A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Effect of Bi-26 (Strain of Bifidobacterium Longum, B. Infantis) Supplementation Versus Placebo on Weight Gain in Underweight Infants
Overview
- Phase
- Phase 3
- Intervention
- Not specified
- Conditions
- Underweight
- Sponsor
- Bill & Melinda Gates Medical Research Institute
- Enrollment
- 40
- Locations
- 4
- Primary Endpoint
- Change From Baseline in Weight-for-age Z Score (WAZ) at Day 56
- Status
- Terminated
- Last Updated
- last year
Overview
Brief Summary
The burden of disease experienced by underweight children is significant, particularly in low- and middle-income countries. Gut dysbiosis, an imbalance in microbial composition, is thought to play a role in nutrient malabsorption leading to underweight infants and failure to thrive. Bifidobacterium longum subspecies infantis (B. infantis) is a commensal bacterial strain important in the breakdown of human milk oligosaccharides (HMOs). A decrease in abundance or absence of B. infantis could lead to inadequate HMO processing, elevating intestinal pH and increasing the risk of pathogen overgrowth. Bi-26 is a B. infantis probiotic strain that is being evaluated in this study for its impact on weight gain and other health outcomes in underweight infants.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participant must be between 30 days and 120 days of age (inclusive), at the time of enrollment (study Day 1)
- •Hospitalized for acute non-surgical illness
- •Completed acute stabilization phase of treatment, including fluid rehydration and antibiotic course, prior to enrollment (study Day 1)
- •WAZ at enrollment (study Day 1) is less than negative 2 (\<-2)
- •Participant's parent(s)/legal guardian is capable of giving informed consent which includes agreement to comply with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol
- •Participant's parent(s)/legal guardian agrees to stay in contact with the study site for the duration of the study, provide updated contact information as necessary, and have no current plans to relocate from the study area for the duration of the study
- •Participant's parent(s)/legal guardian has easy access to reliable refrigeration (for storage of investigational product)
- •Participant receives some feedings from breastmilk and mother intends to continue breastfeeding.
Exclusion Criteria
- •Congenital condition (suspected or confirmed) that the investigator considers likely to interfere with feeding or with normal growth and development
- •Infant has not been discharged from hospital since birth or has not been at home for at least one week since birth
- •Infant hospitalized with septic shock during current hospitalization
- •Infant required mechanical ventilation during current hospitalization
- •Infant with acute kidney injury on hospital admission
- •Infant with severe jaundice and suspected kernicterus
- •Infant receiving treatment for suspected or confirmed tuberculosis, or suspected or confirmed human immunodeficiency virus (HIV) infection
- •Ongoing infant antibiotic (e.g. as prophylaxis in sickle cell disease) and/or probiotic usage
- •Ongoing maternal antibiotic and/or probiotic usage for breast-feeding infants
- •Inability of participant's parent(s)/legal guardian to comply with protocol requirements, as per investigator assessment.
Outcomes
Primary Outcomes
Change From Baseline in Weight-for-age Z Score (WAZ) at Day 56
Time Frame: Baseline (Day 1) to Day 56
The Weight-for-Age Z-score (WAZ) is an anthropometric measure used to classify a child's nutritional status. The WAZ measures the number of standard deviations of a child's actual weight from the median weight of children of the same age based on the World Health Organization (WHO) child growth standards (reference population). WAZ of 0 represents the median weight for age in the reference population. WAZ ≥-3 to \<-2 standard deviations below the WHO child growth standards median is considered moderately underweight and WAZ \<-3 is considered severely underweight. Least Squares Mean, 95% Confidence Interval, and p-value was derived from mixed model repeated measures with treatment and visit as factors and baseline WAZ, baseline age (days), and study intervention compliance as covariates. The treatment\*visit interaction terms were included and used to estimate the adjusted mean difference in Change from Baseline in WAZ between Bi-26 and Placebo.
Secondary Outcomes
- Change From Baseline in Weight to Day 56(Baseline (Day 1) to Day 56)
- Change From Baseline in WAZ Over Time Through Day 90(Baseline (Day 1) to Day 90)
- Percentage of Participants With a ≥ 0.3, ≥ 0.4, and ≥ 0.5 Change in WAZ From Baseline at Day 56(Baseline (Day 1) to Day 56)
- Percentage of Participants Who Achieved a Score of WAZ > -2 at Day 56(At Day 56)
- Percentage of Participants Re-hospitalized(Baseline to Day 56)
- Number of Participants Reporting Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs(Up to Day 90)
- Percentage of Participants With Presence of B. Infantis in Stool(At Days 1, 28, 56 and 90)