Healthy Outcomes for Muscle with Exercise in T1D (HOME T1D)

Targeting Vascular and Skeletal Muscle Health to Improve Quality of Life in Males and Females with Type 1 Diabetes

Over 300,000 people in Canada suffer from Type 1 Diabetes (T1D), a chronic condition whose incidence rate has been increasing in Canada every year by 5.1% (higher than the global average). While exogenous insulin injections allow those with T1D to live, it is not a cure, and those with T1D develop severe complications (kidney failure, cardiovascular disease). Strategies to regress the development of these complications, minimize healthcare system burden, and save the lives of Canadians are urgently needed.

Undertaking regular exercise is an obvious strategy for those with T1D and has many well-established health benefits. Despite these benefits, adults with T1D exercise less frequently due to fear of severe hypoglycemia and a lack of knowledge of effective exercise strategies. Adding to this complexity, the investigators have recently shown that males and females elicit differential impairments in skeletal muscle metabolism in response to T1D. These differences may extend to the peripheral microvasculature and may lead to sexual dimorphism in the health benefits of exercise for those with T1D. Ultimately, developing a healthy muscle mass, including microvasculature, will help mitigate dysglycemic and dyslipidemic fluctuations and improve insulin sensitivity.

The overarching purpose of this proposed study is to determine the impact of T1D on human skeletal muscle and its microvasculature over the lifespan in males and females, and its responses to exercise training and detraining.

Study Overview

• Status: Recruiting
• Conditions: Diabetes Mellitus, Type 1
• Intervention / Treatment: Behavioral: Exercise; Behavioral: De-training

• Study Type: Interventional
• Enrollment (Estimated): 168
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Thomas J Hawke, PhD; Phone Number: 22372 905-525-9140; Email: hawke@mcmaster.ca
• Study Contact Backup: Name: Irena A Rebalka, PhD; Phone Number: 26868 905-525-9140; Email: rebalka@mcmaster.ca

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8S 4L8
      • Recruiting
      • McMaster University
      • Contact: Rebecca Leone; Phone Number: 905-525-9140; Email: rleone@mcmaster.ca
      • Contact: Thomas J Hawke, PhD
      • Contact: Irena A Rebalka, PhD
      • Contact: Maureen MacDonald, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age of 18-30 or 45-65
• Sedentary or recreationally active, as defined by self-reported activity levels below the recommended 150-minute minimum of moderate-to-vigorous intensity physical activity per week

Exclusion Criteria:

• Chronic use of anti-inflammatory, glucocorticoid, or other pain-relief medication
• History of daily cannabis, tobacco, or nicotine use within six months of study initiation
• BMI >30kg/m2
• Prediabetes
• Type 2 diabetes
• Health conditions that put the subject at risk to participate in exercise during this study
• Atypical or Grade 2b diabetic sensorimotor polyneuropathy
• More than one lifetime event of hospitalization for diabetic ketoacidosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Twelve-week Exercise; Study participants will participate in an exercise program consisting of aerobic and resistance exercise. This arm will last twelve weeks.	Behavioral: Exercise; Exercise training.
Experimental: One-week Detraining; Study participants will undergo unilateral knee immobilization for a one-week period.	Behavioral: De-training; Exercise de-training via unilateral knee immobilization.
Experimental: Four-week Re-training; Study participants will once again participate in an exercise program consisting of aerobic and resistance exercise. This arm will last four weeks.	Behavioral: Exercise; Exercise training.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The effect of T1D on skeletal muscle health, quantified by physiological parameters (detailed in description)	Individuals with T1D as well as their age, sex, and BMI-matched control counterparts will undergo various physiological assessments to evaluate their muscle health: strength/aerobic fitness testing, compartmental body composition assessment, blood analysis, glucose monitoring, muscle biopsy, motor neuron function evaluation, and assessments of muscle microvascular structure and function. All metrics will be compared between individuals with T1D and their non-T1D counterparts.	At time of study start (baseline characteristics)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The effect of twelve weeks of exercise on skeletal muscle health compared to baseline, quantified by physiological parameters (detailed in description)	Following baseline assessments, study participants will undergo a combined aerobic and resistance training program for twelve weeks. Following twelve weeks of participation in this exercise program, all study participants will undergo various physiological assessments to evaluate their muscle health: strength/aerobic fitness testing, compartmental body composition assessment, blood analysis, glucose monitoring, muscle biopsy, motor neuron function evaluation, and assessments of muscle microvascular structure and function.	Twelve weeks following study initiation
The acute effect of a detraining period on skeletal muscle health compared to baseline, quantified by physiological parameters (detailed in description)	Following completion of the aforementioned twelve week exercise program, study participants will undergo a seven-day detraining period consisting of unilateral knee immobilization using a hinged knee-joint immobilization brace. Immediately following this immobilization period, all study participants will undergo various physiological assessments to evaluate their muscle health: strength/aerobic fitness testing, compartmental body composition assessment, blood analysis, glucose monitoring, muscle biopsy, motor neuron function evaluation, and assessments of muscle microvascular structure and function.	Thirteen weeks following study initiation
The effect of a detraining period on skeletal muscle health compared to baseline, quantified by physiological parameters (detailed in description)	Following completion of the aforementioned twelve week exercise program, study participants will undergo a seven-day detraining period consisting of unilateral knee immobilization using a hinged knee-joint immobilization brace. Four weeks after this immobilization period, all study participants will undergo various physiological assessments to evaluate their muscle health: strength/aerobic fitness testing, compartmental body composition assessment, blood analysis, glucose monitoring, muscle biopsy, motor neuron function evaluation, and assessments of muscle microvascular structure and function.	Seventeen weeks following study initiation

Collaborators and Investigators

• Sponsor: McMaster University
• Investigators: Principal Investigator: Thomas J Hawke, PhD, McMaster University

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2023
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2027

Study Registration Dates

• First Submitted: January 25, 2023
• First Submitted That Met QC Criteria: February 13, 2023
• First Posted (Actual): February 23, 2023

Study Record Updates

• Last Update Posted (Estimated): December 5, 2024
• Last Update Submitted That Met QC Criteria: December 3, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Autoimmune Diseases; Immune System Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: 15516

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Participant data - after deidentification.
• IPD Sharing Time Frame: Starting in May 2024
• IPD Sharing Access Criteria: Investigators whose proposed use of the data has been approved by an independent internal committee identified for this purpose.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No