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

NCT ID: NCT05025852

Last Updated: 2024-01-16

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 220 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-05-11
• Study Completion Date: 2026-05-31

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

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Metformin exposed in utero

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

No interventions assigned to this group

Placebo exposed in utero

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

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

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

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sunnybrook Research Institute

OTHER

Sponsor Role: collaborator

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

Mount Sinai Hospital, Canada

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Denice Feig, MD

Role: PRINCIPAL_INVESTIGATOR

Mount Sinai Hospital, Toronto, ON, Canada

Locations

Campbelltown Hospital

Campbelltown, New South Wales, Australia

Site Status: RECRUITING

Mater Misericordiae

Brisbane, Queensland, Australia

Site Status: RECRUITING

Alberta Children's Hospital

Calgary, Alberta, Canada

Site Status: RECRUITING

Stollery Children's Hospital

Edmonton, Alberta, Canada

Site Status: RECRUITING

British Columbia Children's Hospital

Vancouver, British Columbia, Canada

Site Status: COMPLETED

Children's Health Research Institute of Manitoba (CHRIM)

Winnipeg, Manitoba, Canada

Site Status: COMPLETED

IWK Health Centre

Halifax, Nova Scotia, Canada

Site Status: COMPLETED

St Joseph's Health Care

London, Ontario, Canada

Site Status: RECRUITING

The Scarborough Hospital

Scarborough Village, Ontario, Canada

Site Status: RECRUITING

Mount Sinai Hospital

Toronto, Ontario, Canada

Site Status: RECRUITING

Hospital Maisonneuve-Rosemont

Montreal, Quebec, Canada

Site Status: RECRUITING

Chuq-Chul

Québec, Quebec, Canada

Site Status: COMPLETED

Countries

Australia; Canada

Central Contacts

Siobhan Tobin, HonBSc

Role: CONTACT

mitytykes@sunnybrook.ca

416-480-5631

Gail Klein, MSc

Role: CONTACT

gail.klein@sunnybrook.ca

416-480-5632

Facility Contacts

David Simmons, MD

Role: primary

Josephine Laurie, MD

Role: primary

Jospehine Ho, MD

Role: primary

Andrea Haqq, MD

Role: primary

Selina Liu, MD

Role: primary

Afshan Zahedi, MD

Role: primary

Denice Feig, MD

Role: primary

Laurent Legault, MD

Role: primary

Other Identifiers

CTO 3632

Identifier Type: -

Identifier Source: org_study_id