Twice Weekly Steroids and Exercise as Therapy for DMD

Study Overview
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Brief Summary
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The study team will determine the potential of low dose twice weekly prednisone and whether exercise training can synergize to delay disease progression and improve muscle strength/physical function in boys with Duchenne muscular dystrophy (DMD). Current standard of care (daily prednisone) is associated with adverse side effects. Evidence from DMD mouse models suggest that weekly dosing provides same efficacy without side effects. Appropriate exercise may also benefit but this area has not been adequately explored.

Official Title
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Impact and Interplay of Corticosteroid Regimen and Exercise Training on DMD Muscle Function

Conditions
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Duchenne Muscular Dystrophy (DMD)

Intervention / Treatment
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* Drug: Prednisone
* Behavioral: In-home Exercise Training
* Drug: Prednisone plus exercise


Participation Criteria
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Eligibility Criteria
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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 and 4) absence of dystrophin expression, as determined by immunostain or Western blot (<2%) and/or DNA confirmation of dystrophin mutation. Age 5.0 to 9 years: a lower age limit of 5.0 years is selected as children younger than that are likely unable to cooperate and comply with all of the exercise measures as needed. An upper age limit of 9 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. Aim 1 only: GC-naïve at baseline (and prior 6 months) Aim 2 only: on stable daily GC regimen for 6 months prior to baseline Exclusion Criteria: Contraindication to an MR examination (e.g. aneurysm clip, severe claustrophobia, magnetic implants) Presence of unstable medical problems, significant concomitant illness including cardiomyopathy or cardiac conduction abnormalities Presence of a secondary condition that impacts muscle function or muscle metabolism (e.g. myasthenia gravis, endocrine disorder, mitochondrial disease) Presence of a secondary condition leading to developmental delay or impaired motor control (e.g. cerebral palsy) Presence of an unstable medical condition (e.g. uncontrolled seizure disorder) Behavioral problems causing an inability to cooperate during testing or understand exercise instruction Participation in other forms of drug or gene therapy during the period of the study

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 9 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Daily Glucocorticoid (GC)<br>Existing data from age-matched, ambulatory, on daily GC therapy, and similar exclusion criteria will be selected from the ImagingDMD database to serve as a historical control. | |
| Active Comparator: Twice weekly glucocorticoid with or without exercise<br>Patients will be randomized to one of 2 groups: Twice weekly prednisone alone for 12 months Twice weekly prednisone for 6 months followed by twice weekly prednisone plus 6 months of structured, supervised and home-based exercise training. | Drug: Prednisone<br>* A 12-month treatment period with twice weekly, low-dose prednisone (dose of 0.75 mg/kg per day).<br>* Other names: Glucocorticoid (GC);|
| Active Comparator: Daily glucocorticoid with exercise<br>Patients on daily glucocorticoids will undergo 6 months of structured, supervised and home-based exercise training. | Drug: Prednisone<br>* A 12-month treatment period with twice weekly, low-dose prednisone (dose of 0.75 mg/kg per day).<br>* Other names: Glucocorticoid (GC);Behavioral: In-home Exercise Training<br>* For boys on current standard of care (daily glucocorticoid use), 6-months in-home, remotely supervised exercise training program involving a combination of aerobic and isometric leg strength exercises.<br>Drug: Prednisone plus exercise<br>* Twice weekly prednisone for 6 months followed by twice weekly prednisone plus exercise for 6 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in BMI | Participant body mass index change (weight and height will be combined to report BMI in kg/m^2) over the course of one year | Baseline up to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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steroid side effects, low dose steroid regimen, exercise training therapy