Myotonic Dystrophy Type 1 and Resistance Exercise (STYRK DM1)

Recovery After Moderate-Heavy Resistance Exercise in Myotonic Dystrophy Type 1-patients

The purpose of this study is to investigate the response after one bout of moderate-heavy resistance exercise in patients suffering from Myotonic Dystrophy type 1. There is still doubt about if these patients could benefit from resistance exercise, or if this mode of exercise is detrimental to their mobility and health. We aim to monitor the subjects during the recovery phase and investigate recovery in several ways.

Study Overview

• Status: Completed
• Conditions: Myotonic Dystrophy 1
• Intervention / Treatment: Other: Moderate-Heavy Resistance Exercise

Detailed Description

Myotonic dystrophy type 1 (DM1) is an autosomal, dominantly inherited, muscular disease and the most common muscular dystrophy amongst adults. The disease is characterized by progressive myopathy and myotonia, first evident in the distal parts of the body: calves and forearms, further progressing towards proximal parts. A recent review by Voet and co-workers (2013) concludes that exercise is safe for DM1-patients, and based on our current knowledge, DM1-patients should be able to gain positive adaptations from exercise. However, the physiological outcomes of an exercise stimulus are not well studied in this population and because of alterations in important Ca2+ handling systems the recovery processes might be significantly different from healthy muscles.

The aim of this study is to investigate the acute responses to moderate-heavy resistance exercise in DM1-patients. We aim to establish a timeline for recovery of muscle strength, measured as maximal voluntary contraction. In line with this, we want to investigate if any muscular damage has occurred with both direct and indirect measures, and possible mechanisms leading to muscle damage, i.e. impaired Ca2+ handling.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Truls Raastad, PhD; Phone Number: +47 23 26 23 28; Email: truls.raastad@nih.no
• Study Contact Backup: Name: Vilde Handegard, MSc; Phone Number: +47 23 26 23 47; Email: vilde.handegard@nih.no

Study Locations

• Norway
  • Oslo, Norway, 0863
    • Norwegian School of Sport Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Confirmed Myotonic Dystrophy type 1-diagnosis

Exclusion Criteria:

• Non-ambulatory
• Injuries to muscle-skeletal-system that prevents resistance exercise
• Severe affection of the cardiovascular system
• Cognitive affection
• Lives more than one hour from test site

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DM1-Ex; Moderate-heavy resistance exercise of one leg in DM1-patients	Other: Moderate-Heavy Resistance Exercise; Leg press: 3 x 8 repetitions at 75% of 1 repetition maximum, 3 minutes rest between sets. Knee extension: 3 x 6 repetitions at 85% of 1 repetition maximum, 3 minutes rest between sets.
Experimental: Ctrl-Ex; Moderate-heavy resistance exercise of one leg in healthy participants	Other: Moderate-Heavy Resistance Exercise; Leg press: 3 x 8 repetitions at 75% of 1 repetition maximum, 3 minutes rest between sets. Knee extension: 3 x 6 repetitions at 85% of 1 repetition maximum, 3 minutes rest between sets.
No Intervention: Ctrl-Rest; Control leg (i.e. no exercise) in healthy participants
No Intervention: DM1-Rest; Control leg (i.e. no exercise) in DM1-patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in muscle strength	Recovery of knee extension torque	Baseline, and 5 minutes, 3 hours, 24 hours, 48 hours, and 71 hours after exercise

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscle protein synthesis rate	Rate of muscle protein synthesis in m. vastus lateralis between baseline and 27 hours after final session of resistance exercise	Baseline and 27 hours after final session of resistance exercise
Muscle protein breakdown rate	Rate of muscle protein breakdown in m. vastus lateralis between baseline and 27 hours after final session of resistance exercise	Baseline and 27 hours after final session of resistance exercise

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in muscle damage	Myofibrillar disruption and necrosis observed in muscle tissue samples from m. vastus lateralis with electron microscopy	Baseline and 27 hours after final session of resistance exercise
Change in muscle regeneration	Appearance of macrophages, satellite cell localization, and disruption of membrane in single muscle fibers and cross-sections using confocal microscopy	Baseline and 27 hours after final session of resistance exercise
Change in calcium cycling	Calcium cycling in muscle tissue samples from m. vastus lateralis	Baseline and 27 hours after final session of resistance exercise
Change in contractile function	Assessment of contractile function in single muscle fibers from m. vastus lateralis	Baseline and 27 hours after final session of resistance exercise
Change in calcium-related protein abundances	Levels of protein and phosphorylation status using Western blotting	Baseline and 27 hours after final session of resistance exercise
Muscle fiber type	Fiber type composition in samples from m. vastus lateralis	Baseline
Muscle fiber type	Fiber type composition in samples from m. vastus lateralis	27 hours after final session of resistance exercise
Change in heat shock proteins	Localization and expression of heat shock proteins using Western blotting and Immunohistochemistry	Baseline and 27 hours after final session of resistance exercise
Change in anabolic signaling	Expression and phosphorylation status of central mediators in anabolic signaling pathways using Western blotting	Baseline and 27 hours after final session of resistance exercise
Change in autophagy	Expression and phosphorylation status of central mediators in pathways regulating muscle protein breakdown using Western blotting	Baseline and 27 hours after final session of resistance exercise
Change in biomarkers of muscle damage	Levels of serum Creatine kinase, Myoglobin, and Troponin I	Baseline, and 3 hours, 24 hours, 48 hours, 71 hours, and 96 hours after exercise
Change in biomarker of muscle damage	Level of titin-N fragment in urine	Baseline, and 20 hours, 44 hours, 68 hours, and 92 hours after exercise
Change in Fatigue	Electrical stimulation of m. vastus lateralis and m. vastus medialis at 10, 20, 50, and 80 Hz	Baseline, and 1 hour after exercise
Change in muscle stiffness	Muscle stiffness measured with shear wave elastography in static and dynamic conditions	Baseline, and 50 minutes after exercise
Change in muscle soreness	Subjective rating of muscle soreness using a visual analogue scale (0-10)	Baseline, and 3 hours, 24 hours, 48 hours, and 71 hours after exercise
Change in muscle swelling	Thickness of m. vastus lateralis using ultrasound B-mode	Baseline, and 3 hours, 24 hours, 48 hours, and 71 hours after exercise

Collaborators and Investigators

• Sponsor: Norwegian School of Sport Sciences
• Collaborators: University of Oslo; Oslo University Hospital; University of Copenhagen; University of Southern Denmark; Maastricht University
• Investigators: Principal Investigator: Truls Raastad, PhD, Norwegian School of Sport Sciences

Study record dates

Study Major Dates

• Study Start (Actual): June 14, 2021
• Primary Completion (Actual): April 30, 2023
• Study Completion (Actual): April 30, 2023

Study Registration Dates

• First Submitted: May 10, 2021
• First Submitted That Met QC Criteria: August 30, 2021
• First Posted (Actual): September 5, 2021

Study Record Updates

• Last Update Posted (Actual): November 28, 2023
• Last Update Submitted That Met QC Criteria: November 27, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Recovery; Resistance exercise; Muscle function; Muscle protein synthesis; Muscle protein breakdown
• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Muscular Disorders, Atrophic; Heredodegenerative Disorders, Nervous System; Muscular Dystrophies; Myotonic Disorders; Myotonic Dystrophy
• Other Study ID Numbers: STYRK DM1

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