MIGH-T MO: Mitigating Infectious Morbidity and Growth Deficits in HIV Exposed Uninfected infanTs With Human Milk Oligosaccharides

Sponsor

Columbia University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05282485

Collaborator

University of Stellenbosch (Other), University of California, Los Angeles (Other), University of California, San Diego (Other), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)

144

Enrollment

Location

Arms

Anticipated Duration (Months)

3.9

Patients Per Site Per Month

Study Details

Study Description

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 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 investigate whether the synbiotic 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.

Condition or Disease	Intervention/Treatment	Phase
HIV Infant Morbidity Breast Feeding	Dietary Supplement: Synbiotic Dietary Supplement: Maltodextrin	N/A

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 24 weeks of observation off study treatment. Both arms will be followed to 48 weeks of age for assessment of infant outcomes.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

144 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

This study will recruit 144 women (72 will receive the interventional product and 72 will receive the placebo) who are breastfeeding and living with HIV, and their HIV-exposed uninfected children.This study will recruit 144 women (72 will receive the interventional product and 72 will receive the placebo) who are breastfeeding and living with HIV, and their HIV-exposed uninfected children.

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Jun 2, 2022

Anticipated Primary Completion Date :

Jul 1, 2025

Anticipated Study Completion Date :

Jul 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Dietary Supplement: Synbiotic Synbiotic (2'-FL HMO + B. infantis probiotics)
Placebo Comparator: Placebo Group Maltodextrin will be administered to infants from 4 to 24 weeks of age.	Dietary Supplement: Maltodextrin Maltodextrin

Arm

Intervention/Treatment

Experimental: 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.

Dietary Supplement: Synbiotic

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

Placebo Comparator: Placebo Group

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

Dietary Supplement: Maltodextrin

Maltodextrin

Outcome Measures

Primary Outcome Measures

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
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 4-48 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

Secondary Outcome Measures

Infant microbiota-for-age Z scores (MAZ) [4-48 weeks of age]
Infant microbiota-for-age Z scores (MAZ), a measure of infant microbiome maturity, will be compared between the two arms
Infant microbiota diversity [4-48 weeks of age]
Microbiota diversity of taxa will be compared between the two arms
Infant microbiota relative abundance [4-48 weeks of age]
Microbiota relative abundance of taxa will be compared between the two arms
Infant fecal short-chain fatty acid levels [4-48 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 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
Infant plasma HMO levels [4-24 weeks of age]
Infant HMO levels will be measured and 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

Eligibility Criteria

Criteria

Ages Eligible for Study:

3 Weeks to 6 Weeks

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria for Mothers:

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)
Only women who are currently exclusively breastfeeding and intend to breastfeed for at least another 24 weeks
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

Inclusion Criteria for Children:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Worcester Campus of Stellenbosch University (SU)	Stellenbosch	Western Cape	South Africa	7599

Sponsors and Collaborators

Columbia University
University of Stellenbosch
University of California, Los Angeles
University of California, San Diego
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)