Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202404797704972 Date of Registration: 10/04/2024
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Maternal Probiotic Intervention to Improve Gut Health Trial II (MPIGH-2)
Official scientific title Ability of the probiotic VE-818 to reduce enteropathogen colonization and improve environmental enteropathy in pregnant women: a proof of concept and phase II randomized placebo-controlled trial
Brief summary describing the background and objectives of the trial The "Maternal Probiotic Intervention to Improve Gut Health Trial II (MPIGH-II)" is a significant research endeavor undertaken to address pressing health concerns among pregnant women in Chawama, Kuku, and Misisi, Lusaka, Zambia. The impetus for this study arises from the prevalent issue of Environmental Enteric Dysfunction (EED) and the associated colonization of enteropathogens in expectant mothers within these communities. EED, characterized by chronic gut inflammation and compromised nutrient absorption, poses substantial risks not only to maternal health but also to fetal development and long-term child health outcomes. Recognizing the urgent need for effective interventions, the MPIGH-II trial focuses on investigating the efficacy of a novel approach utilizing the probiotic VE-818, administered alongside oral vancomycin, as a potential remedy for reducing enteropathogen colonization and ameliorating EED in pregnant women. This randomized controlled trial spans over 24 months and involves multiple sites, including antenatal clinics and community settings, to ensure comprehensive coverage and diverse participant representation. The trial's overarching objective is to assess the impact of the probiotic intervention on maternal gut health and subsequent implications for both maternal and child well-being. With a meticulously planned sample size across three arms and a follow-up duration extending up to 12 months postpartum, the study aims to provide robust insights into the feasibility and effectiveness of this intervention strategy. By delineating the potential benefits and risks associated with the probiotic regimen, the MPIGH-II trial endeavors to contribute valuable evidence to the field of maternal and child health, with the ultimate goal of informing future interventions aimed at improving gut health outcomes in similar settings.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) II
Disease(s) or condition(s) being studied Nutritional, Metabolic, Endocrine,Paediatrics,Pregnancy and Childbirth
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Treatment: Drugs
Anticipated trial start date 01/04/2024
Actual trial start date
Anticipated date of last follow up 31/03/2026
Actual Last follow-up date
Anticipated target sample size (number of participants) 144
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Permuted block randomization Allocation was determined by the holder of the sequence who is situated off site Masking/blinding used Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group No treatment Not applicable Not applicable This will be an observation only arm. Participants will not receive any intervention. 48 Historical
Experimental Group Vancomycin plus placebo Participants will be treated with 5 days of antibiotic (oral vancomycin 125mg twice daily), followed by a one day wash out period, prior to 14 days with a placebo formulation. Participants will be treated with 5 days of antibiotic (oral vancomycin 125mg twice daily), followed by a one day wash out period, prior to 14 days with a placebo formulation. Participants will be treated with 5 days of antibiotic (oral vancomycin 125mg twice daily), followed by a one day wash out period, prior to 14 days with a placebo formulation. 48
Experimental Group Vancomycin plus VE818 A daily dose of oral vancomycin for 5 days, followed by a 1-day washout period, after which patients will receive 5 capsules of VE-818 per day (at a dose of 2.0x10^09 CFU/capsule). 14 days. Participants randomized to treatment arm will receive a daily dose of oral vancomycin for 5 days, followed by a 1-day washout period, after which patients will receive 5 capsules of VE-818 per day (at a dose of 2.0x10^09 CFU/capsule) for 14 days. 48
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Women aged 18 years or older in the first or early second trimester of pregnancy, living in defined ge-ographical areas of Chawama, Misi and Kuku compounds where, based on previous studies, it can be assumed that environmental enteropathy is prevalent. EMP Pregnancy 2 Trial Protocol Version 0.1, 30th October 2023 Page 22 of 50 Presence of any 2 bacterial pathogens from the list of selected bacterial enteropathogens (non-ty-phoid salmonellae, Shigella spp/enteroinvasive EIEC, Campylobacter spp, ETEC, EPEC, EAEC, EHEC, Aer-omonas spp, Plesiomonas spp, Vibrio cholerae,) in the stool sample detected by TAC (qPCR). Potential participants will not be enrolled if they: • 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 steroids or non-steroidal anti-inflammatory drugs in the preceding 14 days ● have any illness which in the opinion of the investigator will complicate the assessment of safety or efficacy ● have severe anemia as determined using finger stick hemoglobin and Hgb < 8 g/dl.(Ref: WHO/UNICEF/UNU, “Iron Deficiency Anaemia Assessment, Prevention, and Control: A Guide for Programme Managers,” Geneva, 2001) • have any gastrointestinal contraindication to ingestion of a capsule (known or suspected gastrointestinal obstruction, stricture, fistula, gastroparesis, or any swallowing disorder.) • have any contra-indication to the use of vancomycin • 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 • inclusion in any other interventional trial but may be enrolled if/when these disqualifiers have expired. Adult: 18 Year(s)-44 Year(s) 18 Year(s) 55 Year(s) Female
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 18/12/2023 UNIVERSITY OF ZAMBIA BIOMEDICAL RESEARCH ETHICS COMMITTEE
Ethics Committee Address
Street address City Postal code Country
