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

Diabetes Mellitus, Type 2 Clinical Trial

— MiTy Tykes  

Official title:

A Multi-centre Follow up Study of the Effect of In-utero Exposure to Metformin in 5-11 Year Old Offspring of Mothers in the MiTy Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05025852
• Other study ID #: CTO 3632
• Status: Recruiting
• Start date: May 11, 2022
• Est. completion date: May 2026

Study information

• Verified date: January 2024
• Source: Mount Sinai Hospital, Canada
• Contact: Siobhan Tobin, HonBSc
• Phone: 416-480-5631
• Email: mitytykes[@]sunnybrook.ca
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 220
• Est. completion date: May 2026
• Est. primary completion date: May 2026
• Gender: All
• Age group: N/A and older

Eligibility

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).

Related Conditions & MeSH terms

• Child Development
• Child Obesity
• Diabetes Mellitus, Type 2
• Pediatric Obesity
• Pregnancy in Diabetic
• Pregnancy in Diabetics

Locations

Country	Name	City	State
Australia	Mater Misericordiae	Brisbane	Queensland
Australia	Campbelltown Hospital	Campbelltown	New South Wales
Canada	Alberta Children's Hospital	Calgary	Alberta
Canada	Stollery Children's Hospital	Edmonton	Alberta
Canada	IWK Health Centre	Halifax	Nova Scotia
Canada	St Joseph's Health Care	London	Ontario
Canada	Hospital Maisonneuve-Rosemont	Montréal	Quebec
Canada	Chuq-Chul	Quebec City	Quebec
Canada	The Scarborough Hospital	Scarborough	Ontario
Canada	Mount Sinai Hospital	Toronto	Ontario
Canada	British Columbia Children's Hospital	Vancouver	British Columbia
Canada	Children's Health Research Institute of Manitoba (CHRIM)	Winnipeg	Manitoba

Sponsors (3)

Lead Sponsor	Collaborator
Mount Sinai Hospital, Canada	Canadian Institutes of Health Research (CIHR), Sunnybrook Research Institute

Countries where clinical trial is conducted

Australia,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Body Mass Index (BMI) z-score	Using WHO or other appropriate growth charts	5-11 years of age
Secondary	Skinfold measurements	triceps, subscapular and suprailiac skinfold thicknesses	5-11 years of age
Secondary	Sum of skinfold measurements:	sum of triceps, subscapular and suprailiac skinfold thicknesses	5-11 years of age
Secondary	Triceps skinfolds z-scores	Using WHO or other appropriate growth charts	5-11 years of age
Secondary	Ratio of the central to peripheral skinfold ratio	ratio of the central (suprailiac) to peripheral (triceps) skinfold ratio;	5-11 years of age
Secondary	Overweight and obesity status	Defined using WHO or other appropriate growth charts	5-11 years of age
Secondary	Waist circumference	Waist circumference measurement	5-11 years of age
Secondary	Waist to height ratio	Waist and height measurements	5-11 years of age
Secondary	Growth trajectory	Longitudinal growth outcomes will be assessed using adiposity measurements from the MiTy trial (newborns) and at 3, 6, 12, 18 and 24 months from the MiTy Kids trial, to ages 5-11 years in the MiTy Tykes trial.	5-11 years of age
Secondary	Fat mass	Using the Tanita SC-240 bioimpedance analyzer (BIA)	5-11 years of age
Secondary	Percentage of body fat	Using the Tanita SC-240 bioimpedance analyzer (BIA)	5-11 years of age
Secondary	Measures of insulin resistance and metabolic syndrome	The following measurements combined will contribute to the assessment of insulin resistance and metabolic syndrome: fasting glucose, fasting insulin, fasting insulin-to-glucose ratio, and the HOMA-IR, serum levels of leptin, adiponectin and lipids	5-11 years of age
Secondary	Neurocognitive development	Attention Deficit Hyperactivity Disorder (ADHD)-5 Rating scale	5-11 years of age
Secondary	Neurocognitive development	Children's Communication Checklist (CCC-2)	5-11 years of age
Secondary	Neurocognitive development	Social Responsiveness Scale (SRS-2)	5-11 years of age