Clinical trial NCT05282485: Mitigating Infectious Morbidity and Growth Deficits in HIV Exposed Uninfected infanTs With Human Milk Oligosaccharides
Official title: Mitigating Infectious Morbidity and Growth Deficits in HIV Exposed Uninfected infanTs With Human Milk Oligosaccharides
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: HIV
Infant Morbidity
Breast Feeding
Keywords: HIV
Infant Morbidity
Infant Growth
Breastmilk
Probiotic
Synbiotic
HIV-exposed Uninfected Infants
B. infantis
Human Milk Oligosaccharides
2'-Fucosyllactose
Infant neurodevelopment
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: University of Stellenbosch
name: University of California, Los Angeles
name: University of California, San Diego
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2022-03-16
Enrollment: 144
Sex: ALL
Minimum age (years): 3
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study will recruit 144 women living with HIV and their HIV-exposed uninfected children (72 will receive the interventional product and 72 will receive the placebo). All of the women in the study will have breastfed or are currently breastfeeding their children.
Primary purpose: PREVENTION

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.

Eligibility 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)
* 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

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.

Primary outcomes:
measure: Proportion of infants with infectious morbidity from 4-24 weeks
timeFrame: 4-24 weeks of age
measure: Infant length for age Z scores (LAZ) from 4-24 weeks
timeFrame: 4-24 weeks of age
measure: Proportion of infants with infectious morbidity from 4-48 weeks
timeFrame: 4-48 weeks of age
measure: Infant length for age Z scores (LAZ) from 4-48 weeks
timeFrame: 4-48 weeks of age
Secondary outcomes:
measure: Infant weight for age (WAZ) and weight for length (WLZ) Z scores from 4-24 weeks
timeFrame: 4-24 weeks of age
measure: Infant weight for age (WAZ) and weight for length (WLZ) Z scores from 4-48 weeks
timeFrame: 4-48 weeks of age
measure: Infant length for age (LAZ), weight for age (WAZ) and weight for length (WLZ) Z scores from 4-72 weeks
timeFrame: 4-72 weeks of age
measure: Infant microbiota-for-age Z scores (MAZ)
timeFrame: 4-72 weeks of age
measure: Infant microbiota diversity
timeFrame: 4-72 weeks of age
measure: Infant microbiota relative abundance
timeFrame: 4-72 weeks of age
measure: Infant fecal short-chain fatty acid levels
timeFrame: 4-72 weeks of age
measure: Infant plasma metabolite levels
timeFrame: 4-24 weeks of age
measure: Infant plasma inflammatory markers and growth hormone levels
timeFrame: 4-48 weeks of age
measure: Infant plasma HMO levels
timeFrame: 4-24 weeks of age
measure: Proportion of infants with Adverse Events (AEs)/Serious Adverse Event (SAEs)
timeFrame: Through 24 weeks of age
measure: Proportion of infants with tolerability symptoms
timeFrame: Through 8 weeks of age
measure: Proportion of infants with severe infectious morbidity
timeFrame: 4-48 weeks of age
measure: Infant neurodevelopment milestones
timeFrame: 48-72 weeks
Other outcomes:
Locations:
city: Stellenbosch
country: South Africa
facility: Worcester Campus of Stellenbosch University (SU)
state: Western Cape
Study officials:
affiliation: Columbia University Assistant Professor
name: Rupak Shivakoti, PhD
role: PRINCIPAL_INVESTIGATOR
References: