Clinical trial NCT05923333: B. Infantis Supplementation to Improve Immunity in Infants Exposed to HIV
Official title: Bifidobacterium Infantis Supplementation in Early Life to Improve Immunity in Infants Exposed to HIV: a Randomized, Placebo-controlled, Double-blind Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Hiv
Vaccine Reaction
Microbial Colonization
Infant Development
Lead sponsor: University of Cape Town
Sponsor class: OTHER
Collaborators: name: Seattle Children's Hospital
name: University of Stellenbosch
name: Institute for Systems Biology
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: University of Washington
First posted: 2023-06-28
Enrollment: 200
Sex: ALL
Minimum age (years): 0
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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. Infants will be followed over 36 weeks with extensive collection of meta-data and samples.

Eligibility criteria: Inclusion Criteria Mother:

* 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
* Planning on exclusively breastfeeding the infant for the first 6 months of life

Inclusion Criteria Infant:

* Documented HIV seronegative at birth
* Born at term (completed at least 37 weeks of gestation)
* Birth weight \>2.4kgs

Exclusion Criteria:

* 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
* Known contraindications to components of the interventional products
* Taking additional probiotics or prebiotics
* Any condition that in the opinion of the investigator would make participation in the trial unsafe

Primary outcomes:
measure: Gut microbiome
timeFrame: 4 weeks of age
measure: Markers of intestinal inflammation and microbial translocation
timeFrame: 4 - 36 weeks of age
measure: BCG vaccine respone
timeFrame: 7 weeks of age
measure: BCG vaccine respone
timeFrame: 36 weeks of age
Secondary outcomes:
measure: Longitudinal succession in gut microbiota composition, diversity and function
timeFrame: 4 - 36 weeks of age
measure: Stool metabolome
timeFrame: 4 weeks of age
measure: T cell subsets frequencies
timeFrame: 4 - 36 weeks of age
Other outcomes:
measure: Presence of total B. infantis and B. infantis Rosell®-33 in stool
timeFrame: 4 - 36 weeks of age
measure: Infant neurodevelopment milestones
timeFrame: 24 and 36 weeks of age
measure: Infant growth
timeFrame: 4 - 36 weeks of age
measure: All-cause infectious morbidity
timeFrame: 4 - 36 weeks of age
measure: Vaccine antibody titres
timeFrame: 4 - 36 weeks of age
Locations:
city: Cape Town
country: South Africa
facility: Khayelitsha Site B Midwife Obstetric Unit
Study officials:
affiliation: Seattle Children's Hospital
name: Heather Jaspan, MD PHD
role: PRINCIPAL_INVESTIGATOR
References: