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NCT Number: NCT05923333

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

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

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Key information

Conditions

HIV Acquired Immunodeficiency Syndrome Blood-Borne Infections Communicable Diseases Disease Attributes Genital Diseases HIV Infections Immune System Diseases Immunologic Deficiency Syndromes Infant Development Infections Lentivirus Infections Microbial Colonization Pathologic Processes Pathological Conditions, Signs and Symptoms RNA Virus Infections Retroviridae Infections Sexually Transmitted Diseases Sexually Transmitted Diseases, Viral Slow Virus Diseases Urogenital Diseases Vaccine Reaction Virus Diseases

Age range

0 day–50 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Khayelitsha Site B Midwife Obstetric Unit

Cape Town, South Africa

Location status: Recruiting

Location contact

Busi Tyhenge

CONTACT

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

B. infantis Rosell®-33

Dietary Supplement

B. infantis Rosell®-33 + maltodextrin

Placebo

Dietary Supplement

Maltodextrin

Primary outcomes

  1. Gut microbiome

    Time frame: 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

  2. Markers of intestinal inflammation and microbial translocation

    Time frame: 4 - 36 weeks of age

    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

  3. BCG vaccine respone

    Time frame: 7 weeks of age

    Frequencies of total net cytokine producing cells in response to stimulation with BCG will be compared between arms.

  4. BCG vaccine respone

    Time frame: 36 weeks of age

    Frequencies of total net cytokine producing cells in response to stimulation with BCG will be compared between arms.

Secondary outcomes

  1. Longitudinal succession in gut microbiota composition, diversity and function

    Time frame: 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.

  2. Stool metabolome

    Time frame: 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.

  3. T cell subsets frequencies

    Time frame: 4 - 36 weeks of age

    T cell subsets frequencies will be compared cross-sectionally between groups

Other outcomes

  1. Presence of total B. infantis and B. infantis Rosell®-33 in stool

    Time frame: 4 - 36 weeks of age

    qPCR will be used to assess whether B. infantis Rosell®-33 colonized.

  2. Infant neurodevelopment milestones

    Time frame: 24 and 36 weeks of age

    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.

  3. Infant growth

    Time frame: 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.

  4. All-cause infectious morbidity

    Time frame: 4 - 36 weeks of age

    Infectious morbidity data will be quantify and compare occurrence of infectious morbidity outcomes between randomisation arms.

  5. Vaccine antibody titres

    Time frame: 4 - 36 weeks of age

    Antibody titres to early childhood vaccines will be assessed and compared by treatment arm.

Study contacts

Contact information is provided by the study sponsor or research team.

Anna-Ursula Happel, PhD

CONTACT

[email protected]

+ 27 21 406 6823

Heather Jaspan, MD PHD

CONTACT

[email protected]

2068543336

Sponsors and collaborators

Lead sponsor

University of Cape Town

Other

Collaborators

  • 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

Registry information

Official study title

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

Acronym: BifIID

Important dates

Study start
2023
Primary completion
2026
Study completion
2027
First posted
Jun 28, 2023
Registry last updated
Aug 22, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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