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

NCT07207434 | Recruiting Phase 2 DMC

• 1 other identifier: 2024-9410-27780
• 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. 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

Conditions

Environmental Enteric Dysfunction (EED); Stunting

Keywords

probiotic; microbiome; pregnant women; capscan device; urine LR; VE818; Pakistan; malnourished children; biomarkers; EED

Outcome Measures

Primary Outcomes (1)

• Change in the Mean Count of 11 Selected Fecal Bacterial Pathogen Groups as Measured by TAC-qPCR between enrollment and 2 weeks after completion of the 14-day course with Placebo or VE818

  The primary endpoint is the change in the mean count in the number of 11 selected fecal bacterial pathogen groups present between enrollment 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 enrollment 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 as Measured by TAC-qPCR

  Enrollment, Day 6 (18 weeks gestation), Day 21, Day 35 (23 weeks gestation), Day 63 (28 weeks gestation), and 7 days post-partum.

• Engraftment of VE818 strains in pregnant women as Measured by Shotgun Metagenomic Sequencing

  At Day 21, Day 35 (23 weeks gestation), Day 63 (28 weeks gestation), and 7 days post-partum.

• Change from Enrollment in the Concentration of a Panel of Plasma Biomarkers as Measured by ELISA

  At Enrollment, Day 6 (18 weeks gestation), Day 35 (23 weeks gestation), and Day 63 (28 weeks gestation).

• Change from Enrollment in the Concentration of a Panel of Fecal Biomarkers as Measured by ELISA

  At Enrollment, Day 6 (18 weeks gestation), Day 21, Day 35 (23 weeks gestation), Day 63 (28 weeks gestation), and 7 days post-partum

• Change from Enrollment in Intestinal Permeability as Measured by Lactulose/Rhamnose (LR) Ratio

  At Enrollment and Day 35 (23 weeks gestation).

Other Outcomes (19)

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

  Second (13 to 28 weeks of gestation) and third trimester of pregnancy (28 to 40 weeks of gestation)

• Difference in fetal growth trajectories

  At gestational weeks 16, 20, 24, 28, 32, and 36

• Difference in placental insufficiency

  At gestational weeks 28, 32, and 36

Study Arms (3)

Oral vancomycin + VE818

ACTIVE COMPARATOR

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

Drug: Oral Vancomycin; Drug: VE818

Oral vancomycin + Placebo

PLACEBO COMPARATOR

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

Drug: Oral Vancomycin; Drug: Placebo

Observation only arm

NO INTERVENTION

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.

Interventions

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 + Placebo; Oral vancomycin + VE818

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

Eligibility Criteria

• Age: 18 Years - 49 Years
• Gender Eligibility Details: All pregnant women in their first or early second trimester of pregnancy, residing in the Matiari district, who meet the eligibility criteria described below.
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

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
• 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 -
• 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

• Aga Khan University: lead
• Bill and Melinda Gates Foundation: collaborator
• International Centre for Diarrhoeal Disease Research, Bangladesh: collaborator
• University of Zambia: collaborator
• Institut Pasteur de Dakar: collaborator

Study Sites (1)

Mother and Child Health Research and Training Center, AKU

Matiari, Sindh, 71000, Pakistan

RECRUITING

MeSH Terms

Conditions

Growth Disorders

Interventions

Vancomycin

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Study Officials

• Asad Ali Syed, MPH

  Aga Khan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Asad Ali Syed, MPH

CONTACT

+92 2134864233; asad.ali@aku.edu

Sheraz Ahmed, Masters

CONTACT

+92222760394; sheraz.ahmed@aku.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: 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 Trial 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. Samples will be run and analysed using TID only, with all data cleaning and re-assays carried out blinded. The trial statistician will unblind the lab data once the databases are finalised.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 16, 2025
• First Posted: October 6, 2025
• Study Start: August 30, 2025
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: October 6, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be available within 24 months of study completion.
• Access Criteria: Data access requests will be reviewed by the Trial Management Group. Requestors will be required to sign a Data Access Agreement.

Locations

PA (1)