Maternal Betaine Supplementation During Breastfeeding

Developing more efficient and cost-effective prevention strategies to slow down the worldwide epidemic of obesity and chronic metabolic disease has become a public health imperative. Our previous results in humans demonstrate that lower breast milk betaine levels were associated with faster infant postnatal growth, a strong and potentially modifiable risk factor of future obesity. Betaine is a trimethylated derivative of glycine, which is present in multiple foods and occurs naturally in breast milk. In this study, we will perform a double-blind randomized placebo-controlled pilot clinical study, in which maternal diet will be supplemented with betaine for 3 months during breastfeeding; infant's growth and adiposity will be monitored until 12 months of age, and breast milk composition and gut microbiota analyzed.

Study Overview

• Status: Recruiting
• Conditions: Overweight and Obesity
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Betaine

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Carles Lerin, PhD; Phone Number: (+34) 93 600 97 51; Email: clerin@fsjd.org

Study Locations

• Spain
  • Barcelona, Spain, 08950
    • Recruiting
    • Hospital Sant Joan de Deu
    • Sub-Investigator: Marta Ramon Krauel, MD PhD
    • Principal Investigator: Carles Lerin, PhD
    • Contact: Carles Lerin, PhD; Phone Number: (+34) 93 600 97 51; Email: clerin@fsjd.org
    • Contact: Marta Ramon Krauel, MD PhD; Phone Number: 71263 (+34) 93 280 40 00; Email: mramonk@sjdhospitalbarcelona.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Maternal Pre-pregnancy BMI between 25 and 40.
• Willing to exclusively breastfeed for ≥ 3 months
• Infant gestational age at birth > 37 weeks
• Infant birth weigth > -1 standard deviations
• Absence of infant disease or malformations at birth

Exclusion Criteria:

• Multiple pregnancy
• Lactose intolerance
• CBS deficiency (inherited disease)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; 400 mg of lactose daily for 12 weeks	Dietary supplement: Placebo; The intervention with supplement will start during the first 48h after birth and will last for 12 weeks
Experimental: Supplement; 400 mg of betaine daily for 12 weeks	Dietary supplement: Betaine; The intervention with supplement will start during the first 48h after birth and will last for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from birth weight-for-length z score at 1 month	Weight and length will be measured at different time-points and combined to calculate weight-for-length z scores.	Birth and 1 month
Change from birth weight-for-length z score at 3 months	Weight and length will be measured at different time-points and combined to calculate weight-for-length z scores.	Birth and 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from birth weight-for-length z score at 6 months	Weight and length will be measured at different time-points and combined to calculate weight-for-length z scores.	Birth and 6 months
Change from birth weight-for-length z score at 12 months	Weight and length will be measured at different time-points and combined to calculate weight-for-length z scores.	Birth and 12 months
Infant Body composition	Total body and abdominal fat mass measured by DXA scan	3 and 12 months
Breast milk concentration of betaine and related metabolites	We will quantify betaine and related metabolites in maternal breast milk samples	1 and 3 months
Maternal circulating concentration of betaine and related metabolites	We will quantify betaine and related metabolites in maternal plasma samples	1 and 3 months
Infant urine concentration of betaine and related metabolites	We will quantify betaine and related metabolites in infant urine samples	1, 3, and 6, and 12 months
Infant gut microbiome composition	DNA from infant fecal samples will be sequenced to quantify abundance of the different bacterial groups.	1, 3, 6, and 12 months
Maternal gut microbiome composition	DNA from maternal fecal samples will be sequenced to quantify abundance of the different bacterial groups.	1 and 3 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Breast milk microbiota composition	DNA from breast milk samples will be sequenced to quantify abundance of the different bacterial groups.	1 and 3 months
Breast milk metabolome	Liquid chromatography coupled to mass spectrometry will be used to obtain a comprehensive metabolic profile of breast milk samples	1 and 3 months
Child development (ASQ-3 questionnaire)	Developmental progress will be evaluated with the parental reported ASQ-3 questionnaires	1, 3, 6, and 12 months

Collaborators and Investigators

• Sponsor: Fundació Sant Joan de Déu

Study record dates

Study Major Dates

• Study Start (Actual): February 11, 2021
• Primary Completion (Anticipated): December 31, 2021
• Study Completion (Anticipated): June 30, 2022

Study Registration Dates

• First Submitted: November 9, 2020
• First Submitted That Met QC Criteria: November 16, 2020
• First Posted (Actual): November 18, 2020

Study Record Updates

• Last Update Posted (Actual): April 27, 2021
• Last Update Submitted That Met QC Criteria: April 26, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Body Weight; Overweight; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Gastrointestinal Agents; Hypolipidemic Agents; Lipid Regulating Agents; Lipotropic Agents; Betaine
• Other Study ID Numbers: PIC-206-19

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