HMOs on Infant Gut Microbiota Modulation and Development of the Immune System in Healthy Infants (BELIEF)

The Effect of Human Milk Oligosaccharides on Infant Gut Microbiota Modulation, Development of the Immune System and Health Later in Life: The BELIEF Study

The goal of this clinical trial is to learn how a mixture of human milk oligosaccharides impacts the development of the infant microbiota, the immune maturation and how the interaction between the microbiota and immune maturation may impact both short and long term health of the infant.

The participants will:

• Consume the investigational products (active/placebo) for 6 months
• Legal guardians/parents to the participant to collect stool samples from the diapers at home
• Legal guardians/parents to the participant to report gastrointestinal symptoms, signs of infections in an electronic questionnaire
• Visit the clinic for checkups and dried blood sample collection

For reference, a group of breastfed infants will be included. They will undergo the same procedures apart from consuming the investigational product (active/placebo). 230 participants (115 in each intervention arm) will be randomized to an intervention and 104 participants will be recruited for the reference group, giving a total sample size of 334 participants.

The intervention trial will be reported in two steps, first step covering the intervention phase from birth to 6 months; and step two includes both the intervention phase (0-6 months) and the follow-up period from 6-12 months. Informed consents for the possibility to preform long-term follow-up will be obtained.

Study Overview

• Status: Not yet recruiting
• Conditions: Healthy Infants
• Intervention / Treatment: Other: Human Milk Oligosaccharides; Other: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 334
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Diana Høtoft; Phone Number: +4523486730; Email: diahoe@clin.au.dk

Study Locations

• Denmark
  • Aarhus, Denmark, 8200
    • Aarhus University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• All infants which parents has decided mode of feeding

Exclusion Criteria:

• Premature birth

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Human Milk Oligosaccharides; Human Milk Oligosaccharides (HMO)	Other: Human Milk Oligosaccharides; Human Milk Oligosaccharides provided in a commercially available infant formula powder, fed daily ad libitum from enrollement to 6 months of age
Placebo Comparator: Placebo; Identical commercial Infant Formula without human milk oligosaccharides, fed daily ad libitum from enrollement to 6 months of age	Other: Placebo; An identical commercially available infant formula powder without Human Milk Oligosaccharides, fed daily ad libitum from enrollement to 6 months of age
No Intervention: Breastfed reference group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total abundance of bifidobacteria at 3 months of age	Abundance of fecal bifidobacteria measured by quantitative PCR	Fecal samples collected at 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infant fecal pH at 3 months of age	Fecal pH measured in fecal water at 3 months of age	Fecal samples collected at 3 months of age

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infant growth	Infant weight, length, and head circumference will be aggregated to determine infant growth status	1 week, 2 weeks, 1, 2, 3 and 6 months and 0-12 months
Infant intestinal transit time	Intestinal transit time estimated by sweet-corn transit time through the gastrointestinal tract	9 months and 12 months
Frequency of Infections	Measured as episodes of respiratory and gastrointestinal infections within the first 6 months of age.	1 week, 2 weeks, 1, 2, 3 and 6 months
Infant crying and fussing	Measured as frequency/duration of crying and fussing assessed as parent-reported in the Infant Health Questionnaire	1 week, 2 weeks, 1, 2, 3 and 6 months
General health status of infants	General health status measured as number of health care visits and illness diagnosis	0-12 months
Infant stool frequency	Changes in stool frequency and consistency measured from birth through to 6 months of age assessed as parent-reported in the Infant Health Questionnaire	1 week, 2 weeks, 1, 2, 3 and 6 months
Infant fecal immunoglobulins	Changes in fecal immunoglobulins from infant fecal samples	1 week, 2 weeks, 1, 2, 3 and 6 months and 0-12 months
Infant blood immunoglobulins	Changes in immunoglobulins measured in dried blood spots	3, 6 and 12 months
Characterization of Infant gut metabolome	Characterization and changes in the Infant fecal metabolome as assessed by targeted and untargeted metabolomics	1 week, 2 weeks, 1, 2, 3, 6, 9 and 12 months
Characterization of the Infant blood metabolome	Characterization and changes of the Infant blood metabolome as assessed by targeted and untargeted metabolomics from dried blood spots	3, 6 and 12 months
Characterization of the Infant gut microbiome composition	Changes in gut microbiome composition analyzed by DNA/RNA sequencing of fecal samples.	1 week, 2 weeks, 1, 2, 3, 6, 9 and 12 months
Characterization of Infant blood cytokine profiles	Changes in pro-inflammatory and anti-inflammatory cytokines profiles from dried blood spots	3, 6 and 12 months
Characterization of Infant fecal cytokines profiles	Changes in pro-inflammatory and anti-inflammatory cytokines profiles measured in fecal samples	1 week, 2 weeks, 1, 2, 3 and 6 months and 0-12 months

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: University of Copenhagen; Chr Hansen; Technical University of Denmark
• Investigators: Principal Investigator: Lars H Pedersen, Professor, PhD, MD, Aarhus University Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): August 1, 2027

Study Registration Dates

• First Submitted: September 20, 2024
• First Submitted That Met QC Criteria: October 7, 2024
• First Posted (Actual): October 8, 2024

Study Record Updates

• Last Update Posted (Actual): October 8, 2024
• Last Update Submitted That Met QC Criteria: October 7, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: infants; gastrointestinal microbiome; immune development; gastrointestinal well-being; infant formula fed
• Other Study ID Numbers: HND-IN-054

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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