.e., worse QOL) than placebo (P<0.001), indicating significant between-group heterogeneity. Mean baseline-adjusted change in LCQ score at Day 14 was greater for BC1036 [mean (SD) 2.4±3.5] compared to placebo [mean (SD) score 2.2±3.0], but did not reach statistical significance (P=0.60). Mean cough severity VAS score decreased to a greater extent in the BC1036 group compared to placebo, but again the results were not statistically significant (-12.2±23.28 in BC1036 group and -11.0±21.34 in placebo group at Day 14, P=0.688). There was no significant change in pulmonary function measurements. The adverse event (AE) profile was similar in both groups. This study showed that BC1036 was well tolerated and, although the primary endpoint did not achieve statistical significance, the magnitude of improvement was greater with BC1036 compared to placebo with respect to improving QOL and reducing cough severity. ClinicalTrials.gov: NCT01656668.

Participant experiences from chronic administration of a multivitamin versus placebo on subjective health and wellbeing: a double-blind qualitative analysis of a randomised controlled trial

Directory of Open Access Journals (Sweden)

Sarris Jerome

2012-12-01

Full Text Available Abstract Background While many randomised controlled trials have been conducted on multivitamins, to our knowledge no qualitative research exploring the subjective experience of taking a multivitamin during a clinical trial has been reported. Methods Semi-structured and open-ended written questions were incorporated into a 16-week double-blind, randomised, placebo-controlled, parallel groups trial of once-daily multivitamin administration. At the final study visit (week 16, three open-ended questions were posed to elucidate any positive, negative or unusual experiences from taking either the multivitamin or matched placebo. Qualitative thematic analysis was undertaken by researchers who were blind as to treatment condition of participants, and triangulation (independent analysis from three researchers was employed to ensure methodological rigour. Participant’s experiences were categorised as “positive” or “negative” and a Chi Square analysis was then applied to each of the experiential themes, to compare experiences between the multivitamin and placebo groups, (subdividing the groups by gender. Usual experiences were categorised and discussed separately. Results Of the 182 participants enrolled, 116 completed the study and qualitative data were available from 114 participants. Thematic analysis revealed significant effects in favour of the multivitamin over placebo for participants experiencing increased energy levels (p=.022 and enhanced mood (p=.027. The beneficial effect on energy levels was particularly evident among female participants. A trend was found for participants reporting better sleep in the multivitamin over placebo. The multivitamin and placebo groups did not significantly differ in perceived positive or negative effects in areas relating to other aspects of mental function or physical health. No significant negative effects were revealed, although there was a non-significant trend for more people in the multivitamin

Elevated serum magnesium associated with SGLT2 inhibitor use in type 2 diabetes patients: a meta-analysis of randomised controlled trials.

Science.gov (United States)

Tang, Huilin; Zhang, Xi; Zhang, Jingjing; Li, Yufeng; Del Gobbo, Liana C; Zhai, Suodi; Song, Yiqing

2016-12-01

By analysing available evidence from randomised controlled trials (RCTs), we aimed to examine whether and to what extent sodium-glucose cotransporter 2 (SGLT2) inhibitors affect serum electrolyte levels in type 2 diabetes patients. We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL) and ClinicalTrials.gov up to 24 May 2016 for published RCTs of SGLT2 inhibitors that reported changes in serum electrolyte levels. Weighted mean differences (WMD) between each SGLT2 inhibitor and placebo were calculated using a random-effects model. Dose-dependent relationships for each SGLT2 inhibitor were evaluated using meta-regression analysis. Eighteen eligible RCTs, including 15,309 patients and four SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin and ipragliflozin) were evaluated. In patients without chronic kidney disease, each SGLT2 inhibitor significantly increased serum magnesium levels compared with placebo (canagliflozin: WMD 0.06 mmol/l for 100 mg and 0.09 mmol/l for 300 mg; dapagliflozin: WMD 0.1 mmol/l for 10 mg; empagliflozin: WMD 0.04 mmol/l for 10 mg and 0.07 mmol/l for 25 mg; and ipragliflozin: WMD 0.05 mmol/l for 50 mg). Canagliflozin increased serum magnesium in a linear dose-dependent manner (p = 0.10). Serum phosphate was significantly increased by dapagliflozin. Serum sodium appeared to significantly differ by SGLT2 inhibitor type. No significant changes in serum calcium and potassium were observed. Findings were robust after including trials involving patients with chronic kidney disease. SGLT2 inhibitors marginally increased serum magnesium levels in type 2 diabetes patients indicating a drug class effect. Further investigations are required to examine the clinical significance of elevated magnesium levels in individuals with type 2 diabetes.

Supplementation of standard antibiotic therapy with oral probiotics for bacterial vaginosis and aerobic vaginitis: a randomised, double-blind, placebo-controlled trial.

Science.gov (United States)

Heczko, Piotr B; Tomusiak, Anna; Adamski, Paweł; Jakimiuk, Artur J; Stefański, Grzegorz; Mikołajczyk-Cichońska, Aleksandra; Suda-Szczurek, Magdalena; Strus, Magdalena

2015-12-03

This multicentre, randomised, double-blind, placebo-controlled trial was performed to determine whether the use of oral probiotic preparation (prOVag®) containing three Lactobacillus strains together with standard metronidazole treatment and also targeted antibiotic treatment (following the failure of metronidazole therapy) could reduce the recurrence rates of bacterial vaginosis (BV) and aerobic vaginitis (AV). Patients at private gynaecological clinics in Poland with histories of recurrent BV/AV and current symptoms were randomly allocated to receive metronidazole and probiotic or placebo, and assessed monthly on visits II and III-V. The total number of study visits was 5-6 (I, II, II bis - if applicable, III, IV, V). One probiotic or placebo capsule was administered with metronidazole/targeted antibiotic twice daily for 10 days; during follow up, patients took one capsule daily for 10 days perimenstrually. Clinical examination and vaginal swabbing were performed at each visit. Primary outcomes were clinical or microbiological BV/AV recurrence and probiotic safety. Secondary outcomes were vaginal pH, Nugent score, and Lactobacillus counts in the vaginal microbiota. Safety analysis was performed in 578 (probiotic, n = 285; placebo, n = 293) 18-50-year-old women who were randomised. BV/AV was confirmed microbiologically in 241 (probiotic, n = 118; placebo, n = 123) participants, who continued the trial. Data from 154 (probiotic, n = 73; placebo, n = 81) participants who completed the study were analysed to determine the efficacy of prOVag. Additional analyses included 37 (probiotic, n = 22; placebo, n = 15) participants who received targeted antibiotics and probiotics or placebo. prOVag lengthened the time to clinical relapse of BV/AV symptoms up to 51 % (p vaginal pH and Nugent score, and increased vaginal Lactobacillus counts following standard treatment. This study demonstrated that oral probiotics lengthened remission in

Effectiveness of Lactobacillus helveticus and Lactobacillus rhamnosus for the management of antibiotic-associated diarrhoea in healthy adults: a randomised, double-blind, placebo-controlled trial.

Science.gov (United States)

Evans, Malkanthi; Salewski, Ryan P; Christman, Mary C; Girard, Stephanie-Anne; Tompkins, Thomas A

2016-07-01

Broad-spectrum antibiotic use can disrupt the gastrointestinal microbiota resulting in diarrhoea. Probiotics may be beneficial in managing this type of diarrhoea. The aim of this 10-week randomised, double-blind, placebo-controlled, parallel study was to investigate the effect of Lactobacillus helveticus R0052 and Lactobacillus rhamnosus R0011 supplementation on antibiotic-associated diarrhoea in healthy adults. Subjects were randomised to receive 1 week of amoxicillin-clavulanic acid (875 mg/125 mg) once per day, plus a daily dose of 8×109 colony-forming units of a multi-strain probiotic (n 80) or placebo (n 80). The probiotic or placebo intervention was maintained for 1 week after completion of the antibiotic. Primary study outcomes of consistency and frequency of bowel movements were not significantly different between the probiotic and placebo groups. The secondary outcomes of diarrhoea-like defecations, Gastrointestinal Symptoms Rating Scale scores, safety parameters and adverse events were not significantly different between the probiotic intervention and the placebo. A post hoc analysis on the duration of diarrhoea-like defecations showed that probiotic intervention reduced the length of these events by 1 full day (probiotic, 2·70 (sem 0·36) d; placebo, 3·71 (sem 0·36) d; P=0·037; effect size=0·52). In conclusion, this study provides novel evidence that L. helveticus R0052 and L. rhamnosus R0011 supplementation significantly reduced the duration of diarrhoea-like defecations in healthy adults receiving antibiotics.

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

Science.gov (United States)

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.

Melatonin versus Placebo in Children with Autism Spectrum Conditions and Severe Sleep Problems Not Amenable to Behaviour Management Strategies: A Randomised Controlled Crossover Trial

Science.gov (United States)

Wright, Barry; Sims, David; Smart, Siobhan; Alwazeer, Ahmed; Alderson-Day, Ben; Allgar, Victoria; Whitton, Clare; Tomlinson, Heather; Bennett, Sophie; Jardine, Jenni; McCaffrey, Nicola; Leyland, Charlotte; Jakeman, Christine; Miles, Jeremy

2011-01-01

Twenty-two children with autism spectrum disorders who had not responded to supported behaviour management strategies for severe dysomnias entered a double blind, randomised, controlled crossover trial involving 3 months of placebo versus 3 months of melatonin to a maximum dose of 10 mg. 17 children completed the study. There were no significant…

An international randomised placebo-controlled trial of a four-component combination pill ("polypill" in people with raised cardiovascular risk.

Directory of Open Access Journals (Sweden)

Anthony Rodgers

Full Text Available There has been widespread interest in the potential of combination cardiovascular medications containing aspirin and agents to lower blood pressure and cholesterol ('polypills' to reduce cardiovascular disease. However, no reliable placebo-controlled data are available on both efficacy and tolerability.We conducted a randomised, double-blind placebo-controlled trial of a polypill (containing aspirin 75 mg, lisinopril 10 mg, hydrochlorothiazide 12.5 mg and simvastatin 20 mg in 378 individuals without an indication for any component of the polypill, but who had an estimated 5-year cardiovascular disease risk over 7.5%. The primary outcomes were systolic blood pressure (SBP, LDL-cholesterol and tolerability (proportion discontinued randomised therapy at 12 weeks follow-up.At baseline, mean BP was 134/81 mmHg and mean LDL-cholesterol was 3.7 mmol/L. Over 12 weeks, polypill treatment reduced SBP by 9.9 (95% CI: 7.7 to 12.1 mmHg and LDL-cholesterol by 0.8 (95% CI 0.6 to 0.9 mmol/L. The discontinuation rates in the polypill group compared to placebo were 23% vs 18% (RR 1.33, 95% CI 0.89 to 2.00, p = 0.2. There was an excess of side effects known to the component medicines (58% vs 42%, p = 0.001, which was mostly apparent within a few weeks, and usually did not warrant cessation of trial treatment.This polypill achieved sizeable reductions in SBP and LDL-cholesterol but caused side effects in about 1 in 6 people. The halving in predicted cardiovascular risk is moderately lower than previous estimates and the side effect rate is moderately higher. Nonetheless, substantial net benefits would be expected among patients at high risk.Australian New Zealand Clinical Trials Registry ACTRN12607000099426.

Improved glycemic control in patients with advanced type 2 diabetes mellitus taking Urtica dioica leaf extract: a randomized double-blind placebo-controlled clinical trial.

Science.gov (United States)

Kianbakht, Saeed; Khalighi-Sigaroodi, Farahnaz; Dabaghian, Fataneh Hashem

2013-01-01

Advanced type 2 diabetes mellitus (T2DM) needing insulin therapy is common. Most conventional anti-hyperglycemic drugs have limited efficacies and significant side effects, so that better anti-hyperglycemic agents are needed. Urtica dioica L. (nettle) leaves have insulin secretagogue, PPARgamma agonistic, and alpha-glucosidase inhibitory effects. Moreover, nettle leaves are used in traditional medicine as an anti-hyperglycemic agent to treat diabetes mellitus. Thus, efficacy and safety of nettle in the treatment of patients with advanced type 2 diabetes mellitus needing insulin were studied. In this randomized double-blind placebo-controlled clinical trial, we evaluated the effects of taking nettle leaf extract (one 500 mg capsule every 8 hours for 3 months) combined with the conventional oral anti-hyperglycemic drugs on the blood levels of fasting glucose, postprandial glucose, glycosylated hemoglobin (HbA1c), creatinine and liver enzymes SGOT and SGPT, and systolic and diastolic blood pressures in 46 patients and compared with the placebo group (n = 46). At the endpoint, the extract lowered the blood levels of fasting glucose, 2 hours postprandial glucose, and HbA1c significantly (p 0.05) compared with placebo. Nettle may safely improve glycemic control in type 2 diabetic patients needing insulin therapy.

Efficacy of vildagliptin for prevention of postpartum diabetes in women with a recent history of insulin-requiring gestational diabetes: A phase II, randomized, double-blind, placebo-controlled study

Directory of Open Access Journals (Sweden)

Sandra Hummel

2018-03-01

Full Text Available Objective: Women with insulin-requiring gestational diabetes mellitus (GDM are at high risk of developing diabetes within a few years postpartum. We implemented this phase II study to test the hypothesis that vildagliptin, a dipeptidyl peptidase-4 inhibitor, is superior to placebo in terms of reducing the risk of postpartum diabetes. Methods: Women with insulin-requiring GDM were randomized to either placebo or 50 mg vildagliptin twice daily for 24 months followed by a 12-month observation period (EudraCT: 2007-000634-39. Both groups received lifestyle counseling. The primary efficacy outcomes were the diagnosis of diabetes (American Diabetes Association (ADA criteria or impaired fasting glucose (IFG/impaired glucose tolerance (IGT. Results: Between 2008 and 2015, 113 patients (58 vildagliptin, 55 placebo were randomized within 2.2–10.4 (median 8.6 months after delivery. At the interim analysis, nine diabetic events and 28 IFG/IGT events had occurred. Fifty-two women withdrew before completing the treatment phase. Because of the low diabetes rate, the study was terminated. Lifestyle adherence was similar in both groups. At 24 months, the cumulative probability of postpartum diabetes was 3% and 5% (hazard ratio: 1.03; 95% confidence interval: 0.15–7.36 and IFG/IGT was 43% and 22% (hazard ratio: 0.55; 95% confidence interval: 0.26–1.19 in the placebo and vildagliptin groups, respectively. Vildagliptin was well tolerated with no unexpected adverse events. Conclusions: The study did not show significant superiority of vildagliptin over placebo in terms of reducing the risk of postpartum diabetes. However, treatment was safe and suggested some improvements in glycemic control, insulin resistance, and β-cell function. The study identified critical issues in performing clinical trials in the early postpartum period in women with GDM hampering efficacy assessments. With this knowledge, we have set a basis for which properly powered trials could

Safety and immunogenicity of RV3-BB human neonatal rotavirus vaccine administered at birth or in infancy: a randomised, double-blind, placebo-controlled trial.

Science.gov (United States)

Bines, Julie E; Danchin, Margaret; Jackson, Pamela; Handley, Amanda; Watts, Emma; Lee, Katherine J; West, Amanda; Cowley, Daniel; Chen, Mee-Yew; Barnes, Graeme L; Justice, Frances; Buttery, Jim P; Carlin, John B; Bishop, Ruth F; Taylor, Barry; Kirkwood, Carl D

2015-12-01

Despite the success of rotavirus vaccines, suboptimal vaccine efficacy in regions with a high burden of disease continues to present a challenge to worldwide implementation. A birth dose strategy with a vaccine developed from an asymptomatic neonatal rotavirus strain has the potential to address this challenge and provide protection from severe rotavirus disease from birth. This phase 2a randomised, double-blind, three-arm, placebo-controlled safety and immunogenicity trial was undertaken at a single centre in New Zealand between Jan 13, 2012, and April 17, 2014. Healthy, full-term (≥36 weeks gestation) babies, who weighed at least 2500 g, and were 0-5 days old at the time of randomisation were randomly assigned (1:1:1; computer-generated; telephone central allocation) according to a concealed block randomisation schedule to oral RV3-BB vaccine with the first dose given at 0-5 days after birth (neonatal schedule), to vaccine with the first dose given at about 8 weeks after birth (infant schedule), or to placebo. The primary endpoint was cumulative vaccine take (serum immune response or stool shedding of vaccine virus after any dose) after three doses. The immunogenicity analysis included all randomised participants with available outcome data. This trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611001212943. 95 eligible participants were randomised, of whom 89 were included in the primary analysis. A cumulative vaccine take was detected in 27 (90%) of 30 participants in the neonatal schedule group after three doses of RV3-BB vaccine compared with four (13%) of 32 participants in the placebo group (difference in proportions 0·78, 95% CI 0·55-0·88; pvaccine take after three doses compared with eight (25%) of 32 participants in the placebo group (difference in proportions 0·68, 0·44-0·81; pvaccine was not associated with an increased frequency of fever or gastrointestinal symptoms compared with placebo. RV3-BB vaccine was

Randomised clinical trial: evaluation of the efficacy of mesalazine (mesalamine) suppositories in patients with ulcerative colitis and active rectal inflammation -- a placebo-controlled study.

Science.gov (United States)

Watanabe, M; Nishino, H; Sameshima, Y; Ota, A; Nakamura, S; Hibi, T

2013-08-01

Mesalazine suppositories are recommended and widely used as the standard therapy in induction and maintenance of remission for proctitis. To evaluate the efficacy of mesalazine suppositories in patients with ulcerative colitis (UC) and rectal inflammation; and in patient groups categorised by the extent of lesions. This study was a phase III multicentre, randomised, double-blind, placebo-controlled, parallel-group study. Mild-to-moderate UC patients with rectal inflammation were randomly assigned either a 1 g mesalazine or placebo suppository. The suppository was administered in the rectum once daily for 4 weeks. The primary efficacy end point was the rate of endoscopic remission (mucosal score of 0 or 1) after 4 weeks. The endoscopic remission rates after 4 weeks in the mesalazine and placebo suppository groups were 81.5% and 29.7%, respectively, and the superiority of mesalazine to placebo was confirmed (P suppositories in all types of UC patients with rectal inflammation was confirmed for the first time in a double-blind, placebo-controlled, parallel-group study (JapicCTI- 111421). © 2013 John Wiley & Sons Ltd.

Reduction of fatigue in Sjögren syndrome with rituximab: results of a randomised, double-blind, placebo-controlled pilot study.

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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.

Effect of eltrombopag on platelet counts and bleeding during treatment of chronic idiopathic thrombocytopenic purpura: a randomised, double-blind, placebo-controlled trial.

Science.gov (United States)

Bussel, James B; Provan, Drew; Shamsi, Tahir; Cheng, Gregory; Psaila, Bethan; Kovaleva, Lidia; Salama, Abdulgabar; Jenkins, Julian M; Roychowdhury, Debasish; Mayer, Bhabita; Stone, Nicole; Arning, Michael

2009-02-21

Eltrombopag is an oral, non-peptide, thrombopoietin-receptor agonist that stimulates thrombopoiesis, leading to increased platelet production. This study assessed the efficacy, safety, and tolerability of once daily eltrombopag 50 mg, and explored the efficacy of a dose increase to 75 mg. In this phase III, randomised, double-blind, placebo-controlled study, adults from 63 sites in 23 countries with chronic idiopathic thrombocytopenic purpura (ITP), platelet counts less than 30 000 per muL of blood, and one or more previous ITP treatment received standard care plus once-daily eltrombopag 50 mg (n=76) or placebo (n=38) for up to 6 weeks. Patients were randomly assigned in a 2:1 ratio of eltrombopag:placebo by a validated randomisation system. After 3 weeks, patients with platelet counts less than 50 000 per microL could increase study drug to 75 mg. The primary endpoint was the proportion of patients achieving platelet counts 50 000 per microL or more at day 43. All participants who received at least one dose of their allocated treatment were included in the analysis. This study is registered with ClinicalTrials.gov, number NCT00102739. 73 patients in the eltrombopag group and 37 in the placebo group were included in the efficacy population and were evaluable for day-43 analyses. 43 (59%) eltrombopag patients and six (16%) placebo patients responded (ie, achieved platelet counts >/=50 000 per microL; odds ratio [OR] 9.61 [95% CI 3.31-27.86]; ptime during the study than did those receiving placebo (OR 0.49 [95% CI 0.26-0.89]; p=0.021). The frequency of grade 3-4 adverse events during treatment (eltrombopag, two [3%]; placebo, one [3%]) and adverse events leading to study discontinuation (eltrombopag, three [4%]; placebo, two [5%]), were similar in both groups. Eltrombopag is an effective treatment for managment of thrombocytopenia in chronic ITP.

A randomised, placebo-controlled trial of transcranial pulsed electromagnetic fields in patients with multiple chemical sensitivity

DEFF Research Database (Denmark)

Tran, Marie Thi Dao; Skovbjerg, Sine; Arendt-Nielsen, Lars

2017-01-01

was the Life Impact Scale (LIS) of the Quick Environmental Exposure and Sensitivity Inventory (QEESI). Secondary outcomes were the Symptom Severity Scale (SSS) and the Chemical Intolerance Scale of QEESI. RESULTS: A total of 39 participants were randomised to PEMF or placebo treatment. No significant...... difference was observed on QEESI LIS between groups with a mean change score of -5.9 in the PEMF group compared with -1.5 in the placebo group (p=0.35, effect size=-0.31). However, a significant decrease was detected on QEESI SSS within and between groups with a mean change score of -11.3 in the PEMF group...

Low dose aspirin as adjuvant treatment for venous leg ulceration: pragmatic, randomised, double blind, placebo controlled trial (Aspirin4VLU).

Science.gov (United States)

Jull, Andrew; Wadham, Angela; Bullen, Chris; Parag, Varsha; Kerse, Ngaire; Waters, Jill

2017-11-24

Objective  To determine the effect of low dose aspirin on ulcer healing in patients with venous leg ulcers. Design  Pragmatic, community based, parallel group, double blind, randomised controlled trial. Setting  Five community nursing centres in New Zealand. Participants  251 adults with venous leg ulcers who could safely be treated with aspirin or placebo: 125 were randomised to aspirin and 126 to placebo. Interventions  150 mg oral aspirin daily or matching placebo for up to 24 weeks treatment, with compression therapy as standard background treatment. Main outcome measures  The primary outcome was time to complete healing of the reference ulcer (largest ulcer if more than one ulcer was present). Secondary outcomes included proportion of participants healed, change in ulcer area, change in health related quality of life, and adverse events. Analysis was by intention to treat. Results  The median number of days to healing of the reference ulcer was 77 in the aspirin group and 69 in the placebo group (hazard ratio 0.85, 95% confidence interval 0.64 to 1.13, P=0.25). The number of participants healed at the endpoint was 88 (70%) in the aspirin group and 101 (80%) in the placebo group (risk difference -9.8%, 95% confidence interval -20.4% to 0.9%, P=0.07). Estimated change in ulcer area was 4.1 cm 2 in the aspirin group and 4.8 cm 2 in the placebo group (mean difference -0.7 cm 2 , 95% confidence interval -1.9 to 0.5 cm 2 , P=0.25). 40 adverse events occurred among 29 participants in the aspirin group and 37 adverse events among 27 participants in the placebo group (incidence rate ratio 1.1, 95% confidence interval 0.7 to 1.7, P=0.71). Conclusion  Our findings do not support the use of low dose aspirin as adjuvant treatment for venous leg ulcers. Trial registration  ClinicalTrials.gov NCT02158806. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

The effect of oxcarbazepine in peripheral neuropathic pain depends on pain phenotype: a randomised, double-blind, placebo-controlled phenotype-stratified study

DEFF Research Database (Denmark)

Demant, Dyveke T; Lund, Karen; Vollert, Jan

2014-01-01

In neuropathic pain it has been suggested that pain phenotype based on putative pain mechanisms may predict response to treatment. This was a randomised, double-blind, placebo-controlled, and phenotype-stratified study with 2 6-week treatment periods of oxcarbazepine (1800-2400mg) and placebo...... patients: 31 with the irritable and 52 with the nonirritable nociceptor phenotype. In the total sample, oxcarbazepine relieved pain of 0.7 points (on a numeric rating scale 0-10; 95% confidence interval [CI] 0.4-1.4) more than placebo (P=0.015) and there was a significant interaction between treatment....... The primary efficacy measure was change in median pain intensity between baseline and the last week of treatment measured on an 11-point numeric rating scale, and the primary objective was to compare the effect of oxcarbazepine in patients with and without the irritable nociceptor phenotype as defined...

Soy in hypercholesterolaemia: a double-blind, placebo-controlled trial.

Science.gov (United States)

Puska, P; Korpelainen, V; Høie, L H; Skovlund, E; Lahti, T; Smerud, K T

2002-04-01

To study whether Abacor, a product based on isolated soy protein with high and standardised levels of isoflavones and cotyledon soy fibres, was more effective in lowering total and LDL cholesterol than placebo. Randomised, placebo-controlled, double-blind, parallel group, single centre study. Primary care in Joensuu, North Karelia, Finland. Subjects were screened from the patient database of the health centre; 30 were randomised to the Abacor group and 30 subjects to placebo. Eight subjects were withdrawn, six from the active group, two from the placebo group. The preparations were given as two daily liquid supplements in addition to the subjects' regular diets for 6 weeks. Abacor showed a statistically significant lipid-lowering effect as compared to placebo, although an unexpected reduction was seen in the placebo group. The estimated difference between active treatment and placebo was 0.25 mmol/l (95% CI 0.01, 0.50; P=0.049) for total cholesterol, corresponding to reductions of 8.3 and 5.1%, respectively. The difference in reduction of LDL-cholesterol was 0.27 mmol/l (95% CI 0.06, 0.49; P=0.014) and corresponded to a reduction of 13.2% in the active treatment group, and 8.0% in the placebo group. Abacor showed a rapid onset of effect, as compared with placebo. During a wash-out period of 4 weeks after treatment, the subjects returned to pre-treatment cholesterol levels. Added to a regular diet, Abacor significantly reduced LDL-cholesterol and total cholesterol. These beneficial effects occurred within 6 weeks of treatment.

Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage (TICH-2): an international randomised, placebo-controlled, phase 3 superiority trial.

Science.gov (United States)

Sprigg, Nikola; Flaherty, Katie; Appleton, Jason P; Al-Shahi Salman, Rustam; Bereczki, Daniel; Beridze, Maia; Christensen, Hanne; Ciccone, Alfonso; Collins, Ronan; Czlonkowska, Anna; Dineen, Robert A; Duley, Lelia; Egea-Guerrero, Juan Jose; England, Timothy J; Krishnan, Kailash; Laska, Ann Charlotte; Law, Zhe Kang; Ozturk, Serefnur; Pocock, Stuart J; Roberts, Ian; Robinson, Thompson G; Roffe, Christine; Seiffge, David; Scutt, Polly; Thanabalan, Jegan; Werring, David; Whynes, David; Bath, Philip M

2018-05-26

Tranexamic acid can prevent death due to bleeding after trauma and post-partum haemorrhage. We aimed to assess whether tranexamic acid reduces haematoma expansion and improves outcome in adults with stroke due to intracerebral haemorrhage. We did an international, randomised placebo-controlled trial in adults with intracerebral haemorrhage from acute stroke units at 124 hospital sites in 12 countries. Participants were randomly assigned (1:1) to receive 1 g intravenous tranexamic acid bolus followed by an 8 h infusion of 1 g tranexamic acid or a matching placebo, within 8 h of symptom onset. Randomisation was done centrally in real time via a secure website, with stratification by country and minimisation on key prognostic factors. Treatment allocation was concealed from patients, outcome assessors, and all other health-care workers involved in the trial. The primary outcome was functional status at day 90, measured by shift in the modified Rankin Scale, using ordinal logistic regression with adjustment for stratification and minimisation criteria. All analyses were done on an intention-to-treat basis. This trial is registered with the ISRCTN registry, number ISRCTN93732214. We recruited 2325 participants between March 1, 2013, and Sept 30, 2017. 1161 patients received tranexamic acid and 1164 received placebo; the treatment groups were well balanced at baseline. The primary outcome was assessed for 2307 (99%) participants. The primary outcome, functional status at day 90, did not differ significantly between the groups (adjusted odds ratio [aOR] 0·88, 95% CI 0·76-1·03, p=0·11). Although there were fewer deaths by day 7 in the tranexamic acid group (101 [9%] deaths in the tranexamic acid group vs 123 [11%] deaths in the placebo group; aOR 0·73, 0·53-0·99, p=0·0406), there was no difference in case fatality at 90 days (250 [22%] vs 249 [21%]; adjusted hazard ratio 0·92, 95% CI 0·77-1·10, p=0·37). Fewer patients had serious adverse events after tranexamic

Effect of Tribulus terrestris, ginger, saffron, and Cinnamomum on menopausal symptoms: a randomised, placebo-controlled clinical trial.

Science.gov (United States)

Taavoni, Simin; Ekbatani, Neda Nazem; Haghani, Hamid

2017-03-01

Menopausal symptoms experienced by women vary widely, and while many women transition through menopause with manageable symptoms, others experience severe symptoms, which may impair their quality of life. The purpose of this study was to determine the effect of Tribulus terrestris , ginger, saffron, and Cinnamomum on menopausal symptoms. A randomised, triple-blind, controlled trial design was used for this study. The participants were 80 postmenopausal women aged 50-60 years. A demographic data form and the Menopause Rating Scale were used to collect data. The women were randomly divided into two groups, each of which received either an Aphrodit capsule or a placebo twice a day for four weeks. The two bottles looked exactly the same, so that the investigator and the participants were not aware of the contents of the bottles. Each Aphrodit capsule contained 40 mg of Tribulus terrestris , 12.27 mg of Zingiber officinale , 3 mg of Crocus sativus extract, and 11 mg of Cinnamomum zeylanicum , while the placebo capsules contained 50 mg of starch. Descriptive and inferential statistics were used to analyse the data. A statistically significant change was reported in the menopausal symptoms of the intervention group compared with the placebo group. The results of the study demonstrate that the Aphrodit capsule was effective in reducing menopausal symptoms.

Efficacy of a microencapsulated iron pyrophosphate-fortified fruit juice: a randomised, double-blind, placebo-controlled study in Spanish iron-deficient women.

Science.gov (United States)

Blanco-Rojo, Ruth; Pérez-Granados, Ana M; Toxqui, Laura; González-Vizcayno, Carmen; Delgado, Marco A; Vaquero, M Pilar

2011-06-01

Fe-deficiency anaemia is a worldwide health problem. We studied the influence of consuming an Fe-fortified fruit juice on Fe status in menstruating women. A randomised, double-blind, placebo-controlled study of 16 weeks of duration was performed. Subjects were randomised into two groups: the P group (n 58) or the F group (n 64), and consumed, as a supplement to their usual diet, 500 ml/d of a placebo fruit juice or an Fe-fortified fruit juice, respectively. The Fe-fortified fruit juice, containing microencapsulated iron pyrophosphate, provided 18 mg Fe/d (100 % of the RDA). At baseline and monthly, dietary intake, body weight and Fe parameters were determined: total erythrocytes, haematocrit, mean corpuscular volume (MCV), red blood cell distribution width (RDW), Hb, serum Fe, serum ferritin, serum transferrin, transferrin saturation, soluble transferrin receptor (sTfR) and zinc protoporphyrin (ZnPP). The fruit juice consumption involved increased intake of carbohydrates and vitamin C, and increased BMI within normal limits. Ferritin was higher in the F group after week 4 (P juice improves Fe status and may be used to prevent Fe-deficiency anaemia.

Effect of low-protein diet on kidney function in diabetic nephropathy: meta-analysis of randomised controlled trials.

Science.gov (United States)

Nezu, Uru; Kamiyama, Hiroshi; Kondo, Yoshinobu; Sakuma, Mio; Morimoto, Takeshi; Ueda, Shinichiro

2013-05-28

To evaluate the effect of low-protein diet on kidney function in patients with diabetic nephropathy. A systematic review and a meta-analysis of randomised controlled trials. MEDLINE, EMBASE, Cochrane Library, ClinicalTrials.gov, International Standard Randomised Controlled Trial Number (ISRCTN) Register and University Hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR) from inception to 10 December 2012. Internet searches were also carried out with general search engines (Google and Google Scholar). Randomised controlled trials that compared low-protein diet versus control diet and assessed the effects on kidney function, proteinuria, glycaemic control or nutritional status. The primary outcome was a change in the glomerular filtration rate (GFR). The secondary outcomes were changes in proteinuria, post-treatment value of glycated haemoglobin A1C (HbA1c) and post-treatment value of serum albumin. The results were summarised as the mean difference for continuous outcomes and pooled by the random effects model. Subgroup analyses and sensitivity analyses were conducted regarding patient characteristics, intervention period, methodological quality and assessment of diet compliance. The assessment of diet compliance was performed based on the actual protein intake ratio (APIR) of the low-protein diet group to the control group. We identified 13 randomised controlled trials enrolling 779 patients. A low-protein diet was associated with a significant improvement in GFR (5.82 ml/min/1.73 m(2), 95% CI 2.30 to 9.33, I(2)=92%; n=624). This effect was consistent across the subgroups of type of diabetes, stages of nephropathy and intervention period. However, GFR was improved only when diet compliance was fair (8.92, 95% CI 2.75 to 15.09, I(2)=92% for APIR <0.9 and 0.03, 95% CI -1.49 to 1.56, I(2)=90% for APIR ≥0.9). Proteinuria and serum albumin were not differed between the groups. HbA1c was slightly but significantly decreased in the low-protein diet

Efficacy of a multimodal physiotherapy treatment program for hip osteoarthritis: a randomised placebo-controlled trial protocol

Directory of Open Access Journals (Sweden)

Forbes Andrew

2010-10-01

Full Text Available Abstract Background Hip osteoarthritis (OA is a common condition leading to pain, disability and reduced quality of life. There is currently limited evidence to support the use of conservative, non-pharmacological treatments for hip OA. Exercise and manual therapy have both shown promise and are typically used together by physiotherapists to manage painful hip OA. The aim of this randomised controlled trial is to compare the efficacy of a physiotherapy treatment program with placebo treatment in reducing pain and improving physical function. Methods The trial will be conducted at the University of Melbourne Centre for Health, Exercise and Sports Medicine. 128 participants with hip pain greater or equal to 40/100 on visual analogue scale (VAS and evidence of OA on x-ray will be recruited. Treatment will be provided by eight community physiotherapists in the Melbourne metropolitan region. The active physiotherapy treatment will comprise a semi-structured program of manual therapy and exercise plus education and advice. The placebo treatment will consist of sham ultrasound and the application of non-therapeutic gel. The participants and the study assessor will be blinded to the treatment allocation. Primary outcomes will be pain measured by VAS and physical function recorded on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC immediately after the 12 week intervention. Participants will also be followed up at 36 weeks post baseline. Conclusions The trial design has important strengths of reproducibility and reflecting contemporary physiotherapy practice. The findings from this randomised trial will provide evidence for the efficacy of a physiotherapy program for painful hip OA. Trial Registration Australian New Zealand Clinical Trials Registry reference: ACTRN12610000439044

Efficacy of a multimodal physiotherapy treatment program for hip osteoarthritis: a randomised placebo-controlled trial protocol

Science.gov (United States)

2010-01-01

Background Hip osteoarthritis (OA) is a common condition leading to pain, disability and reduced quality of life. There is currently limited evidence to support the use of conservative, non-pharmacological treatments for hip OA. Exercise and manual therapy have both shown promise and are typically used together by physiotherapists to manage painful hip OA. The aim of this randomised controlled trial is to compare the efficacy of a physiotherapy treatment program with placebo treatment in reducing pain and improving physical function. Methods The trial will be conducted at the University of Melbourne Centre for Health, Exercise and Sports Medicine. 128 participants with hip pain greater or equal to 40/100 on visual analogue scale (VAS) and evidence of OA on x-ray will be recruited. Treatment will be provided by eight community physiotherapists in the Melbourne metropolitan region. The active physiotherapy treatment will comprise a semi-structured program of manual therapy and exercise plus education and advice. The placebo treatment will consist of sham ultrasound and the application of non-therapeutic gel. The participants and the study assessor will be blinded to the treatment allocation. Primary outcomes will be pain measured by VAS and physical function recorded on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) immediately after the 12 week intervention. Participants will also be followed up at 36 weeks post baseline. Conclusions The trial design has important strengths of reproducibility and reflecting contemporary physiotherapy practice. The findings from this randomised trial will provide evidence for the efficacy of a physiotherapy program for painful hip OA. Trial Registration Australian New Zealand Clinical Trials Registry reference: ACTRN12610000439044 PMID:20946621

Text message-based diabetes self-management support (SMS4BG): study protocol for a randomised controlled trial.

Science.gov (United States)

Dobson, Rosie; Whittaker, Robyn; Jiang, Yannan; Shepherd, Matthew; Maddison, Ralph; Carter, Karen; Cutfield, Richard; McNamara, Catherine; Khanolkar, Manish; Murphy, Rinki

2016-04-02

Addressing the increasing prevalence, and associated disease burden, of diabetes is a priority of health services internationally. Interventions to support patients to effectively self-manage their condition have the potential to reduce the risk of costly and debilitating complications. The utilisation of mobile phones to deliver self-management support allows for patient-centred care at the frequency and intensity that patients desire from outside the clinic environment. Self-Management Support for Blood Glucose (SMS4BG) is a novel text message-based intervention for supporting people with diabetes to improve self-management behaviours and achieve better glycaemic control and is tailored to individual patient preferences, demographics, clinical characteristics, and culture. This study aims to assess whether SMS4BG can improve glycaemic control in adults with poorly controlled diabetes. This paper outlines the rationale and methods of the trial. A two-arm, parallel, randomised controlled trial will be conducted across New Zealand health districts. One thousand participants will be randomised at a 1:1 ratio to receive SMS4BG, a theoretically based and individually tailored automated text message-based diabetes self-management support programme (intervention) in addition to usual care, or usual care alone (control). The primary outcome is change in glycaemic control (HbA1c) at 9 months. Secondary outcomes include glycaemic control at 3 and 6 months, self-efficacy, self-care behaviours, diabetes distress, health-related quality of life, perceived social support, and illness perceptions. Cost information and healthcare utilisation will also be collected as well as intervention satisfaction and interaction. This study will provide information on the effectiveness of a text message-based self-management support tool for people with diabetes. If found to be effective it has the potential to provide individualised support to people with diabetes across New Zealand (and

Rituximab for childhood-onset, complicated, frequently relapsing nephrotic syndrome or steroid-dependent nephrotic syndrome: a multicentre, double-blind, randomised, placebo-controlled trial.

Science.gov (United States)

Iijima, Kazumoto; Sako, Mayumi; Nozu, Kandai; Mori, Rintaro; Tuchida, Nao; Kamei, Koichi; Miura, Kenichiro; Aya, Kunihiko; Nakanishi, Koichi; Ohtomo, Yoshiyuki; Takahashi, Shori; Tanaka, Ryojiro; Kaito, Hiroshi; Nakamura, Hidefumi; Ishikura, Kenji; Ito, Shuichi; Ohashi, Yasuo

2014-10-04

Rituximab could be an effective treatment for childhood-onset, complicated, frequently relapsing nephrotic syndrome (FRNS) and steroid-dependent nephrotic syndrome (SDNS). We investigated the efficacy and safety of rituximab in patients with high disease activity. We did a multicentre, double-blind, randomised, placebo-controlled trial at nine centres in Japan. We screened patients aged 2 years or older experiencing a relapse of FRNS or SDNS, which had originally been diagnosed as nephrotic syndrome when aged 1-18 years. Patients with complicated FRNS or SDNS who met all other criteria were eligible for inclusion after remission of the relapse at screening. We used a computer-generated sequence to randomly assign patients (1:1) to receive rituximab (375 mg/m(2)) or placebo once weekly for 4 weeks, with age, institution, treatment history, and the intervals between the previous three relapses as adjustment factors. Patients, guardians, caregivers, physicians, and individuals assessing outcomes were masked to assignments. All patients received standard steroid treatment for the relapse at screening and stopped taking immunosuppressive agents by 169 days after randomisation. Patients were followed up for 1 year. The primary endpoint was the relapse-free period. Safety endpoints were frequency and severity of adverse events. Patients who received their assigned intervention were included in analyses. This trial is registered with the University Hospital Medical Information Network clinical trials registry, number UMIN000001405. Patients were centrally registered between Nov 13, 2008, and May 19, 2010. Of 52 patients who underwent randomisation, 48 received the assigned intervention (24 were given rituximab and 24 placebo). The median relapse-free period was significantly longer in the rituximab group (267 days, 95% CI 223-374) than in the placebo group (101 days, 70-155; hazard ratio: 0·27, 0·14-0·53; p<0·0001). Ten patients (42%) in the rituximab group and six (25

Placebo-controlled comparison of captopril, metoprolol, and hydrochlorothiazide therapy in non-insulin-dependent diabetic patients with primary hypertension

DEFF Research Database (Denmark)

Gall, M A; Rossing, P; Skøtt, P

1992-01-01

The antihypertensive effect of captopril, metoprolol, and hydrochlorothiazide was compared in 23 non-insulin-dependent (NIDDM) diabetic patients less than or equal to 75 years of age, with borderline to moderate primary hypertension. In a double blind, placebo-controlled cross-over trial...

Drug treatment of bothersome lower urinary tract symptoms after ureteric JJ-stent insertion: A contemporary, comparative, prospective, randomised placebo-controlled study, single-centre experience.

Science.gov (United States)

Hekal, Ihab A

2016-12-01

To provide a guide for medication to alleviate bothersome lower urinary tract symptoms (LUTS) in patients after JJ ureteric stenting. Between June 2011 and June 2015, a prospective randomised placebo-controlled study was conducted on 200 consecutive cases of ureteric stones that required JJ stents. All patients had signed informed consent and JJ-stent placement confirmed by X-ray. The patients were randomised into five groups: A, solifenacin 5 mg; B, trospium chloride 20 mg; C, antispasmodic; and E, α-blocker; and a placebo group (D). A standard model was created to lessen patient selection bias. Eligible patients were enrolled and assessed for side-effects and bothersome LUTS using the validated Ureteric Stent Symptoms Questionnaire. Appropriate statistical analysis was carried out. In all, 150 male patients in the five groups were compared. LUTS were less in groups A and B ( P  JJ-stent insertion, anti-muscarinic medication, namely solifenacin 5 mg or trospium chloride 20 mg, was the best. The advantage of trospium over solifenacin is in the control of frequency rather than the other symptoms. Addition of an α-blocker (alfuzosin 10 mg) is valuable when nocturia is the predominant symptom.

A novel reflux inhibitor lesogaberan (AZD3355) as add-on treatment in patients with GORD with persistent reflux symptoms despite proton pump inhibitor therapy: a randomised placebo-controlled trial

NARCIS (Netherlands)

Boeckxstaens, Guy E.; Beaumont, Hanneke; Hatlebakk, Jan G.; Silberg, Debra G.; Björck, Karin; Karlsson, Maria; Denison, Hans

2011-01-01

o evaluate the efficacy and tolerability of add-on treatment with lesogaberan (AZD3355), a novel reflux inhibitor, in patients with persistent gastro-oesophageal reflux disease (GORD) symptoms despite proton pump inhibitor (PPI) therapy. double-blind, placebo-controlled, randomised, parallel-group,

A Double-Blind, Randomised, Placebo-Controlled Trial of EMLA® Cream (Eutectic Lidocaine/Prilocaine Cream) for Analgesia Prior to Cryotherapy of Plantar Warts in Adults.

Science.gov (United States)

Lee, Siew Hui; Pakdeethai, Janthorn; Toh, Matthias P H S; Aw, Derrick C W

2014-10-01

Cryotherapy with liquid nitrogen is an effective, safe and convenient form of treatment for plantar warts. EMLA® cream (eutectic mixture of lidocaine 2.5% and prilocaine 2.5%) is a topical local anaesthetic agent that has proven to be effective and well tolerated in the relief of pain associated with various minor interventions in numerous clinical settings. In a single-centre, double-blind, randomised placebo-controlled study, 64 subjects were randomised into 2 groups. The subjects had a thick layer of EMLA® cream or placebo cream applied to pared plantar wart(s) and onto the surrounding margin of 1 mm to 2 mm under occlusion for 60 minutes prior to receiving cryotherapy. The pain of cryotherapy was evaluated by the subjects using a self-administered Visual Analogue Scale (VAS) immediately after the cryotherapy. There was no statistical difference between the mean VAS score for EMLA® cream (47.0 ± 21.4 mm) and placebo (48.9 ± 22.0 mm). Those with more than 1 wart had a significantly higher VAS score than those with only 1 wart (59.1 ± 21.8 vs. 44.3 ± 20.4, P cryotherapy. We conclude that the application of EMLA® cream prior to cryotherapy does not reduce the pain associated with cryotherapy.

Efficacy of vildagliptin for prevention of postpartum diabetes in women with a recent history of insulin-requiring gestational diabetes: A phase II, randomized, double-blind, placebo-controlled study.

Science.gov (United States)

Hummel, Sandra; Beyerlein, Andreas; Pfirrmann, Markus; Hofelich, Anna; Much, Daniela; Hivner, Susanne; Bunk, Melanie; Herbst, Melanie; Peplow, Claudia; Walter, Markus; Kohn, Denise; Hummel, Nadine; Kratzsch, Jürgen; Hummel, Michael; Füchtenbusch, Martin; Hasford, Joerg; Ziegler, Anette-G

2018-03-01

Women with insulin-requiring gestational diabetes mellitus (GDM) are at high risk of developing diabetes within a few years postpartum. We implemented this phase II study to test the hypothesis that vildagliptin, a dipeptidyl peptidase-4 inhibitor, is superior to placebo in terms of reducing the risk of postpartum diabetes. Women with insulin-requiring GDM were randomized to either placebo or 50 mg vildagliptin twice daily for 24 months followed by a 12-month observation period (EudraCT: 2007-000634-39). Both groups received lifestyle counseling. The primary efficacy outcomes were the diagnosis of diabetes (American Diabetes Association (ADA) criteria) or impaired fasting glucose (IFG)/impaired glucose tolerance (IGT). Between 2008 and 2015, 113 patients (58 vildagliptin, 55 placebo) were randomized within 2.2-10.4 (median 8.6) months after delivery. At the interim analysis, nine diabetic events and 28 IFG/IGT events had occurred. Fifty-two women withdrew before completing the treatment phase. Because of the low diabetes rate, the study was terminated. Lifestyle adherence was similar in both groups. At 24 months, the cumulative probability of postpartum diabetes was 3% and 5% (hazard ratio: 1.03; 95% confidence interval: 0.15-7.36) and IFG/IGT was 43% and 22% (hazard ratio: 0.55; 95% confidence interval: 0.26-1.19) in the placebo and vildagliptin groups, respectively. Vildagliptin was well tolerated with no unexpected adverse events. The study did not show significant superiority of vildagliptin over placebo in terms of reducing the risk of postpartum diabetes. However, treatment was safe and suggested some improvements in glycemic control, insulin resistance, and β-cell function. The study identified critical issues in performing clinical trials in the early postpartum period in women with GDM hampering efficacy assessments. With this knowledge, we have set a basis for which properly powered trials could be performed in women with recent GDM. TRIAL REGISTRATION

Effect of Tribulus terrestris, ginger, saffron, and Cinnamomum on menopausal symptoms: a randomised, placebo-controlled clinical trial

Science.gov (United States)

Taavoni, Simin; Haghani, Hamid

2017-01-01

Menopausal symptoms experienced by women vary widely, and while many women transition through menopause with manageable symptoms, others experience severe symptoms, which may impair their quality of life. The purpose of this study was to determine the effect of Tribulus terrestris, ginger, saffron, and Cinnamomum on menopausal symptoms. A randomised, triple-blind, controlled trial design was used for this study. The participants were 80 postmenopausal women aged 50–60 years. A demographic data form and the Menopause Rating Scale were used to collect data. The women were randomly divided into two groups, each of which received either an Aphrodit capsule or a placebo twice a day for four weeks. The two bottles looked exactly the same, so that the investigator and the participants were not aware of the contents of the bottles. Each Aphrodit capsule contained 40 mg of Tribulus terrestris, 12.27 mg of Zingiber officinale, 3 mg of Crocus sativus extract, and 11 mg of Cinnamomum zeylanicum, while the placebo capsules contained 50 mg of starch. Descriptive and inferential statistics were used to analyse the data. A statistically significant change was reported in the menopausal symptoms of the intervention group compared with the placebo group. The results of the study demonstrate that the Aphrodit capsule was effective in reducing menopausal symptoms. PMID:28546803

Effect of Tribulus terrestris , ginger, saffron, and Cinnamomum on menopausal symptoms: a randomised, placebo-controlled clinical trial

Directory of Open Access Journals (Sweden)

Simin Taavoni

2017-04-01

Full Text Available Menopausal symptoms experienced by women vary widely, and while many women transition through menopause with manageable symptoms, others experience severe symptoms, which may impair their quality of life. The purpose of this study was to determine the effect of Tribulus terrestris , ginger, saffron, and Cinnamomum on menopausal symptoms. A randomised, triple-blind, controlled trial design was used for this study. The participants were 80 postmenopausal women aged 50–60 years. A demographic data form and the Menopause Rating Scale were used to collect data. The women were randomly divided into two groups, each of which received either an Aphrodit capsule or a placebo twice a day for four weeks. The two bottles looked exactly the same, so that the investigator and the participants were not aware of the contents of the bottles. Each Aphrodit capsule contained 40 mg of Tribulus terrestris , 12.27 mg of Zingiber officinale, 3 mg of Crocus sativus extract, and 11 mg of Cinnamomum zeylanicum, while the placebo capsules contained 50 mg of starch. Descriptive and inferential statistics were used to analyse the data. A statistically significant change was reported in the menopausal symptoms of the intervention group compared with the placebo group. The results of the study demonstrate that the Aphrodit capsule was effective in reducing menopausal symptoms.

Dietary nitrate supplementation improves reaction time in type 2 diabetes: development and application of a novel nitrate-depleted beetroot juice placebo.

Science.gov (United States)

Gilchrist, Mark; Winyard, Paul G; Fulford, Jon; Anning, Christine; Shore, Angela C; Benjamin, Nigel

2014-08-31

In this substudy of the effect of dietary nitrate on blood pressure, endothelial function, and insulin sensitivity in type 2 diabetes, we report the development of a novel nitrate depleted beetroot juice for use clinical trials and determine if dietary nitrate supplementation improved cognitive function in patients with type 2 diabetes mellitus. Beetroot juice was treated with the anion exchange resin Purolite A520e. UV-vis-spectrophotometry, and a blind taste test were performed along with determination of sugar content, measurement of ascorbate and dehydroascorbate, the ionic composition of juice and Proton NMR. Subsequently, 27 patients, age 67.2±4.9 years, (18 male) were recruited for a double blind, randomised, placebo-controlled crossover trial. Participants were randomised to begin in either order beetroot juice (nitrate content 7.5 mmol per 250 ml) or placebo (nitrate depleted beetroot juice nitrate content 0.002 mmol per 250 ml). At the end of each 2 week supplementation period cognitive function was assessed using E-prime, E-Studio software with 5 separate tests being performed. The tests utilised in the present study have been adapted from the Cambridge Neuropsychological Test Automated Battery (CANTAB). The differences in the UV-vis spectra were comparable to the natural variation found in differing cultivars. There were no discernable differences in taste, sugar content, or Proton NMR. Ascorbate and dehydroascorbate were undetectable in either juice. After 2 weeks of beetroot juice simple reaction time was significantly quicker in the active arm at 327±40 ms versus 341.8±52.7 ms in the placebo arm, mean difference 13.9±25.6 ms (95% CI 3.8-24.0 ms), p=0.009. No other measures of cognitive function differed between treatment arms. We have developed an effective placebo beetroot juice for use in trials of supplementation of dietary nitrate. Two weeks supplementation of the diet with 7.5 mmol of nitrate per day caused a significant improvement in

Efficacy of early administration of escitalopram on depressive and emotional symptoms and neurological dysfunction after stroke: a multicentre, double-blind, randomised, placebo-controlled study.

Science.gov (United States)

Kim, Jong S; Lee, Eun-Jae; Chang, Dae-Il; Park, Jong-Ho; Ahn, Seong Hwan; Cha, Jae-Kwan; Heo, Ji Hoe; Sohn, Sung-Il; Lee, Byung-Chul; Kim, Dong-Eog; Kim, Hahn Young; Kim, Seongheon; Kwon, Do-Young; Kim, Jei; Seo, Woo-Keun; Lee, Jun; Park, Sang-Won; Koh, Seong-Ho; Kim, Jin Young; Choi-Kwon, Smi

2017-01-01

Mood and emotional disturbances are common in patients with stroke, and adversely affect the clinical outcome. We aimed to evaluate the efficacy of early administration of escitalopram to reduce moderate or severe depressive symptoms and improve emotional and neurological dysfunction in patients with stroke. This was a placebo controlled, double-blind trial done at 17 centres in South Korea. Patients who had had an acute stroke within the past 21 days were randomly assigned in a 1:1 ratio to receive oral escitalopram (10 mg/day) or placebo for 3 months. Randomisation was done with permuted blocks stratified by centre, via a web-based system. The primary endpoint was the frequency of moderate or severe depressive symptoms (Montgomery-Åsberg Depression Rating Scale [MADRS] ≥16). Endpoints were assessed at 3 months after randomisation in the full analysis set (patients who took study medication and underwent assessment of primary endpoint after randomisation), in all patients who were enrolled and randomly assigned (intention to treat), and in all patients who completed the trial (per-protocol analysis). This trial is registered with ClinicalTrials.gov, number NCT01278498. Between Jan 27, 2011, and June 30, 2014, 478 patients were assigned to placebo (n=237) or escitalopram (n=241); 405 were included in the full analysis set (195 in the placebo group, 210 in the escitalopram group). The primary outcome did not differ by study group in the full analysis set (25 [13%] patients in the placebo group vs 27 [13%] in the escitalopram group; odds ratio [OR] 1·00, 95% CI 0·56-1·80; p>0·99) or in the intention-to-treat analysis (34 [14%] vs 35 [15%]; OR 1·01, 95% CI 0·61-1·69, p=0·96). The study medication was generally well tolerated; the most common adverse events were constipation (14 [6%] patients who received placebo vs 14 [6%] who received escitalopram), muscle pain (16 [7%] vs ten [4%]), and insomnia (12 [5%] vs 12 [5%]). Diarrhoea was more common in the

Regorafenib plus best supportive care versus placebo plus best supportive care in Asian patients with previously treated metastatic colorectal cancer (CONCUR): a randomised, double-blind, placebo-controlled, phase 3 trial.

Science.gov (United States)

Li, Jin; Qin, Shukui; Xu, Ruihua; Yau, Thomas C C; Ma, Brigette; Pan, Hongming; Xu, Jianming; Bai, Yuxian; Chi, Yihebali; Wang, Liwei; Yeh, Kun-Huei; Bi, Feng; Cheng, Ying; Le, Anh Tuan; Lin, Jen-Kou; Liu, Tianshu; Ma, Dong; Kappeler, Christian; Kalmus, Joachim; Kim, Tae Won

2015-06-01

In the international randomised phase 3 CORRECT trial (NCT01103323), regorafenib significantly improved overall survival versus placebo in patients with treatment-refractory metastatic colorectal cancer. Of the 760 patients in CORRECT, 111 were Asian (mostly Japanese). This phase 3 trial was done to assess regorafenib in a broader population of Asian patients with refractory metastatic colorectal cancer than was studied in CORRECT. In this randomised, double-blind, placebo-controlled, parallel-group, phase 3 trial done in 25 hospitals in mainland China, Hong Kong, South Korea, Taiwan, and Vietnam, we recruited Asian patients aged 18 years or older with progressive metastatic colorectal cancer who had received at least two previous treatment lines or were unable to tolerate standard treatments. Patients had to have an Eastern Cooperative Oncology Group performance status of 0 or 1, life expectancy of at least 3 months, and adequate bone marrow, liver, and renal function, without other uncontrolled medical disorders. We randomly allocated patients (2:1; with a computer-generated unicentric randomisation list [prepared by the study funder] and interactive voice response system; block size of six; stratified by metastatic site [single vs multiple organs] and time from diagnosis of metastatic disease [regorafenib 160 mg once daily or placebo on days 1-21 of each 28 day cycle; patients in both groups were also to receive best supportive care. Participants, investigators, and the study funder were masked to treatment assignment. The primary endpoint was overall survival, and we analysed data on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT01584830. Between April 29, 2012, and Feb 6, 2013, we screened 243 patients and randomly assigned 204 patients to receive either regorafenib (136 [67%]) or placebo (68 [33%]). After a median follow-up of 7·4 months (IQR 4·3-12·2), overall survival was significantly better with regorafenib

Effects of liraglutide on cardiovascular risk biomarkers in patients with type 2 diabetes and albuminuria

DEFF Research Database (Denmark)

von Scholten, Bernt Johan; Persson, Frederik; Rosenlund, Signe

2017-01-01

-regional pro-atrial natriuretic peptide (MR-proANP); and 5) Copeptin, in type 2 diabetes patients with albuminuria. In a randomised, double-blind, placebo-controlled, cross-over trial we enrolled patients with type 2 diabetes and persistent albuminuria (urinary albumin-to-creatinine ratio (UACR) > 30 mg...

Mulberry-extract improves glucose tolerance and decreases insulin concentrations in normoglycaemic adults: Results of a randomised double-blind placebo-controlled study.

Directory of Open Access Journals (Sweden)

Mark Lown

Full Text Available High sugar and refined carbohydrate intake is associated with weight gain, increased incidence of diabetes and is linked with increased cardiovascular mortality. Reducing the health impact of poor quality carbohydrate intake is a public health priority. Reducose, a proprietary mulberry leaf extract (ME, may reduce blood glucose responses following dietary carbohydrate intake by reducing absorption of glucose from the gut.A double-blind, randomised, repeat measure, phase 2 crossover design was used to study the glycaemic and insulinaemic response to one reference product and three test products at the Functional Food Centre, Oxford Brooks University, UK. Participants; 37 adults aged 19-59 years with a BMI ≥ 20kg/m2 and ≤ 30kg/m2. The objective was to determine the effect of three doses of mulberry-extract (Reducose versus placebo on blood glucose and insulin responses when co-administered with 50g maltodextrin in normoglycaemic healthy adults. We also report the gastrointestinal tolerability of the mulberry extract.Thirty-seven participants completed the study: The difference in the positive Incremental Area Under the Curve (pIAUC (glucose (mmol / L x h for half, normal and double dose ME compared with placebo was -6.1% (-18.2%, 5.9%; p = 0.316, -14.0% (-26.0%, -2.0%; p = 0.022 and -22.0% (-33.9%, -10.0%; p<0.001 respectively. The difference in the pIAUC (insulin (mIU / L x h for half, normal and double dose ME compared with placebo was -9.7% (-25.8%, 6.3%; p = 0.234, -23.8% (-39.9%, -7.8%; p = 0.004 and -24.7% (-40.8%, -8.6%; p = 0.003 respectively. There were no statistically significant differences between any of the 4 groups in the odds of experiencing one or more gastrointestinal symptoms (nausea, abdominal cramping, distension or flatulence.Mulberry leaf extract significantly reduces total blood glucose rise after ingestion of maltodextrin over 120 minutes. The pattern of effect demonstrates a classical dose response curve with

Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial.

Science.gov (United States)

Bruix, Jordi; Qin, Shukui; Merle, Philippe; Granito, Alessandro; Huang, Yi-Hsiang; Bodoky, György; Pracht, Marc; Yokosuka, Osamu; Rosmorduc, Olivier; Breder, Valeriy; Gerolami, René; Masi, Gianluca; Ross, Paul J; Song, Tianqiang; Bronowicki, Jean-Pierre; Ollivier-Hourmand, Isabelle; Kudo, Masatoshi; Cheng, Ann-Lii; Llovet, Josep M; Finn, Richard S; LeBerre, Marie-Aude; Baumhauer, Annette; Meinhardt, Gerold; Han, Guohong

2017-01-07

There are no systemic treatments for patients with hepatocellular carcinoma (HCC) whose disease progresses during sorafenib treatment. We aimed to assess the efficacy and safety of regorafenib in patients with HCC who have progressed during sorafenib treatment. In this randomised, double-blind, parallel-group, phase 3 trial done at 152 sites in 21 countries, adults with HCC who tolerated sorafenib (≥400 mg/day for ≥20 of last 28 days of treatment), progressed on sorafenib, and had Child-Pugh A liver function were enrolled. Participants were randomly assigned (2:1) by a computer-generated randomisation list and interactive voice response system and stratified by geographical region, Eastern Cooperative Oncology Group performance status, macrovascular invasion, extrahepatic disease, and α-fetoprotein level to best supportive care plus oral regorafenib 160 mg or placebo once daily during weeks 1-3 of each 4-week cycle. Investigators, patients, and the funder were masked to treatment assignment. The primary endpoint was overall survival (defined as time from randomisation to death due to any cause) and analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01774344. Between May 14, 2013, and Dec 31, 2015, 843 patients were screened, of whom 573 were enrolled and randomised (379 to regorafenib and 194 to placebo; population for efficacy analyses), and 567 initiated treatment (374 received regorafenib and 193 received placebo; population for safety analyses). Regorafenib improved overall survival with a hazard ratio of 0·63 (95% CI 0·50-0·79; one-sided p<0·0001); median survival was 10·6 months (95% CI 9·1-12·1) for regorafenib versus 7·8 months (6·3-8·8) for placebo. Adverse events were reported in all regorafenib recipients (374 [100%] of 374) and 179 (93%) of 193 placebo recipients. The most common clinically relevant grade 3 or 4 treatment-emergent events were hypertension (57 patients [15%] in the regorafenib group

Role of oral tramadol 50 mg in reducing pain associated with outpatient hysteroscopy: A randomised double-blind placebo-controlled trial.

Science.gov (United States)

Hassan, AbdelGany; Haggag, Hisham

2016-02-01

Several drugs have been used to reduce hysteroscopy-associated pain. Although the Royal College of Obstetricians and Gynaecologists has recommended against the use of opiates in outpatient hysteroscopy, we wished to investigate if opioids can be used if the appropriate opioid was given in the appropriate dose. To study the effectiveness of tramadol 50 mg in reducing pain associated with outpatient hysteroscopy. A prospective randomised double-blind placebo-controlled trial conducted in the outpatient hysteroscopy clinic at Cairo University Hospital. Main outcome measures were the severity of pain during the procedure, immediately after the procedure and 30 minutes later assessed by a visual analogue scale (VAS). VAS of 0 indicates no pain and VAS of 10 indicates the worst possible pain. A total of 140 women who had diagnostic outpatient hysteroscopy were randomised to receive oral tramadol 50 mg or placebo one h before performing outpatient hysteroscopy. There was no difference between the groups in the age, parity, duration of the procedures or indications of hysteroscopy. The median pain score was significantly lower in the tramadol group during the procedure (5 vs 6; P = 0.013), immediately after the procedure (3 vs 4; P pain evoked by the procedure and the drug was well tolerated by women. © 2016 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Delivering early care in diabetes evaluation (DECIDE: a protocol for a randomised controlled trial to assess hospital versus home management at diagnosis in childhood diabetes

Directory of Open Access Journals (Sweden)

Robling Michael

2011-01-01

Full Text Available Abstract Background There is increased incidence of new cases of type 1 diabetes in children younger than 15 years. The debate concerning where best to manage newly diagnosed children continues. Some units routinely admit children to hospital whilst others routinely manage children at home. A Cochrane review identified the need for a large well-designed randomised controlled trial to investigate any significant differences in comprehensive short and long-term outcomes between the two approaches. The DECIDE study will address these knowledge gaps, providing high quality evidence to inform national and international policy and practice. Methods/Design This is a multi-centre randomised controlled trial across eight UK paediatric diabetes centres. The study aims to recruit 240 children newly diagnosed with type 1 diabetes and their parents/carers. Eligible patients (aged 0-17 years will be remotely randomised to either 'hospital' or 'home' management. Parents/carers of patients will also be recruited. Nursing management of participants and data collection will be co-ordinated by a project nurse at each centre. Data will be collected for 24 months after diagnosis; at follow up appointments at 3, 12 and 24 months and every 3-4 months at routine clinic visits. The primary outcome measure is patients' glycosylated haemoglobin (HbA1c at 24 months after diagnosis. Additional measurements of HbA1c will be made at diagnosis and 3 and 12 months later. HbA1c concentrations will be analysed at a central laboratory. Secondary outcome measures include length of stay at diagnosis, growth, adverse events, quality of life, anxiety, coping with diabetes, diabetes knowledge, home/clinic visits, self-care activity, satisfaction and time off school/work. Questionnaires will be sent to participants at 1, 12 and 24 months and will include a questionnaire, developed and validated to measure impact of the diagnosis on social activity and independence. Additional

Atorvastatin reduces T-cell activation and exhaustion among HIV-infected cART-treated suboptimal immune responders in Uganda: a randomised crossover placebo-controlled trial.

