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.: PACTR202310762132359 Date of Approval: 24/10/2023
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Probiotic For the Improvement of Environmental Enteropathy in Pregnant Women in Senegal ( PROFE-Sen )
Official scientific title Ability of the Probiotic Vivomixx to Improve Environmental Enteropathy in Pregnant Women: a Proof of Concept Trial
Brief summary describing the background and objectives of the trial Stunting in young children refers to attenuated linear growth. In the year 2020, 149.2 million children under the age of 5 were stunted, accounting for 22% of stunting globally. Stunting has short- and long-term consequences of increased morbidity and mortality, impairment of neurocognitive development , impaired responses to oral vaccines, and increased risk of non-communicable diseases. Stunting is partly driven by Environmental Enteric Dysfunction (EED), an enteropathic condition characterised by altered gut permeability, infiltration of immune cells and changes in villous architecture and cell differentiation. EED may help explain why nutritional supplementation either during pregnancy or early childhood has minimal value in correcting childhood stunting. Probiotics may serve to overcome the problem of EED through all mechanisms of pathogenicity, by providing additional bacteria that may help in intestinal decolonization of pathogenic microorganisms (changing the microbiological niche), promoting epithelial healing, improving nutrient absorption, and restoration of an appropriate immune balance between tolerance and responsiveness. This trial will explore the conceptual framework, that a well known probiotic, that can improve the composition of the gut microbiota, can reduce biomarkers of intestinal inflammation and gut health. This will restore healthy microbial signalling to the host epithelium, ameliorate barrier function through secretion of mucus and antimicrobial factors, and improve nutrient availability. 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.
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Digestive System,Pregnancy and Childbirth
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Treatment: Other
Anticipated trial start date 30/11/2023
Actual trial start date
Anticipated date of last follow up 30/08/2024
Actual Last follow-up date
Anticipated target sample size (number of participants) 76
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
NCT05501470 ClinicalTrials.gov
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 from a statistics book Sealed opaque envelopes Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Probiotic arm Daily Dose 8 weeks Participant in the experimental arm will receive a daily dose of the probiotic for 8 weeks and Participant in the control arm will receive a daily dose of a placebo for 8 weeks. 38
Control Group Placebo arm Daily dose 8 weeks Participant in the control arm will receive a daily dose of a placebo for 8 weeks. 38 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
• Any pregnant woman in the second trimester of pregnancy (confirmed by ultrasound) • Adult (18 years old) • living in defined geographical areas of Guediawaye • Full understanding and consent agreement to participate in protocol as planned • Had diarrhea, defined as the release of three or more loose stools per 24 hours in the previous 14 days. • Have taken antibiotics or probiotics in the previous 14 days • Have taken non-steroidal anti-inflammatory drugs or corticosteroids in the previous 14 days • Have hemoglobin <8g/dl • Have multiple pregnancies • Have a disease that, in the investigator’s opinion, would complicate the assessment of safety or efficacy. • Have a gastrointestinal contraindication to ingesting a capsule (known or suspected gastrointestinal obstruction, stenosis, fistula, gastroparesis or any swallowing disorder). • Have plans to leave Guédiawaye during the follow-up period • Included in any other interventional trial However, they may be included in the trial when these criteria have expired. Adult: 19 Year-44 Year 18 Year(s) 49 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 22/06/2023 Comite National d Ethique pour la Recherche en Sante
Ethics Committee Address
Street address City Postal code Country
Rue Aime Cesaire Dakar NA Senegal
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome 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 and 56
Secondary Outcome Reduction in enteropathogen colonisation 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 Day 1 and 56
Secondary Outcome Impact of Vivomixx on the structure and function of the microbiome Change in relative abundance values of alpha and beta diversity pre- and post-treatment samples. Day 1 and 56
Secondary Outcome Vivomixx Reduction in permeability Reduction in LR ratio in Vivomixx compared to placebo groups Day 1 and 56
Secondary Outcome Impact of the host metabolome in pregnant woman Change in the metabolome, Untargeted urine, and plasma (and fecal) metabolome before and after the intervention. Day 1 and 56
Secondary Outcome Rate of weight gain in the 2nd trimester of pregnancy Weight gain velocity in the 2nd trimester of pregnancy Day 1 and 56
Secondary Outcome Variability in endpoints across geographies and participating laboratories Measurements of variability, including standard deviations and kappa values; Preliminary work across all sites using identical kits and harmonised SOPs Day 1 and 56
Secondary Outcome CapScan success rate in delivering an assessment of the microbiome throughout the gut Recovery of useful data from CapScan; completion of whole gut microbiome profiles Day 1 and Day 56
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Wakhinane Health Care Center Guediawaye Dakar Senegal
FUNDING SOURCES
Name of source Street address City Postal code Country
Bill and Melinda Gates Foundation 500 Fifth Avenue North Seattle Seattle WA 98109 United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Institut Pasteur Dakar 36 Avenue pasteur Dakar B.P. 220 Senegal Charities/Societies/Foundation
COLLABORATORS
Name Street address City Postal code Country
International Centre for Diarrhoeal Disease Research 68 Shaheed Tajuddin Ahmed Sarani Mohakhali Dhaka 1212 Dhaka Bangladesh
Aga Khan University Stadium Road Karachi 74800 Karachi 3500 Pakistan
Tropical Gastroenterology and Nutrition Group TROPGAN 26 Copper Road Kampala South lusaka Zambia
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Yakhya Dieye yakhya.dieye@pasteur.sn +221774012735 36 Avenue pasteur
City Postal code Country Position/Affiliation
Dakar Senegal Head of the microbiology division
Role Name Email Phone Street address
Public Enquiries Billo Tall billo.tall@pasteur.sn +221775358135 36 avenue pasteur
City Postal code Country Position/Affiliation
dakar Senegal Research Assistant
Role Name Email Phone Street address
Scientific Enquiries Billo Tall billo.tall@pasteur.sn +221775358135 36 avenue pasteur
City Postal code Country Position/Affiliation
dakar Senegal reseach assistant
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes The study protocol and summary results will summary will be made available on reasonable request to Prinicpal investigator Clinical Study Report,Study Protocol Within 12 months of the study completion date Upon reasonable request to the principal investigators
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