B. Infantis Supplementation to Improve Immunity in Infants Exposed to HIV
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age0-50
SponsorUniversity of Cape Town
About this trial
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
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Willing and able to provide signed and dated informed consent form
18 years of age or older
Documented HIV seropositive
Antiretroviral therapy initiated before the third trimester of pregnancy
Disqualifiers
Severe illnesses, e.g. Sepsis
current TB or known household TB contact
Chronic disorder or medications (other than antiretrovirals and cotrimoxazole prophylaxis) that in the opinion of the investigator would alter immunity
Pregnancy or delivery complications including birth asphyxia, seizures, sepsis, major congenital anomalies or congenital infections
Trial design
Design model
Parallel
Treatments tested in this trial
B. infantis Rosell®-33
Dietary supplementB. infantis Rosell®-33 + maltodextrin
Placebo
Dietary supplementMaltodextrin
Treatment groups
200 Participants
are divided into 2 treatment groupsGroup A: B. infantis Rosell®-33Active comparator 1 intervention
Group B: PlaceboPlacebo comparator 1 intervention
Trial outcomes
Primary outcomes
1
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
Time frame
4 weeks of age2
Markers of intestinal inflammation and microbial translocation
Concentration of 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
Time frame
4 - 36 weeks of age3
BCG vaccine respone
Frequencies of total net cytokine producing cells in response to stimulation with BCG will be compared between arms.
Time frame
7 weeks of age4
BCG vaccine respone
Frequencies of total net cytokine producing cells in response to stimulation with BCG will be compared between arms.
Time frame
36 weeks of ageSecondary outcomes
1
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.
Time frame
4 - 36 weeks of age2
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.
Time frame
4 weeks of age3
T cell subsets frequencies
T cell subsets frequencies will be compared cross-sectionally between groups
Time frame
4 - 36 weeks of ageOther outcomes
1
Presence of total B. infantis and B. infantis Rosell®-33 in stool
qPCR will be used to assess whether B. infantis Rosell®-33 colonized.
Time frame
4 - 36 weeks of age2
Infant neurodevelopment milestones
Comprehensive neurodevelopment assessment will be conducted, e.g. using the Bayley Scales of Infant and Toddler Development, 3rd edition, or similar assessment tools, and developmental scores compared between the two arms, as well as the proportion of infants passing each developmental area assessed. Higher scores indicate better outcomes.
Time frame
24 and 36 weeks of age3
Infant growth
Infant anthropometry will be recorded at each visit to calculate infant length for age (LAZ), weight for age (WAZ) and weight for length (WLZ) Z scores and will be compared between the two arms.
Time frame
4 - 36 weeks of age4
All-cause infectious morbidity
Infectious morbidity data will be quantify and compare occurrence of infectious morbidity outcomes between randomisation arms.
Time frame
4 - 36 weeks of ageSponsors and contacts
Click on the lead sponsor to view all of their trials.
University of Cape Town
Lead sponsor
Seattle Children's Hospital
Collaborator
University of Stellenbosch
Collaborator
Institute for Systems Biology
Collaborator
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Collaborator
University of Washington
Collaborator
Source ClinicalTrials.gov