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Nakanjako, Damalie; Ssinabulya, Isaac; Nabatanzi, Rose; Bayigga, Lois; Kiragga, Agnes; Joloba, Moses; Kaleebu, Pontiano; Kambugu, Andrew D; Kamya, Moses R; Sekaly, Rafick; Elliott, Alison; Mayanja-Kizza, Harriet

2015-03-01

T-cell activation independently predicts mortality, poor immune recovery and non-AIDS illnesses during combination antiretroviral therapy (cART). Atorvastatin showed anti-immune activation effects among HIV-infected cART-naïve individuals. We investigated whether adjunct atorvastatin therapy reduces T-cell activation among cART-treated adults with suboptimal immune recovery. A randomised double-blind placebo-controlled crossover trial, of atorvastatin 80 mg daily vs. placebo for 12 weeks, was conducted among individuals with CD4 increase <295 cells/μl after seven years of suppressive cART. Change in T-cell activation (CD3 + CD4 + /CD8 + CD38 + HLADR+) and in T-cell exhaustion (CD3 + CD4 + /CD8 + PD1 + ) was measured using flow cytometry. Thirty patients were randomised, 15 to each arm. Atorvastatin resulted in a 28% greater reduction in CD4 T-cell activation (60% reduction) than placebo (32% reduction); P = 0.001. Atorvastatin also resulted in a 35% greater reduction in CD8-T-cell activation than placebo (49% vs. 14%, P = 0.0009), CD4 T-cell exhaustion (27% vs. 17% in placebo), P = 0.001 and CD8 T-cell exhaustion (27% vs. 16%), P = 0.004. There was no carry-over/period effect. Expected adverse events were comparable in both groups, and no serious adverse events were reported. Atorvastatin reduced T-cell immune activation and exhaustion among cART-treated adults in a Ugandan cohort. Atorvastatin adjunct therapy should be explored as a strategy to improve HIV treatment outcomes among people living with HIV in sub-Saharan Africa. © 2014 John Wiley & Sons Ltd.

Ultrasound guided injection of dexamethasone versus placebo for treatment of plantar fasciitis: protocol for a randomised controlled trial

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Gilheany Mark F

2010-07-01

Full Text Available Abstract Background Plantar fasciitis is the most commonly reported cause of chronic pain beneath the heel. Management of this condition commonly involves the use of corticosteroid injection in cases where less invasive treatments have failed. However, despite widespread use, only two randomised trials have tested the effect of this treatment in comparison to placebo. These trials currently offer the best available evidence by which to guide clinical practice, though both were limited by methodological issues such as insufficient statistical power. Therefore, the aim of this randomised trial is to compare the effect of ultrasound-guided corticosteroid injection versus placebo for treatment of plantar fasciitis. Methods The trial will be conducted at the La Trobe University Podiatry Clinic and will recruit 80 community-dwelling participants. Diagnostic ultrasound will be used to diagnose plantar fasciitis and participants will be required to meet a range of selection criteria. Participants will be randomly allocated to one of two treatment arms: (i ultrasound-guided injection of the plantar fascia with 1 mL of 4 mg/mL dexamethasone sodium phosphate (experimental group, or (ii ultrasound-guided injection of the plantar fascia with 1 mL normal saline (control group. Blinding will be applied to participants and the investigator performing procedures, measuring outcomes and analysing data. Primary outcomes will be pain measured by the Foot Health Status Questionnaire and plantar fascia thickness measured by ultrasound at 4, 8 and 12 weeks. All data analyses will be conducted on an intention-to-treat basis. Conclusion This will be a randomised trial investigating the effect of dexamethasone injection on pre-specified treatment outcomes in people with plantar fasciitis. Within the parameters of this protocol, the trial findings will be used to make evidence-based recommendations regarding the use of corticosteroid injection for treatment of this

The effects of transdermal testosterone and oestrogen therapy on dry eye in postmenopausal women: a randomised, placebo-controlled, pilot study.

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Golebiowski, Blanka; Badarudin, Noor; Eden, John; Gerrand, Leanne; Robinson, Jennifer; Liu, Jinzhu; Hampel, Ulrike; You, Jingjing; Stapleton, Fiona

2017-07-01

Sex hormones could provide a future treatment avenue for dry eye post menopause. However, there are few well-controlled studies. This study investigates the impact of testosterone and oestrogen on dry eye symptoms and signs in postmenopausal women. A randomised double-blind placebo-controlled pilot study was conducted involving 40 women with dry eye (age 63.9±5.1 years, 13.2±6.3 years post menopause). Ten women were assigned to each of four treatment groups: transdermal testosterone, oestradiol, testosterone/oestradiol combination and placebo. Assessment at baseline and after 8 weeks: ocular symptoms, tear osmolarity, tear stability, tear secretion, meibomian gland assessment, corneal and conjunctival sensitivity, serum concentrations of 17β-oestradiol, 3-α-androstanediol-glucuronide and dehydroepiandrosterone sulfate. Differences from placebo were examined using one-way analysis of variance and Dunnett's t-test. Within-group analyses included paired t-tests and Spearman correlation. Dryness intensity after 8 weeks was significantly worse in the oestrogen group compared with placebo (p=0.04). No significant changes in other symptoms, tear function, meibomian gland function, lid morphology, corneal or conjunctival sensitivity were observed in any of the groups when compared with the change in placebo after 8 weeks. Within-group analyses showed increased tear secretion in the testosterone/oestradiol combination group (p=0.03) and a strong association between increased serum androgen and improved tear stability in the testosterone group (ρ=0.83,p=0.01). Oestrogen supplementation may worsen ocular symptoms in postmenopausal women with dry eye, whereas no impact of testosterone therapy on symptoms was apparent. The positive effects of oestrogen and testosterone on tear function require confirmation in a larger study, with sample size calculated from the data generated herein. Placebo control is essential in studies of dry eye therapies. ACTRN

The effect of motivational interviewing on glycaemic control and perceived competence of diabetes self-management in patients with type 1 and type 2 diabetes mellitus after attending a group education programme: a randomised controlled trial

DEFF Research Database (Denmark)

Rosenbek Minet, L K; Wagner, L; Lønvig, E M

2011-01-01

education programme, 349 patients were randomised to either a usual care control group or an intervention group, which received up to five individual counselling sessions in 1 year based on MI, in addition to usual care. A randomised parallel design was used and open-label allocation was done by random...... diabetes mellitus, were over 18 years of age and had participated in a 4 day group education programme offered at a diabetes clinic at a university hospital in Denmark. Exclusion criteria included pregnancy, severe debilitating disease and cognitive deficit. Out of 469 patients who attended the group...... diabetes self-care, compared with usual care. RESULTS: Out of the 176 included in the control group and 173 in the intervention group, 153 and 145 were analysed in the groups, respectively. When using the baseline value as covariate there were no significant differences in change score between the two...

Momordica charantia for type 2 diabetes mellitus.

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Ooi, Cheow Peng; Yassin, Zaitun; Hamid, Tengku-Aizan

2012-08-15

Momordica charantia (bitter gourd) is not only a nutritious vegetable but it is also used in traditional medical practices to treat type 2 diabetes mellitus. Experimental studies with animals and humans suggested that the vegetable has a possible role in glycaemic control. To assess the effects of mormodica charantia for type 2 diabetes mellitus. Several electronic databases were searched, among these were The Cochrane Library (Issue 1, 2012), MEDLINE, EMBASE, CINAHL, SIGLE and LILACS (all up to February 2012), combined with handsearches. No language restriction was used. We included randomised controlled trials (RCTs) that compared momordica charantia with placebo or a control intervention, with or without pharmacological or non-pharmacological interventions. Two authors independently extracted data. Risk of bias of the trials was evaluated using the parameters of randomisation, allocation concealment, blinding, completeness of outcome data, selective reporting and other potential sources of bias. A meta-analysis was not performed given the quality of data and the variability of preparations of momordica charantia used in the interventions (no similar preparation was tested twice). Four randomised controlled trials with up to three months duration and investigating 479 participants met the inclusion criteria. Risk of bias of these trials (only two studies were published as a full peer-reviewed publication) was generally high. Two RCTs compared the effects of preparations from different parts of the momordica charantia plant with placebo on glycaemic control in type 2 diabetes mellitus. There was no statistically significant difference in the glycaemic control with momordica charantia preparations compared to placebo. When momordica charantia was compared to metformin or glibenclamide, there was also no significant change in reliable parameters of glycaemic control. No serious adverse effects were reported in any trial. No trial investigated death from any cause

Oral doxycycline for the prevention of postoperative trachomatous trichiasis in Ethiopia: a randomised, double-blind, placebo-controlled trial

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Esmael Habtamu, PhD

2018-05-01

Full Text Available Summary: Background: Trachomatous trichiasis is treated surgically to prevent sight loss. Unfavourable surgical outcomes remain a major challenge. We investigated the hypothesis that doxycycline might reduce the risk of postoperative trichiasis following surgery in patients with trachomatous trichiasis through anti-matrix metalloproteinase and anti-inflammatory activity. Methods: In this randomised, double-blind, placebo-controlled trial, adults (aged >18 years with upper lid trachomatous trichiasis in association with tarsal conjunctive scarring were recruited through community-based screening and surgical outreach campaigns in Ethiopia. Individuals who had previously had eyelid surgery were excluded. Participants were randomly assigned (1:1, with random block sizes of four or six, to receive oral doxycycline (100 mg once a day or placebo for 28 days immediately after trichiasis surgery. Randomisation was stratified by surgeon. Patients, investigators, surgeons, and all other study team members were masked to study group allocation and treatment. Participants were examined at 10 days, and 1, 6, and 12 months after surgery. The primary outcome was the cumulative proportion of individuals who developed postoperative trichiasis by 12 months. Primary analyses were done in all participants who attended at least one of the four follow-up assessments. Safety analyses were done in all participants who attended either the 10 day or 1 month follow-up assessments. This trial is registered with the Pan African Clinical Trials Registry, number PACTR201512001370307. Findings: Between Dec 21, 2015, and April 6, 2016, 1000 patients with trichiasis were enrolled and randomly assigned to treatment (499 patients to doxycycline, 501 patients to placebo. All but one participant attended at least one follow-up assessment. Thus, 999 participants were assessed for the primary outcome: 498 in the doxycycline group and 501 in the placebo group. By month 12, 58 (12% of

Administration of misoprostol by trained traditional birth attendants to prevent postpartum haemorrhage in homebirths in Pakistan: a randomised placebo-controlled trial.

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Mobeen, N; Durocher, J; Zuberi, Nf; Jahan, N; Blum, J; Wasim, S; Walraven, G; Hatcher, J

2011-02-01

to determine if misoprostol is safe and efficacious in preventing postpartum haemorrhage (PPH) when administered by trained traditional birth attendants (TBA) at home deliveries. a randomised, double-blind, placebo-controlled trial. Chitral, Khyber Pakhtunkhwa Province, Pakistan. a total of 1119 women giving birth at home. from June 2006 to June 2008, consenting women were randomised to receive 600 microg oral misoprostol (n = 534) or placebo (n = 585) after delivery to determine whether misoprostol reduced the incidence of PPH (≥ 500 ml). the primary outcomes were measured blood loss ≥ 500 ml after delivery and drop in haemoglobin >2 g/dl from before to after delivery. oral misoprostol was associated with a significant reduction in the rate of PPH (≥ 500 ml) (16.5 versus 21.9%; relative risk 0.76, 95% CI 0.59-0.97). There were no measurable differences between study groups for drop in haemoglobin >2 g/dl (relative risk 0.79, 95% CI 0.62-1.02); but significantly fewer women receiving misoprostol had a drop in haemoglobin >3 g/dl, compared with placebo (5.1 versus 9.6%; relative risk 0.53, 95% CI 0.34-0.83). Shivering and chills were significantly more common with misoprostol. There were no maternal deaths among participants. postpartum administration of 600 microg oral misoprostol by trained TBAs at home deliveries reduces the rate of PPH by 24%. Given its ease of use and low cost, misoprostol could reduce the burden of PPH in community settings where universal oxytocin prophylaxis is not feasible. Continual training and skill-building for TBAs, along with monitoring and evaluation of programme effectiveness, should accompany any widespread introduction of this drug.

Web-based cognitive behavioural therapy (W-CBT for diabetes patients with co-morbid depression: Design of a randomised controlled trial

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Pouwer Frans

2008-02-01

Full Text Available Abstract Background Depression is common among people with diabetes, negatively affecting quality of life, treatment adherence and diabetes outcomes. In routine clinical care, diabetes patients have limited access to mental health services and depression therefore often remains untreated. Web-based therapy could potentially be an effective way to improve the reach of psychological care for diabetes patients, at relatively low costs. This study seeks to test the effectiveness of a web-based self-help depression programme for people with diabetes and co-morbid depression. Methods/Design The effectiveness of a web-based self-help course for adults with diabetes with co-morbid depression will be tested in a randomised trial, using a wait-list controlled design. The intervention consists of an 8-week, moderated self-help course that is tailored to the needs of persons living with diabetes and is offered on an individual basis. Participants receive feedback on their homework assignments by e-mail from their coach. We aim to include 286 patients (143/143, as power analyses showed that this number is needed to detect an effect size of 0.35, with measurements at baseline, directly after completing the web-based intervention and at 1, 3, 4 and 6 months follow-up. Patients in the control condition are placed on a waiting list, and follow the course 12 weeks after randomisation. Primary outcomes are depressive symptoms and diabetes-specific emotional distress. Secondary outcomes are satisfaction with the course, perceived health status, self-care behaviours, glycaemic control, and days in bed/absence from work. Questionnaires are administered via the Internet. Discussion The intervention being trialled is expected to help improve mood and reduce diabetes-specific emotional distress in diabetes patients with depression, with subsequent beneficial effects on diabetes self-care and glycaemic outcomes. When proven efficacious, the intervention could be

Tasimelteon for non-24-hour sleep-wake disorder in totally blind people (SET and RESET): two multicentre, randomised, double-masked, placebo-controlled phase 3 trials.

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Lockley, Steven W; Dressman, Marlene A; Licamele, Louis; Xiao, Changfu; Fisher, Dennis M; Flynn-Evans, Erin E; Hull, Joseph T; Torres, Rosarelis; Lavedan, Christian; Polymeropoulos, Mihael H

2015-10-31

Most totally blind people have non-24-hour sleep-wake disorder (non-24), a rare circadian rhythm disorder caused by an inability of light to reset their circadian pacemaker. In two consecutive placebo-controlled trials (SET and RESET), we assessed safety and efficacy (in terms of circadian entrainment and maintenance) of once-daily tasimelteon, a novel dual-melatonin receptor agonist. We undertook the placebo-controlled, randomised, double-masked trials in 27 US and six German clinical research centres and sleep centres. We screened totally blind adults (18-75 years of age), who were eligible for the randomisation phase of SET if they had a non-24-hour circadian period (τ) of 24·25 h or longer (95% CI greater than 24·0 and up to 24·9 h), as calculated from measurements of urinary 6-sulphatoxymelatonin rhythms. For SET, we used block randomisation to assign patients (1:1) to receive tasimelteon (20 mg) or placebo every 24 h at a fixed clock time 1 h before target bedtime for 26 weeks. Patients who entered the open-label group receiving tasimelteon in SET or who did not meet the SET inclusion criteria but did meet the RESET inclusion criteria were screened for RESET. A subset of the patients who entered the open-label group before the RESET study and who had eligible τ values were screened for RESET after completing the open-label treatment. In RESET, we withdrew tasimelteon in a randomised manner (1:1) in patients who responded (ie, entrained) after a tasimelteon run-in period. Entrainment was defined as having τ of 24·1 h or less and a 95% CI that included 24·0 h. In SET, the primary endpoint was the proportion of entrained patients, assessed in the intention-to-treat population. The planned step-down primary endpoint assessed the proportion of patients who had a clinical response (entrainment at month 1 or month 7 plus clinical improvement, measured by the Non-24 Clinical Response Scale). In RESET, the primary endpoint was the proportion of non

The protocol of the Oslo Study of Clonidine in Elderly Patients with Delirium; LUCID: a randomised placebo-controlled trial.

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Neerland, Bjørn Erik; Hov, Karen Roksund; Bruun Wyller, Vegard; Qvigstad, Eirik; Skovlund, Eva; MacLullich, Alasdair M J; Bruun Wyller, Torgeir

2015-02-10

Delirium affects 15% of hospitalised patients and is linked with poor outcomes, yet few pharmacological treatment options exist. One hypothesis is that delirium may in part result from exaggerated and/or prolonged stress responses. Dexmedetomidine, a parenterally-administered alpha2-adrenergic receptor agonist which attenuates sympathetic nervous system activity, shows promise as treatment in ICU delirium. Clonidine exhibits similar pharmacodynamic properties and can be administered orally. We therefore wish to explore possible effects of clonidine upon the duration and severity of delirium in general medical inpatients. The Oslo Study of Clonidine in Elderly Patients with Delirium (LUCID) is a randomised, placebo-controlled, double-blinded, parallel group study with 4-month prospective follow-up. We will recruit 100 older medical inpatients with delirium or subsyndromal delirium in the acute geriatric ward. Participants will be randomised to oral clonidine or placebo until delirium free for 2 days (Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria), or after a maximum of 7 days treatment. Assessment of haemodynamics (blood pressure, heart rate and electrocardiogram) and delirium will be performed daily until discharge or a maximum of 7 days after end of treatment. The primary endpoint is the trajectory of delirium over time (measured by Memorial Delirium Assessment Scale). Secondary endpoints include the duration of delirium, use of rescue medication for delirium, pharmacokinetics and pharmacodynamics of clonidine, cognitive function after 4 months, length of hospital stay and need for institutionalisation. LUCID will explore the efficacy and safety of clonidine for delirium in older medical inpatients. ClinicalTrials.gov NCT01956604. EudraCT Number: 2013-000815-26.

Effect of 50 000 IU vitamin A given with BCG vaccine on mortality in infants in Guinea-Bissau: randomised placebo controlled trial

DEFF Research Database (Denmark)

Diness, B.R.; Roth, A.; Nante, E.

2008-01-01

Objective To investigate the effect of high dose vitamin A supplementation given with BCG vaccine at birth in an African setting with high infant mortality. Design Randomised placebo controlled trial. Setting Bandim Health Project's demographic surveillance system in Guinea-Bissau, covering.......84 (0.55 to 1.27) compared with 1.39 (0.90 to 2.14) in girls (P for interaction=0.10). An explorative analysis revealed a strong interaction between vitamin A and season of administration. Conclusions Vitamin A supplementation given with BCG vaccine at birth had no significant benefit in this African...

Repeated nebulisation of non-viral CFTR gene therapy in patients with cystic fibrosis: a randomised, double-blind, placebo-controlled, phase 2b trial.

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Alton, Eric W F W; Armstrong, David K; Ashby, Deborah; Bayfield, Katie J; Bilton, Diana; Bloomfield, Emily V; Boyd, A Christopher; Brand, June; Buchan, Ruaridh; Calcedo, Roberto; Carvelli, Paula; Chan, Mario; Cheng, Seng H; Collie, D David S; Cunningham, Steve; Davidson, Heather E; Davies, Gwyneth; Davies, Jane C; Davies, Lee A; Dewar, Maria H; Doherty, Ann; Donovan, Jackie; Dwyer, Natalie S; Elgmati, Hala I; Featherstone, Rosanna F; Gavino, Jemyr; Gea-Sorli, Sabrina; Geddes, Duncan M; Gibson, James S R; Gill, Deborah R; Greening, Andrew P; Griesenbach, Uta; Hansell, David M; Harman, Katharine; Higgins, Tracy E; Hodges, Samantha L; Hyde, Stephen C; Hyndman, Laura; Innes, J Alastair; Jacob, Joseph; Jones, Nancy; Keogh, Brian F; Limberis, Maria P; Lloyd-Evans, Paul; Maclean, Alan W; Manvell, Michelle C; McCormick, Dominique; McGovern, Michael; McLachlan, Gerry; Meng, Cuixiang; Montero, M Angeles; Milligan, Hazel; Moyce, Laura J; Murray, Gordon D; Nicholson, Andrew G; Osadolor, Tina; Parra-Leiton, Javier; Porteous, David J; Pringle, Ian A; Punch, Emma K; Pytel, Kamila M; Quittner, Alexandra L; Rivellini, Gina; Saunders, Clare J; Scheule, Ronald K; Sheard, Sarah; Simmonds, Nicholas J; Smith, Keith; Smith, Stephen N; Soussi, Najwa; Soussi, Samia; Spearing, Emma J; Stevenson, Barbara J; Sumner-Jones, Stephanie G; Turkkila, Minna; Ureta, Rosa P; Waller, Michael D; Wasowicz, Marguerite Y; Wilson, James M; Wolstenholme-Hogg, Paul

2015-09-01

Lung delivery of plasmid DNA encoding the CFTR gene complexed with a cationic liposome is a potential treatment option for patients with cystic fibrosis. We aimed to assess the efficacy of non-viral CFTR gene therapy in patients with cystic fibrosis. We did this randomised, double-blind, placebo-controlled, phase 2b trial in two cystic fibrosis centres with patients recruited from 18 sites in the UK. Patients (aged ≥12 years) with a forced expiratory volume in 1 s (FEV1) of 50-90% predicted and any combination of CFTR mutations, were randomly assigned, via a computer-based randomisation system, to receive 5 mL of either nebulised pGM169/GL67A gene-liposome complex or 0.9% saline (placebo) every 28 days (plus or minus 5 days) for 1 year. Randomisation was stratified by % predicted FEV1 (<70 vs ≥70%), age (<18 vs ≥18 years), inclusion in the mechanistic substudy, and dosing site (London or Edinburgh). Participants and investigators were masked to treatment allocation. The primary endpoint was the relative change in % predicted FEV1. The primary analysis was per protocol. This trial is registered with ClinicalTrials.gov, number NCT01621867. Between June 12, 2012, and June 24, 2013, we randomly assigned 140 patients to receive placebo (n=62) or pGM169/GL67A (n=78), of whom 116 (83%) patients comprised the per-protocol population. We noted a significant, albeit modest, treatment effect in the pGM169/GL67A group versus placebo at 12 months' follow-up (3.7%, 95% CI 0.1-7.3; p=0.046). This outcome was associated with a stabilisation of lung function in the pGM169/GL67A group compared with a decline in the placebo group. We recorded no significant difference in treatment-attributable adverse events between groups. Monthly application of the pGM169/GL67A gene therapy formulation was associated with a significant, albeit modest, benefit in FEV1 compared with placebo at 1 year, indicating a stabilisation of lung function in the treatment group. Further improvements in

Efficacy of metformin in pregnant obese women: a randomised controlled trial.

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Chiswick, Carolyn A; Reynolds, Rebecca M; Denison, Fiona C; Whyte, Sonia A; Drake, Amanda J; Newby, David E; Walker, Brian R; Forbes, Shareen; Murray, Gordon D; Quenby, Siobhan; Wray, Susan; Norman, Jane E

2015-01-14

Increasing evidence suggests obesity has its origins prior to birth. There is clear correlation between maternal obesity, high birthweight and offspring risk of obesity in later life. It is also clear that women who are obese during pregnancy are at greater risk of adverse outcomes, including gestational diabetes and stillbirth. The mechanism(s) by which obesity causes these problems is unknown, although hyperglycaemia and insulin resistance are strongly implicated. We present a protocol for a study to test the hypothesis that metformin will improve insulin sensitivity in obese pregnant women, thereby reducing the incidence of high birthweight babies and other pregnancy complications. The Efficacy of Metformin in Pregnant Obese Women, a Randomised controlled (EMPOWaR) trial is a double-masked randomised placebo-controlled trial to determine whether metformin given to obese (body mass index >30 kg/m(2)) pregnant women from 16 weeks' gestation until delivery reduces the incidence of high birthweight babies. A secondary aim is to test the mechanism(s) of any effect. Obese women with a singleton pregnancy and normal glucose tolerance will be recruited prior to 16 weeks' gestation and prescribed study medication, metformin or placebo, to be taken until delivery. Further study visits will occur at 28 and 36 weeks' gestation for glucose tolerance testing and to record anthropometric measurements. Birth weight and other measurements will be recorded at time of delivery. Anthropometry of mother and baby will be performed at 3 months postdelivery. As of January 2014, 449 women had been randomised across the UK. The study will be conducted in accordance with the principles of Good Clinical Practice. A favourable ethical opinion was obtained from Scotland A Research Ethics Committee, reference number 10/MRE00/12. Results will be disseminated at conferences and published in peer-reviewed journals. ISRCTN51279843. Published by the BMJ Publishing Group Limited. For

The LeucoPatch® system in the management of hard-to-heal diabetic foot ulcers: study protocol for a randomised controlled trial.

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Game, Frances; Jeffcoate, William; Tarnow, Lise; Day, Florence; Fitzsimmons, Deborah; Jacobsen, Judith

2017-10-10

Diabetic foot ulcers are a common and severe complication of diabetes mellitus. Standard treatment includes debridement, offloading, management of infection and revascularisation where appropriate, although healing times may be long. The LeucoPatch® device is used to generate an autologous platelet-rich fibrin and leucocyte wound dressing produced from the patient's own venous blood by centrifugation, but without the addition of any reagents. The final product comprises a thin, circular patch composed predominantly of fibrin together with living platelets and leucocytes. Promising results have been obtained in non-controlled studies this system, but this now needs to be tested in a randomised controlled trial (RCT). If confirmed, the LeucoPatch® may become an important new tool in the armamentarium in the management of diabetic foot ulcers which are hard-to-heal. People with diabetes and hard-to-heal ulcers of the foot will receive either pre-specified good standard care or good standard care supplemented by the application of the LeucoPatch® device. The primary outcome will be the percentage of ulcers healed within 20 weeks. Healing will be defined as complete epithelialisation without discharge that is maintained for 4 weeks and is confirmed by an observer blind to randomisation group. Ulcers of the foot are a major source of morbidity to patients with diabetes and costs to health care economies. The study population is designed to be as inclusive as possible with the aim of maximising the external validity of any findings. The primary outcome measure is healing within 20 weeks of randomisation and the trial also includes a number of secondary outcome measures. Among these are rate of change in ulcer area as a predictor of the likelihood of eventual healing, minor and major amputation of the target limb, the incidence of infection and quality of life. International Standard Randomised Controlled Trial, ISRCTN27665670 . Registered on 5 July 2013.

Impact of chromium dinicocysteinate supplementation on inflammation, oxidative stress, and insulin resistance in type 2 diabetic subjects: an exploratory analysis of a randomized, double-blind, placebo-controlled study

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Zainulabedin M. Saiyed

2016-09-01

Full Text Available Background: Chromium dinicocysteinate (CDNC is a unique chromium complex consisting of chromium, niacin, and L-cysteine. Previous preclinical and clinical studies support the safety and efficacy of CDNC in modulating oxidative stress, vascular inflammation, and glycemia in type 2 diabetes. Objective: Herein, we report the results of several exploratory analyses conducted on type 2 diabetic subjects who previously participated in a 3-month randomized, double-blind, placebo-controlled trial and were treated with only metformin as standard diabetic care in addition to receiving the test supplementations. Design: Results from 43 metformin users, who were randomly assigned to receive either placebo (P, n=13, chromium picolinate (CP, 400 µg elemental Cr3+/day, n=12, or CDNC (400 µg elemental Cr3+/day, n=18, were analyzed for blood markers of vascular inflammation, insulin resistance, and oxidative stress at baseline and at 3 months of supplementation. Results: A statistically significant decrease in insulin resistance in the CDNC-supplemented cohort compared to placebo (p=0.01 was observed at 3 months. The CDNC group also demonstrated a significant reduction in insulin levels (p=0.03, protein carbonyl (p=0.02, and in TNF-α (p=0.03 compared to the placebo group. The CP group only showed a significant reduction in protein carbonyl levels (p=0.03 versus placebo. Conclusions: When controlling for diabetes medication, CDNC supplementation showed beneficial effects on blood markers of vascular inflammation, insulin resistance, and oxidative stress compared to placebo. The findings suggest that CDNC supplementation has potential as an adjunct therapy for individuals with type 2 diabetes.

Metformin versus Placebo in Obese Pregnant Women without Diabetes Mellitus.

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Syngelaki, Argyro; Nicolaides, Kypros H; Balani, Jyoti; Hyer, Steve; Akolekar, Ranjit; Kotecha, Reena; Pastides, Alice; Shehata, Hassan

2016-02-04

Obesity is associated with an increased risk of adverse pregnancy outcomes. Lifestyle-intervention studies have not shown improved outcomes. Metformin improves insulin sensitivity and in pregnant patients with gestational diabetes it leads to less weight gain than occurs in those who do not take metformin. In this double-blind, placebo-controlled trial, we randomly assigned pregnant women without diabetes who had a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of more than 35 to receive metformin, at a dose of 3.0 g per day, or placebo (225 women in each group) from 12 to 18 weeks of gestation until delivery. The BMI was calculated at the time of study entry (12 to 18 weeks of gestation). The primary outcome was a reduction in the median neonatal birth-weight z score by 0.3 SD (equivalent to a 50% reduction, from 20% to 10%, in the incidence of large-for-gestational-age neonates). Secondary outcomes included maternal gestational weight gain and the incidence of gestational diabetes and of preeclampsia, as well as the incidence of adverse neonatal outcomes. Randomization was performed with the use of computer-generated random numbers. The analysis was performed according to the intention-to-treat principle. A total of 50 women withdrew consent during the trial, which left 202 women in the metformin group and 198 in the placebo group. There was no significant between-group difference in the median neonatal birth-weight z score (0.05 in the metformin group [interquartile range, -0.71 to 0.92] and 0.17 in the placebo group [interquartile range, -0.62 to 0.89], P=0.66). The median maternal gestational weight gain was lower in the metformin group than in the placebo group (4.6 kg [interquartile range, 1.3 to 7.2] vs. 6.3 kg [interquartile range, 2.9 to 9.2], Pmetformin group than in the placebo group. There were no significant between-group differences in the incidence of gestational diabetes, large

Safety and efficacy of repeated injections of botulinum toxin A in peripheral neuropathic pain (BOTNEP): a randomised, double-blind, placebo-controlled trial.

Science.gov (United States)

Attal, Nadine; de Andrade, Daniel C; Adam, Frédéric; Ranoux, Danièle; Teixeira, Manoel J; Galhardoni, Ricardo; Raicher, Irina; Üçeyler, Nurcan; Sommer, Claudia; Bouhassira, Didier

2016-05-01

Data from previous studies suggest that botulinum toxin A has analgesic effects against peripheral neuropathic pain, but the quality of the evidence is low. We aimed to assess the safety and efficacy of repeated administrations of botulinum toxin A in patients with neuropathic pain. We did a randomised, double-blind, placebo-controlled trial at two outpatient clinics in France (Clinical Pain Centre, Ambroise Paré Hospital, APHP, Boulogne-Billancourt, and Neurological Centre, Hôpital Dupuytren, Limoges) and one in Brazil (Neurological Department, Hospital das Clínicas da FMUSP, São Paulo). Patients aged 18-85 years with peripheral neuropathic pain were randomly assigned (1:1) by block randomisation, according to a centralised schedule, to receive two subcutaneous administrations of botulinum toxin A (up to 300 units) or placebo, 12 weeks apart. All patients and investigators were masked to treatment assignment. The primary outcome was the efficacy of botulinum toxin A versus placebo, measured as the change from baseline in self-reported mean weekly pain intensity over the course of 24 weeks from the first administration. The primary efficacy analysis was a mixed-model repeated-measures analysis in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT01251211. Between Oct 2, 2010, and Aug 2, 2013, 152 patients were enrolled, of whom 68 were randomly assigned (34 per group), and 66 (37 [56%] men) were included in the primary analysis (34 in the botulinum toxin A group and 32 in the placebo group). Botulinum toxin A reduced pain intensity over 24 weeks compared with placebo (adjusted effect estimate -0·77, 95% CI -0·95 to -0·59; pbotulinum toxin A group and 17 (53%) of those in the placebo group (p=1·0). Severe pain was experienced by ten (29%) participants in the botulinum toxin A group and 11 (34%) in the placebo group (p=0·8). Two administrations of botulinum toxin A, each of which comprised several injections, have a

The BRAIN TRIAL: a randomised, placebo controlled trial of a Bradykinin B2 receptor antagonist (Anatibant in patients with traumatic brain injury

Directory of Open Access Journals (Sweden)

Rätsep Indrek

2009-12-01

Full Text Available Abstract Background Cerebral oedema is associated with significant neurological damage in patients with traumatic brain injury. Bradykinin is an inflammatory mediator that may contribute to cerebral oedema by increasing the permeability of the blood-brain barrier. We evaluated the safety and effectiveness of the non-peptide bradykinin B2 receptor antagonist Anatibant in the treatment of patients with traumatic brain injury. During the course of the trial, funding was withdrawn by the sponsor. Methods Adults with traumatic brain injury and a Glasgow Coma Scale score of 12 or less, who had a CT scan showing an intracranial abnormality consistent with trauma, and were within eight hours of their injury were randomly allocated to low, medium or high dose Anatibant or to placebo. Outcomes were Serious Adverse Events (SAE, mortality 15 days following injury and in-hospital morbidity assessed by the Glasgow Coma Scale (GCS, the Disability Rating Scale (DRS and a modified version of the Oxford Handicap Scale (HIREOS. Results 228 patients out of a planned sample size of 400 patients were randomised. The risk of experiencing one or more SAEs was 26.4% (43/163 in the combined Anatibant treated group, compared to 19.3% (11/57 in the placebo group (relative risk = 1.37; 95% CI 0·76 to 2·46. All cause mortality in the Anatibant treated group was 19% and in the placebo group 15.8% (relative risk 1.20, 95% CI 0.61 to 2.36. The mean GCS at discharge was 12.48 in the Anatibant treated group and 13.0 in the placebo group. Mean DRS was 11.18 Anatibant versus 9.73 placebo, and mean HIREOS was 3.94 Anatibant versus 3.54 placebo. The differences between the mean levels for GCS, DRS and HIREOS in the Anatibant and placebo groups, when adjusted for baseline GCS, showed a non-significant trend for worse outcomes in all three measures. Conclusion This trial did not reach the planned sample size of 400 patients and consequently, the study power to detect an increase in

The BRAIN TRIAL: a randomised, placebo controlled trial of a Bradykinin B2 receptor antagonist (Anatibant) in patients with traumatic brain injury.

Science.gov (United States)

Shakur, Haleema; Andrews, Peter; Asser, Toomas; Balica, Laura; Boeriu, Cristian; Quintero, Juan Diego Ciro; Dewan, Yashbir; Druwé, Patrick; Fletcher, Olivia; Frost, Chris; Hartzenberg, Bennie; Mantilla, Jorge Mejia; Murillo-Cabezas, Francisco; Pachl, Jan; Ravi, Ramalingam R; Rätsep, Indrek; Sampaio, Cristina; Singh, Manmohan; Svoboda, Petr; Roberts, Ian

2009-12-03

Cerebral oedema is associated with significant neurological damage in patients with traumatic brain injury. Bradykinin is an inflammatory mediator that may contribute to cerebral oedema by increasing the permeability of the blood-brain barrier. We evaluated the safety and effectiveness of the non-peptide bradykinin B2 receptor antagonist Anatibant in the treatment of patients with traumatic brain injury. During the course of the trial, funding was withdrawn by the sponsor. Adults with traumatic brain injury and a Glasgow Coma Scale score of 12 or less, who had a CT scan showing an intracranial abnormality consistent with trauma, and were within eight hours of their injury were randomly allocated to low, medium or high dose Anatibant or to placebo. Outcomes were Serious Adverse Events (SAE), mortality 15 days following injury and in-hospital morbidity assessed by the Glasgow Coma Scale (GCS), the Disability Rating Scale (DRS) and a modified version of the Oxford Handicap Scale (HIREOS). 228 patients out of a planned sample size of 400 patients were randomised. The risk of experiencing one or more SAEs was 26.4% (43/163) in the combined Anatibant treated group, compared to 19.3% (11/57) in the placebo group (relative risk = 1.37; 95% CI 0.76 to 2.46). All cause mortality in the Anatibant treated group was 19% and in the placebo group 15.8% (relative risk 1.20, 95% CI 0.61 to 2.36). The mean GCS at discharge was 12.48 in the Anatibant treated group and 13.0 in the placebo group. Mean DRS was 11.18 Anatibant versus 9.73 placebo, and mean HIREOS was 3.94 Anatibant versus 3.54 placebo. The differences between the mean levels for GCS, DRS and HIREOS in the Anatibant and placebo groups, when adjusted for baseline GCS, showed a non-significant trend for worse outcomes in all three measures. This trial did not reach the planned sample size of 400 patients and consequently, the study power to detect an increase in the risk of serious adverse events was reduced. This trial

Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial.

Science.gov (United States)

Cuzick, Jack; Sestak, Ivana; Forbes, John F; Dowsett, Mitch; Knox, Jill; Cawthorn, Simon; Saunders, Christobel; Roche, Nicola; Mansel, Robert E; von Minckwitz, Gunter; Bonanni, Bernardo; Palva, Tiina; Howell, Anthony

2014-03-22

Aromatase inhibitors effectively prevent breast cancer recurrence and development of new contralateral tumours in postmenopausal women. We assessed the efficacy and safety of the aromatase inhibitor anastrozole for prevention of breast cancer in postmenopausal women who are at high risk of the disease. Between Feb 2, 2003, and Jan 31, 2012, we recruited postmenopausal women aged 40-70 years from 18 countries into an international, double-blind, randomised placebo-controlled trial. To be eligible, women had to be at increased risk of breast cancer (judged on the basis of specific criteria). Eligible women were randomly assigned (1:1) by central computer allocation to receive 1 mg oral anastrozole or matching placebo every day for 5 years. Randomisation was stratified by country and was done with blocks (size six, eight, or ten). All trial personnel, participants, and clinicians were masked to treatment allocation; only the trial statistician was unmasked. The primary endpoint was histologically confirmed breast cancer (invasive cancers or non-invasive ductal carcinoma in situ). Analyses were done by intention to treat. This trial is registered, number ISRCTN31488319. 1920 women were randomly assigned to receive anastrozole and 1944 to placebo. After a median follow-up of 5·0 years (IQR 3·0-7·1), 40 women in the anastrozole group (2%) and 85 in the placebo group (4%) had developed breast cancer (hazard ratio 0·47, 95% CI 0·32-0·68, pbreast cancers after 7 years was 5·6% in the placebo group and 2·8% in the anastrozole group. 18 deaths were reported in the anastrozole group and 17 in the placebo group, and no specific causes were more common in one group than the other (p=0·836). Anastrozole effectively reduces incidence of breast cancer in high-risk postmenopausal women. This finding, along with the fact that most of the side-effects associated with oestrogen deprivation were not attributable to treatment, provides support for the use of anastrozole in

5 year efficacy of a bivalent killed whole-cell oral cholera vaccine in Kolkata, India: a cluster-randomised, double-blind, placebo-controlled trial.

Science.gov (United States)

Bhattacharya, Sujit K; Sur, Dipika; Ali, Mohammad; Kanungo, Suman; You, Young Ae; Manna, Byomkesh; Sah, Binod; Niyogi, Swapan K; Park, Jin Kyung; Sarkar, Banwarilal; Puri, Mahesh K; Kim, Deok Ryun; Deen, Jacqueline L; Holmgren, Jan; Carbis, Rodney; Dhingra, Mandeep Singh; Donner, Allan; Nair, G Balakrish; Lopez, Anna Lena; Wierzba, Thomas F; Clemens, John D

2013-12-01

Efficacy and safety of a two-dose regimen of bivalent killed whole-cell oral cholera vaccine (Shantha Biotechnics, Hyderabad, India) to 3 years is established, but long-term efficacy is not. We aimed to assess protective efficacy up to 5 years in a slum area of Kolkata, India. In our double-blind, cluster-randomised, placebo-controlled trial, we assessed incidence of cholera in non-pregnant individuals older than 1 year residing in 3933 dwellings (clusters) in Kolkata, India. We randomly allocated participants, by dwelling, to receive two oral doses of modified killed bivalent whole-cell cholera vaccine or heat-killed Escherichia coli K12 placebo, 14 days apart. Randomisation was done by use of a computer-generated sequence in blocks of four. The primary endpoint was prevention of episodes of culture-confirmed Vibrio cholerae O1 diarrhoea severe enough for patients to seek treatment in a health-care facility. We identified culture-confirmed cholera cases among participants seeking treatment for diarrhoea at a study clinic or government hospital between 14 days and 1825 days after receipt of the second dose. We assessed vaccine protection in a per-protocol population of participants who had completely ingested two doses of assigned study treatment. 69 of 31 932 recipients of vaccine and 219 of 34 968 recipients of placebo developed cholera during 5 year follow-up (incidence 2·2 per 1000 in the vaccine group and 6·3 per 1000 in the placebo group). Cumulative protective efficacy of the vaccine at 5 years was 65% (95% CI 52-74; pcholera vaccines. Established long-term efficacy of this vaccine could assist policy makers formulate rational vaccination strategies to reduce overall cholera burden in endemic settings. Bill & Melinda Gates Foundation and the governments of South Korea and Sweden. Copyright © 2013 Elsevier Ltd. All rights reserved.

Presenting risk information to people with diabetes: evaluating effects and preferences for different formats by a web-based randomised controlled trial.

Science.gov (United States)

Edwards, Adrian; Thomas, Richard; Williams, Rhys; Ellner, Andrew L; Brown, Polly; Elwyn, Glyn

2006-11-01

Web-based patient information is widespread and information on the benefits and risks of treatments is often difficult to understand. We therefore evaluated different risk presentation formats - numerical, graphical and others - addressing the pros and cons of tight control versus usual treatment approaches for diabetes. Randomised controlled trial. Online. Publicity disseminated via Diabetes UK. People with diabetes or their carers. Control group information based on British Medical Journal 'Best Treatments'. Four intervention groups received enhanced information resources: (1) detailed numerical information (absolute/relative risk, numbers-needed-to-treat); (2) 'anchoring' to familiar risks or descriptions; (3) graphical (bar charts, thermometer scales, crowd figure formats); (4) combination of 1-3. Decision conflict scale (DCS, a measure of uncertainty); satisfaction with information; further free text responses for qualitative content analysis. Seven hundred and ten people visited the website and were randomised. Five hundred and eight completed the questionnaire for quantitative data. Mean DCS scores ranged from 2.12 to 2.24 for the five randomisation groups, indicating neither clear delay or vacillation about decisions (usually DCS>2.5) nor tending to make decisions (usually DCSOnline evaluation of different risk representation formats was feasible. There was a lack of intervention effects on quantitative outcomes, perhaps reflecting already well-informed participants from the Diabetes UK patient organisation. The large qualitative dataset included many comments about what participants found helpful as formats for communicating risk information. These findings assist the design of online decision aids and the representation of risk information. The challenge is to provide more information, in appropriate and clear formats, but without risking information overload. Interactive web designs hold much promise to achieve this.

Effect of 50,000 IU vitamin A given with BCG vaccine on mortality in infants in Guinea-Bissau: randomised placebo controlled trial.

Science.gov (United States)

Benn, Christine Stabell; Diness, Birgitte Rode; Roth, Adam; Nante, Ernesto; Fisker, Ane Baerent; Lisse, Ida Maria; Yazdanbakhsh, Maria; Whittle, Hilton; Rodrigues, Amabelia; Aaby, Peter

2008-06-21

To investigate the effect of high dose vitamin A supplementation given with BCG vaccine at birth in an African setting with high infant mortality. Randomised placebo controlled trial. Setting Bandim Health Project's demographic surveillance system in Guinea-Bissau, covering approximately 90,000 inhabitants. Participants 4345 infants due to receive BCG. Infants were randomised to 50,000 IU vitamin A or placebo and followed until age 12 months. Mortality rate ratios. 174 children died during follow-up (mortality=47/1000 person-years). Vitamin A supplementation was not significantly associated with mortality; the mortality rate ratio was 1.07 (95% confidence interval 0.79 to 1.44). The effect was 1.00 (0.65 to 1.56) during the first four months and 1.13 (0.75 to 1.68) from 4 to 12 months of age. The mortality rate ratio in boys was 0.84 (0.55 to 1.27) compared with 1.39 (0.90 to 2.14) in girls (P for interaction=0.10). An explorative analysis revealed a strong interaction between vitamin A and season of administration. Vitamin A supplementation given with BCG vaccine at birth had no significant benefit in this African setting. Although little doubt exists that vitamin A supplementation reduces mortality in older children, a global recommendation of supplementation for all newborn infants may not contribute to better survival. Clinical trials NCT00168597.

A double-blind, randomized, placebo-controlled clinical trial on benfotiamine treatment in patients with diabetic nephropathy.

Science.gov (United States)

Alkhalaf, Alaa; Klooster, Astrid; van Oeveren, Willem; Achenbach, Ulrike; Kleefstra, Nanne; Slingerland, Robbert J; Mijnhout, G Sophie; Bilo, Henk J G; Gans, Reinold O B; Navis, Gerjan J; Bakker, Stephan J L

2010-07-01

To investigate the effect of benfotiamine on urinary albumin excretion (UAE) and the tubular damage marker kidney injury molecule-1 (KIM-1) in patients with type 2 diabetes and nephropathy. Patients with type 2 diabetes and UAE equivalent to 15-300 mg/24 h, despite ACE inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs), were randomly assigned to 12 weeks of benfotiamine (900 mg/day) (n = 39) or placebo (n = 43). Compared with placebo, benfotiamine treatment resulted in significant improvement of thiamine status (P Benfotiamine treatment did not significantly decrease 24-h UAE or 24-h KIM-1 excretion. In patients with type 2 diabetes and nephropathy, high-dose benfotiamine treatment for 12 weeks in addition to ACE-Is or ARBs did not reduce UAE or KIM-1 excretion, despite improvement of thiamine status.

A randomised, double-blind, placebo-controlled, multicentre study of the safety and efficacy of BIOBYPASS (AdGVVEGF121.10NH) gene therapy in patients with refractory advanced coronary artery disease: the NOVA trial

DEFF Research Database (Denmark)

Kastrup, Jens; Jørgensen, Erik; Fuchs, Shmuel

2011-01-01

Genes encoding vascular endothelial growth factor (VEGF) can potentially augment myocardial perfusion in patients with coronary artery disease (CAD). We conducted a randomised, double-blind, placebo-controlled gene therapy study with the adenovirus carrying VEGF121 (BIOBYPASS [AdGVVEGF121.10NH])....

A poly-herbal blend (Herbagut®) on adults presenting with gastrointestinal complaints: a randomised, double-blind, placebo-controlled study.

Science.gov (United States)

Lopresti, Adrian L; Gupta, Hemant; Smith, Stephen J

2018-03-20

To evaluate the efficacy and tolerability of a poly-herbal formulation, Herbagut, for the treatment of gastrointestinal symptoms and its effect on quality of life parameters in patients presenting with self-reported, unsatisfactory bowel habits. This was a randomised, double-blind, placebo-controlled trial. Fifty adults with self-reported unsatisfactory bowel habits, primarily characterised by chronic constipation were randomly allocated to take Herbagut or a matching placebo for 28 days. Efficacy of gastrointestinal changes was measured by the completion of a patient daily diary evaluating changes in stool type (Bristol Stool Form Scale), ease of bowel movements, and feeling of complete evacuation; and the Gastrointestinal Symptom Rating Scale (GSRS). Changes in quality of life were also examined using the World Health Organization Quality of Life - abbreviated version (WHOQOL-BREF), and the Patient Assessment of Constipation-Quality of Life (PAC-QOL). All participants completed the 28-day trial with no adverse events reported. Compared to the placebo, weekly bowel movements increased over time (p pain, constipation, diarrhoea, indigestion, and reflux also decreased significantly in people taking Herbagut compared to placebo (p < .001, for all domains). Moreover, quality of life significantly improved in the Herbagut group compared to placebo as indicated by significantly greater improvement in WHOQOL-BREF domain ratings for overall quality of life, social relations, environmental health, psychological health, and physical health (p < .001, for all domains); and PAC-QOL domain ratings for physical discomfort, psychosocial discomfort, worries and concerns, and life satisfaction (p < .001, for all domains). The changes were considered clinically meaningful as evidenced by their large effect sizes. Herbagut ingestion over a 28-day period resulted in improvements in several gastrointestinal symptoms and overall quality of life. Further investigation

HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: evidence from genetic analysis and randomised trials

Science.gov (United States)

Swerdlow, Daniel I; Preiss, David; Kuchenbaecker, Karoline B; Holmes, Michael V; Engmann, Jorgen E L; Shah, Tina; Sofat, Reecha; Stender, Stefan; Johnson, Paul C D; Scott, Robert A; Leusink, Maarten; Verweij, Niek; Sharp, Stephen J; Guo, Yiran; Giambartolomei, Claudia; Chung, Christina; Peasey, Anne; Amuzu, Antoinette; Li, KaWah; Palmen, Jutta; Howard, Philip; Cooper, Jackie A; Drenos, Fotios; Li, Yun R; Lowe, Gordon; Gallacher, John; Stewart, Marlene C W; Tzoulaki, Ioanna; Buxbaum, Sarah G; van der A, Daphne L; Forouhi, Nita G; Onland-Moret, N Charlotte; van der Schouw, Yvonne T; Schnabel, Renate B; Hubacek, Jaroslav A; Kubinova, Ruzena; Baceviciene, Migle; Tamosiunas, Abdonas; Pajak, Andrzej; Topor-Madry, Romanvan; Stepaniak, Urszula; Malyutina, Sofia; Baldassarre, Damiano; Sennblad, Bengt; Tremoli, Elena; de Faire, Ulf; Veglia, Fabrizio; Ford, Ian; Jukema, J Wouter; Westendorp, Rudi G J; de Borst, Gert Jan; de Jong, Pim A; Algra, Ale; Spiering, Wilko; der Zee, Anke H Maitland-van; Klungel, Olaf H; de Boer, Anthonius; Doevendans, Pieter A; Eaton, Charles B; Robinson, Jennifer G; Duggan, David; Kjekshus, John; Downs, John R; Gotto, Antonio M; Keech, Anthony C; Marchioli, Roberto; Tognoni, Gianni; Sever, Peter S; Poulter, Neil R; Waters, David D; Pedersen, Terje R; Amarenco, Pierre; Nakamura, Haruo; McMurray, John J V; Lewsey, James D; Chasman, Daniel I; Ridker, Paul M; Maggioni, Aldo P; Tavazzi, Luigi; Ray, Kausik K; Seshasai, Sreenivasa Rao Kondapally; Manson, JoAnn E; Price, Jackie F; Whincup, Peter H; Morris, Richard W; Lawlor, Debbie A; Smith, George Davey; Ben-Shlomo, Yoav; Schreiner, Pamela J; Fornage, Myriam; Siscovick, David S; Cushman, Mary; Kumari, Meena; Wareham, Nick J; Verschuren, W M Monique; Redline, Susan; Patel, Sanjay R; Whittaker, John C; Hamsten, Anders; Delaney, Joseph A; Dale, Caroline; Gaunt, Tom R; Wong, Andrew; Kuh, Diana; Hardy, Rebecca; Kathiresan, Sekar; Castillo, Berta A; van der Harst, Pim; Brunner, Eric J; Tybjaerg-Hansen, Anne; Marmot, Michael G; Krauss, Ronald M; Tsai, Michael; Coresh, Josef; Hoogeveen, Ronald C; Psaty, Bruce M; Lange, Leslie A; Hakonarson, Hakon; Dudbridge, Frank; Humphries, Steve E; Talmud, Philippa J; Kivimäki, Mika; Timpson, Nicholas J; Langenberg, Claudia; Asselbergs, Folkert W; Voevoda, Mikhail; Bobak, Martin; Pikhart, Hynek; Wilson, James G; Reiner, Alex P; Keating, Brendan J; Hingorani, Aroon D; Sattar, Naveed

2015-01-01

Summary Background Statins increase the risk of new-onset type 2 diabetes mellitus. We aimed to assess whether this increase in risk is a consequence of inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the intended drug target. Methods We used single nucleotide polymorphisms in the HMGCR gene, rs17238484 (for the main analysis) and rs12916 (for a subsidiary analysis) as proxies for HMGCR inhibition by statins. We examined associations of these variants with plasma lipid, glucose, and insulin concentrations; bodyweight; waist circumference; and prevalent and incident type 2 diabetes. Study-specific effect estimates per copy of each LDL-lowering allele were pooled by meta-analysis. These findings were compared with a meta-analysis of new-onset type 2 diabetes and bodyweight change data from randomised trials of statin drugs. The effects of statins in each randomised trial were assessed using meta-analysis. Findings Data were available for up to 223 463 individuals from 43 genetic studies. Each additional rs17238484-G allele was associated with a mean 0·06 mmol/L (95% CI 0·05–0·07) lower LDL cholesterol and higher body weight (0·30 kg, 0·18–0·43), waist circumference (0·32 cm, 0·16–0·47), plasma insulin concentration (1·62%, 0·53–2·72), and plasma glucose concentration (0·23%, 0·02–0·44). The rs12916 SNP had similar effects on LDL cholesterol, bodyweight, and waist circumference. The rs17238484-G allele seemed to be associated with higher risk of type 2 diabetes (odds ratio [OR] per allele 1·02, 95% CI 1·00–1·05); the rs12916-T allele association was consistent (1·06, 1·03–1·09). In 129 170 individuals in randomised trials, statins lowered LDL cholesterol by 0·92 mmol/L (95% CI 0·18–1·67) at 1-year of follow-up, increased bodyweight by 0·24 kg (95% CI 0·10–0·38 in all trials; 0·33 kg, 95% CI 0·24–0·42 in placebo or standard care controlled trials and −0·15 kg, 95% CI −0·39 to 0·08 in intensive

Immediate Effect of Needling at CV-12 (Zhongwan) Acupuncture Point on Blood Glucose Level in Patients with Type 2 Diabetes Mellitus: A Pilot Randomized Placebo-Controlled Trial.

Science.gov (United States)

Kumar, Ranjan; Mooventhan, A; Manjunath, Nandi Krishnamurthy

2017-08-01

Diabetes mellitus is a major global health problem. Needling at CV-12 has reduced blood glucose level in diabetic rats. The aim of this study was to evaluate the effect of needling at CV-12 (Zhongwan) on blood glucose level in patients with type 2 diabetes mellitus (T2DM). Forty T2DM patients were recruited and randomized into either the acupuncture group or placebo control group. The participants in the acupuncture group were needled at CV-12 (4 cun above the center of the umbilicus), and those in the placebo control group were needled at a placebo point on the right side of the abdomen (1 cun beside the CV-12). For both groups, the needle was retained for 30 minutes. Assessments were performed prior to and after the intervention. Statistical analysis was performed using SPSS version 16. There was a significant reduction in random blood glucose level in the acupuncture group compared to baseline. No such significant change was observed in the placebo control group. The result of this study suggests that 30 minutes of needling at CV-12 might be useful in reducing blood glucose level in patients with T2DM. Copyright © 2017. Published by Elsevier B.V.

Sweeten, soother and swaddle for retinopathy of prematurity screening: a randomised placebo controlled trial.

LENUS (Irish Health Repository)

O'Sullivan, A

2012-02-01

OBJECTIVE: To assess the efficacy of oral sucrose combined with swaddling and non-nutritive suck (NNS) as a method for reducing pain associated with retinopathy of prematurity (ROP) screening. DESIGN: Randomised placebo controlled study. SETTING: Tertiary level neonatal intensive care unit. SAMPLE: 40 infants undergoing primary eye examination for ROP screening. INTERVENTION: The control group were swaddled, and received 0.2 ml of sterile water given by mouth using a syringe and a soother. The intervention group were swaddled, and received 0.2 ml of sucrose 24% given by mouth using a syringe and a soother. RESULTS: 40 infants were included in the study. There was no difference in mean gestational age at birth, mean birth weight or corrected gestational age at first examination between both groups. The sucrose group had a significantly lower median Neonatal Pain, Agitation and Sedation Scale (N-PASS) score during ROP screening, initially following insertion of the speculum (6.5 vs 5, p=0.02) and subsequently during scleral indentation (9.5 vs 7.5, p=0.03). Fewer infants experienced episodes of desaturations or bradycardia in the intervention group (1 vs 4, p=0.18). CONCLUSION: ROP screening is a necessary but recognised painful procedure. Sucrose combined with NNS and swaddling reduced the behavioural and physiological pain responses. However, pain scores remained consistently high and appropriate pain relief for ROP screening remains a challenge.

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

Science.gov (United States)

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

2014-01-01

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

The impact of electronic education on metabolic control indicators in patients with diabetes who need insulin: a randomised clinical control trial.

Science.gov (United States)

Moattari, Marzieh; Hashemi, Maryam; Dabbaghmanesh, Mohammad H

2013-01-01

To determine the impact of electronic education on metabolic control indicators in patients with diabetes who were insulin dependent. Education can play an important role in controlling diabetes. Electronic (web-based, telehealth) education may be an efficient way to improve the patients' ability to control this disease. Randomised clinical control study. The participants in this clinical study were 48 insulin-dependent patients referred to diabetes centres in Shiraz, Iran. Serum concentrations of haemoglobin A(1C) , fasting blood sugar, triglycerides and high-density and low-density lipoprotein cholesterol were measured. Then the participants were divided randomly into control and experimental groups (n = 24). Participants in the experimental group received a specially designed electronic education programme for twelve weeks. The main components of the programme were a consultation service, quick answers to patients' questions, contact with the healthcare team and educational materials. At the end of the intervention period, all serum values were measured again in both groups. The data were compared using spss v 13·5 software. Serum concentrations of haemoglobin A(1C) (p education programme was useful in lowering two metabolic indicators of diabetes. Electronic education can be associated with increased health and patient satisfaction, and can eliminate the need to train personnel. © 2012 Blackwell Publishing Ltd.

Tofacitinib in patients with ankylosing spondylitis: a phase II, 16-week, randomised, placebo-controlled, dose-ranging study.

Science.gov (United States)

van der Heijde, Désirée; Deodhar, Atul; Wei, James C; Drescher, Edit; Fleishaker, Dona; Hendrikx, Thijs; Li, David; Menon, Sujatha; Kanik, Keith S

2017-08-01

To compare efficacy and safety of various doses of tofacitinib, an oral Janus kinase inhibitor, with placebo in patients with active ankylosing spondylitis (AS, radiographic axial spondyloarthritis). In this 16-week (12-week treatment, 4-week washout), phase II, multicentre, dose-ranging trial, adult patients with active AS were randomised (N=51, 52, 52, 52, respectively) to placebo or tofacitinib 2, 5 or 10 mg twice daily. The primary efficacy endpoint was Assessment of SpondyloArthritis International Society 20% improvement (ASAS20) response rate at week 12. Secondary endpoints included objective measures of disease activity, patient-reported outcomes and MRI of sacroiliac joints and spine. Safety was monitored. Emax model analysis of the primary endpoint predicted a tofacitinib 10 mg twice daily ASAS20 response rate of 67.4%, 27.3% higher than placebo. Supportive normal approximation analysis demonstrated tofacitinib 5 mg twice daily ASAS20 response rate significantly higher than placebo (80.8% vs 41.2%; ptofacitinib 2 and 10 mg twice daily demonstrated greater response rate than placebo (51.9% and 55.8%, respectively; not significant). Secondary endpoints generally demonstrated greater improvements with tofacitinib 5 and 10 mg twice daily than placebo. Objective (including MRI) endpoints demonstrated clear dose response. Adverse events were similar across treatment groups with no unexpected safety findings. Dose-dependent laboratory outcome changes returned close to baseline by week 16. Tofacitinib 5 and 10 mg twice daily demonstrated greater clinical efficacy versus placebo in reducing signs, symptoms and objective endpoints of active AS in adult patients with a similar 12-week safety profile as reported in other indications. NCT01786668. 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/.

Self-monitoring of Blood Glucose in Non-Insulin Treated Type 2 Diabetes (The SMBG Study): study protocol for a randomised controlled trial.

Science.gov (United States)

Parsons, Sharon; Luzio, Stephen; Bain, Stephen; Harvey, John; McKenna, Jillian; Khan, Atir; Rice, Sam; Watkins, Alan; Owens, David R

2017-01-26

The benefit of Self-monitoring of Blood Glucose (SMBG) in people with non-insulin treated type 2 diabetes remains unclear with inconsistent evidence from randomised controlled trials fuelling the continued debate. Lack of a consistent finding has been attributed to variations in study population and design, including the SMBG intervention. There is a growing consensus that structured SMBG, whereby the person with diabetes and health care provider are educated to detect patterns of glycaemic abnormality and take appropriate action according to the blood glucose profiles, can prove beneficial in terms of lowering HbA1c and improving overall well-being. Despite this, many national health agencies continue to issue guidelines restricting the use of SMBG in non-insulin treated type 2 diabetes. The SMBG Study is a 12 month, multi-centre, randomised controlled trial in people with type 2 diabetes not on insulin therapy who have poor glycaemic control (HbA1c ≥58 mmol/mol / 7.5%). The participants will be randomised into three comparative groups: Group 1 will act as a control group and receive their usual diabetes care; Group 2 will undertake structured SMBG with clinical review every 3 months; Group 3 will undertake structured SMBG with additional monthly telecare support from a trained study nurse. A total of 450 participants will be recruited from 16 primary and secondary care sites across Wales and England. The primary outcome measure will be HbA1c at 12 months with secondary measures to include weight, BMI, total cholesterol and HbA1c levels at 3, 6, 9 and 12 months. Participant well-being and attitude towards SMBG will be monitored throughout the course of the study. Recruitment began in December 2012 with the last participant visit due in September 2016. This study will attempt to answer the question of whether structured SMBG provides any benefits to people with poorly controlled type 2 diabetes who are not being treated with insulin. The data will also

Randomised controlled trials of homeopathy in humans: characterising the research journal literature for systematic review.

Science.gov (United States)

Mathie, Robert T; Hacke, Daniela; Clausen, Jürgen; Nicolai, Ton; Riley, David S; Fisher, Peter

2013-01-01

A new programme of systematic reviews of randomised controlled trials (RCTs) in homeopathy will distinguish important attributes of RCT records, including: placebo controlled versus other-than-placebo (OTP) controlled; individualised versus non-individualised homeopathy; peer-reviewed (PR) versus non peer-reviewed (NPR) sources. (a) To outline the methods used to search and categorise the RCT literature; (b) to report details of the records retrieved; (c) to compare our retrieved records with those reported in two previous systematic reviews (Linde et al., 1997; Shang et al., 2005). Ten major electronic databases were searched for records published up to the end of 2011. A record was accepted for subsequent systematic review if it was a substantive report of a clinical trial of homeopathic treatment or prophylaxis in humans, randomised and controlled, and published in a PR or NPR journal. 489 records were potentially eligible: 226 were rejected as non-journal, minor or repeat publications, or lacking randomisation and/or controls and/or a 'homeopathic' intervention; 263 (164 PR, 99 NPR) were acceptable for systematic review. The 263 accepted records comprised 217 (137 PR, 80 NPR) placebo-controlled RCTs, of which 121 were included by, 66 were published after, and 30 were potentially eligible for, but not listed by, Linde or Shang. The 137 PR records of placebo-controlled RCTs comprise 41 on individualised homeopathy and 96 on non-individualised homeopathy. Our findings clarify the RCT literature in homeopathy. The 263 accepted journal papers will be the basis for our forthcoming programme of systematic reviews. Copyright © 2012 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

Oral prenylation inhibition with lonafarnib in chronic hepatitis D infection: a proof-of-concept randomised, double-blind, placebo-controlled phase 2A trial

Science.gov (United States)

Koh, Christopher; Canini, Laetitia; Dahari, Harel; Zhao, Xiongce; Uprichard, Susan L; Haynes-Williams, Vanessa; Winters, Mark A; Subramanya, Gitanjali; Cooper, Stewart L; Pinto, Peter; Wolff, Erin F; Bishop, Rachel; Han, Ma Ai Thanda; Cotler, Scott J; Kleiner, David E; Keskin, Onur; Idilman, Ramazan; Yurdaydin, Cihan; Glenn, Jeffrey S; Heller, Theo

2015-01-01

Summary Background Therapies for chronic hepatitis delta virus (HDV) infection are unsatisfactory. Prenylation is essential for HDV and inhibition abrogates HDV production in experimental models. In a proof-of-concept study, we aimed to assess the effect on HDV RNA levels, safety, and tolerability of the prenylation inhibitor lonafarnib in patients with chronic delta hepatitis. Methods In this phase 2A double-blind, randomised, placebo-controlled study, patients aged 18 years or older with chronic HDV infection were randomly assigned (3:1 in group 1 and 2:1 in group 2) to receive lonafarnib 100 mg (group 1) or lonafarnib 200 mg (group 2) twice daily for 28 days with 6 months’ follow-up. Participants were randomised by random-number tables blocked in groups of four without stratification. Both groups enrolled six treatment participants and two placebo participants. Group 1 placebo patients received open-label lonafarnib as group 2 participants. The primary therapeutic endpoint was a decrease in HDV RNA viral titre in serum and the primary safety endpoint was the ability to tolerate the drug at the prescribed dose for the full 4-week duration, defined as drug discontinuation due to intolerance or grade 3/4 adverse events. This trial is registered with ClinicalTrials.gov, number NCT01495585. Findings Between Jan 19, 2012, and April 28, 2014, 14 patients were enrolled, of whom eight were assigned to group 1 and six were assigned to group 2. At day 28, compared with placebo, mean log HDV RNA declines from baseline were −0.73 log IU/mL in group 1 (95% CI 0.17–1.31; p=0.03) and −1.54 log IU/mL in group 2 (1.21–1.93; p<0.0001). Lonafarnib serum concentrations correlated with HDV RNA change (r2=0.78, p<0.0001). Model fits show that hepatitis B surface antigen (HBsAg) remained stable after a short pharmacological delay (0.75 days [SE 0.24]), lonafarnib effectiveness in blocking HDV production was greater in group 2 than in group 1 (0.952 [SE 0.06] vs 0.739 [0

Study protocol for a randomised, double-blinded, placebo-controlled, clinical trial of S-ketamine for pain treatment in patients with chronic pancreatitis (RESET trial)

DEFF Research Database (Denmark)

Juel, Jacob; Olesen, Søren Schou; Olesen, Anne Estrup

2015-01-01

are randomised to receive 8 h of intravenous S-ketamine followed by oral S-ketamine, or matching placebo, for 4 weeks. To improve blinding, 1 mg of midazolam will be added to active and placebo treatment. The primary end point is clinical pain relief as assessed by a daily pain diary. Secondary end points......INTRODUCTION: Chronic pancreatitis (CP) is an inflammatory disease that causes irreversible damage to pancreatic tissue. Pain is its most prominent symptom. In the absence of pathology suitable for endoscopic or surgical interventions, pain treatment usually includes opioids. However, opioids often...... have limited efficacy. Moreover, side effects are common and bothersome. Hence, novel approaches to control pain associated with CP are highly desirable. Sensitisation of the central nervous system is reported to play a key role in pain generation and chronification. Fundamental to the process...

