B. Infantis Supplementation to Improve Immunity in Infants Exposed to HIV

Hiv Clinical Trial

— BifIID  

Official title:

Bifidobacterium Infantis Supplementation in Early Life to Improve Immunity in Infants Exposed to HIV: a Randomized, Placebo-controlled, Double-blind Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05923333
• Other study ID #: 697/2022
• Secondary ID: R01HD109089PACTR
• Status: Recruiting
• Phase: N/A
• Start date: August 11, 2023
• Est. completion date: June 2027

Study information

• Verified date: January 2024
• Source: University of Cape Town
• Contact: Heather Jaspan, MD PHD
• Phone: 2068543336
• Email: hbjaspan[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: June 2027
• Est. primary completion date: June 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 0 Days to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Communicable Diseases
• Hiv
• Infant Development
• Infections
• Microbial Colonization
• Vaccine Reaction

Intervention

Dietary Supplement:
• B. infantis Rosell®-33
B. infantis Rosell®-33 + maltodextrin
• Placebo
Maltodextrin

Locations

Country	Name	City	State
South Africa	Khayelitsha Site B Midwife Obstetric Unit	Cape Town

Sponsors (6)

Lead Sponsor	Collaborator
University of Cape Town	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Institute for Systems Biology, Seattle Children's Hospital, University of Stellenbosch, University of Washington

Country where clinical trial is conducted

South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Presence of total B. infantis and B. infantis Rosell®-33 in stool	qPCR will be used to assess whether B. infantis Rosell®-33 colonized.	4 - 36 weeks of age
Other	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.	24 and 36 weeks of age
Other	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.	4 - 36 weeks of age
Other	All-cause infectious morbidity	Infectious morbidity data will be quantify and compare occurrence of infectious morbidity outcomes between randomisation arms.	4 - 36 weeks of age
Other	Vaccine antibody titres	Antibody titres to early childhood vaccines will be assessed and compared by treatment arm.	4 - 36 weeks of age
Primary	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	4 weeks of age
Primary	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	4 - 36 weeks of age
Primary	BCG vaccine respone	Frequencies of total net cytokine producing cells in response to stimulation with BCG will be compared between arms.	7 weeks of age
Primary	BCG vaccine respone	Frequencies of total net cytokine producing cells in response to stimulation with BCG will be compared between arms.	36 weeks of age
Secondary	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 of age
Secondary	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 of age
Secondary	T cell subsets frequencies	T cell subsets frequencies will be compared cross-sectionally between groups	4 - 36 weeks of age