Mitigating Infectious Morbidity and Growth Deficits in HIV Exposed Uninfected infanTs With Human Milk Oligosaccharides (MIGH-T MO)
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| ClinicalTrials.gov Identifier: NCT05282485 |
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Recruitment Status :
Recruiting
First Posted : March 16, 2022
Last Update Posted : October 12, 2022
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Sponsor:
Columbia University
Collaborators:
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)
Information provided by (Responsible Party):
Rupak Shivakoti, Columbia University
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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 | Not Applicable |
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 Type : | Interventional (Clinical Trial) |
| Estimated 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. |
| 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 : | June 2, 2022 |
| Estimated Primary Completion Date : | July 2025 |
| Estimated Study Completion Date : | July 2025 |
| Arm | Intervention/treatment |
|---|---|
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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.
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Dietary Supplement: Synbiotic
Synbiotic (2'-FL HMO + B. infantis probiotics) |
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Placebo Comparator: Placebo Group
Maltodextrin will be administered to infants from 4 to 24 weeks of age.
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Dietary Supplement: Maltodextrin
Maltodextrin |
Primary Outcome Measures :
- Proportion of infants with infectious morbidity from 4-24 weeks [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 4-48 weeks of age ]Microbiota diversity of taxa will be compared between the two arms
- Infant microbiota relative abundance [ Time Frame: 4-48 weeks of age ]Microbiota relative abundance of taxa will be compared between the two arms
- Infant fecal short-chain fatty acid levels [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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
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| Ages Eligible for Study: | 3 Weeks to 6 Weeks (Child) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | Yes |
Criteria
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.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05282485
Contacts
| Contact: Rupak Shivakoti, PhD | 212-305-7232 | rs3895@cumc.columbia.edu |
Locations
| South Africa | |
| Worcester Campus of Stellenbosch University (SU) | Recruiting |
| Stellenbosch, Western Cape, South Africa, 7599 | |
| Contact: Amy Slogrove, MD, PhD | |
| Principal Investigator: Amy Slogrove, MD, PhD | |
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)
Investigators
| Principal Investigator: | Rupak Shivakoti, PhD | Columbia University Assistant Professor |
| Responsible Party: | Rupak Shivakoti, Assistant Professor, Columbia University |
| ClinicalTrials.gov Identifier: | NCT05282485 |
| Other Study ID Numbers: |
AAAT8393 R01HD105492 ( U.S. NIH Grant/Contract ) |
| First Posted: | March 16, 2022 Key Record Dates |
| Last Update Posted: | October 12, 2022 |
| Last Verified: | October 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Rupak Shivakoti, Columbia University:
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HIV Infant Morbidity Infant Growth Breastmilk Probiotic |
Synbiotic HIV-exposed Uninfected Infants B. infantis Human Milk Oligosaccharides 2'-Fucosyllactose |
Additional relevant MeSH terms:
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Communicable Diseases Infections Disease Attributes Pathologic Processes |