Clinical trial NCT05922683: Maternal Probiotic Intervention to Improve Gut Health
Official title: Ability of the Probiotic Vivomixx to Improve Environmental Enteropathy in Pregnant Women: a Proof of Concept Trial in Bangladesh, Pakistan, Senegal, and Zambia
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Environmental Enteric Dysfunction
Stunting
Keywords: probiotic
microbiome
pregnant women
capscan device
urine LR
vivomixx
pakistan
malnourished children
biomarkers
EED
Lead sponsor: Aga Khan University
Sponsor class: OTHER
Collaborators: name: Bill and Melinda Gates Foundation
name: International Centre for Diarrhoeal Disease Research, Bangladesh
name: University of Zambia
name: Institut Pasteur de Dakar
First posted: 2023-06-28
Enrollment: 76
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Reduction in inflammation and epithelial damage in pregnant women with environmental enteropathy
timeFrame: Day 0 (screening) - Day 56
Secondary outcomes:
measure: Reduction in enteropathogen colonisation
timeFrame: Day 1 - Day 56
measure: Impact of Vivomixx on the structure and function of the microbiome
timeFrame: Day 1 - Day 56
measure: Vivomixx Reduction in permeability
timeFrame: Day 1 - Day 56
measure: Impact of the host metabolome in pregnant woman
timeFrame: Day 1 - Day 56
measure: Rate of weight gain in the 2nd trimester of pregnancy
timeFrame: Day 1 - Day 56
measure: Variability in endpoints across geographies and participating laboratories
timeFrame: Day 1 - Day 56
Other outcomes:
measure: CapScan success rate in delivering an assessment of the microbiome throughout the gut
timeFrame: Day 1 - Day 56
measure: Impact on growth of the infant
timeFrame: Day 189 - Day 554
measure: Impact of Vivomixx on intra-uterine growth restriction velocity
timeFrame: Day 1 - 161 Days
Locations:
city: Matiari
country: Pakistan
facility: Mother and Child Health Research and Training Center
state: Sindh
Study officials:
affiliation: Aga Khan University Hospital, Karachi
name: Asad Ali, MPH
role: PRINCIPAL_INVESTIGATOR
References: