Trial no.:	PACTR202404835984424	Date of Registration:	26/04/2024
Trial Status:	Registered in accordance with WHO and ICMJE standards

TRIAL DESCRIPTION

Public title

Maternal Probiotic Intervention to Improve Gut Health-Trial II (MPIGH-II)

Official scientific title

Ability of VE818 to reduce enteropathogen colonization and improve environmental enteropathy in pregnant women: a proof of concept and phase II randomized placebo-controlled trial in Bangladesh, Pakistan, Zambia and Burkina Faso

Brief summary describing the background and objectives of the trial

In 2020, 149.2 million children under the age of 5 were affected by stunting, representing 22% of the world children population under 5. This is thus a serious public health concern linked to increased disease, mortality, and long-term neurocognitive issues. This condition is often connected to Environmental Enteropathy (EE), a disorder marked by intestinal damage which impairs nutrient absorption and weakens immune responses. EE disrupts gut health, where the intestinal microbiome plays a critical role by interacting with the immune system, enhancing nutrient absorption, and contributing to overall energy needs through fermentation processes. Until now, research on child stunting has primarily focused on early childhood. However, it's increasingly recognized that stunting often originates in utero, leading to growing interest in the health of reproductive age and pregnant women. In this regard, The Lancet's 2021 series on maternal and child undernutrition asserts that "investments aimed at reducing undernutrition among women are crucial not only for the health of the women themselves but also for the health and nutrition of their children." In Burkina Faso, child stunting and micronutrient deficiencies pose major challenges. Despite high rates of iron supplementation during pregnancy, anemia rates remain high due to EE, which hinders the absorption of nutrients. This underscores the limited effectiveness of current interventions and the potential of targeting maternal EE to improve outcomes both for mothers and their children. Our study aims to explore the potential of microbiota-targeted interventions to improve gut health and reduce stunting.

Type of trial

RCT

Acronym (If the trial has an acronym then please provide)

MPIGH II

Disease(s) or condition(s) being studied

Digestive System,Nutritional, Metabolic, Endocrine,Pregnancy and Childbirth

Sub-Disease(s) or condition(s) being studied

Purpose of the trial

Treatment: Drugs

Anticipated trial start date

01/10/2024

Actual trial start date

Anticipated date of last follow up

31/12/2026

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	Simple randomization using a randomization table created by a computer software program	Sealed opaque envelopes	Masking/blinding used	Care giver/Provider,Participants

INTERVENTIONS
Intervention type	Intervention name	Dose	Duration	Intervention description	Group size	Nature of control
Experimental Group	Treatment Arm	Participants randomized to treatment arm will receive a 3 x 250 mg daily dose of a specific antibiotic (vancomycin) for 5 days, followed by a 1-day washout period, after which participants will receive a 5 capsules of approximately 2 x 10^9 CFU/capsule of VE818 administered once a day for 14 days.	The total duration of threatment is: 5 days of vancomycin + 1 day of washout + 14 days of VE818 = 20 days	Participants randomized to treatment arm will receive a 3 x 250 mg daily dose of a specific antibiotic (vancomycin) for 5 days, followed by a 1-day washout period, after which participants will receive a 5 capsules of approximately 2 x 10^9 CFU/capsule of VE818 administered once a day for 14 days.	48
Control Group	Observation Arm	Participants in this group will not be given any intervention	Participants are observed for 20 days	Participants in this group will not be given any intervention. They are simply observed for 20 days	48	Uncontrolled
Control Group	Placebo Arm	Participants randomized to placebo arm will receive a 3 x 250 mg daily dose of oral vancomycin for 5 days, followed by a 1-day washout period, after which participants will receive 5 placebo capsules administered once a day for 14 days	The duration of the intervention is: 5 days of vancomicyn + 1 day of washout + 14 days of placebo = 20 days	Participants randomized to placebo arm will receive a 3 x 250 mg daily of oral vancomycin for 5 days, followed by a 1-day washout period, after which participants will receive 5 placebo capsules administered once a day for 14 days	48	Placebo

