BifIID: B. Infantis Supplementation to Improve Immunity in Infants Exposed to HIV
Study Details
Study Description
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
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markers of intestinal inflammation and microbial translocation at 4 weeks of life
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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:
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longitudinal succession of the gut microbiota composition, diversity and function
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relative and absolute abundance of B. infantis in infant stool during the first 36 weeks of life
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stool metabolome
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T cell subset ontogeny during the first 9 months of life.
Exploratory objectives are to evaluate whether B. infantis Rosell®-33 supplementation improves:
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infant growth
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all-cause morbidity
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neurodevelopment during the first 9 months of life
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antibody responses to early childhood vaccines
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
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
- 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. Infants will be followed over 36 weeks with extensive collection of meta-data and samples.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: B. infantis Rosell®-33 Participants will receive 8 x 109 CFU B. infantis Rosell®-33 per dose (single microbial active ingredient) and carrier material (maltodextrin) for 28 days from day 1-3 of life. |
Dietary Supplement: B. infantis Rosell®-33
B. infantis Rosell®-33 + maltodextrin
|
| Placebo Comparator: Placebo Participants will receive placebo (containing all materials besides B. infantis Rosell®-33) for 28 days from day 1-3 of life. |
Dietary Supplement: Placebo
Maltodextrin
|
Outcome Measures
Primary Outcome Measures
- Gut microbiome [4 weeks of age]
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
- Markers of intestinal inflammation and microbial translocation [4 - 36 weeks of age]
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
- BCG vaccine respone [7 weeks of age]
Frequencies of total net cytokine producing cells in response to stimulation with BCG will be compared between arms.
- BCG vaccine respone [36 weeks of age]
Frequencies of total net cytokine producing cells in response to stimulation with BCG will be compared between arms.
Secondary Outcome Measures
- Longitudinal succession in gut microbiota composition, diversity and function [4 - 36 weeks of age]
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.
- Stool metabolome [4 weeks of age]
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.
- T cell subsets frequencies [4 - 36 weeks of age]
T cell subsets frequencies will be compared cross-sectionally between groups
Other Outcome Measures
- Presence of total B. infantis and B. infantis Rosell®-33 in stool [4 - 36 weeks of age]
qPCR will be used to assess whether B. infantis Rosell®-33 colonized.
- Infant neurodevelopment milestones [24 and 36 weeks of age]
comprehensive neurodevelopment assessment will be conducted and developmental scores compared between the two arms.
- Infant growth [4 - 36 weeks of age]
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.
- All-cause infectious morbidity [4 - 36 weeks of age]
Infectious morbidity data will be quantify and compare occurrence of infectious morbidity outcomes between randomisation arms.
- Vaccine antibody titres [4 - 36 weeks of age]
Antibody titres to early childhood vaccines will be assessed and compared by treatment arm.
Eligibility Criteria
Criteria
Inclusion Criteria Mother:
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Willing and able to provide signed and dated informed consent form
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18 years of age or older
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Documented HIV seropositive
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Antiretroviral therapy initiated before the third trimester of pregnancy
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Planning on exclusively breastfeeding the infant for the first 6 months of life
Inclusion Criteria Infant:
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Documented HIV seronegative at birth
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Born at term (completed at least 37 weeks of gestation)
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Birth weight >2.4kgs
Exclusion Criteria:
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Severe illnesses, e.g. Sepsis
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current TB or known household TB contact
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Chronic disorder or medications (other than antiretrovirals and cotrimoxazole prophylaxis) that in the opinion of the investigator would alter immunity
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Pregnancy or delivery complications including birth asphyxia, seizures, sepsis, major congenital anomalies or congenital infections
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Known contraindications to components of the interventional products
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Taking additional probiotics or prebiotics
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Any condition that in the opinion of the investigator would make participation in the trial unsafe
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- University of Cape Town
- Seattle Children's Hospital
- University of Stellenbosch
- Institute for Systems Biology
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- University of Washington
Investigators
- Principal Investigator: Heather Jaspan, MD PHD, Seattle Children's Research Institute
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 697/2022
- R01HD109089
- PACTR202301748714019