Ability of the Probiotic VE818 to Reduce Enteropathogen Colonization and Improve Environmental Enteropathy in Pregnant Women: A Proof-of-Concept and Phase II Randomized Placebo-Controlled Trial in Bangladesh, Pakistan, Zambia, and Burkina Faso.
Objectives: The primary objective is to assess if administration of oral vancomycin followed by VE818 to pregnant women colonized with at least 2 out of 11 selected bacterial enteropathogens results in a significant change in the mean count of these organisms between the baseline and 2 weeks after completion of the intervention (Study Day 35d +2), compared to oral vancomycin followed by placebo.
Methods: Pregnant women will be recruited in antenatal clinics and in the community in Matlab in Bangladesh, Bobo-Dioulasso in Burkina Faso, Matiari in Pakistan, and Lusaka in Zambia. Study population will be women aged 18 years or older in the first trimester or early second trimester of pregnancy. Study procedures will be explained in detail and written consent will be taken before enrollment. Those women who give consent to participation will undergo a screening process which will check if any exclusion criteria are fulfilled. After consent and screening they will be randomized into either of the three arms: intervention arm (oral vancomycin followed by VE818), placebo-control arm (oral vancomycin followed by placebo), or observation-only arm. The allocation sequence will be generated by the trial statistician using a code with block permutation. The participant will remain free to withdraw at any time from the trial without giving reasons and without prejudicing her further treatment. Biological samples, including blood, saliva, urine, stool, vaginal swab, and intestinal luminal contents through CapScan. CapScan is a non-invasive device (capsule) that collects gastrointestinal samples along the gastrointestinal tract following ingestion and passes into stool. Outcome measures/variables: The primary endpoint is the change in the mean count in the number of 11 selected fecal bacterial pathogen groups present between baseline and 2 weeks after completion of the 14-day course with Placebo or VE818 (Study arms 2 and 3), which corresponds to 35th day, +2 from the first dose of oral vancomycin. The 11 enteropathogen targets will be detected by customized real-time quantitative PCR-based TaqMan Array Cards (TAC-qPCR) and include the following organisms: Aeromonas, Campylobacter coli, Campylobacter jejuni, Campylobacter Pan, Enteroaggregative Escherichia coli (E. coli), Enteropathogenic E. coli, Enterotoxigenic E. coli, Plesiomonas, Shigella\_Enteroinvasive E. coli (EIEC), Salmonella and Klebsiella pneumoniae.
• Women aged 18 years or older in their first or early second trimester of pregnancy (13-17 weeks of gestational age \[GA\]), living in defined geographical areas of Bangladesh (Matlab), Pakistan, Zambia, and Burkina Faso, where it can be assumed that environmental enteropathy is prevalent
• AND
• Presence of any 2 out of 11 selected bacterial pathogen targets (Aeromonas, Campylobacter coli, Campylobacter jejuni, Campylobacter Pan, Enteroaggregative Escherichia coli, Enteropathogenic Escherichia coli, Enterotoxigenic Escherichia coli, Plesiomonas, Shigella\_EIEC, Salmonella and Klebsiella pneumoniae in fecal samples measured by TAC-qPCR.
• AND
• Presence of any of the following WASH conditions -
⁃ 1\. use surface water, unimproved water, or limited water for drinking; OR 2. use surface water, unimproved water, or limited water for cooking; OR 3. use surface water, unimproved water, or limited water for washing utensils; OR 4. practice open defecation, use unimproved sanitation (toilet facility), or limited sanitation (toilet facility); OR 5. lack facility or have limited facility for handwashing