Prophylactic antibiotics to prevent pneumonia and other complications after measles: community based randomised double blind placebo controlled trial in Guinea-Bissau.

Science.gov (United States)

Garly, May-Lill; Balé, Carlitos; Martins, Cesário Lourenco; Whittle, Hilton C; Nielsen, Jens; Lisse, Ida M; Aaby, Peter

2006-12-16

To investigate whether prophylactic antibiotics can prevent complications of measles. Community based, randomised, double blind, placebo controlled trial. Bandim Health Project study area in Bissau, Guinea-Bissau, west Africa. 84 patients with measles during a measles epidemic in Bissau in 1998 (fewer than originally planned owing to interruption by war). Sulfamethoxazole-trimethoprim (co-trimoxazole) or placebo for seven days. Pneumonia and admission to hospital. Also weight change during the first month of infection, diarrhoea, severe fever, oral thrush, stomatitis, conjunctivitis, and otitis media. The median age of the patients with measles was 5.4 (range 0.49-24.8) years. One of 46 participants who received co-trimoxazole developed pneumonia, in contrast to six of 38 participants who received placebo (odds ratio 0.08 (95% confidence interval 0 to 0.56), adjusted for age group). The number needed to treat was 7 (4 to 48). All three participants admitted to hospital had received placebo (P=0.09). The weight gain during the first month after inclusion was 15 (2-29) g/day in the placebo group and 32 (23-42) g/day in the co-trimoxazole group (P=0.04, adjusted for age group, weight for age at inclusion, measles vaccination status, and duration of disease). Significantly less conjunctivitis occurred among recipients of co-trimoxazole than placebo, as well as a non-significant tendency to less diarrhoea, severe fever, oral thrush, and stomatitis. Complications of otitis media were the same in the two groups. The group that received prophylactic antibiotics had less pneumonia and conjunctivitis and had significantly higher weight gains in the month after inclusion. The results indicate that prophylactic antibiotics may have an important role in the management of measles infection in low income countries. Clinical trials NCT00168532.

A randomised, double blind, placebo-controlled trial of a fixed dose of N-acetyl cysteine in children with autistic disorder.

Science.gov (United States)

Dean, Olivia M; Gray, Kylie M; Villagonzalo, Kristi-Ann; Dodd, Seetal; Mohebbi, Mohammadreza; Vick, Tanya; Tonge, Bruce J; Berk, Michael

2017-03-01

Oxidative stress, inflammation and heavy metals have been implicated in the aetiology of autistic disorder. N-acetyl cysteine has been shown to modulate these pathways, providing a rationale to trial N-acetyl cysteine for autistic disorder. There are now two published pilot studies suggesting efficacy, particularly in symptoms of irritability. This study aimed to explore if N-acetyl cysteine is a useful treatment for autistic disorder. This was a placebo-controlled, randomised clinical trial of 500 mg/day oral N-acetyl cysteine over 6 months, in addition to treatment as usual, in children with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision diagnosis of autistic disorder. The study was conducted in Victoria, Australia. The primary outcome measures were the Social Responsiveness Scale, Children's Communication Checklist-Second Edition and the Repetitive Behavior Scale-Revised. Additionally, demographic data, the parent-completed Vineland Adaptive Behavior Scales, Social Communication Questionnaire and clinician-administered Autism Diagnostic Observation Schedule were completed. A total of 102 children were randomised into the study, and 98 (79 male, 19 female; age range: 3.1-9.9 years) attended the baseline appointment with their parent/guardian, forming the Intention to Treat sample. There were no differences between N-acetyl cysteine and placebo-treated groups on any of the outcome measures for either primary or secondary endpoints. There was no significant difference in the number and severity of adverse events between groups. This study failed to demonstrate any benefit of adjunctive N-acetyl cysteine in treating autistic disorder. While this may reflect a true null result, methodological issues particularly the lower dose utilised in this study may be confounders.

The effect of dipeptidyl peptidase 4 inhibition on gastric volume, satiation and enteroendocrine secretion in Type 2 diabetes: a double blind, placebo-controlled crossover study

DEFF Research Database (Denmark)

Vella, Adrian; Bock, Gerlies; Giesler, Paula D

2008-01-01

with type 2 diabetes. Methods: In a double blind, placebo-controlled crossover design, 14 subjects with type 2 diabetes received vildagliptin (50mg bid) or placebo for 10-days in random order separated by a 2-week washout. On day 7, fasting and post-meal gastric volumes were measured by a (99m...... ingested was recorded and symptoms similarly measured using VAS. Results: Vildagliptin raised plasma GLP-1 concentrations. However, fasting (248 + 21 vs. 247 + 19ml, p= 0.98) and fed (746 + 28 vs. 772 + 26ml, p= 0.54) gastric volumes, did not differ when subjects received vildagliptin or placebo. Treatment...... with vildagliptin did not alter the maximum tolerated volume of Ensure((R)) (1657 + 308 vs. 1389 + 197 ml, p= 0.15) or water compared to placebo (1371 + 141 vs. 1172 + 156 ml, p= 0.23). Vildagliptin was associated with decreased PYY concentrations 60 minutes after initiation of the meal (166 +/- 27 vs. 229 +/- 34...

Pregabalin versus placebo in targeting pro-nociceptive mechanisms to prevent chronic pain after whiplash injury in at-risk individuals - a feasibility study for a randomised controlled trial.

Science.gov (United States)

Nikles, J; Keijzers, G; Mitchell, G; Schug, S; Ware, R; McLean, S A; Connelly, L; Gibson, S; Farrell, S F; Sterling, M

2018-01-17

Whiplash-associated disorders (WAD) are an enormous and costly burden to Australian society. Up to 50% of people who experience a whiplash injury will never fully recover. Whiplash is resistant to treatment and no early management approach has yet been shown to prevent chronic pain. The early presence of central sensitization is associated with poor recovery. Pregabalin's effects on central sensitization indicate the potential to prevent or modulate these processes after whiplash injury and to improve health outcomes, but this has not been investigated. This paper describes the protocol for a feasibility study for a randomised controlled trial of pregabalin plus evidence-based advice compared to placebo plus evidence-based advice for individuals with acute whiplash injury who are at risk of poor recovery. This double blind, placebo-controlled randomised feasibility study will examine the feasibility and potential effectiveness of pregabalin and evidence-based advice (intervention) compared to placebo and evidence-based advice (control) for individuals with acute whiplash injury at risk of poor recovery. Thirty participants (15 per group) aged 18-65 years with Grade II WAD, within 48 hours of injury and currently experiencing at least moderate pain (NRS: ≥ 5/10) will be recruited from Emergency Departments of public hospitals in Queensland, Australia. Pregabalin will be commenced at 75 mg bd and titrated up to 300 mg bd as tolerated for 4 weeks followed by 1 week of weaning. The feasibility of trial procedures will be tested, as well as the potential effect of the intervention on the outcomes. The primary outcome of neck pain intensity at 3 months from randomisation will be compared between the treatment groups using standard analysis of variance techniques. Feasibility and potential effectiveness data will inform an appropriately powered full trial, which if successful, will provide an effective and cost-effective intervention for a costly and treatment

The Diabetes Care Project: an Australian multicentre, cluster randomised controlled trial [study protocol].

Science.gov (United States)

Leach, Matthew J; Segal, Leonie; Esterman, Adrian; Armour, Caroline; McDermott, Robyn; Fountaine, Tim

2013-12-20

Diabetes mellitus is an increasingly prevalent metabolic disorder that is associated with substantial disease burden. Australia has an opportunity to improve ways of caring for the growing number of people with diabetes, but this may require changes to the way care is funded, organised and delivered. To inform how best to care for people with diabetes, and to identify the extent of change that is required to achieve this, the Diabetes Care Project (DCP) will evaluate the impact of two different, evidence-based models of care (compared to usual care) on clinical quality, patient and provider experience, and cost. The DCP uses a pragmatic, cluster randomised controlled trial design. Accredited general practices that are situated within any of the seven Australian Medicare Locals/Divisions of General Practice that have agreed to take part in the study were invited to participate. Consenting practices will be randomly assigned to one of three treatment groups for approximately 18 to 22 months: (a) control group (usual care); (b) Intervention 1 (which tests improvements that could be made within the current funding model, facilitated through the use of an online chronic disease management network); or (c) Intervention 2 (which includes the same components as Intervention 1, as well as altered funding to support voluntary patient registration with their practice, incentive payments and a care facilitator). Adult patients who attend the enrolled practices and have established (≥12 month's duration) type 1 diabetes mellitus or newly diagnosed or established type 2 diabetes mellitus are invited to participate. Multiple outcomes will be studied, including changes in glycosylated haemoglobin (primary outcome), changes in other biochemical and clinical metrics, incidence of diabetes-related complications, quality of life, clinical depression, success of tailored care, patient and practitioner satisfaction, and budget sustainability. This project responds to a need for robust

Golimumab in patients with active rheumatoid arthritis who have previous experience with tumour necrosis factor inhibitors: results of a long-term extension of the randomised, double-blind, placebo-controlled GO-AFTER study through week 160

NARCIS (Netherlands)

Smolen, Josef S.; Kay, Jonathan; Landewé, Robert B. M.; Matteson, Eric L.; Gaylis, Norman; Wollenhaupt, Jurgen; Murphy, Frederick T.; Zhou, Yiying; Hsia, Elizabeth C.; Doyle, Mittie K.

2012-01-01

The aim of this study was to assess long-term golimumab therapy in patients with rheumatoid arthritis (RA) who discontinued previous tumour necrosis factor alpha (TNFα) inhibitor(s) for any reason. Results through week 24 of this multicentre, randomised, double-blind, placebo-controlled study of

Field assessment of a novel household-based water filtration device: a randomised, placebo-controlled trial in the Democratic Republic of Congo.

Science.gov (United States)

Boisson, Sophie; Kiyombo, Mbela; Sthreshley, Larry; Tumba, Saturnin; Makambo, Jacques; Clasen, Thomas

2010-09-10

Household water treatment can improve the microbiological quality of drinking water and may prevent diarrheal diseases. However, current methods of treating water at home have certain shortcomings, and there is evidence of bias in the reported health impact of the intervention in open trial designs. We undertook a randomised, double-blinded, placebo-controlled trial among 240 households (1,144 persons) in rural Democratic Republic of Congo to assess the field performance, use and effectiveness of a novel filtration device in preventing diarrhea. Households were followed up monthly for 12 months. Filters and placebos were monitored for longevity and for microbiological performance by comparing thermotolerant coliform (TTC) levels in influent and effluent water samples. Mean longitudinal prevalence of diarrhea was estimated among participants of all ages. Compliance was assessed through self-reported use and presence of water in the top vessel of the device at the time of visit. Over the 12-month follow-up period, data were collected for 11,236 person-weeks of observation (81.8% total possible). After adjusting for clustering within the household, the longitudinal prevalence ratio of diarrhoea was 0.85 (95% confidence interval: 0.61-1.20). The filters achieved a 2.98 log reduction in TTC levels while, for reasons that are unclear, the placebos achieved a 1.05 log reduction (pwater the previous day. The filter maintained a constant flow rate over time, though 12.4% of filters were damaged during the course of the study. While the filter was effective in improving water quality, our results provide little evidence that it was protective against diarrhea. The moderate reduction observed nevertheless supports the need for larger studies that measure impact against a neutral placebo. Current Controlled Trials ISRCTN03844341.

Targeting intensive versus conventional glycaemic control for type 1 diabetes mellitus

DEFF Research Database (Denmark)

Kähler, Pernille; Grevstad, Berit; Almdal, Thomas

2014-01-01

OBJECTIVE: To assess the benefits and harms of targeting intensive versus conventional glycaemic control in patients with type 1 diabetes mellitus. DESIGN: A systematic review with meta-analyses and trial sequential analyses of randomised clinical trials. DATA SOURCES: The Cochrane Library, MEDLINE......, EMBASE, Science Citation Index Expanded and LILACS to January 2013. STUDY SELECTION: Randomised clinical trials that prespecified different targets of glycaemic control in participants at any age with type 1 diabetes mellitus were included. DATA EXTRACTION: Two authors independently assessed studies...... for inclusion and extracted data. RESULTS: 18 randomised clinical trials included 2254 participants with type 1 diabetes mellitus. All trials had high risk of bias. There was no statistically significant effect of targeting intensive glycaemic control on all-cause mortality (risk ratio 1.16, 95% CI 0.65 to 2...

Vorinostat in patients with advanced malignant pleural mesothelioma who have progressed on previous chemotherapy (VANTAGE-014): a phase 3, double-blind, randomised, placebo-controlled trial.

Science.gov (United States)

Krug, Lee M; Kindler, Hedy L; Calvert, Hilary; Manegold, Christian; Tsao, Anne S; Fennell, Dean; Öhman, Ronny; Plummer, Ruth; Eberhardt, Wilfried E E; Fukuoka, Kazuya; Gaafar, Rabab M; Lafitte, Jean-Jacques; Hillerdal, Gunnar; Chu, Quincy; Buikhuisen, Wieneke A; Lubiniecki, Gregory M; Sun, Xing; Smith, Margaret; Baas, Paul

2015-04-01

Vorinostat is a histone deacetylase inhibitor that changes gene expression and protein activity. On the basis of the clinical benefit reported in patients with malignant pleural mesothelioma treated in a phase 1 study of vorinostat, we designed this phase 3 trial to investigate whether vorinostat given as a second-line or third-line therapy improved patients' overall survival. This double-blind, randomised, placebo-controlled trial was done in 90 international centres. Patients with measurable advanced malignant pleural mesothelioma and disease progression after one or two previous systemic regimens were eligible. After stratification for Karnofsky performance status, histology, and number of previous chemotherapy regimens, patients were randomly assigned (1:1) by use of an interactive voice response system with a block size of four to either treatment with vorinostat or placebo. Patients received oral vorinostat 300 mg (or matching placebo) twice daily on days 1, 2, 3, 8, 9, 10, 15, 16, and 17 of a 21-day cycle. The primary endpoints were overall survival and safety and tolerability of vorinostat. The primary efficacy comparison was done in the intention-to-treat population, and safety and tolerability was assessed in the treated population. This trial is registered with ClinicalTrials.gov, number NCT00128102. From July 12, 2005, to Feb 14, 2011, 661 patients were enrolled and randomly assigned to receive either vorinostat (n=329) or placebo (n=332) and included in the intention-to-treat analysis. Median overall survival for vorinostat was 30·7 weeks (95% CI 26·7-36·1) versus 27·1 weeks (23·1-31·9) for placebo (hazard ratio 0·98, 95% CI 0·83-1·17, p=0·86). The most common grade 3 or worse adverse events for patients treated with vorinostat were fatigue or malaise (51 [16%] patients in the vorinostat group vs 25 [8%] in the placebo group]) and dyspnoea (35 [11%] vs 45 [14%]). In this randomised trial, vorinostat given as a second-line or third

Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.

Science.gov (United States)

Chan, Arlene; Delaloge, Suzette; Holmes, Frankie A; Moy, Beverly; Iwata, Hiroji; Harvey, Vernon J; Robert, Nicholas J; Silovski, Tajana; Gokmen, Erhan; von Minckwitz, Gunter; Ejlertsen, Bent; Chia, Stephen K L; Mansi, Janine; Barrios, Carlos H; Gnant, Michael; Buyse, Marc; Gore, Ira; Smith, John; Harker, Graydon; Masuda, Norikazu; Petrakova, Katarina; Zotano, Angel Guerrero; Iannotti, Nicholas; Rodriguez, Gladys; Tassone, Pierfrancesco; Wong, Alvin; Bryce, Richard; Ye, Yining; Yao, Bin; Martin, Miguel

2016-03-01

Neratinib, an irreversible tyrosine-kinase inhibitor of HER1, HER2, and HER4, has clinical activity in patients with HER2-positive metastatic breast cancer. We aimed to investigate the efficacy and safety of 12 months of neratinib after trastuzumab-based adjuvant therapy in patients with early-stage HER2-positive breast cancer. We did this multicentre, randomised, double-blind, placebo-controlled, phase 3 trial at 495 centres in Europe, Asia, Australia, New Zealand, and North and South America. Eligible women (aged ≥18 years, or ≥20 years in Japan) had stage 1-3 HER2-positive breast cancer and had completed neoadjuvant and adjuvant trastuzumab therapy up to 2 years before randomisation. Inclusion criteria were amended on Feb 25, 2010, to include patients with stage 2-3 HER2-positive breast cancer who had completed trastuzumab therapy up to 1 year previously. Patients were randomly assigned (1:1) to receive oral neratinib 240 mg per day or matching placebo. The randomisation sequence was generated with permuted blocks stratified by hormone receptor status (hormone receptor-positive [oestrogen or progesterone receptor-positive or both] vs hormone receptor-negative [oestrogen and progesterone receptor-negative]), nodal status (0, 1-3, or ≥4), and trastuzumab adjuvant regimen (sequentially vs concurrently with chemotherapy), then implemented centrally via an interactive voice and web-response system. Patients, investigators, and trial sponsors were masked to treatment allocation. The primary outcome was invasive disease-free survival, as defined in the original protocol, at 2 years after randomisation. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00878709. Between July 9, 2009, and Oct 24, 2011, we randomly assigned 2840 women to receive neratinib (n=1420) or placebo (n=1420). Median follow-up time was 24 months (IQR 20-25) in the neratinib group and 24 months (22-25) in the placebo group. At 2 year follow-up, 70

Efficacy of a Monovalent Human-Bovine (116E) Rotavirus Vaccine in Indian Infants: A Randomised Double Blind Placebo Controlled Trial

Science.gov (United States)

Bhandari, Nita; Rongsen-Chandola, Temsunaro; Bavdekar, Ashish; John, Jacob; Antony, Kalpana; Taneja, Sunita; Goyal, Nidhi; Kawade, Anand; Kang, Gagandeep; Rathore, Sudeep Singh; Juvekar, Sanjay; Muliyil, Jayaprakash; Arya, Alok; Shaikh, Hanif; Abraham, Vinod; Vrati, Sudhanshu; Proschan, Michael; Kohberger, Robert; Thiry, Georges; Glass, Roger; Greenberg, Harry B; Curlin, George; Mohan, Krishna; Harshavardhan, GVJA; Prasad, Sai; Rao, TS; Boslego, John; Bhan, Maharaj Kishan

2015-01-01

Background Rotavirus is the most common cause of severe dehydrating gastroenteritis in developing countries. Safe, effective, and affordable rotavirus vaccines are needed for developing countries. Methods In a double-blind placebo controlled multicentre trial, 6799 infants aged 6 to 7 weeks were randomised to receive three doses of an oral human-bovine natural reassortant vaccine (116E) or placebo at ages 6, 10, and 14 weeks. Primary outcome was severe (≥11 on the Vesikari scale) rotavirus gastroenteritis. Efficacy outcomes and adverse events were ascertained through active surveillance. Findings At analyses, the median age was 17·2 months; over 96% subjects received all three doses of the vaccine/placebo and ~1% were lost to follow up. 4532 and 2267 subjects were randomly assigned to receive vaccine and placebo, respectively. The per protocol analyses included 4354 subjects in the vaccine and 2187 subjects in the placebo group. 71 events of severe rotavirus gastroenteritis were reported in 4752 person years among the vaccinees compared to 76 events in 2360 person years in the placebo recipients; vaccine efficacy against severe rotavirus gastroenteritis was 53·6% (95% CI 35·0–66·9; Protavirus gastroenteritis episode was 55 (95% CI 37–97). The incidence of severe rotavirus gastroenteritis/100 person years was 1·5 in vaccine and 3·2 in placebo group and an incidence rate ratio of 0·46 (95% CI 0·33–0·65). The absolute rate reduction for severe rotavirus gastroenteritis was 1·7 (95% CI 2·5–0·9). Efficacy against severe gastroenteritis of any aetiology was 18·6% (95% CI 1·9–32·3); it was 24·1% (95% CI 5·8–38·7) in the first year of life. The prevalence of immediate, solicited, and serious adverse events were similar in both groups. There were six cases of intussusception amongst 4532 vaccinees and two amongst 2267 placebo recipients (P=0·73). All intussusception cases occurred after the third dose. Among vaccine and placebo recipients

Poor uptake of an online intervention in a cluster randomised controlled trial of online diabetes education for rural general practitioners.

Science.gov (United States)

Paul, Christine L; Piterman, Leon; Shaw, Jonathan E; Kirby, Catherine; Forshaw, Kristy L; Robinson, Jennifer; Thepwongsa, Isaraporn; Sanson-Fisher, Robert W

2017-03-23

In Australia, rural and remote communities have high rates of diabetes-related death and hospitalisation. General practitioners (GPs) play a major role in diabetes detection and management. Education of GPs could optimise diabetes management and improve patient outcomes at a population level. The study aimed to describe the uptake of a continuing medical education intervention for rural GPs and its impact on the viability of a cluster randomised controlled trial of the effects of continuing medical education on whole-town diabetes monitoring and control. Trial design: the cluster randomised controlled trial involved towns as the unit of allocation and analysis with outcomes assessed by de-identified pathology data (not reported here). The intervention programme consisted of an online active learning module, direct electronic access to specialist advice and performance feedback. Multiple rounds of invitation were used to engage GPs with the online intervention content. Evidence-based strategies (e.g. pre-notification, rewards, incentives) were incorporated into the invitations to enrol in the programme. Recruitment to the programme was electronically monitored through the hosting software package during the study intervention period. Eleven matched pairs of towns were included in the study. There were 146 GPs in the 11 intervention towns, of whom 34 (23.3%) enrolled in the programme, and 8 (5.5%) completed the online learning module. No town had more than 10% of the resident GPs complete the learning module. There were no contacts made by GPs regarding requests for specialist advice. Consequently, the trial was discontinued. There is an ongoing need to engage primary care physicians in improving diabetes monitoring and management in rural areas. Online training options, while notionally attractive and accessible, are not likely to have high levels of uptake, even when evidence-based recruitment strategies are implemented. Australian New Zealand Clinical Trials

A randomized, double-blind, crossover, placebo-controlled trial of 6 weeks benfotiamine treatment on postprandial vascular function and variables of autonomic nerve function in Type 2 diabetes.

Science.gov (United States)

Stirban, A; Pop, A; Tschoepe, D

2013-10-01

In a pilot study we suggested that benfotiamine, a thiamine prodrug, prevents postprandial endothelial dysfunction in people with Type 2 diabetes mellitus. The aim of this study was to test these effects in a larger population. In a double-blind, placebo-controlled, randomized, crossover study, 31 people with Type 2 diabetes received 900 mg/day benfotiamine or a placebo for 6 weeks (with a washout period of 6 weeks between). At the end of each treatment period, macrovascular and microvascular function were assessed, together with variables of autonomic nervous function in a fasting state, as well as 2, 4 and 6 h following a heated, mixed test meal. Participants had an impaired baseline flow-mediated dilatation (2.63 ± 2.49%). Compared with the fasting state, neither variable changed postprandially following the placebo treatment. The 6 weeks' treatment with high doses of benfotiamine did not alter this pattern, either in the fasting state or postprandially. Among a subgroup of patients with the highest flow-mediated dilatation, following placebo treatment there was a significant postprandial flow-mediated dilatation decrease, while this effect was attenuated by benfotiamine pretreatment. In people with Type 2 diabetes and markedly impaired fasting flow-mediated dilatation, a mixed test meal does not further deteriorate flow-mediated dilatation or variables of microvascular or autonomic nervous function. Because no significant deterioration of postprandial flow-mediated dilatation, microvascular or autonomic nervous function tests occurred after placebo treatment, a prevention of the postprandial deterioration of these variables with benfotiamine was not feasible. © 2013 The Authors. Diabetic Medicine © 2013 Diabetes UK.

Safety and efficacy of edaravone in well defined patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled trial.

Science.gov (United States)

2017-07-01

In a previous phase 3 study in patients with amyotrophic lateral sclerosis (ALS), edaravone did not show a significant difference in the Revised ALS Functional Rating Scale (ALSFRS-R) score compared with placebo. Post-hoc analysis of these data revealed that patients in an early stage with definite or probable diagnosis of ALS, defined by the revised El Escorial criteria, who met a select set of inclusion criteria showed a greater magnitude of effect than did the full study population. We aimed to substantiate this post-hoc result and assess safety and efficacy of edaravone in a phase 3 trial that focused on patients with early stage ALS who met the post-hoc analysis inclusion criteria. In this phase 3, randomised, double-blind, parallel-group study, patients aged 20-75 years with ALS of grade 1 or 2 in the Japan ALS Severity Classification, scores of at least 2 points on all 12 items of ALSFRS-R, forced vital capacity of 80% or more, definite or probable ALS according to the revised El Escorial criteria, and disease duration of 2 years or less were recruited from 31 hospitals in Japan. Eligible patients also had a decrease of 1-4 points in the ALSFRS-R score during a 12-week observation period before randomisation. Patients meeting all criteria were then randomly assigned 1:1 to receive 60 mg intravenous edaravone or intravenous saline placebo for 6 cycles (4 weeks per cycle with 2 weeks on, 2 weeks off) for a total treatment duration of 24 weeks. In cycle 1, the study drug or placebo was administered once per day for 14 days within a 14 day period, followed by the drug-free period. In cycle 2 and thereafter, the study drug or placebo was administered for 10 days within a 14 day period, followed by a 2 week drug-free period. Participants and investigators, including those assessing outcomes, were masked to treatment allocation. The primary efficacy outcome was the change in ALSFRS-R score from the baseline to 24 weeks (or at discontinuation if this was after the

Efficacy and safety of dupilumab in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical treatments: a randomised, placebo-controlled, dose-ranging phase 2b trial.

Science.gov (United States)

Thaçi, Diamant; Simpson, Eric L; Beck, Lisa A; Bieber, Thomas; Blauvelt, Andrew; Papp, Kim; Soong, Weily; Worm, Margitta; Szepietowski, Jacek C; Sofen, Howard; Kawashima, Makoto; Wu, Richard; Weinstein, Steven P; Graham, Neil M H; Pirozzi, Gianluca; Teper, Ariel; Sutherland, E Rand; Mastey, Vera; Stahl, Neil; Yancopoulos, George D; Ardeleanu, Marius

2016-01-02

Data from early-stage studies suggested that interleukin (IL)-4 and IL-13 are requisite drivers of atopic dermatitis, evidenced by marked improvement after treatment with dupilumab, a fully-human monoclonal antibody that blocks both pathways. We aimed to assess the efficacy and safety of several dose regimens of dupilumab in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical treatments. In this randomised, placebo-controlled, double-blind study, we enrolled patients aged 18 years or older who had an Eczema Area and Severity Index (EASI) score of 12 or higher at screening (≥16 at baseline) and inadequate response to topical treatments from 91 study centres, including hospitals, clinics, and academic institutions, in Canada, Czech Republic, Germany, Hungary, Japan, Poland, and the USA. Patients were randomly assigned (1:1:1:1:1:1), stratified by severity (moderate or severe, as assessed by Investigator's Global Assessment) and region (Japan vs rest of world) to receive subcutaneous dupilumab: 300 mg once a week, 300 mg every 2 weeks, 200 mg every 2 weeks, 300 mg every 4 weeks, 100 mg every 4 weeks, or placebo once a week for 16 weeks. We used a central randomisation scheme, provided by an interactive voice response system. Drug kits were coded, providing masking to treatment assignment, and allocation was concealed. Patients on treatment every 2 weeks and every 4 weeks received volume-matched placebo every week when dupilumab was not given to ensure double blinding. The primary outcome was efficacy of dupilumab dose regimens based on EASI score least-squares mean percentage change (SE) from baseline to week 16. Analyses included all randomly assigned patients who received one or more doses of study drug. This trial is registered with ClinicalTrials.gov, number NCT01859988. Between May 15, 2013, and Jan 27, 2014, 452 patients were assessed for eligibility, and 380 patients were randomly assigned. 379 patients received one or more

Efficacy and cost-effectiveness of a physiotherapy program for chronic rotator cuff pathology: A protocol for a randomised, double-blind, placebo-controlled trial

Science.gov (United States)

Bennell, Kim; Coburn, Sally; Wee, Elin; Green, Sally; Harris, Anthony; Forbes, Andrew; Buchbinder, Rachelle

2007-01-01

Background Chronic rotator cuff pathology (CRCP) is a common shoulder condition causing pain and disability. Physiotherapy is often the first line of management for CRCP yet there is little conclusive evidence to support or refute its effectiveness and no formal evaluation of its cost-effectiveness. Methods/Design This randomised, double-blind, placebo-controlled trial will involve 200 participants with CRCP recruited from medical practices, outpatient departments and the community via print and radio media. Participants will be randomly allocated to a physiotherapy or placebo group using concealed allocation stratified by treating physiotherapist. Both groups will receive 10 sessions of individual standardised treatment over 10 weeks from one of 10 project physiotherapists. For the following 12 weeks, the physiotherapy group will continue a home exercise program and the placebo group will receive no treatment. The physiotherapy program will comprise shoulder joint and spinal mobilisation, soft tissue massage, postural taping, and home exercises for scapular control, posture and rotator cuff strengthening. The placebo group will receive inactive ultrasound and gentle application of an inert gel over the shoulder region. Blinded assessment will be conducted at baseline and at 10 weeks and 22 weeks after randomisation. The primary outcome measures are self reported questionnaires including the shoulder pain and disability index (SPADI), average pain on an 11-point numeric rating scale and participant perceived global rating of change. Secondary measures include Medical Outcomes Study 36-item short form (SF-36), Assessment of Quality of Life index, numeric rating scales for shoulder pain and stiffness, participant perceived rating of change for pain, strength and stiffness, and manual muscle testing for shoulder strength using a handheld dynamometer. To evaluate cost-effectiveness, participants will record the use of all health-related treatments in a log

Efficacy and cost-effectiveness of a physiotherapy program for chronic rotator cuff pathology: A protocol for a randomised, double-blind, placebo-controlled trial

Directory of Open Access Journals (Sweden)

Harris Anthony

2007-08-01

Full Text Available Abstract Background Chronic rotator cuff pathology (CRCP is a common shoulder condition causing pain and disability. Physiotherapy is often the first line of management for CRCP yet there is little conclusive evidence to support or refute its effectiveness and no formal evaluation of its cost-effectiveness. Methods/Design This randomised, double-blind, placebo-controlled trial will involve 200 participants with CRCP recruited from medical practices, outpatient departments and the community via print and radio media. Participants will be randomly allocated to a physiotherapy or placebo group using concealed allocation stratified by treating physiotherapist. Both groups will receive 10 sessions of individual standardised treatment over 10 weeks from one of 10 project physiotherapists. For the following 12 weeks, the physiotherapy group will continue a home exercise program and the placebo group will receive no treatment. The physiotherapy program will comprise shoulder joint and spinal mobilisation, soft tissue massage, postural taping, and home exercises for scapular control, posture and rotator cuff strengthening. The placebo group will receive inactive ultrasound and gentle application of an inert gel over the shoulder region. Blinded assessment will be conducted at baseline and at 10 weeks and 22 weeks after randomisation. The primary outcome measures are self reported questionnaires including the shoulder pain and disability index (SPADI, average pain on an 11-point numeric rating scale and participant perceived global rating of change. Secondary measures include Medical Outcomes Study 36-item short form (SF-36, Assessment of Quality of Life index, numeric rating scales for shoulder pain and stiffness, participant perceived rating of change for pain, strength and stiffness, and manual muscle testing for shoulder strength using a handheld dynamometer. To evaluate cost-effectiveness, participants will record the use of all health

The effect of changing movement and posture using motion-sensor biofeedback, versus guidelines-based care, on the clinical outcomes of people with sub-acute or chronic low back pain-a multicentre, cluster-randomised, placebo-controlled, pilot trial

DEFF Research Database (Denmark)

Kent, Peter; Laird, Robert; Haines, Terry

2015-01-01

sample size calculations for a fully powered trial. METHODS: A multicentre (8 clinics), cluster-randomised, placebo-controlled pilot trial compared two groups of patients seeking medical or physiotherapy primary care for sub-acute and chronic back pain. It was powered for longitudinal analysis...

Efficacy and safety of dextromethorphan/quinidine at two dosage levels for diabetic neuropathic pain: a double-blind, placebo-controlled, multicenter study.

Science.gov (United States)

Shaibani, Aziz I; Pope, Laura E; Thisted, Ronald; Hepner, Adrian

2012-02-01

To evaluate dextromethorphan coadministered with quinidine as treatment of diabetic peripheral neuropathic pain. In a 13-week, phase 3, randomized controlled trial, 379 adults with daily symmetric diabetic peripheral neuropathy (DPN) leg pain for ≥3 months received double-blind placebo, dextromethorphan/quinidine (DMQ) 45/30 mg, or DMQ 30/30 mg, administered once daily for 7 days and twice daily thereafter. Efficacy measures included four pain rating scales applied daily using patient diaries, and another two applied at five clinic visits. On all six scales, DMQ 45/30 mg was significantly superior to placebo, including the primary efficacy analysis, which utilized mixed-effects modeling to test all scores on an 11-point numerical Pain Rating Scale (P < 0.0001). Sensitivity analyses gave consistent results. Efficacy vs placebo was also seen for diary ratings of present pain intensity, and pain interference with sleep and with activities (all P < 0.0001). Among clinic visit assessments, DMQ 45/30 mg demonstrated greater leg pain relief (P = 0.0002) and greater reduction of leg pain intensity (P = 0.0286) vs placebo. The efficacy of DMQ 30/30 mg was numerically less than for 45/30 mg but for most outcomes remained significantly greater vs placebo. Adverse events were mostly mild or moderate and of expected types. Discontinuation for adverse events in the DMQ groups was at least twice as common as placebo. Throughout a 13-week trial, DMQ was effective, with an acceptable safety profile, for treatment of DPN pain. Other fixed-dose combinations of DMQ should be studied to improve overall tolerability while maintaining significant efficacy. Wiley Periodicals, Inc.

PLACEBO-CONTROLLED STUDY OF MYCOPHENOLATE MOFETIL COMBINED WITH CYCLOSPORINE AND CORTICOSTEROIDS FOR PREVENTION OF ACUTE REJECTION

NARCIS (Netherlands)

GRINYO, J; GROTH, C; PICHLMAYR, R; SADEK, SA; VANRENTERGHEM, Y; BEHREND, M; LUCK, R; MORESO, F; PEETERS, J; RODICIO, J; MORALES, J; ALBRECHTSEN, D; FAUCHALD, P; SADEK, S; LODGE, J; SOULILLOU, JP; CANTAROVICH, D; van Son, W; Tegzess, Adam; WAGNER, K; ERHARD, J; BRATTSTROM, C; MJORNSTEDT, L; WIESEL, M; CARL, S; NEUMAYER, HH; HAUSER, [No Value; LANG, P; BOURGEON, B; TUFVESON, G; GANNEDAHL, G; EKBERG, H; PERSSON, N; TARANTINO, A; CAMPISE, M; THIEL, G; ZEILER, M; HENE, R; LIGTENBERG, G; MORGAN, A; RIGG, K; HOOFTMAN, L; HUTCHINSON, K

1995-01-01

Preliminary studies suggested that mycophenolate mofetil (MMF), which inhibits proliferation of T and B cells, may reduce the frequency of acute rejection after renal transplantation. Our randomised, double-blind, multicentre, placebo-controlled study compared the efficacy and safety of MMF with

Efficacy of pentavalent rotavirus vaccine against severe rotavirus gastroenteritis in infants in developing countries in sub-Saharan Africa: a randomised, double-blind, placebo-controlled trial.

Science.gov (United States)

Armah, George E; Sow, Samba O; Breiman, Robert F; Dallas, Michael J; Tapia, Milagritos D; Feikin, Daniel R; Binka, Fred N; Steele, A Duncan; Laserson, Kayla F; Ansah, Nana A; Levine, Myron M; Lewis, Kristen; Coia, Michele L; Attah-Poku, Margaret; Ojwando, Joel; Rivers, Stephen B; Victor, John C; Nyambane, Geoffrey; Hodgson, Abraham; Schödel, Florian; Ciarlet, Max; Neuzil, Kathleen M

2010-08-21

Rotavirus gastroenteritis causes many deaths in infants in sub-Saharan Africa. Because rotavirus vaccines have proven effective in developed countries but had not been tested in developing countries, we assessed efficacy of a pentavalent rotavirus vaccine against severe disease in Ghana, Kenya, and Mali between April, 2007, and March, 2009. In our multicentre, double-blind, placebo-controlled trial, undertaken in rural areas of Ghana and Kenya and an urban area of Mali, we randomly assigned infants aged 4-12 weeks without symptoms of gastrointestinal disorders in a 1:1 ratio to receive three oral doses of pentavalent rotavirus vaccine 2 mL or placebo at around 6 weeks, 10 weeks, and 14 weeks of age. Infants with HIV infection were not excluded. Randomisation was done by computer-generated randomisation sequence in blocks of six. We obtained data for gastrointestinal symptoms from parents on presentation to health-care facilities and clinical data were obtained prospectively by clinicians. The primary endpoint was severe rotavirus gastroenteritis (Vesikari score >or=11), detected by enzyme immunoassay, arising 14 days or more after the third dose of placebo or vaccine to end of study (March 31, 2009; around 21 months of age). Analysis was per protocol; infants who received scheduled doses of vaccine or placebo without intervening laboratory-confirmed naturally occurring rotavirus disease earlier than 14 days after the third dose and had complete clinical and laboratory results were included in the analysis. This study is registered with ClinicalTrials.gov, number NCT00362648. 5468 infants were randomly assigned to receive pentavalent rotavirus vaccine (n=2733) or placebo (n=2735). 2357 infants assigned to vaccine and 2348 assigned to placebo were included in the per-protocol analysis. 79 cases of severe rotavirus gastroenteritis were reported in 2610.6 person-years in the vaccine group, compared with 129 cases in 2585.9 person-years in the placebo group, resulting

Efficacy of metformin on glycemic control and weight in drug-naive type 2 diabetes mellitus patients: A systematic review and meta-analysis of placebo-controlled randomized trials.

Science.gov (United States)

Piera-Mardemootoo, Carole; Lambert, Philippe; Faillie, Jean-Luc

2018-02-21

Metformin is recommended as the first-line treatment of type 2 diabetes mellitus. Despite its common use, few studies have been conducted to precisely measure the efficacy of metformin versus placebo as a first-line treatment. This study aims to assess the precise effects of metformin monotherapy on glycemic control and weight in drug-naive patients with type 2 diabetes mellitus. Medline ® and Cochrane databases were searched until March 19, 2016 to perform a systematic review and meta-analysis of placebo-controlled randomized trials evaluating metformin monotherapy in drug-naive patients with type 2 diabetes mellitus. Assessed outcomes include glycemic control (fasting plasma glucose, glycosated hemoglobin) and weight. Overall, 16 studies (1140 patients) were selected. Compared to placebo, metformin monotherapy was associated with decreased glycosated hemoglobin by 0.95% at 3 months (95% CI: 0.50 to 1.39, I 2 =87%) and 1.32% at 6 months (95% CI: 1.01 to 1.62, I 2 =71%), and decreased fasting plasma glucose by 1.92mmol/L at 1 month (95% CI: 0.11 to 3.74, I 2 =88%), 1.79mmol/L at 3 months (95% CI: 0.92 to 2.66, I 2 =88%) and 2.14mmol/L at 6 months (95% CI: 1.17 to 3.12, I 2 =82%). No significant difference was demonstrated for the comparisons of weight due to relatively small number of studies retrieved from the literature resulting in insufficient statistical power. This study provides the precise effects of metformin monotherapy regarding the decreases in fasting plasma glucose and glycosated hemoglobin that physician can expected in drug-naive patients with type 2 diabetes mellitus. No evidence was found for the effects on weight. Copyright © 2018 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

Bell's Palsy in Children (BellPIC): protocol for a multicentre, placebo-controlled randomized trial.

Science.gov (United States)

Babl, Franz E; Mackay, Mark T; Borland, Meredith L; Herd, David W; Kochar, Amit; Hort, Jason; Rao, Arjun; Cheek, John A; Furyk, Jeremy; Barrow, Lisa; George, Shane; Zhang, Michael; Gardiner, Kaya; Lee, Katherine J; Davidson, Andrew; Berkowitz, Robert; Sullivan, Frank; Porrello, Emily; Dalziel, Kim Marie; Anderson, Vicki; Oakley, Ed; Hopper, Sandy; Williams, Fiona; Wilson, Catherine; Williams, Amanda; Dalziel, Stuart R

2017-02-13

Bell's palsy or acute idiopathic lower motor neurone facial paralysis is characterized by sudden onset paralysis or weakness of the muscles to one side of the face controlled by the facial nerve. While there is high level evidence in adults demonstrating an improvement in the rate of complete recovery of facial nerve function when treated with steroids compared with placebo, similar high level studies on the use of steroids in Bell's palsy in children are not available. The aim of this study is to assess the utility of steroids in Bell's palsy in children in a randomised placebo-controlled trial. We are conducting a randomised, triple-blinded, placebo controlled trial of the use of prednisolone to improve recovery from Bell's palsy at 1 month. Study sites are 10 hospitals within the Australian and New Zealand PREDICT (Paediatric Research in Emergency Departments International Collaborative) research network. 540 participants will be enrolled. To be eligible patients need to be aged 6 months to Bell's palsy to one of the participating hospital emergency departments. Patients will be excluded in case of current use of or contraindications to steroids or if there is an alternative diagnosis. Participants will receive either prednisolone 1 mg/kg/day to a maximum of 50 mg/day or taste matched placebo for 10 days. The primary outcome is complete recovery by House-Brackmann scale at 1 month. Secondary outcomes include assessment of recovery using the Sunnybrook scale, the emotional and functional wellbeing of the participants using the Pediatric Quality of Life Inventory and Child Health Utility 9D Scale, pain using Faces Pain Scale Revised or visual analogue scales, synkinesis using a synkinesis assessment questionnaire and health utilisation costs at 1, 3 and 6 months. Participants will be tracked to 12 months if not recovered earlier. Data analysis will be by intention to treat with primary outcome presented as differences in proportions and an odds ratio

Informed consent and placebo effects: a content analysis of information leaflets to identify what clinical trial participants are told about placebos.

Directory of Open Access Journals (Sweden)

Felicity L Bishop

Full Text Available Placebo groups are used in randomised clinical trials (RCTs to control for placebo effects, which can be large. Participants in trials can misunderstand written information particularly regarding technical aspects of trial design such as randomisation; the adequacy of written information about placebos has not been explored. We aimed to identify what participants in major RCTs in the UK are told about placebos and their effects.We conducted a content analysis of 45 Participant Information Leaflets (PILs using quantitative and qualitative methodologies. PILs were obtained from trials on a major registry of current UK clinical trials (the UKCRN database. Eligible leaflets were received from 44 non-commercial trials but only 1 commercial trial. The main limitation is the low response rate (13.5%, but characteristics of included trials were broadly representative of all non-commercial trials on the database. 84% of PILs were for trials with 50:50 randomisation ratios yet in almost every comparison the target treatments were prioritized over the placebos. Placebos were referred to significantly less frequently than target treatments (7 vs. 27 mentions, p<001 and were significantly less likely than target treatments to be described as triggering either beneficial effects (1 vs. 45, p<001 or adverse effects (4 vs. 39, p<001. 8 PILs (18% explicitly stated that the placebo treatment was either undesirable or ineffective.PILs from recent high quality clinical trials emphasise the benefits and adverse effects of the target treatment, while largely ignoring the possible effects of the placebo. Thus they provide incomplete and at times inaccurate information about placebos. Trial participants should be more fully informed about the health changes that they might experience from a placebo. To do otherwise jeopardises informed consent and is inconsistent with not only the science of placebos but also the fundamental rationale underpinning placebo controlled

Efficacy and safety of strontium ranelate in the treatment of knee osteoarthritis: results of a double-blind, randomised placebo-controlled trial

Directory of Open Access Journals (Sweden)

Jean-Yves Reginster

2013-01-01

Full Text Available Objective. Background Strontium ranelate is currently used for osteoporosis. The international, double-blind, randomised, placebo-controlled Strontium ranelate Efficacy in Knee OsteoarthrItis triAl evaluated its effect on radiological progression of knee osteoarthritis.Methods. Patients with knee osteoarthritis (Kellgren and Lawrence grade 2 or 3, and joint space width (JSW 2.5-5 mm were randomly allocated to strontium ranelate 1 g/day (n=558, 2 g/day (n=566 or placebo (n=559. The primary endpoint was radiographical change in JSW (medial tibiofemoral compartment over 3 years versus placebo. Secondary endpoints included radiological progression, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC score, and knee pain. The trial is registered (ISRCTN41323372.Results. The intention-to-treat population included 1371 patients. Treatment with strontium ranelate was associated with smaller degradations in JSW than placebo (1 g/day: -0.23 (SD 0.56 mm; 2 g/day: -0.27 (SD 0.63 mm; placebo:-0.37 (SD 0.59 mm; treatment-placebo differences were 0.14 (SE 0.04, 95% CI 0.05 to 0.23, p<0.001 for 1 g/day and 0.10 (SE 0.04, 95% CI 0.02 to 0.19, p=0.018 for 2 g/day. Fewer radiological progressors were observed withstrontium ranelate (p<0.001 and p=0.012 for 1 and 2 g/day. There were greater reductions in total WOMAC score (p=0.045, pain subscore (p=0.028, physical function subscore (p=0.099 and knee pain (p=0.065 with strontium ranelate 2 g/day. Strontium ranelate was well tolerated. Conclusions. Treatment with strontium ranelate 1 and 2 g/day is associated with a significant effect on structure in patients with knee osteoarthritis, and a beneficial effect on symptoms for strontium ranelate 2 g/day.Additional supplementary data are published online only. To view these files please visit the journal online (http://dx.doi. org/10.1136/annrheumdis-2012-202231

Prevention of preterm delivery with vaginal progesterone in women with preterm labour (4P): randomised double-blind placebo-controlled trial.

Science.gov (United States)

Martinez de Tejada, B; Karolinski, A; Ocampo, M C; Laterra, C; Hösli, I; Fernández, D; Surbek, D; Huespe, M; Drack, G; Bunader, A; Rouillier, S; López de Degani, G; Seidenstein, E; Prentl, E; Antón, J; Krähenmann, F; Nowacki, D; Poncelas, M; Nassif, J C; Papera, R; Tuma, C; Espoile, R; Tiberio, O; Breccia, G; Messina, A; Peker, B; Schinner, E; Mol, B W; Kanterewicz, L; Wainer, V; Boulvain, M; Othenin-Girard, V; Bertolino, M V; Irion, O

2015-01-01

To evaluate the effectiveness of 200 mg of daily vaginal natural progesterone to prevent preterm birth in women with preterm labour. Multicentre, randomised, double-blind, placebo-controlled trial. Twenty-nine centres in Switzerland and Argentina. A total of 385 women with preterm labour (24(0/7) to 33(6/7) weeks of gestation) treated with acute tocolysis. Participants were randomly allocated to either 200 mg daily of self-administered vaginal progesterone or placebo within 48 hours of starting acute tocolysis. Primary outcome was delivery before 37 weeks of gestation. Secondary outcomes were delivery before 32 and 34 weeks, adverse effects, duration of tocolysis, re-admissions for preterm labour, length of hospital stay, and neonatal morbidity and mortality. The study was ended prematurely based on results of the intermediate analysis. Preterm birth occurred in 42.5% of women in the progesterone group versus 35.5% in the placebo group (relative risk [RR] 1.2; 95% confidence interval [95% CI] 0.93-1.5). Delivery at <32 and <34 weeks did not differ between the two groups (12.9 versus 9.7%; [RR 1.3; 95% CI 0.7-2.5] and 19.7 versus 12.9% [RR 1.5; 95% CI 0.9-2.4], respectively). The duration of tocolysis, hospitalisation, and recurrence of preterm labour were comparable between groups. Neonatal morbidity occurred in 44 (22.8%) cases on progesterone versus 35 (18.8%) cases on placebo (RR: 1.2; 95% CI 0.82-1.8), whereas there were 4 (2%) neonatal deaths in each study group. There is no evidence that the daily administration of 200 mg vaginal progesterone decreases preterm birth or improves neonatal outcome in women with preterm labour. © 2014 Royal College of Obstetricians and Gynaecologists.

Effect of Moringa oleifera Leaf Capsules on Glycemic Control in Therapy-Naïve Type 2 Diabetes Patients: A Randomized Placebo Controlled Study

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Rutchaporn Taweerutchana

2017-01-01

Full Text Available Background. Studies showed effects of Moringa oleifera (MO on lowering blood sugar levels in animal and diabetes patients. The aims of this study were to determine the effect of MO leaf capsules on glucose control in therapy-naïve type 2 diabetes mellitus (T2DM and to evaluate its safety. Method. This was a prospective randomized placebo controlled study. Therapy-naïve T2DM was randomly assigned to receive either 8 grams per day of MO leaf capsules (MO leaf group or placebo for 4 weeks. Clinical and laboratory characteristics were recorded at screening and at the end of 4-week study. 9-point plasma glucose was obtained before and every week during the study. Results. Thirty-two T2DM patients were enrolled. The mean age was 55 years and the mean HbA1C was 7.0%. There was no significant difference in FPG and HbA1C between groups. MO leaf group had SBP reduction by 5 mmHg as compared to baseline but this difference had no statistical significance. There were no adverse effects of MO leaf. Conclusions. Moringa oleifera leaf had no effect on glycemic control and no adverse effects in T2DM. Interestingly, this study demonstrated that MO leaf had a tendency on blood pressure reduction in T2DM, and this result needs further investigation.

The effects of coenzyme Q10 supplementation on cardiometabolic markers in overweight type 2 diabetic patients with stable myocardial infarction: A randomized, double-blind, placebo-controlled trial

Directory of Open Access Journals (Sweden)

Seyyed Mehdi Mirhashemi

2016-09-01

Full Text Available BACKGROUND: Limited data are present that have assessed the effects of coenzyme Q10 (CoQ10 intake on cardiometabolic markers in type 2 diabetic patients with coronary heart disease (CHD. This study was done to determine the effects of CoQ10 administration on cardiometabolic markers in overweight diabetic patients with stable myocardial infarction. METHODS: This randomized double-blind placebo-controlled clinical trial was done among 60 diabetic patients with CHD aged 45-75 years old. Subjects were randomly allocated into two groups to receive either 100 mg/day CoQ10 supplements (n = 30 or placebo (n = 30 for 8 weeks. RESULTS: Compared with the placebo, CoQ10 intake led to a significant reduction in serum interleukin 6 (IL-6 (-1.7 ± 1.6 vs. 0.8 ± 1.7 ng/l, P < 0.001 and protein carbonyl (PCO levels (-0.2 ± 0.3 vs. 0.1 ± 0.2 nmol/mg protein, P < 0.001. Supplementation with CoQ10 did not affect serum lipoprotein(a, advanced glycation end-products and thiol concentrations compared with the placebo. CONCLUSION: Overall, this study indicated that CoQ10 intake after 8 weeks among diabetic patients with the stable CHD had beneficial effects on serum IL-6 and PCO levels, but did not alter other cardiometabolic markers.  

Treatment satisfaction with tadalafil or tamsulosin vs placebo in men with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH): results from a randomised, placebo-controlled study.

Science.gov (United States)

Oelke, Matthias; Giuliano, François; Baygani, Simin K; Melby, Thomas; Sontag, Angelina

2014-10-01

To assess treatment satisfaction with tadalafil or tamsulosin vs placebo in a 12-week, randomised, double-blind study of men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH). After a 4-week placebo lead-in period, men aged ≥45 years with an International Prostate Symptom Score (IPSS) of ≥13 and a maximum urinary flow rate of ≥4 to ≤15 mL/s received placebo (172 men), tadalafil 5 mg (171), or tamsulosin 0.4 mg (168) once daily for 12 weeks. Treatment Satisfaction Scale-BPH (TSS-BPH) responses were assessed based on median treatment differences using the van Elteren test. Overall treatment satisfaction was greater for tadalafil vs placebo (P = 0.005), based on greater satisfaction with efficacy (P = 0.003); neither overall treatment satisfaction nor satisfaction with efficacy was greater for tamsulosin vs placebo (P ≥ 0.409). For individual questions, 66.5% of men rated tadalafil treatment as 'effective/very effective' (Question 1, Q1) vs placebo (P = 0.011), 72.6% would 'definitely/probably recommend their treatment' (Q3; P = 0.043), 71.8% were generally 'very satisfied/satisfied with their medication' (Q8; P BPH by baseline age (≤65/>65 years), history of erectile dysfunction (yes/no), LUTS/BPH severity (IPSSplacebo, with only borderline difference for men without prior therapy. Treatment satisfaction was greater with tadalafil vs placebo, with no significant difference between tamsulosin and placebo. © 2014 The Authors. BJU International © 2014 BJU International.

Radiotherapy for Graves' orbitopathy : randomised placebo-controlled study

NARCIS (Netherlands)

Mourits, MP; van Kempen-Harteveld, ML; Garcia, MBG; Koppeschaar, HPF; Tick, L; Terwee, CB

2000-01-01

Background The best treatment (steroids, irradiation, or both) for moderately severe Graves' orbitopathy, a self-limiting disease is not known. We tested the efficacy of external beam irradiation compared with sham-irradiation. Methods In a double-blind randomised clinical trial, 30 patients with

Radial extracorporeal shock-wave therapy in patients with chronic rotator cuff tendinitis: a prospective randomised double-blind placebo-controlled multicentre trial.

Science.gov (United States)

Kolk, A; Yang, K G Auw; Tamminga, R; van der Hoeven, H

2013-11-01

The aim of this study was to determine the effect of radial extracorporeal shock-wave therapy (rESWT) on patients with chronic tendinitis of the rotator cuff. This was a randomised controlled trial in which 82 patients (mean age 47 years (24 to 67)) with chronic tendinitis diagnosed clinically were randomly allocated to a treatment group who received low-dose rESWT (three sessions at an interval 10 to 14 days, 2000 pulses, 0.11 mJ/mm(2), 8 Hz) or to a placebo group, with a follow-up of six months. The patients and the treating orthopaedic surgeon, who were both blinded to the treatment, evaluated the results. A total of 44 patients were allocated to the rESWT group and 38 patients to the placebo group. A visual analogue scale (VAS) score for pain, a Constant-Murley (CMS) score and a simple shoulder test (SST) score significantly improved in both groups at three and six months compared with baseline (all p ≤ 0.012). The mean VAS was similar in both groups at three (p = 0.43) and six months (p = 0.262). Also, the mean CMS and SST scores were similar in both groups at six months (p = 0.815 and p = 0.834, respectively). It would thus seem that low-dose rESWT does not reduce pain or improve function in patients chronic rotator cuff tendinitis compared with placebo treatment.

The effect of motivational interviewing on glycaemic control and perceived competence of diabetes self-management in patients with type 1 and type 2 diabetes mellitus after attending a group education programme: a randomised controlled trial.

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Rosenbek Minet, L K; Wagner, L; Lønvig, E M; Hjelmborg, J; Henriksen, J E

2011-07-01

The aim of this study was to measure the efficacy of motivational interviewing (MI) compared with usual care on changes in glycaemic control and competence of diabetes self-management in patients with diabetes mellitus. Patients were eligible if they had type 1 or 2 diabetes mellitus, were over 18 years of age and had participated in a 4 day group education programme offered at a diabetes clinic at a university hospital in Denmark. Exclusion criteria included pregnancy, severe debilitating disease and cognitive deficit. Out of 469 patients who attended the group education programme, 349 patients were randomised to either a usual care control group or an intervention group, which received up to five individual counselling sessions in 1 year based on MI, in addition to usual care. A randomised parallel design was used and open-label allocation was done by random permuted blocks, with allocation concealment by sequentially numbered, sealed, opaque envelopes. The primary outcome was glycated haemoglobin (HbA(1c)). Analysis regarding measurements of glycated haemoglobin (HbA(1c)) and competence of self-management (using the Problem Areas in Diabetes Scale [PAID] and Perceived Competence for Diabetes Scale [PCDS]) was based on 298 participants followed for a 24 month period. Data were collected at the Department of Endocrinology at Odense University Hospital. Our hypotheses were that MI could: (1) reduce HbA(1c) levels; (2) increase self-efficacy; and (3) increase diabetes self-care, compared with usual care. Out of the 176 included in the control group and 173 in the intervention group, 153 and 145 were analysed in the groups, respectively. When using the baseline value as covariate there were no significant differences in change score between the two study groups with regard to mean level of HbA(1c) (0.131, p = 0.221), PAID scores (-1.793, p = 0.191) or PCDS scores (0.017, p = 0.903) at the 24 month follow-up, using a mixed effects regression model. The

B vitamins to enhance treatment response to antidepressants in middle-aged and older adults: results from the B-VITAGE randomised, double-blind, placebo-controlled trial.

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Almeida, Osvaldo P; Ford, Andrew H; Hirani, Varsha; Singh, Vash; vanBockxmeer, Frank M; McCaul, Kieran; Flicker, Leon

2014-12-01

Depression is common and the efficacy of antidepressants is suboptimal. High plasma homocysteine has been consistently associated with depression, and treatment with certain B vitamins demonstrably reduces its concentration. To determine whether vitamins B6, B12 and folic acid enhance response to antidepressant treatment over 52 weeks. Randomised, double-blind, placebo-controlled trial of citalopram (20-40 g) together with 0.5 mg of vitamin B12, 2 mg of folic acid and 25 mg of vitamin B6 for 52 weeks (Australian and New Zealand Clinical Trials Registry: 12609000256279). Participants were community-dwelling adults aged 50 years or over with DSM-IV-TR major depression. We measured severity of symptoms with the Montgomery-Åsberg Depression Rating Scale (MADRS). The primary outcome was remission of the depressive episode after 12, 26 and 52 weeks. Secondary outcomes included reduction of MADRS scores over time and relapse of major depression after recovery by week 12. Results In total, 153 people were randomised (76 placebo, 77 vitamins). Remission of symptoms was achieved by 78.1 and 79.4% of participants treated with placebo and vitamins by week 12 (P = 0.840), by 76.5 and 85.3% at week 26 and 75.8 and 85.5% at week 52 (effect of intervention over 52 weeks: odds ratio (OR) = 2.49, 95% CI 1.12-5.51). Group differences in MADRS scores over time were not significant (P = 0.739). The risk of subsequent relapse among those who had achieved remission of symptoms at week 12 was lower in the vitamins than placebo group (OR = 0.33, 95% CI 0.12-0.94). B vitamins did not increase the 12-week efficacy of antidepressant treatment, but enhanced and sustained antidepressant response over 1 year. Replication of these findings would mandate that treatment guidelines adopt the adjunctive use of B vitamins as a safe and inexpensive strategy to manage major depression in middle-aged and older adults. Royal College of Psychiatrists.

Benefits of Semelil (ANGIPARSTM on oxidant-antioxidant balance in diabetic patients; A randomized, double-blind placebo controlled clinical trial

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M Hemmatabadi

2010-01-01

Full Text Available "n "nBackground and the purpose of the study: Diabetes mellitus is one of the most common chronic diseases in the world with dreadful complications which not only is debilating for the patients but also puts a big burden on the health system.One of the mechanisms by which the complications of diabetes occur is imbalance in the oxidant-antioxidant equilibrium in the body and therefore many studies have been performed to either correct this equilibrium or delay the occurrence of the complications. "nMethods:In this randomized, double-blind placebo-controlled clinical trial, a total number of 61 subjects were divided into two groups and the antioxidant effects of a novel herbal drug, Semelil,was compared with placebo. Baseline laboratory tests including a complete blood count, fasting blood sugar,lipid profile,fasting plasma insulin, liver and renal function tests plus tumor necrotizing factor α (TNFα and C-reactive protein (CRP and homocystein were performed. Total antioxidant power assay, cellular lipid peroxidation assay, and nuclear damage (deoxyguanosine and carbonly molecules were also measured to help determination of state of antioxidants- oxidants equilibrium in serum. "nResult:Apart from deoxyguanosine, no significant change was found in TNFα or CRP levels in the studied group who received Semelil.Conclusion: Mechanisms other than antioxidant effects are involved for Semelil in the treatment of diabetic foot ulcers.

Meal sequence and glucose excursion, gastric emptying and incretin secretion in type 2 diabetes: a randomised, controlled crossover, exploratory trial.

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Kuwata, Hitoshi; Iwasaki, Masahiro; Shimizu, Shinobu; Minami, Kohtaro; Maeda, Haruyo; Seino, Susumu; Nakada, Koji; Nosaka, Chihiro; Murotani, Kenta; Kurose, Takeshi; Seino, Yutaka; Yabe, Daisuke

2016-03-01

Investigation of dietary therapy for diabetes has focused on meal size and composition; examination of the effects of meal sequence on postprandial glucose management is limited. The effects of fish or meat before rice on postprandial glucose excursion, gastric emptying and incretin secretions were investigated. The experiment was a single centre, randomised controlled crossover, exploratory trial conducted in an outpatient ward of a private hospital in Osaka, Japan. Patients with type 2 diabetes (n = 12) and healthy volunteers (n = 10), with age 30-75 years, HbA1c 9.0% (75 mmol/mol) or less, and BMI 35 kg/m(2) or less, were randomised evenly to two groups by use of stratified randomisation, and subjected to meal sequence tests on three separate mornings; days 1 and 2, rice before fish (RF) or fish before rice (FR) in a crossover fashion; and day 3, meat before rice (MR). Pre- and postprandial levels of glucose, insulin, C-peptide and glucagon as well as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide were evaluated. Gastric emptying rate was determined by (13)C-acetate breath test involving measurement of (13)CO2 in breath samples collected before and after ingestion of rice steamed with (13)C-labelled sodium acetate. Participants, people doing measurements or examinations, and people assessing the outcomes were not blinded to group assignment. FR and MR in comparison with RF ameliorated postprandial glucose excursion (AUC-15-240 min-glucose: type 2 diabetes, FR 2,326.6 ± 114.7 mmol/l × min, MR 2,257.0 ± 82.3 mmol/l × min, RF 2,475.6 ± 87.2 mmol/l × min [p Japan Society for Promotion of Science, Japan Association for Diabetes Education and Care, and Japan Vascular Disease Research Foundation.

Libertas: rationale and study design of a multicentre, Phase II, double-blind, randomised, placebo-controlled investigation to evaluate the efficacy, safety and tolerability of locally applied NRL001 in patients with faecal incontinence.

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Siproudhis, L; Jones, D; Shing, R Ng Kwet; Walker, D; Scholefield, J H

2014-03-01

Faecal incontinence affects up to 8% of adults. Associated social isolation and subsequent depression can have devastating effects on quality of life (QoL). Faecal incontinence is an underreported health problem as the social isolation and stigma that patients experience makes it difficult for sufferers to discuss their condition with a physician. There have been few well-designed, placebo-controlled clinical trials of treatment for faecal incontinence and little clinical evidence is available to inform the most appropriate management strategies. Libertas, a robustly designed study will investigate the efficacy and safety of NRL001 (1R,2S-methoxamine), an α1 -adrenoceptor agonist, in the treatment of faecal incontinence. Libertas is a multicentre, Phase II, double-blind, randomised, placebo-controlled, parallel group study. Patient recruitment took place across 55 study centres in Europe. Patients suffering with faecal incontinence were randomised into four groups (approximately 110 each) to receive once daily self-administered doses of NRL001 (5, 7.5 or 10 mg or placebo in a suppository formulation) for 8 weeks. The primary objective of Libertas is to assess the impact of once daily administration of NRL001 on the severity and frequency of incontinence episodes as assessed by the Wexner score at 4 weeks, compared with placebo. Secondary outcomes include measures of efficacy of NRL001 compared with placebo following 8 weeks treatment; safety and tolerability; evaluation of plasma pharmacokinetics; establishment of any pharmacokinetic/pharmacodynamic relationship to adverse events; dose-response relationship; the efficacy of NRL001 therapy at 4 and 8 weeks assessed by the Vaizey score; and QoL using the Faecal Incontinence Quality of Life and the EQ-5D-5L Healthcare Questionnaires following 4 and 8 weeks NRL001 therapy. Overall patient satisfaction with the treatment will also be evaluated. This is the first randomised controlled study to investigate the efficacy

Hyperglycaemia in early pregnancy: the Treatment of Booking Gestational diabetes Mellitus (TOBOGM) study. A randomised controlled trial.

