Ability of the Probiotic Vivomixx to Improve Environmental Enteropathy in Pregnant Women: a Proof of Concept Trial in Bangladesh, Pakistan, Senegal, and Zambia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 76
- 试验地点
- 1
- 主要终点
- Reduction in inflammation and epithelial damage in pregnant women with environmental enteropathy
研究概览
简要总结
There is an urgent need to identify interventions that can improve the supportive uterine environment in which the fetus establishes his/her growth. Investigators believe that this necessitates improving the delivery of nutrients to the mother, and in turn that requires a healthy microbiota. Reducing intestinal inflammation will also have a profound impact on maternal and fetal immunity, though there is limited information on the impact of maternal health on placental function. This trial will determine if a well-established probiotic, Vivomixx, can modulate the maternal microbiota and ameliorate the maternal environmental enteropathy which compromises growth in the first 1000 days. This trial is the first in a proposed series of proof-of-concept intervention studies that are intended to provide data to enable a rational selection of interventions to be evaluated at scale in future large-scale trials.
This initial study will also serve the purpose of developing a harmonized multi-site Experimental Medicine Platform across four countries (Bangladesh, Pakistan, Senegal, Zambia). Harmonized procedures will develop the capacity to deliver high-quality trials for the evaluation of potential interventions to improve maternal nutritional status and growth in utero. To this end, measuring and understanding variability in endpoint measurements is a key deliverable.
详细描述
76 healthy pregnant women in their second trimester will be enrolled and will be randomized to receive either probiotic or placebo for 8 weeks. It will be a double-blind trial.
Pregnant women will be recruited in the community through demographic surveillance system established in Matiari, Pakistan. The study staff will approach the potential participants and will introduce them to this study. If Participants agree, a screening consent form will be taken in which investigators will assess them clinically and will measure their hemoglobin level and gestational ultrasound for confirmation of their trimester/gestational weeks. Based on the screening results and clinical staff assessment, women will be enrolled after taking trial participation consent.
Once the participant is enrolled, investigators will collect blood, urine LR, and stool samples (flash frozen and CapScan) before giving either a placebo or probiotic(which will be replenished after every 3 days). investigators will then follow them weekly for compliance and adverse event data collection for 56 days (8 weeks). investigators will again collect the same blood and stool samples after completion of 56 days. An additional visit at 36 weeks will be done to record weight and for a gestational ultrasound. Pregnancy outcomes will be recorded and then the child will be followed at 3,6,9 and 12 weeks for anthropometry and morbidity data collection. Gestational ultrasounds will be performed at screening at 20, 28 and 36 weeks of gestation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Randomisation will be carried out using sealed envelopes, using a randomisation code prepared by the trial statistician, which will be stratified by study centre. Each woman who gives consent will be given a trial identification (TID) number which will match the number on the randomisation envelopes.
The trial will be blinded with an identical placebo (microcrystalline cellulose, prepared by Mendes SA, Lugano). Samples will be run and analysed using TID only, with all data cleaning and re-assays carried out blinded. The trial statistician will unblind lab data once databases are finalised.
入排标准
- 年龄范围
- 18 Years 至 49 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Women over the age of 18 in their second trimester of pregnancy living in defined geographical areas of Matiari, where it can be assumed that environmental enteropathy is universal.
排除标准
- •have had diarrhoea, defined as the passage of three or more loose stools per 24 hours, in the preceding 14 days;
- •have taken antibiotics or probiotics in the preceding 14 days;
- •have taken non-steroidal anti-inflammatory drugs or steroids in the preceding 14 days;
- •have haemoglobin concentration <8g/dl;
- •have any illness which in the opinion of the investigator will complicate assessment of safety or efficacy;
- •have any gastrointestinal contraindication to ingestion of a capsule (known or suspected gastrointestinal obstruction, stricture, fistula, gastroparesis, or any swallowing disorder);
- •have a plan to leave the study area within the follow-up period;
- •but may be enrolled if/when these disqualifiers have expired.
研究组 & 干预措施
Vivomixx
Participant in the treatment arm will receive a daily dose of the probiotic Vivomixx for 8 weeks.
干预措施: Vivomixx (Drug)
Vivomixx
Participant in the treatment arm will receive a daily dose of the probiotic Vivomixx for 8 weeks.
干预措施: CapScan® (Device)
Placebo
Participant in the control arm will receive a daily dose of a placebo (microcrystalline maltose) for 8 weeks.
干预措施: CapScan® (Device)
结局指标
主要结局
Reduction in inflammation and epithelial damage in pregnant women with environmental enteropathy
时间窗: Day 0 (screening) - Day 56
Percentage change (mean, unweighted) in a multiple panels of biomarkers between baseline and last sample collected after 56 days of treatment, compared to a control group.
次要结局
- Vivomixx Reduction in permeability(Day 1 - Day 56)
- Impact of the host metabolome in pregnant woman(Day 1 - Day 56)
- Reduction in enteropathogen colonisation(Day 1 - Day 56)
- Rate of weight gain in the 2nd trimester of pregnancy(Day 1 - Day 56)
- Variability in endpoints across geographies and participating laboratories(Day 1 - Day 56)
- Impact of Vivomixx on the structure and function of the microbiome(Day 1 - Day 56)
研究者
Dr Syed Asad Ali
professor
Aga Khan University