Mitigating Infectious Morbidity and Growth Deficits in HIV Exposed Uninfected infanTs With Human Milk Oligosaccharides

NCT ID: NCT05282485

Last Updated: 2025-11-24

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 140 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-02
• Study Completion Date: 2026-09-15

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.

Conditions

HIV; Infant Morbidity; Breast Feeding

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Synbiotic Group

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.

Group Type: EXPERIMENTAL

Synbiotic

Intervention Type: DIETARY_SUPPLEMENT

Synbiotic (2'-FL HMO + B. infantis probiotics)

Placebo Group

Maltodextrin will be administered to infants from 4 to 24 weeks of age.

Group Type: PLACEBO_COMPARATOR

Maltodextrin

Intervention Type: DIETARY_SUPPLEMENT

Maltodextrin

Interventions

Synbiotic

Synbiotic (2'-FL HMO + B. infantis probiotics)

Intervention Type: DIETARY_SUPPLEMENT

Maltodextrin

Maltodextrin

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Greater than 18 years of age
• For HIV-exposed uninfected children (CHEU): Mothers living with HIV documented based on medical record and with viral suppression (i.e., <400 copies/mL viral load) documented at delivery
• For HIV-unexposed uninfected children (CHUU): Mothers without HIV (document HIV-negative test result at delivery or screening)
• Women who initiated breastfeeding of their infant including:

• Women who currently exclusively breastfeed their infants, or
• Women who breastfed their infants for a period but are no longer breastfeeding, or
• Women who are currently breastfeeding their infants in addition to feeding them formula milk or solids
• For women with HIV: Those currently on first-line standard of care antiretroviral therapy that was initiated a minimum of 12 weeks prior to delivery of the infant included in this study
• Participant has a cell phone that can be used for calls and messages
• Agreement to adhere to Lifestyle Considerations throughout study duration

• 3-6 weeks of age
• Delivered from a singleton pregnancy
• For children of mothers with HIV: At least one HIV diagnostic nucleic acid amplification test prior to enrollment which is negative and no positive test
• Child is well enough to have established full breastfeeding by the time of enrollment

Exclusion Criteria

• 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.

• Minimum Eligible Age: 3 Weeks
• Maximum Eligible Age: 6 Weeks
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Stellenbosch

OTHER

Sponsor Role: collaborator

University of California, Los Angeles

OTHER

Sponsor Role: collaborator

University of California, San Diego

OTHER

Sponsor Role: collaborator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

Columbia University

OTHER

Sponsor Role: lead

Responsible Party

Rupak Shivakoti

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Rupak Shivakoti, PhD

Role: PRINCIPAL_INVESTIGATOR

Columbia University Assistant Professor

Locations

Worcester Campus of Stellenbosch University (SU)

Stellenbosch, Western Cape, South Africa

Countries

South Africa

References

Shivakoti R, Laughton B, Shafiq M, Schoeman E, Glashoff RH, Barnabas S, Fry S, Leu CS, Wang S, Bode L, Aldrovandi G, Kuhn L, Slogrove AL. Feasibility Study of a Powder-Based Supplement Intervention for a future Synbiotic Trial in Breastfed Children from South Africa. Res Sq [Preprint]. 2023 May 15:rs.3.rs-2842773. doi: 10.21203/rs.3.rs-2842773/v1.

Reference Type: DERIVED

PMID: 37293067 (View on PubMed)

Shivakoti R, Slogrove AL, Laughton B, Shafiq M, Schoeman E, Glashoff RH, Leu CS, Wang S, Bode L, Aldrovandi G, Kuhn L. Mitigating Infectious morbidity and Growth deficits in HIV-exposed uninfected infanTs with human Milk Oligosaccharide (MIGH-T MO): a randomised trial protocol. BMJ Open. 2022 Dec 30;12(12):e069116. doi: 10.1136/bmjopen-2022-069116.

Reference Type: DERIVED

PMID: 36585139 (View on PubMed)

Other Identifiers

R01HD105492

Identifier Type: NIH

Identifier Source: secondary_id

View Link

AAAT8393

Identifier Type: -

Identifier Source: org_study_id