Maternal Probiotic Intervention to Improve Gut Health

NCT05922683 | Completed Phase 2 DMC

• 1 other identifier: 51975
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 1

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.

Conditions

Environmental Enteric Dysfunction; Stunting

Keywords

probiotic; microbiome; pregnant women; capscan device; urine LR; vivomixx; pakistan; malnourished children; biomarkers; EED

Outcome Measures

Primary Outcomes (1)

• Reduction in inflammation and epithelial damage in pregnant women with environmental enteropathy

  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.

  Day 0 (screening) - Day 56

Secondary Outcomes (6)

• Reduction in enteropathogen colonisation

  Day 1 - Day 56

• Impact of Vivomixx on the structure and function of the microbiome

  Day 1 - Day 56

• Vivomixx Reduction in permeability

  Day 1 - Day 56

• Impact of the host metabolome in pregnant woman

  Day 1 - Day 56

• Rate of weight gain in the 2nd trimester of pregnancy

  Day 1 - Day 56

Other Outcomes (3)

• CapScan success rate in delivering an assessment of the microbiome throughout the gut

  Day 1 - Day 56

• Impact on growth of the infant

  Day 189 - Day 554

• Impact of Vivomixx on intra-uterine growth restriction velocity

  Day 1 - 161 Days

Study Arms (2)

Vivomixx

EXPERIMENTAL

Participant in the treatment arm will receive a daily dose of the probiotic Vivomixx for 8 weeks.

Drug: Vivomixx; Device: CapScan®

Placebo

PLACEBO COMPARATOR

Participant in the control arm will receive a daily dose of a placebo (microcrystalline maltose) for 8 weeks.

Device: CapScan®

Interventions

Vivomixx DRUG

Vivomixx (a mixture of Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus casei, Lactobacillus delbrueckii subspecies bulgaricus, Streptococcus salivarius subspecies thermophiles, Bifidobacterium breve, Bifidobacterium longum, and Bifidobacterium infantis), as VivomixxAll consenting participants will be randomized into the treatment to control arm, receiving either Vivomixx or a placebo for 8 weeks. During the study, women will visit the healthcare center or vice-versa on a bi-weekly basis to receive sachets of Vivomixx or a placebo according to their trial arm.

Also known as: VSL#3

Vivomixx

CapScan® DEVICE

The only non-standard sample collection instrument is the CapScan device. The CapScan Collection Capsule ("Capsule") is a non-invasive device that collects gastrointestinal samples along the GI tract that are then analyzed outside the body. Samples collected by the Capsule will be expressed, then undergo DNA sequencing and mass spectrometric analysis to determine the identity and function of the bacterial and host cells in the different regions of the GI tract and compared to similar analyses conducted on concomitantly collected stool samples.

Placebo; Vivomixx

Eligibility Criteria

• Age: 18 Years - 49 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

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

Matiari, Sindh, 71000, Pakistan

Location

MeSH Terms

Conditions

Growth Disorders

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Asad Ali, MPH

  Aga Khan University Hospital, Karachi

  PRINCIPAL INVESTIGATOR

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 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 (microcrystalline cellulose, prepared by Mendes SA, Lugano). Samples will be run and analysed using TID only, with all data cleaning and re-assays carried out blinded. The trial statistician will unblind lab data once databases are finalised.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: June 20, 2023
• First Posted: June 28, 2023
• Study Start: August 9, 2023
• Primary Completion: June 30, 2024
• Study Completion: June 30, 2025
• Last Updated: July 16, 2025

Record last verified: 2025-07

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)