The Effect of In-utero Exposure to Metformin in 5-11 Year Old Offspring of Mothers in the MiTy Trial

NCT05025852 | Completed

• 1 other identifier: CTO 3632
• Study Type: observational
• Target: 132
• Locations: 2 countries
• Sites: 12

Brief Summary

The incidence of diabetes in pregnancy is rising, with rates of 1 in 7 pregnancies globally. Metformin is used for type 2 diabetes (T2DM) outside of pregnancy and is now increasingly prescribed during pregnancy. There are some concerns as metformin crosses the placenta and effects on offspring exposed during pregnancy are unknown. Animal and human evidence indicate that metformin may create an atypical in-utero environment similar to under-nutrition which has been associated with adult obesity. This is supported by studies in children of mothers treated with metformin in other populations where an increase in childhood obesity was found at 4-9 years of age. We now have evidence from the MiTy trial, that offspring of metformin-exposed women with T2DM have less large infants and are less adipose at birth, but are also more likely to be small for gestational age (SGA). These effects could lead to benefit or harm in the long-term. Offspring of MiTy mothers are currently being followed up to 2 years. Given that long-term effects may not be evident until 5 years of age, it is imperative to follow these children longer. Goals/Research Aims:To determine whether in-utero exposure to metformin, in offspring of women with T2DM, is beneficial or harmful in the long-term. Research Questions: 1. In offspring of women with T2DM, how does treatment with metformin during pregnancy affect a) adiposity b) growth over time c) metabolic syndrome d) cognitive and behavioral measures:2. What factors predict altered childhood adiposity and insulin resistance in these offspring? Primary Outcome: Body mass index (BMI) z-score. Secondary Outcomes: 1) other measures of adiposity (i.e. skinfolds, 2) growth over time 3) measures of insulin resistance 4) adipocytokines 5)neurodevelopment Expected Outcomes Given these increasing concerns, this study will inform the best treatment for pregnant mothers with diabetes by studying the long-term outcomes of children exposed to metformin during pregnancy.

Conditions

Diabetes Mellitus, Type 2; Pregnancy in Diabetic; Child Obesity; Child Development

Outcome Measures

Primary Outcomes (1)

• Body Mass Index (BMI) z-score

  Using WHO or other appropriate growth charts

  5-11 years of age

Secondary Outcomes (14)

• Skinfold measurements

  5-11 years of age

• Sum of skinfold measurements:

  5-11 years of age

• Triceps skinfolds z-scores

  5-11 years of age

• Ratio of the central to peripheral skinfold ratio

  5-11 years of age

• Overweight and obesity status

  5-11 years of age

Study Arms (2)

Metformin exposed in utero

Offspring of mothers who were exposed to metformin during pregnancy in the MiTy trial.

Placebo exposed in utero

Offspring of mothers who were not exposed to metformin during pregnancy in the MiTy trial.

Eligibility Criteria

• Sex: all
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Offspring of women with type 2 diabetes who participated in the MiTy trial will be recruited for participation.

You may qualify if:

• Liveborn offspring of women who participated in the MiTy trial.

You may not qualify if:

• Offspring with major congenital anomalies that would affect growth or development (these children have already been excluded from MiTy Kids).

Sponsors & Collaborators

• Mount Sinai Hospital, Canada: lead
• Sunnybrook Research Institute: collaborator
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (12)

Campbelltown Hospital

Campbelltown, New South Wales, Australia

Location

Mater Misericordiae

Brisbane, Queensland, Australia

Location

Alberta Children's Hospital

Calgary, Alberta, T3B 6A8, Canada

Location

Stollery Children's Hospital

Edmonton, Alberta, T6G 2B7, Canada

Location

British Columbia Children's Hospital

Vancouver, British Columbia, V6H 3N1, Canada

Location

Children's Health Research Institute of Manitoba (CHRIM)

Winnipeg, Manitoba, R3E 3P4, Canada

Location

IWK Health Centre

Halifax, Nova Scotia, B3K 6R8, Canada

Location

St Joseph's Health Care

London, Ontario, N6A 4V2, Canada

Location

The Scarborough Hospital

Scarborough Village, Ontario, M1P 2V5, Canada

Location

Mount Sinai Hospital

Toronto, Ontario, Canada

Location

Hospital Maisonneuve-Rosemont

Montreal, Quebec, H1T 2M4, Canada

Location

Chuq-Chul

Québec, Quebec, G1V 4G2, Canada

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

A blood sample will be taken to be analyzed for markers of metabolic syndrome.

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Pregnancy in Diabetics; Pediatric Obesity

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Obesity; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Denice Feig, MD

  Mount Sinai Hospital, Toronto, ON, Canada

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2021
• First Posted: August 27, 2021
• Study Start: May 11, 2022
• Primary Completion: April 30, 2025
• Study Completion: April 30, 2025
• Last Updated: September 24, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Start date: two years after the publication of the study results (main publication). No planned end date.
• Access Criteria: The data will be stored in a controlled-access database, for which access is limited to researchers who submit a study plan to the Steering Committee, and who sign an agreement to use the coded study data only for that research.

Locations

AU (2); CA (10)