Maternal Probiotic Intervention to Improve Gut Health

Phase 2

Active, not recruiting

• Conditions: Stunting; Environmental Enteric Dysfunction
• Interventions: Drug: Vivomixx; Device: CapScan®

• Registration Number: NCT05922683
• Lead Sponsor: Aga Khan University

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study First Submitted: 2023-06-20
• Study First Submitted QC: 2023-06-20
• Study First Posted: 2023-06-28
• Study Start: 2023-08-09
• Primary Completion: 2024-06-30
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-29
• Last Update Posted: 2025-01-31
• Study Completion: 2025-06-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Female
• Target Recruitment: 76

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Vivomixx	CapScan®	Participant in the treatment arm will receive a daily dose of the probiotic Vivomixx for 8 weeks.
Vivomixx	Vivomixx	Participant in the treatment arm will receive a daily dose of the probiotic Vivomixx for 8 weeks.
Placebo	CapScan®	Participant in the control arm will receive a daily dose of a placebo (microcrystalline maltose) for 8 weeks.

Primary Outcome Measures

Name	Time	Method
Reduction in inflammation and epithelial damage in pregnant women with environmental enteropathy	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.

Secondary Outcome Measures

Name	Time	Method
Vivomixx Reduction in permeability	Day 1 - Day 56	Reduction in LR ratio in Vivomixx compared to placebo groups
Impact of the host metabolome in pregnant woman	Day 1 - Day 56	Change in the metabolome, Untargeted urine, and plasma (and fecal) metabolome before and after the intervention.
Reduction in enteropathogen colonisation	Day 1 - Day 56	Reduction in colonisation with specific enteropathogens (Salmonella, Shigella, Campylobacter, ETEC, EPEC, EAEC, rotavirus, norovirus, Giardia and Cryptosporidium), by qPCR, between baseline and last sample collected after 56 days of treatment, in Vivomixx compared to placebo groups
Rate of weight gain in the 2nd trimester of pregnancy	Day 1 - Day 56	Weight gain velocity in the 2nd trimester of pregnancy
Variability in endpoints across geographies and participating laboratories	Day 1 - Day 56	Measurements of variability, including standard deviations and kappa values; Preliminary work across all sites using identical kits and harmonised SOPs
Impact of Vivomixx on the structure and function of the microbiome	Day 1 - Day 56	Change in relative abundance values of alpha and beta diversity pre- and post-treatment samples.

Trial Locations

Locations (1)

Mother and Child Health Research and Training Center; 🇵🇰 Matiari, Sindh, Pakistan