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Simmons, David; Hague, William M; Teede, Helena J; Cheung, N Wah; Hibbert, Emily J; Nolan, Christopher J; Peek, Michael J; Girosi, Federico; Cowell, Christopher T; Wong, Vincent W-M; Flack, Jeff R; McLean, Mark; Dalal, Raiyomand; Robertson, Annette; Rajagopal, Rohit

2018-05-28

Gestational diabetes mellitus (GDM) causes adverse pregnancy outcomes that can be averted by treatment from 24-28 weeks' gestation. Assessing and treating women for overt diabetes in pregnancy (ODIP) at the first antenatal clinic booking is now recommended in international guidelines. As a consequence, women with milder hyperglycaemia are being diagnosed and treated for early GDM, but randomised controlled trial (RCTs) assessing the benefits and harms of such treatment have not been undertaken. The Treatment Of Booking Gestational diabetes Mellitus (TOBOGM) study is a multi-centre RCT examining whether diagnosing and treating GDM diagnosed at booking improves pregnancy outcomes. Methods and analysis: 4000 adult pregnant women (lean body mass. The primary maternal outcome is pre-eclampsia. Ethics approval: South Western Sydney Local Health District Research and Ethics Office (reference, 15/LPOOL/551). Dissemination of results: Peer-reviewed publications, scientific meetings, collaboration with research groups undertaking comparable studies, discussions with guideline groups and policy makers. Australian New Zealand Clinical Trials Registry, ACTRN12616000924459.

Co-crystal of Tramadol-Celecoxib in Patients with Moderate to Severe Acute Post-surgical Oral Pain: A Dose-Finding, Randomised, Double-Blind, Placebo- and Active-Controlled, Multicentre, Phase II Trial.

Science.gov (United States)

López-Cedrún, José; Videla, Sebastián; Burgueño, Miguel; Juárez, Inma; Aboul-Hosn, Samir; Martín-Granizo, Rafael; Grau, Joan; Puche, Miguel; Gil-Diez, José-Luis; Hueto, José-Antonio; Vaqué, Anna; Sust, Mariano; Plata-Salamán, Carlos; Monner, Antoni

2018-06-01

Co-crystal of tramadol-celecoxib (CTC), containing equimolar quantities of the active pharmaceutical ingredients (APIs) tramadol and celecoxib (100 mg CTC = 44 mg rac-tramadol hydrochloride and 56 mg celecoxib), is a novel API-API co-crystal for the treatment of pain. We aimed to establish the effective dose of CTC for treating acute pain following oral surgery. A dose-finding, double-blind, randomised, placebo- and active-controlled, multicentre (nine Spanish hospitals), phase II study (EudraCT number: 2011-002778-21) was performed in male and female patients aged ≥ 18 years experiencing moderate to severe pain following extraction of two or more impacted third molars requiring bone removal. Eligible patients were randomised via a computer-generated list to receive one of six single-dose treatments (CTC 50, 100, 150, 200 mg; tramadol 100 mg; and placebo). The primary efficacy endpoint was the sum of pain intensity difference (SPID) over 8 h assessed in the per-protocol population. Between 10 February 2012 and 13 February 2013, 334 patients were randomised and received study treatment: 50 mg (n = 55), 100 mg (n = 53), 150 mg (n = 57), or 200 mg (n = 57) of CTC, 100 mg tramadol (n = 58), or placebo (n = 54). CTC 100, 150, and 200 mg showed significantly higher efficacy compared with placebo and/or tramadol in all measures: SPID (0-8 h) (mean [standard deviation]): - 90 (234), - 139 (227), - 173 (224), 71 (213), and 22 (228), respectively. The proportion of patients experiencing treatment-emergent adverse events was lower in the 50 (12.7% [n = 7]), 100 (11.3% [n = 6]), and 150 (15.8% [n = 9]) mg CTC groups, and similar in the 200 mg (29.8% [n = 17]) CTC group, compared with the tramadol group (29.3% [n = 17]), with nausea, dizziness, and vomiting the most frequent events. Significant improvement in the benefit-risk ratio was observed for CTC (doses ≥ 100 mg) over tramadol and placebo in

The Efficacy and Safety of Chinese Herbal Medicine Jinlida as Add-On Medication in Type 2 Diabetes Patients Ineffectively Managed by Metformin Monotherapy: A Double-Blind, Randomized, Placebo-Controlled, Multicenter Trial

OpenAIRE

Lian, Fengmei; Tian, Jiaxing; Chen, Xinyan; Li, Zhibin; Piao, Chunli; Guo, Junjie; Ma, Licheng; Zhao, Lijuan; Xia, Chengdong; Wang, Chong-Zhi; Yuan, Chun-Su; Tong, Xiaolin

2015-01-01

Background Metformin plays an important role in diabetes treatment. Studies have shown that the combined use of oral hypoglycemic medications is more effective than metformin monotherapy. In this double-blind, randomized, placebo-controlled, multicenter trial, we evaluated whether Jinlida, a Chinese herbal medicine, enhances the glycemic control of metformin in type 2 diabetes patients whose HbA1c was ineffectively controlled with metformin alone. Methods A total of 186 diabetes patients were...

Evaluation of an online interactive Diabetes Needs Assessment Tool (DNAT versus online self-directed learning: a randomised controlled trial

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Kellner Thomas

2011-06-01

Full Text Available Abstract Background Methods for the dissemination, understanding and implementation of clinical guidelines need to be examined for their effectiveness to help doctors integrate guidelines into practice. The objective of this randomised controlled trial was to evaluate the effectiveness of an interactive online Diabetes Needs Assessment Tool (DNAT (which constructs an e-learning curriculum based on individually identified knowledge gaps, compared with self-directed e-learning of diabetes guidelines. Methods Health professionals were randomised to a 4-month learning period and either given access to diabetes learning modules alone (control group or DNAT plus learning modules (intervention group. Participants completed knowledge tests before and after learning (primary outcome, and surveys to assess the acceptability of the learning and changes to clinical practice (secondary outcomes. Results Sixty four percent (677/1054 of participants completed both knowledge tests. The proportion of nurses (5.4% was too small for meaningful analysis so they were excluded. For the 650 doctors completing both tests, mean (SD knowledge scores increased from 47.4% (12.6 to 66.8% (11.5 [intervention group (n = 321, 64%] and 47.3% (12.9 to 67.8% (10.8 [control group (n = 329, 66%], (ANCOVA p = 0.186. Both groups were satisfied with the usability and usefulness of the learning materials. Seventy seven percent (218/284 of the intervention group reported combining the DNAT with the recommended reading materials was "very useful"/"useful". The majority in both groups (184/287, 64.1% intervention group and 206/299, 68.9% control group [95% CI for the difference (-2.8 to 12.4] reported integrating the learning into their clinical practice. Conclusions Both groups experienced a similar and significant improvement in knowledge. The learning materials were acceptable and participants incorporated the acquired knowledge into practice. Trial registration ISRCTN: ISRCTN67215088

Electric field-navigated transcranial magnetic stimulation for chronic tinnitus: a randomized, placebo-controlled study.

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Sahlsten, Hanna; Virtanen, Juuso; Joutsa, Juho; Niinivirta-Joutsa, Katri; Löyttyniemi, Eliisa; Johansson, Reijo; Paavola, Janika; Taiminen, Tero; Sjösten, Noora; Salonen, Jaakko; Holm, Anu; Rauhala, Esa; Jääskeläinen, Satu K

2017-09-01

Repetitive transcranial magnetic stimulation (rTMS) may alleviate tinnitus. We evaluated effects of electric field (E-field) navigated rTMS targeted according to tinnitus pitch. No controlled studies have investigated anatomically accurate E-field-rTMS for tinnitus. Effects of E-field-rTMS were evaluated in a prospective randomised placebo-controlled 6-month follow-up study on parallel groups. Patients received 10 sessions of 1 Hz rTMS or placebo targeted to the left auditory cortex corresponding to tonotopic representation of tinnitus pitch. Effects were evaluated immediately after treatment and at 1, 3 and 6 months. Primary outcome measures were visual analogue scores (VAS 0-100) for tinnitus intensity, annoyance and distress, and the Tinnitus Handicap Inventory (THI). Thirty-nine patients (mean age 50.3 years). The mean tinnitus intensity (F 3  = 15.7, p tinnitus, differences between active and placebo groups remained non-significant, due to large placebo-effect and wide inter-individual variation.

Comparative randomised controlled clinical trial of a herbal eye drop with artificial tear and placebo in computer vision syndrome.

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Biswas, N R; Nainiwal, S K; Das, G K; Langan, U; Dadeya, S C; Mongre, P K; Ravi, A K; Baidya, P

2003-03-01

A comparative randomised double masked multicentric clinical trial has been conducted to find out the efficacy and safety of a herbal eye drop preparation, itone eye drops with artificial tear and placebo in 120 patients with computer vision syndrome. Patients using computer for at least 2 hours continuosly per day having symptoms of irritation, foreign body sensation, watering, redness, headache, eyeache and signs of conjunctival congestion, mucous/debris, corneal filaments, corneal staining or lacrimal lake were included in this study. Every patient was instructed to put two drops of either herbal drugs or placebo or artificial tear in the eyes regularly four times for 6 weeks. Objective and subjective findings were recorded at bi-weekly intervals up to six weeks. Side-effects, if any, were also noted. In computer vision syndrome the herbal eye drop preparation was found significantly better than artificial tear (p computer vision syndrome.

Effects of 12 weeks of treatment with fermented milk on blood pressure, glucose metabolism and markers of cardiovascular risk in patients with type 2 diabetes

DEFF Research Database (Denmark)

Hove, K D; Brøns, C; Færch, K

2015-01-01

helveticus on BP, glycaemic control and cardiovascular risk factors in T2D. DESIGN: A randomised, double-blinded, prospective, placebo-controlled study. METHODS: In one arm of a factorial study design, 41 patients with T2D were randomised to receive 300 ml milk fermented with L. helveticus (Cardi04 yogurt......OBJECTIVE: Studies have indicated a blood pressure (BP)-lowering effect of milk-derived peptides in non-diabetic individuals, but the cardiometabolic effects of such peptides in patients with type 2 diabetes (T2D) are not known. We investigated the effect of milk fermented with Lactobacillus......) (n=23) or 300 ml artificially acidified milk (placebo yogurt) (n=18) for 12 weeks. BPs were measured over 24-h, and blood samples were collected in the fasting state and during a meal test before and after the intervention. RESULTS: Cardi04 yogurt did not reduce 24-h, daytime or nighttime systolic...

A natural seaweed derived mineral supplement (Aquamin F for knee osteoarthritis: A randomised, placebo controlled pilot study

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Kuskowski Michael A

2009-02-01

Full Text Available Abstract Background Osteoarthritis (OA is a slowly destructive process that may be influenced by a nutritional mineral balance in the body. Methods This small, double blind, placebo controlled pilot study investigated the impact of treatment with a natural multi-mineral supplement from seaweed (Aquamin on 6 minute walking distance (6 MWD, range of motion (ROM, and pain and joint mobility measured by the Western Ontario and McMaster Universities (WOMAC Osteoarthritis Index in subjects with moderate to severe OA of the knee during gradual withdrawal of non-steroidal anti-inflammatory drugs (NSAIDs that were being used daily for pain management. Subjects (n = 29 with moderate to severe OA of the knee were randomised to receive either Aquamin (2400 mg/d or Placebo for up to 12 weeks. Results Of the 29 subjects initially randomized, only 22 subjects proceeded to treatment due to 7 subjects not meeting study selection criteria at baseline. Fourteen subjects completed the study and an ITT analysis (n = 22 of the data showed no significant differences in WOMAC scores however, the data did reveal significant improvements in passive and active extension ROM (0.83° ± 1.54 vs. -1.54° ± 2.43; difference, 5.2° ± 2.2, p = 0.028 and 6 MWD (150 ± 48 ft vs. 12.5 ± 31.5 ft; difference, 136 ± 57 ft, p = 0.03 in the Aquamin group compared to the placebo group; respectively, following a 50% reduction in NSAID use. The treatments were well tolerated and the adverse event profiles were not significantly different between the groups. Conclusion This small preliminary study suggests Aquamin may increase range of motion and walking distances in subjects with OA of the knee and may allow partial withdrawal of NSAIDs over 12 weeks of treatment. Additional research is needed to confirm these preliminary observations. Trial registration NCT00755482

Optimising corticosteroid injection for lateral epicondylalgia with the addition of physiotherapy: A protocol for a randomised control trial with placebo comparison

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Brooks Peter

2009-06-01

Full Text Available Abstract Background Corticosteroid injection and physiotherapy are two commonly prescribed interventions for management of lateral epicondylalgia. Corticosteroid injections are the most clinically efficacious in the short term but are associated with high recurrence rates and delayed recovery, while physiotherapy is similar to injections at 6 weeks but with significantly lower recurrence rates. Whilst practitioners frequently recommend combining physiotherapy and injection to overcome harmful effects and improve outcomes, study of the benefits of this combination of treatments is lacking. Clinicians are also faced with the paradox that the powerful anti-inflammatory corticosteroid injections work well, albeit in the short term, for a non-inflammatory condition like lateral epicondylalgia. Surprisingly, these injections have not been rigorously tested against placebo injections. This study primarily addresses both of these issues. Methods A randomised placebo-controlled clinical trial with a 2 × 2 factorial design will evaluate the clinical efficacy, cost-effectiveness and recurrence rates of adding physiotherapy to an injection. In addition, the clinical efficacy and adverse effects of corticosteroid injection beyond that of a placebo saline injection will be studied. 132 participants with a diagnosis of lateral epicondylalgia will be randomly assigned by concealed allocation to one of four treatment groups – corticosteroid injection, saline injection, corticosteroid injection with physiotherapy or saline injection with physiotherapy. Physiotherapy will comprise 8 sessions of elbow manipulation and exercise over an 8 week period. Blinded follow-up assessments will be conducted at baseline, 4, 8, 12, 26 and 52 weeks after randomisation. The primary outcome will be a participant rating of global improvement, from which measures of success and recurrence will be derived. Analyses will be conducted on an intention-to-treat basis using linear

Safety and efficacy of AMG 334 for prevention of episodic migraine: a randomised, double-blind, placebo-controlled, phase 2 trial.

Science.gov (United States)

Sun, Hong; Dodick, David W; Silberstein, Stephen; Goadsby, Peter J; Reuter, Uwe; Ashina, Messoud; Saper, Joel; Cady, Roger; Chon, Yun; Dietrich, Julie; Lenz, Robert

2016-04-01

The calcitonin gene-related peptide (CGRP) pathway is a promising target for preventive therapies in patients with migraine. We assessed the safety and efficacy of AMG 334, a fully human monoclonal antibody against the CGRP receptor, for migraine prevention. In this multicentre, randomised, double-blind, placebo-controlled, phase 2 trial, patients aged 18-60 years with 4 to 14 migraine days per month were enrolled at 59 headache and clinical research centres in North America and Europe, and randomly assigned in a 3:2:2:2 ratio to monthly subcutaneous placebo, AMG 334 7 mg, AMG 334 21 mg, or AMG 334 70 mg using a sponsor-generated randomisation sequence centrally executed by an interactive voice response or interactive web response system. Study site personnel, patients, and the sponsor study personnel were masked to the treatment assignment. The primary endpoint was the change in monthly migraine days from baseline to the last 4 weeks of the 12-week double-blind treatment phase. The primary endpoint was calculated using the least squares mean at each timepoint from a generalised linear mixed-effect model for repeated measures. Safety endpoints were adverse events, clinical laboratory values, vital signs, and anti-AMG 334 antibodies. The study is registered with ClinicalTrials.gov, number NCT01952574. An open-label extension phase of up to 256 weeks is ongoing and will assess the long-term safety of AMG 334. From Aug 6, 2013, to June 30, 2014, 483 patients were randomly assigned to placebo (n=160), AMG 334 7 mg (n=108), AMG 334 21 mg (n=108), or AMG 334 70 mg (n=107). The mean change in monthly migraine days at week 12 was -3·4 (SE 0·4) days with AMG 334 70 mg versus -2·3 (0·3) days with placebo (difference -1·1 days [95% CI -2·1 to -0·2], p=0·021). The mean reductions in monthly migraine days with the 7 mg (-2·2 [SE 0·4]) and the 21 mg (-2·4 [0·4]) doses were not significantly different from that with placebo. Adverse events were recorded in 82 (54

No effect of Pindolol on postural hypotension in type 1 (insulin-dependent) diabetic patients with autonomic neuropathy. A randomised double-blind controlled study

DEFF Research Database (Denmark)

Dejgård, A; Hilsted, J

1988-01-01

of this therapy we performed a double-blind placebo controlled cross-over study with Pindolol (15 mg/day). Eight Type 1 (insulin-dependent) diabetic patients with autonomic neuropathy and signs and symptoms of orthostatic hypotension (systolic blood pressure decrease greater than 30 mm Hg when standing......) participated in the study. Patients were treated for 10 weeks. Clinical examinations were performed every fortnight and patients registered postural symptoms twice daily on a visual analog scale. No significant changes were seen in blood pressure recordings, heart-rate or visual analog scale registration...... during treatment with Pindolol compared to placebo. Our study does not support the suggestion that Pindolol is a valuable drug for treatment of diabetic patients with autonomic neuropathy and postural giddiness....

Comparison of metformin and insulin versus insulin alone for type 2 diabetes: systematic review of randomised clinical trials with meta-analyses and trial sequential analyses.

Science.gov (United States)

Hemmingsen, Bianca; Christensen, Louise Lundby; Wetterslev, Jørn; Vaag, Allan; Gluud, Christian; Lund, Søren S; Almdal, Thomas

2012-04-19

To compare the benefits and harms of metformin and insulin versus insulin alone as reported in randomised clinical trials of patients with type 2 diabetes. Systematic review of randomised clinical trials with meta-analyses and trial sequential analyses. The Cochrane Library, Medline, Embase, Science Citation Index Expanded, Latin American Caribbean Health Sciences Literature, and Cumulative Index to Nursing and Allied Health Literature until March 2011. We also searched abstracts presented at the American Diabetes Association and European Association for the Study of Diabetes Congresses, contacted relevant trial authors and pharmaceutical companies, hand searched reference lists of included trials, and searched the US Food and Drug Administration website. Two authors independently screened titles and abstracts for randomised clinical trials comparing metformin and insulin versus insulin alone (with or without placebo) in patients with type 2 diabetes, older than 18 years, and with an intervention period of at least 12 weeks. We included trials irrespective of language, publication status, predefined outcomes, antidiabetic interventions used before randomisation, and reported outcomes. We included 26 randomised trials with 2286 participants, of which 23 trials with 2117 participants could provide data. All trials had high risk of bias. Data were sparse for outcomes relevant to patients. Metformin and insulin versus insulin alone did not significantly affect all cause mortality (relative risk 1.30, 95% confidence interval 0.57 to 2.99) or cardiovascular mortality (1.70, 0.35 to 8.30). Trial sequential analyses showed that more trials were needed before reliable conclusions could be drawn regarding these outcomes. In a fixed effect model, but not in a random effects model, severe hypoglycaemia was significantly more frequent with metformin and insulin than with insulin alone (2.83, 1.17 to 6.86). In a random effects model, metformin and insulin resulted in reduced Hb

Safety and efficacy of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis (REGAIN): a phase 3, randomised, double-blind, placebo-controlled, multicentre study.

Science.gov (United States)

Howard, James F; Utsugisawa, Kimiaki; Benatar, Michael; Murai, Hiroyuki; Barohn, Richard J; Illa, Isabel; Jacob, Saiju; Vissing, John; Burns, Ted M; Kissel, John T; Muppidi, Srikanth; Nowak, Richard J; O'Brien, Fanny; Wang, Jing-Jing; Mantegazza, Renato

2017-12-01

Complement is likely to have a role in refractory generalised myasthenia gravis, but no approved therapies specifically target this system. Results from a phase 2 study suggested that eculizumab, a terminal complement inhibitor, produced clinically meaningful improvements in patients with anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis. We further assessed the efficacy and safety of eculizumab in this patient population in a phase 3 trial. We did a phase 3, randomised, double-blind, placebo-controlled, multicentre study (REGAIN) in 76 hospitals and specialised clinics in 17 countries across North America, Latin America, Europe, and Asia. Eligible patients were aged at least 18 years, with a Myasthenia Gravis-Activities of Daily Living (MG-ADL) score of 6 or more, Myasthenia Gravis Foundation of America (MGFA) class II-IV disease, vaccination against Neisseria meningitides, and previous treatment with at least two immunosuppressive therapies or one immunosuppressive therapy and chronic intravenous immunoglobulin or plasma exchange for 12 months without symptom control. Patients with a history of thymoma or thymic neoplasms, thymectomy within 12 months before screening, or use of intravenous immunoglobulin or plasma exchange within 4 weeks before randomisation, or rituximab within 6 months before screening, were excluded. We randomly assigned participants (1:1) to either intravenous eculizumab or intravenous matched placebo for 26 weeks. Dosing for eculizumab was 900 mg on day 1 and at weeks 1, 2, and 3; 1200 mg at week 4; and 1200 mg given every second week thereafter as maintenance dosing. Randomisation was done centrally with an interactive voice or web-response system with patients stratified to one of four groups based on MGFA disease classification. Where possible, patients were maintained on existing myasthenia gravis therapies and rescue medication was allowed at the study physician's discretion. Patients, investigators

Chinese Medicinal Formula (MHGWT for Relieving Diabetic Neuropathic Pain: A Randomized, Double-Blind, Placebo-Controlled Trial

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Chia-I Tsai

2013-01-01

Full Text Available Objective. To investigate the effects of modified Hungqi Guizhi Wuwu Tang (MHGWT, a formula that comprises Chinese medicinal herbs, in relieving neuropathic pain in diabetics. Method. Between March 2008 and April 2009, 112 participants were randomly assigned to either the MHGWT group, whose members received MHGWT (n=56, or the control group, whose members received a placebo (n=56. Diabetic neuropathic pain (DNP was rated using the 15-item Short-Form Brief Pain Inventory (SF-BPI, the 17-item Short-Form McGill Pain Questionnaire (SF-MPQ, the 13-item Modified Michigan Neuropathy Screening Instrument (MMNSI, and the 36-item “SF-36.” Nerve conduction studies (NCSs were performed before and after treatment. Results. After 12 weeks of treatment, the SF-MPQ and SF-BPI scores of the MHGWT group were significantly (P0.05 reduced, and no significant difference in NCS level was observed between the groups (P>0.05. Conclusions. MHGWT shows promise in relieving DNP and deserves further investigation.

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

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

2017-09-02

Noise-induced hearing loss is a leading cause of occupational and recreational injury and disease, and a major determinant of age-related hearing loss. No therapeutic agent has been approved for the prevention or treatment of this disorder. In animal models, glutathione peroxidase 1 (GPx1) activity is reduced after acute noise exposure. Ebselen, a novel GPx1 mimic, has been shown to reduce both temporary and permanent noise-induced hearing loss in preclinical studies. We assessed the safety and efficacy of ebselen for the prevention of noise-induced hearing loss in young adults in a phase 2 clinical trial. In this single-centre, randomised, double-blind, placebo-controlled phase 2 trial, healthy adults aged 18-31 years were randomly assigned (1:1:1:1) at the University of Florida (Gainsville, FL, USA) to receive ebselen 200 mg, 400 mg, or 600 mg, or placebo orally twice daily for 4 days, beginning 2 days before a calibrated sound challenge (4 h of pre-recorded music delivered by insert earphones). Randomisation was done with an allocation sequence generated by an independent third party. The primary outcome was mean temporary threshold shift (TTS) at 4 kHz measured 15 min after the calibrated sound challenge by pure tone audiometry; a reduction of 50% in an ebselen dose group compared with the placebo group was judged to be clinically relevant. All participants who received the calibrated sound challenge and at least one dose of study drug were included in the efficacy analysis. All randomly assigned patients were included in the safety analysis. This trial is registered with ClinicalTrials.gov, number NCT01444846. Between Jan 11, 2013, and March 24, 2014, 83 participants were enrolled and randomly assigned to receive ebselen 200 mg (n=22), 400 mg (n=20), or 600 mg (n=21), or placebo (n=20). Two participants in the 200 mg ebselen group were discontinued from the study before the calibrated sound challenge because they no longer met the inclusion criteria; these

Harms associated with taking nalmefene for substance use and impulse control disorders: A systematic review and meta-analysis of randomised controlled trials.

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Karina Glies Vincents Johansen

Full Text Available Nalmefene is a newly approved drug for alcohol use disorder, but the risk of harms has not been evaluated from empirical trial evidence.To assess the harm of nalmefene administered to individuals diagnosed with substance use or impulse control disorders by performing a systematic review and meta-analysis of randomised controlled trials.A search was performed in Cochrane Central Register of Controlled Trials (CENTRAL, 2014, MEDLINE via PubMed (1950, EMBASE via Ovid (1974, and Clinicaltrials.gov through December 2014.This study included only randomised controlled trials with placebo or active controls that administered nalmefene to adult individuals for treating impulse control and/or substance use disorders. Both published and unpublished randomised controlled trials were eligible for inclusion.Internal validity was assessed using the Cochrane risk-of-bias tool. Published information from the trials was supplemented by contact between reviewers and industry sponsor. Data were combined using two meta-approaches in fixed effects models; Peto Odds Ratios and risk differences were reported with 95% confidence intervals (95%CIs.Number of patients with serious adverse events, including specific psychiatric serious adverse events and withdrawals due to adverse events.Of 20 potentially relevant studies, 15 randomised controlled trials met the inclusion criteria, and 8 of these provided data enabling the meta-analysis. Overall, serious adverse events did not occur more often in the nalmefene group than in the placebo group (Peto Odds Ratio = 0.97 [95% CI 0.64-1.44]; P = 0.86. Risk of psychiatric serious adverse events was slightly elevated, albeit not at a statistically significant level (Peto Odds Ratio = 1.32 [95% CI 0.62, 2.83]; P = 0.47. Withdrawals due to adverse events were significantly more likely to occur with nalmefene compared to placebo (Peto Odds Ratio = 3.22 [95% CI 2.46-4.22]; P<0.001.The three-fold increased risk of withdrawal from

Static magnetic field therapy for symptomatic diabetic neuropathy: a randomized, double-blind, placebo-controlled trial.

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Weintraub, Michael I; Wolfe, Gil I; Barohn, Richard A; Cole, Steven P; Parry, Gareth J; Hayat, Ghazala; Cohen, Jeffrey A; Page, Jeffrey C; Bromberg, Mark B; Schwartz, Sherwyn L

2003-05-01

To determine if constant wearing of multipolar, static magnetic (450G) shoe insoles can reduce neuropathic pain and quality of life (QOL) scores in symptomatic diabetic peripheral neuropathy (DPN). Randomized, placebo-control, parallel study. Forty-eight centers in 27 states. Three hundred seventy-five subjects with DPN stage II or III were randomly assigned to wear constantly magnetized insoles for 4 months; the placebo group wore similar, unmagnetized device. Nerve conduction and/or quantified sensory testing were performed serially. Daily visual analog scale scores for numbness or tingling and burning and QOL issues were tabulated over 4 months. Secondary measures included nerve conduction changes, role of placebo, and safety issues. Analysis of variance (ANOVA), analysis of covariance (ANCOVA), and chi-square analysis were performed. There were statistically significant reductions during the third and fourth months in burning (mean change for magnet treatment, -12%; for sham, -3%; P<.05, ANCOVA), numbness and tingling (magnet, -10%; sham, +1%; P<.05, ANCOVA), and exercise-induced foot pain (magnet, -12%; sham, -4%; P<.05, ANCOVA). For a subset of patients with baseline severe pain, statistically significant reductions occurred from baseline through the fourth month in numbness and tingling (magnet, -32%; sham, -14%; P<.01, ANOVA) and foot pain (magnet, -41%; sham, -21%; P<.01, ANOVA). Static magnetic fields can penetrate up to 20mm and appear to target the ectopic firing nociceptors in the epidermis and dermis. Analgesic benefits were achieved over time.

The Efficacy and Safety of Chinese Herbal Medicine Jinlida as Add-On Medication in Type 2 Diabetes Patients Ineffectively Managed by Metformin Monotherapy: A Double-Blind, Randomized, Placebo-Controlled, Multicenter Trial.

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Lian, Fengmei; Tian, Jiaxing; Chen, Xinyan; Li, Zhibin; Piao, Chunli; Guo, Junjie; Ma, Licheng; Zhao, Lijuan; Xia, Chengdong; Wang, Chong-Zhi; Yuan, Chun-Su; Tong, Xiaolin

2015-01-01

Metformin plays an important role in diabetes treatment. Studies have shown that the combined use of oral hypoglycemic medications is more effective than metformin monotherapy. In this double-blind, randomized, placebo-controlled, multicenter trial, we evaluated whether Jinlida, a Chinese herbal medicine, enhances the glycemic control of metformin in type 2 diabetes patients whose HbA1c was ineffectively controlled with metformin alone. A total of 186 diabetes patients were enrolled in this double-Blind, randomized, placebo-controlled, multicenter trial. Subjects were randomly allocated to receive either Jinlida (9 g) or the placebo TID for 12 consecutive weeks. All subjects in both groups also continuously received their metformin without any dose change. During this 12-week period, the HbA1c, FPG, 2 h PG, body weight, BMI were assessed. HOMA insulin resistance (HOMA-IR) and β-cell function (HOMA-β) were also evaluated. At week 12, compared to the HbA1c level from week 0, the level of the Jinlida group was reduced by 0.92 ± 1.09% and that of the placebo group was reduced by 0.53 ± 0.94%. The 95% CI was 0.69-1.14 for the Jinlida group vs. 0.34-0.72 for the placebo group. There was a very significant HbA1c reduction between the two groups after 12 weeks (p Jinlida group and placebo group were reduced from week 0. There were a very significant FG and 2 h PG level reductions between the two groups after 12 weeks (both p Jinlida group also showed improved β-cell function with a HOMA-β increase (p Jinlida significantly enhanced the hypoglycemic action of metformin when the drug was used alone. This Chinese herbal medicine may have a clinical value as an add-on medication to metformin monotherapy. Chinese Clinical Trial Register ChiCTR-TRC-13003159.

Efficacy of Bacillus coagulans Unique IS2 in treatment of irritable bowel syndrome in children: a double blind, randomised placebo controlled study.

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Sudha, M Ratna; Jayanthi, N; Aasin, M; Dhanashri, R D; Anirudh, T

2018-04-26

The efficacy of the probiotic strain, Bacillus coagulans Unique IS2 in the treatment of Irritable Bowel Syndrome (IBS) was evaluated in children. A total of 141 children of either sex in the age group 4-12 years, diagnosed with IBS according to the Rome III criteria, participated in the double-blind randomised controlled trial. Children received either B. coagulans Unique IS2 chewable tablets or placebo once daily for eight weeks followed by a two week follow-up period. Reduction in pain intensity as well as other symptoms associated with Irritable Bowel Syndrome like abdominal discomfort, bloating, distension, sense of incomplete evacuation, straining at stool, urgency of bowel movement, passage of gas and mucus, and bowel habit satisfaction were assessed. B. coagulans Unique IS2 treated group showed a greater reduction in pain scores as evaluated by a weekly pain intensity scale. There was a significant reduction (Pcoagulans Unique IS2 treated group as compared to the placebo group. This study demonstrates the efficacy of B. coagulans Unique IS2 in reducing the symptoms of Irritable Bowel Syndrome in children in the age group of 4-12 years.

Study protocol; Thyroid hormone Replacement for Untreated older adults with Subclinical hypothyroidism - a randomised placebo controlled Trial (TRUST).

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Stott, David J; Gussekloo, Jacobijn; Kearney, Patricia M; Rodondi, Nicolas; Westendorp, Rudi G J; Mooijaart, Simon; Kean, Sharon; Quinn, Terence J; Sattar, Naveed; Hendry, Kirsty; Du Puy, Robert; Den Elzen, Wendy P J; Poortvliet, Rosalinde K E; Smit, Jan W A; Jukema, J Wouter; Dekkers, Olaf M; Blum, Manuel; Collet, Tinh-Hai; McCarthy, Vera; Hurley, Caroline; Byrne, Stephen; Browne, John; Watt, Torquil; Bauer, Douglas; Ford, Ian

2017-02-03

Subclinical hypothyroidism (SCH) is a common condition in elderly people, defined as elevated serum thyroid-stimulating hormone (TSH) with normal circulating free thyroxine (fT4). Evidence is lacking about the effect of thyroid hormone treatment. We describe the protocol of a large randomised controlled trial (RCT) of Levothyroxine treatment for SCH. Participants are community-dwelling subjects aged ≥65 years with SCH, diagnosed by elevated TSH levels (≥4.6 and ≤19.9 mU/L) on a minimum of two measures ≥ three months apart, with fT4 levels within laboratory reference range. The study is a randomised double-blind placebo-controlled parallel group trial, starting with levothyroxine 50 micrograms daily (25 micrograms in subjects hypothyroid symptoms and fatigue / vitality) on the thyroid-related quality of life questionnaire (ThyPRO) at one year. The study has 80% power (at p = 0.025, 2-tailed) to detect a change with levothyroxine treatment of 3.0% on the hypothyroid scale and 4.1% on the fatigue / vitality scale with a total target sample size of 750 patients. Secondary outcomes include general health-related quality of life (EuroQol), fatal and non-fatal cardiovascular events, handgrip strength, executive cognitive function (Letter Digit Coding Test), basic and instrumental activities of daily living, haemoglobin, blood pressure, weight, body mass index and waist circumference. Patients are monitored for specific adverse events of interest including incident atrial fibrillation, heart failure and bone fracture. This large multicentre RCT of levothyroxine treatment of subclinical hypothyroidism is powered to detect clinically relevant change in symptoms / quality of life and is likely to be highly influential in guiding treatment of this common condition. Clinicaltrials.gov NCT01660126 ; registered 8th June 2012.

The effectiveness of the Austrian disease management programme for type 2 diabetes: a cluster-randomised controlled trial

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Klima Gert

2010-11-01

Full Text Available Abstract Background Disease management programmes (DMPs are costly and impose additional work load on general practitioners (GPs. Data on their effectiveness are inconclusive. We therefore conducted a cluster-randomised controlled trial to evaluate the effectiveness of the Austrian DMP for diabetes mellitus type 2 on HbA1c and quality of care for adult patients in primary care. Methods All GPs of Salzburg-province were invited to participate. After cluster-randomisation by district, all patients with diabetes type 2 were recruited consecutively from 7-11/2007. The DMP, consisting mainly of physician and patient education, standardised documentation and agreement on therapeutic goals, was implemented in the intervention group while the control group received usual care. We aimed to show superiority of the intervention regarding metabolic control and process quality. The primary outcome measure was a change in HbA1c after one year. Secondary outcomes were days in the hospital, blood pressure, lipids, body mass index (BMI, enrolment in patient education and regular guideline-adherent examination. Blinding was not possible. Results 92 physicians recruited 1489 patients (649 intervention, 840 control. After 401 ± 47 days, 590 intervention-patients and 754 controls had complete data. In the intention to treat analysis (ITT of all 1489 patients, HbA1c decreased 0.41% in the intervention group and 0.28% in controls. The difference of -0.13% (95% CI -0.24; -0.02 was significant at p = 0.026. Significance was lost in mixed models adjusted for baseline value and cluster-effects (adjusted mean difference -0.03 (95% CI -0.15; 0.09, p = 0.607. Of the secondary outcome measures, BMI and cholesterol were significantly reduced in the intervention group compared to controls in ITT after adjustments (-0.53 kg/m²; 95% CI -1.03;-0.02; p = 0.014 and -0.10 mmol/l; 95% CI -0.21; -0.003; p = 0.043. Additionally, more patients received patient education (49.5% vs. 20

The effect of empagliflozin on oxidative nucleic acid modifications in patients with type 2 diabetes

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Larsen, Emil List; Cejvanovic, Vanja; Kjær, Laura Kofoed

2017-01-01

Introduction Cardiovascular disease is the leading cause of morbidity and mortality in patients with type 2 diabetes (T2D). Although glycaemic control reduces microvascular complications, the effect of intensive treatment strategies or individual drugs on macrovascular diseases is still debated....... RNA oxidation is associated with increased mortality in patients with T2D. Inspired by animal studies showing effect of a sodium-glucose cotransporter-2 (SGLT-2) inhibitor (empagliflozin) on oxidative stress and a recent trial evaluating empagliflozin that demonstrated improved cardiovascular outcomes...... in patients with T2D at high risk of cardiovascular events, we hypothesise that empagliflozin lowers oxidative stress. Methods and analysis In this randomised, double-blinded and placebo-controlled study, 34 adult males with T2D will be randomised (1:1) to empagliflozin or placebo once daily for 14 days...

Pharmacokinetics and pharmacodynamics of vildagliptin in patients with type 2 diabetes mellitus

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He, Yan-Ling; Serra, Denise; Wang, Yibin

2007-01-01

BACKGROUND: Vildagliptin is a dipeptidyl peptidase IV (DPP-4) inhibitor currently under development for the treatment of type 2 diabetes mellitus. OBJECTIVES: To assess the pharmacokinetic and pharmacodynamic characteristics and tolerability of vildagliptin at doses of 10 mg, 25 mg and 100 mg twice...... daily following oral administration in patients with type 2 diabetes. METHODS: Thirteen patients with type 2 diabetes were enrolled in this randomised, double-blind, double-dummy, placebo-controlled, four-period, crossover study. Patients received vildagliptin 10 mg, 25 mg and 100 mg as well as placebo...... twice daily for 28 days. RESULTS: Vildagliptin was absorbed rapidly (median time to reach maximum concentration 1 hour) and had a mean terminal elimination half-life ranging from 1.32 to 2.43 hours. The peak concentration and total exposure increased in an approximately dose-proportional manner...

Negative pressure wound therapy after partial diabetic foot amputation: a multicentre, randomised controlled trial.

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Armstrong, David G; Lavery, Lawrence A

2005-11-12

Diabetic foot wounds, particularly those secondary to amputation, are very complex and difficult to treat. We investigated whether negative pressure wound therapy (NPWT) improves the proportion and rate of wound healing after partial foot amputation in patients with diabetes. We enrolled 162 patients into a 16-week, 18-centre, randomised clinical trial in the USA. Inclusion criteria consisted of partial foot amputation wounds up to the transmetatarsal level and evidence of adequate perfusion. Patients who were randomly assigned to NPWT (n=77) received treatment with dressing changes every 48 h. Control patients (n=85) received standard moist wound care according to consensus guidelines. NPWT was delivered through the Vacuum Assisted Closure (VAC) Therapy System. Wounds were treated until healing or completion of the 112-day period of active treatment. Analysis was by intention to treat. This study has been registered with , number NCT00224796. More patients healed in the NPWT group than in the control group (43 [56%] vs 33 [39%], p=0.040). The rate of wound healing, based on the time to complete closure, was faster in the NPWT group than in controls (p=0.005). The rate of granulation tissue formation, based on the time to 76-100% formation in the wound bed, was faster in the NPWT group than in controls (p=0.002). The frequency and severity of adverse events (of which the most common was wound infection) were similar in both treatment groups. NPWT delivered by the VAC Therapy System seems to be a safe and effective treatment for complex diabetic foot wounds, and could lead to a higher proportion of healed wounds, faster healing rates, and potentially fewer re-amputations than standard care.

Veterinary homeopathy: systematic review of medical conditions studied by randomised trials controlled by other than placebo.

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Mathie, Robert T; Clausen, Jürgen

2015-09-15

No systematic review has previously been carried out on randomised controlled trials (RCTs) of veterinary homeopathy in which the control group was an intervention other than placebo (OTP). For eligible peer-reviewed RCTs, the objectives of this study were to assess the risk of bias (RoB) and to quantify the effect size of homeopathic intervention compared with an active comparator or with no treatment. Our systematic review approach complied fully with the PRISMA 2009 Checklist. Cochrane methods were applied to assess RoB and to derive effect size using standard meta-analysis methods. Based on a thorough and systematic literature search, the following key attributes of the published research were distinguished: individualised homeopathy (n = 1 RCT)/non-individualised homeopathy (n = 19); treatment (n = 14)/prophylaxis (n = 6); active controls (n = 18)/untreated controls (n = 2). The trials were highly diverse, representing 12 different medical conditions in 6 different species. No trial had sufficiently low RoB to be judged as reliable evidence: 16 of the 20 RCTs had high RoB; the remaining four had uncertain RoB in several domains of assessment. For three trials with uncertain RoB and without overt vested interest, it was inconclusive whether homeopathy combined with conventional intervention was more or was less effective than conventional intervention alone for modulation of immune response in calves, or in the prophylaxis of cattle tick or of diarrhoea in piglets. Due to the poor reliability of their data, OTP-controlled trials do not currently provide useful insight into the effectiveness of homeopathy in animals.

Promoting physical activity in sedentary elderly Malays with type 2 diabetes: a protocol for randomised controlled trial

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Sazlina, Shariff-Ghazali; Browning, Colette Joy; Yasin, Shajahan

2012-01-01

Introduction Like many countries Malaysia is facing an increase in the number of people with type 2 diabetes mellitus diabetes (T2DM) and modifiable lifestyle factors such as sedentary behaviour are important drivers of this increase. The level of physical activity is low among elderly Malay people. In Malaysia, strategies to promote physical activity in elderly Malay people with T2DM are not well documented in the research literature. This paper discusses an intervention to increase physical activity in elderly Malay people with T2DM. The aim of our study was to evaluate the effectiveness of personalised feedback alone and in combination with peer support in promoting and maintaining physical activity in comparison with usual care. Methods and analysis A three-arm randomised controlled trial will be conducted among sedentary Malay adults aged 60 years and above with T2DM attending an urban primary healthcare clinic in Malaysia. The participants will be randomised into three groups for a 12-week intervention with a follow-up at 24 and 36 weeks to assess adherence. The primary outcome of this study is pedometer-determined physical activity. Glycaemic and blood pressure control, body composition, cardiorespiratory fitness, balance, lipid profile, health-related quality of life, psychological well-being, social support and self-efficacy for exercise are the secondary measures. Linear mixed models will be used to determine the effect of the intervention over time and between groups. Ethical and dissemination The Monash University Human Research Ethics Committee and the Malaysian Ministry of Health's Medical Research Ethics Committee approved this protocol. The findings of this study will be presented at international conferences and published in peer-reviewed journals. Trial registration This study protocol has been registered with the Malaysian National Medical Research Registry and with the Current Controlled Trial Ltd (http://www.controlled

Promoting physical activity in sedentary elderly Malays with type 2 diabetes: a protocol for randomised controlled trial.

Science.gov (United States)

Sazlina, Shariff-Ghazali; Browning, Colette Joy; Yasin, Shajahan

2012-01-01

Like many countries Malaysia is facing an increase in the number of people with type 2 diabetes mellitus diabetes (T2DM) and modifiable lifestyle factors such as sedentary behaviour are important drivers of this increase. The level of physical activity is low among elderly Malay people. In Malaysia, strategies to promote physical activity in elderly Malay people with T2DM are not well documented in the research literature. This paper discusses an intervention to increase physical activity in elderly Malay people with T2DM. The aim of our study was to evaluate the effectiveness of personalised feedback alone and in combination with peer support in promoting and maintaining physical activity in comparison with usual care. A three-arm randomised controlled trial will be conducted among sedentary Malay adults aged 60 years and above with T2DM attending an urban primary healthcare clinic in Malaysia. The participants will be randomised into three groups for a 12-week intervention with a follow-up at 24 and 36 weeks to assess adherence. The primary outcome of this study is pedometer-determined physical activity. Glycaemic and blood pressure control, body composition, cardiorespiratory fitness, balance, lipid profile, health-related quality of life, psychological well-being, social support and self-efficacy for exercise are the secondary measures. Linear mixed models will be used to determine the effect of the intervention over time and between groups. ETHICAL AND DISSEMINATION: The Monash University Human Research Ethics Committee and the Malaysian Ministry of Health's Medical Research Ethics Committee approved this protocol. The findings of this study will be presented at international conferences and published in peer-reviewed journals. This study protocol has been registered with the Malaysian National Medical Research Registry and with the Current Controlled Trial Ltd (http://www.controlled-trials.com/ISRCTN71447000/).

Mediating the effect of self-care management intervention in type 2 diabetes: A meta-analysis of 47 randomised controlled trials

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Minet, Lisbeth; Møller, Sine; Vach, Werner

2010-01-01

OBJECTIVE: To perform a meta-analysis assessing the effects of self-care management interventions in improving glycaemic control in type 2 diabetes by analysing the impact of different study characteristics on the effect size. METHODS: A literature search in eight scientific databases up...... to November 2007 included original studies of randomised controlled trials involving adult patients diagnosed with type 2 diabetes and evaluating a self-care management intervention. RESULTS: The 47 included studies yielded 7677 participants. The analysis showed a 0.36% (95% CI 0.21-0.51) improvement...... in glycaemic control in people who received self-care management treatment. In the univariate meta-regression sample size (effect size 0.42%, p=0.007) and follow-up period (effect size 0.49%, p=0.017) were identified to have significant effect on the effect size in favour of small studies and short follow...

Impact of probiotic Saccharomyces boulardii on the gut microbiome composition in HIV-treated patients: A double-blind, randomised, placebo-controlled trial.

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Villar-García, Judit; Güerri-Fernández, Robert; Moya, Andrés; González, Alicia; Hernández, Juan J; Lerma, Elisabet; Guelar, Ana; Sorli, Luisa; Horcajada, Juan P; Artacho, Alejandro; D Auria, Giuseppe; Knobel, Hernando

2017-01-01

Dysbalance in gut microbiota has been linked to increased microbial translocation, leading to chronic inflammation in HIV-patients, even under effective HAART. Moreover, microbial translocation is associated with insufficient reconstitution of CD4+T cells, and contributes to the pathogenesis of immunologic non-response. In a double-blind, randomised, placebo-controlled trial, we recently showed that, compared to placebo, 12 weeks treatment with probiotic Saccharomyces boulardii significantly reduced plasma levels of bacterial translocation (Lipopolysaccharide-binding protein or LBP) and systemic inflammation (IL-6) in 44 HIV virologically suppressed patients, half of whom (n = 22) had immunologic non-response to antiretroviral therapy (Saccharomyces boulardii is due to modified gut microbiome composition, with a decrease of some species associated with higher systemic levels of microbial translocation and inflammation. In this study, we used 16S rDNA gene amplification and parallel sequencing to analyze the probiotic impact on the composition of the gut microbiome (faecal samples) in these 44 patients randomized to receive oral supplementation with probiotic or placebo for 12 weeks. Compared to the placebo group, in individuals treated with probiotic we observed lower concentrations of some gut species, such as those of the Clostridiaceae family, which were correlated with systemic levels of bacterial translocation and inflammation markers. In a sub-study of these patients, we observed significantly higher parameters of microbial translocation (LBP, soluble CD14) and systemic inflammation in immunologic non-responders than in immunologic responders, which was correlated with a relative abundance of specific gut bacterial groups (Lachnospiraceae genus and Proteobacteria). Thus, in this work, we propose a new therapeutic strategy using the probiotic yeast S. boulardii to modify gut microbiome composition. Identifying pro-inflammatory species in the gut microbiome

Randomised controlled trial of Lactobacillus rhamnosus (LGG) versus placebo in children presenting to the emergency department with acute gastroenteritis: the PECARN probiotic study protocol

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Schnadower, David; Tarr, Phillip I; Charles, Casper T; Gorelick, Marc H; Dean, Michael J; O’Connell, Karen J; Mahajan, Prashant; Chun, Thomas H; Bhatt, Seema R; Roskind, Cindy G; Powell, Elizabeth C; Rogers, Alexander J; Vance, Cheryl; Sapien, Robert E; Gao, Feng; Freedman, Stephen B

2017-01-01

Introduction Acute gastroenteritis (AGE) is a common and burdensome condition that affects millions of children worldwide each year. Currently available strategies are limited to symptomatic management, treatment and prevention of dehydration and infection control; no disease-modifying interventions exist. Probiotics, defined as live microorganisms beneficial to the host, have shown promise in improving AGE outcomes, but existing studies have sufficient limitations such that the use of probiotics cannot currently be recommended with confidence. Here we present the methods of a large, rigorous, randomised, double-blind placebo-controlled study to assess the effectiveness and side effect profile of Lactobacillus rhamnosus GG (LGG) (ATCC 53103) in children with AGE. Methods and analysis The study is being conducted in 10 US paediatric emergency departments (EDs) within the federally funded Pediatric Emergency Care Applied Research Network, in accordance with current SPIRIT and CONSORT statement recommendations. We will randomise 970 children presenting to participating EDs with AGE to either 5 days of treatment with LGG (1010colony-forming unit twice a day) or placebo between July 2014 to December 2017. The main outcome is the occurrence of moderate-to-severe disease over time, as defined by the Modified Vesikari Scale. We also record adverse events and side effects related to the intervention. We will conduct intention-to-treat analyses and use an enrichment design to restore the statistical power in case the presence of a subpopulation with a substantially low treatment effect is identified. Ethics and dissemination Institutional review board approval has been obtained at all sites, and data and material use agreements have been established between the participating sites. The results of the trial will be published in peer-reviewed journals. A deidentified public data set will be made available after the completion of all study procedures. Trial registration number

Effects of exercise training using resistance bands on glycaemic control and strength in type 2 diabetes mellitus: a meta-analysis of randomised controlled trials.

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McGinley, Samantha K; Armstrong, Marni J; Boulé, Normand G; Sigal, Ronald J

2015-04-01

Resistance exercise using free weights or weight machines improves glycaemic control and strength in people with type 2 diabetes. Resistance band training is potentially less expensive and more accessible, but the effects of resistance band training on glycaemic control and strength in this population are not well understood. This paper aims to systematically review and meta-analyse the effect of resistance band training on haemoglobin A1c (HbA1c) and strength in adults with type 2 diabetes. Database searches were performed in August 2013 (MEDLINE, SPORTDiscus, EMBASE, and CINAHL). Reference lists of eligible articles were hand-searched for additional studies. Randomised trials evaluating the effects of resistance band training in adults with type 2 diabetes on HbA1c or objectively measured strength were selected. Baseline and post-intervention HbA1c and strength were extracted for the intervention and control groups. Details of the exercise interventions and methodological quality were collected. Seven trials met inclusion criteria. Post-intervention-weighted mean HbA1c was nonsignificantly lower in exercise groups compared to control groups [weighted mean difference (WMD) = -0.18 percentage points (-1.91 mmol/mol); P = 0.27]. Post-intervention strength was significantly higher in the exercise groups compared to the control groups in the lower extremities (WMD = 21.90 kg; P diabetes.

GLP-1-Based Therapies Have No Microvascular Effects in Type 2 Diabetes Mellitus: An Acute and 12-Week Randomized, Double-Blind, Placebo-Controlled Trial.

Science.gov (United States)

Smits, Mark M; Tonneijck, Lennart; Muskiet, Marcel H A; Hoekstra, Trynke; Kramer, Mark H H; Diamant, Michaela; Serné, Erik H; van Raalte, Daniël H

2016-10-01

To assess the effects of glucagon-like peptide (GLP)-1-based therapies (ie, GLP-1 receptor agonists and dipeptidyl peptidase-4 inhibitors) on microvascular function in patients with type 2 diabetes mellitus. We studied 57 patients with type 2 diabetes mellitus (mean±SD age: 62.8±6.9 years; body mass index: 31.8±4.1 kg/m(2); HbA1c [glycated hemoglobin] 7.3±0.6%) in an acute and 12-week randomized, placebo-controlled, double-blind trial conducted at the Diabetes Center of the VU University Medical Center. In the acute study, the GLP-1 receptor agonist exenatide (therapeutic concentrations) or placebo (saline 0.9%) was administered intravenously. During the 12-week study, patients received the GLP-1 receptor agonist liraglutide (1.8 mg daily), the dipeptidyl peptidase-4 inhibitor sitagliptin (100 mg daily), or matching placebos. Capillary perfusion was assessed by nailfold skin capillary videomicroscopy and vasomotion by laser Doppler fluxmetry, in the fasting state and after a high-fat mixed meal. In neither study, treatment affected fasting or postprandial capillary perfusion compared with placebo (P>0.05). In the fasting state, acute exenatide infusion increased neurogenic vasomotion domain power, while reducing myogenic domain power (both P12-week study, no effects on vasomotion were observed. Despite modest changes in vasomotion, suggestive of sympathetic nervous system activation and improved endothelial function, acute exenatide infusion does not affect skin capillary perfusion in type 2 diabetes mellitus. Twelve-week treatment with liraglutide or sitagliptin has no effect on capillary perfusion or vasomotion in these patients. Our data suggest that the effects of GLP-1-based therapies on glucose are not mediated through microvascular responses. © 2016 American Heart Association, Inc.

Cannabinoids in attention-deficit/hyperactivity disorder: A randomised-controlled trial.

Science.gov (United States)

Cooper, Ruth E; Williams, Emma; Seegobin, Seth; Tye, Charlotte; Kuntsi, Jonna; Asherson, Philip

2017-08-01

Adults with ADHD describe self-medicating with cannabis, with some reporting a preference for cannabis over ADHD medications. A small number of psychiatrists in the US prescribe cannabis medication for ADHD, despite there being no evidence from randomised controlled studies. The EMA-C trial (Experimental Medicine in ADHD-Cannabinoids) was a pilot randomised placebo-controlled experimental study of a cannabinoid medication, Sativex Oromucosal Spray, in 30 adults with ADHD. The primary outcome was cognitive performance and activity level using the QbTest. Secondary outcomes included ADHD and emotional lability (EL) symptoms. From 17.07.14 to 18.06.15, 30 participants were randomly assigned to the active (n=15) or placebo (n=15) group. For the primary outcome, no significant difference was found in the ITT analysis although the overall pattern of scores was such that the active group usually had scores that were better than the placebo group (Est=-0.17, 95%CI-0.40 to 0.07, p=0.16, n=15/11 active/placebo). For secondary outcomes Sativex was associated with a nominally significant improvement in hyperactivity/impulsivity (p=0.03) and a cognitive measure of inhibition (p=0.05), and a trend towards improvement for inattention (p=0.10) and EL (p=0.11). Per-protocol effects were higher. Results did not meet significance following adjustment for multiple testing. One serious (muscular seizures/spasms) and three mild adverse events occurred in the active group and one serious (cardiovascular problems) adverse event in the placebo group. Adults with ADHD may represent a subgroup of individuals who experience a reduction of symptoms and no cognitive impairments following cannabinoid use. While not definitive, this study provides preliminary evidence supporting the self-medication theory of cannabis use in ADHD and the need for further studies of the endocannabinoid system in ADHD. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.

Probiotics [LGG-BB12 or RC14-GR1] versus placebo as prophylaxis for urinary tract infection in persons with spinal cord injury [ProSCIUTTU]: a study protocol for a randomised controlled trial.

Science.gov (United States)

Lee, Bonsan Bonne; Toh, Swee-Ling; Ryan, Suzanne; Simpson, Judy M; Clezy, Kate; Bossa, Laetitia; Rice, Scott A; Marial, Obaydullah; Weber, Gerard; Kaur, Jasbeer; Boswell-Ruys, Claire; Goodall, Stephen; Middleton, James; Tudehope, Mark; Kotsiou, George

2016-04-16

Urinary tract infections [UTIs] are very common in people with Spinal Cord Injury [SCI]. UTIs are increasingly difficult and expensive to treat as the organisms that cause them become more antibiotic resistant. Among the SCI population, there is a high rate of multi-resistant organism [MRO] colonisation. Non-antibiotic prevention strategies are needed to prevent UTI without increasing resistance. Probiotics have been reported to be beneficial in preventing UTIs in post-menopausal women in several in vivo and in vitro studies. The main aim of this study is to determine whether probiotic therapy with combinations of Lactobacillus reuteri RC-14 + Lactobacillus rhamnosus GR-1 [RC14-GR1] and/or Lactobacillus rhamnosus GG + Bifidobacterium BB-12 [LGG-BB12] are effective in preventing UTI in people with SCI compared to placebo. This is a multi-site randomised double-blind double-dummy placebo-controlled factorial design study conducted in New South Wales, Australia. All participants have a neurogenic bladder as a result of spinal injury. Recruitment started in April 2011. Participants are randomised to one of four arms, designed for factorial analysis of LGG-BB12 and/or RC14-GR1 v Placebo. This involves 24 weeks of daily oral treatment with RC14-GR1 + LGG-BB12, RC14-GR1 + placebo, LGG-BB12 + placebo or two placebo capsules. Randomisation is stratified by bladder management type and inpatient status. Participants are assessed at baseline, three months and six months for Short Form Health Survey [SF-36], microbiological swabs of rectum, nose and groin; urine culture and urinary catheters for subjects with indwelling catheters. A bowel questionnaire is administered at baseline and three months to assess effect of probiotics on bowel function. The primary outcome is time from randomisation to occurrence of symptomatic UTI. The secondary outcomes are change of MRO status and bowel function, quality of life and cost-effectiveness of probiotics in persons

Pain relief of sore throat with a new anti-inflammatory throat lozenge, ibuprofen 25 mg: A randomised, double-blind, placebo-controlled, international phase III study.

Science.gov (United States)

Bouroubi, Athmane; Donazzolo, Yves; Donath, Franck; Eccles, Ron; Russo, Marc; Harambillet, Nadine; Gautier, Stéphanie; Montagne, Agnès

2017-09-01

The aim of this study was to compare the efficacy and safety of a new oromucosal ibuprofen form, ibuprofen 25 mg lozenge, in single and repeat dosing for up to 4 days, to the matched placebo, in the treatment of acute sore throat pain in adults. In this randomised, double-blind, placebo-controlled trial, adult patients with non-streptococcal sore throat and signs of moderate-to-severe associated pain (≥5 on the objective Tonsillo-Pharyngitis Assessment 21-point scale and ≥60 mm on the subjective 0-100 mm visual analogue Sore Throat Pain Intensity Scale [STPIS]) were assigned ibuprofen 25 mg (n=194) or matching placebo (n=191) lozenge treatment. Efficacy was assessed (at the investigating centre up to 2 hours after first dosing, then on an ambulatory basis) by parameters derived from patient's scores on scales of pain relief, pain intensity, and global efficacy assessment. The primary efficacy end-point was the time-weighted TOTal PAin Relief (TOTPAR) over 2 hours after first dosing using the Sore Throat Relief Scale (STRS). Safety and local tolerability were assessed. Ibuprofen 25 mg was superior to placebo on numerous pain relief parameters; TOTPAR was significantly higher with ibuprofen 25 mg over 2 hours after first dosing (Ppain (n=128), after an average 4 days (Prelief of sore throat pain and is as well tolerated as placebo. ClinicalTrials.gov, NCT01785862. © 2017 John Wiley & Sons Ltd.

The gait and balance of patients with diabetes can be improved: a randomised controlled trial.

Science.gov (United States)

Allet, L; Armand, S; de Bie, R A; Golay, A; Monnin, D; Aminian, K; Staal, J B; de Bruin, E D

2010-03-01

Gait characteristics and balance are altered in diabetic patients. Little is known about possible treatment strategies. This study evaluates the effect of a specific training programme on gait and balance of diabetic patients. This was a randomised controlled trial (n=71) with an intervention (n=35) and control group (n=36). The intervention consisted of physiotherapeutic group training including gait and balance exercises with function-orientated strengthening (twice weekly over 12 weeks). Controls received no treatment. Individuals were allocated to the groups in a central office. Gait, balance, fear of falls, muscle strength and joint mobility were measured at baseline, after intervention and at 6-month follow-up. The trial is closed to recruitment and follow-up. After training, the intervention group increased habitual walking speed by 0.149 m/s (pbalance (time to walk over a beam, balance index recorded on Biodex balance system), their performance-oriented mobility, their degree of concern about falling, their hip and ankle plantar flexor strength, and their hip flexion mobility compared with the control group. After 6 months, all these variables remained significant except for the Biodex sway index and ankle plantar flexor strength. Two patients developed pain in their Achilles tendon: the progression for two related exercises was slowed down. Specific training can improve gait speed, balance, muscle strength and joint mobility in diabetic patients. Further studies are needed to explore the influence of these improvements on the number of reported falls, patients' physical activity levels and quality of life. ClinicalTrials.gov NCT00637546 This work was supported by the Swiss National Foundation (SNF): PBSKP-123446/1/

A randomised controlled trial of oxytocin 5IU and placebo infusion versus oxytocin 5IU and 30IU infusion for the control of blood loss at elective caesarean section--pilot study. ISRCTN 40302163.

LENUS (Irish Health Repository)

Murphy, Deirdre J

2012-02-01

OBJECTIVE: To compare the blood loss at elective lower segment caesarean section with administration of oxytocin 5IU bolus versus oxytocin 5IU bolus and oxytocin 30IU infusion and to establish whether a large multi-centre trial is feasible. STUDY DESIGN: Women booked for an elective caesarean section were recruited to a pilot randomised controlled trial and randomised to either oxytocin 5IU bolus and placebo infusion or oxytocin 5IU bolus and oxytocin 30IU infusion. We wished to establish whether the study design was feasible and acceptable and to establish sample size estimates for a definitive multi-centre trial. The outcome measures were total estimated blood loss at caesarean section and in the immediate postpartum period and the need for an additional uterotonic agent. RESULTS: A total of 115 women were randomised and 110 were suitable for analysis (5 protocol violations). Despite strict exclusion criteria 84% of the target population were considered eligible for study participation and of those approached only 15% declined to participate and 11% delivered prior to the planned date. The total mean estimated blood loss was lower in the oxytocin infusion arm compared to placebo (567 ml versus 624 ml) and fewer women had a major haemorrhage (>1000 ml, 14% versus 17%) or required an additional uterotonic agent (5% versus 11%). A sample size of 1500 in each arm would be required to demonstrate a 3% absolute reduction in major haemorrhage (from baseline 10%) with >80% power. CONCLUSION: An additional oxytocin infusion at elective caesarean section may reduce blood loss and warrants evaluation in a large multi-centre trial.

A randomised double-blind placebo-controlled pilot trial of a combined extract of sage, rosemary and melissa, traditional herbal medicines, on the enhancement of memory in normal healthy subjects, including influence of age.

Science.gov (United States)

Perry, N S L; Menzies, R; Hodgson, F; Wedgewood, P; Howes, M-J R; Brooker, H J; Wesnes, K A; Perry, E K

2018-01-15

To evaluate for the first time the effects of a combination of sage, rosemary and melissa (Salvia officinalis L., Rosmarinus officinalis L. and Melissa officinalis L.; SRM), traditional European medicines, on verbal recall in normal healthy subjects. To devise a suitable study design for assessing the clinical efficacy of traditional herbal medicines for memory and brain function. Forty-four normal healthy subjects (mean age 61 ± 9.26y SD; m/f 6/38) participated in this study. A double-blind, randomised, placebo-controlled pilot study was performed with subjects randomised into an active and placebo group. The study consisted of a single 2-week term ethanol extract of SRM that was chemically-characterised using high resolution LC-UV-MS/MS analysis. Immediate and delayed word recall were used to assess memory after taking SRM or placebo (ethanol extract of Myrrhis odorata (L.) Scop.). In addition analysis was performed with subjects divided into younger and older subgroups (≤ 62 years mean age n = 26: SRM n = 10, Placebo n = 16; ≥ 63 years n = 19: SRM n = 13, Placebo n = 6). Overall there were no significant differences between treatment and placebo change from baseline for immediate or delayed word recall. However subgroup analysis showed significant improvements to delayed word recall in the under 63 year age group (p memory in healthy subjects under 63 years of age. Short- and long- term supplementation with SRM extract merits more robust investigation as an adjunctive treatment for patients with Alzheimer's disease and in the general ageing population. The study design proved a simple cost effective trial protocol to test the efficacy of herbal medicines on verbal episodic memory, with future studies including broader cognitive assessment. Copyright © 2017 Elsevier GmbH. All rights reserved.

Randomised clinical trial: alginate (Gaviscon Advance) vs. placebo as add-on therapy in reflux patients with inadequate response to a once daily proton pump inhibitor.

Science.gov (United States)

Reimer, C; Lødrup, A B; Smith, G; Wilkinson, J; Bytzer, P

2016-04-01

Many reflux patients remain symptomatic on a standard dose of proton pump inhibitor (PPI). Alginates decrease the number of reflux events by forming a raft on top of the stomach content and thus offer a supplemental mechanism of action to acid suppression. To assess the efficacy of an alginate (Gaviscon Advance, Reckitt Benckiser, Slough, UK) on reflux symptoms in patients with persistent symptoms despite once daily PPI. This was a multicentre, randomised, placebo-controlled, 7-day double-blind trial preceded by a 7-day run-in period. Reflux symptoms were assessed using the Heartburn Reflux Dyspepsia Questionnaire (HRDQ). Based on symptom score during run-in, eligible patients were randomised to Gaviscon Advance 10 mL four times a day or placebo in addition to a once daily PPI. The primary endpoint was change in HRDQ score post-treatment compared to baseline. One hundred and thirty-six patients were randomised. Change in HRDQ reflux score was significantly greater for Gaviscon Advance (mean: -5.0, s.d.: 4.7) than for placebo (mean: -3.5, s.d.: 5.5) with an LS mean difference of 1.6 [95% CI -3.1 to -0.1], P = 0.03. A decrease in the mean (s.d.) number of nights with symptoms was observed from 3.6 (2.8) to 3.0 (3.0) in the placebo group and from 3.9 (2.8) to 2.2 (2.7) for the Gaviscon Advance group. This reduction was significantly greater in the Gaviscon Advance group than in the placebo group [LS mean difference = -0.9, 95% CI (-1.6 to -0.2), P < 0.01]. In patients with residual reflux symptoms despite PPI treatment, adding an alginate offers additional decrease in the burden of reflux symptoms (EudraCT/IND Number: 2011-005486-21). © 2016 John Wiley & Sons Ltd.

Effects of 12 weeks' treatment with a proton pump inhibitor on insulin secretion, glucose metabolism and markers of cardiovascular risk in patients with type 2 diabetes

DEFF Research Database (Denmark)

Hove, K D; Brøns, Charlotte; Færch, Kai Erik Vinther

2013-01-01

Recent studies suggest that proton pump inhibitor treatment may increase insulin secretion and improve glucose metabolism in type 2 diabetes. In a randomised double-blind prospective placebo-controlled 2 × 2 factorial study, we examined the effect of esomeprazole on insulin secretion, HbA(1c...

Low-dose adrenaline, promethazine, and hydrocortisone in the prevention of acute adverse reactions to antivenom following snakebite: a randomised, double-blind, placebo-controlled trial.

Directory of Open Access Journals (Sweden)

H Asita de Silva

2011-05-01

Full Text Available 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.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.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.

The Hawthorne Effect: a randomised, controlled trial

Directory of Open Access Journals (Sweden)

van Haselen Robbert

2007-07-01

Full Text Available Abstract Background The 'Hawthorne Effect' may be an important factor affecting the generalisability of clinical research to routine practice, but has been little studied. Hawthorne Effects have been reported in previous clinical trials in dementia but to our knowledge, no attempt has been made to quantify them. Our aim was to compare minimal follow-up to intensive follow-up in participants in a placebo controlled trial of Ginkgo biloba for treating mild-moderate dementia. Methods Participants in a dementia trial were randomised to intensive follow-up (with comprehensive assessment visits at baseline and two, four and six months post randomisation or minimal follow-up (with an abbreviated assessment at baseline and a full assessment at six months. Our primary outcomes were cognitive functioning (ADAS-Cog and participant and carer-rated quality of life (QOL-AD. Results We recruited 176 participants, mainly through general practices. The main analysis was based on Intention to treat (ITT, with available data. In the ANCOVA model with baseline score as a co-variate, follow-up group had a significant effect on outcome at six months on the ADAS-Cog score (n = 140; mean difference = -2.018; 95%CI -3.914, -0.121; p = 0.037 favouring the intensive follow-up group, and on participant-rated quality of life score (n = 142; mean difference = -1.382; 95%CI -2.642, -0.122; p = 0.032 favouring minimal follow-up group. There was no significant difference on carer quality of life. Conclusion We found that more intensive follow-up of individuals in a placebo-controlled clinical trial of Ginkgo biloba for treating mild-moderate dementia resulted in a better outcome than minimal follow-up, as measured by their cognitive functioning. Trial registration Current controlled trials: ISRCTN45577048

Effect angiotensin II receptor blockers on glomerular filtration rate in patients with incipient diabetic nephropathy

International Nuclear Information System (INIS)

Dragovic, T.; Ajdinovic, B.; Endocrinology Clinic

2004-01-01

Glomerular filtration rate (GFR) was calculated in patients with incipient diabetic nephropathy with an aim to evaluate the effect of angiotensin receptor blockator valsartan on GFR stabilisation to physiological levels. Investigation was done as a prospective, randomised, placebo controlled study, on 20 patients with diabetes mellitus, type I (age 25 years, disease lasting 14 years). In all patients was detected incipient diabetic nephropathy with daily urinary albumin excretion in range from 30 mg to 300 mg. Patients were randomised in two groups: 10 patients were treated with 80 mg /day valsartan, during 6 months, second group (10 patients) were on placebo at the same period. GFR, as a clearance of 51Cr-EDTA, was calculated at the start and at the end of the study. In the first patients group during investigation period, GFR was decreased from 150, 1 ml/min/1.73m 2 to physiological level of 127 ml/min/1,73m 2 (p 2 at the start, 139,9 ml/min/l.73m 2 at the end of the study).On the basis of these results it was concluded that 80 mg/day in 6 month valsartan therapy decreased GFR to physiological levels in patients with incipient diabetic nephropathy. (authors)

Breast size increment during pregnancy and breastfeeding in mothers with polycystic ovary syndrome: a follow-up study of a randomised controlled trial on metformin versus placebo.

Science.gov (United States)

Vanky, E; Nordskar, J J; Leithe, H; Hjorth-Hansen, A K; Martinussen, M; Carlsen, S M

2012-10-01

To study the significance of breast size increment in pregnancy, and the impact of metformin during pregnancy on breastfeeding in women with polycystic ovary syndrome (PCOS). A follow-up study of a randomised controlled trial (the PregMet study). Eleven secondary care centres. Women with PCOS during pregnancy and postpartum. Women with PCOS were randomised to treatment with metformin or placebo from the first trimester to delivery. Questionnaires were sent to 240 participants 1 year postpartum: 186 responded. Pre-pregnancy and late-pregnancy brassiere size and breastfeeding patterns were registered, and androgen levels were measured in the mothers. No difference in breast size increment and breastfeeding were found between the placebo and metformin groups. Breast size increment correlated positively with the duration of both exclusive and partial breastfeeding, whereas body mass index (BMI) correlated negatively with the duration of partial breastfeeding. Dehydroepiandrostenedione-sulphate (DHEAS), testosterone and free testosterone index (FTI) in pregnancy did not correlate with breast size increment or duration of breastfeeding. Women with no change in breast size were more obese, had higher blood pressure, serum triglycerides and fasting insulin levels, and had a shorter duration of breastfeeding compared with those with breast size increment. Metformin and androgens had no impact on breastfeeding. Women with PCOS who had no breast size increment in pregnancy seem to be more metabolically disturbed and less able to breastfeed. © 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2012 RCOG.

Chronic Effects of a Wild Green Oat Extract Supplementation on Cognitive Performance in Older Adults: A Randomised, Double-Blind, Placebo-Controlled, Crossover Trial

Directory of Open Access Journals (Sweden)

Narelle M. Berry

2012-05-01

Full Text Available Background and aim: Preliminary evaluation of a wild green oat extract (WGOE (Neuravena^® ELFA^®955, Frutarom, Switzerland revealed an acute cognitive benefit of supplementation. This study investigated whether regular daily WGOE supplementation would result in sustained cognitive improvements. Method: A 12-week randomised, double-blind, placebo-controlled cross-over trial of WGOE supplementation (1500 mg/day versus placebo was undertaken in 37 healthy adults aged 67 ± 0.8 years (mean ± SEM. Cognitive assessments included the Stroop colour-word test, letter cancellation, the rule-shift task, a computerised multi-tasking test battery and the trail-making task. All assessments were conducted in Week 12 and repeated in Week 24 whilst subjects were fasted and at least 18 h after taking the last dose of supplement. Result: Chronic WGOE supplementation did not affect any measures of cognition. Conclusion: It appears that the cognitive benefit of acute WGOE supplementation does not persist with chronic treatment in older adults with normal cognition. It remains to be seen whether sustained effects of WGOE supplementation may be more evident in those with mild cognitive impairment.

Community based yoga classes for type 2 diabetes: an exploratory randomised controlled trial

Directory of Open Access Journals (Sweden)

Drincevic Desanka

2009-02-01

Full Text Available Abstract Background Yoga is a popular therapy for diabetes but its efficacy is contested. The aim of this study was to explore the feasibility of researching community based yoga classes in Type 2 diabetes with a view to informing the design of a definitive, multi-centre trial Methods The study design was an exploratory randomised controlled trial with in-depth process evaluation. The setting was two multi-ethnic boroughs in London, UK; one with average and one with low mean socio-economic deprivation score. Classes were held at a sports centre or GP surgery. Participants were 59 people with Type 2 diabetes not taking insulin, recruited from general practice lists or opportunistically by general practice staff. The intervention group were offered 12 weeks of a twice-weekly 90-minute yoga class; the control group was a waiting list for the yoga classes. Both groups received advice and leaflets on healthy lifestyle and were encouraged to exercise. Primary outcome measure was HbA1c. Secondary outcome measures included attendance, weight, waist circumference, lipid levels, blood pressure, UKPDS cardiovascular risk score, diabetes-related quality of life (ADDQoL, and self-efficacy. Process measures were attendance at yoga sessions, self-reported frequency of practice between taught sessions, and qualitative data (interviews with patients and therapists, ethnographic observation of the yoga classes, and analysis of documents including minutes of meetings, correspondence, and exercise plans. Results Despite broad inclusion criteria, around two-thirds of the patients on GP diabetic registers proved ineligible, and 90% of the remainder declined to participate. Mean age of participants was 60 +/- 10 years. Attendance at yoga classes was around 50%. Nobody did the exercises regularly at home. Yoga teachers felt that most participants were unsuitable for 'standard' yoga exercises because of limited flexibility, lack of basic fitness, co-morbidity, and lack

Effects of biphasic, basal-bolus or basal insulin analogue treatments on carotid intima-media thickness in patients with type 2 diabetes mellitus

DEFF Research Database (Denmark)

Lundby-Christensen, Louise; Vaag, Allan; Tarnow, Lise

2016-01-01

OBJECTIVE: To assess the effect of 3 insulin analogue regimens on change in carotid intima-media thickness (IMT) in patients with type 2 diabetes. DESIGN AND SETTING: Investigator-initiated, randomised, placebo-controlled trial with a 2×3 factorial design, conducted at 8 hospitals in Denmark....... PARTICIPANTS AND INTERVENTIONS: Participants with type 2 diabetes (glycated haemoglobin (HbA1c)≥7.5% (≥58 mmol/mol), body mass index >25 kg/m(2)) were, in addition to metformin versus placebo, randomised to 18 months open-label biphasic insulin aspart 1-3 times daily (n=137) versus insulin aspart 3 times daily......: Carotid IMT change did not differ between 3 insulin regimens despite differences in HbA1c, weight gain and insulin doses. The trial only reached 46% of planned sample size and lack of power may therefore have affected our results. TRIAL REGISTRATION NUMBER: NCT00657943....

Renal outcomes with aliskiren in patients with type 2 diabetes

DEFF Research Database (Denmark)

Heerspink, Hiddo J Lambers; Persson, Frederik; Brenner, Barry M

2016-01-01

ALTITUDE trial, 8561 patients with type 2 diabetes and chronic kidney disease or cardiovascular disease were randomly assigned (1:1) to receive aliskiren 300 mg per day or placebo as an adjunct to ACE inhibitors or ARBs. Randomisation was stratified on the basis of baseline urinary albumin......Background: The primary results of the ALTITUDE trial showed no benefit of aliskiren on renal outcomes (doubling of serum creatinine and end-stage renal disease) when used as an adjunct to angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) in patients with type 2...... diabetes and chronic kidney disease or cardiovascular disease. We did a prespecified analysis of the ALTITUDE trial to analyse the effects of aliskiren on surrogate renal outcomes in all patients and on primary renal outcomes in subgroups of patients. Methods: In the double-blind, randomised, controlled...

Effect of fenofibrate on uric acid and gout in type 2 diabetes: a post-hoc analysis of the randomised, controlled FIELD study.

Science.gov (United States)

Waldman, Boris; Ansquer, Jean-Claude; Sullivan, David R; Jenkins, Alicia J; McGill, Neil; Buizen, Luke; Davis, Timothy M E; Best, James D; Li, Liping; Feher, Michael D; Foucher, Christelle; Kesaniemi, Y Antero; Flack, Jeffrey; d'Emden, Michael C; Scott, Russell S; Hedley, John; Gebski, Val; Keech, Anthony C

2018-04-01

Gout is a painful disorder and is common in type 2 diabetes. Fenofibrate lowers uric acid and reduces gout attacks in small, short-term studies. Whether fenofibrate produces sustained reductions in uric acid and gout attacks is unknown. In the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial, participants aged 50-75 years with type 2 diabetes were randomly assigned to receive either co-micronised fenofibrate 200 mg once per day or matching placebo for a median of 5 years follow-up. We did a post-hoc analysis of recorded on-study gout attacks and plasma uric acid concentrations according to treatment allocation. The outcomes of this analysis were change in uric acid concentrations and risk of on-study gout attacks. The FIELD study is registered with ISRCTN, number ISRCTN64783481. Between Feb 23, 1998, and Nov 3, 2000, 9795 patients were randomly assigned to fenofibrate (n=4895) or placebo (n=4900) in the FIELD study. Uric acid concentrations fell by 20·2% (95% CI 19·9-20·5) during the 6-week active fenofibrate run-in period immediately pre-randomisation (a reduction of 0·06 mmol/L or 1 mg/dL) and remained -20·1% (18·5-21·7, puric acid concentration higher than 0·36 mmol/L and 13·9% in those with baseline uric acid concentration higher than 0·42 mmol/L, compared with 3·4% and 5·7%, respectively, in the fenofibrate group. Risk reductions were similar among men and women and those with dyslipidaemia, on diuretics, and with elevated uric acid concentrations. For participants with elevated baseline uric acid concentrations despite taking allopurinol at study entry, there was no heterogeneity of the treatment effect of fenofibrate on gout risk. Taking account of all gout events, fenofibrate treatment halved the risk (HR 0·48, 95% CI 0·37-0·60; puric acid concentrations by 20%, and almost halved first on-study gout events over 5 years of treatment. Fenofibrate could be a useful adjunct for preventing gout in diabetes. None. Copyright �

Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib: an international, multicentre, prospective, randomised, placebo-controlled phase 3 trial (GRID)

Science.gov (United States)

Demetri, George D; Reichardt, Peter; Kang, Yoon-Koo; Blay, Jean-Yves; Rutkowski, Piotr; Gelderblom, Hans; Hohenberger, Peter; Leahy, Michael; von Mehren, Margaret; Joensuu, Heikki; Badalamenti, Giuseppe; Blackstein, Martin; Cesne, Axel Le; Schöffski, Patrick; Maki, Robert G; Bauer, Sebastian; Nguyen, Binh Bui; Xu, Jianming; Nishida, Toshirou; Chung, John; Kappeler, Christian; Kuss, Iris; Laurent, Dirk; Casali, Paolo

2013-01-01

Summary Background To date, only two agents, imatinib and sunitinib, have shown clinical benefit in patients with gastrointestinal stromal tumours (GISTs), but almost all metastatic GISTs eventually develop resistance to these agents, resulting in fatal disease progression. This phase 3 trial assessed efficacy and safety of regorafenib in patients with metastatic and/or unresectable GIST progressing after failure of at least imatinib and sunitinib. Methods Patients were randomised 2:1 to receive either regorafenib 160 mg orally daily or placebo, plus best supportive care in both arms, for the first 3 weeks of each 4-week cycle. The primary endpoint was progression-free survival (PFS). Upon disease progression, patients on placebo could cross over to regorafenib. Secondary endpoints included overall survival (OS), objective response rate, disease control rate (DCR: rate of durable stable disease lasting for ≥12 weeks plus complete or partial responses), and safety. This trial is registered at ClinicalTrials.gov (NCT01271712). Results From January to August 2011, 240 patients were screened at 57 centres in 17 countries, and 199 patients were randomised to receive regorafenib (n=133) or matching placebo (n=66). Median PFS per independent blinded central review was 4·8 months and 0·9 months, respectively (hazard ratio [HR] 0·27, 95% confidence interval [CI] 0·19–0·39; pregorafenib, resulting in no significant difference in OS between study arms (HR 0·77, 95% CI 0·42–1·41; p=0·199). A best response of partial response or stable disease was observed in 101/133 patients (75·9%) on regorafenib and 23/66 patients (34·8%) on placebo. DCR was 52·6% (70/133 patients) and 9·1% (6/66 patients), respectively. Drug-related adverse events were reported in 130 (98·5%) of 132 regorafenib patients and 45 (68·2%) of 66 placebo patients. The most common grade ≥3 regorafenib-related adverse events were hypertension (31/132, 23·5%), hand–foot skin reaction (26

Effectiveness of mobile phone messaging in prevention of type 2 diabetes by lifestyle modification in men in India: a prospective, parallel-group, randomised controlled trial.

Science.gov (United States)

Ramachandran, Ambady; Snehalatha, Chamukuttan; Ram, Jagannathan; Selvam, Sundaram; Simon, Mary; Nanditha, Arun; Shetty, Ananth Samith; Godsland, Ian F; Chaturvedi, Nish; Majeed, Azeem; Oliver, Nick; Toumazou, Christofer; Alberti, K George; Johnston, Desmond G

2013-11-01

Type 2 diabetes can often be prevented by lifestyle modification; however, successful lifestyle intervention programmes are labour intensive. Mobile phone messaging is an inexpensive alternative way to deliver educational and motivational advice about lifestyle modification. We aimed to assess whether mobile phone messaging that encouraged lifestyle change could reduce incident type 2 diabetes in Indian Asian men with impaired glucose tolerance. We did a prospective, parallel-group, randomised controlled trial between Aug 10, 2009, and Nov 30, 2012, at ten sites in southeast India. Working Indian men (aged 35-55 years) with impaired glucose tolerance were randomly assigned (1:1) with a computer-generated randomisation sequence to a mobile phone messaging intervention or standard care (control group). Participants in the intervention group received frequent mobile phone messages compared with controls who received standard lifestyle modification advice at baseline only. Field staff and participants were, by necessity, not masked to study group assignment, but allocation was concealed from laboratory personnel as well as principal and co-investigators. The primary outcome was incidence of type 2 diabetes, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00819455. We assessed 8741 participants for eligibility. 537 patients were randomly assigned to either the mobile phone messaging intervention (n=271) or standard care (n=266). The cumulative incidence of type 2 diabetes was lower in those who received mobile phone messages than in controls: 50 (18%) participants in the intervention group developed type 2 diabetes compared with 73 (27%) in the control group (hazard ratio 0·64, 95% CI 0·45-0·92; p=0·015). The number needed to treat to prevent one case of type 2 diabetes was 11 (95% CI 6-55). One patient in the control group died suddenly at the end of the first year. We recorded no other serious adverse events. Mobile

Managing with Learning Disability and Diabetes: OK-Diabetes - a case-finding study and feasibility randomised controlled trial.

Science.gov (United States)

House, Allan; Bryant, Louise; Russell, Amy M; Wright-Hughes, Alexandra; Graham, Liz; Walwyn, Rebecca; Wright, Judy M; Hulme, Claire; O'Dwyer, John L; Latchford, Gary; Meer, Shaista; Birtwistle, Jacqueline C; Stansfield, Alison; Ajjan, Ramzi; Farrin, Amanda

2018-05-01

Obesity and type 2 diabetes are common in adults with a learning disability. It is not known if the principles of self-management can be applied in this population. To develop and evaluate a case-finding method and undertake an observational study of adults with a learning disability and type 2 diabetes, to develop a standardised supported self-management (SSM) intervention and measure of adherence and to undertake a feasibility randomised controlled trial (RCT) of SSM versus treatment as usual (TAU). Observational study and an individually randomised feasibility RCT. Three cities in West Yorkshire, UK. In the observational study: adults aged > 18 years with a mild or moderate learning disability, who have type 2 diabetes that is not being treated with insulin and who are living in the community. Participants had mental capacity to consent to research and to the intervention. In the RCT participants had glycated haemoglobin (HbA 1c ) levels of > 6.5% (48 mmol/mol), a body mass index (BMI) of > 25 kg/m 2 or self-reported physical activity below national guideline levels. Standardised SSM. TAU supported by an easy-read booklet. (1) The number of eligible participants identified and sources of referral; (2) current living and support arrangements; (3) current health state, including level of HbA 1c , BMI and waist circumference, blood pressure and lipids; (4) mood, preferences for change; (5) recruitment and retention in RCT; (6) implementation and adherence to the intervention; (7) completeness of data collection and values for candidate primary outcomes; and (8) qualitative data on participant experience of the research process and intervention. In the observational study we identified 147 eligible consenting participants. The mean age was 54.4 years. In total, 130 out of 147 (88%) named a key supporter, with 113 supporters (77%) being involved in diabetes management. The mean HbA 1c level was 54.5 mmol/mol [standard deviation (SD) 14.8 mmol/mol; 7

Internet-delivered cognitive behaviour therapy for depression in people with diabetes: study protocol for a randomised controlled trial.

Science.gov (United States)

Robins, Lisa; Newby, Jill; Wilhelm, Kay; Smith, Jessica; Fletcher, Therese; Ma, Trevor; Finch, Adam; Campbell, Lesley; Andrews, Gavin

2015-01-01

Depression substantially contributes to the personal burden and healthcare costs of living with diabetes mellitus (DM). Comorbid depression and DM are associated with poorer quality of life, poorer self-management and glycemic control, increased risk for DM complications and higher mortality rates, and higher health service utilization. Depression remains under-recognized and undertreated in people with DM, which may, in part, result from barriers associated with accessing face-to-face treatment. This study will examine the efficacy of an internet-based cognitive behaviour therapy programme for major depressive disorder (iCBT-MDD) in people with DM. A CONSORT 2010 compliant, registered randomised controlled trial of the intervention (iCBT-MDD) versus a treatment as usual control group will be conducted. The study will include 100 adults aged 18 years and over with a diagnosis of type 1 or type 2 DM and self-reported symptoms that satisfy MDD which will enable us to detect a statistically significant difference with a group effect size of 0.6 at a power of 80% and significance level of p=0.05. Participants will be randomised to receive the iCBT-MDD programme immediately, or to wait 10 weeks before accessing the programme. Primary outcomes will be self-reported depression severity, DM-related distress, and glycemic control (glycosylated hemoglobin). Secondary outcomes will be general distress and disability, generalized anxiety, lifestyle behaviours, somatization, eating habits, alcohol use, and acceptability of the iCBT programme to participants, and practicality for clinicians. Data will be analyzed with linear mixed models for each outcome measure. The Human Research Ethics Committee of St Vincent's Hospital Australia have given ethics approval (HREC/13/SVH/291). Results will be disseminated via peer-reviewed publication and social media channels of Australian Diabetes Consumer Representative Bodies. The trial is registered with the Australian and New Zealand

Erythropoietin in traumatic brain injury: study protocol for a randomised controlled trial.

LENUS (Irish Health Repository)

Nichol, Alistair

2015-02-08

Traumatic brain injury is a leading cause of death and disability worldwide. Laboratory and clinical studies demonstrate a possible beneficial effect of erythropoietin in improving outcomes in the traumatic brain injury cohort. However, there are concerns regarding the association of erythropoietin and thrombosis in the critically ill. A large-scale, multi-centre, blinded, parallel-group, placebo-controlled, randomised trial is currently underway to address this hypothesis.

Walking or vitamin B for cognition in older adults with mild cognitive impairment? A randomised controlled trial

NARCIS (Netherlands)

Uffelen, J.G.Z. van; Chinapaw, M.J.M.; Mechelen, W. van; Hopman-Rock, M.

2008-01-01

Objective: To examine the effects of aerobic exercise or vitamin B supplementation on cognitive function in older adults with mild cognitive impairment (MCI). Design: Randomised placebo-controlled trial. Setting: General community. Participants: Community-dwelling adults aged 70-80 with MCI.

Prolonged-release melatonin versus placebo for benzodiazepine discontinuation in patients with schizophrenia or bipolar disorder

DEFF Research Database (Denmark)

Baandrup, Lone; Lindschou, Jane; Winkel, Per

2016-01-01

OBJECTIVES: We assessed if prolonged-release melatonin can facilitate withdrawal of long-term benzodiazepine usage in patients with schizophrenia or bipolar disorder. METHODS: Randomised, placebo-controlled, blinded, parallel superiority trial of 24 weeks duration. Participants were randomised...... to prolonged-release melatonin 2 mg daily versus matching placebo and were continuously guided to gradually reduce their usual benzodiazepine dosage. The primary outcome was mean benzodiazepine daily dosage at 24 weeks. Secondary outcomes included pattern of benzodiazepine dosage over time, benzodiazepine...... cessation proportion, and benzodiazepine withdrawal symptoms. RESULTS: In total, 86 patients (21-74 years) were enrolled: 42 were randomised to melatonin versus 44 to placebo. We found no significant effect of melatonin on mean benzodiazepine dosage at 24 weeks (melatonin group 8.01 mg versus placebo group...

Rationale and study design for a randomised controlled trial to reduce sedentary time in adults at risk of type 2 diabetes mellitus: project stand (Sedentary Time ANd diabetes

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Wilmot Emma G

2011-12-01

Full Text Available Abstract Background The rising prevalence of Type 2 Diabetes Mellitus (T2DM is a major public health problem. There is an urgent need for effective lifestyle interventions to prevent the development of T2DM. Sedentary behaviour (sitting time has recently been identified as a risk factor for diabetes, often independent of the time spent in moderate-to-vigorous physical activity. Project STAND (Sedentary Time ANd Diabetes is a study which aims to reduce sedentary behaviour in younger adults at high risk of T2DM. Methods/Design A reduction in sedentary time is targeted using theory driven group structured education. The STAND programme is subject to piloting and process evaluation in line with the MRC framework for complex interventions. Participants are encouraged to self-monitor and self-regulate their behaviour. The intervention is being assessed in a randomised controlled trial with 12 month follow up. Inclusion criteria are a aged 18-40 years with a BMI in the obese range; b 18-40 years with a BMI in the overweight range plus an additional risk factor for T2DM. Participants are randomised to the intervention (n = 89 or control (n = 89 arm. The primary outcome is a reduction in sedentary behaviour at 12 months as measured by an accelerometer (count Conclusions This is the first UK trial to address sedentary behaviour change in a population of younger adults at risk of T2DM. The results will provide a platform for the development of a range of future multidisciplinary interventions in this rapidly expanding high-risk population. Trial registration Current controlled trials ISRCTN08434554, MRC project 91409.

Effects of Semelil (ANGIPARSTM on diabetic peripheral neuropathy: A randomized, double-blind Placebo-controlled clinical trial

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S Bakhshayeshi

2011-03-01

Full Text Available "n Background and the purpose of the study: Diabetic neuropathy is the most common diabetic complication that often is accompanied by significant morbidity, mortality and economic burden. The purpose of this study was evaluation of effect of Semelil (ANGIPARSTM, a new herbal drug for treatment of diabetic foot ulcers or diabetic peripheral neuropathy. "nMethods: In this double blind clinical trial, 49 type 2 diabetes patients with different degrees of neuropathy were evaluated in two groups (ANGIPARSTM and placebo groups. All patients were assessed at the start and 12 weeks after treatment, with laboratory tests, United Kingdom screening test, Michigan neuropathy screening score, Michigan diabetic neuropathy score, vibration perception thresholds, nerve conduction study, monofilament test and visual analog scale. "nResults: Michigan diabetic neuropathy score was decreased notably in ANGIPARSTM group. In the nerve conduction study, appropriate meaningful changes were observed in the distal latency and amplitude in the motor Ulnar nerve in ANGIPARSTM group. Conclusion: The results showed limited evidence of efficacy of ANGIPARSTM in diabetic neuropathy treatment and more studies with a larger sample size and longer duration are required.

The Effectiveness of Green Tea or Green Tea Extract on Insulin Resistance and Glycemic Control in Type 2 Diabetes Mellitus: A Meta-Analysis

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Jinyue Yu

2017-08-01

Full Text Available Green tea or green tea extract (GT/GTE has been demonstrated to reduce insulin resistance and improve glycemic control. However, evidence for this health beneficial effect is inconsistent. This systematic review evaluated the effect of GT/GTE on insulin resistance and glycemic control in people with pre-diabetes/type 2 diabetes mellitus (T2DM. Ovid MEDLINE, Embase, AMED, Web of Science, and the Cochrane Library were searched up to April 2017 for randomised controlled trials of participants with pre-diabetes or T2DM, where the intervention was GT/GTE. Meta-analysis was performed to assess the standardised mean difference (SMD in biomarkers of insulin resistance and glycemic control between GT/GTE and placebo groups. Six studies (n=382 were pooled into random-effects meta-analysis. Overall, no differences were found between GT/GTE and the placebo for glycosylated hemoglobin (HbA1c: SMD, −0.32; 95% confidence interval [CI], −0.86 to 0.23, homeostatic model assessment for insulin resistance (HOMA-IR: SMD, 0.10; 95% CI, −0.17 to 0.38, fasting insulin (SMD, −0.25; 95% CI, −0.64 to 0.15, and fasting glucose (SMD, −0.10; 95% CI, −0.50 to 0.30. No evidence support the consumption of GT/GTE could reduce the levels of HbA1c, HOMA-IR, fasting insulin, or fasting glucose in people with pre-diabetes/T2DM. However, the studies included were small and of varying quality.

Intervening before the onset of Type 1 diabetes

DEFF Research Database (Denmark)

Reimers, Jesper Irving

2003-01-01

AIMS/HYPOTHESIS: To set up a clinical trial to establish whether nicotinamide can prevent or delay clinical onset of Type 1 diabetes. METHOD: The European Nicotinamide Diabetes Intervention Trial is a randomised, double-blind, placebo-controlled intervention trial undertaken in 18 European...... countries, Canada and the USA. Entry criteria were a first-degree family history of Type 1 diabetes, age 3-40 years, confirmed islet cell antibody (ICA) levels greater than or equal to 20 JDF units, and a non-diabetic OGTT; the study group was further characterised by intravenous glucose tolerance testing......) centile in 34%. Additional islet autoantibodies were identified in 354 trial entrants. Diabetes-associated HLA class II haplotypes were found in 84% of the younger age group and 80% of the older group. The protective haplotype HLA-DQA1*0102-DQB1*0602 was found in 10% overall. CONCLUSIONS...

NILVAD protocol: a European multicentre double-blind placebo-controlled trial of nilvadipine in mild-to-moderate Alzheimer's disease

NARCIS (Netherlands)

Lawlor, B.; Kennelly, S.; O'Dwyer, S.; Cregg, F.; Walsh, C.; Coen, R.; Kenny, R.A.; Howard, R.; Murphy, C.; Adams, J.; Daly, L.; Segurado, R.; Gaynor, S.; Crawford, F.; Mullan, M.; Lucca, U.; Banzi, R.; Pasquier, F.; Breuilh, L.; Riepe, M.; Kalman, J.; Wallin, A.; Borjesson, A.; Molloy, W.; Tsolaki, M.; Olde Rikkert, M.G.M.

2014-01-01

INTRODUCTION: This study is a European multicentre, randomised, double-blind, placebo-controlled trial investigating the efficacy and safety of nilvadipine as a disease course modifying treatment for mild-to-moderate Alzheimer's disease (AD) in a phase III study that will run for a period of 82

PISA. The effect of paracetamol (acetaminophen and ibuprofen on body temperature in acute stroke: Protocol for a phase II double-blind randomised placebo-controlled trial [ISRCTN98608690

Directory of Open Access Journals (Sweden)

Kappelle Jaap

2002-03-01

Full Text Available Abstract Background During the first days after stroke, one to two fifths of the patients develop fever or subfebrile temperatures. Body temperature is a strong prognostic factor after stroke. Pharmacological reduction of temperature in patients with acute ischaemic stroke may improve their functional outcome. Previously, we studied the effect of high dose (6 g daily and low dose (3 g daily paracetamol (acetaminophen in a randomised placebo-controlled trial of 75 patients with acute ischemic stroke. In the high-dose paracetamol group, mean body temperature at 12 and 24 hours after start of treatment was 0.4°C lower than in the placebo group. The effect of ibuprofen, another potent antipyretic drug, on body-core temperature in normothermic patients has not been studied. Aim The aim of the present trial is to study the effects of high-dose paracetamol and ibuprofen on body temperature in patients with acute ischaemic stroke, and to study the safety of these treatments. Design Seventy-five (3 × 25 patients with acute ischaemic stroke confined to the anterior circulation will be randomised to treatment with either: 400 mg ibuprofen, 1000 mg acetaminophen, or with placebo 6 times daily during 5 days. Body-temperatures will be measured with a rectal electronic thermometer at the start of treatment and after 24 hours. An infrared tympanic thermometer will be used to monitor body temperature at 2-hour intervals during the first 24 hours and at 12-hour intervals thereafter. The primary outcome measure will be rectal temperature at 24 hours after the start of treatment. The study results will be analysed on an intent-to-treat basis, but an on-treatment analysis will also be performed. No formal interim analysis will be carried out.

Placebo interventions for all clinical conditions

DEFF Research Database (Denmark)

Hróbjartsson, Asbjørn; Gøtzsche, Peter C

2010-01-01

Placebo interventions are often claimed to substantially improve patient-reported and observer-reported outcomes in many clinical conditions, but most reports on effects of placebos are based on studies that have not randomised patients to placebo or no treatment. Two previous versions of this re...... of this review from 2001 and 2004 found that placebo interventions in general did not have clinically important effects, but that there were possible beneficial effects on patient-reported outcomes, especially pain. Since then several relevant trials have been published.......Placebo interventions are often claimed to substantially improve patient-reported and observer-reported outcomes in many clinical conditions, but most reports on effects of placebos are based on studies that have not randomised patients to placebo or no treatment. Two previous versions...

Effect of Improving Dietary Quality on Arterial Stiffness in Subjects with Type 1 and Type 2 Diabetes: A 12 Months Randomised Controlled Trial

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Kristina S. Petersen

2016-06-01

Full Text Available People with diabetes have accelerated arterial stiffening. The aim of this study was to determine the effect of increasing fruit, vegetable and dairy intake for 12 months on carotid femoral pulse wave velocity (cfPWV, augmentation index (AIx, and central blood pressure (cBP, compared to a usual diet control, in people with type 1 and type 2 diabetes. In a 12 months randomised controlled trial, cfPWV, AIx and cBP were measured every 3 months. The intervention group received dietary counselling to increase consumption of fruit (+1 serving/day; 150 g/day, vegetables (+2 servings/day; 150 g/day and dairy (+1 serving/day; 200–250 g/day at baseline, 1, 3, 6 and 9 months. The control group continued on their usual diet. One hundred and nine participants were randomised and 92 (intervention n = 45; control n = 47 completed. At 3 months, fruit (184 g/day; p = 0.001 and dairy (83 g/day; p = 0.037 intake increased in the intervention group compared with the control group but this increase was not maintained at 12 months. After adjustment for baseline measurements there was no time by treatment effect for central systolic or diastolic BP, AIx or cfPWV. A time effect existed for AIx which modestly increased over time. Peripheral diastolic BP and central pulse pressure were improved in the intervention group compared with the control group at 12 months. In the cohort with type 1 and type 2 diabetes, improving dietary quality by increasing consumption of fruit, vegetables and dairy did not improve cBP, AIx or cfPWV, compared with a control group continuing on their usual diet, after 12 months.

A meta-analysis of randomised placebo-controlled treatment trials for depression and anxiety in Parkinson's disease.

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Lakkhina Troeung

Full Text Available Psychopharmacotherapy currently constitutes the first-line treatment for depression and anxiety in Parkinson's disease (PD however the efficacy of antidepressant treatments in PD is unclear. Several alternative treatments have been suggested as potentially more viable alternatives including dopamine agonists, repetitive transcranial magnetic stimulation, and cognitive behavioural therapy (CBT.A meta-analysis of randomised placebo-controlled trials for depression and/or anxiety in PD was conducted to systematically examine the efficacy of current treatments for depression and anxiety in PD.Nine trials were included. There was only sufficient data to calculate a pooled effect for antidepressant therapies. The pooled effect of antidepressants for depression in PD was moderate but non-significant (d = .71, 95% CI = -1.33 to 3.08. The secondary effect of antidepressants on anxiety in PD was large but also non-significant (d = 1.13, 95% CI = -.67 to 2.94. Two single-trials of non-pharmacological treatments for depression in PD resulted in significant large effects; Omega-3 supplementation (d = .92, 95% CI = .15 to 1.69 and CBT (d = 1.57, 95% CI = 1.06 to 2.07, and warrant further exploration.There remains a lack of controlled trials for both pharmacological and non-pharmacological treatments for depression and anxiety in PD which limits the conclusions which can be drawn. While the pooled effects of antidepressant therapies in PD were non-significant, the moderate to large magnitude of each pooled effect is promising. Non-pharmacological approaches show potential for depression in PD however more research is required.

Systematic Review and Meta-analysis: Placebo Rates in Induction and Maintenance Trials of Ulcerative Colitis

NARCIS (Netherlands)

Jairath, Vipul; Zou, Guangyong; Parker, Claire E.; Macdonald, John K.; Mosli, Mahmoud H.; Khanna, Reena; Shackelton, Lisa M.; Vandervoort, Margaret K.; AlAmeel, Turki; Al Beshir, Mohammad; AlMadi, Majid; Al-Taweel, Talal; Atkinson, Nathan S. S.; Biswas, Sujata; Chapman, Thomas P.; Dulai, Parambir S.; Glaire, Mark A.; Hoekman, Daniel; Koutsoumpas, Andreas; Minas, Elizabeth; Samaan, Mark A.; Travis, Simon; D'Haens, Geert; Levesque, Barrett G.; Sandborn, William J.; Feagan, Brian G.

2016-01-01

Minimisation of the placebo responses in randomised controlled trials [RCTs] is essential for efficient evaluation of new interventions. Placebo rates have been high in ulcerative colitis [UC] clinical trials, and factors influencing this are poorly understood. We quantify placebo response and

Multiple behaviour change intervention and outcomes in recently diagnosed type 2 diabetes: the ADDITION-Plus randomised controlled trial.

Science.gov (United States)

Griffin, Simon J; Simmons, Rebecca K; Prevost, A Toby; Williams, Kate M; Hardeman, Wendy; Sutton, Stephen; Brage, Søren; Ekelund, Ulf; Parker, Richard A; Wareham, Nicholas J; Kinmonth, Ann Louise

2014-07-01

The aim of this study was to assess whether or not a theory-based behaviour change intervention delivered by trained and quality-assured lifestyle facilitators can achieve and maintain improvements in physical activity, dietary change, medication adherence and smoking cessation in people with recently diagnosed type 2 diabetes. An explanatory randomised controlled trial was conducted in 34 general practices in Eastern England (Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen Detected Diabetes in Primary Care-Plus [ADDITION-Plus]). In all, 478 patients meeting eligibility criteria (age 40 to 69 years with recently diagnosed screen or clinically detected diabetes) were individually randomised to receive either intensive treatment (n = 239) or intensive treatment plus a theory-based behaviour change intervention led by a facilitator external to the general practice team (n = 239). Randomisation was central and independent using a partial minimisation procedure to balance stratifiers between treatment arms. Facilitators taught patients skills to facilitate change in and maintenance of key health behaviours, including goal setting, self-monitoring and building habits. Primary outcomes included physical activity energy expenditure (individually calibrated heart rate monitoring and movement sensing), change in objectively measured fruit and vegetable intake (plasma vitamin C), medication adherence (plasma drug levels) and smoking status (plasma cotinine levels) at 1 year. Measurements, data entry and laboratory analysis were conducted with staff unaware of participants' study group allocation. Of 475 participants still alive, 444 (93%; intervention group 95%, comparison group 92%) attended 1-year follow-up. There were no significant differences between groups in physical activity (difference: +1.50 kJ kg(-1) day(-1); 95% CI -1.74, 4.74), plasma vitamin C (difference: -3.84 μmol/l; 95% CI -8.07, 0.38), smoking (OR 1.37; 95% CI 0.77, 2.43) and

A short course of metformin does not reduce OHSS in a GnRH antagonist cycle for women with PCOS undergoing IVF: a randomised placebo-controlled trial.

Science.gov (United States)

Jacob, S L; Brewer, C; Tang, T; Picton, H M; Barth, J H; Balen, A H

2016-12-01

Does 'metformin' reduce the incidence of ovarian hyperstimulation syndrome (OHSS) for women with polycystic ovary syndrome (PCOS) undergoing a GnRH antagonist assisted conception treatment cycle? A short course of metformin does not reduce the incidence of OHSS for women with PCOS undergoing a GnRH antagonist treatment cycle. Metformin does reduce the incidence of OHSS in a GnRH-agonist treatment cycle. A randomised placebo-controlled trial (RCT) using metformin or placebo. Randomisation was blinded to both patient and investigator, using a random permuted blocks method with a 50:50 allocation ratio. The study was completed over 5 years (2009-2014) with 153 randomised patients. A sample size calculation based on the incidence of OHSS was completed prospectively suggesting a minimum of 146 recruits was required for the trial with a power of 80% and a type 1 error of 0.05. All patients met the Rotterdam criteria for PCOS and were treated with a standard GnRH antagonist IVF/ICSI treatment cycle in a tertiary infertility clinic. The study medication was started prior to stimulation and continued to oocyte retrieval. Of the 153 patients, 77 received metformin and 76 placebo. There was no reduction in the incidence of moderate-severe OHSS (Placebo (PLA) 12.2%, metformin (MET) = 16%, 95% CI -0.08-0.16, P = 0.66). There was no difference in total gonadotrophin dose (PLA = 1200, MET = 1200, 95% CI -118.67-118.67, P = 0.75), oocytes retrieved (PLA = 15, MET = 14, 95% CI -2.37-4.37, P = 0.66) or fertilisation rate (PLA = 60.7%, MET = 53.3%, 95% CI -0.96-14.94, P = 0.07). However, using metformin resulted in a reduced clinical pregnancy rate (CPR) per cycle started (PLA = 48.7%, MET = 28.6%, 95% CI 0.04-0.35, P = 0.02) and live birth rate (PLA = 51.6%, MET = 27.6%, 95% CI 0.05-0.40, P = 0.02). Furthermore, when ethnicity was taken into account there was a significant reduction in pregnancy outcome for the South Asian population irrespective of metformin or

Combination of a structured aerobic and resistance exercise improves glycaemic control in pregnant women diagnosed with gestational diabetes mellitus. A randomised controlled trial.

Science.gov (United States)

Sklempe Kokic, Iva; Ivanisevic, Marina; Biolo, Gianni; Simunic, Bostjan; Kokic, Tomislav; Pisot, Rado

2017-10-18

Gestational diabetes mellitus, defined as any carbohydrate intolerance first diagnosed during pregnancy, is associated with a variety of adverse outcomes, both for the mother and her child. To investigate the impact of a structured exercise programme which consisted of aerobic and resistance exercises on the parameters of glycaemic control and other health-related outcomes in pregnant women diagnosed with gestational diabetes mellitus. Thirty-eight pregnant women diagnosed with gestational diabetes mellitus were randomised to two groups. Experimental group was treated with standard antenatal care for gestational diabetes mellitus, and regular supervised exercise programme plus daily brisk walks of at least 30min. Control group received only standard antenatal care for gestational diabetes mellitus. The exercise programme was started from the time of diagnosis of diabetes until birth. It was performed two times per week and sessions lasted 50-55min. The experimental group had lower postprandial glucose levels at the end of pregnancy (P<0.001). There was no significant difference between groups in the level of fasting glucose at the end of pregnancy. Also, there were no significant differences in the rate of complications during pregnancy and birth, need for pharmacological therapy, maternal body mass and body fat percentage gains during pregnancy, and neonatal Apgar scores, body mass and ponderal index. Neonatal body mass index was higher in the experimental group (P=0.035). The structured exercise programme had a beneficial effect on postprandial glucose levels at the end of pregnancy. Copyright © 2017 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

Magnet therapy for the relief of pain and inflammation in rheumatoid arthritis (CAMBRA: A randomised placebo-controlled crossover trial

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Richmond Stewart J

2008-09-01

Full Text Available Abstract Background Rheumatoid arthritis is a common inflammatory autoimmune disease. Although disease activity may be managed effectively with prescription drugs, unproven treatments such as magnet therapy are sometimes used as an adjunct for pain control. Therapeutic devices incorporating permanent magnets are widely available and easy to use. Magnets may also be perceived as a more natural and less harmful alternative to analgesic compounds. Of interest to health service researchers is the possibility that magnet therapy might help to reduce the economic burden of managing chronic musculoskeletal disorders. Magnets are extremely cheap to manufacture and prolonged treatment involves a single cost. Despite this, good quality scientific evidence concerning the safety, effectiveness and cost-effectiveness of magnet therapy is scarce. The primary aim of the CAMBRA trial is to investigate the effectiveness of magnet therapy for relieving pain and inflammation in rheumatoid arthritis. Methods/Design The CAMBRA trial employs a randomised double-blind placebo-controlled crossover design. Participant will each wear four devices: a commercially available magnetic wrist strap; an attenuated wrist strap; a demagnetised wrist strap; and a copper bracelet. Device will be allocated in a randomised sequence and each worn for five weeks. The four treatment phases will be separated by wash out periods lasting one week. Both participants and researchers will be blind, as far as feasible, to the allocation of experimental and control devices. In total 69 participants will be recruited from general practices within the UK. Eligible patients will have a verified diagnosis of rheumatoid arthritis that is being managed using drugs, and will be experiencing chronic pain. Outcomes measured will include pain, inflammation, disease activity, physical function, medication use, affect, and health related costs. Data will be collected using questionnaires, diaries, manual

Impact of probiotic Saccharomyces boulardii on the gut microbiome composition in HIV-treated patients: A double-blind, randomised, placebo-controlled trial.

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Judit Villar-García

Full Text Available Dysbalance in gut microbiota has been linked to increased microbial translocation, leading to chronic inflammation in HIV-patients, even under effective HAART. Moreover, microbial translocation is associated with insufficient reconstitution of CD4+T cells, and contributes to the pathogenesis of immunologic non-response. In a double-blind, randomised, placebo-controlled trial, we recently showed that, compared to placebo, 12 weeks treatment with probiotic Saccharomyces boulardii significantly reduced plasma levels of bacterial translocation (Lipopolysaccharide-binding protein or LBP and systemic inflammation (IL-6 in 44 HIV virologically suppressed patients, half of whom (n = 22 had immunologic non-response to antiretroviral therapy (<270 CD4+Tcells/μL despite long-term suppressed viral load. The aim of the present study was to investigate if this beneficial effect of the probiotic Saccharomyces boulardii is due to modified gut microbiome composition, with a decrease of some species associated with higher systemic levels of microbial translocation and inflammation. In this study, we used 16S rDNA gene amplification and parallel sequencing to analyze the probiotic impact on the composition of the gut microbiome (faecal samples in these 44 patients randomized to receive oral supplementation with probiotic or placebo for 12 weeks. Compared to the placebo group, in individuals treated with probiotic we observed lower concentrations of some gut species, such as those of the Clostridiaceae family, which were correlated with systemic levels of bacterial translocation and inflammation markers. In a sub-study of these patients, we observed significantly higher parameters of microbial translocation (LBP, soluble CD14 and systemic inflammation in immunologic non-responders than in immunologic responders, which was correlated with a relative abundance of specific gut bacterial groups (Lachnospiraceae genus and Proteobacteria. Thus, in this work, we propose

Inositol for the prevention of neural tube defects: a pilot randomised controlled trial.

Science.gov (United States)

Greene, Nicholas D E; Leung, Kit-Yi; Gay, Victoria; Burren, Katie; Mills, Kevin; Chitty, Lyn S; Copp, Andrew J

2016-03-28

Although peri-conceptional folic acid (FA) supplementation can prevent a proportion of neural tube defects (NTD), there is increasing evidence that many NTD are FA non-responsive. The vitamin-like molecule inositol may offer a novel approach to preventing FA-non-responsive NTD. Inositol prevented NTD in a genetic mouse model, and was well tolerated by women in a small study of NTD recurrence. In the present study, we report the Prevention of Neural Tube Defects by Inositol (PONTI) pilot study designed to gain further experience of inositol usage in human pregnancy as a preliminary trial to a future large-scale controlled trial to evaluate efficacy of inositol in NTD prevention. Study subjects were UK women with a previous NTD pregnancy who planned to become pregnant again. Of 117 women who made contact, ninety-nine proved eligible and forty-seven agreed to be randomised (double-blind) to peri-conceptional supplementation with inositol plus FA or placebo plus FA. In total, thirty-three randomised pregnancies produced one NTD recurrence in the placebo plus FA group (n 19) and no recurrences in the inositol plus FA group (n 14). Of fifty-two women who declined randomisation, the peri-conceptional supplementation regimen and outcomes of twenty-two further pregnancies were documented. Two NTD recurred, both in women who took only FA in their next pregnancy. No adverse pregnancy events were associated with inositol supplementation. The findings of the PONTI pilot study encourage a large-scale controlled trial of inositol for NTD prevention, but indicate the need for a careful study design in view of the unwillingness of many high-risk women to be randomised.

Short-term efficacy of physical interventions in osteoarthritic knee pain. A systematic review and meta-analysis of randomised placebo-controlled trials

Directory of Open Access Journals (Sweden)

Bogen Bård

2007-06-01

Full Text Available Abstract Background Treatment efficacy of physical agents in osteoarthritis of the knee (OAK pain has been largely unknown, and this systematic review was aimed at assessing their short-term efficacies for pain relief. Methods Systematic review with meta-analysis of efficacy within 1–4 weeks and at follow up at 1–12 weeks after the end of treament. Results 36 randomised placebo-controlled trials (RCTs were identified with 2434 patients where 1391 patients received active treatment. 33 trials satisfied three or more out of five methodological criteria (Jadad scale. The patient sample had a mean age of 65.1 years and mean baseline pain of 62.9 mm on a 100 mm visual analogue scale (VAS. Within 4 weeks of the commencement of treatment manual acupuncture, static magnets and ultrasound therapies did not offer statistically significant short-term pain relief over placebo. Pulsed electromagnetic fields offered a small reduction in pain of 6.9 mm [95% CI: 2.2 to 11.6] (n = 487. Transcutaneous electrical nerve stimulation (TENS, including interferential currents, electro-acupuncture (EA and low level laser therapy (LLLT offered clinically relevant pain relieving effects of 18.8 mm [95% CI: 9.6 to 28.1] (n = 414, 21.9 mm [95% CI: 17.3 to 26.5] (n = 73 and 17.7 mm [95% CI: 8.1 to 27.3] (n = 343 on VAS respectively versus placebo control. In a subgroup analysis of trials with assumed optimal doses, short-term efficacy increased to 22.2 mm [95% CI: 18.1 to 26.3] for TENS, and 24.2 mm [95% CI: 17.3 to 31.3] for LLLT on VAS. Follow-up data up to 12 weeks were sparse, but positive effects seemed to persist for at least 4 weeks after the course of LLLT, EA and TENS treatment was stopped. Conclusion TENS, EA and LLLT administered with optimal doses in an intensive 2–4 week treatment regimen, seem to offer clinically relevant short-term pain relief for OAK.

Randomised clinical trial

DEFF Research Database (Denmark)

Reimer, C; Lødrup, A; Smith, G

2016-01-01

of an alginate (Gaviscon Advance, Reckitt Benckiser, Slough, UK) on reflux symptoms in patients with persistent symptoms despite once daily PPI. MethodsThis was a multicentre, randomised, placebo-controlled, 7-day double-blind trial preceded by a 7-day run-in period. Reflux symptoms were assessed using...

Cardiovascular safety and efficacy of the PCSK9 inhibitor evolocumab in patients with and without diabetes and the effect of evolocumab on glycaemia and risk of new-onset diabetes: a prespecified analysis of the FOURIER randomised controlled trial.

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Sabatine, Marc S; Leiter, Lawrence A; Wiviott, Stephen D; Giugliano, Robert P; Deedwania, Prakash; De Ferrari, Gaetano M; Murphy, Sabina A; Kuder, Julia F; Gouni-Berthold, Ioanna; Lewis, Basil S; Handelsman, Yehuda; Pineda, Armando Lira; Honarpour, Narimon; Keech, Anthony C; Sever, Peter S; Pedersen, Terje R

2017-12-01

The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab reduced LDL cholesterol and cardiovascular events in the FOURIER trial. In this prespecified analysis of FOURIER, we investigated the efficacy and safety of evolocumab by diabetes status and the effect of evolocumab on glycaemia and risk of developing diabetes. FOURIER was a randomised trial of evolocumab (140 mg every 2 weeks or 420 mg once per month) versus placebo in 27 564 patients with atherosclerotic disease who were on statin therapy, followed up for a median of 2·2 years. In this prespecified analysis, we investigated the effect of evolocumab on cardiovascular events by diabetes status at baseline, defined on the basis of patient history, clinical events committee review of medical records, or baseline HbA 1c of 6·5% (48 mmol/mol) or greater or fasting plasma glucose (FPG) of 7·0 mmol/L or greater. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, hospital admission for unstable angina, or coronary revascularisation. The key secondary endpoint was a composite of cardiovascular death, myocardial infarction, or stroke. We also assessed the effect of evolocumab on glycaemia, and on the risk of new-onset diabetes among patients without diabetes at baseline. HbA 1c was measured at baseline then every 24 weeks and FPG was measured at baseline, week 12, week 24, and every 24 weeks thereafter, and potential cases of new-onset diabetes were adjudicated centrally. In a post-hoc analysis, we also investigated the effects on glycaemia and diabetes risk in patients with prediabetes (HbA 1c 5·7-6·4% [39-46 mmol/mol] or FPG 5·6-6·9 mmol/L) at baseline. FOURIER is registered with ClinicalTrials.gov, number NCT01764633. At study baseline, 11 031 patients (40%) had diabetes and 16 533 (60%) did not have diabetes (of whom 10 344 had prediabetes and 6189 had normoglycaemia). Evolocumab significantly reduced cardiovascular outcomes

Binocular treatment of amblyopia using videogames (BRAVO): study protocol for a randomised controlled trial.

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Guo, Cindy X; Babu, Raiju J; Black, Joanna M; Bobier, William R; Lam, Carly S Y; Dai, Shuan; Gao, Tina Y; Hess, Robert F; Jenkins, Michelle; Jiang, Yannan; Kowal, Lionel; Parag, Varsha; South, Jayshree; Staffieri, Sandra Elfride; Walker, Natalie; Wadham, Angela; Thompson, Benjamin

2016-10-18

Amblyopia is a common neurodevelopmental disorder of vision that is characterised by visual impairment in one eye and compromised binocular visual function. Existing evidence-based treatments for children include patching the nonamblyopic eye to encourage use of the amblyopic eye. Currently there are no widely accepted treatments available for adults with amblyopia. The aim of this trial is to assess the efficacy of a new binocular, videogame-based treatment for amblyopia in older children and adults. We hypothesise that binocular treatment will significantly improve amblyopic eye visual acuity relative to placebo treatment. The BRAVO study is a double-blind, randomised, placebo-controlled multicentre trial to assess the effectiveness of a novel videogame-based binocular treatment for amblyopia. One hundred and eight participants aged 7 years or older with anisometropic and/or strabismic amblyopia (defined as ≥0.2 LogMAR interocular visual acuity difference, ≥0.3 LogMAR amblyopic eye visual acuity and no ocular disease) will be recruited via ophthalmologists, optometrists, clinical record searches and public advertisements at five sites in New Zealand, Canada, Hong Kong and Australia. Eligible participants will be randomised by computer in a 1:1 ratio, with stratification by age group: 7-12, 13-17 and 18 years and older. Participants will be randomised to receive 6 weeks of active or placebo home-based binocular treatment. Treatment will be in the form of a modified interactive falling-blocks game, implemented on a 5th generation iPod touch device viewed through red/green anaglyphic glasses. Participants and those assessing outcomes will be blinded to group assignment. The primary outcome is the change in best-corrected distance visual acuity in the amblyopic eye from baseline to 6 weeks post randomisation. Secondary outcomes include distance and near visual acuity, stereopsis, interocular suppression, angle of strabismus (where applicable) measured at

The effects of topical heat therapy on chest pain in patients with acute coronary syndrome: a randomised double-blind placebo-controlled clinical trial.

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Mohammadpour, Ali; Mohammadian, Batol; Basiri Moghadam, Mehdi; Nematollahi, Mahmoud Reza

2014-12-01

To investigate the effects of local heat therapy on chest pain in patients with acute coronary syndrome. Chest pain is a very common complaint in patients with acute coronary syndrome. It is managed both pharmacologically and nonpharmacologically. Pharmacological pain management is associated with different side effects. This was a randomised double-blind placebo-controlled clinical trial conducted in 2013. A convenience sample of 66 patients with acute coronary syndrome was selected from a coronary care unit of a local teaching hospital affiliated to Gonabad University of Medical Sciences, Gonabad, Iran. Patients were randomly assigned to either the experimental or the placebo group. Patients in the experimental and the placebo groups received local heat therapy using a hot pack warmed to 50 and 37 °C, respectively. We assessed chest pain intensity, duration and frequency as well as the need for opioid analgesic therapy both before and after the study. The study instrument consisted of a demographic questionnaire, the McGill Pain Questionnaire, and a data sheet for documenting pain frequency and duration as well as the need for analgesic therapy. The placebo heat therapy did not significantly decrease the intensity, the duration and the frequency of pain episodes. However, pain intensity, duration and frequency in the experimental group decreased significantly after the study. Moreover, the groups differed significantly in terms of the need for opioid analgesic therapy neither before nor after the intervention. Local heat therapy is an effective intervention for preventing and relieving chest pain in patients with acute coronary syndrome. Effective pain management using local heat therapy could help nurses play an important role in providing effective care to patients with acute coronary syndrome and in minimising adverse effects associated with pain medications. © 2014 John Wiley & Sons Ltd.

Oral dextrose for analgesia in neonates during nasogastric tube insertion: a randomised controlled trial.

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Ravishankar, Arjun; Thawani, Rajat; Dewan, Pooja; Das, Saurabhi; Kashyap, Archana; Batra, Prerna; Faridi, Moonis Mohammed Akbar

2014-02-01

This study aims to determine if oral dextrose solution can mitigate the pain response to nasogastric tube (NGT) insertion in neonates. The study was a double-blinded, placebo-controlled, randomised controlled trial. One hundred and fifty consecutive neonates were randomised into three groups to receive 25% dextrose (D25), or 10% dextrose (D10) or placebo (distilled water). An NGT was inserted after giving 2 mL of one of the solutions orally. Pain response was assessed using the Premature Infant Pain Profile (PIPP), and the duration of cry was noted within 60 s of the intervention. Total PIPP score, duration of cry, change in heart rate and oxygen saturation (SpO2 ) were compared among the three groups. Neonates who received D25 had significantly lesser pain response to NGT insertion in terms of lower PIPP score (P < 0.05) and duration of cry (P = 0.001) compared to D10. There was a significantly smaller increase in heart rate and decrease in SpO2 (P < 0.05). In comparison with placebo, D10 significantly decreased duration of cry (P < 0.05) but not PIPP score. Oral D25 was effective in reducing the pain response during NGT insertion in neonates when compared with oral D10 and placebo. Oral D10 was not found to have a potent analgesic effect for the same. © 2013 The Authors. Journal of Paediatrics and Child Health © 2013 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial.

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Thiele, Elizabeth A; Marsh, Eric D; French, Jacqueline A; Mazurkiewicz-Beldzinska, Maria; Benbadis, Selim R; Joshi, Charuta; Lyons, Paul D; Taylor, Adam; Roberts, Claire; Sommerville, Kenneth

2018-03-17

Patients with Lennox-Gastaut syndrome, a rare, severe form of epileptic encephalopathy, are frequently treatment resistant to available medications. No controlled studies have investigated the use of cannabidiol for patients with seizures associated with Lennox-Gastaut syndrome. We therefore assessed the efficacy and safety of cannabidiol as an add-on anticonvulsant therapy in this population of patients. In this randomised, double-blind, placebo-controlled trial done at 24 clinical sites in the USA, the Netherlands, and Poland, we investigated the efficacy of cannabidiol as add-on therapy for drop seizures in patients with treatment-resistant Lennox-Gastaut syndrome. Eligible patients (aged 2-55 years) had Lennox-Gastaut syndrome, including a history of slow (caregivers, investigators, and individuals assessing data were masked to group assignment. The primary endpoint was percentage change from baseline in monthly frequency of drop seizures during the treatment period, analysed in all patients who received at least one dose of study drug and had post-baseline efficacy data. All randomly assigned patients were included in the safety analyses. This study is registered with ClinicalTrials.gov, number NCT02224690. Between April 28, 2015, and Oct 15, 2015, we randomly assigned 171 patients to receive cannabidiol (n=86) or placebo (n=85). 14 patients in the cannabidiol group and one in the placebo group discontinued study treatment; all randomly assigned patients received at least one dose of study treatment and had post-baseline efficacy data. The median percentage reduction in monthly drop seizure frequency from baseline was 43·9% (IQR -69·6 to -1·9) in the cannibidiol group and 21·8% (IQR -45·7 to 1·7) in the placebo group. The estimated median difference between the treatment groups was -17·21 (95% CI -30·32 to -4·09; p=0·0135) during the 14-week treatment period. Adverse events occurred in 74 (86%) of 86 patients in the cannabidiol group and 59 (69%) of

Effectiveness of single dose rifampicin in preventing leprosy in close contacts of patients with newly diagnosed leprosy: cluster randomised controlled trial

NARCIS (Netherlands)

Moet, F. Johannes; Pahan, David; Oskam, Linda; Richardus, Jan H.; van Brakel, Wim H.; Klatser, Paul R.; Saunderson, Paul R.; Smith, W. Cairns S.; Withington, Steve G.; Richardus, Jan Hendrik; Schuring, Ron P.; Faber, Roel; Borsboom, Gerard J. J. M.

2008-01-01

OBJECTIVE: To determine the effectiveness of chemoprophylaxis using a single dose of rifampicin to prevent leprosy in close contacts. DESIGN: Single centre, double blind, cluster randomised, placebo controlled trial. SETTING: Leprosy control programme in two districts of northwest Bangladesh with a

A Randomized, Double-Blind, Placebo-Controlled Trial of Adjunctive Metformin Therapy in Overweight/Obese Youth with Type 1 Diabetes.

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Benjamin Udoka Nwosu

Full Text Available Insulin resistance has been proposed as one of the causes of poor glycemic control in overweight/obese youth with type 1 diabetes (T1D. However, the role of adjunctive metformin, an insulin sensitizer, on glycemic control in these patients is unclear.To compare the effect of metformin vs. placebo on hemoglobin A1c (HbA1c, total daily dose (TDD of insulin, and other parameters in overweight/obese youth with T1D.Adjunctive metformin therapy will improve glycemic control in overweight/obese youth with T1D.A 9-mo randomized, double-blind, placebo controlled trial of metformin and placebo in 28 subjects (13m/15f of ages 10-20years (y, with HbA1c >8% (64 mmol/mol, BMI >85%, and T1D > 12 months was conducted at a university outpatient facility. The metformin group consisted of 15 subjects (8 m/ 7f, of age 15.0 ± 2.5 y; while the control group was made up of 13 subjects (5m/ 8f, of age 14.5 ± 3.1y. All participants employed a self-directed treat-to-target insulin regimen based on a titration algorithm of (-2-0-(+2 units to adjust their long-acting insulin dose every 3rd day from -3 mo through +9 mo to maintain fasting plasma glucose (FPG between 90-120 mg/dL (5.0-6.7 mmol/L. Pubertal maturation was determined by Tanner stage.Over the course of the 9 months of observation, the between-treatment differences in HbA1c of 0.4% (9.85% [8.82 to 10.88] for placebo versus 9.46% [8.47 to 10.46] for metformin was not significant (p = 0.903. There were non-significant reduction in fasting plasma glucose (189.4 mg/dL [133.2 to 245.6] for placebo versus 170.5 mg/dL [114.3 to 226.7] for metformin, (p = 0.927; total daily dose (TDD of short-acting insulin per kg body weight/day(p = 0.936; and the TDD of long-acting insulin per kg body weight per day (1.15 units/kg/day [0.89 to 1.41] for placebo versus 0.90 units/kg/day [0.64 to 1.16] for metformin (p = 0.221. There was no difference in the occurrence of hypoglycemia between the groups.This 9-month RCT of adjunctive

Acupuncture treatment for pain: systematic review of randomised clinical trials with acupuncture, placebo acupuncture, and no acupuncture groups

DEFF Research Database (Denmark)

Madsen, Matias Vested; Gøtzsche, Peter C; Hróbjartsson, Asbjørn

2009-01-01

OBJECTIVES: To study the analgesic effect of acupuncture and placebo acupuncture and to explore whether the type of the placebo acupuncture is associated with the estimated effect of acupuncture. DESIGN: Systematic review and meta-analysis of three armed randomised clinical trials. DATA SOURCES......: Cochrane Library, Medline, Embase, Biological Abstracts, and PsycLIT. Data extraction and analysis Standardised mean differences from each trial were used to estimate the effect of acupuncture and placebo acupuncture. The different types of placebo acupuncture were ranked from 1 to 5 according...... to assessment of the possibility of a physiological effect, and this ranking was meta-regressed with the effect of acupuncture. DATA SYNTHESIS: Thirteen trials (3025 patients) involving a variety of pain conditions were eligible. The allocation of patients was adequately concealed in eight trials...

Targeting intensive glycaemic control versus targeting conventional glycaemic control for type 2 diabetes mellitus

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Hemmingsen, Bianca; Lund, Søren; Gluud, Christian

2013-01-01

Patients with type 2 diabetes mellitus (T2D) have an increased risk of cardiovascular disease and mortality compared to the background population. Observational studies report an association between reduced blood glucose and reduced risk of both micro- and macrovascular complications in patients...... with T2D. Our previous systematic review of intensive glycaemic control versus conventional glycaemic control was based on 20 randomised clinical trials that randomised 29 ,986 participants with T2D. We now report our updated review....

Long term treatment with metformin in patients with type 2 diabetes and vitamin B 12

Directory of Open Access Journals (Sweden)

Yu V Pankratova

2012-12-01

Full Text Available Реферат по статье: De Jager J, Kooy A, Lehert P, Wulffelé MG, van der Kolk J, Bets D, Verburg J, Donker AJ, Stehouwer CD. Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomised placebo controlled trial. BMJ. 2010 May 20;340:c2181.

Impact of an educational DVD on anxiety and glycaemic control in women diagnosed with gestational diabetes mellitus (GDM): A randomised controlled trial.

