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

Phase 3

Terminated

Conditions: Underweight
Paediatrics

Interventions: Dietary Supplement: Placebo
Dietary Supplement: B. infantis Bi-26

Registration Number: NCT05952076

Lead Sponsor: Bill & Melinda Gates Medical Research Institute

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 40

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Maltodextrin: Placebo administered daily
Bi-26 supplementation	B. infantis Bi-26	Bi-26 administered daily.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Weight-for-age Z Score (WAZ) at Day 56	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 Outcome Measures

Name	Time	Method
Change From Baseline in Weight to Day 56	Baseline (Day 1) 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.
Change From Baseline in WAZ Over Time Through Day 90	Baseline (Day 1) to 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.
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	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.
Percentage of Participants Who Achieved a Score of WAZ > -2 at Day 56	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.
Percentage of Participants Re-hospitalized	Baseline to Day 56	Hospitalizations are due to acute non-surgical illness. Percentage of participants re-hospitalized at Day 56 has been presented
Number of Participants Reporting Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs	Up to Day 90	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.
Percentage of Participants With Presence of B. Infantis in Stool	At Days 1, 28, 56 and 90	Stool samples were collected at defined time points to analyze the present of B.infantis.

Trial Locations

Locations (4): Medical Facility A
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Islamabad, Islamabad Capital Territory, Pakistan
Medical Facility B
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Islamabad, Islamabad Capital Territory, Pakistan
Medical Facility C
🇵🇰
Islamabad, Islamabad Capital Territory, Pakistan
Medical Facility
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Rawalpindi, Punjab, Pakistan