Twice Weekly Steroids and Exercise as Therapy for DMD

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

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.

Study Overview

• Status: Completed
• Conditions: Duchenne Muscular Dystrophy (DMD)
• Intervention / Treatment: Drug: Prednisone; Behavioral: Exercise Training on standard steroid regimen; Drug: Exercise training on twice-weekly steroids

Detailed Description

This innovative proposal focuses on developing an efficacious therapeutic strategy involving low dose twice weekly glucocorticoid (GC) administration and exercise training for boys affected with Duchenne muscular dystrophy (DMD), a currently incurable disease characterized by rapidly progressive muscle weakness, early loss of ambulation and death. While GC are the only proven treatment to reduce fibrosis and delay loss of ambulation in DMD, chronic daily administration (which is most commonly prescribed) is associated with adverse, often debilitating effects. As an alternate dosing regimen, weekend-only use was shown to retain the benefits and have less impact on weight gain and linear growth, however high doses were used and associated with behavioral issues. Recent work in mice suggests that the same daily dose administered transiently may be effective and have a greater impact on gains in muscle mass, strength and resistance to fatigue compared to daily dosing due to differential effects on gene expression signaling pathways important for muscle remodeling. Exercise, which also induces signaling pathways that lead to remodeling in healthy muscle, may beneficially impact pathophysiology of DMD by recruiting compensatory pathways. Although high intensity or eccentric actions are damaging to dystrophic muscle, a few studies suggest that submaximal exercise is safe and may delay the loss of muscle function in boys with DMD. Despite these exploratory studies suggesting potential, there is a paucity of research on exercise, which reflects our current lack of understanding of specific exercise prescription parameters (type, intensity, target muscle groups) that may be safe and effective for patients with DMD, as well as lack of accessibility to exercise equipment that appropriately and sufficiently induces adaptation in dystrophic muscle. The objective of this work is to define an efficacious GC regimen with minimal side effects, and understand if exercise training can potentially delay disease progression, reverse secondary effects of disuse, and induce beneficial adaptations in boys with DMD.

AIM 1: To determine the 12-month impact of a low dose (0.75 mg/kg x 2 days of prednisone) regimen on weight gain, DMD muscle pathophysiology and physical function. We hypothesize that compared to the standard daily regimen, a twice-weekly regimen will have less impact on body mass index, and equal improvements in the 1-year change in physical function and muscle fat fraction.

AIM 2: To determine impact of a 6-month in-home, moderate intensity, leg exercise training program on muscle pathophysiology and physical function in DMD.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 8 years (Child)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Daily Glucocorticoid (GC); 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; 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; A 12-month treatment period with twice weekly, low-dose prednisone (dose of 0.75 mg/kg per day).; Other Names: Glucocorticoid (GC)
Active Comparator: Daily glucocorticoid with exercise; Patients on daily glucocorticoids will undergo 6 months of structured, supervised and home-based exercise training.	Drug: Prednisone; A 12-month treatment period with twice weekly, low-dose prednisone (dose of 0.75 mg/kg per day).; Other Names: Glucocorticoid (GC); Behavioral: Exercise Training on standard steroid regimen; 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.; Other Names: no other names apply; Drug: Exercise training on twice-weekly steroids; Twice weekly prednisone for 6 months followed by twice weekly prednisone plus exercise for 6 months.; Other Names: no other names apply

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: U.S. Army Medical Research and Development Command
• Investigators: Principal Investigator: Tanja Taivassalo, MD, University of Florida

Study record dates

Study Major Dates

• Study Start (Actual): July 30, 2020
• Primary Completion (Actual): December 4, 2024
• Study Completion (Actual): September 4, 2025

Study Registration Dates

• First Submitted: March 24, 2020
• First Submitted That Met QC Criteria: March 24, 2020
• First Posted (Actual): March 26, 2020

Study Record Updates

• Last Update Posted (Actual): March 13, 2026
• Last Update Submitted That Met QC Criteria: March 12, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: exercise training; novel steroid regimen; twice-weekly prednisone; leg cycling; isometric strengthening
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Muscular Disorders, Atrophic; Muscular Dystrophies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Muscular Dystrophy, Duchenne; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pharmacologic Actions; Chemical Actions and Uses; Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Pregnadienediols; Adrenal Cortex Hormones; Prednisone; Glucocorticoids
• Other Study ID Numbers: IRB201901339; MD 180023 (Other Grant/Funding Number: U.S. Army Medical Research and Development Command); OCR27142 (Other Identifier: UF OnCore)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No