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.: PACTR202301748714019 Date of Approval: 24/01/2023
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Bifidobacterium infantis supplementation in early life to improve immunity in infants exposed to HIV: a randomized, placebo-controlled, double-blind trial
Official scientific title Bifidobacterium infantis supplementation in early life to improve immunity in infants exposed to HIV: a randomized, placebo-controlled, double-blind trial
Brief summary describing the background and objectives of the trial Brief Summary: The primary objectives of this study are to evaluate the effect of early-life B. infantis Rosell®-33 supplementation in infants exposed to HIV on: Gut microbiome composition and diversity at 4 weeks of life; Markers of intestinal inflammation and microbial translocation at 4 weeks of life; Th1 cytokine responses to BCG at 7 weeks and 36 weeks of life The secondary objectives include to evaluate the effect of B. infantis Rosell®-33 supplementation on: Longitudinal succession of the gut microbiota composition, diversity and function; Relative and absolute abundance of B. infantis in infant stool during the first 36 weeks of life; Stool metabolome; T cell subset ontogeny during the first 9 months of life. Exploratory objectives are to evaluate whether B. infantis Rosell®-33 supplementation improves: infant growth all-cause morbidity neurodevelopment during the first 9 months of life antibody responses to early childhood vaccines Detailed Description: Infants who are born to mothers with HIV (exposed but uninfected; iHEU) are at higher risk of morbidity and display multiple immune alterations compared to infants who are HIV-unexposed (iHU). Easily implementable strategies to improve immunity of iHEU, and possibly subsequent health outcomes, are needed. iHEU have altered gut microbiome composition and bifidobacterial depletion, and relative abundance of Bifidobacterium infantis has been associated with immune ontogeny, including humoral and cellular vaccine responses. Therefore, a randomized trial of B. infantis Rosell®-33 versus placebo given during the first month of life in South African iHEU will be conducted. This is a parallel, randomised, controlled study. Two-hundred breastfed iHEU will be enrolled from the Khayelitsha Site B Midwife Obstetric Unit in Cape Town, South Africa and 1:1 randomised to receive 8 x109 CFU B. infantis Rosell®-33 daily or placebo for the first 4 weeks of life, starting on day 1-3 of life.
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Infections and Infestations,Microbial Colonization and Infant Development,Paediatrics,Pregnancy and Childbirth
Sub-Disease(s) or condition(s) being studied HIV/AIDS
Purpose of the trial Early detection /Screening
Anticipated trial start date 01/07/2023
Actual trial start date
Anticipated date of last follow up 30/06/2027
Actual Last follow-up date
Anticipated target sample size (number of participants) 200
Actual target sample size (number of participants)
Recruitment status 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 Allocation was determined by the holder of the sequence who is situated off site 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 Active 1 sachet daily 26 days Each sachet contains ~8 x10^9 CFU of B. infantis Rosell®-33 manufactured by Lallemand Health Solutions 100
Control Group Placebo 1 sachet daily 26 days Each sachet will contain a placebo to the B. infantis 100 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Mother: 1) Willing and able to provide signed and dated informed consent form 2) 18 years of age or older 3) Documented HIV seropositive 4) Antiretroviral therapy initiated before the third trimester of pregnancy 5) Planning on exclusively breastfeeding the infant for the first 6 months of life Infant: Documented HIV seronegative at birth Born at term (completed at least 37 weeks of gestation) Birth weight >2.4kgs Mother: 1) Complications during pregnancy and delivery such as gestational diabetes, obesity (BMI> 35 prior to pregnancy), chorioamnionitis and eclampsia 2) Active TB or other infectious diseases 3) Administration of probiotics, prebiotics or immunoregulatory products Infant: 1) Hypoxic injury/ seizures/ sepsis/ Intrauterine growth retardation 2) Administration of probiotics, prebiotics or immunoregulatory products 3) Any condition that in the opinion of the investigator would make participation in the trial unsafe Infant: 0 Month-23 Month 0 Day(s) 9 Month(s) Both
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 10/03/2023 University of Cape Town Human Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
E53-Room 46, Old Main Building Groote Schuur Hospital Observatory 7925 Cape Town 7925 South Africa
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Gut microbiome Alpha (Shannon) and Beta (Bray Curtis and UniFrac) diversity metrics on the entire microbial communities, assessed by bacterial shotgun metagenomics of infant stool, will be compared between treatment arms Week 4
Secondary Outcome Longitudinal succession in gut microbiota composition, diversity and function Longitudinal multi-omic variation will be visualized using PCoA and tSNE plots, and cross-sectional differences in multi-omic profiles will be assessed using PERMANOVAs. 4-36 weeks
Secondary Outcome Stool metabolome For cross-sectional metabolite differential abundance analyses, we will use generalized linear regression (continuous dependent variable) and logistic regression (Boolean dependent variable) with an FDR correction. 4 weeks
Primary Outcome Markers of intestinal inflammation and microbial translocation Markers of intestinal inflammation and microbial translocation (Lipocalin-2 (Lcn-2), sCD163, I-FABP and LBP measured by ELISA in infant plasma) will be compared cross-sectionally at each time point between groups using Mann-Whitney U tests 4-36 weeks
Primary Outcome BCG vaccine respone Frequencies of total net cytokine producing cells in response to stimulation with BCG will be compared between arms. 7 weeks
Primary Outcome BCG vaccine respone Frequencies of total net cytokine producing cells in response to stimulation with BCG will be compared between arms. 36 weeks
Secondary Outcome T cell subsets frequencies T cell subsets frequencies will be compared cross-sectionally between groups 4-36 weeks
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Khayelitsha Site B Midwife Obstetrics Unit Lwandle Road, Site B Khayelitsha Cape Town 7784 South Africa
FUNDING SOURCES
Name of source Street address City Postal code Country
National Institute of Health 9000 Rockville Pike, Bethesda Maryland 20892 United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor University of Cape Town Anzio Road Cape Town 7925 South Africa University
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Heather Jaspan heather.jaspan@uct.ac.za +27216501974 Anzio Road
City Postal code Country Position/Affiliation
Cape Town 7925 South Africa Associate Professor
Role Name Email Phone Street address
Public Enquiries Anna Happel anna.happel@uct.ac.za +27214066823 Anzio Road
City Postal code Country Position/Affiliation
Cape Town 7925 South Africa Research Fellow
Role Name Email Phone Street address
Scientific Enquiries Heather Jaspan heather.jaspan@uct.ac.za +27216501974 Anzio Road
City Postal code Country Position/Affiliation
Cape Town 7925 South Africa Associate Professor
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Access to trial IPD can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). Analytic Code,Study Protocol Beginning 3 months and ending 36 months following article publication. Qualified researchers engaging in independent scientific research can request access to data from the PI by submitting a research proposal and analysis plan. The research team will review the proposal and if approved, share data.
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