Strength Training in Duchenne Muscular Dystrophy
Condition: Duchenne Muscular Dystrophy
MeSH terms: Muscular Dystrophies; Muscular Dystrophy, Duchenne
Study type: Interventional

Summary: 
      Duchenne muscular dystrophy (DMD) is a debilitating neuromuscular disease that causes muscle
      breakdown, weakness, and eventual death. Over the last 40 years parents have received little
      guidance on the potential of exercise as a therapeutic strategy to maintain muscle function.
      It is well known that high intensity exercise and eccentric contractions can result in muscle
      damage in dystrophic muscle, yet the absence of muscle loading will conversely result in
      muscle wasting. Recent research in rodent models and milder forms of muscular dystrophy
      supports earlier studies that resistance exercise may have beneficial effects for maintenance
      of muscle mass in dystrophic muscle. However, careful and systematic investigation into the
      safety and feasibility of resistance exercise is needed to consider its implementation in
      boys with DMD.

      The goal of this project is to assess the safety and feasibility of a home based mild to
      moderate-intensity strengthening exercise program in boys with Duchenne muscular dystrophy
      (DMD). Evidence from milder forms of muscular dystrophy and mouse models of DMD suggests that
      strengthening exercise may be beneficial for these children, but this area has not been
      adequately explored using human subjects. The results of this study should provide
      information to assist in the development of scientifically based recommendations concerning
      optimal exercise parameters for patients with DMD.
    

Detailed description: 
      The overall objective of this pilot study is to assess whether a mild to moderate-intensity
      strengthening exercise program can be safely implemented in boys with DMD. In Aim 1, the
      investigators will determine the dose response and safety of mild to moderate-intensity
      isometric resistance exercise in children with DMD. Twelve ambulatory boys with DMD will
      participate in an isometric exercise dosing protocol, in which the load is progressively
      increased. In this early proof of concept pilot study, two large muscle groups will be
      studied: the knee extensors and the knee flexors. T2 weighted magnetic resonance imaging
      (MRI) of the thigh muscles will be used to monitor evidence of muscle damage at each
      intensity level and determine a safe exercise range. Other safety measures will include a
      verbal pain rating scale, clinical examination, and serum creatine kinase (CK) levels. In Aim
      2, the investigators will implement a pilot intervention study to examine the feasibility and
      safety of a 12 week in-home isometric strengthening program in children with DMD. In this
      study, 20 boys with DMD will be randomized to either an exercise group or a control group.
      Ten boys with DMD randomized to the exercise group will complete a progressive exercise
      program using the parameters and dose identified in Aim 1. Assessment of strength and safety
      will be performed at regular time intervals throughout the study. Ten boys with DMD
      randomized to not participate in an exercise intervention will be tested at similar time
      intervals and serve as controls. The data from this pilot study will serve to perform the
      power analysis needed to design an appropriately powered clinical intervention study.
    

Intervention name(s): Aim 2 Exercise group; Aim 1 Exercise Dosing; Aim 2 Control group
Intervention type(s): Procedure; Procedure; Procedure
Intervention description(s): The experimental group will participate in an isometric exercise strengthening intervention with a frequency of ~three times/week for 12 weeks. Training will include using a custom-built exercise set-up and a live monitoring system for all of the subjects who participate in the experimental group. Progression of the exercise program will only occur after safety assessments at weeks 3, 6, and 9. The safety assessments to occur at baseline, 1 week, 6 weeks, and 12 weeks include T2 MRI, Spectroscopic relaxometry, pain rating scale, and CK levels. The safety assessments to occur at 3 weeks and 9 weeks include the pain rating scale and CK levels. Participants in this group may also be tested for strength assessments (of the knee flexors and extensors) and time to climb 4 stairs.; The maximal voluntary contraction (MVC) will be determined for each subject. The first four subjects will exercise at an intensity of ~30% of the subject's MVC. Subjects will be asked to perform ~4 sets of 6 reps of knee extension and knee flexion contractions. 48hs after the exercise is completed a safety assessment will be performed for muscle damage. If none has occurred, four additional subjects will perform the exercise at the next level of intensity (~50% MVC). Similarly, if no damage has occurred at ~50% MVC, four more subjects exercise at ~70% MVC. All safety measures will be performed 48hrs after the exercise has been completed at each of the levels. These safety assessments include T2 MRI, Spectroscopic relaxometry, pain rating scale, and CK levels.; This group will receive safety assessments at baseline, 1 week, 6 weeks, and 12 weeks including T2 MRI, Spectroscopic relaxometry, pain rating scale, and CK levels. They will also receive safety assessments at 3 weeks and 9 weeks that will include the pain rating scale and CK levels. Participants in this group may also be tested for strength assessments (of the knee flexors and extensors) and time to climb 4 stairs.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Health Services Research
Keywords: Exercise; Strength training