Strength Training in Duchenne Muscular Dystrophy

NCT ID: NCT02421523

Last Updated: 2019-03-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-05-30
• Study Completion Date: 2018-10-08

Brief 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.

Conditions

Duchenne Muscular Dystrophy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: HEALTH_SERVICES_RESEARCH
• Blinding Strategy: NONE

Study Groups

Aim 2 Exercise group

The 10 subjects randomized to the experimental group will participate in an isometric exercise strengthening intervention of the knee extensor and knee flexor muscles in both legs with a frequency of \~three times/week for 12 weeks.

Group Type: EXPERIMENTAL

Aim 2 Exercise group

Intervention Type: PROCEDURE

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.

Aim 2 Control group

The 10 subjects randomized to the control group will not participate in any exercise program during the 12 weeks and will be instructed to continue with their normal activities.

Group Type: ACTIVE_COMPARATOR

Aim 2 Control group

Intervention Type: PROCEDURE

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.

Aim 1 Exercise Dosing

In order to implement a pilot home exercise intervention, the dose response and safety of this intervention must first be determined. We will enroll 12 boys with DMD for this aim and testing will be performed on the right leg.

Group Type: EXPERIMENTAL

Aim 1 Exercise Dosing

Intervention Type: PROCEDURE

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.

Interventions

Aim 2 Exercise group

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.

Intervention Type: PROCEDURE

Aim 1 Exercise Dosing

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.

Intervention Type: PROCEDURE

Aim 2 Control group

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.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Diagnosis of DMD confirmed by

1. clinical history with features before the age of five

2. physical examination

3. elevated serum creatine kinase level

4. absence of dystrophin expression, as determined by immunostain or Western blot (<2%) and/or DNA confirmation of dystrophin mutation.

• Age 7 to 10.5 years: a lower age limit of 7 years was selected, since in our experience children younger than 7 years are likely unable to cooperate and comply with all of the exercise measures as needed. An upper age limit of 10.5 years has been set as boys with DMD tend to reach a rapid progression into a late ambulatory phase soon after this age.
• Ambulatory at the time of the first visit, defined as the ability to walk for at least 100 m without an external assistive device and able to climb four stairs.
• Currently using corticosteroids (prednisone or deflazacort) as prescribed by a physician.

Exclusion Criteria

• Contraindication to an MR examination (e.g. aneurysm clip, severe claustrophobia, magnetic implants)
• Presence of a condition in control subjects or a secondary condition in boys with DMD that impacts muscle function or muscle metabolism (e.g. myasthenia gravis, endocrine disorder, mitochondrial disease)
• Secondary condition leading to developmental delay or impaired motor control (e.g. cerebral palsy)
• Secondary condition that impacts muscle function or muscle metabolism (e.g. myasthenia gravis, endocrine disorder, mitochondrial disease)
• Unstable medical condition (e.g. uncontrolled seizure disorder)
• Behavioral problems causing an inability to cooperate during testing

• Minimum Eligible Age: 7 Years
• Maximum Eligible Age: 10 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

NIH

Sponsor Role: collaborator

University of Florida

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Donovan J Lott, PhD, PT

Role: PRINCIPAL_INVESTIGATOR

University of Florida

Locations

University of Florida

Gainesville, Florida, United States

Countries

United States

Other Identifiers

1R21AR064949-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB201400874-N

Identifier Type: -

Identifier Source: org_study_id