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| ID | Type | Description | Link |
|---|---|---|---|
| R01HD109089 | U.S. NIH Grant/Contract | View source | |
| PACTR202301748714019 | Registry Identifier | Pan African Clinical Trials Registry |
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| Name | Class |
|---|---|
| Seattle Children's Hospital | OTHER |
| University of Stellenbosch | OTHER |
| Institute for Systems Biology | OTHER |
| Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) |
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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:
The secondary objectives include to evaluate the effect of B. infantis Rosell®-33 supplementation on:
Exploratory objectives are to evaluate whether B. infantis Rosell®-33 supplementation improves:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| B. infantis Rosell®-33 | Active Comparator | 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. |
|
| Placebo | Placebo Comparator | Participants will receive placebo (containing all materials besides B. infantis Rosell®-33) for 28 days from day 1-3 of life. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| B. infantis Rosell®-33 | Dietary Supplement | B. infantis Rosell®-33 + maltodextrin |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| 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 |
| 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 |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Stool metabolome |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| 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. |
Inclusion Criteria Mother:
Inclusion Criteria Infant:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Heather Jaspan, MD PHD | Contact | 2068543336 | hbjaspan@gmail.com | |
| Anna-Ursula Happel, PhD | Contact | + 27 21 406 6823 | anna.happel@uct.ac.za |
| Name | Affiliation | Role |
|---|---|---|
| Heather Jaspan, MD PHD | Seattle Children's Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Khayelitsha Site B Midwife Obstetric Unit | Recruiting | Cape Town | South Africa |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37853370 | Derived | Happel AU, Rametse L, Perumaul B, Diener C, Gibbons SM, Nyangahu DD, Donald KA, Gray C, Jaspan HB. Bifidobacterium infantis supplementation versus placebo in early life to improve immunity in infants exposed to HIV: a protocol for a randomized trial. BMC Complement Med Ther. 2023 Oct 18;23(1):367. doi: 10.1186/s12906-023-04208-0. |
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| ID | Term |
|---|---|
| D000163 | Acquired Immunodeficiency Syndrome |
| D003141 | Communicable Diseases |
| ID | Term |
|---|---|
| D015658 | HIV Infections |
| D000086982 | Blood-Borne Infections |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
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| NIH |
| University of Washington | OTHER |
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| Placebo |
| Dietary Supplement |
Maltodextrin |
|
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 |
| T cell subsets frequencies | T cell subsets frequencies will be compared cross-sectionally between groups | 4 - 36 weeks of age |
| 24 and 36 weeks of age |
| 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 |
| 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 |
| Vaccine antibody titres | Antibody titres to early childhood vaccines will be assessed and compared by treatment arm. | 4 - 36 weeks of age |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D012897 | Slow Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |