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

NCT ID: NCT07207434

Last Updated: 2025-10-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 144 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-08-30
• Study Completion Date: 2026-12-31

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.

Relevance: This trial aims to investigate the concept that a probiotic or live biotherapeutic product, capable of improving gut microbiota composition, can also displace enteropathogens and reduce biomarkers of intestinal inflammation, thereby promoting 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 from the community of Matiari in Pakistan. The 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 one 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 the 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 the 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

Detailed Description

A total of 144 pregnant women in their second trimester will be enrolled. Subsequently, 96 will be randomized to receive an antibiotic for 5 days, followed by a 1-day washout period (1 week), and then either a probiotic or a placebo for 2 weeks. It will be a double-blind trial.

Pregnant women will be recruited in the community through a 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 administered. During this, investigators will conduct a clinical assessment and measure the participants' hemoglobin levels. Additionally, a gestational ultrasound will be performed to confirm the trimester/gestational weeks, and a stool TAC will be collected to detect the presence of enteropathogens. Based on the screening results and clinical staff assessment, women will be enrolled after giving their consent to participate in the trial.

Once the participant is enrolled, investigators will collect blood, urine, LR, Vaginal Swab, and stool samples (flash frozen and CapScan) before giving them antibiotics and then either a placebo or probiotic (which will be replenished daily).

Investigators will then follow them daily for compliance and adverse event data collection for both antibiotic and then either a placebo or probiotic for 21 days (3 weeks). Investigators will collect blood, urine, LR, Vaginal Swab, and stool samples (flash frozen and CapScan) after completing the intervention.

The investigator will also conduct interval visits at different timepoints. Gestational ultrasounds, BIA, Skinfold, and Anthropometry will be performed at screening at 16, 20, 24, 28, 32, and 36 weeks of gestation.

Pregnancy outcomes will be recorded, and then the 1-month post-birth follow-up of mother and child will be done for anthropometry and morbidity data collection.

Conditions

Environmental Enteric Dysfunction (EED); Stunting

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Oral vancomycin + VE818

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

Drug: Oral Vancomycin 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

Group Type: ACTIVE_COMPARATOR

Oral Vancomycin

Intervention Type: 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

VE818

Intervention Type: 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 + Placebo

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

Drug: Oral Vancomycin 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

Group Type: PLACEBO_COMPARATOR

Oral Vancomycin

Intervention Type: 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

Placebo

Intervention Type: DRUG

Enteric capsules filled with approximately 400mg of microcrystalline cellulose (bulking agent)

Observation only arm

The observational arm is a no-intervention control group within a Phase II randomized controlled trial that enrolls pregnant women colonized with at least 2 out of 11 selected bacterial enteropathogens recruited from community. This arm includes 48 participants per site (192 total across 4 sites) randomized in a 1:1:1 ratio alongside two intervention arms (oral vancomycin + placebo and oral vancomycin + VE818), with participants followed at comparable timepoints including baseline assessments, multiple visits during pregnancy, delivery, and up to 1 month postpartum for comprehensive evaluation of mother-infant dyads without receiving any study intervention.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Oral Vancomycin

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

Intervention Type: DRUG

VE818

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

Intervention Type: DRUG

Placebo

Enteric capsules filled with approximately 400mg of microcrystalline cellulose (bulking agent)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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
• 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.
• 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

Exclusion Criteria

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
• have a plan to leave the study area within the follow-up period
• are participating in any other interventional trial
• belong to a household from which another woman is already enrolled in the study
• but may be enrolled if/when these disqualifiers have expired.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 49 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Bill and Melinda Gates Foundation

OTHER

Sponsor Role: collaborator

International Centre for Diarrhoeal Disease Research, Bangladesh

OTHER

Sponsor Role: collaborator

University of Zambia

OTHER

Sponsor Role: collaborator

Institut Pasteur de Dakar

OTHER

Sponsor Role: collaborator

Aga Khan University

OTHER

Sponsor Role: lead

Responsible Party

Dr Syed Asad Ali

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Asad Ali Syed, MPH

Role: PRINCIPAL_INVESTIGATOR

Aga Khan University

Locations

Mother and Child Health Research and Training Center, AKU

Matiari, Sindh, Pakistan

Site Status: RECRUITING

Countries

Pakistan

Central Contacts

Asad Ali Syed, MPH

Role: CONTACT

asad.ali@aku.edu

+92 2134864233

Sheraz Ahmed, Masters

Role: CONTACT

sheraz.ahmed@aku.edu

+92222760394 ext. 149

Facility Contacts

Sheraz Ahmed, MSc

Role: primary

sheraz.ahmed@aku.edu

+923343131087

Fayaz Ahmed Umrani, M.B.B.S

Role: backup

fayaz.umrani@aku.edu

+923337009960

Other Identifiers

2024-9410-27780

Identifier Type: -

Identifier Source: org_study_id