HivBifIIDNCT05923333
B. Infantis Supplementation to Improve Immunity in Infants Exposed to HIV
A study testing B. infantis Rosell®-33 in people with Hiv and Vaccine Reaction, run by University of Cape Town at 1 site in South Africa.
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… Read more about this study
- Who is it for?
- Ages 0 days to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Hiv, Vaccine Reaction, Microbial Colonization
- What is being tested?
- B. infantis Rosell®-33
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 200 participants
- Where
- 1 siteSouth Africa
- Study dates
- 11 Aug 2023to Jun 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 days to 50 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- 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
- Documented HIV seronegative at birth
- Born at term (completed at least 37 weeks of gestation)
- Birth weight >2.4kgs
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
South Africa1 site, 1 recruiting
- Recruiting
Khayelitsha Site B Midwife Obstetric Unit
Cape Town
Busi Tyhenge
About this study
Official title: Bifidobacterium Infantis Supplementation in Early Life to Improve Immunity in Infants Exposed to HIV: a Randomized, Placebo-controlled, Double-blind Trial
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
Read more
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
Read the 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.
- Conditions
- Hiv, Vaccine Reaction, Microbial Colonization, Infant Development
- Being tested
- B. infantis Rosell®-33, Placebo
- Medical subject headings
- Acquired Immunodeficiency Syndrome, Communicable Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
B. infantis Rosell®-33Dietary supplement
- infantis Rosell®-33 + maltodextrin
PlaceboDietary supplement
Maltodextrin
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Dietary Supplement: B. infantis Rosell®-33 |
| Placebo | Placebo comparator | Participants will receive placebo (containing all materials besides B. infantis Rosell®-33) for 28 days from day 1-3 of life. Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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.
Measured: 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.
Measured: 36 weeks of age
Secondary outcomes (3)
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.
Measured: 4 - 36 weeks of age
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.
Measured: 4 weeks of age
T cell subsets frequencies
T cell subsets frequencies will be compared cross-sectionally between groups
Measured: 4 - 36 weeks of age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jun 2023
- Study start11 Aug 2023
- Primary completionJun 2026 (estimated)
- Study completionJun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HivStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Cape Town
- Sponsor type
- University, hospital or other
- Collaborators
- 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
- Responsible party
- Principal investigator, Anna-Ursula Happel, University of Cape Town
- Investigators
- Heather Jaspan, MD PHD, Principal investigator, Seattle Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05923333
- Sponsor's protocol ID
- 697/2022
- Other IDs
- R01HD109089, PACTR202301748714019
- Acronym
- BifIID
- Status last verified
- Aug 2024
- First submitted
- 19 Jun 2023
- Last updated
- 22 Aug 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 37853370
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bifidobacterium Infantis Supplementation in Early Life to Improve Immunity in Infants Exposed to HIV: a Randomized, Placebo-controlled, Double-blind Trial
- ClinicalTrials.gov ID
- NCT05923333
- Acronym / sponsor ID
- BifIID / 697/2022
- Conditions
- Hiv, Vaccine Reaction, Microbial Colonization, Infant Development
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- University of Cape TownUniversity, hospital or other
- Collaborators
- 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
- Study start
- 11 Aug 2023 (actual)
- Primary completion
- Jun 2026 (estimated)
- Study completion
- Jun 2027 (estimated)
- First posted
- 28 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| B. infantis Rosell®-33 | Active comparator | Dietary Supplement: B. infantis Rosell®-33Participants 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 | Dietary Supplement: PlaceboParticipants will receive placebo (containing all materials besides B. infantis Rosell®-33) for 28 days from day 1-3 of life. |
Who may qualify
- Ages
- 0 days to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| B. infantis Rosell®-33B. infantis Rosell®-33 + maltodextrin | Dietary supplement | B. infantis Rosell®-33 |
| PlaceboMaltodextrin | Dietary supplement | Placebo |
Primary outcome
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
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
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.
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.
3 secondary outcomes
Longitudinal succession in gut microbiota composition, diversity and function
Time frame: 4 - 36 weeks of age
Stool metabolome
Time frame: 4 weeks of age
T cell subsets frequencies
Time frame: 4 - 36 weeks of age
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2024.
- Derived from this study: PubMed 37853370Happel 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Heather Jaspan, MD PHD principal investigator
Seattle Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing B. infantis Rosell®-33 in people with Hiv and Vaccine Reaction, run by University of Cape Town at 1 site in South Africa.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Heather Jaspan, MD PHD (2068543336, hbjaspan@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Gut microbiome (time frame: 4 weeks of age). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05923333, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2024.