Maternal Probiotic Intervention to Improve Gut Health - Trial II - Bangladesh

NCT06817031 | Enrolling By Invitation Phase 2 DMC

• 1 other identifier: PR-24002
• Study Type: interventional
• Target: 144
• Locations: 1 country
• Sites: 1

Brief Summary

Burden: Environmental Enteric Dysfunction (EED) is an enteropathic condition characterised by altered gut permeability, infiltration of immune cells and changes in villous architecture and cell differentiation. EED is a major reason of malnourishment, poor neurological development, stunting, oral vaccine failure, and infection. It is believed that EED is responsible for 40% of all childhood stunting. Knowledge gap: To date the focus of research on childhood stunting has been on the young child. It is increasingly appreciated, however, that stunting often begins in utero and the focus has shifted to women's health and pregnancy. Results from rural Bangladesh reveal poor gestational weight gain that ultimately leads to intrauterine growth restriction, low birth weight and ultimately stunting and wasting. Another study recently completed in slum settlements of Dhaka, Bangladesh demonstrated a high prevalence of EED among undernourished women. Intestinal histopathology was abnormal in more than 80% of women. We postulate that growth retardation in utero is a consequence of EED in the mother during pregnancy and lactation. This leads to systemic inflammation, which lead to disadvantageous partitioning of nutrients, and reduced nutrient availability. Relevance: This trial will explore the conceptual framework that a probiotic or live biotherapeutic product that can improve the composition of gut microbiota, can also displace enteropathogens and reduce biomarkers of intestinal inflammation to promote gut health. This will restore healthy microbial signalling to the host epithelium, ameliorate barrier function through secretion of mucus and antimicrobial factors, and improve nutrient availability. Objectives: The primary objective is to assess if administration of oral vancomycin followed by VE818 to pregnant women colonised 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, Matiari in Pakistan, Lusaka in Zambia and, and Bobo-Dioulasso in Burkina Faso. 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 randomised 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

Conditions

Environmental Enteric Dysfunction

Keywords

probiotic, environmental enteropathy, pregnancy, maternal, gut health, microbiome

Outcome Measures

Primary Outcomes (1)

• Change in the mean count in the number of 11 selected fecal bacterial pathogen groups present between baseline and endline

  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.

  Between baseline and 2 weeks after completion of the 14-day course with Placebo or VE818

Secondary Outcomes (9)

• Change in prevalence of specific enteropathogens not included in the primary endpoint in pregnant women

  Baseline, day 6, day 21, day 35, day 63 and 7 day post-partum

• Engraftment of VE818 strains in pregnant women

  day 21, day 35, day 63 and 7 day post-partum

• Change in a panel of plasma biomarkers in pregnant women as measured by ELISA

  Baseline, day 6, day 35, and day 63

• Change in a panel of fecal biomarkers in pregnant women as measured by ELISA

  Baseline, day 6, day 21, day 35, day 63 and 7 day post-partum

• Change in intestinal permeability as measured by Lactulose/Rhamnose (LR) ratio in pregnant women

  Baseline and day 35

Other Outcomes (18)

• Difference in the rate of weight gain during the second and third trimester of pregnancy

  Second and third trimester of pregnancy

• Difference in fetal growth trajectories

  16 weeks, 20 weeks, 24 weeks, 28 weeks, 32 weeks and 36 weeks of gestation

• Difference in placental insufficiency

  28 weeks, 32 weeks, and 36 weeks of gestation

Study Arms (3)

Observation only arm

NO INTERVENTION

oral vancomycin + placebo

PLACEBO COMPARATOR

Drug: Placebo; Drug: Oral Vancomycin

oral vancomycin + VE818

ACTIVE COMPARATOR

Drug: VE818; Drug: Oral Vancomycin

Interventions

VE818 DRUG

VE818, is an 11-strain bacterial consortium rationally designed by Vedanta Biosciences Inc., to displace enteropathogens and reduce intestinal inflammation in pregnant women

oral vancomycin + VE818

Placebo DRUG

Enteric Capsules filled with approximately 400mg of Microcrystalline Cellulose (bulking agent)

oral vancomycin + placebo

Oral Vancomycin DRUG

Oral vancomycin in capsule form will be administered three times daily for 5 days at 250mg per dose. Because oral vancomycin is a non-absorbable antibiotic, the likelihood of systemic absorption is minimal and therefore, it is not associated with the adverse events attributable to the intravenous formulation

oral vancomycin + VE818; oral vancomycin + placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 -
• use surface water, unimproved water, or limited water for drinking; OR
• use surface water, unimproved water, or limited water for cooking; OR
• use surface water, unimproved water, or limited water for washing utensils; OR
• practice open defecation, use unimproved sanitation (toilet facility), or limited sanitation (toilet facility); OR
• lack facility or have limited facility for handwashing

You may not qualify if:

• Potential participants will not be enrolled if they:
• have MUAC ≥30 cm
• are carrying more than one fetus (i.e., multiple pregnancy)
• have diarrhea, defined as the passage of three or more loose stools per 24 hours, or have had diarrhea in the preceding 14 days
• have fever or an active infection
• have taken antibiotics or probiotics in the preceding 14 days
• have taken steroids or non-steroidal anti-inflammatory drugs in the preceding 14 days
• have severe anemia as determined using finger stick Hb \< 8 g/dl
• have a history of chronic digestive disease
• have any gastrointestinal contraindication to ingestion of a capsule (known or suspected gastrointestinal obstruction, stricture, fistula, gastroparesis, or any swallowing disorder)
• have known immunocompromised status (known history of HIV infection, autoimmune disease, diabetes mellitus, etc.)
• have known drug hypersensitivity/allergy/intolerance
• have chronic disease or any other illness or condition which in the opinion of the investigator will complicate the assessment of safety or efficacy
• are medically disqualified: Any potential participant who is deemed medically unfit for trial enrollment by a non-study healthcare provider, due to the presence of severe or unstable health conditions that could compromise safety or interfere with the study outcomes, will be excluded from participation
• have a plan to observe fast any time during the intervention period

Sponsors & Collaborators

• Bill and Melinda Gates Foundation: collaborator
• International Centre for Diarrhoeal Disease Research, Bangladesh: lead

Study Sites (1)

International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b)

Chāndpur, Bangladesh

Location

MeSH Terms

Interventions

Vancomycin

Intervention Hierarchy (Ancestors)

Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 4, 2025
• First Posted: February 10, 2025
• Study Start: April 20, 2025
• Primary Completion: April 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: December 10, 2025

Record last verified: 2025-12

Locations

BA (1)