ELIGIBILITY CRITERIA
List inclusion criteria	List exclusion criteria	Age Category	Minimum age	Maximum age	Gender
1. Women aged 18 years or older in the first or early second trimester of pregnancy, 2. living in defined geographical areas 3. Presence of any 2 bacterial pathogens from the list of 11 selected bacterial enteropathogens (Aeromonas, Campylobacter coli, Campylobacter jejuni, Campylobacter Pan, Enteroaggregative Escherichia coli, Entero-pathogenic Escherichia coli, Enterotoxigenic Escherichia coli, Enterohaemorrhagic Escherichia coli (EHEC) Plesiomonas, Shigella_EIEC, Salmonella and Vibrio cholera ) in the fecal sample detected by TAC (qPCR).	Potential participants will not be enrolled if they: • have had diarrhea, defined as the passage of three or more loose fecals per 24 hours, in the preceding 2 weeks before randomization • have a fever or an active infection • have a history of chronic digestive disease • have taken antibiotics or probiotics in the preceding 2 weeks before randomization • have taken steroids or non-steroidal anti-inflammatory drugs in the preceding 2 weeks before randomization • have any illness which in the opinion of the investigator will complicate the assessment of safety or efficacy. Exclude pregnant women with 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 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 • known hypersensitivity/allergy/intolerance to any ingredient in vancomycin or the VE818 study formulation • known immunocompromised status (known history of HIV infection, autoimmune disease, diabetes mellitus, etc.,). but may be enrolled if/when these disqualifiers have expired.	Adult: 18 Year(s)-44 Year(s)	18 Year(s)	45 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

07/02/2024

Comite d ethique pour la recherche en sante

Ethics Committee Address
Street address	City	Postal code	Country
03 BP 7009 Ouagadougou	Ouagadougou	03	Burkina Faso

OUTCOMES
Type of outcome	Outcome	Timepoint(s) at which outcome measured
Primary Outcome	The primary outcome is the change in the mean count of 11 targeted fecal bacterial pathogen group present between baseline and 35th day after randomization. The list of 11 selected pathogens to be detected by TAC (qPCR) includes Aeromonas, Campylobacter coli, Campylobacter jejuni, Campylobacter Pan, Enteroaggregative E. Coli, Enteropathogenic E. Coli, Enterotoxigenic E. Coli, Plesiomonas, Shigella_EIEC, Salmonella and Vibrio cholera	2 weeks afer the last dose of the intervention
Secondary Outcome	Change in the average count and relative abundance of specific enteric pathogens (Salmonella, Shigella, Campylobacter, ETEC, EPEC, EAEC, rotavirus, norovirus, Giardia, and Cryptosporidium) detected in stool by TAC-qPCR in pregnant women at Day 21, Day 35, Day 63, and 7 days postpartum, compared to the placebo arm and the observation arm.	7 days postpartum
Secondary Outcome	Persistence of VE818 strains in pregnant women, measured by shotgun metagenomic sequencing of fecal samples and CapScan collected at Day 21, Day 35, Day 63, and 7 days postpartum.	7 days postpartum
Secondary Outcome	Change in the concentration of intestinal inflammation biomarkers (myeloperoxidase, neopterin, calprotectin, and lipocalin) in pregnant women measured by ELISA between the start of the study (before and after oral vancomycin treatment) and Day 21, Day 35, Day 63, and 7 days postpartum, compared to the placebo arm and the observation arm.	7 days postpartum
Secondary Outcome	Change in intestinal permeability measured by the Lactulose/Rhamnose (LR) ratio in pregnant women between the start of the study (before oral vancomycin treatment) and Day 35, compared to the placebo arm and the observation arm.	35 days after intervention start
Secondary Outcome	Change in alpha and beta diversity of the fecal microbiota in pregnant women measured by shotgun metagenomic sequencing between the start of the study (before and after oral vancomycin treatment) and Day 21, Day 35, Day 63, and 7 days postpartum, compared to the placebo arm and the observation arm.	7 days postpartum
Secondary Outcome	Change in alpha and beta diversity of the vaginal microbiome in pregnant women measured by shotgun metagenomic sequencing between the start of the study (before and after oral vancomycin treatment) and Day 21, Day 35, and Day 63, compared to the placebo arm and the observation arm.	21 days, 35 days and 63 days after the start of intervention
Secondary Outcome	Change in alpha and beta diversity of the oral microbiome in pregnant women measured by shotgun metagenomic sequencing between the start of the study (before oral vancomycin treatment), and Day 21 and Day 35, compared to the placebo arm and the observation arm.	21 days and 35 days after the start of the intervention
Secondary Outcome	Change in the blood, fecal, and urinary metabolome in pregnant women between the start of the study (before and after oral vancomycin treatment), and Day 21, Day 35, and Day 63, compared to the placebo arm and the observation arm.	21 days, 35 days and 63 days after the start of the intervention
Secondary Outcome	Change in the concentration of a panel of blood biomarkers (CRP, AGP, sCD14, LBP, CD163 and iFABP) in pregnant women as measured by ELISA between the start of the study (before and after oral vancomycin pretreatment) and Day 35 and Day 63 in the treatment arm compared to the placebo arm and the observation-only arm.	35 days and 63 days after the start of the study

