Impact of Bi-26 Supplementation on Weight Gain in Underweight Infants

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

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.

Study Overview

• Status: Terminated
• Conditions: Underweight; Paediatrics
• Intervention / Treatment: Dietary supplement: B. infantis Bi-26; Dietary supplement: Placebo

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 3

Contacts and Locations

Study Locations

• Pakistan
  • Islamabad Capital Territory
    • Islamabad, Islamabad Capital Territory, Pakistan, 44000
      • Medical Facility A
    • Islamabad, Islamabad Capital Territory, Pakistan, 44000
      • Medical Facility B
    • Islamabad, Islamabad Capital Territory, Pakistan, 44000
      • Medical Facility C
  • Punjab
    • Lahore, Punjab, Pakistan, 54000
      • Medical facility
    • Rawalpindi, Punjab, Pakistan, 46000
      • Medical facility

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

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)
• Any sex
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bi-26 supplementation; Bi-26 administered daily.	Dietary supplement: B. infantis Bi-26; A once-daily oral dose of Bi-26 will be provided to infants for 28 days.
Placebo Comparator: Placebo; Maltodextrin: Placebo administered daily	Dietary supplement: Placebo; A once-daily oral dose of placebo maltodextrin will be provided to infants for 28 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Weight-for-age Z Score (WAZ) at 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.	Baseline (Day 1) to Day 56

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Weight to Day 56	Weight (grams) was summarized using descriptive statistics. Baseline (Day 1) was defined as the last available value prior to the participant receiving the first dose of the study intervention. Change from Baseline was defined as post-dose visit value minus Baseline value.	Baseline (Day 1) to Day 56
Change From Baseline in WAZ Over Time Through Day 90	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.	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	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.	Baseline (Day 1) to Day 56
Percentage of Participants Who Achieved a Score of WAZ > -2 at 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.	At Day 56
Percentage of Participants Re-hospitalized	Hospitalizations are due to acute non-surgical illness. Percentage of participants re-hospitalized at Day 56 has been presented	Baseline to Day 56
Number of Participants Reporting Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs	An adverse event (AE) is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE is considered treatment emergent if it started on or after the date of first dose of study intervention administration. Serious TEAE is any untoward medical occurrences at any dose of study medication that: results in death; is life threatening; requires inpatient hospitalization or causes prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect and is an important medical event.	Up to Day 90
Percentage of Participants With Presence of B. Infantis in Stool	Stool samples were collected at defined time points to analyze the present of B.infantis.	At Days 1, 28, 56 and 90

Collaborators and Investigators

• Sponsor: Bill & Melinda Gates Medical Research Institute
• Investigators: Study Director: Gates MRI, Bill & Melinda Gates Medical Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): July 3, 2023
• Primary Completion (Actual): December 26, 2023
• Study Completion (Actual): January 29, 2024

Study Registration Dates

• First Submitted: July 11, 2023
• First Submitted That Met QC Criteria: July 11, 2023
• First Posted (Actual): July 19, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 25, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Weight-for-age Z score; Underweight infants; Bifidobacterium longum, B. infantis; Bi-26 supplementation
• Additional Relevant MeSH Terms: Body Weight; Body Weight Changes; Weight Gain; Thinness
• Other Study ID Numbers: Gates MRI-MNK01-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All IPD data that underlie results in a publication.
• IPD Sharing Time Frame: This will be done within 12months of the study completion date.
• IPD Sharing Access Criteria: Anonymized participant level data may be shared with external researchers in accordance with the trial participants' written and executed informed consent document and any local or applicable regulations on data sharing. Qualified researchers may submit a request for anonymized participant level data along with a research proposal to Gates MRI for review. The types of supporting information that could be shared with external researchers include: the Study Protocol, Statistical Analysis Plan, Informed Consent Form, Clinical Study Report, and analytic code. A data sharing agreement must be in place before any clinical trial data are shared. There are additional circumstances that may prevent the sharing of data with external researchers, including but not limited to contractual obligations to existing partners and any restrictions imposed by regulatory bodies.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No