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Efficacy of a bovine colostrum and egg-based intervention in acute childhood diarrhoea in Guatemala: a randomised, double-blind, placebo-controlled trial.

ABSTRACT: Treatments for paediatric diarrhoeal disease are limited. We assessed the impact of a bovine colostrum and egg-based treatment designed to reduce diarrhoea duration through non-specific and pathogen-directed mechanisms in children.Randomised, double-blind, placebo-controlled trial of PTM202, derived from bovine colostrum and hyperimmune hen's egg on the duration of acute diarrhoeal disease in Guatemalan children. PTM202 contains specific immunoglobulins that target rotavirus, enterotoxigenic Escherichia coli, Shiga toxin-producing E. coli and Salmonella. Children aged 6-35 months presenting to three sites (one rural and two urban) with acute non-bloody diarrhoea were computer randomised to receive three daily doses of PTM202 or placebo. The primary outcome was the post-treatment duration of diarrhoea assessed in the per protocol population. Diarrhoeal pathogens were identified in stool by multiplex PCR (FilmArray Gastrointestinal-Panel, BioFire, Salt Lake City, Utah, USA). Key secondary outcomes included postdiarrhoeal weight gain and impact on diarrhoeal duration stratified by study site and presence of PTM202-targeted organisms in stool at enrolment. Safety was assessed in all participants.From 9 March 2015 to 25 January 2016, 325 children were enrolled, and 301 (154 intervention and 147 placebo) were analysed for the primary outcome. No difference in diarrhoea duration was observed between intervention and placebo in the total population, but a significant reduction was observed in the treatment group among children with at least one targeted pathogen in stool (HR=1.46, P=0.02), an effect most pronounced in urban subjects (HR 2.20, P=0.007) who had fewer stool pathogens and better nutritional status. No impact on 2-week or 4-week weight gain was noted. No adverse events attributed to PTM202 occurred.Results demonstrate the potential to target specific pathogens occurring in children with acute non-bloody diarrhoea and shorten illness duration using a novel, safe, nutrition-based intervention. PTM202 may represent a new tool to ameliorate the effects of acute diarrhoeal disease in low/middle-income populations.NCT02385773; Results.

SUBMITTER: Gaensbauer JT

PROVIDER: S-EPMC5728299 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Efficacy of a bovine colostrum and egg-based intervention in acute childhood diarrhoea in Guatemala: a randomised, double-blind, placebo-controlled trial.

Gaensbauer James T JT Melgar Mario A MA Calvimontes Diva M DM Lamb Molly M MM Asturias Edwin J EJ Contreras-Roldan Ingrid L IL Dominguez Samuel R SR Robinson Christine C CC Berman Stephen S

BMJ global health 20171204 4

<h4>Background</h4>Treatments for paediatric diarrhoeal disease are limited. We assessed the impact of a bovine colostrum and egg-based treatment designed to reduce diarrhoea duration through non-specific and pathogen-directed mechanisms in children.<h4>Methods</h4>Randomised, double-blind, placebo-controlled trial of PTM202, derived from bovine colostrum and hyperimmune hen's egg on the duration of acute diarrhoeal disease in Guatemalan children. PTM202 contains specific immunoglobulins that ta ...[more]

PMID: 29259822

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Project description:BackgroundRotavirus 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.MethodsWe 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).Findings4532 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; p<0·0001) in the first year of life. The number of infants needed to be immunised to prevent one severe rotavirus gastroenteritis episode was 55 (95% CI 37-97). The incidence of severe rotavirus gastroenteritis per 100 person-years was 1·5 in the vaccine group and 3·2 in the placebo group, with an incidence rate ratio of 0·46 (95% CI 0·33-0·65). Prevalence of immediate, solicited, and serious adverse events was similar in both groups. One case of urticaria in the vaccine group and one each of acute gastroenteritis and suspected sepsis in the placebo group were regarded as related to the study product. We recorded six cases of intussusception in the vaccine group and two in the placebo group, all of which happened after the third dose. 25 (<1%) infants in the vaccine group and 17 (<1%) in the placebo group died; no death was regarded as related to the study product.InterpretationMonovalent human-bovine (116E) rotavirus vaccine is effective and well tolerated in Indian infants.FundingDepartment of Biotechnology and the Biotechnology Industry Research Assistance Council, Government of India; Bill & Melinda Gates Foundation to PATH, USA; Research Council of Norway; UK Department for International Development; National Institutes of Health, Bethesda, USA; and Bharat Biotech International, Hyderabad, India.