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Draffin, Claire R; Alderdice, Fiona A; McCance, David R; Maresh, Michael; Harper, Roy; Patterson, Christopher C; Bernatavicius, Giovanna; Brennan, Sarah F; Gough, Aisling; McSorley, Oonagh; Holmes, Valerie A

2017-04-01

The diagnosis of gestational diabetes mellitus (GDM) during pregnancy can lead to anxiety. This study evaluated the impact of an innovative patient-centred educational DVD on anxiety and glycaemic control in women newly diagnosed with GDM. 150 multi-ethnic women, aged 19-44years, from three UK hospitals were randomised to either usual care plus DVD (DVD group, n=77) or usual care alone (control group, n=73) at GDM diagnosis. Primary outcomes were anxiety (State-Trait Anxiety Inventory) and mean 1-h postprandial capillary self-monitored blood glucose for all meals, on day prior to follow-up. No significant difference between the DVD and control group were reported, for anxiety (37.7±11.7 vs 36.2±10.9; mean difference after adjustment for covariates (95% CI) 2.5 (-0.8, 5.9) or for mean 1-h postprandial glucose for all meals (6.9±0.9 vs 7.0±1.2mmol/L; -0.2 (-0.5, 0.2). However, the DVD group had significantly lower postprandial breakfast glucose compared to the control group (6.8±1.2 vs 7.4±1.9mmol/L; -0.5 (-1.1, -gestational diabetes. Copyright © 2017 Elsevier B.V. All rights reserved.

General lack of use of placebo in prophylactic, randomised, controlled trials in adult migraine. A systematic review

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Hougaard, Anders; Tfelt-Hansen, Peer

2016-01-01

of placebo control in such trials has not been systematically assessed. METHODS: We performed a systematic review of all comparative RCTs of prophylactic drug treatment of migraine published in English from 2002 to 2014. PubMed was searched using the Cochrane Highly Sensitive Search Strategy for identifying...... reports of RCTs. RESULTS: A placebo arm was used in requiring more than 75,000 patient days, no difference...... was identified across treatment arms and conclusions regarding drug superiority could not be drawn. CONCLUSIONS: The majority of comparative, prophylactic migraine RCTs do not include a placebo arm. Failure to include a placebo arm may result in failure to demonstrate efficacy of potentially effective migraine...

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

Science.gov (United States)

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

2011-02-21

controversy, and the challenges that exist even when ethics committee approval has been granted. It showed that a placebo-controlled trial could be conducted in principle, albeit with difficulty. It also highlighted that not only does a placebo-controlled trial in surgery have to be ethically and scientifically acceptable but that it also must be a feasible course of action. The place of placebo-controlled surgical trials more generally is likely to be limited and require specific circumstances to be met. Suggested criteria are presented. The trial was assigned ISRCTN02328576 through http://controlled-trials.com/ in June 2006. The first patient was randomised to the pilot in July 2007.

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

Directory of Open Access Journals (Sweden)

McDonald AM

2011-02-01

surgical placebos, the ethical issues underpinning this controversy, and the challenges that exist even when ethics committee approval has been granted. It showed that a placebo-controlled trial could be conducted in principle, albeit with difficulty. It also highlighted that not only does a placebo-controlled trial in surgery have to be ethically and scientifically acceptable but that it also must be a feasible course of action. The place of placebo-controlled surgical trials more generally is likely to be limited and require specific circumstances to be met. Suggested criteria are presented. Trial registration number The trial was assigned ISRCTN02328576 through http://controlled-trials.com/ in June 2006. The first patient was randomised to the pilot in July 2007.

Prophylactic Oral Dextrose Gel for Newborn Babies at Risk of Neonatal Hypoglycaemia: A Randomised Controlled Dose-Finding Trial (the Pre-hPOD Study).

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Hegarty, Joanne Elizabeth; Harding, Jane Elizabeth; Gamble, Gregory David; Crowther, Caroline Anne; Edlin, Richard; Alsweiler, Jane Marie

2016-10-01

Neonatal hypoglycaemia is common, affecting up to 15% of newborns, and can cause brain damage. Currently, there are no strategies, beyond early feeding, to prevent neonatal hypoglycaemia. Our aim was to determine a dose of 40% oral dextrose gel that will prevent neonatal hypoglycaemia in newborn babies at risk. We conducted a randomised, double-blind, placebo-controlled dose-finding trial of buccal dextrose gel to prevent neonatal hypoglycaemia at two hospitals in New Zealand. Babies at risk of hypoglycaemia (infant of a mother with diabetes, late preterm delivery, small or large birthweight, or other risk factors) but without indication for admission to a neonatal intensive care unit (NICU) were randomly allocated either to one of four treatment groups: 40% dextrose at one of two doses (0.5 ml/kg = 200 mg/kg, or 1 ml/kg = 400 mg/kg), either once at 1 h of age or followed by three additional doses of dextrose (0.5 ml/kg before feeds in the first 12 h); or to one of four corresponding placebo groups. Treatments were administered by massaging gel into the buccal mucosa. The primary outcome was hypoglycaemia (dextrose gel (relative risk [RR] 0.68; 95% confidence interval [CI] 0.47-0.99, p = 0.04) but was not significantly different between dose groups (p = 0.21). Compared to multiple doses, single doses of gel were better tolerated, quicker to administer, and less messy, but these limitations were not different between dextrose and placebo gel groups. Babies who received any dose of dextrose gel were less likely to develop hypoglycaemia than those who received placebo (RR 0.79; 95% CI 0.64-0.98, p = 0.03; number needed to treat = 10, 95% CI 5-115). Rates of NICU admission were similar (RR 0.64; 95% CI 0.33-1.25, p = 0.19), but admission for hypoglycaemia was less common in babies randomised to dextrose gel (RR 0.46; 95% CI 0.21-1.01, p = 0.05). Rates of breastfeeding were similar in both groups. Adverse effects were uncommon and not different between groups. A

Treatment with L-citrulline and metformin in Duchenne muscular dystrophy: study protocol for a single-centre, randomised, placebo-controlled trial.

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Hafner, Patricia; Bonati, Ulrike; Rubino, Daniela; Gocheva, Vanya; Zumbrunn, Thomas; Gueven, Nuri; Fischer, Dirk

2016-08-03

Duchenne muscular dystrophy (DMD) is an X-linked recessive disease that affects 1 in 3500-6000 male births. Despite broad research aiming to improve muscle function as well as heart and brain function, sufficient therapeutic efficacy has not yet been achieved and current therapeutic management is still supportive. In a recent pilot trial, oral treatment with L-arginine and metformin showed consistent changes of muscular metabolism both in vitro and in vivo by raising NO levels and expression of mitochondrial proteins in the skeletal muscle tissue of patients with DMD. This randomised, double-blind, placebo-controlled trial aims to demonstrate the superiority of L-citrulline and metformin therapy over placebo in DMD patients with regard to the Motor Function Measure (MFM) D1 subscore (primary endpoint) as well as additional clinical and subclinical tests. A total of 40-50 ambulant patients with DMD will be recruited at the outpatient department of the University of Basel Children's Hospital (Switzerland), as well as from the DMD patient registries of Switzerland, Germany and Austria. Patients will be randomly allocated to one of the two arms of the study and will receive either a combination of L-citrulline and metformin or placebo for 26 weeks. Co-medication with glucocorticoids is allowed. The primary endpoint is the change of the MFM D1 subscore from baseline to week 26 under L-citrulline and metformin therapy. Secondary endpoints will include the motor function measure (MFM) and its items and subscores, the 6-minute walking test, timed function tests and quantitative muscle testing. Furthermore, quantitative muscle MRI assessment to evaluate the muscle fat fraction as well as safety and biomarker laboratory analyses from blood will be included. For comparison, muscle metabolism and mitochondrial function will be analysed in 10-20 healthy age-matched male children. The aim of this study is to test if a 6-month treatment of a combination of L-citrulline and

Randomised clinical trial: the clinical efficacy and safety of an alginate-antacid (Gaviscon Double Action) versus placebo, for decreasing upper gastrointestinal symptoms in symptomatic gastroesophageal reflux disease (GERD) in China.

Science.gov (United States)

Sun, J; Yang, C; Zhao, H; Zheng, P; Wilkinson, J; Ng, B; Yuan, Y

2015-10-01

There is a paucity of large-scale studies evaluating the clinical benefit of the Gaviscon Double Action (DA) alginate-antacid formulation for treating gastroesophageal reflux disease (GERD) symptoms. Randomised double-blind placebo-controlled parallel-group study to evaluate efficacy and safety of Gaviscon DA in reducing heartburn, regurgitation and dyspepsia symptoms in individuals with mild-to-moderate GERD in China. Participants with symptomatic GERD (n = 1107) were randomised to receive Gaviscon DA or placebo (two tablets four times daily) for seven consecutive days. The primary endpoint compared the change in Reflux Disease Questionnaire (RDQ) score for the GERD (heartburn + regurgitation) dimension between Gaviscon DA and placebo. Secondary endpoints compared the change in RDQ scores for individual heartburn, regurgitation and dyspepsia dimensions, overall treatment evaluation (OTE) scores and incidence of adverse events (AEs). Mean RDQ GERD scores: 2.51 for Gaviscon DA and 2.50 for placebo at baseline; 1.25 for Gaviscon DA and 1.46 for placebo post treatment. Gaviscon DA was statistically superior to placebo in reducing GERD and dyspepsia RDQ scores [least-squares mean (LSM) difference: GERD -0.21, P GERD symptoms was observed both in those with non-erosive and those with erosive reflux disease (LSM difference -0.14 [P = 0.038] and -0.29 [P GERD. ClinicalTrials.gov: NCT01869491. © 2015 The Authors. Alimentary Pharmacology & Therapeutics Published by John Wiley & Sons Ltd.

Multicentre randomised placebo-controlled trial of oral anticoagulation with apixaban in systemic sclerosis-related pulmonary arterial hypertension: the SPHInX study protocol.

Science.gov (United States)

Calderone, Alicia; Stevens, Wendy; Prior, David; Nandurkar, Harshal; Gabbay, Eli; Proudman, Susanna M; Williams, Trevor; Celermajer, David; Sahhar, Joanne; Wong, Peter K K; Thakkar, Vivek; Dwyer, Nathan; Wrobel, Jeremy; Chin, Weng; Liew, Danny; Staples, Margaret; Buchbinder, Rachelle; Nikpour, Mandana

2016-12-08

Systemic sclerosis (SSc) is a severe and costly multiorgan autoimmune connective tissue disease characterised by vasculopathy and fibrosis. One of the major causes of SSc-related death is pulmonary arterial hypertension (PAH), which develops in 12-15% of patients with SSc and accounts for 30-40% of deaths. In situ thrombosis in the small calibre peripheral pulmonary vessels resulting from endothelial dysfunction and an imbalance of anticoagulant and prothrombotic mediators has been implicated in the complex pathophysiology of SSc-related PAH (SSc-PAH), with international clinical guidelines recommending the use of anticoagulants for some types of PAH, such as idiopathic PAH. However, anticoagulation has not become part of standard clinical care for patients with SSc-PAH as only observational evidence exists to support its use. Therefore, we present the rationale and methodology of a phase III randomised controlled trial (RCT) to evaluate the efficacy, safety and cost-effectiveness of anticoagulation in SSc-PAH. This Australian multicentre RCT will compare 2.5 mg apixaban with placebo, in parallel treatment groups randomised in a 1:1 ratio, both administered twice daily for 3 years as adjunct therapy to stable oral PAH therapy. The composite primary outcome measure will be the time to death or clinical worsening of PAH. Secondary outcomes will include functional capacity, health-related quality of life measures and adverse events. A cost-effectiveness analysis of anticoagulation versus placebo will also be undertaken. Ethical approval for this RCT has been granted by the Human Research Ethics Committees of all participating centres. An independent data safety monitoring board will review safety and tolerability data for the duration of the trial. The findings of this RCT are to be published in open access journals. ACTRN12614000418673, Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence

Effects of electroacupuncture on stress-related symptoms in medical students: a randomised placebo-controlled study.

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Dias, Marcio; Vellarde, Guillermo Coca; Olej, Beni; Teófilo Salgado, Ana Emília; de Barros Rezende, Ighor

2014-02-01

To assess the effects of electroacupuncture (EA) on relieving stress-related symptoms-sleep disorders, anxiety, depression and burnout-in medical students. Eighty-two students were randomised into an EA treatment group (n=30), a sham TENS group (n=18) and an untreated control group (n=34). EA was applied at a continuous frequency of 2 Hz to the limbs, face, ears and scalp for 20 min once a week, over 6-8 weeks. Sham transcutaneous electrical nerve stimulation (TENS) was performed on similar sites for the same number of times in each session and for the same length of time. Outcome measurements included a comparison of the indices obtained by different self-applied questionnaires before and after treatment. The surveys used were the Mini-Sleep Questionnaire (MSQ), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), the Beck Depression and Anxiety Inventories (BDI and BAI) and the Maslach Burnout Inventory-Student Survey (MBI-SS), in addition to the Quality of Life Questionnaire-abbreviated version (WHOQOL-bref). EA significantly improved scores on the MSQ, PSQI, BDI and the cynicism and academic efficacy (AE) dimensions of the MBI-SS in relation to the control. Sleep quality (MSQ) improved from 36.9 (SD 7.6) to 25.0 (5.7) with EA, 37.6 (6.0) to 32.1 (6.9) with sham TENS, and 36.5 (5.9) to 33.6 (6.7) in the controls (p=0.0000). Compared with the sham TENS group, EA significantly reduced scores on the PSQI. Score improvements in the sham TENS group in relation to control group were significant in the MSQ, BDI and AE. In the EA group, the number of students with better scores after intervention was significantly higher for the MSQ, PSQI, ESS and BAI. This only occurred for the MSQ in the sham TENS group and for the MSQ and ESS in the control group. EA significantly reduced stress-related mental symptoms. The improvement obtained by sham TENS compared with the control group confirmed the presence of a placebo effect resulting from the treatment ritual.

Double-blind, randomised study of the effect of combined treatment with vitamin C and E on albuminuria in Type 2 diabetic patients

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Gaede, P; Poulsen, H E; Parving, H H

2001-01-01

AIMS: Elevated levels of urinary albumin excretion rate (AER) predict high risk for progressing to end-stage renal disease. In streptozotocin-induced diabetes, supplementation with vitamin C or E reduces albuminuria and glomerular hypertrophy. We tested the hypothesis that supplementation of both...... vitamin C and E in pharmacological doses lowers AER in Type 2 diabetic patients with persistent micro/macroalbuminuria. METHODS: Thirty Type 2 diabetic patients with AER 30-300 mg/24 h were included in a double-blind randomised, cross-over trial. Patients received vitamin C (1250 mg) and vitamin E (680 IU......) per day or matching placebo for 4 weeks with a 3-week wash-out period between treatment periods in random order. RESULTS: Combined treatment with vitamin C and E reduced AER by 19% (95% CI 6-34%) (p = 0.04), geometric mean 197 mg/24 h (95% CI 114-341 mg/24 h) vs. 243 mg/24 h (146-404 mg/24 h...

Liraglutide vs insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus (LEAD-5 met+SU): a randomised controlled trial

DEFF Research Database (Denmark)

Russell-Jones, D; Vaag, A; Schmitz, O

2009-01-01

groups at all times. RESULTS: The number of patients analysed as intention to treat were: liraglutide n = 230, placebo n = 114, insulin glargine n = 232. Liraglutide reduced HbA(1c) significantly vs glargine (1.33% vs 1.09%; -0.24% difference, 95% CI 0.08, 0.39; p = 0.0015) and placebo (-1.09% difference......Hg; -4.5 mmHg difference, 95% CI 6.8, -2.2; p = 0.0001) but not vs placebo (p = 0.0791). Rates of hypoglycaemic episodes (major, minor and symptoms only, respectively) were 0.06, 1.2 and 1.0 events/patient/year, respectively, in the liraglutide group (vs 0, 1.3, 1.8 and 0, 1.0, 0.5 with glargine...... produced significant improvement in glycaemic control and bodyweight compared with placebo and insulin glargine. The difference vs insulin glargine in HbA(1c) was within the predefined non-inferiority margin. TRIAL REGISTRATION: ClinicalTrials.gov NCT00331851. FUNDING: The study was funded by Novo Nordisk...

The Efficacy and Safety of Chinese Herbal Medicine Jinlida as Add-On Medication in Type 2 Diabetes Patients Ineffectively Managed by Metformin Monotherapy: A Double-Blind, Randomized, Placebo-Controlled, Multicenter Trial.

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Fengmei Lian

Full Text Available Metformin plays an important role in diabetes treatment. Studies have shown that the combined use of oral hypoglycemic medications is more effective than metformin monotherapy. In this double-blind, randomized, placebo-controlled, multicenter trial, we evaluated whether Jinlida, a Chinese herbal medicine, enhances the glycemic control of metformin in type 2 diabetes patients whose HbA1c was ineffectively controlled with metformin alone.A total of 186 diabetes patients were enrolled in this double-Blind, randomized, placebo-controlled, multicenter trial. Subjects were randomly allocated to receive either Jinlida (9 g or the placebo TID for 12 consecutive weeks. All subjects in both groups also continuously received their metformin without any dose change. During this 12-week period, the HbA1c, FPG, 2 h PG, body weight, BMI were assessed. HOMA insulin resistance (HOMA-IR and β-cell function (HOMA-β were also evaluated.At week 12, compared to the HbA1c level from week 0, the level of the Jinlida group was reduced by 0.92 ± 1.09% and that of the placebo group was reduced by 0.53 ± 0.94%. The 95% CI was 0.69-1.14 for the Jinlida group vs. 0.34-0.72 for the placebo group. There was a very significant HbA1c reduction between the two groups after 12 weeks (p < 0.01. Both FG and 2 h PG levels of the Jinlida group and placebo group were reduced from week 0. There were a very significant FG and 2 h PG level reductions between the two groups after 12 weeks (both p < 0.01. The Jinlida group also showed improved β-cell function with a HOMA-β increase (p < 0.05. No statistical significance was observed in the body weight and BMI changes. No serious adverse events were reported.Jinlida significantly enhanced the hypoglycemic action of metformin when the drug was used alone. This Chinese herbal medicine may have a clinical value as an add-on medication to metformin monotherapy.Chinese Clinical Trial Register ChiCTR-TRC-13003159.

Efficacy and safety of lesogaberan in gastro-oesophageal reflux disease: a randomised controlled trial.

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Shaheen, Nicholas J; Denison, Hans; Björck, Karin; Karlsson, Maria; Silberg, Debra G

2013-09-01

Lesogaberan (AZD3355) is a novel γ-aminobutyric acid B-type receptor agonist designed to treat gastro-oesophageal reflux disease (GERD) by inhibiting transient lower oesophageal sphincter relaxations. A randomised, double-blind, placebo-controlled, multi-centre phase IIb study was performed to assess the efficacy and safety of lesogaberan as an add-on to proton pump inhibitor (PPI) therapy in patients with GERD who are partially responsive to PPI therapy (ClinicalTrials.gov reference: NCT01005251). In total, 661 patients were randomised to receive 4 weeks of placebo or 60, 120, 180 or 240 mg of lesogaberan twice daily, in addition to ongoing PPI therapy. Symptoms were measured using the Reflux Symptom Questionnaire electronic Diary. Response to treatment was defined as having an average of ≥ 3 additional days per week of not more than mild GERD symptoms during treatment compared with baseline. In the primary analysis, 20.9%, 25.6%, 23.5% and 26.2% of patients responded to the 60, 120, 180 and 240 mg twice daily lesogaberan doses, respectively, and 17.9% responded to placebo. The response to the 240 mg twice daily dose was statistically significantly greater than the response to placebo using a one-sided test at the predefined significance level of p < 0.1. However, the absolute increases in the proportions of patients who responded to lesogaberan compared with placebo were low. Lesogaberan was generally well tolerated, although six patients receiving lesogaberan developed reversible elevated alanine transaminase levels. In patients with GERD symptoms partially responsive to PPI therapy, lesogaberan was only marginally superior to placebo in achieving an improvement in symptoms.

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

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Li Li

2010-05-01

Full Text Available Abstract 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 ® 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

Nigella sativa improves glycemic control and ameliorates oxidative stress in patients with type 2 diabetes mellitus: placebo controlled participant blinded clinical trial.

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Huda Kaatabi

Full Text Available Oxidative stress plays an important role in pathogenesis of diabetes mellitus and its complications. Our previous study has shown glucose lowering effect produced by 3 months supplementation of Nigella sativa (NS in combination with oral hypoglycemic drugs among type 2 diabetics. This study explored the long term glucose lowering effect (over one year of NS in patients with type 2 diabetes mellitus on oral hypoglycemic drugs and to study its effect on redox status of such patients.114 type 2 diabetic patients on standard oral hypoglycemic drugs were assigned into 2 groups by convenience. The control group (n = 57 received activated charcoal as placebo and NS group (n = 57 received 2g NS, daily, for one year in addition to their standard medications. Fasting blood glucose (FBG, glycosylated hemoglobin (HbA1c, C- peptide, total antioxidant capacity (TAC, superoxide dismutase (SOD, catalase (CAT, glutathione and thiobarbituric acid reactive substances (TBARS at the baseline, and every 3 months thereafter were determined. Insulin resistance and β-cell activity were calculated using HOMA 2 calculator.Comparison between the two groups showed a significant drop in FBG (from 180 ± 5.75 to 180 ± 5.59 in control Vs from 195 ± 6.57 to 172 ± 5.83 in NS group, HbA1c (from 8.2 ± 0.12 to 8.5 ± 0.14 in control VS from 8.6 ± 0.13 to 8.2 ± 0.14 in NS group, and TBARS (from 48.3 ± 6.89 to 52.9 ± 5.82 in control VS from 54.1 ± 4.64 to 41.9 ± 3.16 in NS group, in addition to a significant elevation in TAC, SOD and glutathione in NS patients compared to controls. In NS group, insulin resistance was significantly lower, while β-cell activity was significantly higher than the baseline values during the whole treatment period.Long term supplementation with Nigella sativa improves glucose homeostasis and enhances antioxidant defense system in type 2 diabetic patients treated with oral hypoglycemic drugs.Clinical Trials Registry-India (CTRI CTRI/2013/06/003781.

Effect of a fermented dietary supplement containing chromium and zinc on metabolic control in patients with type 2 diabetes: a randomized, placebo-controlled, double-blind cross-over study

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Yu-Mi Lee

2016-06-01

Full Text Available Background: For the increasing development of type 2 diabetes dietary habits play an important role. In this regard, dietary supplements are of growing interest to influence the progression of this disease. Objective: The aim of this study was to investigate the effect of a cascade-fermented dietary supplement based on fruits, nuts, and vegetables fortified with chromium and zinc on metabolic control in patients with type 2 diabetes mellitus. Methods: This was a randomized, placebo-controlled, double-blind, intervention study under free-living conditions using a cross-over design. Thirty-six patients with type 2 diabetes mellitus were enrolled and randomized either to receive a cascade-fermented dietary supplement enriched with chromium (100 µg/d and zinc (15 mg/d or a placebo similar in taste but without supplements, over a period of 12 weeks. After a wash-out period of 12 weeks, the patients received the other test product. The main outcome variable was the levels of glycated hemoglobin (HbA1c. Other outcome variables were fasting blood glucose, fructosamine, and lipid parameters. Results: Thirty-one patients completed the study. HbA1c showed no relevant changes during both treatment periods, nor was there a relevant difference between the two treatments (HbA1c: p=0.48. The same results were found for fructosamine and fasting glucose (fructosamine: p=0.9; fasting glucose: p=0.31. In addition, there was no effect on lipid metabolism. Conclusion: This intervention study does not provide evidence that a cascade-fermented plant-based dietary supplement enriched with a combination of chromium and zinc improves glucose metabolism in patients with type 2 diabetes mellitus under free-living conditions.

MRI findings in men on active surveillance for prostate cancer. Does dutasteride make MRI visible lesions less conspicuous? Results from a placebo-controlled, randomised clinical trial

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Giganti, Francesco [University College London Hospital NHS Foundation Trust, Department of Radiology, London (United Kingdom); University College London, Division of Surgery and Interventional Science, London (United Kingdom); Moore, Caroline M.; Robertson, Nicola L.; Emberton, Mark [University College London, Division of Surgery and Interventional Science, London (United Kingdom); University College London Hospital NHS Foundation Trust, Department of Urology, London (United Kingdom); McCartan, Neil [University College London, Division of Surgery and Interventional Science, London (United Kingdom); Jameson, Charles [University College London Hospital NHS Foundation Trust, Department of Pathology, London (United Kingdom); Bott, Simon R.J. [Frimley Park Hospital, Department of Urology, Surrey (United Kingdom); Winkler, Mathias [Imperial College NHS Trust, Department of Urology, Charing Cross Hospital, London (United Kingdom); Gambarota, Giulio [INSERM, Rennes (France); Universite de Rennes 1, Rennes (France); Whitcher, Brandon [Klarismo, London (United Kingdom); Imperial College London, Department of Mathematics, London (United Kingdom); Castro, Ramiro [GlaxoSmithKline, Research and Development, Philadelphia, PA (United States); Allen, Clare; Kirkham, Alex [University College London Hospital NHS Foundation Trust, Department of Radiology, London (United Kingdom)

2017-11-15

To investigate changes in the Apparent Diffusion Coefficient (ADC) using diffusion-weighted imaging (DWI) in men on active surveillance for prostate cancer taking dutasteride 0.5 mg or placebo. We analysed 37 men, randomised to 6 months of daily dutasteride (n = 18) or placebo (n = 19), undergoing 3T multi-parametric Magnetic Resonance Imaging (mpMRI) scans at baseline and 6 months. Images were reviewed blind to treatment allocation and clinical information. Mean ADC of peripheral (PZ) and transition (TZ) zones, and MR-suspicious lesions were compared between groups over 6 months. Conspicuity was defined as the PZ divided by tumour ADC, and its change over 6 months was assessed. A decrease in mean conspicuity in the dutasteride group (but not the controls) was seen over 6 months (1.54 vs 1.38; p = 0.025). Absolute changes in ADC and conspicuity were significantly different between placebo and dutasteride groups at 6 months: (-0.03 vs 0.08, p = 0.033) and (0.11 vs -0.16, p = 0.012), as were percentage changes in the same parameters: (-2.27% vs 8.56% p = 0.048) and (9.25% vs -9.89% p = 0.013). Dutasteride was associated with increased tumour ADC and reduced conspicuity. A lower threshold for triggering biopsy might be considered in men on dutasteride undergoing mpMRI for prostate cancer. (orig.)

MOR103, a human monoclonal antibody to granulocyte–macrophage colony-stimulating factor, in the treatment of patients with moderate rheumatoid arthritis: results of a phase Ib/IIa randomised, double-blind, placebo-controlled, dose-escalation trial

Science.gov (United States)

Behrens, Frank; Tak, Paul P; Østergaard, Mikkel; Stoilov, Rumen; Wiland, Piotr; Huizinga, Thomas W; Berenfus, Vadym Y; Vladeva, Stoyanka; Rech, Juergen; Rubbert-Roth, Andrea; Korkosz, Mariusz; Rekalov, Dmitriy; Zupanets, Igor A; Ejbjerg, Bo J; Geiseler, Jens; Fresenius, Julia; Korolkiewicz, Roman P; Schottelius, Arndt J; Burkhardt, Harald

2015-01-01

Objectives To determine the safety, tolerability and signs of efficacy of MOR103, a human monoclonal antibody to granulocyte–macrophage colony-stimulating factor (GM-CSF), in patients with rheumatoid arthritis (RA). Methods Patients with active, moderate RA were enrolled in a randomised, multicentre, double-blind, placebo-controlled, dose-escalation trial of intravenous MOR103 (0.3, 1.0 or 1.5 mg/kg) once a week for 4 weeks, with follow-up to 16 weeks. The primary outcome was safety. Results Of the 96 randomised and treated subjects, 85 completed the trial (n=27, 24, 22 and 23 for pooled placebo and MOR103 0.3, 1.0 and 1.5 mg/kg, respectively). Treatment emergent adverse events (AEs) in the MOR103 groups were mild or moderate in intensity and generally reported at frequencies similar to those in the placebo group. The most common AE was nasopharyngitis. In two cases, AEs were classified as serious because of hospitalisation: paronychia in a placebo subject and pleurisy in a MOR103 0.3 mg/kg subject. Both patients recovered fully. In exploratory efficacy analyses, subjects in the MOR103 1.0 and 1.5 mg/kg groups showed significant improvements in Disease Activity Score-28 scores and joint counts and significantly higher European League Against Rheumatism response rates than subjects receiving placebo. MOR103 1.0 mg/kg was associated with the largest reductions in disease activity parameters. Conclusions MOR103 was well tolerated and showed preliminary evidence of efficacy in patients with active RA. The data support further investigation of this monoclonal antibody to GM-CSF in RA patients and potentially in those with other immune-mediated inflammatory diseases. Trial registration number NCT01023256 PMID:24534756

Brexanolone (SAGE-547 injection) in post-partum depression: a randomised controlled trial.

Science.gov (United States)

Kanes, Stephen; Colquhoun, Helen; Gunduz-Bruce, Handan; Raines, Shane; Arnold, Ryan; Schacterle, Amy; Doherty, James; Epperson, C Neill; Deligiannidis, Kristina M; Riesenberg, Robert; Hoffmann, Ethan; Rubinow, David; Jonas, Jeffrey; Paul, Steven; Meltzer-Brody, Samantha

2017-07-29

Post-partum depression is a serious mood disorder in women that might be triggered by peripartum fluctuations in reproductive hormones. This phase 2 study investigated brexanolone (USAN; formerly SAGE-547 injection), an intravenous formulation of allopregnanolone, a positive allosteric modulator of γ-aminobutyric acid (GABA A ) receptors, for the treatment of post-partum depression. For this double-blind, randomised, placebo-controlled trial, we enrolled self-referred or physician-referred female inpatients (≤6 months post partum) with severe post-partum depression (Hamilton Rating Scale for Depression [HAM-D] total score ≥26) in four hospitals in the USA. Eligible women were randomly assigned (1:1), via a computer-generated randomisation program, to receive either a single, continuous intravenous dose of brexanolone or placebo for 60 h. Patients and investigators were masked to treatment assignments. The primary efficacy endpoint was the change from baseline in the 17-item HAM-D total score at 60 h, assessed in all randomised patients who started infusion of study drug or placebo and who had a completed baseline HAM-D assessment and at least one post-baseline HAM-D assessment. Patients were followed up until day 30. This trial is registered with ClinicalTrials.gov, number NCT02614547. This trial was done between Dec 15, 2015 (first enrolment), and May 19, 2016 (final visit of the last enrolled patient). 21 women were randomly assigned to the brexanolone (n=10) and placebo (n=11) groups. At 60 h, mean reduction in HAM-D total score from baseline was 21·0 points (SE 2·9) in the brexanolone group compared with 8·8 points (SE 2·8) in the placebo group (difference -12·2, 95% CI -20·77 to -3·67; p=0·0075; effect size 1·2). No deaths, serious adverse events, or discontinuations because of adverse events were reported in either group. Four of ten patients in the brexanolone group had adverse events compared with eight of 11 in the placebo group. The most

Reduced viscosity Barley β-Glucan versus placebo: a randomized controlled trial of the effects on insulin sensitivity for individuals at risk for diabetes mellitus

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Schmelzer Wade

2011-08-01

Full Text Available Abstract Background Prior studies suggest soluble fibers may favorably affect glucose/insulin metabolism. Methods This prospective, randomized, placebo controlled, double blind, parallel group trial evaluated 50 generally healthy subjects without prior diagnosis of diabetes mellitus (44 completers, who were administered beverages containing placebo (control, lower dose (3 g/d, or higher dose (6 g/d reduced viscosity barley β-glucan (BBG extract. Subjects (68% women mean age 56 years, Body Mass Index (BMI 32 kg/m2 and baseline fasting plasma glucose 102 mg/dl were instructed to follow a weight-maintaining Therapeutic Lifestyle Changes (TLC diet and consumed three 11 oz study beverages daily with meals for 12 weeks. The four primary study endpoint measures were plasma glucose and insulin [each fasting and post-Oral Glucose Tolerance Testing (OGTT]. Results Compared to placebo, administration of 3 g/d BBG over 12 weeks significantly reduced glucose incremental Area Under the Curve (iAUC measures during OGTT and 6 g/d BBG over 12 weeks significantly reduced fasting insulin as well as the related homeostasis model assessment of insulin resistance (HOMA-IR. Beverages were generally well tolerated with no serious adverse experiences and no significant differences between groups for adverse experiences. Per protocol instruction, subjects maintained body weight. Conclusions These findings suggest 6 g/d BBG consumed in a beverage over 12 weeks may improve insulin sensitivity among hyperglycemic individuals with no prior diagnosis of diabetes mellitus, and who experience no change in body weight. Trial Registration ClinicalTrials.gov Identifier: NCT01375803.

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

Science.gov (United States)

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.

A randomised placebo-controlled trial of a traditional Chinese herbal formula in the treatment of primary dysmenorrhoea.

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Lan Lan Liang Yeh

Full Text Available BACKGROUND: Most traditional Chinese herbal formulas consist of at least four herbs. Four-Agents-Decoction (Si Wu Tang is a documented eight hundred year old formula containing four herbs and has been widely used to relieve menstrual discomfort in Taiwan. However, no specific effect had been systematically evaluated. We applied Western methodology to assess its effectiveness and safety for primary dysmenorrhoea and to evaluate the compliance and feasibility for a future trial. METHODOLOGY/PRINCIPAL FINDINGS: A randomised, double-blind, placebo-controlled, pilot clinical trial was conducted in an ad hoc clinic setting at a teaching hospital in Taipei, Taiwan. Seventy-eight primary dysmenorrheic young women were enrolled after 326 women with self-reported menstrual discomfort in the Taipei metropolitan area of Taiwan were screened by a questionnaire and subsequently diagnosed by two gynaecologists concurrently with pelvic ultrasonography. A dosage of 15 odorless capsules daily for five days starting from the onset of bleeding or pain was administered. Participants were followed with two to four cycles for an initial washout interval, one to two baseline cycles, three to four treatment cycles, and three follow-up cycles. Study outcome was pain intensity measured by using unmarked horizontal visual analog pain scale in an online daily diary submitted directly by the participants for 5 days starting from the onset of bleeding or pain of each menstrual cycle. Overall-pain was the average pain intensity among days in pain and peak-pain was the maximal single-day pain intensity. At the end of treatment, both the overall-pain and peak-pain decreased in the Four-Agents-Decoction (Si Wu Tang group and increased in the placebo group; however, the differences between the two groups were not statistically significant. The trends persisted to follow-up phase. Statistically significant differences in both peak-pain and overall-pain appeared in the first follow

Intra-articular hyaluronan is without clinical effect in knee osteoarthritis: a multicentre, randomised, placebo-controlled, double-blind study of 337 patients followed for 1 year

DEFF Research Database (Denmark)

Jørgensen, Anette; Stengaard-Pedersen, Kristian; Simonsen, Lars Ole

2010-01-01

Objective To examine the long-term efficacy and safety of five intra-articular injections with hyaluronan in knee osteoarthritis. Methods A multicentre, randomised, placebo-controlled double-blind study of 337 patients fulfilling the American College of Rheumatology (ACR) criteria for knee...... osteoarthritis (clinical and laboratory) and with a Lequesne algofunctional index score (LFI) of 10 or greater. Patients received a hyaluronan product (sodium hyaluronate; Hyalgan) (n= 167) or saline (n= 170) intra-articularly weekly for 5 weeks and were followed up to 1 year. Time to recurrence was the primary...... efficacy parameter. LFI, pain on walking 50 m based on visual analogue scale (VAS pain 50 m), paracetamol consumption, patients' global assessment, Nottingham health profile, joint effusion and number of responders were secondary efficacy parameters. The efficacy parameters were analysed by intention...

Intra-articular hyaluronan is without clinical effect in knee osteoarthritis: a multicentre, randomised, placebo-controlled, double-blind study of 337 patients followed for 1 year

DEFF Research Database (Denmark)

Jørgensen, Anette; Stengaard-Pedersen, Kristian; Simonsen, Ole

2010-01-01

OBJECTIVE: To examine the long-term efficacy and safety of five intra-articular injections with hyaluronan in knee osteoarthritis. METHODS: A multicentre, randomised, placebo-controlled double-blind study of 337 patients fulfilling the American College of Rheumatology (ACR) criteria for knee...... osteoarthritis (clinical and laboratory) and with a Lequesne algofunctional index score (LFI) of 10 or greater. Patients received a hyaluronan product (sodium hyaluronate; Hyalgan) (n=167) or saline (n=170) intra-articularly weekly for 5 weeks and were followed up to 1 year. Time to recurrence was the primary...... the ACR criteria for osteoarthritis of the knee with moderate to severe disease activity (LFI > or = 10), five intra-articular injections of hyaluronan did not improve pain, function, paracetamol consumption or other efficacy parameters 3, 6, 9 and 12 months after the treatment....

Efficacy of a monovalent human-bovine (116E) rotavirus vaccine in Indian infants: a randomised, double-blind, placebo-controlled trial.

Science.gov (United States)

Bhandari, Nita; Rongsen-Chandola, Temsunaro; Bavdekar, Ashish; John, Jacob; Antony, Kalpana; Taneja, Sunita; Goyal, Nidhi; Kawade, Anand; Kang, Gagandeep; Rathore, Sudeep Singh; Juvekar, Sanjay; Muliyil, Jayaprakash; Arya, Alok; Shaikh, Hanif; Abraham, Vinod; Vrati, Sudhanshu; Proschan, Michael; Kohberger, Robert; Thiry, Georges; Glass, Roger; Greenberg, Harry B; Curlin, George; Mohan, Krishna; Harshavardhan, G V J A; Prasad, Sai; Rao, T S; Boslego, John; Bhan, Maharaj Kishan

2014-06-21

Rotavirus is the most common cause of severe dehydrating gastroenteritis in developing countries. Safe, effective, and affordable rotavirus vaccines are needed in these countries. We aimed to assess the efficacy and tolerability of a monovalent human-bovine rotavirus vaccine for severe rotavirus gastroenteritis in low-resource urban and rural settings in India. We did a randomised double-blind, placebo-controlled, multicentre trial at three sites in Delhi (urban), Pune (rural), and Vellore (urban and rural) between March 11, 2011, and Nov 5, 2012. Infants aged 6-7 weeks were randomly assigned (2:1), via a central interactive voice or web response system with a block size of 12, to receive either three doses of oral human-bovine natural reassortant vaccine (116E) or placebo at ages 6-7 weeks, 10 weeks, and 14 weeks. Infants' families, study investigators, paediatricians in referral hospitals, laboratory staff, and committee members were all masked to treatment allocation. The primary outcome was incidence of severe rotavirus gastroenteritis (≥11 on the Vesikari scale). Efficacy outcomes and adverse events were ascertained through active surveillance. Analysis was by intention to treat and per protocol. The trial is registered with Clinical Trial Registry-India (CTRI/2010/091/000102) and ClinicalTrials.gov (NCT01305109). 4532 infants were assigned to receive the 116E vaccine and 2267 to receive placebo, of whom 4354 (96%) and 2187 (96%) infants, respectively, were included in the primary per-protocol efficacy analysis. 71 events of severe rotavirus gastroenteritis were reported in 4752 person-years in infants in the vaccine group compared with 76 events in 2360 person-years in those in the placebo group; vaccine efficacy against severe rotavirus gastroenteritis was 53·6% (95% CI 35·0-66·9; p=0·0013) and 56·4% (36·6-70·1; protavirus gastroenteritis episode was 55 (95% CI 37-97). The incidence of severe rotavirus gastroenteritis per 100 person-years was 1·5

Published and not fully published double-blind, randomised, controlled trials with oral naratriptan in the treatment of migraine

DEFF Research Database (Denmark)

Tfelt-Hansen, Peer Carsten

2011-01-01

Naratriptan 2.5 mg is now an over-the-counter drug in Germany. This should increase the interest in drug. The GSK Trial Register was searched for published and unpublished double-blind, randomised, controlled trials (RCTs) concerning the use of naratriptan in migraine. Only 7 of 17 RCTs are publi......Naratriptan 2.5 mg is now an over-the-counter drug in Germany. This should increase the interest in drug. The GSK Trial Register was searched for published and unpublished double-blind, randomised, controlled trials (RCTs) concerning the use of naratriptan in migraine. Only 7 of 17 RCTs...... are published in full. Naratriptan 2.5 mg is superior to placebo for acute migraine treatment in 6 RCTs, but inferior to sumatriptan 100 mg and rizatriptan 10 mg in one RCT each. This dose of naratriptan has no more adverse events than placebo. Naratriptan 1 mg b.i.d. has some effect in the short...

Treatment of antipsychotic-associated obesity with a GLP-1 receptor agonist—protocol for an investigator-initiated prospective, randomised, placebo-controlled, double-blinded intervention study: the TAO study protocol

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Ishøy, Pelle L; Knop, Filip K; Broberg, Brian V; Baandrup, Lone; Fagerlund, Birgitte; Jørgensen, Niklas R; Andersen, Ulrik B; Rostrup, Egill; Glenthøj, Birte Y; Ebdrup, Bjørn H

2014-01-01

Introduction Antipsychotic medication is widely associated with dysmetabolism including obesity and type 2 diabetes, cardiovascular-related diseases and early death. Obesity is considered the single most important risk factor for cardiovascular morbidity and mortality. Interventions against antipsychotic-associated obesity are limited and insufficient. Glucagon-like peptide-1 (GLP-1) receptor agonists are approved for the treatment of type 2 diabetes, but their bodyweight-lowering effects have also been recognised in patients with non-diabetes. The primary endpoint of this trial is weight loss after 3 months of treatment with a GLP-1 receptor agonist (exenatide once weekly) in patients with non-diabetic schizophrenia with antipsychotic-associated obesity. Secondary endpoints include physiological and metabolic measurements, various psychopathological and cognitive measures, and structural and functional brain MRI. Methods and analysis 40 obese patients with schizophrenia or schizoaffective disorder treated with antipsychotic drugs will be randomised to subcutaneous injection of exenatide once weekly (2 mg) or placebo for 3 months, adjunctive to their antipsychotic treatment. Ethics and dissemination The trial has been approved by the Danish Health and Medicines Authority, the National Committee on Health Research Ethics and the Danish Data Protection Agency. Trial participation presupposes theoral and written patient informed consent. An external, independent monitoring committee (Good Clinical Practice Unit at Copenhagen University Hospital) will monitor the study according to the GCP Guidelines. Trial data, including positive, negative and inconclusive results, will be presented at national and international scientific meetings and conferences. Papers will be submitted to peer-reviewed journals. Trial registration ClinicalTrials.gov identifier: NCT01794429; National Committee on Health Research Ethics project number: 36378; EudraCT nr: 2012-005404-17; The

Randomised trial of neonatal hypoglycaemia prevention with oral dextrose gel (hPOD): study protocol.

Science.gov (United States)

Harding, Jane E; Hegarty, Joanne E; Crowther, Caroline A; Edlin, Richard; Gamble, Greg; Alsweiler, Jane M

2015-09-16

Neonatal hypoglycaemia is common, affecting up to 15% of newborn babies and 50% of those with risk factors (preterm, infant of a diabetic, high or low birthweight). Hypoglycaemia can cause brain damage and death, and babies born at risk have an increased risk of developmental delay in later life. Treatment of hypoglycaemia usually involves additional feeding, often with infant formula, and admission to Neonatal Intensive Care for intravenous dextrose. This can be costly and inhibit the establishment of breast feeding. Prevention of neonatal hypoglycaemia would be desirable, but there are currently no strategies, beyond early feeding, for prevention of neonatal hypoglycaemia. Buccal dextrose gel is safe and effective in treatment of hypoglycaemia. The aim of this trial is to determine whether 40% dextrose gel given to babies at risk prevents neonatal hypoglycaemia and hence reduces admission to Neonatal Intensive Care. Randomised, multicentre, placebo controlled trial. Babies at risk of hypoglycaemia (preterm, infant of a diabetic, small or large), less than 1 h old, with no apparent indication for Neonatal Intensive Care Unit admission and mother intends to breastfeed. Trial entry & randomisation: Eligible babies of consenting parents will be allocated by online randomisation to the dextrose gel group or placebo group, using a study number and corresponding trial intervention pack. Babies will receive a single dose of 0.5 ml/kg study gel at 1 h after birth; either 40% dextrose gel (200 mg/kg) or 2% hydroxymethylcellulose placebo. Gel will be massaged into the buccal mucosal and followed by a breast feed. Primary study outcome: Admission to Neonatal Intensive Care. 2,129 babies are required to detect a decrease in admission to Neonatal Intensive Care from 10-6% (two-sided alpha 0.05, 90% power, 5% drop-out rate). This study will investigate whether admission to Neonatal Intensive Care can be prevented by prophylactic oral dextrose gel; a simple, cheap and painless

RESPIRE 2: a phase III placebo-controlled randomised trial of ciprofloxacin dry powder for inhalation in non-cystic fibrosis bronchiectasis.

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Aksamit, Timothy; De Soyza, Anthony; Bandel, Tiemo-Joerg; Criollo, Margarita; Elborn, J Stuart; Operschall, Elisabeth; Polverino, Eva; Roth, Katrin; Winthrop, Kevin L; Wilson, Robert

2018-01-01

We evaluated the efficacy and safety of ciprofloxacin dry powder for inhalation (DPI) in patients with non-cystic fibrosis bronchiectasis, two or more exacerbations in the previous year and predefined sputum bacteria.Patients were randomised 2:1 to twice-daily ciprofloxacin DPI 32.5 mg or placebo in 14- or 28-day on/off treatment cycles for 48 weeks. Primary end-points were time to first exacerbation and frequency of exacerbations. Enrolling countries and α level split (0.049 and 0.001 for 14- and 28-day cycles, respectively) differed from RESPIRE 1.Patients were randomised to ciprofloxacin DPI (14 days on/off (n=176) or 28 days on/off (n=171)) or placebo (14 days on/off (n=88) or 28 days on/off (n=86)). The exacerbation rate was low across treatment arms (mean±sd 0.6±0.9). Active treatment showed trends to prolonged time to first exacerbation (ciprofloxacin DPI 14 days on/off: hazard ratio 0.87, 95.1% CI 0.62-1.21; p=0.3965; ciprofloxacin DPI 28 days on/off: hazard ratio 0.71, 99.9% CI 0.39-1.27; p=0.0511) and reduced frequency of exacerbations (ciprofloxacin DPI 14 days on/off: incidence rate ratio 0.83, 95.1% CI 0.59-1.17; p=0.2862; ciprofloxacin DPI 28 days on/off: incidence rate ratio 0.55, 99.9% CI 0.30-1.02; p=0.0014), although neither achieved statistical significance. Ciprofloxacin DPI was well tolerated.Trends towards clinical benefit were seen with ciprofloxacin DPI, but primary end-points were not met. Copyright ©ERS 2018.

Efficacy of the Hydroalcoholic Extract of Tribulus terrestris on the Serum Glucose and Lipid Profile of Women With Diabetes Mellitus: A Double-Blind Randomized Placebo-Controlled Clinical Trial.

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Samani, Nasrin Babadaei; Jokar, Azam; Soveid, Mahmood; Heydari, Mojtaba; Mosavat, Seyed Hamdollah

2016-10-01

Considering traditional use of Tribulus terrestris in diabetes and proven antihyperglycemic and antihyperlipidemic effects of T terrestris in animal studies, we aimed to evaluate the efficacy of the hydroalcoholic extract of T terrestris on the serum glucose and lipid profile of women with non-insulin-dependent diabetes mellitus. Ninety-eight women with diabetes mellitus type 2 were randomly allocated to receive the T terrestris (1000 mg/d) or placebo for 3 months. The patients were evaluated in terms of the fasting blood glucose, 2-hour postprandial glucose, glycosylated hemoglobin, and lipid profile. Tribulus terrestris showed a significant blood glucose-lowering effect in diabetic women compared to placebo (P terrestris group was significantly reduced compared with placebo, while no significant effect was observed in the triglyceride and high-density lipoprotein levels. The study showed preliminary promising hypoglycemic effect of T terrestris in women with diabetes mellitus type 2. © The Author(s) 2016.

The effects of vitamin D supplementation on wound healing and metabolic status in patients with diabetic foot ulcer: A randomized, double-blind, placebo-controlled trial.

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Razzaghi, Reza; Pourbagheri, Hamideh; Momen-Heravi, Mansooreh; Bahmani, Fereshteh; Shadi, Jafar; Soleimani, Zahra; Asemi, Zatollah

2017-04-01

This study was conducted to evaluate the effects of vitamin D supplementation on wound healing and metabolic status in patients with diabetic foot ulcer (DFU). This randomized, double-blind, placebo-controlled trial was performed among 60 patients with grade 3 DFU according to "Wagner-Meggitt's" criteria. Participants were randomly divided into two groups (each 30 participants) and received either 50,000IU vitamin D supplements every 2weeks for 12weeks (group A) or placebo (group B). Fasting blood samples were taken at study baseline and after 12-week intervention to determine related markers. After 12weeks of intervention, compared with the placebo, vitamin D supplementation resulted in a significant reduction in ulcer length (-2.1±1.1 vs. -1.1±1.1cm, P=0.001), width (-2.0±1.2 vs. -1.1±1.0cm, P=0.02) and depth (-1.0±0.5 vs. -0.5±0.5cm, Phealing due to its effect on improved glycemic control. Copyright © 2016 Elsevier Inc. All rights reserved.

Long-term effect of inhaled budesonide in mild and moderate chronic obstructive pulmonary disease: a randomised controlled trial

DEFF Research Database (Denmark)

Vestbo, Jørgen; Sørensen, T; Lange, Peter

1999-01-01

BACKGROUND: Little is known about the long-term efficacy of inhaled corticosteroids in chronic obstructive pulmonary disease (COPD). We investigated the efficacy of inhaled budesonide on decline in lung function and respiratory symptoms in a 3-year placebo-controlled study of patients with COPD....... METHODS: We used a parallel-group, randomised, double-blind, placebo-controlled design in a singlecentre study, nested in a continuing epidemiological survey (the Copenhagen City Heart Study). Inclusion criteria were as follows: no asthma; a ratio of forced expiratory volume in 1 s (FEV1) and vital...... capacity of 0.7 or less; FEV1 which showed no response (budesonide, 800 microg plus 400 microg daily for 6 months followed by 400 microg twice daily for 30 months, or placebo...

Seladelpar (MBX-8025), a selective PPAR-δ agonist, in patients with primary biliary cholangitis with an inadequate response to ursodeoxycholic acid: a double-blind, randomised, placebo-controlled, phase 2, proof-of-concept study.

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Jones, David; Boudes, Pol F; Swain, Mark G; Bowlus, Christopher L; Galambos, Michael R; Bacon, Bruce R; Doerffel, Yvonne; Gitlin, Norman; Gordon, Stuart C; Odin, Joseph A; Sheridan, David; Wörns, Markus-Alexander; Clark, Virginia; Corless, Linsey; Hartmann, Heinz; Jonas, Mark E; Kremer, Andreas E; Mells, George F; Buggisch, Peter; Freilich, Bradley L; Levy, Cynthia; Vierling, John M; Bernstein, David E; Hartleb, Marek; Janczewska, Ewa; Rochling, Fedja; Shah, Hemant; Shiffman, Mitchell L; Smith, John H; Choi, Yun-Jung; Steinberg, Alexandra; Varga, Monika; Chera, Harinder; Martin, Robert; McWherter, Charles A; Hirschfield, Gideon M

2017-10-01

Many patients with primary biliary cholangitis have an inadequate response to first-line therapy with ursodeoxycholic acid. Seladelpar is a potent, selective agonist for the peroxisome proliferator-activated receptor-delta (PPAR-δ), which is implicated in bile acid homoeostasis. This first-in-class study evaluated the anti-cholestatic effects and safety of seladelpar in patients with an inadequate response to ursodeoxycholic acid. The study was a 12-week, double-blind, placebo-controlled, phase 2 trial of patients with alkaline phosphatase of at least 1·67 times the upper limit of normal (ULN) despite treatment with ursodeoxycholic acid. Patients, recruited at 29 sites in North America and Europe, were randomly assigned to placebo, seladelpar 50 mg/day, or seladelpar 200 mg/day while ursodeoxycholic acid was continued. Randomisation was done centrally (1:1:1) by a computerised system using an interactive voice-web response system with a block size of three. Randomisation was stratified by region (North America and Europe). The primary outcome was the percentage change from baseline in alkaline phosphatase over 12 weeks, analysed in the modified intention-to-treat (ITT) population (any randomised patient who received at least one dose of medication and had at least one post-baseline alkaline phosphatase evaluation). This study is registered with ClinicalTrials.gov (NCT02609048) and the EU Clinical Trials Registry (EudraCT2015-002698-39). Between Nov 4, 2015, and May 26, 2016, 70 patients were screened at 29 sites in North America and Europe. During recruitment, three patients treated with seladelpar developed fully reversible, asymptomatic grade 3 alanine aminotransferase increases (one on 50 mg, two on 200 mg), ranging from just over five to 20 times the ULN; as a result, the study was terminated after 41 patients were randomly assigned. The modified ITT population consisted of 12 patients in the placebo group, 13 in the seladelpar 50 mg group, and 10 in the

Influence of GABA and GABA-producing Lactobacillus brevis DPC 6108 on the development of diabetes in a streptozotocin rat model.

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Marques, T M; Patterson, E; Wall, R; O'Sullivan, O; Fitzgerald, G F; Cotter, P D; Dinan, T G; Cryan, J F; Ross, R P; Stanton, C

2016-06-01

The aim of this study was to investigate if dietary administration of γ-aminobutyric acid (GABA)-producing Lactobacillus brevis DPC 6108 and pure GABA exert protective effects against the development of diabetes in streptozotocin (STZ)-induced diabetic Sprague Dawley rats. In a first experiment, healthy rats were divided in 3 groups (n=10/group) receiving placebo, 2.6 mg/kg body weight (bw) pure GABA or L. brevis DPC 6108 (~10(9)microorganisms). In a second experiment, rats (n=15/group) were randomised to five groups and four of these received an injection of STZ to induce type 1 diabetes. Diabetic and non-diabetic controls received placebo [4% (w/v) yeast extract in dH2O], while the other three diabetic groups received one of the following dietary supplements: 2.6 mg/kg bw GABA (low GABA), 200 mg/kg bw GABA (high GABA) or ~10(9) L. brevis DPC 6108. L. brevis DPC 6108 supplementation was associated with increased serum insulin levels (Pfood intake. Insulin was decreased (P0.05), compared with non-diabetic controls while all other diabetic groups displayed reduced diversity (P<0.05). L. brevis DPC 6108 attenuated hyperglycaemia induced by diabetes but additional studies are needed to understand the mechanisms involved in this reduction.

Structured self-management education maintained over two years in insufficiently controlled type 2 diabetes patients: the ERMIES randomised trial in Reunion Island

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Debussche Xavier

2012-08-01

Full Text Available Abstract Background Self-management education programs can reduce the complications and mortality in type 2 diabetes. The need to structure these programs for outpatient and community care with a vision for long-term maintenance has been recognised. In Reunion Island, an area affected by epidemiological and nutritional transition, diabetes affects 18% of the adult population over 30 years, with major social disparities, poor glycaemic control and frequent cardiovascular complications. Methods/Design ERMIES is a randomised controlled trial designed to test the efficacy of a long-term (2 years structured group self management educational intervention in improving blood glucose in non-recent, insufficiently controlled diabetes. After an initial structured educational cycle carried out blind for the intervention arm, patients will be randomised in two parallel group arms of 120 subjects: structured on-going group with educational intervention maintained over two years, versus only initial education. Education sessions are organised through a regional diabetes management network, and performed by trained registered nurses at close quarters. The educational approach is theoretically based (socio-constructivism, social contextualisation, empowerment, action planning and reproducible, thanks to curricula and handouts for educators and learners. The subjects will be recruited from five hospital outpatient settings all over Reunion Island. The main eligibility criteria include: age ≥18 years, type 2 diabetes treated for more than one year, HbA1c ≥ 7.5% for ≥3 months, without any severe evolving complication (ischaemic or proliferative retinopathy, severe renal insufficiency, coronaropathy or evolving foot lesion, and absence of any major physical or cognitive handicap. The primary outcome measure is HbA1c evolution between inclusion and 2 years. The secondary outcome measures include anthropometric indicators, blood pressure, lipids

The effect of enriched chicory inulin on liver enzymes, calcium homeostasis and hematological parameters in patients with type 2 diabetes mellitus: A randomized placebo-controlled trial.

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Farhangi, Mahdieh Abbasalizad; Javid, Ahmad Zare; Dehghan, Parvin

2016-08-01

Type 2 diabetic mellitus (T2DM) as one of the main causes of morbidity and mortality is associated with immune system disturbances and metabolic abnormalities. In the current study we aimed to evaluate the effects of enriched chicory inulin supplementation on liver enzymes, serum calcium and phosphorous concentrations and hematological parameters in patients with T2DM. Forty-six diabetic females patients were randomly allocated into intervention (n=27) and control (n=22) groups. Subjects in the intervention group received a daily dose of 10g of chicory and subjects in control group received a placebo for two months. Anthropometric variables, glucose homeostasis, hematological parameters and metabolic indices including serum alanine aminotransfersae (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), calcium and phosphorous as well as creatinine concentrations, glomerular filtration rate (GFR) and blood pressure were assessed at the beginning and end of the trial. Significant reductions in fasting serum glucose (FSG), Hb A1C, AST and ALP concentrations were observed in chicory-treated group. Systolic and diastolic blood pressures were also reduced in chicory-treated group. Serum calcium significantly increased after chicory supplementation but no change in placebo treated group has been occurred (P=0.014). Supplementation with enriched chicory for two months significantly reduced hematocrit and mean corpuscular volume (MCV) values (Pliver function tests, blood pressure and reduction in hematologic risk factors of diabetes in female patients with T2DM. Further studies in both genders are needed to generalize these findings to total population. Copyright © 2016 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

A complex behavioural change intervention to reduce the risk of diabetes and prediabetes in the pre-conception period in Malaysia: study protocol for a randomised controlled trial.

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Skau, Jutta K H; Nordin, Awatef Binti Amer; Cheah, Julius C H; Ali, Roslinah; Zainal, Ramli; Aris, Tahir; Ali, Zainudin Mohd; Matzen, Priya; Biesma, Regien; Aagaard-Hansen, Jens; Hanson, Mark A; Norris, Shane A

2016-04-27

Over the past two decades, the population of Malaysia has grown rapidly and the prevalence of diabetes mellitus in Malaysia has dramatically increased, along with the frequency of obesity, hyperlipidaemia and hypertension. Early-life influences play an important role in the development of non-communicable diseases. Indeed, maternal lifestyle and conditions such as gestational diabetes mellitus or obesity can affect the risk of diabetes in the next generation. Lifestyle changes can help to prevent the development of type 2 diabetes mellitus. This is a protocol for an unblinded, community-based, randomised controlled trial in two arms to evaluate the efficacy of a complex behavioural change intervention, combining motivational interviewing provided by a community health promoter and access to a habit formation mobile application, among young Malaysian women and their spouses prior to pregnancy. Eligible subjects will be Malaysian women in the age group 20 to 39 years, who are nulliparous, not diagnosed with diabetes and own a smartphone. With an alpha-value of 0.05, a statistical power of 90 %, 264 subjects will need to complete the study. Subjects with their spouses will be randomised to either the intervention or the control arm for an 8-month period. The primary endpoint is change in waist circumference from baseline to end of intervention period and secondary endpoints are changes in anthropometric parameters, biochemical parameters, change in health literacy level, dietary habits, physical activity and stress level. Primary endpoint and the continuous secondary endpoints will be analysed in a linear regression model, whereas secondary endpoints on an ordinal scale will be analysed by using the chi-squared test. A multivariate linear model for the primary endpoint will be undertaken to account for potential confounders. This study has been approved by the Medical Research and Ethics Committee of the Ministry of Health Malaysia (protocol number: NMRR-14

A blinded randomised placebo-controlled trial investigating the efficacy of morphine analgesia for procedural pain in infants: Trial protocol.

Science.gov (United States)

Slater, Rebeccah; Hartley, Caroline; Moultrie, Fiona; Adams, Eleri; Juszczak, Ed; Rogers, Richard; Norman, Jane E; Patel, Chetan; Stanbury, Kayleigh; Hoskin, Amy; Green, Gabrielle

2016-11-15

Infant pain has both immediate and long-term negative consequences, yet in clinical practice it is often undertreated. To date, few pain-relieving drugs have been tested in infants. Morphine is a potent analgesic that provides effective pain relief in adults, but there is inconclusive evidence for its effectiveness in infants. The purpose of this study is to establish whether oral morphine provides effective analgesia for procedural pain in infants. A blinded, placebo-controlled, parallel-group randomized, phase II, clinical trial will be undertaken to determine whether morphine sulphate administered orally prior to clinically-required retinopathy of prematurity (ROP) screening and heel lancing provides effective analgesia. 
156 infants between 34 and 42 weeks' gestational age who require a clinical heel lance and ROP screening on the same test occasion will be included in the trial. Infants will be randomised to receive either a single dose of morphine sulphate (100 μg/kg) or placebo. Each infant will be monitored for 48 hours and safety data will be collected during the 24 hours following drug administration. The primary outcome will be the Premature Infant Pain Profile-revised (PIPP-R) score 30 seconds after ROP screening. The co-primary outcome will be the magnitude of nociceptive-specific brain activity evoked by a clinically-required heel lance. Infant clinical stability will be assessed by comparing the number of episodes of bradycardia, tachycardia, desaturation and apnoea, and changes in respiratory support requirements in the 24-hour periods before and after the clinical intervention. In addition, drug safety will be assessed by considering the occurrence of apnoeic and hypotensive episodes requiring intervention in the 24-hour period following drug administration. This study has been published as an Accepted Protocol Summary by The Lancet .

Pharmacokinetics, Safety and Cognitive Function Profile of Rupatadine 10, 20 and 40 mg in Healthy Japanese Subjects: A Randomised Placebo-Controlled Trial.

Directory of Open Access Journals (Sweden)

Jörg Täubel

Full Text Available Rupatadine is a marketed second generation antihistamine, with anti-PAF activity, indicated for symptomatic treatment of allergic rhinitis and urticaria. This study was conducted to evaluate the pharmacokinetics (PK, pharmacodynamics (PD, safety and tolerability of rupatadine in healthy Japanese subjects after single and multiple oral doses.In this randomised, double-blind, placebo-controlled study, 27 male and female healthy Japanese subjects were administered single and multiple escalating rupatadine dose of 10, 20 and 40 mg or placebo. Blood samples were collected at different time points for PK measurements and subjects were assessed for safety and tolerability. The effect of rupatadine on cognitive functioning was evaluated by means of computerized cognitive tests: rapid visual information processing (RVP, reaction time (RT, spatial working memory (SWM and visual analogue scales (VAS.Exposure to rupatadine as measured by Cmax and AUC was found to increase in a dose dependent manner over the dose range of 10-40 mg for both single and multiple dose administration. The safety assessments showed that all treatment related side effects were of mild intensity and there were no serious adverse events (SAEs or withdrawals due to treatment-emergent adverse events (TEAEs in this study. The therapeutic dose of rupatadine did not show any CNS impairment in any of the cognitive tests.This study demonstrated that rupatadine is safe and well tolerated by Japanese healthy subjects. The PK-PD profile confirmed previous experience with rupatadine.

Effect of clinical response to active drugs and placebo on antipsychotics and mood stabilizers relative efficacy for bipolar depression and mania: A meta-regression analysis.

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Bartoli, Francesco; Clerici, Massimo; Di Brita, Carmen; Riboldi, Ilaria; Crocamo, Cristina; Carrà, Giuseppe

2018-04-01

Randomised placebo-controlled trials investigating treatments for bipolar disorder have been hampered by wide variations of active drugs and placebo clinical response rates. It is important to estimate whether the active drug or placebo response has a greater influence in determining the relative efficacy of drugs for psychosis (antipsychotics) and relapse prevention (mood stabilisers) for bipolar depression and mania. We identified 53 randomised, placebo-controlled trials assessing antipsychotic or mood stabiliser monotherapy ('active drugs') for bipolar depression or mania. We carried out random-effects meta-regressions, estimating the influence of active drugs and placebo response rates on treatment relative efficacy. Meta-regressions showed that treatment relative efficacy for bipolar mania was influenced by the magnitude of clinical response to active drugs ( p=0.002), but not to placebo ( p=0.60). On the other hand, treatment relative efficacy for bipolar depression was influenced by response to placebo ( p=0.047), but not to active drugs ( p=0.98). Despite several limitations, our unexpected findings showed that antipsychotics / mood stabilisers relative efficacy for bipolar depression seems unrelated to active drugs response rates, depending only on clinical response to placebo. Future research should explore strategies to reduce placebo-related issues in randomised, placebo-controlled trials for bipolar depression.

Randomised controlled trial of mesalazine in IBS.

Science.gov (United States)

Barbara, Giovanni; Cremon, Cesare; Annese, Vito; Basilisco, Guido; Bazzoli, Franco; Bellini, Massimo; Benedetti, Antonio; Benini, Luigi; Bossa, Fabrizio; Buldrini, Paola; Cicala, Michele; Cuomo, Rosario; Germanà, Bastianello; Molteni, Paola; Neri, Matteo; Rodi, Marcello; Saggioro, Alfredo; Scribano, Maria Lia; Vecchi, Maurizio; Zoli, Giorgio; Corinaldesi, Roberto; Stanghellini, Vincenzo

2016-01-01

Low-grade intestinal inflammation plays a role in the pathophysiology of IBS. In this trial, we aimed at evaluating the efficacy and safety of mesalazine in patients with IBS. We conducted a phase 3, multicentre, tertiary setting, randomised, double-blind, placebo-controlled trial in patients with Rome III confirmed IBS. Patients were randomly assigned to either mesalazine, 800 mg, or placebo, three times daily for 12 weeks, and were followed for additional 12 weeks. The primary efficacy endpoint was satisfactory relief of abdominal pain/discomfort for at least half of the weeks of the treatment period. The key secondary endpoint was satisfactory relief of overall IBS symptoms. Supportive analyses were also performed classifying as responders patients with a percentage of affirmative answers of at least 75% or >75% of time. A total of 185 patients with IBS were enrolled from 21 centres. For the primary endpoint, the responder patients were 68.6% in the mesalazine group versus 67.4% in the placebo group (p=0.870; 95% CI -12.8 to 15.1). In explorative analyses, with the 75% rule or >75% rule, the percentage of responders was greater in the mesalazine group with a difference over placebo of 11.6% (p=0.115; 95% CI -2.7% to 26.0%) and 5.9% (p=0.404; 95% CI -7.8% to 19.4%), respectively, although these differences were not significant. For the key secondary endpoint, overall symptoms improved in the mesalazine group and reached a significant difference of 15.1% versus placebo (p=0.032; 95% CI 1.5% to 28.7%) with the >75% rule. Mesalazine treatment was not superior than placebo on the study primary endpoint. However, a subgroup of patients with IBS showed a sustained therapy response and benefits from a mesalazine therapy. ClincialTrials.gov number, NCT00626288. 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/

Effects of Silybum marianum (L.) Gaertn. (silymarin) extract supplementation on antioxidant status and hs-CRP in patients with type 2 diabetes mellitus: a randomized, triple-blind, placebo-controlled clinical trial.

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Ebrahimpour Koujan, Soraiya; Gargari, Bahram Pourghassem; Mobasseri, Majid; Valizadeh, Hadi; Asghari-Jafarabadi, Mohammad

2015-02-15

Diabetes is a serious metabolic disorder and oxidative stress and inflammation contribute to its pathogenesis and complications. Since Silybum marianum (L.) Gaertn. (silymarin) extract is an antioxidant with anti-inflammatory properties, this randomized clinical trial was conducted to evaluate the effects of silymarin supplementation on oxidative stress indices and hs-CRP in type 2 diabetes mellitus patients. For the present paralleled, randomized, triple-blinded, placebo-controlled clinical trial, 40 type 2 diabetes patients aged 25-50 yr old and on stable medication were recruited from the Iranian Diabetes Society and endocrinology clinics in East Azarbayjan (Tabriz, Iran) and randomly assigned into two groups. Patients in the silymarin treatment group received 140 mg, thrice daily of dried extracts of Silybum marianum (n = 20) and those in the placebo group (n = 20) received identical placebos for 45 days. Data pertaining to height, weight, waist circumference and BMI, as well as food consumption, were collected at base line and at the conclusion of the study. Fasting blood samples were obtained and antioxidant indices and hs-CRP were assessed at baseline, as well as at the end of the trial. All 40 patients completed the study and did not report any adverse effects or symptoms with the silymarin supplementation. Silymarin supplementation significantly increased superoxide dismutase (SOD), glutathione peroxidase (GPX) activity and total antioxidant capacity (TAC) compared to patients taking the placebo, by 12.85%, 30.32% and 8.43%, respectively (p concentration significantly decreased by 12.01% (p antioxidant indices (SOD, GPX and TAC) and decrease hs-CRP levels in T2DM patients. Copyright © 2015. Published by Elsevier GmbH.

Randomized, double-blind, placebo-controlled, clinical study on the effect of Diabetinol® on glycemic control of subjects with impaired fasting glucose

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Evans M

2015-06-01

Full Text Available Malkanthi Evans,1 William V Judy,2 Dale Wilson,3 John A Rumberger,4 Najla Guthrie,1 1KGK Synergize Inc., London, ON, Canada; 2SIBR Research Inc., Bradenton, FL, USA; 3London Health Sciences Center, University of Western Ontario, London, ON, Canada; 4Princeton Longevity Center, Princeton, NJ, USA Background: This study investigated the efficacy of Diabetinol® in people with diabetes on medication but not meeting the American Association of Clinical Endocrinologists and American Diabetes Association glycemic, blood pressure, and lipid targets. Subjects and methods: Fifty subjects, aged 18–75 years, with fasting blood glucose ≤15.4 mmol/L, hemoglobin A1c levels ≤12%, and a body mass index between 25 and 40 kg/m2, were enrolled in a 24-week, randomized, double-blind, placebo-controlled, parallel study. Diabetinol® or placebo was administered as 2×525 mg capsules/day. Results: In the Diabetinol® group, 14.3% versus 0% in the placebo group, 33.3% versus 15.4% in placebo, 20.0% versus 12.5% in placebo, and 83.3% versus 60% in placebo achieved the American Association of Clinical Endocrinologists and American Diabetes Association targets for hemoglobin A1c, low-density lipoprotein, total cholesterol, and systolic blood pressure, respectively. There was no difference in the maximum concentration (Cmax of serum glucose or area under the curve (AUC0–240 minutes. The time to Cmax was longer for participants on Diabetinol® than placebo group at week 12 (P=0.01. Fasting blood glucose increased from baseline to week 24 in both groups; however, this increase was 14.3 mg/dL lower in the Diabetinol® group versus placebo. The Diabetinol® group showed an increase of 5.53 mg/dL in fasting insulin at week 12 (P=0.09 and 3.2 mg/dL at week 24 (P=0.41 over and above the placebo group. A decrease of 1.5% in total cholesterol, 5.8% in low-density lipoprotein, and a 1.6% increase in high-density lipoprotein concentrations were seen in the Diabetinol® group

Resveratrol as Add-on Therapy in Subjects With Well-Controlled Type 2 Diabetes: A Randomized Controlled Trial.

NARCIS (Netherlands)

Timmers, S.; Ligt, M. de; Phielix, E.; Weijer, T. van de; Hansen, J.; Moonen-Kornips, E.; Schaart, G.; Kunz, I.; Hesselink, M.K.; Schrauwen-Hinderling, V.B.; Schrauwen, P.

2016-01-01

OBJECTIVE: To determine whether resveratrol supplementation can improve insulin sensitivity and promote overall metabolic health on top of standard diabetes care. RESEARCH DESIGN AND METHODS: Seventeen subjects with well-controlled type 2 diabetes (T2D) were treated with placebo and 150 mg/day

Bifidobacterium breve BBG-001 in very preterm infants: a randomised controlled phase 3 trial.

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Costeloe, Kate; Hardy, Pollyanna; Juszczak, Edmund; Wilks, Mark; Millar, Michael R

2016-02-13

Probiotics may reduce necrotising enterocolitis and late-onset sepsis after preterm birth. However, there has been concern about the rigour and generalisability of some trials and there is no agreement about whether or not they should be used routinely. We aimed to test the effectiveness of the probiotic Bifidobacterium breve BBG-001 to reduce necrotising enterocolitis, late-onset sepsis, and death in preterm infants. In this multicentre, randomised controlled phase 3 study (the PiPS trial), we recruited infants born between 23 and 30 weeks' gestational age within 48 h of birth from 24 hospitals in southeast England. Infants were randomly assigned (1:1) to probiotic or placebo via a minimisation algorithm randomisation programme. The probiotic intervention was B breve BBG-001 suspended in dilute elemental infant formula given enterally in a daily dose of 8·2 to 9·2 log10 CFU; the placebo was dilute infant formula alone. Clinicians and families were masked to allocation. The primary outcomes were necrotising enterocolitis (Bell stage 2 or 3), blood culture positive sepsis more than 72 h after birth; and death before discharge from hospital. All primary analyses were by intention to treat. This trial is registered with ISRCTN, number 05511098 and EudraCT, number 2006-003445-17. Between July 1, 2010, and July 31, 2013, 1315 infants were recruited; of whom 654 were allocated to probiotic and 661 to placebo. Five infants had consent withdrawn after randomisation, thus 650 were analysed in the probiotic group and 660 in the placebo group. Rates of the primary outcomes did not differ significantly between the probiotic and placebo groups. 61 infants (9%) in the probiotic group had necrotising enterocolitis compared with 66 (10%) in the placebo group (adjusted risk ratio 0·93 (95% CI 0·68-1·27); 73 (11%) infants in the probiotics group had sepsis compared with 77 (12%) in the placebo group (0·97 (0·73-1·29); and 54 (8%) deaths occurred before discharge home in the

Financial disincentives? A three-armed randomised controlled trial of the effect of financial Incentives  in Diabetic Eye Assessment  by Screening (IDEAS) trial.

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Judah, Gaby; Darzi, Ara; Vlaev, Ivo; Gunn, Laura; King, Derek; King, Dominic; Valabhji, Jonathan; Bicknell, Colin

2018-05-23

Conflicting evidence exists regarding the impact of financial incentives on encouraging attendance at medical screening appointments. The primary aim was to determine whether financial incentives increase attendance at diabetic eye screening in persistent non-attenders. A three-armed randomised controlled trial was conducted in London in 2015. 1051 participants aged over 16 years, who had not attended eye screening appointments for 2 years or more, were randomised (1.4:1:1 randomisation ratio) to receive the usual invitation letter (control), an offer of £10 cash for attending screening (fixed incentive) or a 1 in 100 chance of winning £1000 (lottery incentive) if they attend. The primary outcome was the proportion of invitees attending screening, and a comparative analysis was performed to assess group differences. Pairwise comparisons of attendance rates were performed, using a conservative Bonferroni correction for independent comparisons. 34/435 (7.8%) of control, 17/312 (5.5%) of fixed incentive and 10/304 (3.3%) of lottery incentive groups attended. Participants who received any incentive were significantly less likely to attend their appointment compared with controls (risk ratio (RR)=0.56; 95% CI 0.34 to 0.92). Those in the probabilistic incentive group (RR=0.42; 95% CI 0.18 to 0.98), but not the fixed incentive group (RR=1.66; 95% CI 0.65 to 4.21), were significantly less likely to attend than those in the control group. Financial incentives, particularly lottery-based incentives, attract fewer patients to diabetic eye screening than standard invites in this population. Financial incentives should not be used to promote screening unless tested in context, as they may negatively affect attendance rates. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Effect of homocysteine-lowering nutrients on blood lipids: results from four randomised, placebo-controlled studies in healthy humans.

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Margreet R Olthof

2005-05-01

Full Text Available BACKGROUND: Betaine (trimethylglycine lowers plasma homocysteine, a possible risk factor for cardiovascular disease. However, studies in renal patients and in obese individuals who are on a weight-loss diet suggest that betaine supplementation raises blood cholesterol; data in healthy individuals are lacking. Such an effect on cholesterol would counteract any favourable effect on homocysteine. We therefore investigated the effect of betaine, of its precursor choline in the form of phosphatidylcholine, and of the classical homocysteine-lowering vitamin folic acid on blood lipid concentrations in healthy humans. METHODS AND FINDINGS: We measured blood lipids in four placebo-controlled, randomised intervention studies that examined the effect of betaine (three studies, n = 151, folic acid (two studies, n = 75, and phosphatidylcholine (one study, n = 26 on plasma homocysteine concentrations. We combined blood lipid data from the individual studies and calculated a weighted mean change in blood lipid concentrations relative to placebo. Betaine supplementation (6 g/d for 6 wk increased blood LDL cholesterol concentrations by 0.36 mmol/l (95% confidence interval: 0.25-0.46, and triacylglycerol concentrations by 0.14 mmol/l (0.04-0.23 relative to placebo. The ratio of total to HDL cholesterol increased by 0.23 (0.14-0.32. Concentrations of HDL cholesterol were not affected. Doses of betaine lower than 6 g/d also raised LDL cholesterol, but these changes were not statistically significant. Further, the effect of betaine on LDL cholesterol was already evident after 2 wk of intervention. Phosphatidylcholine supplementation (providing approximately 2.6 g/d of choline for 2 wk increased triacylglycerol concentrations by 0.14 mmol/l (0.06-0.21, but did not affect cholesterol concentrations. Folic acid supplementation (0.8 mg/d had no effect on lipid concentrations. CONCLUSIONS: Betaine supplementation increased blood LDL cholesterol and triacylglycerol

Variation of inflammatory parameters after sibutramine treatment compared to placebo in type 2 diabetic patients.

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Derosa, G; Maffioli, P; Ferrari, I; Palumbo, I; Randazzo, S; D'Angelo, A; Cicero, A F G

2011-10-01

The efficacy of sibutramine has been demonstrated in randomized trials in obese/overweight patients including those with type 2 diabetes mellitus (T2DM). Our objective was to evaluate the effects of 1-year treatment with sibutramine compared to placebo on body weight, glycaemic control, lipid profile, and inflammatory parameters in type 2 diabetic patients. Two hundred and forty-six patients with uncontrolled T2DM [glycated haemoglobin (HbA(1c) ) > 8·0%] in therapy with different oral hypoglycaemic agents or insulin were randomized to take 10 mg of sibutramine or placebo for 12 months. We evaluated at baseline, and after 3, 6, 9, and 12 months these parameters: body weight, body mass index (BMI), HbA(1c) , fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides (Tg), leptin, tumour necrosis factor-α (TNF-α), adiponectin (ADN), vaspin, high sensitivity C-reactive protein (Hs-CRP). We observed a decrease of body weight after 9 and 12 months in the group treated with sibutramine, but not in the control group. Regarding glycaemic and lipid profile, although there are differences seen over time within each of the groups, we did not obtain any significant differences between the two groups. Both placebo and sibutramine gave a similar improvement of HOMA-IR, leptin, TNF-α, ADN, and Hs-CRP. No vaspin variations were observed in either group. Sibutramine resulted in a decrease in body weight at 9 months and at 12 months that was not observed with placebo. Although there were differences seen over time within each of the groups, there were no significant differences between groups for any other parameter that we measured. © 2010 The Authors. JCPT © 2010 Blackwell Publishing Ltd.

Weight Maintenance with Litramine (IQP-G-002AS: A 24-Week Double-Blind, Randomized, Placebo-Controlled Study

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Barbara Grube

2015-01-01

Full Text Available Background. Litramine (IQP-G-002AS was shown to be effective and safe for weight loss in overweight and obese subjects. However, long-term effectiveness on maintenance of body weight loss has yet to be ascertained. Objective. To assess effect of Litramine on maintenance of body weight loss. Methods. A double-blind, randomised, placebo-controlled trial on overweight and obese patients was conducted over two sites in Germany for 24 weeks. Subjects with documented previous weight loss of 3% over the last 3–6 months were randomised to groups given either Litramine (3 g/day or a matching placebo. Primary endpoints were difference of mean body weight (kg between baseline and end of study and maintenance of initially lost body weight in verum group, where maintenance is defined as ≤1% weight gain. Results. Subjects who were taking Litramine lost significantly more body weight compared to the subjects taking placebo who gained weight instead (-0.62±1.55 kg versus 1.62±1.48 kg, p<0.001. More importantly, 92% of subjects in Litramine group were able to maintain their body weight after initial weight loss, versus 25% in placebo group. No serious adverse events were reported throughout. Conclusion. Litramine is effective and safe for long-term body weight maintenance. Trial Registration. This trial is registered with Clinicaltrials.gov identifier: NCT01505387.

Gongronema Latifolium delays gastric emptying of semi-solid meals ...

African Journals Online (AJOL)

The aim of the study was to investigate sonographically the effect of Gongronema latifolium on gastric emptying of semi-solid meals in diabetic dogs. Twenty-five alloxan-induced diabetic dogs were randomly allotted into five groups of five dogs each in a randomised placebo-controlled study. These are placebo, prokinetic ...

Group cognitive behavioural therapy and weight regain after diet in type 2 diabetes: results from the randomised controlled POWER trial.

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Berk, Kirsten A; Buijks, Hanneke I M; Verhoeven, Adrie J M; Mulder, Monique T; Özcan, Behiye; van 't Spijker, Adriaan; Timman, Reinier; Busschbach, Jan J; Sijbrands, Eric J

2018-04-01

Weight-loss programmes for adults with type 2 diabetes are less effective in the long term owing to regain of weight. Our aim was to determine the 2 year effectiveness of a cognitive behavioural group therapy (group-CBT) programme in weight maintenance after diet-induced weight loss in overweight and obese adults with type 2 diabetes, using a randomised, parallel, non-blinded, pragmatic study design. We included 158 obese adults (median BMI 36.3 [IQR 32.5-40.0] kg/m 2 ) with type 2 diabetes from the outpatient diabetes clinic of Erasmus MC, the Netherlands, who achieved ≥5% weight loss on an 8 week very low calorie diet. Participants were randomised (stratified by weight loss) to usual care or usual care plus group-CBT (17 group sessions). The primary outcomes were the between-group differences after 2 years in: (1) body weight; and (2) weight regain. Secondary outcomes were HbA 1c levels, insulin dose, plasma lipid levels, depression, anxiety, self-esteem, quality of life, fatigue, physical activity, eating disorders and related cognitions. Data were analysed using linear mixed modelling. During the initial 8 week dieting phase, the control group (n = 75) lost a mean of 10.0 (95% CI 9.1, 10.9) kg and the intervention group (n = 83) lost 9.2 (95% CI 8.4, 10.0) kg (p = 0.206 for the between-group difference). During 2 years of follow-up, mean weight regain was 4.7 (95% CI 3.0, 6.3) kg for the control group and 4.0 (95% CI 2.3, 5.6) kg for the intervention group, with a between-group difference of -0.7 (95% CI -3.1, 1.6) kg (p = 0.6). The mean difference in body weight at 2 years was -1.2 (95% CI -7.7, 5.3) kg (p = 0.7). None of the secondary outcomes differed between the two groups. Despite increased treatment contact, a group-CBT programme for long-term weight maintenance after an initial ≥5% weight loss from dieting in obese individuals with type 2 diabetes was not superior to usual care alone. Trialregister.nl NTR2264 FUNDING: The

Safety and immunogenicity of a novel recombinant adenovirus type-5 vector-based Ebola vaccine in healthy adults in China: preliminary report of a randomised, double-blind, placebo-controlled, phase 1 trial.

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Zhu, Feng-Cai; Hou, Li-Hua; Li, Jing-Xin; Wu, Shi-Po; Liu, Pei; Zhang, Gui-Rong; Hu, Yue-Mei; Meng, Fan-Yue; Xu, Jun-Jie; Tang, Rong; Zhang, Jin-Long; Wang, Wen-Juan; Duan, Lei; Chu, Kai; Liang, Qi; Hu, Jia-Lei; Luo, Li; Zhu, Tao; Wang, Jun-Zhi; Chen, Wei

2015-06-06

Up to now, all tested Ebola virus vaccines have been based on the virus strain from the Zaire outbreak in 1976. We aimed to assess the safety and immunogenicity of a novel recombinant adenovirus type-5 vector-based Ebola vaccine expressing the glycoprotein of the 2014 epidemic strain. We did this randomised, double-blind, placebo-controlled, phase 1 clinical trial at one site in Taizhou County, Jiangsu Province, China. Healthy adults (aged 18-60 years) were sequentially enrolled and randomly assigned (2:1), by computer-generated block randomisation (block size of six), to receive placebo, low-dose adenovirus type-5 vector-based Ebola vaccine, or high-dose vaccine. Randomisation was pre-stratified by dose group. All participants, investigators, and laboratory staff were masked to treatment allocation. The primary safety endpoint was occurrence of solicited adverse reactions within 7 days of vaccination. The primary immunogenicity endpoints were glycoprotein-specific antibody titres and T-cell responses at day 28 after the vaccination. Analysis was by intention to treat. The study is registered with ClinicalTrials.gov, number NCT02326194. Between Dec 28, 2014, and Jan 9, 2015, 120 participants were enrolled and randomly assigned to receive placebo (n=40), low-dose vaccine (n=40), or high-dose vaccine. Participants were followed up for 28 days. Overall, 82 (68%) participants reported at least one solicited adverse reaction within 7 days of vaccination (n=19 in the placebo group vs n=27 in the low-dose group vs n=36 in the high-dose group; p=0·0002). The most common reaction was mild pain at the injection site, which was reported in eight (20%) participants in the placebo group, 14 (35%) participants in the low-dose group, and 29 (73%) participants in the high-dose vaccine group (pvaccine groups at both day 14 (geometric mean titre 421·4 [95% CI 249·7-711·3] and 820·5 [598·9-1124·0], respectively; pday 28 (682·7 [424·3-1098·5] and 1305·7 [970·1-1757·2

RETRACTED: Treatment of postoperative emetic symptoms with granisetron in women undergoing abdominal hysterectomy: a randomized, double-blind, placebo-controlled, dose-ranging study

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MD Yoshitaka Fujii

2004-07-01

Fujii Y, Tanaka H, Somekawa Y. Treatment of postoperative emetic symptoms with granisetron in women undergoing abdominal hysterectomy: a randomised, double-blind, placebo-controlled, dose-ranging study. Current Therapeutic Research 2004;65:321–9. https://www.sciencedirect.com/science/article/pii/S0011393X04800018

Pralidoxime in acute organophosphorus insecticide poisoning--a randomised controlled trial.

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Michael Eddleston

2009-06-01

Full Text Available Poisoning with organophosphorus (OP insecticides is a major global public health problem, causing an estimated 200,000 deaths each year. Although the World Health Organization recommends use of pralidoxime, this antidote's effectiveness remains unclear. We aimed to determine whether the addition of pralidoxime chloride to atropine and supportive care offers benefit.We performed a double-blind randomised placebo-controlled trial of pralidoxime chloride (2 g loading dose over 20 min, followed by a constant infusion of 0.5 g/h for up to 7 d versus saline in patients with organophosphorus insecticide self-poisoning. Mortality was the primary outcome; secondary outcomes included intubation, duration of intubation, and time to death. We measured baseline markers of exposure and pharmacodynamic markers of response to aid interpretation of clinical outcomes. Two hundred thirty-five patients were randomised to receive pralidoxime (121 or saline placebo (114. Pralidoxime produced substantial and moderate red cell acetylcholinesterase reactivation in patients poisoned by diethyl and dimethyl compounds, respectively. Mortality was nonsignificantly higher in patients receiving pralidoxime: 30/121 (24.8% receiving pralidoxime died, compared with 18/114 (15.8% receiving placebo (adjusted hazard ratio [HR] 1.69, 95% confidence interval [CI] 0.88-3.26, p = 0.12. Incorporating the baseline amount of acetylcholinesterase already aged and plasma OP concentration into the analysis increased the HR for patients receiving pralidoxime compared to placebo, further decreasing the likelihood that pralidoxime is beneficial. The need for intubation was similar in both groups (pralidoxime 26/121 [21.5%], placebo 24/114 [21.1%], adjusted HR 1.27 [95% CI 0.71-2.29]. To reduce confounding due to ingestion of different insecticides, we further analysed patients with confirmed chlorpyrifos or dimethoate poisoning alone, finding no evidence of benefit.Despite clear reactivation of

An evaluation of Croí MyAction community lifestyle modification programme compared to standard care to reduce progression to diabetes/pre-diabetes in women with prior gestational diabetes mellitus (GDM): study protocol for a randomised controlled trial.

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Infanti, Jennifer J; Dunne, Fidelma P; O'Dea, Angela; Gillespie, Paddy; Gibson, Irene; Glynn, Liam G; Noctor, Eoin; Newell, John; McGuire, Brian E

2013-05-02

Universal screening using the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria has identified a prevalence of gestational diabetes mellitus (GDM) of 12.4% in women living in Ireland. Women with prior GDM are at increased risk of developing type 2 diabetes later in life. A number of risk factors linked to the development of type 2 diabetes are potentially modifiable through lifestyle and behaviour changes, and medical management. No previous Irish studies have adequately investigated the efficacy of lifestyle intervention programmes in reducing these risk factors in women with prior GDM. Through a two-group, parallel randomised controlled trial (RCT), this study aims to assess the clinical impact, cost-effectiveness and psychological experience of the Croí MyAction intensive lifestyle modification programme for women with prior GDM. A total of 54 women with a history of GDM and persistent post-partum glucose dysfunction (impaired glucose tolerance (IGT) or impaired fasting glucose (IFG)), are randomly assigned to a control arm (n=27) or to the Croí MyAction intervention group (n=27). The control arm receives usual health care advice--written information on diet and lifestyle changes for reducing diabetes risks and visits with general practitioners as required. The intervention group receives usual health care as per the control group in addition to attending a 12-week intensive lifestyle modification programme known as Croí MyAction. Croí MyAction involves 2.5 hour sessions once per week (for 12 weeks) comprising a group exercise programme, group health promotion or education seminars, and one-to-one meetings with a multidisciplinary health care team to personalise risk factor reductions. Randomisation and allocation to the intervention arms is carried out by an independent researcher, ensuring that the allocation sequence is concealed from study researchers until the interventions are assigned. The primary analysis is based on

Progesterone for the prevention of preterm birth in twin pregnancy (STOPPIT): a randomised, double-blind, placebo-controlled study and meta-analysis.

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Norman, Jane E; Mackenzie, Fiona; Owen, Philip; Mactier, Helen; Hanretty, Kevin; Cooper, Sarah; Calder, Andrew; Mires, Gary; Danielian, Peter; Sturgiss, Stephen; MacLennan, Graeme; Tydeman, Graham; Thornton, Steven; Martin, Bill; Thornton, James G; Neilson, James P; Norrie, John

2009-06-13

Women with twin pregnancy are at high risk for spontaneous preterm delivery. Progesterone seems to be effective in reducing preterm birth in selected high-risk singleton pregnancies, albeit with no significant reduction in perinatal mortality and little evidence of neonatal benefit. We investigated the use of progesterone for prevention of preterm birth in twin pregnancy. In this double-blind, placebo-controlled trial, 500 women with twin pregnancy were recruited from nine UK National Health Service clinics specialising in the management of twin pregnancy. Women were randomised, by permuted blocks of randomly mixed sizes, either to daily vaginal progesterone gel 90 mg (n=250) or to placebo gel (n=250) for 10 weeks from 24 weeks' gestation. All study personnel and participants were masked to treatment assignment for the duration of the study. The primary outcome was delivery or intrauterine death before 34 weeks' gestation. Analysis was by intention to treat. Additionally we undertook a meta-analysis of published and unpublished data to establish the efficacy of progesterone in prevention of early (<34 weeks' gestation) preterm birth or intrauterine death in women with twin pregnancy. This study is registered, number ISRCTN35782581. Three participants in each group were lost to follow-up, leaving 247 analysed per group. The combined proportion of intrauterine death or delivery before 34 weeks of pregnancy was 24.7% (61/247) in the progesterone group and 19.4% (48/247) in the placebo group (odds ratio [OR] 1.36, 95% CI 0.89-2.09; p=0.16). The rate of adverse events did not differ between the two groups. The meta-analysis confirmed that progesterone does not prevent early preterm birth in women with twin pregnancy (pooled OR 1.16, 95% CI 0.89-1.51). Progesterone, administered vaginally, does not prevent preterm birth in women with twin pregnancy. Chief Scientist Office of the Scottish Government Health Directorate.

Go4it; study design of a randomised controlled trial and economic evaluation of a multidisciplinary group intervention for obese adolescents for prevention of diabetes mellitus type 2

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Weijs Peter JM

2008-12-01

Full Text Available Abstract Background In the Netherlands, the first adolescents with diabetes mellitus type 2 as a result of obesity have recently been diagnosed. Therefore, it is very important that programs aiming at the prevention of type 2 diabetes of obese adolescents are developed and evaluated. Methods Go4it is a multidisciplinary group treatment that focuses on: 1 increasing awareness of the current dietary and physical activity behaviour (i.e. energy balance behaviour, 2 improving diet, 3 decreasing sedentary behaviour, 4 increasing levels of physical activity, and 5 coping with difficult situations. Go4it consists of 7 sessions with an interval of 2–3 weeks. The effectiveness of the multidisciplinary group treatment compared with usual care (i.e. referral to a dietician was evaluated in a randomised controlled trial. We examined effects on BMI(sds, body composition, energy expenditure, glucose tolerance and insulin resistance (primary outcome measure, as well as dietary and physical activity behaviour and quality of life. An economic evaluation from a societal perspective was conducted alongside the randomised trial to evaluate the cost-effectiveness of the multidisciplinary treatment program vs. usual care. Discussion In this paper we described a multidisciplinary treatment program (Go4it for obese adolescents and the design of a randomised controlled trial and economic evaluation to evaluate its effectiveness and cost-effectiveness. Trial registration Netherlands Trial Register (ISRCTN27626398.

Efficacy and Safety of Analgesic Treatment for Depression in People with Advanced Dementia: Randomised, Multicentre, Double-Blind, Placebo-Controlled Trial (DEP.PAIN.DEM).

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Erdal, Ane; Flo, Elisabeth; Aarsland, Dag; Ballard, Clive; Slettebo, Dagrun D; Husebo, Bettina S

2018-05-03

Chronic pain and depression often co-occur, and pain may exacerbate depression in people with dementia. The objective of this study was to assess the efficacy and safety of analgesic treatment for depression in nursing home patients with advanced dementia and clinically significant depressive symptoms. We conducted a multicentre, parallel-group, double-blind, placebo-controlled trial in 47 nursing homes, including 162 nursing home patients aged ≥ 60 years with dementia (Mini-Mental State Examination ≤ 20) and depression (Cornell Scale for Depression in Dementia ≥ 8). Patients were randomised to receive active analgesic treatment (paracetamol or buprenorphine transdermal system) or identical placebo for 13 weeks. The main outcome measure was the change in depression (Cornell Scale for Depression in Dementia) from baseline to 13 weeks, assessed using linear mixed models with fixed effects for time, intervention and their interaction in the models. Secondary outcomes were to assess whether any change in depression was secondary to change in pain (Mobilisation-Observation-Behaviour-Intensity-Dementia-2 Pain Scale) and adverse events. The mean depression change was - 0.66 (95% confidence interval - 2.27 to 0.94) in the active group (n = 80) and - 3.30 (- 4.68 to -1.92) in the placebo group (n = 82). The estimated treatment effect was 2.64 (0.55-4.72, p = 0.013), indicating that analgesic treatment had no effect on depressive symptoms from baseline to 13 weeks while placebo appeared to ameliorate depressive symptoms. There was no significant reduction in pain in the active treatment group (paracetamol and buprenorphine combined) vs. placebo; however, a subgroup analysis demonstrated a significant reduction in pain for paracetamol vs. placebo [by - 1.11 (- 2.16 to - 0.06, p = 0.037)] from week 6 to 13 without a change in depression. Buprenorphine did not have significant effects on depression [3.04 (- 0.11 to 6.19), p = 0

Effect of irbesartan on nitrotyrosine generation in non-hypertensive diabetic patients.

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Ceriello, A; Assaloni, R; Da Ros, R; Maier, A; Quagliaro, L; Piconi, L; Esposito, K; Giugliano, D

2004-09-01

Oxidative stress is involved in the pathogenesis of microangiopathic and macroangiopathic diabetic complications. The results of recent trials suggest that type 1 angiotensin II (AT-1) receptor blockers may prevent or delay nephropathy and cardiovascular disease in diabetic patients, independently of their anti-hypertensive action. There is evidence that AT-1 receptor blockers can work as intracellular antioxidants. This study investigated whether the AT-1 receptor blocker irbesartan is able to reduce nitrotyrosine formation in non-hypertensive diabetic patients under fasting conditions and during acute hyperglycaemia. A total of 40 non-hypertensive, non-microalbuminuric Type 2 diabetic patients and 20 healthy, normotensive subjects were recruited for this study. Diabetic patients followed a randomised, double-blind, placebo-controlled, crossover protocol, taking either irbesartan (150 mg orally, twice daily) or placebo for 60 days. Fasting glucose and nitrotyrosine were measured at baseline and at the end of each treatment period. An OGTT was also performed at the same time intervals, during which plasma glucose and nitrotyrosine levels were monitored. Compared with baseline measurements, treatment with irbesartan (0.57+/-0.4 vs 0.35+/-0.3 micromol/l, peffective in counterbalancing nitrotyrosine formation during acute hyperglycaemia. Our results may help to elucidate how AT-1 receptor blockers exert their beneficial effect independently of their BP-lowering activity.

A randomized, double-blind, placebo-controlled, phase II clinical trial to investigate the efficacy and safety of oral DA-1229 in patients with type 2 diabetes mellitus who have inadequate glycaemic control with diet and exercise.

Science.gov (United States)

Jung, Chang Hee; Park, Cheol-Young; Ahn, Kyu-Joeng; Kim, Nan-Hee; Jang, Hak-Chul; Lee, Moon-Kyu; Park, Joong-Yeol; Chung, Choon-Hee; Min, Kyung-Wan; Sung, Yeon-Ah; Park, Jeong-Hyun; Kim, Sung Jin; Lee, Hyo Jung; Park, Sung-Woo

2015-03-01

DA-1229 is a novel, potent and selective dipeptidyl peptidase-4 (DPP-IV) inhibitor that is orally bioavailable. We aimed to evaluate the optimal dose, efficacy and safety of DA-1229, in Korean subjects with type 2 diabetes mellitus suboptimally controlled with diet and exercise. We enrolled 158 patients (mean age, 53 years and a mean BMI, 25.6 kg/m(2) ). The mean baseline fasting plasma glucose level, HbA1c and duration of diabetes were 8.28 mmol/L, 7.6% (60 mmol/mol) and 3.9 years, respectively. After 2 or 6 weeks of an exercise and diet program followed by 2 weeks of a placebo period, the subjects were randomized into one of four groups for a 12-week active treatment period: placebo, 2.5, 5 or 10 mg of DA-1229. All three doses of DA-1229 significantly reduced HbA1c from baseline compared to the placebo group (-0.09 in the placebo group vs. -0.56, -0.66 and -0.61% in 2.5, 5 and 10-mg groups, respectively) but without any significant differences between the doses. Insulin secretory function, as assessed by homeostasis model assessment β-cell, the insulinogenic index, 2-h oral glucose tolerance test (OGTT) C-peptide and post-OGTT C-peptide area under the curve (AUC)0-2h, significantly improved with DA-1229 treatment. The incidence of adverse events was similar between the treatment groups and DA-1229 did not affect body weight or induce hypoglycaemic events. DA-1229 monotherapy (5 mg for 12 weeks) improved HbA1c, fasting plasma glucose level, OGTT results and β-cell function. This drug was well tolerated in Korean subjects with type 2 diabetes mellitus. © 2014 The Authors. Diabetes/Metabolism Research and Reviews published by John Wiley & Sons, Ltd.

Heartburn treatment in primary care: randomised, double blind study for 8 weeks

Science.gov (United States)

Hatlebakk, Jan G; Hyggen, Arild; Madsen, Per H; Walle, Per O; Schulz, Tom; Mowinckel, Petter; Bernklev, Tomm; Berstad, Arnold

1999-01-01

Objective To compare the effects and tolerability of omeprazole and cisapride with that of placebo for control of heartburn in primary care patients. Design Randomised, double blind, placebo controlled study. Setting 65 primary care practices in Norway. Participants 483 untreated patients with complaints of heartburn ⩾3 days a week, with at most grade 1 reflux oesophagitis. Interventions Omeprazole 20 mg once daily, cisapride 20 mg twice daily, or placebo for 8 weeks. Main outcome measures Adequate control of heartburn, defined as ⩽1 day of the past 7 days with no more than mild heartburn, after 4 weeks of treatment. Results In the all patients treated analysis, adequate control of heartburn was achieved in 71% of patients taking omeprazole, 22% taking cisapride, and 18% taking placebo after 4 weeks of treatment (omeprazole v cisapride and placebo, Pheartburn whereas cisapride 20 mg twice daily was not significantly more effective than placebo. Key messagesIn primary care patients, heartburn is commonly treated empiricallyMost randomised clinical trials of treatment for heartburn have been conducted in specialist care, and documentation for empirical treatment is limitedOmeprazole was significantly more effective than cisapride or placebo in controlling heartburn and other symptoms of gastro-oesophageal reflux after 2, 4, and 8 weeks, whereas cisapride did not differ significantly from placeboOmeprazole should be considered as a first choice for empirical treatment of heartburn in primary care PMID:10463897

Randomised controlled trials of veterinary homeopathy: characterising the peer-reviewed research literature for systematic review.

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Mathie, Robert T; Hacke, Daniela; Clausen, Jürgen

2012-10-01

Systematic review of the research evidence in veterinary homeopathy has never previously been carried out. This paper presents the search methods, together with categorised lists of retrieved records, that enable us to identify the literature that is acceptable for future systematic review of randomised controlled trials (RCTs) in veterinary homeopathy. All randomised and controlled trials of homeopathic intervention (prophylaxis and/or treatment of disease, in any species except man) were appraised according to pre-specified criteria. The following databases were systematically searched from their inception up to and including March 2011: AMED; Carstens-Stiftung Homeopathic Veterinary Clinical Research (HomVetCR) database; CINAHL; Cochrane Central Register of Controlled Trials; Embase; Hom-Inform; LILACS; PubMed; Science Citation Index; Scopus. One hundred and fifty records were retrieved; 38 satisfied the acceptance criteria (substantive report of a clinical treatment or prophylaxis trial in veterinary homeopathic medicine randomised and controlled and published in a peer-reviewed journal), and were thus eligible for future planned systematic review. Approximately half of the rejected records were theses. Seven species and 27 different species-specific medical conditions were represented in the 38 papers. Similar numbers of papers reported trials of treatment and prophylaxis (n=21 and n=17 respectively) and were controlled against placebo or other than placebo (n=18, n=20 respectively). Most research focused on non-individualised homeopathy (n=35 papers) compared with individualised homeopathy (n=3). The results provide a complete and clarified view of the RCT literature in veterinary homeopathy. We will systematically review the 38 substantive peer-reviewed journal articles under the main headings: treatment trials; prophylaxis trials. Copyright © 2012 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

Adjuvant sunitinib or sorafenib for high-risk, non-metastatic renal-cell carcinoma (ECOG-ACRIN E2805): a double-blind, placebo-controlled, randomised, phase 3 trial

Science.gov (United States)

Haas, Naomi B; Manola, Judith; Uzzo, Robert G; Flaherty, Keith T; Wood, Christopher G; Kane, Christopher; Jewett, Michael; Dutcher, Janice P; Atkins, Michael B; Pins, Michael; Wilding, George; Cella, David; Wagner, Lynne; Matin, Surena; Kuzel, Timothy M; Sexton, Wade J; Wong, Yu-Ning; Choueiri, Toni K; Pili, Roberto; Puzanov, Igor; Kohli, Manish; Stadler, Walter; Carducci, Michael; Coomes, Robert; DiPaola, Robert S

2016-01-01

Summary Background Renal-cell carcinoma is highly vascular, and proliferates primarily through dysregulation of the vascular endothelial growth factor (VEGF) pathway. We tested sunitinib and sorafenib, two oral anti-angiogenic agents that are effective in advanced renal-cell carcinoma, in patients with resected local disease at high risk for recurrence. Methods In this double-blind, placebo-controlled, randomised, phase 3 trial, we enrolled patients at 226 study centres in the USA and Canada. Eligible patients had pathological stage high-grade T1b or greater with completely resected non-metastatic renal-cell carcinoma and adequate cardiac, renal, and hepatic function. Patients were stratified by recurrence risk, histology, Eastern Cooperative Oncology Group (ECOG) performance status, and surgical approach, and computerised double-blind randomisation was done centrally with permuted blocks. Patients were randomly assigned (1:1:1) to receive 54 weeks of sunitinib 50 mg per day orally throughout the first 4 weeks of each 6 week cycle, sorafenib 400 mg twice per day orally throughout each cycle, or placebo. Placebo could be sunitinib placebo given continuously for 4 weeks of every 6 week cycle or sorafenib placebo given twice per day throughout the study. The primary objective was to compare disease-free survival between each experimental group and placebo in the intention-to-treat population. All treated patients with at least one follow-up assessment were included in the safety analysis. This trial is registered with ClinicalTrials.gov, number NCT00326898. Findings Between April 24, 2006, and Sept 1, 2010, 1943 patients from the National Clinical Trials Network were randomly assigned to sunitinib (n=647), sorafenib (n=649), or placebo (n=647). Following high rates of toxicity-related discontinuation after 1323 patients had enrolled (treatment discontinued by 193 [44%] of 438 patients on sunitinib, 199 [45%] of 441 patients on sorafenib), the starting dose of each

Drug therapy for improving walking distance in intermittent claudication: a systematic review and meta-analysis of robust randomised controlled studies

DEFF Research Database (Denmark)

Momsen, A H; Jensen, Martin Bach; Norager, C B

2009-01-01

of the databases to February 2009. In addition, reference lists were manually searched. REVIEW METHODS: Based upon a power calculation, only robust (n>56), peer-reviewed, double-blinded, randomised and placebo-controlled trials were included. The main outcomes evaluated were maximal walking distance (MWD) and pain...

Screening for type 2 diabetes and population mortality over 10 years (ADDITION-Cambridge): a cluster-randomised controlled trial.

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Simmons, Rebecca K; Echouffo-Tcheugui, Justin B; Sharp, Stephen J; Sargeant, Lincoln A; Williams, Kate M; Prevost, A Toby; Kinmonth, Ann Louise; Wareham, Nicholas J; Griffin, Simon J

2012-11-17

The increasing prevalence of type 2 diabetes poses a major public health challenge. Population-based screening and early treatment for type 2 diabetes could reduce this growing burden. However, uncertainty persists around the benefits of screening for type 2 diabetes. We assessed the effect of a population-based stepwise screening programme on mortality. In a pragmatic parallel group, cluster-randomised trial, 33 general practices in eastern England were randomly assigned by the method of minimisation in an unbalanced design to: screening followed by intensive multifactorial treatment for people diagnosed with diabetes (n=15); screening plus routine care of diabetes according to national guidelines (n=13); and a no-screening control group (n=5). The study population consisted of 20,184 individuals aged 40-69 years (mean 58 years), at high risk of prevalent undiagnosed diabetes, on the basis of a previously validated risk score. In screening practices, individuals were invited to a stepwise programme including random capillary blood glucose and glycated haemoglobin (HbA(1c)) tests, a fasting capillary blood glucose test, and a confirmatory oral glucose tolerance test. The primary outcome was all-cause mortality. All participants were flagged for mortality surveillance by the England and Wales Office of National Statistics. Analysis was by intention-to-screen and compared all-cause mortality rates between screening and control groups. This study is registered, number ISRCTN86769081. Of 16,047 high-risk individuals in screening practices, 15,089 (94%) were invited for screening during 2001-06, 11,737 (73%) attended, and 466 (3%) were diagnosed with diabetes. 4137 control individuals were followed up. During 184,057 person-years of follow up (median duration 9·6 years [IQR 8·9-9·9]), there were 1532 deaths in the screening practices and 377 in control practices (mortality hazard ratio [HR] 1·06, 95% CI 0·90-1·25). We noted no significant reduction in

A randomised, double-blind, placebo-controlled trial of nightly sildenafil citrate to preserve erectile function after radiation treatment for prostate cancer

International Nuclear Information System (INIS)

Ilic, Dragan; Hindson, Ben; Duchesne, Gillian; Millar, Jeremy L.

2013-01-01

Erectile dysfunction (ED) is a common adverse event associated with treatment for prostate cancer. This study aimed to identify whether early, regular use of sildenafil after radiation treatment for prostate cancer is effective at reducing the rate of ED at 2 years. A randomised controlled trial with 27 men planned for radiation treatment for localised prostate cancer recruited from a single radiotherapy centre in Australia. Men were randomised to receive daily sildenafil, or a placebo tablet, for 6 months. The primary end-point was erectile function, as measured by the International Index of Erectile Function (IIEF) score, at 2-year follow-up. The abridged IIEF-5 survey was also used during the treatment period, and could be derived from the full IIEF at other time-points. Two-sided Student's t-tests and Mann–Whitney U-tests were used for the analysis of continuous outcomes, with Fisher's exact test for dichotomous outcomes. No difference was seen at 2 years in the primary end-point, and IIEF scores did not differ significantly between groups during the study. Men in the sildenafil group exhibited significantly better IIEF-5 scores at 4 weeks (P=0.02) and 6 months (P=0.02). There was no difference in erectile function scores between the two groups throughout the treatment period. No significant difference in adverse events was identified between the two groups. There was no evidence from this trial that sildenafil provides long-term erectile function for patients while on medication. Regular use of sildenafil may improve short-term sexual function for patients while on medication. Larger trials are required to examine the effectiveness of implementing sildenafil for prostate cancer patients undergoing radiation treatment.

Short and long-term effects of irbesartan on intradialytic central haemodynamics: A randomised double-blind placebo-controlled one-year intervention trial (the SAFIR study)

DEFF Research Database (Denmark)

Peters, Christian Daugaard; Kjærgaard, Krista Dybtved; Jensen, Jens Dam

2014-01-01

), stroke volume (SV), central blood volume (CBV), total peripheral resistance (TPR), mean arterial BP (MAP), and heart rate (HR) were measured within the first (HDSTART) and last (HDEND) 30 minutes during HD using the Transonic saline dilution technique. Results Eighty-two patients were randomised (placebo....../ARB: 41/41). Predialytic systolic BP decreased significantly, but similarly in both groups during the study period. The total number of IDH episodes was (placebo/ARB) 22/25 (P=0.7). Mean HDSTART and mean HDEND CO, SV, TPR, HR, and MAP were stable and similar in the two groups, whereas CBV increased...... equally and significantly over time. The mean intradialytic haemodynamic response showed decreased CO, SV, MAP, and CBV, whereas HR increased from HDSTART to HDEND. TPR did not change significantly. Overall, this pattern remained stable over time in both groups and there was no significant impact of ARB...

Use of drug therapy in the management of symptomatic ureteric stones in hospitalised adults: a multicentre, placebo-controlled, randomised controlled trial and cost-effectiveness analysis of a calcium channel blocker (nifedipine) and an alpha-blocker (tamsulosin) (the SUSPEND trial).

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Pickard, Robert; Starr, Kathryn; MacLennan, Graeme; Kilonzo, Mary; Lam, Thomas; Thomas, Ruth; Burr, Jennifer; Norrie, John; McPherson, Gladys; McDonald, Alison; Shearer, Kirsty; Gillies, Katie; Anson, Kenneth; Boachie, Charles; N'Dow, James; Burgess, Neil; Clark, Terry; Cameron, Sarah; McClinton, Samuel

2015-08-01

Ureteric colic, the term used to describe the pain felt when a stone passes down the ureter from the kidney to the bladder, is a frequent reason for people to seek emergency health care. Treatment with the muscle-relaxant drugs tamsulosin hydrochloride (Petyme, TEVA UK Ltd) and nifedipine (Coracten(®), UCB Pharma Ltd) as medical expulsive therapy (MET) is increasingly being used to improve the likelihood of spontaneous stone passage and lessen the need for interventional procedures. However, there remains considerable uncertainty around the effectiveness of these drugs for routine use. To determine whether or not treatment with either tamsulosin 400 µg or nifedipine 30 mg for up to 4 weeks increases the rate of spontaneous stone passage for people with ureteric colic compared with placebo, and whether or not it is cost-effective for the UK NHS. A pragmatic, randomised controlled trial comparing two active drugs, tamsulosin and nifedipine, against placebo. Participants, clinicians and trial staff were blinded to treatment allocation. A cost-utility analysis was performed using data gathered during trial participation. Urology departments in 24 UK NHS hospitals. Adults aged between 18 and 65 years admitted as an emergency with a single ureteric stone measuring ≤ 10 mm, localised by computerised tomography, who were able to take trial medications and complete trial procedures. Eligible participants were randomised 1 : 1 : 1 to take tamsulosin 400 µg, nifedipine 30 mg or placebo once daily for up to 4 weeks to make the following comparisons: tamsulosin or nifedipine (MET) versus placebo and tamsulosin versus nifedipine. The primary effectiveness outcome was the proportion of participants who spontaneously passed their stone. This was defined as the lack of need for active intervention for ureteric stones at up to 4 weeks after randomisation. This was determined from 4- and 12-week case-report forms completed by research staff, and from the 4

Effects of trans fatty acids on glucose homeostasis: a meta-analysis of randomized, placebo-controlled clinical trials123

OpenAIRE

Aronis, Konstantinos N; Khan, Sami M; Mantzoros, Christos S

2012-01-01

Background: Although evidence from cohort studies has suggested that trans fatty acid (TFA) consumption may be associated with insulin resistance and diabetes, randomized placebo-controlled trials (RCTs) have yielded conflicting results.

Metabolic effect of Gum Arabic (Acacia Senegal in patients with Type 2 Diabetes Mellitus (T2DM: Randomized, placebo controlled double blind trial

Directory of Open Access Journals (Sweden)

Rasha Babiker

2017-03-01

Full Text Available Background:Gum Arabic (GA is a water-soluble dietary fiber, indigestible to both humans and animals. While GAcurrently does not have any therapeutic potential, ithas nutritional value andsome effects on metabolism of glucose and lipids. Thus, theaim of this study is to assess the effect of GA on serum level of glucose, lipids,and the BMI in type 2 diabetic patients.Methods:A double-blind randomizedplacebo-controlled trial took placeat Academy Charity Teaching Hospital (ACTH in Sudan between August 2014 to February 2015. The trial was conducted intype 2 diabetic patients who were on regular oral hypoglycemicdrugs andhad HbA1C ≥ 6.5%. Patients excluded from the study included those on insulin, any patient with a metabolic or gastrointestinal disease,and any patient with history of drug addiction and alcoholism. Other patients excluded were patients who had previous allergic reactionsto GA in addition topatients who were pregnant or plannedfor conception within 6 months. 120 patients were invited to participate in this trial. 100 patients gave consent and wererandomizedto GA and placebo groups. The GA group was given 30 g of Acacia Senegaland the placebo group was given 5 g of placebodaily for 3 months. The outcomesassessedwereprimarily the effect of GA on glucose levels in addition to the effects on levels of lipids and BMI in type 2 diabetic patients.Results:The GA group showed significant reduction in fasting plasma glucose (FPG andHbA1c(P<0.05 within the GA group. Moreover, GA supplementation improvedlipid profiles; decreasedLDL-Cholesterol by 5.95%, total Cholesterol by 8.28% and triglyceride by 10.95% from baseline levels. HDL-Cholesterol showedsignificant increase by 19.89% within GA group(P<0.05, BMI was decreased significantly by 2.06% (95% CI: −0.98; −0.16, P<0.05.Conclusions:Gum Arabic is a dietary supplement for improving nutrition of type 2 diabetic patients; it has demonstrateda good effect on improving their poor glycemic

Chinese herbal medicine for diabetic peripheral neuropathy.

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Chen, Wei; Zhang, Yin; Li, Xinxue; Yang, Guoyan; Liu, Jian Ping

2013-10-06

Chinese herbal medicine is frequently used for treating diabetic peripheral neuropathy in China. Many controlled trials have been undertaken to investigate its efficacy.This is an update of a Cochrane review that was first published in the year 2011. To assess the beneficial effects and harms of Chinese herbal medicine for people with diabetic peripheral neuropathy. On 14 May 2012, we searched the Cochrane Neuromuscular Disease Group Specialized Register CENTRAL (2012, Issue 4 in The Cochrane Library), MEDLINE (January 1966 to May 2012), EMBASE (January 1980 to May 2012), AMED (January 1985 to May 2012) and in October 2012, the Chinese Biomedical Database (CBM) (1979 to October 2012), Chinese National Knowledge Infrastructure Database (CNKI) (1979 to October 2012), and VIP Chinese Science and Technique Journals Database (1989 to October 2012). We searched for unpublished literature in the Chinese Conference Papers Database, and Chinese Dissertation Database (from inception to October 2012). There were no language or publication restrictions. We included randomised controlled trials of Chinese herbal medicine (with a minimum of four weeks treatment duration) for people with diabetic peripheral neuropathy compared with placebo, no intervention, or conventional interventions. Trials of herbal medicine plus a conventional drug versus the drug alone were also included. Two authors independently extracted data and evaluated trial quality. We contacted study authors for additional information. Forty-nine randomised trials involving 3639 participants were included. All trials were conducted and published in China. Thirty-eight different herbal medicines were tested in these trials, including four single herbs (extracts from a single herb), eight traditional Chinese patent medicines, and 26 self concocted Chinese herbal compound prescriptions. The trials reported on global symptom improvement (including improvement in numbness or pain) and changes in nerve conduction

MOR103, a human monoclonal antibody to granulocyte-macrophage colony-stimulating factor, in the treatment of patients with moderate rheumatoid arthritis: results of a phase Ib/IIa randomised, double-blind, placebo-controlled, dose-escalation trial.

Science.gov (United States)

Behrens, Frank; Tak, Paul P; Østergaard, Mikkel; Stoilov, Rumen; Wiland, Piotr; Huizinga, Thomas W; Berenfus, Vadym Y; Vladeva, Stoyanka; Rech, Juergen; Rubbert-Roth, Andrea; Korkosz, Mariusz; Rekalov, Dmitriy; Zupanets, Igor A; Ejbjerg, Bo J; Geiseler, Jens; Fresenius, Julia; Korolkiewicz, Roman P; Schottelius, Arndt J; Burkhardt, Harald

2015-06-01

To determine the safety, tolerability and signs of efficacy of MOR103, a human monoclonal antibody to granulocyte-macrophage colony-stimulating factor (GM-CSF), in patients with rheumatoid arthritis (RA). Patients with active, moderate RA were enrolled in a randomised, multicentre, double-blind, placebo-controlled, dose-escalation trial of intravenous MOR103 (0.3, 1.0 or 1.5 mg/kg) once a week for 4 weeks, with follow-up to 16 weeks. The primary outcome was safety. Of the 96 randomised and treated subjects, 85 completed the trial (n=27, 24, 22 and 23 for pooled placebo and MOR103 0.3, 1.0 and 1.5 mg/kg, respectively). Treatment emergent adverse events (AEs) in the MOR103 groups were mild or moderate in intensity and generally reported at frequencies similar to those in the placebo group. The most common AE was nasopharyngitis. In two cases, AEs were classified as serious because of hospitalisation: paronychia in a placebo subject and pleurisy in a MOR103 0.3 mg/kg subject. Both patients recovered fully. In exploratory efficacy analyses, subjects in the MOR103 1.0 and 1.5 mg/kg groups showed significant improvements in Disease Activity Score-28 scores and joint counts and significantly higher European League Against Rheumatism response rates than subjects receiving placebo. MOR103 1.0 mg/kg was associated with the largest reductions in disease activity parameters. MOR103 was well tolerated and showed preliminary evidence of efficacy in patients with active RA. The data support further investigation of this monoclonal antibody to GM-CSF in RA patients and potentially in those with other immune-mediated inflammatory diseases. NCT01023256. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

The @RISK Study: Risk communication for patients with type 2 diabetes: design of a randomised controlled trial.

Science.gov (United States)

Welschen, Laura M C; Bot, Sandra D M; Dekker, Jacqueline M; Timmermans, Daniëlle R M; van der Weijden, Trudy; Nijpels, Giel

2010-08-05

Patients with type 2 diabetes mellitus (T2DM) have an increased risk to develop severe diabetes related complications, especially cardiovascular disease (CVD). The risk to develop CVD can be estimated by means of risk formulas. However, patients have difficulties to understand the outcomes of these formulas. As a result, they may not recognize the importance of changing lifestyle and taking medication in time. Therefore, it is important to develop risk communication methods, that will improve the patients' understanding of risks associated with having diabetes, which enables them to make informed choices about their diabetes care.The aim of this study is to investigate the effects of an intervention focussed on the communication of the absolute 10-year risk to develop CVD on risk perception, attitude and intention to change lifestyle behaviour in patients with T2DM. The conceptual framework of the intervention is based on the Theory of Planned Behaviour and the Self-regulation Theory. A randomised controlled trial will be performed in the Diabetes Care System West-Friesland (DCS), a managed care system. Newly referred T2DM patients of the DCS, younger than 75 years will be eligible for the study. The intervention group will be exposed to risk communication on CVD, on top of standard managed care of the DCS. This intervention consists of a simple explanation on the causes and consequences of CVD, and possibilities for prevention. The probabilities of CVD in 10 year will be explained in natural frequencies and visualised by a population diagram. The control group will receive standard managed care. The primary outcome is appropriateness of risk perception. Secondary outcomes are attitude and intention to change lifestyle behaviour and illness perception. Differences between baseline and follow-up (2 and 12 weeks) between groups will be analysed according to the intention-to-treat principle. The study was powered on 120 patients in each group. This innovative risk

Renal and Cardiovascular Effects of sodium–glucose cotransporter 2 (SGLT2) inhibition in combination with loop Diuretics in diabetic patients with Chronic Heart Failure (RECEDE-CHF): protocol for a randomised controlled double-blind cross-over trial

Science.gov (United States)

Mordi, Natalie A; Mordi, Ify R; Singh, Jagdeep S; Baig, Fatima; Choy, Anna-Maria; McCrimmon, Rory J; Struthers, Allan D; Lang, Chim C

2017-01-01

Introduction Type 2 diabetes (T2D) and heart failure (HF) are a frequent combination, where treatment options remain limited. There has been increasing interest around the sodium–glucose cotransporter 2 (SGLT2) inhibitors and their use in patients with HF. Data on the effect of SGLT2 inhibitor use with diuretics are limited. We hypothesise that SGLT2 inhibition may augment the effects of loop diuretics and the benefits of SGLT2 inhibitors may extend beyond those of their metabolic (glycaemic parameters and weight loss) and haemodynamic parameters. The effects of SGLT2 inhibitors as an osmotic diuretic and on natriuresis may underlie the cardiovascular and renal benefits demonstrated in the recent EMPA-REG study. Methods and analysis To assess the effect of SGLT2 inhibitors when used in combination with a loop diuretic, the RECEDE-CHF (Renal and Cardiovascular Effects of SGLT2 inhibition in combination with loop Diuretics in diabetic patients with Chronic Heart Failure) trial is a single-centre, randomised, double-blind, placebo-controlled, cross-over trial conducted in a secondary care setting within NHS Tayside, Scotland. 34 eligible participants, aged between 18 and 80 years, with stable T2D and CHF will be recruited. Renal physiological testing will be performed at two points (week 1 and week 6) on each arm to assess the effect of 25 mg empagliflozin, on the primary and secondary outcomes. Participants will be enrolled in the trial for a total period between 14 and 16 weeks. The primary outcome will assess the effect of empagliflozin versus placebo on urine output. The secondary outcomes are to assess the effect of empagliflozin on glomerular filtration rate, cystatin C, urinary sodium excretion, urinary protein/creatinine ratio and urinary albumin/creatinine ratio when compared with placebo. Ethics and dissemination Ethics approval was obtained by the East of Scotland Research Ethics Service. Results of the trial will be submitted for publication in a peer

Patterns of soil-transmitted helminth infection and impact of four-monthly albendazole treatments in preschool children from semi-urban communities in Nigeria: a double-blind placebo-controlled randomised trial

Directory of Open Access Journals (Sweden)

Jackson Andrew L

2009-02-01

Full Text Available Abstract Background Children aged between one and five years are particularly vulnerable to disease caused by soil-transmitted helminths (STH. Periodic deworming has been shown to improve growth, micronutrient status (iron and vitamin A, and motor and language development in preschool children and justifies the inclusion of this age group in deworming programmes. Our objectives were to describe the prevalence and intensity of STH infection and to investigate the effectiveness of repeated four-monthly albendazole treatments on STH infection in children aged one to four years. Methods The study was carried out in four semi-urban villages situated near Ile-Ife, Osun State, Nigeria. The study was a double-blind placebo-controlled randomised trial. Children aged one to four years were randomly assigned to receive either albendazole or placebo every four months for 12 months with a follow-up at 14 months. Results The results presented here revealed that 50% of the preschool children in these semi-urban communities were infected by one or more helminths, the most prevalent STH being Ascaris lumbricoides (47.6%. Our study demonstrated that repeated four-monthly anthelminthic treatments with albendazole were successful in reducing prevalence and intensity of A. lumbricoides infections. At the end of the follow-up period, 12% and 43% of the children were infected with A. lumbricoides and mean epg was 117 (S.E. 50 and 1740 (S.E. 291 in the treatment and placebo groups respectively compared to 45% and 45% of the children being infected with Ascaris and mean epg being 1095 (S.E. 237 and 1126 (S.E. 182 in the treatment and placebo group respectively at baseline. Conclusion Results from this study show that the moderate prevalence and low intensity of STH infection in these preschool children necessitates systematic treatment of the children in child health programmes. Trial Registration Current controlled trials ISRCTN44215995.

A double-blind randomised, placebo-controlled trial evaluating the influence of oral long-acting muscle relaxant (Mebeverine MR), and insufflation with CO{sub 2} on pain associated with barium enema

Energy Technology Data Exchange (ETDEWEB)

Lowe, A.S.; Chapman, A.H.; Wilson, D.; Culpan, A.G. [Department of Radiology, St. James' s University Hospital, Beckett Street, LS9 7TF, Leeds (United Kingdom)

2003-07-01

Previous investigators have shown significant benefit using CO{sub 2} for bowel insufflation. Others have suggested that the long-acting smooth muscle relaxant, Mebeverine, may be of benefit. We subjected this to a randomised double-blind trial. A total of 181 outpatients were randomised to receive either Mebeverine or placebo as pre-medication, and either air or CO{sub 2} for bowel insufflation, thus creating four treatment groups. Visual-analogue lines were used to record pain scores before, during, and up to 8 h following the enema. All groups showed increased pain scores during the enema, with peak pain scores at the end of the examination, falling to baseline scores by 8 h. Patients receiving the combination of C0{sub 2} and placebo had significantly lower pain scores at 1 and 4 h (P=0.00 and P=0.014, respectively; Kruskal-Wallis test) compared with all other groups. Having Mebeverine as a pre-medication did not significantly lower pain scores compared with placebo, and decreased the amount of benefit received from the CO{sub 2}. We confirm that CO{sub 2} is of benefit in decreasing pain during barium enema, and we recommend its routine use to improve the comfort of patients. Mebeverine is not of benefit, and its use as a pre-medication for enemas is not recommended. (orig.)

The effect of escitalopram versus placebo on perceived stress and salivary cortisol in healthy first-degree relatives of patients with depression-A randomised trial

DEFF Research Database (Denmark)

Knorr, Ulla; Vinberg, Maj; Gether, Ulrik

2012-01-01

The effect of selective serotonin reuptake inhibitors (SSRI) on healthy individuals remains unclear. We tested the hypothesis that escitalopram decreases perceived stress and salivary cortisol. The trial has a randomised, blinded, placebo-controlled, parallel-group design. After informed consent 80...... intervals for the next hour, and at 12:00, 18:00 and 23:00. The salivary cortisol awakening response, all day salivary cortisol, and scale scores on sleep, pain, aggression, quality of life, and perceived stress assessed at entry were compared to values following 4 weeks of intervention. Statistically...... significant decreases were found in awakening salivary cortisol (P=0.04) and in all day salivary cortisol (P=0.02) in the escitalopram group compared with the placebo group. There were no statistically significant differences in perceived stress between the intervention groups. These findings from...

Rationale and design of the ranolazine PH-RV study: a multicentred randomised and placebo-controlled study of ranolazine to improve RV function in patients with non-group 2 pulmonary hypertension.

Science.gov (United States)

Han, Yuchi; Forfia, Paul R; Vaidya, Anjali; Mazurek, Jeremy A; Park, Myung H; Ramani, Gautam; Chan, Stephen Y; Waxman, Aaron B

2018-01-01

A major determining factor on outcomes in patients with pulmonary arterial hypertension (PAH) is right ventricular (RV) function. Ranolazine, which is currently approved for chronic stable angina, has been shown to improve RV function in an animal model and has been shown to be safe in small human studies with PAH. We aim to study the effect of ranolazine on RV function using cardiovascular magnetic resonance (CMR) in patients with pulmonary hypertension (non-group 2 patients) and monitor the effect of ranolazine on metabolism using metabolic profiling and changes of microRNA. This study is a longitudinal, randomised, double-blind, placebo-controlled, multicentre proof-of-concept study in 24 subjects with pulmonary hypertension and RV dysfunction treated with ranolazine over 6 months. Subjects who meet the protocol definition of RV dysfunction (CMR RV ejection fraction (EF) <45%) will be randomised to ranolazine or placebo with a ratio of 2:1. Enrolled subjects will be assessed for functional class, 6 min walk test and health outcome based on SF-36 tool. Peripheral blood will be obtained for N-terminal-pro brain natriuretic peptide, metabolic profiling, and microRNA at baseline and the conclusion of the treatment period. CMR will be performed at baseline and the conclusion of the treatment period. The primary outcome is change in RVEF. The exploratory outcomes include clinical, other CMR parameters, metabolic and microRNA changes. The trial protocol was approved by Institutional Review Boards. The trial findings will be disseminated in scientific journals and meetings. NCT01839110 and NCT02829034; Pre-results.

The effect of motor control exercise versus placebo in patients with chronic low back pain [ACTRN012605000262606

Directory of Open Access Journals (Sweden)

Herbert Robert D

2005-11-01

Full Text Available Abstract Background While one in ten Australians suffer from chronic low back pain this condition remains extremely difficult to treat. Many contemporary treatments are of unknown value. One potentially useful therapy is the use of motor control exercise. This therapy has a biologically plausible effect, is readily available in primary care and it is of modest cost. However, to date, the efficacy of motor control exercise has not been established. Methods This paper describes the protocol for a clinical trial comparing the effects of motor control exercise versus placebo in the treatment of chronic non-specific low back pain. One hundred and fifty-four participants will be randomly allocated to receive an 8-week program of motor control exercise or placebo (detuned short wave and detuned ultrasound. Measures of outcomes will be obtained at follow-up appointments at 2, 6 and 12 months after randomisation. The primary outcomes are: pain, global perceived effect and patient-generated measure of disability at 2 months and recurrence at 12 months. Discussion This trial will be the first placebo-controlled trial of motor control exercise. The results will inform best practice for treating chronic low back pain and prevent its occurrence.

Cost effectiveness of group follow-up after structured education for type 1 diabetes: a cluster randomised controlled trial

Science.gov (United States)

2014-01-01

Background This study examines the cost effectiveness of group follow-up after participation in the Dose Adjustment for Normal Eating (DAFNE) structured education programme for type 1 diabetes. Methods Economic evaluation conducted alongside a cluster randomised controlled trial involving 437 adults with type 1 diabetes in Ireland. Group follow-up involved two group education ‘booster’ sessions post-DAFNE. Individual follow-up involved two standard one-to-one hospital clinic visits. Incremental costs, quality-adjusted life years (QALYs) gained and cost effectiveness were estimated at 18 months. Uncertainty was explored using sensitivity analysis and by estimating cost effectiveness acceptability curves. Results Group follow-up was associated with a mean reduction in QALYs gained of 0.04 per patient (P value, 0.052; 95% CI, −0.08 to 0.01, intra-class correlation (ICC), 0.033) and a mean reduction in total healthcare costs of €772 (P value, 0.020; 95% CI, −1,415 to −128: ICC, 0.016) per patient. At alternative threshold values of €5,000, €15,000, €25,000, €35,000, and €45,000, the probability of group follow-up being cost effective was estimated to be 1.000, 0.762, 0.204, 0.078, and 0.033 respectively. Conclusions The results do not support implementation of group follow-up as the sole means of follow-up post-DAFNE. Given the reported cost savings, future studies should explore the cost effectiveness of alternative models of group care for diabetes. Trial registration Current Controlled Trials ISRCTN79759174 (assigned: 9 February 2007). PMID:24927851

Is low-dose amitriptyline effective in the management of chronic low back pain? Study protocol for a randomised controlled trial.

Science.gov (United States)

Urquhart, Donna M; Wluka, Anita E; Sim, Malcolm R; van Tulder, Maurits; Forbes, Andrew; Gibson, Stephen J; Arnold, Carolyn; Fong, Chris; Anthony, Shane N; Cicuttini, Flavia M

2016-10-22

Low back pain is a major clinical and public health problem, with limited evidence-based treatments. Low-dose antidepressants are commonly used to treat pain in chronic low back pain. However, their efficacy is unproven. The aim of this pragmatic, double-blind, randomised, placebo-controlled trial is to determine whether low-dose amitriptyline (an antidepressant) is more effective than placebo in reducing pain in individuals with chronic low back pain. One hundred and fifty individuals with chronic low back pain will be recruited through hospital and private medical and allied health clinics, advertising in local media and posting of flyers in community locations. They will be randomly allocated to receive either low-dose amitriptyline (25 mg) or an active placebo (benztropine mesylate, 1 mg) for 6 months. The primary outcome measure of pain intensity will be assessed at baseline, 3 and 6 months using validated questionnaires. Secondary measures of self-reported low back disability, work absence and hindrance in the performance of paid/unpaid work will also be examined. Intention-to-treat analyses will be performed. This pragmatic, double-blind, randomised, placebo-controlled trial will provide evidence regarding the effectiveness of low-dose antidepressants compared with placebo in reducing pain, disability, work absenteeism and hindrance in work performance in individuals with chronic low back pain. This trial has major public health and clinical importance as it has the potential to provide an effective approach to the management of chronic low back pain. Australian New Zealand Clinical Trials Registry: ACTRN12612000131853 ; registered on 30 January 2012.

MR spectroscopy of hepatic fat and adiponectin and leptin levels during testosterone therapy in type 2 diabetes: a randomized, double-blinded, placebo-controlled trial

DEFF Research Database (Denmark)

Magnussen, L V; Andersen, P E; Diaz, Alejandro Rafael

2017-01-01

Men with type 2 diabetes mellitus (T2D) often have lowered testosterone levels and an increased risk of cardiovascular disease (CVD). Ectopic fat increases the risk of CVD, whereas subcutaneous gluteofemoral fat protects against CVD and has a beneficial adipokine-secreting profile. Testosterone...... replacement therapy (TRT) may reduce the content of ectopic fat and improve the adipokine profile in men with T2D. A randomized, double-blinded, placebo-controlled study in 39 men aged 50-70 years with T2D and bioavailable testosterone levels...

A randomised controlled trial of intravenous zoledronic acid in malignant pleural disease: a proof of principle pilot study.

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Clive, Amelia O; Hooper, Clare E; Edey, Anthony J; Morley, Anna J; Zahan-Evans, Natalie; Hall, David; Lyburn, Iain; White, Paul; Braybrooke, Jeremy P; Sequeiros, Iara; Lyen, Stephen M; Milton, Tim; Kahan, Brennan C; Maskell, Nick A

2015-01-01

Animal studies have shown Zoledronic Acid (ZA) may diminish pleural fluid accumulation and tumour bulk in malignant pleural disease (MPD). We performed a pilot study to evaluate its effects in humans. We undertook a single centre, double-blind, placebo-controlled trial in adults with MPD. Patients were randomised (1:1) to receive 2 doses of intravenous ZA or placebo, 3 weeks apart and were followed-up for 6 weeks. The co-primary outcomes were change in Visual Analogue Scale (VAS) score measured breathlessness during trial follow-up and change in the initial area under the curve (iAUC) on thoracic Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) from randomisation to week 5. Multiple secondary endpoints were also evaluated. Between January 2010 and May 2013, 30 patients were enrolled, 24 randomised and 4 withdrew after randomisation (1 withdrew consent; 3 had a clinical decline). At baseline, the ZA group were more breathless, had more advanced disease on radiology and worse quality of life than the placebo group. There was no significant difference between the groups with regards change in breathlessness (Adjusted mean difference (AMD) 4.16 (95%CI -4.7 to 13.0)) or change in DCE-MRI iAUC (AMD -15.4 (95%CI -58.1 to 27.3). Two of nine (22%) in the ZA arm had a >10% improvement by modified RECIST (vs 0/11 who received placebo). There was no significant difference in quality of life measured by the QLQ-C30 score (global QOL: AMD -4.1 (-13.0 to 4.9)), side effects or serious adverse event rates. This is the first human study to evaluate ZA in MPD. The study is limited by small numbers and imbalanced baseline characteristics. Although no convincing treatment effect was identified, potential benefits for specific subgroups of patients cannot be excluded. This study provides important information regarding the feasibility of future trials to evaluate the effects of ZA further. UK Clinical Research Network ID 8877 ISRCTN17030426 www.isrctn.com.

A randomised controlled trial of intravenous zoledronic acid in malignant pleural disease: a proof of principle pilot study.

Directory of Open Access Journals (Sweden)

Amelia O Clive

Full Text Available Animal studies have shown Zoledronic Acid (ZA may diminish pleural fluid accumulation and tumour bulk in malignant pleural disease (MPD. We performed a pilot study to evaluate its effects in humans.We undertook a single centre, double-blind, placebo-controlled trial in adults with MPD. Patients were randomised (1:1 to receive 2 doses of intravenous ZA or placebo, 3 weeks apart and were followed-up for 6 weeks. The co-primary outcomes were change in Visual Analogue Scale (VAS score measured breathlessness during trial follow-up and change in the initial area under the curve (iAUC on thoracic Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI from randomisation to week 5. Multiple secondary endpoints were also evaluated.Between January 2010 and May 2013, 30 patients were enrolled, 24 randomised and 4 withdrew after randomisation (1 withdrew consent; 3 had a clinical decline. At baseline, the ZA group were more breathless, had more advanced disease on radiology and worse quality of life than the placebo group. There was no significant difference between the groups with regards change in breathlessness (Adjusted mean difference (AMD 4.16 (95%CI -4.7 to 13.0 or change in DCE-MRI iAUC (AMD -15.4 (95%CI -58.1 to 27.3. Two of nine (22% in the ZA arm had a >10% improvement by modified RECIST (vs 0/11 who received placebo. There was no significant difference in quality of life measured by the QLQ-C30 score (global QOL: AMD -4.1 (-13.0 to 4.9, side effects or serious adverse event rates.This is the first human study to evaluate ZA in MPD. The study is limited by small numbers and imbalanced baseline characteristics. Although no convincing treatment effect was identified, potential benefits for specific subgroups of patients cannot be excluded. This study provides important information regarding the feasibility of future trials to evaluate the effects of ZA further.UK Clinical Research Network ID 8877 ISRCTN17030426 www.isrctn.com.

A randomized, placebo-controlled, double-blind, prospective trial to evaluate the effect of vildagliptin in new-onset diabetes mellitus after kidney transplantation

Directory of Open Access Journals (Sweden)

Hörl Walter H

2010-10-01

Full Text Available Abstract Background New-onset diabetes mellitus after transplantation (NODAT, a frequent and serious complication after transplantation, is associated with decreased graft and patient survival. Currently, it is diagnosed and treated primarily according to existing guidelines for type II diabetes. To date, only a few trials have studied antidiabetic drugs in patients with NODAT. Vildagliptin is a novel dipeptidyl peptidase-4 (DPP-4 inhibitor that improves pancreatic islet function by enhancing both α- and β-cell responsiveness to increased blood glucose. Experimental data show potential protective effects of DPP-4 inhibitors on islet function after exogenous stress stimuli including immunosuppressants. Therefore, the therapy of NODAT with this class of compounds seems attractive. At present, vildagliptin is used to treat type II diabetes as monotherapy or in combination with other antidiabetic drugs, since that it efficiently decreases glycated hemoglobin (HbA1c values. Additionally, vildagliptin has been shown to be safe in patients with moderately impaired kidney function. This study will evaluate the safety and efficacy of vildagliptin monotherapy in renal transplant recipients with recently diagnosed NODAT. Methods/Design This study is a randomized, placebo-controlled, double-blind, prospective phase II trial. Using the results of routinely performed oral glucose tolerance tests (OGTT in stable renal transplant patients at our center, we will recruit patients without a history of diabetes and a 2 h glucose value surpassing 200 mg/dl (11.1 mmol/l. They are randomized to receive either 50 mg vildagliptin or placebo once daily. A total of 32 patients with newly diagnosed NODAT will be included. The primary endpoint is the difference in the 2 h glucose value between baseline and the repeated OGTT performed 3 months after treatment start, compared between the vildagliptin- and the placebo-group. Secondary endpoints include changes in HbA1c and

Walking away from type 2 diabetes: trial protocol of a cluster randomised controlled trial evaluating a structured education programme in those at high risk of developing type 2 diabetes.

Science.gov (United States)

Yates, Thomas; Davies, Melanie J; Henson, Joe; Troughton, Jacqui; Edwardson, Charlotte; Gray, Laura J; Khunti, Kamlesh

2012-05-29

The prevention of type 2 diabetes is a recognised health care priority globally. Within the United Kingdom, there is a lack of research investigating optimal methods of translating diabetes prevention programmes, based on the promotion of a healthy lifestyle, into routine primary care. This study aims to establish the behavioural and clinical effectiveness of a structured educational programme designed to target perceptions and knowledge of diabetes risk and promote a healthily lifestyle, particularly increased walking activity, in a multi-ethnic population at a high risk of developing type 2 diabetes. Cluster randomised controlled trial undertaken at the level of primary care practices. Follow-up will be conducted at 12, 24 and 36 months. The primary outcome is change in objectively measured ambulatory activity. Secondary outcomes include progression to type 2 diabetes, biochemical variables (including fasting glucose, 2-h glucose, HbA1c and lipids), anthropometric variables, quality of life and depression. 10 primary care practices will be recruited to the study (5 intervention, 5 control). Within each practice, individuals at high risk of impaired glucose regulation will be identified using an automated version of the Leicester Risk Assessment tool. Individuals scoring within the 90th percentile in each practice will be invited to take part in the study. Practices will be assigned to either the control group (advice leaflet) or the intervention group, in which participants will be invited to attend a 3 hour structured educational programme designed to promote physical activity and a healthy lifestyle. Participants in the intervention practices will also be invited to attend annual group-based maintenance workshops and will receive telephone contact halfway between annual sessions. The study will run from 2010-2014. This study will provide new evidence surrounding the long-term effectiveness of a diabetes prevention programme run within routine primary care in

Protocol for the Northern Manhattan Diabetes Community Outreach Project. A randomised trial of a community health worker intervention to improve diabetes care in Hispanic adults.

Science.gov (United States)

Palmas, Walter; Teresi, Jeanne A; Findley, Sally; Mejia, Miriam; Batista, Milagros; Kong, Jian; Silver, Stephanie; Luchsinger, Jose A; Carrasquillo, Olveen

2012-01-01

Hispanics in the USA are affected by the diabetes epidemic disproportionately, and they consistently have lower access to care, poorer control of the disease and higher risk of complications. This study evaluates whether a community health worker (CHW) intervention may improve clinically relevant markers of diabetes care in adult underserved Hispanics. The Northern Manhattan Diabetes Community Outreach Project (NOCHOP) is a two-armed randomised controlled trial to be performed as a community-based participatory research study performed in a Primary Care Setting in Northern Manhattan (New York City). 360 Hispanic adults with poorly controlled type 2 diabetes mellitus (haemoglobin A1c >8%), aged 35-70 years, will be randomised at a 1:1 ratio, within Primary Care Provider clusters. The two study arms are (1) a 12-month CHW intervention and (2) enhanced usual care (educational materials mailed at 4-month intervals, preceded by phone calls). The end points, assessed after 12 months, are primary = haemoglobin A1c and secondary = blood pressure and low-density lipoprotein-cholesterol levels. In addition, the study will describe the CHW intervention in terms of components and intensity and will assess its effects on (1) medication adherence, (2) medication intensification, (3) diet and (4) physical activity. All participants will provide informed consent; the study protocol has been approved by the Institutional Review Board of Columbia University Medical Center. CHW interventions hold great promise in improving the well-being of minority populations who suffer from diabetes mellitus. The NOCHOP study will provide valuable information about the efficacy of those interventions vis-à-vis clinically relevant end points and will inform policy makers through a detailed characterisation of the programme and its effects. NCT00787475 at clinicaltrials.gov.

Habitual dietary fibre intake influences gut microbiota response to an inulin-type fructan prebiotic: a randomised, double-blind, placebo-controlled, cross-over, human intervention study.

Science.gov (United States)

Healey, Genelle; Murphy, Rinki; Butts, Christine; Brough, Louise; Whelan, Kevin; Coad, Jane

2018-01-01

Dysbiotic gut microbiota have been implicated in human disease. Diet-based therapeutic strategies have been used to manipulate the gut microbiota towards a more favourable profile. However, it has been demonstrated that large inter-individual variability exists in gut microbiota response to a dietary intervention. The primary objective of this study was to investigate whether habitually low dietary fibre (LDF) v. high dietary fibre (HDF) intakes influence gut microbiota response to an inulin-type fructan prebiotic. In this randomised, double-blind, placebo-controlled, cross-over study, thirty-four healthy participants were classified as LDF or HDF consumers. Gut microbiota composition (16S rRNA bacterial gene sequencing) and SCFA concentrations were assessed following 3 weeks of daily prebiotic supplementation (Orafti® Synergy 1; 16 g/d) or placebo (Glucidex® 29 Premium; 16 g/d), as well as after 3 weeks of the alternative intervention, following a 3-week washout period. In the LDF group, the prebiotic intervention led to an increase in Bifidobacterium (P=0·001). In the HDF group, the prebiotic intervention led to an increase in Bifidobacterium (Pgut microbiota response and are therefore more likely to benefit from an inulin-type fructan prebiotic than those with LDF intakes. Future studies aiming to modulate the gut microbiota and improve host health, using an inulin-type fructan prebiotic, should take habitual dietary fibre intake into account.

EFFECTS OF ANGIOTENSIN II BLOCKADE WITH IRBESARTAN ON INFLAMMATORY MARKERS IN HAEMODIALYSIS PATIENTS: A RANDOMISED DOUBLE BLIND PLACEBO CONTROLLED ONE-YEAR FOLLOW-UP TRIAL (SAFIR STUDY)

DEFF Research Database (Denmark)

Peters, Christian Daugaard; Kjærgaard, Krista Dybtved; Nielsen, Claus H.

as factors using Stata/IC 12.1. Results Eighty-two patients were randomised (placebo/irbesartan: 41/41) and 56 completed one year of treatment. The groups (placebo/irbesartan) were comparable at baseline (mean±SD): Males 26(63%)/30(73%); age 62±14/61±16 years; systolic blood pressure (BP) 145±19/148±21 mm......Hg; HD vintage 168±95/171±93 days; HD time 10±2/11±3 hr/week; urine output 1.3±0.7/1.5±0.8 L/24 h; glomerular filtration rate 4.8/5.7 mL/min/1.73m2. Predialysis systolic BP decreased to the same extent in the irbesartan (–10 mm Hg) and in the placebo arm (–8 mm Hg). Use of additional antihypertensive......(188-1343)/377(213-832) pg/mL; TGF-β 3.2(0.8-13.9)/3.6(1.3-13.8) ng/mL. Overall, there was no significant difference in hsCRP, IL-6, IL-8, and TGF-β between patients receiving placebo, and irbesartan treated patients during the study period, and hsCRP, IL-6, IL-8, and TGF-β were relatively stable during the study period (P...

A Randomised Controlled Trial to Reduce Sedentary Time in Young Adults at Risk of Type 2 Diabetes Mellitus: Project STAND (Sedentary Time ANd Diabetes.

Directory of Open Access Journals (Sweden)

Stuart J H Biddle

Full Text Available Type 2 diabetes mellitus (T2DM, a serious and prevalent chronic disease, is traditionally associated with older age. However, due to the rising rates of obesity and sedentary lifestyles, it is increasingly being diagnosed in the younger population. Sedentary (sitting behaviour has been shown to be associated with greater risk of cardio-metabolic health outcomes, including T2DM. Little is known about effective interventions to reduce sedentary behaviour in younger adults at risk of T2DM. We aimed to investigate, through a randomised controlled trial (RCT design, whether a group-based structured education workshop focused on sitting reduction, with self-monitoring, reduced sitting time.Adults aged 18-40 years who were either overweight (with an additional risk factor for T2DM or obese were recruited for the Sedentary Time ANd Diabetes (STAND RCT. The intervention programme comprised of a 3-hour group-based structured education workshop, use of a self-monitoring tool, and follow-up motivational phone call. Data were collected at three time points: baseline, 3 and 12 months after baseline. The primary outcome measure was accelerometer-assessed sedentary behaviour after 12 months. Secondary outcomes included other objective (activPAL and self-reported measures of sedentary behaviour and physical activity, and biochemical, anthropometric, and psycho-social variables.187 individuals (69% female; mean age 33 years; mean BMI 35 kg/m2 were randomised to intervention and control groups. 12 month data, when analysed using intention-to-treat analysis (ITT and per-protocol analyses, showed no significant difference in the primary outcome variable, nor in the majority of the secondary outcome measures.A structured education intervention designed to reduce sitting in young adults at risk of T2DM was not successful in changing behaviour at 12 months. Lack of change may be due to the brief nature of such an intervention and lack of focus on environmental change

Comparison of neonatal outcomes in women with gestational diabetes with moderate hyperglycaemia on metformin or glibenclamide--a randomised controlled trial.

Science.gov (United States)

George, Anne; Mathews, Jiji E; Sam, Dibu; Beck, Manisha; Benjamin, Santosh J; Abraham, Anuja; Antonisamy, Balevendra; Jana, Atanu K; Thomas, Nihal

2015-02-01

Two oral hypoglycaemic agents, metformin and glibenclamide, have been compared with insulin in separate large randomised controlled trials and have been found to be as effective as insulin in gestational diabetes. However, very few trials have compared metformin with glibenclamide. Of 159 South Indian women with fasting glucose ≥5.5 mmol/l and ≤7.2 mmol/l and/or 2-h post-prandial value ≥6.7 mmol/l and ≤13.9 mmol/l after medical nutritional therapy consented to be randomised to receive either glibenclamide or metformin. 80 women received glibenclamide and 79 received metformin. Neonatal outcomes were assessed by neonatologists who were unaware that the mother was part of a study and were recorded by assessors blinded to the medication the mother was given. The primary outcome was a composite of neonatal outcomes namely macrosomia, hypoglycaemia, need for phototherapy, respiratory distress, stillbirth or neonatal death and birth trauma. Secondary outcomes were birthweight, maternal glycaemic control, pregnancy induced hypertension, preterm birth, need for induction of labour, mode of delivery and complications of delivery. Baseline characteristics were similar but for the higher fasting triglyceride levels in women on metformin. The primary outcome was seen in 35% of the glibenclamide group and 18.9% of the metformin group [95% CI 16.1 (2.5, 29.7); P = 0.02]. The difference in outcome related to a higher rate of neonatal hypoglycaemia in the glibenclamide group (12.5%) versus none in the metformin group [95% CI 12.5(5.3, 19.7); P = 0.001]. Secondary outcomes in both groups were similar. In a south Indian population with gestational diabetes, metformin was associated with better neonatal outcomes than glibenclamide. © 2015 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

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

Science.gov (United States)

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

2016-08-01

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

A randomised controlled trial of the use of aromatherapy and hand massage to reduce disruptive behaviour in people with dementia.

Science.gov (United States)

Fu, Chieh-Yu; Moyle, Wendy; Cooke, Marie

2013-07-10

Aromatherapy and hand massage therapies have been reported to have some benefit for people with dementia who display behavioural symptoms; however there are a number of limitations of reported studies. The aim is to investigate the effect of aromatherapy (3% lavender oil spray) with and without hand massage on disruptive behaviour in people with dementia living in long-term care. In a single blinded randomised controlled trial 67 people with a diagnosis of dementia and a history of disruptive behaviour, from three long-term care facilities were recruited and randomised using a random number table into three groups: (1) Combination (aromatherapy and hand massage) (n = 22), (2) Aromatherapy (n = 23), (3) Placebo control (water spray) (n = 22). The intervention was given twice daily for six weeks. Data on residents' behaviour (CMAI) and cognition (MMSE) were collected before, during and after the intervention. Despite a downward trend in behaviours displayed not one of the interventions significantly reduced disruptive behaviour. Further large-scale placebo controlled studies are required where antipsychotic medication is controlled and a comparison of the methods of application of aromatherapy are investigated. ACTRN12612000917831.

Do prebiotics reduce the number of fever episodes in healthy children in their first year of life : a randomised controlled trial

NARCIS (Netherlands)

van Stuijvenberg, Margriet; Eisses, Annemieke M.; Gruber, Christoph; Mosca, Fabio; Arslanoglu, Sertac; Chirico, Gaetano; Braegger, Christian P.; Riedler, Josef; Boehm, Gunther; Sauer, Pieter J. J.

2011-01-01

The objective of the present study was to assess the effect of adding specific prebiotics to standard formula feeding on the number of fever episodes in the first year of life. In the present randomised, double-blind, placebo-controlled trial in seven centres in five West European countries, 830

Fluoxetine for motor recovery after acute ischaemic stroke (FLAME): a randomised placebo-controlled trial.

Science.gov (United States)

Chollet, François; Tardy, Jean; Albucher, Jean-François; Thalamas, Claire; Berard, Emilie; Lamy, Catherine; Bejot, Yannick; Deltour, Sandrine; Jaillard, Assia; Niclot, Philippe; Guillon, Benoit; Moulin, Thierry; Marque, Philippe; Pariente, Jérémie; Arnaud, Catherine; Loubinoux, Isabelle

2011-02-01

Hemiplegia and hemiparesis are the most common deficits caused by stroke. A few small clinical trials suggest that fluoxetine enhances motor recovery but its clinical efficacy is unknown. We therefore aimed to investigate whether fluoxetine would enhance motor recovery if given soon after an ischaemic stroke to patients who have motor deficits. In this double-blind, placebo-controlled trial, patients from nine stroke centres in France who had ischaemic stroke and hemiplegia or hemiparesis, had Fugl-Meyer motor scale (FMMS) scores of 55 or less, and were aged between 18 years and 85 years were eligible for inclusion. Patients were randomly assigned, using a computer random-number generator, in a 1:1 ratio to fluoxetine (20 mg once per day, orally) or placebo for 3 months starting 5-10 days after the onset of stroke. All patients had physiotherapy. The primary outcome measure was the change on the FMMS between day 0 and day 90 after the start of the study drug. Participants, carers, and physicians assessing the outcome were masked to group assignment. Analysis was of all patients for whom data were available (full analysis set). This trial is registered with ClinicalTrials.gov, number NCT00657163. 118 patients were randomly assigned to fluoxetine (n=59) or placebo (n=59), and 113 were included in the analysis (57 in the fluoxetine group and 56 in the placebo group). Two patients died before day 90 and three withdrew from the study. FMMS improvement at day 90 was significantly greater in the fluoxetine group (adjusted mean 34·0 points [95% CI 29·7-38·4]) than in the placebo group (24·3 points [19·9-28·7]; p=0·003). The main adverse events in the fluoxetine and placebo groups were hyponatraemia (two [4%] vs two [4%]), transient digestive disorders including nausea, diarrhoea, and abdominal pain (14 [25%] vs six [11%]), hepatic enzyme disorders (five [9%] vs ten [18%]), psychiatric disorders (three [5%] vs four [7%]), insomnia (19 [33%] vs 20 [36%]), and partial

A nested mechanistic sub-study into the effect of tranexamic acid versus placebo on intracranial haemorrhage and cerebral ischaemia in isolated traumatic brain injury: study protocol for a randomised controlled trial (CRASH-3 Trial Intracranial Bleeding Mechanistic Sub-Study [CRASH-3 IBMS]).

Science.gov (United States)

Mahmood, Abda; Roberts, Ian; Shakur, Haleema

2017-07-17

Tranexamic acid prevents blood clots from breaking down and reduces bleeding. However, it is uncertain whether tranexamic acid is effective in traumatic brain injury. The CRASH-3 trial is a randomised controlled trial that will examine the effect of tranexamic acid (versus placebo) on death and disability in 13,000 patients with traumatic brain injury. The CRASH-3 trial hypothesizes that tranexamic acid will reduce intracranial haemorrhage, which will reduce the risk of death. Although it is possible that tranexamic acid will reduce intracranial bleeding, there is also a potential for harm. In particular, tranexamic acid may increase the risk of cerebral thrombosis and ischaemia. The protocol detailed here is for a mechanistic sub-study nested within the CRASH-3 trial. This mechanistic sub-study aims to examine the effect of tranexamic acid (versus placebo) on intracranial bleeding and cerebral ischaemia. The CRASH-3 Intracranial Bleeding Mechanistic Sub-Study (CRASH-3 IBMS) is nested within a prospective, double-blind, multi-centre, parallel-arm randomised trial called the CRASH-3 trial. The CRASH-3 IBMS will be conducted in a cohort of approximately 1000 isolated traumatic brain injury patients enrolled in the CRASH-3 trial. In the CRASH-3 IBMS, brain scans acquired before and after randomisation are examined, using validated methods, for evidence of intracranial bleeding and cerebral ischaemia. The primary outcome is the total volume of intracranial bleeding measured on computed tomography after randomisation, adjusting for baseline bleeding volume. Secondary outcomes include progression of intracranial haemorrhage (from pre- to post-randomisation scans), new intracranial haemorrhage (seen on post- but not pre-randomisation scans), intracranial haemorrhage following neurosurgery, and new focal ischaemic lesions (seen on post-but not pre-randomisation scans). A linear regression model will examine whether receipt of the trial treatment can predict haemorrhage

No effect of the FitFor2 exercise programme on blood glucose, insulin sensitivity, and birthweight in pregnant women who were overweight and at risk for gestational diabetes: Results of a randomised controlled trial

NARCIS (Netherlands)

Oostdam, N.; Poppel, M.N.M. van; Wouters, M.G.A.J.; Eekhoff, E.M.W.; Bekedam, D.J.; Kuchenbecker, W.K.H.; Quartero, H.W.P.; Heres, M.H.B.; Mechelen, W. van

2012-01-01

Objective To evaluate the effectiveness of an exercise programme for pregnant women who were overweight or obese and at risk for gestational diabetes mellitus (GDM). Design Randomised controlled trial. Setting Hospitals and midwifery practices in the Netherlands. Population Pregnant women who were

Exploring the optimum approach to the use of CT densitometry in a randomised placebo-controlled study of augmentation therapy in alpha 1-antitrypsin deficiency

DEFF Research Database (Denmark)

Parr, David G; Dirksen, Asger; Piitulainen, Eeva

2009-01-01

lung assessment. The EXAcerbations and CT scan as Lung Endpoints (EXACTLE) trial aimed to clarify the optimum approach to the use of CT densitometry data for the assessment of alpha 1-antitrypsin (AAT) augmentation therapy on the progression of emphysema in AAT deficiency (AATD). METHODS: Patients...... with AATD (n = 77) were randomised to weekly infusions of 60 mg/kg human AAT (Prolastin) or placebo over 2 to 2.5 years. Lung volume was included as a covariate in an endpoint analysis and a comparison was made of different CT densitometric indices (15th percentile lung density [PD15], mean lung density...

The Women's international study of long-duration oestrogen after menopause (WISDOM: a randomised controlled trial

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Meade Tom W

2007-02-01

Full Text Available Abstract Background At the time of feasibility work and final design of the trial there was no randomised control trial evidence for the long-term risks and benefits of hormone replacement therapy. Observational studies had suggested that long term use of estrogen was likely to be associated, amongst other things, with reduced risks of osteoporosis and ischaemic heart disease and increased risks of breast and endometrial cancer. Concomitant use of progestogens had been shown to protect against endometrial cancer, but there were few data showing how progestogen might affect estrogen actions on other conditions. Disease specific risks from observational studies suggested that, overall, long-term HRT was likely to be beneficial. Several studies showed that mortality from all causes was lower in HRT users than in non-users. Some secondary cardiovascular prevention trials were ongoing but evidence was also required for a range of outcomes in healthy women. The WISDOM trial was designed to compare combined estrogen and progestogen versus placebo, and estrogen alone versus combined estrogen and progestogen. During the development of WISDOM the Women's Health Initiative trial was designed, funded and started in the US. Design Randomised, placebo, controlled, trial. Methods The trial was set in general practices in the UK (384, Australia (94, and New Zealand (24. In these practices 284175 women aged 50–69 years were registered with 226282 potentially eligible. We sought to randomise 22300 postmenopausal women aged 50 – 69 and treat for ten years. The interventions were: conjugated equine estrogens, 0.625 mg orally daily; conjugated equine estrogens plus medroxyprogesterone acetate 2.5/5.0 mg orally daily; matched placebo. Primary outcome measures were: major cardiovascular disease, osteoporotic fractures, breast cancer and dementia. Secondary outcomes were: other cancers, all cause death, venous thromboembolism and cerebro-vascular disease. Results

Effect of lactic acid suppositories compared with oral metronidazole and placebo in bacterial vaginosis: a randomised clinical trial.

Science.gov (United States)

Boeke, A J; Dekker, J H; van Eijk, J T; Kostense, P J; Bezemer, P D

1993-01-01

OBJECTIVE--To compare the effect of lactic acid locally, metronidazole orally and placebo in women with bacterial vaginosis. DESIGN--Randomised clinical trial. SETTING--30 general practices in the Netherlands. PATIENTS--125 women consulting the general practitioner for symptomatic bacterial vaginosis. MAIN OUTCOME MEASURES--Duration of subjective symptoms, recurrence of symptoms, clinically diagnosed cure, adverse events. RESULTS--Survival analysis showed a significantly faster disappearance of symptoms in the metronidazole category compared with both lactic acid and placebo (p = 0.0005 metronidazole v placebo, p = 0.0002 metronidazole v lactic acid p = 0.6521 lactic acid v placebo [The stratified Mantel Cox test]). The median duration until absence of symptoms was 21 days for metronidazole and 80 days for placebo. Disappearance of symptoms did not occur in 50% of the lactic acid group in 90 days. Recurrence rates of symptoms were similar over the treatment categories (p = 0.13 metronidazole v placebo and p = 0.12 lactic acid v placebo). After 2 weeks cure rates (cure defined as less than three of four clinical criteria present) were 83%, 49% and 47% for metronidazole, lactic acid and placebo category respectively. At that time cure rates (cure defined as none of three clinical criteria present) were 10%, 0% and 3%. After four weeks and three months these figures were: 55%, 20%, 20% and 64%, 28%, 28%. No differences in adverse events were found between the three interventions. CONCLUSIONS--Lactic acid suppositories are ineffective, metronidazole capsules are effective on signs and symptoms in bacterial vaginosis. A considerable proportion of the patients recover without active medication. PMID:8244360

The beneficial effects of probiotic administration on wound healing and metabolic status in patients with diabetic foot ulcer: A randomized, double-blind, placebo-controlled trial.

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Mohseni, Sima; Bayani, Masomeh; Bahmani, Fereshteh; Tajabadi-Ebrahimi, Maryam; Bayani, Mohammad Ali; Jafari, Parvaneh; Asemi, Zatollah

2018-03-01

This study was conducted to evaluate the effects of probiotic supplementation on wound healing and metabolic status in subjects with diabetic foot ulcer (DFU). This randomized, double-blind, placebo-controlled trial was conducted among 60 subjects (aged 40-85 years old) with grade 3 diabetic foot ulcer. Individuals were randomly divided into 2 groups (30 subjects each group) to receive either probiotic or placebo daily for 12 weeks. After the 12-week intervention, compared with the placebo, probiotic supplementation led to significant reductions in ulcer length (-1.3 ± 0.9 vs. -0.8 ± 0.7 cm, P = .01), width (-1.1 ± 0.7 vs. -0.7 ± 0.7 cm, P = .02), and depth (-0.5 ± 0.3 vs. -0.3 ± 0.3 cm, P = .02). Furthermore, significant reductions in fasting plasma glucose (-29.6 ± 30.3 vs. -5.8 ± 39.8 mg/dL, P = .01), serum insulin concentrations (-4.3 ± 7.9 vs. +0.4 ± 8.5 μIU/mL, P = .03), and haemoglobin A1c (-0.6 ± 0.5 vs. -0.2 ± 0.4%, P = .003) and a significant rise in the quantitative insulin sensitivity check index (+0.01 ± 0.01 vs. -0.01 ± 0.02, P = .003) were seen following supplementation of probiotic compared with the placebo. Additionally, compared with the placebo, probiotic supplementation resulted in significant decreases in serum total cholesterol (-4.8 ± 16.1 vs. +7.0 ± 27.1 mg/dL, P = .04), high-sensitivity C-reactive protein (-9.0 ± 14.7 vs. -1.7 ± 8.6 mg/L, P = .02), plasma malondialdehyde (-0.8 ± 0.8 vs. -0.2 ± 0.8 μmol/L, P = .001), and significant increases in plasma nitric oxide (+6.2 ± 8.2 vs. +0.8 ± 8.0 μmol/L, P = .01) and total antioxidant capacity concentrations (+179.3 ± 97.2 vs. -85.1 ± 203.4 mmol/L, P diabetic foot ulcer had beneficial effects on ulcer size, glycaemic control, total cholesterol, high-sensitivity C-reactive protein, plasma nitric oxide, total antioxidant capacity, and malondialdehyde levels. Copyright © 2017 John Wiley

Memantine in frontotemporal lobar degeneration: A multicenter, randomised, double-blind, placebo-controlled trial

Science.gov (United States)

Boxer, Adam L.; Knopman, David S.; Kaufer, Daniel I.; Grossman, Murray; Onyike, Chiadi; Graf-Radford, Neill; Mendez, Mario; Kerwin, Diana; Lerner, Alan; Wu, Chuang-Kuo; Koestler, Mary; Shapira, Jill; Sullivan, Kathryn; Klepac, Kristen; Lipowski, Kristine; Ullah, Jerin; Fields, Scott; Kramer, Joel H.; Merrilees, Jennifer; Neuhaus, John; Mesulam, M. Marsel; Miller, Bruce L.

2013-01-01

Background Memantine has been used off-label to treat frontotemporal lobar degeneration (FTD). A previous 26 week open label study suggested a transient, modest benefit on neuropsychiatric symptoms as measured by the Neuropsychiatric Inventory (NPI). Methods We performed a randomized, parallel group, double blind, placebo controlled trial of 20 mg memantine taken orally daily for 26 weeks in FTD. Participants met Neary criteria for behavioral variant (bvFTD) or semantic dementia (SD) and had characteristic brain atrophy. Use of cholinesterase inhibitors was prohibited. The objective of the study was to determine whether memantine is an effective treatment for FTD. Individuals were randomized to memantine or matched placebo tablets in blocks of two and four. Primary endpoints were the change in total NPI score and Clinical Global Impression of Change (CGIC) scores after 26 weeks. Secondary outcomes included a neuropsychological battery, and other cognitive, global and activity of daily living measures. Clinicaltrials.gov identifier: NCT00545974 Findings 100 subjects were screened, 81 were randomized, 5 (6%) discontinued and 76 completed all visits. Enrollment numbers were lower than planned due to many subjects’ preference to take memantine or cholinesterase inhibitors off-label rather than participate in a clinical trial. 39 memantine and 42 placebo subjects entered the primary intent to treat analysis. There was no effect of memantine treatment on either the NPI (mean difference [MD] 2.2, 95%CI: −3.9, 8.3, p = 0.47) or CGIC (MD 0, 95%CI: −0.4, 0.4, p = 0.90) after 26 weeks of treatment. Memantine was generally well tolerated, however there were more frequent cognitive adverse events in the memantine group. Interpretation There was no benefit of memantine treatment in bvFTD or SD. These data do not support memantine use in FTD. Funding Forest Research Institute PMID:23290598

Dialysis-associated hypertension treated with Telmisartan--DiaTel: a pilot, placebo-controlled, cross-over, randomized trial.

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Matthias Huber

Full Text Available Treatment of hypertension in hemodialysis (HD patients is characterised by lack of evidence for both the blood pressure (BP target goal and the recommended drug class to use. Telmisartan, an Angiotensin receptor blocker (ARB that is metabolised in the liver and not excreted via HD extracorporeal circuit might be particularly suitable for HD patients. We designed and conducted a randomised, placebo-controlled, double-blind and cross-over trial for treatment of dialysis-associated hypertension with telmisartan 80 mg once daily or placebo on top of standard antihypertensive treatment excluding other Renin-Angiotensin-System (RAS blockers. In 29 patients after randomization we analysed BP after a treatment period of 8 weeks, while 13 started with telmisartan and 16 with placebo; after 8 weeks 11 continued with telmisartan and 12 with placebo after cross-over, respectively. Patients exhibited a significant reduction of systolic pre-HD BP from 141.9±21.8 before to 131.3±17.3 mmHg after the first treatment period with telmisartan or placebo. However, no average significant influence of telmisartan was observed compared to placebo. The latter may be due to a large inter-individual variability of BP responses reaching from a 40 mmHg decrease under placebo to 40 mmHg increase under telmisartan. Antihypertensive co-medication was changed for clinical reasons in 7 out of 21 patients with no significant difference between telmisartan and placebo groups. Our starting hypothesis, that telmisartan on top of standard therapy lowers systolic office BP in HD patients could not be confirmed. In conclusion, this small trial indicates that testing antihypertensive drug efficacy in HD patients is challenging due to complicated standardization of concomitant medication and other confounding factors, e.g. volume status, salt load and neurohormonal activation, that influence BP control in HD patients.Clinicaltrialsregister.eu 2005-005021-60.

Combining escitalopram and cognitive-behavioural therapy for social anxiety disorder: randomised controlled fMRI trial.

Science.gov (United States)

Gingnell, Malin; Frick, Andreas; Engman, Jonas; Alaie, Iman; Björkstrand, Johannes; Faria, Vanda; Carlbring, Per; Andersson, Gerhard; Reis, Margareta; Larsson, Elna-Marie; Wahlstedt, Kurt; Fredrikson, Mats; Furmark, Tomas

2016-09-01

Selective serotonin reuptake inhibitors (SSRIs) and cognitive-behavioural therapy (CBT) are often used concomitantly to treat social anxiety disorder (SAD), but few studies have examined the effect of this combination. To evaluate whether adding escitalopram to internet-delivered CBT (ICBT) improves clinical outcome and alters brain reactivity and connectivity in SAD. Double-blind, randomised, placebo-controlled neuroimaging trial of ICBT combined either with escitalopram (n = 24) or placebo (n = 24), including a 15-month clinical follow-up (trial registration: ISRCTN24929928). Escitalopram+ICBT, relative to placebo+ICBT, resulted in significantly more clinical responders, larger reductions in anticipatory speech state anxiety at post-treatment and larger reductions in social anxiety symptom severity at 15-month follow-up and at a trend-level (P = 0.09) at post-treatment. Right amygdala reactivity to emotional faces also decreased more in the escitalopram+ICBT combination relative to placebo+ICBT, and in treatment responders relative to non-responders. Adding escitalopram improves the outcome of ICBT for SAD and decreased amygdala reactivity is important for anxiolytic treatment response. © The Royal College of Psychiatrists 2016.

Daily co-trimoxazole prophylaxis to prevent mortality in children with complicated severe acute malnutrition: a multicentre, double-blind, randomised placebo-controlled trial.

Science.gov (United States)

Berkley, James A; Ngari, Moses; Thitiri, Johnstone; Mwalekwa, Laura; Timbwa, Molline; Hamid, Fauzat; Ali, Rehema; Shangala, Jimmy; Mturi, Neema; Jones, Kelsey D J; Alphan, Hassan; Mutai, Beatrice; Bandika, Victor; Hemed, Twahir; Awuondo, Ken; Morpeth, Susan; Kariuki, Samuel; Fegan, Gregory

2016-07-01

Children with complicated severe acute malnutrition (SAM) have a greatly increased risk of mortality from infections while in hospital and after discharge. In HIV-infected children, mortality and admission to hospital are prevented by daily co-trimoxazole prophylaxis, despite locally reported bacterial resistance to co-trimoxazole. We aimed to assess the efficacy of daily co-trimoxazole prophylaxis on survival in children without HIV being treated for complicated SAM. We did a multicentre, double-blind, randomised, placebo-controlled study in four hospitals in Kenya (two rural hospitals in Kilifi and Malindi, and two urban hospitals in Mombasa and Nairobi) with children aged 60 days to 59 months without HIV admitted to hospital and diagnosed with SAM. We randomly assigned eligible participants (1:1) to 6 months of either daily oral co-trimoxazole prophylaxis (given as water-dispersible tablets; 120 mg per day for age malnutrition (kwashiorkor), and 1221 (69%) were stunted (length-for-age Z score child-years of observation, 122 (14%) of 887 children in the co-trimoxazole group died, compared with 135 (15%) of 891 in the placebo group (unadjusted hazard ratio [HR] 0·90, 95% CI 0·71-1·16, p=0·429; 16·0 vs 17·7 events per 100 child-years observed (CYO); difference -1·7 events per 100 CYO, 95% CI -5·8 to 2·4]). In the first 6 months of the study (while participants received study medication), 63 suspected grade 3 or 4 associated adverse events were recorded among 57 (3%) children; 31 (2%) in the co-trimoxazole group and 32 (2%) in the placebo group (incidence rate ratio 0·98, 95% CI 0·58-1·65). The most common adverse events of these grades were urticarial rash (grade 3, equally common in both groups), neutropenia (grade 4, more common in the co-trimoxazole group), and anaemia (both grades equally common in both groups). One child in the placebo group had fatal toxic epidermal necrolysis with concurrent Pseudomonas aeruginosa bacteraemia. Daily co

Adjunctive rifampicin to reduce early mortality from Staphylococcus aureus bacteraemia (ARREST: study protocol for a randomised controlled trial

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Thwaites Guy

2012-12-01

Full Text Available Abstract Background Staphylococcus aureus bacteraemia is a common and serious infection, with an associated mortality of ~25%. Once in the blood, S. aureus can disseminate to infect almost any organ, but bones, joints and heart valves are most frequently affected. Despite the infection’s severity, the evidence guiding optimal antibiotic therapy is weak: fewer than 1,500 patients have been included in 16 randomised controlled trials investigating S. aureus bacteraemia treatment. It is uncertain which antibiotics are most effective, their route of administration and duration, and whether antibiotic combinations are better than single agents. We hypothesise that adjunctive rifampicin, given in combination with a standard first-line antibiotic, will enhance killing of S. aureus early in the treatment course, sterilise infected foci and blood faster, and thereby reduce the risk of dissemination, metastatic infection and death. Our aim is to determine whether adjunctive rifampicin reduces all-cause mortality within 14 days and bacteriological failure or death within 12 weeks from randomisation. Methods We will perform a parallel group, randomised (1:1, blinded, placebo-controlled trial in NHS hospitals across the UK. Adults (≥18 years with S. aureus (meticillin-susceptible or resistant grown from at least one blood culture who have received ≤96 h of active antibiotic therapy for the current infection and do not have contraindications to the use of rifampicin will be eligible for inclusion. Participants will be randomised to adjunctive rifampicin (600-900mg/day; orally or intravenously or placebo for the first 14 days of therapy in combination with standard single-agent antibiotic therapy. The co-primary outcome measures will be all-cause mortality up to 14 days from randomisation and bacteriological failure/death (all-cause up to 12 weeks from randomisation. 940 patients will be recruited, providing >80% power to detect 45% and 30% reductions in

Assessing the Effect of High Performance Inulin Supplementation via KLF5 mRNA Expression in Adults with Type 2 Diabetes: A Randomized Placebo Controlled Clinical Trail.

Science.gov (United States)

Ghavami, Abed; Roshanravan, Neda; Alipour, Shahriar; Barati, Meisam; Mansoori, Behzad; Ghalichi, Faezeh; Nattagh-Eshtivan, Elyas; Ostadrahimi, Alireza

2018-03-01

Purpose: The worldwide prevalence of metabolic disorders such as diabetes is increasing rapidly. Currently, the complications of diabetes are the major health concern. The aim of this study was to investigate the effect of high performance (HP) inulin supplementation on glucose homeostasis via KLF5 mRNA expression in adults with type 2 diabetes. Methods: In the present clinical trial conducted for a duration of 6 weeks, 46 volunteers diabetic patients referring to diabetes clinic in Tabriz, Iran, were randomly assigned into intervention (n= 23, consuming 10 gr/d HP inulin) and control groups (n= 23, consuming 10 gr/ d starch). We assessed glycemic and anthropometric indices, blood lipids and plasmatic level of miR-375 as well as KLF5 mRNA expression before and after the intervention. Results: Findings indicated that inulin supplementation significantly decreased fasting plasma glucose (FPG) in comparison to the placebo group (Pinulin supplementation resulted in significant decrease in KLF5 mRNA expression in peripheral blood mononuclear cells (PBMCs) (Fold change: 0.61± 0.11; P-value= 0.001) and significant increase in plasmatic level of miR-375 (Fold change: 3.75± 0.70; P-value=0.004). Conclusion: Considering the improvements of FPG level in diabetic patients, it seems that HP inulin supplementation may be beneficial in controlling diabetes via the expression of some genes. However, further studies are needed to achieve concise conclusions.

Development and Evaluation of a Psychosocial Intervention for Children and Teenagers Experiencing Diabetes (DEPICTED: a protocol for a cluster randomised controlled trial of the effectiveness of a communication skills training programme for healthcare professionals working with young people with type 1 diabetes

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Lowes Lesley

2010-02-01

Full Text Available Abstract Background Diabetes is the third most common chronic condition in childhood and poor glycaemic control leads to serious short-term and life-limiting long-term complications. In addition to optimal medical management, it is widely recognised that psychosocial and educational factors play a key role in improving outcomes for young people with diabetes. Recent systematic reviews of psycho-educational interventions recognise the need for new methods to be developed in consultation with key stakeholders including patients, their families and the multidisciplinary diabetes healthcare team. Methods/design Following a development phase involving key stakeholders, a psychosocial intervention for use by paediatric diabetes staff and not requiring input from trained psychologists has been developed, incorporating a communication skills training programme for health professionals and a shared agenda-setting tool. The effectiveness of the intervention will be evaluated in a cluster-randomised controlled trial (RCT. The primary outcome, to be measured in children aged 4-15 years diagnosed with type 1 diabetes for at least one year, is the effect on glycaemic control (HbA1c during the year after training of the healthcare team is completed. Secondary outcomes include quality of life for patients and carers and cost-effectiveness. Patient and carer preferences for service delivery will also be assessed. Twenty-six paediatric diabetes teams are participating in the trial, recruiting a total of 700 patients for evaluation of outcome measures. Half the participating teams will be randomised to receive the intervention at the beginning of the trial and remaining centres offered the training package at the end of the one year trial period. Discussion The primary aim of the trial is to determine whether a communication skills training intervention for specialist paediatric diabetes teams will improve clinical and psychological outcomes for young people with

Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial.

Science.gov (United States)

2017-05-27

Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage. In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283. Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10

The Happy Life Club™ study protocol: A cluster randomised controlled trial of a type 2 diabetes health coach intervention

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Yang Hui

2011-02-01

Full Text Available Abstract Background The Happy Life Club™ is an intervention that utilises health coaches trained in behavioural change and motivational interviewing techniques to assist with the management of type 2 diabetes mellitus (T2DM in primary care settings in China. Health coaches will support participants to improve modifiable risk factors and adhere to effective self-management treatments associated with T2DM. Methods/Design A cluster randomised controlled trial involving 22 Community Health Centres (CHCs in Fengtai District of Beijing, China. CHCs will be randomised into a control or intervention group, facilitating recruitment of at least 1320 individual participants with T2DM into the study. Participants in the intervention group will receive a combination of both telephone and face-to-face health coaching over 18 months, in addition to usual care received by the control group. Health coaching will be performed by CHC doctors and nurses certified in coach-assisted chronic disease management. Outcomes will be assessed at baseline and again at 6, 12 and 18 months by means of a clinical health check and self-administered questionnaire. The primary outcome measure is HbA1c level. Secondary outcomes include metabolic, physiological and psychological variables. Discussion This cluster RCT has been developed to suit the Chinese health care system and will contribute to the evidence base for the management of patients with T2DM. With a strong focus on self-management and health coach support, the study has the potential to be adapted to other chronic diseases, as well as other regions of China. Trial Registration Current Controlled Trials ISRCTN01010526

Clinical efficacy and safety of a novel tetravalent dengue vaccine in healthy children in Asia: a phase 3, randomised, observer-masked, placebo-controlled trial.

Science.gov (United States)

Capeding, Maria Rosario; Tran, Ngoc Huu; Hadinegoro, Sri Rezeki S; Ismail, Hussain Imam H J Muhammad; Chotpitayasunondh, Tawee; Chua, Mary Noreen; Luong, Chan Quang; Rusmil, Kusnandi; Wirawan, Dewa Nyoman; Nallusamy, Revathy; Pitisuttithum, Punnee; Thisyakorn, Usa; Yoon, In-Kyu; van der Vliet, Diane; Langevin, Edith; Laot, Thelma; Hutagalung, Yanee; Frago, Carina; Boaz, Mark; Wartel, T Anh; Tornieporth, Nadia G; Saville, Melanie; Bouckenooghe, Alain

2014-10-11

An estimated 100 million people have symptomatic dengue infection every year. This is the first report of a phase 3 vaccine efficacy trial of a candidate dengue vaccine. We aimed to assess the efficacy of the CYD dengue vaccine against symptomatic, virologically confirmed dengue in children. We did an observer-masked, randomised controlled, multicentre, phase 3 trial in five countries in the Asia-Pacific region. Between June 3, and Dec 1, 2011, healthy children aged 2-14 years were randomly assigned (2:1), by computer-generated permuted blocks of six with an interactive voice or web response system, to receive three injections of a recombinant, live, attenuated, tetravalent dengue vaccine (CYD-TDV), or placebo, at months 0, 6, and 12. Randomisation was stratified by age and site. Participants were followed up until month 25. Trial staff responsible for the preparation and administration of injections were unmasked to group allocation, but were not included in the follow-up of the participants; allocation was concealed from the study sponsor, investigators, and parents and guardians. Our primary objective was to assess protective efficacy against symptomatic, virologically confirmed dengue, irrespective of disease severity or serotype, that took place more than 28 days after the third injection. The primary endpoint was for the lower bound of the 95% CI of vaccine efficacy to be greater than 25%. Analysis was by intention to treat and per procotol. This trial is registered with ClinicalTrials.gov, number NCT01373281. We randomly assigned 10,275 children to receive either vaccine (n=6851) or placebo (n=3424), of whom 6710 (98%) and 3350 (98%), respectively, were included in the primary analysis. 250 cases of virologically confirmed dengue took place more than 28 days after the third injection (117 [47%] in the vaccine group and 133 [53%] in the control group). The primary endpoint was achieved with 56·5% (95% CI 43·8-66·4) efficacy. We recorded 647 serious adverse

Efficacy of labral repair, biceps tenodesis, and diagnostic arthroscopy for SLAP Lesions of the shoulder: a randomised controlled trial

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Mowinckel Petter

2010-10-01

Full Text Available Abstract Background Surgery for type II SLAP (superior labral anterior posterior lesions of the shoulder is a promising but unproven treatment. The procedures include labral repair or biceps tenodesis. Retrospective cohort studies have suggested that the benefits of tenodesis include pain relief and improved function, and higher patient satisfaction, which was reported in a prospective non-randomised study. There have been no completed randomised controlled trials of surgery for type II SLAP lesions. The aims of this participant and observer blinded randomised placebo-controlled trial are to compare the short-term (6 months and long-term (2 years efficacy of labral repair, biceps tenodesis, and placebo (diagnostic arthroscopy for alleviating pain and improving function for type II SLAP lesions. Methods/Design A double-blind randomised controlled trial are performed using 120 patients, aged 18 to 60 years, with a history for type II SLAP lesions and clinical signs suggesting type II SLAP lesion, which were documented by MR arthrography and arthroscopy. Exclusion criteria include patients who have previously undergone operations for SLAP lesions or recurrent shoulder dislocations, and ruptures of the rotator cuff or biceps tendon. Outcomes will be assessed at baseline, three, six, 12, and 24 months. Primary outcome measures will be the clinical Rowe Score (1988-version and the Western Ontario Instability Index (WOSI at six and 24 months. Secondary outcome measures will include the Shoulder Instability Questionnaire (SIQ, the generic EuroQol (EQ-5 D and EQ-VAS, return to work and previous sports activity, complications, and the number of reoperations. Discussion The results of this trial will be of international importance and the results will be translatable into clinical practice. Trial Registration [ClinicalTrials.gov NCT00586742

Efficacy and Safety of a Single-Pill Combination of Vildagliptin and Metformin in Japanese Patients with Type 2 Diabetes Mellitus: A Randomized, Double-Blind, Placebo-Controlled Trial

OpenAIRE

Odawara, Masato; Yoshiki, Mika; Sano, Misako; Hamada, Izumi; Lukashevich, Valentina; Kothny, Wolfgang

2015-01-01

Introduction The use of dipeptidyl peptidase-4 inhibitors in combination with metformin is increasing in Japanese patients with type 2 diabetes mellitus (T2DM), but no single-pill combination (SPC) is currently available in Japan. The objective of this study was to assess the efficacy and safety of vildagliptin/metformin SPC in Japanese patients with T2DM inadequately controlled with vildagliptin monotherapy. Methods This was a 14-week, randomized, double-blind, parallel-group, placebo-contro...

Treatment of antipsychotic-associated obesity with a GLP-1 receptor agonist: Protocol for an investigator-initiated prospective, randomised, placebo-controlled, double-blinded intervention study – the TAO study

DEFF Research Database (Denmark)

Ishøy, Pelle Lau; Knop, Filip Krag; Broberg, Brian Villumsen

with a GLP-1 receptor agonist (exenatide once-weekly) is safe and facilitates weight loss in non-diabetic schizophrenia patients with antipsychotic-associated obesity. Methods and analysis: Forty obese patients with schizophrenia or schizoaffective disorder treated with antipsychotic drugs will be randomised...

Homeopathic pathogenetic trials produce specific symptoms different from placebo.

Science.gov (United States)

Möllinger, Heribert; Schneider, Rainer; Walach, Harald

2009-04-01

Homeopathy uses information gathered from healthy volunteers taking homeopathic substances (pathogenetic trials) for clinical treatment. It is controversial whether such studies produce symptoms different from those produced by placebo. To test whether homeopathic preparations produce different symptoms than placebo in healthy volunteers. Three armed, double-blind, placebo controlled randomised experimental pathogenetic study in 25 healthy volunteers who took either one of two homeopathic remedies, Natrum muriaticum and Arsenicum album in 30CH or identical placebo. Main outcome parameter was the number of remedy-specific symptoms per group. On average, 6 symptoms typical for Arsenicum album were experienced by participants taking arsenicum album, 5 symptoms typical for Natrum muriaticum by those taking natrum muriaticum, and 11 non-specific symptoms by those in the placebo group. Differences were significant overall (Kruskall Wallis test, p = 0.0002,) and significantly different from placebo (Mann-Whitney test, p = 0.001). Homeopathic remedies produce different symptoms than placebo. Copyright (c) 2009 S. Karger AG, Basel.

Improving glycaemic control and life skills in adolescents with type 1 diabetes: A randomised, controlled intervention study using the Guided Self-Determination-Young method in triads of adolescents, parents and health care providers integrated into routine paediatric outpatient clinics

DEFF Research Database (Denmark)

Husted, Gitte; Thorsteinsson, Birger; Esbensen, Bente Appel

2011-01-01

visits will reduce haemoglobin A1c (HbA1c) concentrations and improve adolescents' life skills compared with a control group. METHODS: Using a mixed methods design comprising a randomised controlled trial and a nested qualitative evaluation, we will recruit 68 adolescents age 13 - 18 years with type 1......ABSTRACT: BACKGROUND: Adolescents with type 1 diabetes face demanding challenges due to conflicting priorities between psychosocial needs and diabetes management. This conflict often results in poor glycaemic control and discord between adolescents and parents. Adolescent-parent conflicts are thus...... are lacking. The Guided Self-Determination method is proven effective in adult care and has been adapted to adolescents and parents (Guided Self-Determination-Young (GSD-Y)) for use in paediatric diabetes outpatient clinics. Our objective is to test whether GSD-Y used in routine paediatric outpatient clinic...

Long-term management of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical corticosteroids (LIBERTY AD CHRONOS): a 1-year, randomised, double-blinded, placebo-controlled, phase 3 trial.

Science.gov (United States)

Blauvelt, Andrew; de Bruin-Weller, Marjolein; Gooderham, Melinda; Cather, Jennifer C; Weisman, Jamie; Pariser, David; Simpson, Eric L; Papp, Kim A; Hong, H Chih-Ho; Rubel, Diana; Foley, Peter; Prens, Errol; Griffiths, Christopher E M; Etoh, Takafumi; Pinto, Pedro Herranz; Pujol, Ramon M; Szepietowski, Jacek C; Ettler, Karel; Kemény, Lajos; Zhu, Xiaoping; Akinlade, Bolanle; Hultsch, Thomas; Mastey, Vera; Gadkari, Abhijit; Eckert, Laurent; Amin, Nikhil; Graham, Neil M H; Pirozzi, Gianluca; Stahl, Neil; Yancopoulos, George D; Shumel, Brad

2017-06-10

Dupilumab (an anti-interleukin-4-receptor-α monoclonal antibody) blocks signalling of interleukin 4 and interleukin 13, type 2/Th2 cytokines implicated in numerous allergic diseases ranging from asthma to atopic dermatitis. Previous 16-week monotherapy studies showed that dupilumab substantially improved signs and symptoms of moderate-to-severe atopic dermatitis with acceptable safety, validating the crucial role of interleukin 4 and interleukin 13 in atopic dermatitis pathogenesis. We aimed to evaluate the long-term efficacy and safety of dupilumab with medium-potency topical corticosteroids versus placebo with topical corticosteroids in adults with moderate-to-severe atopic dermatitis. In this 1-year, randomised, double-blinded, placebo-controlled, phase 3 study (LIBERTY AD CHRONOS), adults with moderate-to-severe atopic dermatitis and inadequate response to topical corticosteroids were enrolled at 161 hospitals, clinics, and academic institutions in 14 countries in Europe, Asia-Pacific, and North America. Patients were randomly assigned (3:1:3) to subcutaneous dupilumab 300 mg once weekly (qw), dupilumab 300 mg every 2 weeks (q2w), or placebo via a central interactive voice/web response system, stratified by severity and global region. All three groups were given concomitant topical corticosteroids with or without topical calcineurin inhibitors where inadvisable for topical corticosteroids. Topical corticosteroids could be tapered, stopped, or restarted on the basis of disease activity. Coprimary endpoints were patients (%) achieving Investigator's Global Assessment (IGA) 0/1 and 2-point or higher improvement from baseline, and Eczema Area and Severity Index 75% improvement from baseline (EASI-75) at week 16. Week 16 efficacy and week 52 safety analyses included all randomised patients; week 52 efficacy included patients who completed treatment by US regulatory submission cutoff. This study is registered with ClinicalTrials.gov, NCT02260986. Between Oct 3, 2014

Two weeks taurine supplementation reverses endothelial dysfunction in young male type 1 diabetics.

LENUS (Irish Health Repository)

Moloney, Michael A

2010-10-01

Type 1 diabetics have a well-recognised risk of accelerated cardiovascular disease. Even in the absence of clinical signs there are detectable abnormalities of conduit vessel function. Our group has previously reported reversal of endothelial dysfunction in diabetics with pravastatin. In young asymptomatic smokers, taurine supplementation has a beneficial impact on macrovascular function, assessed by FMD, and shows an up-regulation of nitric oxide from monocyte-endothelial cell interactions. We hypothesise that taurine supplementation reverses early endothelial abnormalities in young male type 1 diabetics, as assessed by applanation tonometry, brachial artery ultrasound and laser Doppler fluximetry. Asymptomatic, male diabetics (n=9) were scanned prior to treatment and then randomised in a double-blind cross-over fashion to receive either 2 weeks placebo or taurine. Control patients (n=10) underwent a baseline scan. Assessed diabetics had detectable, statistically significant abnormalities when compared with controls, in both arterial stiffness (augmentation index) and brachial artery reactivity (FMD). Both of these parameters were returned to control levels with 2 weeks taurine supplementation. In conclusion, 2 weeks taurine supplementation reverses early, detectable conduit vessel abnormalities in young male diabetics. This may have important implications in the long-term treatment of diabetic patients and their subsequent progression towards atherosclerotic disease.

Effectiveness of personalised feedback alone or combined with peer support to improve physical activity in sedentary older Malays with type 2 diabetes: A randomised controlled trial

Directory of Open Access Journals (Sweden)

Shariff-Ghazali eSazlina

2015-07-01

Full Text Available Introduction: Regular physical activity is an important aspect of self management among older people with type 2 diabetes but many remain inactive. Interventions to improve physical activity levels have been studied but few studies have evaluated the effects of personalised feedback or peer support; and there was no study on older people of Asian heritage. Hence, this trial evaluated whether personalised feedback (PF only or combined with peer support (PS improves physical activity among older Malays with type 2 diabetes (T2DM compared to usual care only. Materials and methods: A three arm randomised controlled trial was conducted in a primary healthcare clinic in Malaysia. 69 sedentary Malays aged 60 years and older with T2DM who received usual diabetes care were randomised to PF or PS interventions or as controls for 12 weeks with follow-ups at weeks 24 and 36. Intervention groups performed unsupervised walking activity and received written feedback on physical activity. The PS group also received group and telephone contacts from trained peer mentors. The primary outcome was pedometer steps. Secondary outcomes were self-reported physical activity, cardiovascular risk factors, cardiorespiratory fitness, balance, quality of life and psychosocial wellbeing. Results: 52 (75.4% completed the 36-week study. The PS group showed greater daily pedometer readings than the PF and controls (p=0.001. The PS group also had greater improvement in weekly duration (p<0.001 and frequency (p<0.001 of moderate intensity physical activity, scores on the Physical Activity Scale for Elderly (p=0.003, six minute walk test (p<0.001 and social support from friends (p=0.032 than PF and control groups. Conclusions: The findings suggest personalised feedback combined with peer support in older Malays with T2DM improved their physical activity levels, cardiorespiratory fitness and support from friends. Trial registration: Current Controlled Trials ISRCTN71447000.

Effect of Saccharomyces boulardii in dog with chronic enteropathies: double-blinded, placebo-controlled study.

Science.gov (United States)

D'Angelo, Simona; Fracassi, Federico; Bresciani, Francesca; Galuppi, Roberta; Diana, Alessia; Linta, Nikolina; Bettini, Giuliano; Morini, Maria; Pietra, Marco

2018-03-03

Saccharomyces boulardii is used to treat acute and chronic enteropathies in humans, but to date, no studies have evaluated the use of this yeast in dogs. The current study, a prospective non-randomised, double-blinded, placebo-controlled study, evaluated the effects of S boulardii in healthy dogs and dogs with chronic enteropathies (CE). Four healthy dogs and 20 dogs with CE were included. In healthy dogs, S boulardii was administered for 10 days. Possible short-term adverse effects were recorded, and quantitative stool cultures for yeasts were performed. In dogs with CE, S boulardii or a placebo was administered in addition to standard treatment protocols. Canine Chronic Enteropathy Clinical Activity Index, abdominal ultrasonography, gastroenteroscopy and histology were performed at the time of diagnosis and after 60 days of treatment. In healthy dogs, S boulardii reached a steady state in five days and was completely eliminated on day 4 after administration. No short-term side effects were seen. Clinical activity index, stool frequency, stool consistency and body condition score improved significantly in dogs with CE receiving S boulardii versus the placebo. In conclusion, S boulardii can be safely used in dogs with CE and seems to achieve better control of clinical signs than standard therapy alone. © British Veterinary Association (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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

Directory of Open Access Journals (Sweden)

Thomas C Darton

2016-08-01

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

Experience of malignancies with oral glucose-lowering drugs in the randomised controlled ADOPT (A Diabetes Outcome Progression Trial) and RECORD (Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycaemia in Diabetes) clinical trials.