Myotonic Dystrophy 1
Conditions
Keywords
Resistance exercise, Recovery, Muscle protein synthesis, Muscle protein breakdown, Muscle function
Brief summary
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.
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.
Interventions
OTHERModerate-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.
Sponsors
Oslo University Hospital
University of Southern Denmark
University of Copenhagen
Maastricht University
University of Oslo
Norwegian School of Sport Sciences
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
OTHER
Masking
SINGLE (Outcomes Assessor)
Intervention model description
Participants in both groups (patients and control) perform unilateral leg resistance exercise, contralateral leg serves as control
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in muscle strength | Baseline, and 5 minutes, 3 hours, 24 hours, 48 hours, and 71 hours after exercise | Recovery of knee extension torque |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Muscle protein synthesis rate | Baseline and 27 hours after final session of resistance exercise | Rate of muscle protein synthesis in m. vastus lateralis between baseline and 27 hours after final session of resistance exercise |
| Muscle protein breakdown rate | Baseline and 27 hours after final session of resistance exercise | Rate of muscle protein breakdown in m. vastus lateralis between baseline and 27 hours after final session of resistance exercise |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in contractile function | Baseline and 27 hours after final session of resistance exercise | Assessment of contractile function in single muscle fibers from m. vastus lateralis |
| Change in calcium-related protein abundances | Baseline and 27 hours after final session of resistance exercise | Levels of protein and phosphorylation status using Western blotting |
| Muscle fiber type | Baseline | Fiber type composition in samples from m. vastus lateralis |
| Change in heat shock proteins | Baseline and 27 hours after final session of resistance exercise | Localization and expression of heat shock proteins using Western blotting and Immunohistochemistry |
| Change in anabolic signaling | Baseline and 27 hours after final session of resistance exercise | Expression and phosphorylation status of central mediators in anabolic signaling pathways using Western blotting |
| Change in autophagy | Baseline and 27 hours after final session of resistance exercise | Expression and phosphorylation status of central mediators in pathways regulating muscle protein breakdown using Western blotting |
| Change in muscle damage | Baseline and 27 hours after final session of resistance exercise | Myofibrillar disruption and necrosis observed in muscle tissue samples from m. vastus lateralis with electron microscopy |
| Change in biomarker of muscle damage | Baseline, and 20 hours, 44 hours, 68 hours, and 92 hours after exercise | Level of titin-N fragment in urine |
| Change in Fatigue | Baseline, and 1 hour after exercise | Electrical stimulation of m. vastus lateralis and m. vastus medialis at 10, 20, 50, and 80 Hz |
| Change in muscle stiffness | Baseline, and 50 minutes after exercise | Muscle stiffness measured with shear wave elastography in static and dynamic conditions |
| Change in muscle soreness | Baseline, and 3 hours, 24 hours, 48 hours, and 71 hours after exercise | Subjective rating of muscle soreness using a visual analogue scale (0-10) |
| Change in muscle swelling | Baseline, and 3 hours, 24 hours, 48 hours, and 71 hours after exercise | Thickness of m. vastus lateralis using ultrasound B-mode |
| Change in biomarkers of muscle damage | Baseline, and 3 hours, 24 hours, 48 hours, 71 hours, and 96 hours after exercise | Levels of serum Creatine kinase, Myoglobin, and Troponin I |
| Change in muscle regeneration | Baseline and 27 hours after final session of resistance exercise | Appearance of macrophages, satellite cell localization, and disruption of membrane in single muscle fibers and cross-sections using confocal microscopy |
| Change in calcium cycling | Baseline and 27 hours after final session of resistance exercise | Calcium cycling in muscle tissue samples from m. vastus lateralis |
Countries
Norway
Outcome results
None listed