Clinical trial NCT04704076: Preventing Infant Malnutrition With Early Supplementation
Official title: Preventing Infant Malnutrition With Early Supplementation, Aim 3
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Underweight
Wasting
Stunting
Breastfeeding
Microbial Colonization
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: International Partnership for Human Development
name: Makerere University
name: Bill and Melinda Gates Foundation
name: University of California, Davis
name: University of Aberdeen
First posted: 2021-01-11
Enrollment: 324
Sex: ALL
Minimum age (years): 0
Maximum age (years): 24
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Background: Worldwide, more than 50 million children under 5 years of age are wasted (weight-for-length/height Z-score (WLZ) \<-2) and over 150 million children under 5 are stunted (length/height-for-age Z-score (LAZ) \<-2); such wasting and stunting often begin during infancy.1 Optimal nutrition can prevent wasting and stunting. Exclusive breastfeeding (EBF) is widely recommended by community health workers, doctors and nurses and provides optimal nutrition for most infants. However, early growth faltering is common for infants in low and middle income countries (LMIC) and can both increase an infant's risk of early mortality and also lead to deficits in attained height and weight throughout childhood. Thus research is needed to determine the most efficacious strategy to promote healthy early growth in LMIC.

Objective: The proposed study will test the efficacy of early small-volume supplementation (ESVS) for increasing weight-for-age z-score (WAZ) at 1 month of age.

Methodology: The PRIMES pilot (Study 3) will be a randomized clinical trial enrolling infants in Guinea-Bissau and Uganda weighing ≥2000g at birth. Infants weighing 2000-2499g at \<6 hours of age (n=144; 72 per site) will be randomized on enrollment to one of two groups: 1) Early Small-Volume Supplementation (ESVS intervention group), which consists of up to 59 mL formula administered daily after breastfeeding through 30 days of age followed by EBF through 6 months of age; or 2) frequent exclusive breastfeeding without any food or fluid other than vitamins, minerals and medications (control) through 6 months of age. Infants weighing 2500-3300g at \<6 hours of age will be weighed again at 4 days of age; those weighing \<2600g at 4 days of age (n=180; 90 per site) will be randomized to the same intervention and control groups. Weight will be measured on all enrolled babies at birth on Day 1 and at 4, 14, 30, 60 and 180 days of age and additional measures including height, MUAC, skinfolds, and hemoglobin will be assessed at other time points. The study's primary outcome will be WAZ at 1 month of age. Secondary outcomes will include WLZ at 1 month of age; WAZ, WLZ and LAZ through 6 months of age; breastfeeding duration and infant intestinal microbiota.


Eligibility criteria: Inclusion Criteria:

* Infant \< 6 hours old
* Infant birth weight 2000-2885g
* Mother intends to breastfeed
* Mother with negative HIV test
* Mother lives in study catchment area and anticipates availability for all study visits
* Mother ≥18 years old

Exclusion Criteria:

* Twins and other multiples
* Infant with known major congenital anomalies including orofacial clefts, neural tube defects or congenital heart defects
* Infant with WHO newborn and respiratory danger signs present:

  * Not feeding well
  * Convulsions
  * Very fast breathing ≥60 breaths/minute
  * Severe chest indrawing
  * No spontaneous movement
  * Lethargic or unconscious
  * Raised temperature \> 37.5 degrees Celsius
  * Hypothermia \<35.5 degrees Celsius
  * Any jaundice in first 24 hours of life or yellow palms or soles at any age
  * Head nodding, nasal flaring or grunting
* Maternal psychiatric or psychosocial barrier to enrollment:

  * Contraindication to breastfeeding at each site as determined by a site's national or sub-national health authorities
  * Mothers unable or unwilling to complete all aspects of the protocol Infant enrolled in another study
  * Mother has had another infant enrolled in PRIMES

Primary outcomes:
measure: Weight-for-age z-score (WAZ) at 30 days of age
timeFrame: 30 days of age
Secondary outcomes:
measure: Weight-for-length z-score (WLZ) at 30 days of age
timeFrame: 30 days of age
measure: Weight-for-length z-score (WLZ) at 180 days of age
timeFrame: 180 days of age
measure: Weight-for-length z-score (WLZ) at 365 days of age
timeFrame: 365 days of age
measure: Weight-for-age z-score (WLZ) at 180 days of age
timeFrame: 180 days of age
measure: Weight-for-age z-score (WLZ) at 365 days of age
timeFrame: 365 days of age
measure: Length-for-age z-score (LAZ) at 180 days of age
timeFrame: 180 days of age
measure: Length-for-age z-score (LAZ) at 365 days of age
timeFrame: 365 days of age
measure: Whether or not breastfeeding continues at 180 days of age
timeFrame: 180 days of age
measure: Abundance of B.infantis in intestinal microbiota
timeFrame: 30 days of age
measure: Abundance of B.infantis in intestinal microbiota
timeFrame: 180 days of age
measure: Neurodevelopment
timeFrame: 180 days of age
measure: Neurodevelopment
timeFrame: 365 days of age
measure: Brain volume
timeFrame: 90 days of age
measure: Brain volume
timeFrame: 180 days of age
measure: Brain volume
timeFrame: 365 days of age
measure: White matter volume
timeFrame: 365 days of age
Other outcomes:
Locations:
city: Bissau
country: Guinea-Bissau
facility: International Partnership for Human Development
city: Kampala
country: Uganda
facility: Makerere University
Study officials:
affiliation: University of California, San Francisco
name: Valerie Flaherman, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ginsburg AS, Braima de Sa A, Nankabirwa V, Co R, Murungi J, Kim MO, Brim R, Namiiro F, Namugga O, Hartigan-O'Connor DJ, Roberts SB, Flaherman V. Randomized controlled trial of early, small-volume formula supplementation among newborns: A study protocol. PLoS One. 2022 Feb 4;17(2):e0263129. doi: 10.1371/journal.pone.0263129. eCollection 2022.