Twice Weekly Steroids and Exercise as Therapy for DMD

University of Florida

Status and phase: Active, not recruiting; Phase 2

Conditions: Duchenne Muscular Dystrophy (DMD)

Treatments: Drug: Prednisone plus exercise; Drug: Prednisone; Behavioral: In-home Exercise Training

Study type: Interventional

Funder types: Other; Other U.S. Federal agency

Identifiers

NCT04322357

MD 180023 (Other Grant/Funding Number)

IRB201901339

OCR27142 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 89 estimated patients

Sex: Male

Ages: 5 to 9 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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89 participants in 3 patient groups

Daily Glucocorticoid (GC)

No Intervention group

Description:

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.

Twice weekly glucocorticoid with or without exercise

Active Comparator group

Description:

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.

Treatment:

Drug: Prednisone

Daily glucocorticoid with exercise

Active Comparator group

Description:

Patients on daily glucocorticoids will undergo 6 months of structured, supervised and home-based exercise training.

Treatment:

Behavioral: In-home Exercise Training

Drug: Prednisone

Drug: Prednisone plus exercise