Nationalist road, Lusaka Lusaka 10101 Zambia
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome The primary endpoint is the change in the mean count of nine selected fecal bacterial pathogens present between baseline and day 35 (acceptable window day 35-37) after randomization, which will be 15 days after the last dose of intervention (for those in arms 1 and 2). The selected pathogens to be detected by TAC (qPCR) include non-typhoid salmonellae, Shigella spp/enteroinvasive EIEC, Campylobacter spp, Enterotoxigenic Escherichia coli (ETEC), Enteropathogenic Escherichia coli (EPEC), Enteroaggregative Escherichia coli (EAEC), Enterohaemorrhagic Escherichia coli (EHEC), Aeromonas spp, Plesiomonas spp, Vibrio cholerae, rotavirus, norovirus, Giardia intestinalis, and Cryptosporidium spp. 15 days after the last dose of intervention
Secondary Outcome • Change in average count and relative abundance of specific enteropathogens (non-typhoid salmo-nellae, Shigella spp/enteroinvasive EIEC, Campylobacter spp, ETEC, EPEC, EAEC, EHEC, Aeromonas spp, Plesiomonas spp, Vibrio cholerae, rotavirus, norovirus, Giardia intestinalis and Cryptosporidium spp) in pregnant women detected in stool by TAC (qPCR) between baseline (before and after oral vancomycin treatment) and the last dose of 14-day VE-818 intervention (21st day, +2), 14 days after the last dose of 14-day VE-818 intervention (35th day, +2), 42 days after the last dose of 14-day VE-818 intervention (63rd day, +2), and 7 day post-partum in Treatment arm, compared to Placebo arm and Observation-only arm • Engraftment of VE-818 organisms in pregnant women measured through stool samples collected at 14 days after the last dose of 14-day VE-818 intervention (35th day, +2), 42 days after the last dose of 14-day VE-818 intervention (63rd day, +2) and 7 days after birth • Change in a panel of fecal biomarkers (myeloperoxidase, neopterin, calprotectin and lipocalin) in pregnant women between baseline (before and after oral vancomycin treatment) and 14 days after the last dose of 14-day VE-818 intervention (21st day, +2), 14 days after the last dose of 14-day in-tervention (35th day, +2), 42 days after the last dose of 14-day intervention (63rd day, +2), and 7 day post-partum in Treatment arm, compared to Placebo arm and Observation-only arm • Change in a panel of plasma biomarkers (CRP, AGP, sCD14, LBP, CD163 and iFABP) in pregnant women between baseline (before and after oral vancomycin treatment) and 14 days after the last dose of 14-day intervention (35th day, +2), 42 days after the last dose of 14-day intervention (63rd day, +2), and 7 day post-partum in Treatment arm, compared to Placebo arm and Observation-only arm • Change in LR ratio in pregnant women between baseline (before oral vancomycin treatment) and 14 days after the last dose of 14-day VE-818 intervention (35 last dose of 14-day VE-818 intervention
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Chawama Hospital Off Esther Lungu Road, Kamwala South Lusaka 10101 Zambia
FUNDING SOURCES
Name of source Street address City Postal code Country
Bill and Melinda Gates Foundation 500 Fifth Avenue North, Seattle, WA 98109 Washington United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor TROPGAN 26 Esther Lungu Road, Kamwala South Lusaka Zambia University
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Paul Kelly m.p.kelly@qmul.ac.uk +260966751875 26 Esther Lungu Road, Kamwala South
City Postal code Country Position/Affiliation
Lusaka Zambia Principal Investigator
Role Name Email Phone Street address
Public Enquiries Milika Sakala milika@tropgan.net +260977608608 26 Esther Lungu Road, Kamwala South
City Postal code Country Position/Affiliation
Lusaka Zambia Trial Coordinators or Managers
Role Name Email Phone Street address
Scientific Enquiries Aaron Tembo aaron@tropgan.net +260962161076 26 Esther Lungu Road, Kamwala South
City Postal code Country Position/Affiliation
Lusaka Zambia Clinical Research and Compliance Manager
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Individual Participant Data (IPD) from this trial will be shared upon request, following approval of a proposal by a review committee. The data shared will be anonymized participant data, including data dictionaries, in a format that is suitable for reanalysis. Requests for access to the data should be directed to Professor Paul Kelly at m.p.kelly@qmul.ac.uk. To gain access, requestors will need to sign a data access agreement. This will specify that the data will only be used for the purposes outlined in the proposal, and that no attempt will be made to identify individual participants. Additionally, summary results of the trial will be made available within 12 months of the study completion date, in accordance with WHO requirements. Informed Consent Form,Study Protocol The Individual Participant Data (IPD) from this trial will be shared within 12 months following the study's completion date, as mandated by WHO requirements. Requests for access to the data will be processed promptly upon receipt and approval of a proposal by a review committee. The access to Individual Participant Data (IPD) from this trial will be granted based on the following key criteria: Submission of a detailed proposal outlining the intended use of the data. Agreement to sign a data access agreement stipulating the terms of data usage, including confidentiality and appropriate data handling. Assurance that the data will only be used for the purposes outlined in the proposal and will not be used to identify individual participants. Compliance with all relevant ethical and legal requirements governing the use of the data. Consideration of the scientific merit of the proposed analysis or research project. Availability of resources to ensure proper handling and protection of the data throughout the access period. Upon meeting these criteria, access to the IPD will be granted following review and approval by the designated review committee.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information