Mitigating Infectious Morbidity and Growth Deficits in HIV Exposed Uninfected infanTs With Human Milk Oligosaccharides
- Conditions
- HIVInfant MorbidityBreast Feeding
- Interventions
- Dietary Supplement: SynbioticDietary Supplement: Maltodextrin
- Registration Number
- NCT05282485
- Lead Sponsor
- Columbia University
- Brief Summary
Primary Objective:
* To evaluate the effects of synbiotics on infectious morbidity and growth while it is in place from 4 to 24 weeks of age.
* To evaluate the effects of synbiotics on infectious morbidity and growth from 4 to 48 weeks of age.
Secondary Objectives:
* To evaluate the effects of synbiotics on growth from 4 to 72 weeks of age.
* To evaluate the effects of synbiotics on infant neurodevelopment at 48 and 72 weeks of age.
* To evaluate the effects of synbiotics on biological measurements while it is in place from 4 to 24 weeks of age.
* To evaluate the effects of synbiotics on biological measurements from 4 to 48 weeks of age.
* To evaluate the effects of synbiotics on gut microbiome and fecal short chain fatty acids from 4 to 72 weeks of age.
* To investigate feasibility, acceptance, tolerability, and behavioral adherence with the intervention.
* To investigate whether the synbiotics reduces infectious morbidity and improves growth in CHEU relative to CHUU.
* To investigate whether infant gut microbiota composition, maturity and function, and markers of inflammation and HMOs at baseline and over time are associated with morbidity and poor growth in CHEU and CHUU.
- Detailed Description
Children who are HIV-exposed uninfected (CHEU), i.e., children born to mothers with HIV but who do not acquire HIV infection, have a higher risk of mortality, infectious morbidity, and growth deficits than children who are HIV-unexposed uninfected (CHUU), i.e., children whose mothers do not have HIV. Prior research has focused on breastfeeding and has pointed to changes in human milk oligosaccharides (HMOs) associated with maternal HIV infection that appear to influence the infant microbiome and thereby lead to these adverse outcomes. A randomized trial of an intervention which combines HMOs and probiotics in breastfed CHEU will be conducted in South Africa to evaluate whether this intervention has the potential to reduce excess infectious morbidity and growth faltering risks observed in CHEU. CHEU will be randomized 1:1 to either a) intervention (synbiotic: 2'-FL HMO + B. infantis probiotic) or b) placebo (Maltodextrin). The study intervention or placebo will be given from 4-24 weeks of age (total 20 weeks), followed by another 48 weeks of observation off study treatment. Both arms will be followed to 72 weeks of age for assessment of infant outcomes.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 144
Not provided
- Severe maternal or infant illness (e.g., maternal: tuberculosis, major psychiatric or neurological conditions; infant: any congenitally-acquired infections, major congenital anomalies)
- Use of immunomodulatory or immunosuppressive drugs in either mother or child prior to enrollment in the study
- For mothers with HIV: Mothers who are not currently receiving antiretroviral therapy or who are on regimens other than the currently recommended first-line standard of care in South Africa i.e., first-line dolutegravir- or efavirenz-based regimens.
- Children infected with HIV
- Mother or infant currently taking probiotics, prebiotics, or fiber supplements; or on any nutritional supplements (e.g., FM85) that impact the outcomes of interest
- Mother or infant currently taking antibiotics for more than 14 days, excluding preventative therapies
- Known allergic reactions to components of the treatment or placebo
- Any condition that, in the opinion of the study staff, would make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the aims of the study.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Synbiotic Group Synbiotic A synbiotic combining 2'-Fucosyllactose (2'-FL) human milk oligosaccharides (HMO) with B.infantis (probiotic) will be administered to infants from 4 to 24 weeks of age. Placebo Group Maltodextrin Maltodextrin will be administered to infants from 4 to 24 weeks of age.
- Primary Outcome Measures
Name Time Method Proportion of infants with infectious morbidity from 4-48 weeks 4-48 weeks of age Infectious morbidity data related to infectious respiratory or gastrointestinal morbidity will be compared between the two arms
Infant length for age Z scores (LAZ) from 4-48 weeks 4-48 weeks of age Infant anthropometry will be recorded at each visit to calculate infant length for age Z scores (LAZ) will be compared between the two arms
Infant length for age Z scores (LAZ) from 4-24 weeks 4-24 weeks of age Infant anthropometry will be recorded at each visit to calculate infant length for age Z scores (LAZ) will be compared between the two arms
Proportion of infants with infectious morbidity from 4-24 weeks 4-24 weeks of age Infectious morbidity data related to infectious respiratory or gastrointestinal morbidity will be compared between the two arms
- Secondary Outcome Measures
Name Time Method Infant microbiota diversity 4-72 weeks of age Microbiota diversity of taxa will be compared between the two arms
Infant fecal short-chain fatty acid levels 4-72 weeks of age Short-chain fatty acid (SCFA) levels in stool samples from infants will be compared between the two arms
Infant plasma metabolite levels 4-24 weeks of age Unbiased metabolomics will be used to investigate whether metabolite levels and major metabolic pathways are different between the two arms
Infant weight for age (WAZ) and weight for length (WLZ) Z scores from 4-24 weeks 4-24 weeks of age Infant anthropometry will be recorded at each visit to calculate infant weight for age (WAZ) and weight for length (WLZ) Z scores and will be compared between the two arms
Infant weight for age (WAZ) and weight for length (WLZ) Z scores from 4-48 weeks 4-48 weeks of age Infant anthropometry will be recorded at each visit to calculate infant weight for age (WAZ) and weight for length (WLZ) Z scores and will be compared between the two arms
Infant length for age (LAZ), weight for age (WAZ) and weight for length (WLZ) Z scores from 4-72 weeks 4-72 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
Infant microbiota-for-age Z scores (MAZ) 4-72 weeks of age Infant microbiota-for-age Z scores (MAZ), a measure of infant microbiome maturity, will be compared between the two arms
Infant plasma inflammatory markers and growth hormone levels 4-48 weeks of age Levels of protein inflammatory markers and growth hormones will be measured using immunoassays and will be compared between the two arms
Proportion of infants with Adverse Events (AEs)/Serious Adverse Event (SAEs) Through 24 weeks of age Proportion of AE/SAEs will be recorded and compared between the two arms to assess the safety of the intervention
Proportion of infants with tolerability symptoms Through 8 weeks of age Digestive tolerability will be assessed and compared between the two arms to assess the safety of the intervention
Proportion of infants with severe infectious morbidity 4-48 weeks of age Severe infectious morbidity (i.e., those requiring hospitalizations) data related to infectious respiratory or gastrointestinal morbidity will be compared between the two arms
Infant microbiota relative abundance 4-72 weeks of age Microbiota relative abundance of taxa will be compared between the two arms
Infant plasma HMO levels 4-24 weeks of age Infant HMO levels will be measured and compared between the two arms
Infant neurodevelopment milestones 48-72 weeks A comprehensive neurodevelopment assessment, i.e., Griffiths III scale, will be conducted on infants at weeks 48 and 72 and the proportion passing each milestone will be compared between the two arms
Trial Locations
- Locations (1)
Worcester Campus of Stellenbosch University (SU)
🇿🇦Stellenbosch, Western Cape, South Africa