RECRUITMENT CENTRES
Name of recruitment centre	Street address	City	Postal code	Country
Health District of Do	Rue 22.108, Yeguere	Bobo Dioulasso		Burkina Faso

FUNDING SOURCES
Name of source	Street address	City	Postal code	Country
Bill and Melinda Gates Foundation	500 Fifth Avenue North, Seattle, WA	Seattle	98109	United States of America

SPONSORS
Sponsor level	Name	Street address	City	Postal code	Country	Nature of sponsor
Primary Sponsor	Ghent University	Sint-Pietersnieuwstraat 33	Ghent	9000	Belgium	University
Secondary Sponsor	IRSS DRO	Avenue de la liberte, 399	Bobo Dioulasso	01	Burkina Faso	Health research institute
Secondary Sponsor	AFRICSANTE	rue 15.35, Ouezzin Ville	Bobo Dioulasso		Burkina Faso	Other Collaborative Groups

COLLABORATORS
Name	Street address	City	Postal code	Country
TROPGAN	H887	Lusaka		Zambia
icddr.	1212	Dhaka		Bangladesh
AKU	74800	Karachi		Pakistan

CONTACT PEOPLE
Role	Name	Email	Phone	Street address
Principal Investigator	Laeticia Celine TOE	LaeticiaCeline.Toe@ugent.be	+3292646035	Coupure links 653
City	Postal code	Country	Position/Affiliation
Ghent	9000	Belgium	Ghent University
Role	Name	Email	Phone	Street address
Principal Investigator	Trenton DAILEY SCHWALIBOG	trenton.daileychwalibog@ugent.be	+33603233614	Coupure links 653
City	Postal code	Country	Position/Affiliation
Ghent	9000	Belgium	Principal Investigator
Role	Name	Email	Phone	Street address
Public Enquiries	Moctar OUEDRAOGO	obmoctar@gmail.com	+22670238198	Ouezzin-Ville
City	Postal code	Country	Position/Affiliation
Bobo Dioulasso		Burkina Faso	Trial Coordinator
Role	Name	Email	Phone	Street address
Scientific Enquiries	Laeticia Celine TOE	laeticiaceline.toe@ugent.be	+22671007272	Ouezzin-Ville
City	Postal code	Country	Position/Affiliation
Bobo Dioulasso	01	Burkina Faso	Institut de Recherche en Sciences de la Sante

REPORTING
Share IPD	Description	Additional Document Types	Sharing Time Frame	Key Access Criteria
Yes	All of the individual participant data collected during the trial, after pseudonymization	Clinical Study Report,Informed Consent Form,Study Protocol	Beginning 9 months and ending 36 months following article publication	The authorities of the country's Ministry of Health The authorities of the country's Ministry of Research Members of the research team Applicant with the agreement of the Principal Investigator
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

Pan African Clinical Trials Registry