Project description:ObjectiveTo assess the efficacy and safety of varenicline (a licensed cigarette smoking cessation aid) in helping users of smokeless tobacco to quit.DesignDouble blind, placebo controlled, parallel group, multicentre, randomised controlled trial.SettingMedical clinics (mostly primary care) in Norway and Sweden.ParticipantsMen and women aged ≥18 who used smokeless tobacco at least eight times a day, with no abstinence period over three months within one year before screening, who wanted to quit all tobacco use. Participants were excluded if they used any other form of tobacco (except smokeless tobacco) or medication to stop smoking within three months of screening or had any pre-existing medical or psychiatric condition.InterventionsVarenicline 1 mg twice daily (titrated during the first week) or placebo for 12 weeks, with 14 weeks' follow-up after treatment.Main outcome measuresThe primary end point was the four week continuous abstinence rate at the end of treatment (weeks 9-12) confirmed with cotinine concentration. A secondary end point was continuous abstinence rate for weeks 9-26. Safety and tolerability were also evaluated.Results431 participants (213 varenicline; 218 placebo) were randomised and received at least one dose of study drug. Participants' demographics and baseline use of smokeless tobacco were similar (89% (189) and 90% (196), respectively, were men; mean age in both groups was 43.9; participants used smokeless tobacco products about 15 times a day, and about 80% first used smokeless tobacco within 30 minutes after awakening). Continuous abstinence rate at week 9-12 was higher in the varenicline group than the placebo group (59% (125) v 39% (85); relative risk 1.60, 95% confidence interval 1.32 to 1.87, P<0.001; risk difference 20%; number needed to treat 5). The advantage of varenicline over placebo persisted through 14 weeks of follow-up (continuous abstinence rate at week 9-26 was 45% (95) v 34% (73); relative risk 1.42, 1.08 to 1.79, P=0.012; risk difference 11%; number needed to treat 9). The most common adverse events in the varenicline group compared with the placebo group were nausea (35% (74) v 6% (14)), fatigue (10% (22) v 7% (15)), headache (10% (22) v 9% (20)), and sleep disorder (10% (22) v 7% (15)). Few adverse events led to discontinuation of treatment (9% (19) and 4% (9), respectively), and serious adverse events occurred in two (1%) and three (1%) participants, respectively.ConclusionVarenicline can help people to give up smokeless tobacco and has an acceptable safety profile. The response rate in the placebo group in this study was high, suggesting a population less resistant to treatment than smokers.Trial registrationNCT00717093.

Project description:BackgroundExenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has neuroprotective effects in preclinical models of Parkinson's disease. We investigated whether these effects would be apparent in a clinical trial.MethodsIn this single-centre, randomised, double-blind, placebo-controlled trial, patients with moderate Parkinson's disease were randomly assigned (1:1) to receive subcutaneous injections of exenatide 2 mg or placebo once weekly for 48 weeks in addition to their regular medication, followed by a 12-week washout period. Eligible patients were aged 25-75 years, had idiopathic Parkinson's disease as measured by Queen Square Brain Bank criteria, were on dopaminergic treatment with wearing-off effects, and were at Hoehn and Yahr stage 2·5 or less when on treatment. Randomisation was by web-based randomisation with a two strata block design according to disease severity. Patients and investigators were masked to treatment allocation. The primary outcome was the adjusted difference in the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor subscale (part 3) in the practically defined off-medication state at 60 weeks. All efficacy analyses were based on a modified intention-to-treat principle, which included all patients who completed any post-randomisation follow-up assessments. The study is registered at ClinicalTrials.gov (NCT01971242) and is completed.FindingsBetween June 18, 2014, and March 13, 2015, 62 patients were enrolled and randomly assigned, 32 to exenatide and 30 to placebo. Our primary analysis included 31 patients in the exenatide group and 29 patients in the placebo group. At 60 weeks, off-medication scores on part 3 of the MDS-UPDRS had improved by 1·0 points (95% CI -2·6 to 0·7) in the exenatide group and worsened by 2·1 points (-0·6 to 4·8) in the placebo group, an adjusted mean difference of -3·5 points (-6·7 to -0·3; p=0·0318). Injection site reactions and gastrointestinal symptoms were common adverse events in both groups. Six serious adverse events occurred in the exenatide group and two in the placebo group, although none in either group were judged to be related to the study interventions.InterpretationExenatide had positive effects on practically defined off-medication motor scores in Parkinson's disease, which were sustained beyond the period of exposure. Whether exenatide affects the underlying disease pathophysiology or simply induces long-lasting symptomatic effects is uncertain. Exenatide represents a major new avenue for investigation in Parkinson's disease, and effects on everyday symptoms should be examined in longer-term trials.FundingMichael J Fox Foundation for Parkinson's Research.

Project description:BackgroundIrbesartan, a long acting selective angiotensin-1 receptor inhibitor, in Marfan syndrome might reduce aortic dilatation, which is associated with dissection and rupture. We aimed to determine the effects of irbesartan on the rate of aortic dilatation in children and adults with Marfan syndrome.MethodsWe did a placebo-controlled, double-blind randomised trial at 22 centres in the UK. Individuals aged 6-40 years with clinically confirmed Marfan syndrome were eligible for inclusion. Study participants were all given 75 mg open label irbesartan once daily, then randomly assigned to 150 mg of irbesartan (increased to 300 mg as tolerated) or matching placebo. Aortic diameter was measured by echocardiography at baseline and then annually. All images were analysed by a core laboratory blinded to treatment allocation. The primary endpoint was the rate of aortic root dilatation. This trial is registered with ISRCTN, number ISRCTN90011794.FindingsBetween March 14, 2012, and May 1, 2015, 192 participants were recruited and randomly assigned to irbesartan (n=104) or placebo (n=88), and all were followed for up to 5 years. Median age at recruitment was 18 years (IQR 12-28), 99 (52%) were female, mean blood pressure was 110/65 mm Hg (SDs 16 and 12), and 108 (56%) were taking β blockers. Mean baseline aortic root diameter was 34·4 mm in the irbesartan group (SD 5·8) and placebo group (5·5). The mean rate of aortic root dilatation was 0·53 mm per year (95% CI 0·39 to 0·67) in the irbesartan group compared with 0·74 mm per year (0·60 to 0·89) in the placebo group, with a difference in means of -0·22 mm per year (-0·41 to -0·02, p=0·030). The rate of change in aortic Z score was also reduced by irbesartan (difference in means -0·10 per year, 95% CI -0·19 to -0·01, p=0·035). Irbesartan was well tolerated with no observed differences in rates of serious adverse events.InterpretationIrbesartan is associated with a reduction in the rate of aortic dilatation in children and young adults with Marfan syndrome and could reduce the incidence of aortic complications.FundingBritish Heart Foundation, the UK Marfan Trust, the UK Marfan Association.

Dataset Information

Efficacy of a bovine colostrum and egg-based intervention in acute childhood diarrhoea in Guatemala: a randomised, double-blind, placebo-controlled trial.

Publications

Efficacy of a bovine colostrum and egg-based intervention in acute childhood diarrhoea in Guatemala: a randomised, double-blind, placebo-controlled trial.

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