Steroids + Exercise for Duchenne Muscular Dystrophy

Overseen By Tanja Taivassalo, PhD

Age: < 18

Sex: Male

Trial Phase: Phase 2

Sponsor: University of Florida

Must be taking: Glucocorticoids

Disqualifiers: Cardiomyopathy, Cerebral palsy, Seizure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a low dose of the steroid prednisone, taken twice a week, can slow Duchenne muscular dystrophy (DMD) progression and improve muscle strength, especially when combined with exercise. The goal is to determine if this approach can match the effectiveness of the current daily prednisone treatment but with fewer side effects. Boys with DMD who can walk at least 100 meters without assistance may be suitable for this study. Participants will be divided into groups, with some taking prednisone alone and others combining it with a structured exercise program. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are participating in Aim 1, you must not have taken glucocorticoids (GC) for 6 months prior. If you are in Aim 2, you need to be on a stable daily GC regimen for 6 months before starting the trial.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop your current medications. However, if you are part of Aim 1, you should not have taken glucocorticoids (a type of steroid) for at least 6 months before starting the trial. If you are part of Aim 2, you should have been on a stable daily glucocorticoid regimen for 6 months before the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that prednisone, a steroid used to reduce inflammation in Duchenne muscular dystrophy (DMD), can improve muscle strength. Although not officially approved for DMD, doctors often prescribe it for this purpose. Studies have found that prednisone helps maintain muscle strength over time, but daily use can cause side effects.

This trial tests a lower dose of prednisone taken twice a week. Research with mice suggests this schedule might provide the same benefits without the usual side effects.

Regarding exercise, studies indicate that mild to moderate exercise programs at home are safe for boys with DMD. These exercises can boost strength and function without causing harm. Using prednisone along with exercise might enhance these benefits.

In summary, taking prednisone twice a week, especially with exercise, could be a safer option with fewer side effects than daily use. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard of care for Duchenne Muscular Dystrophy, which often involves daily glucocorticoid treatments, this trial explores the potential benefits of altering the frequency and combining it with exercise. One exciting aspect is the twice-weekly prednisone regimen, which could reduce side effects associated with daily dosing while maintaining effectiveness. Additionally, integrating structured exercise could enhance muscle function and slow disease progression, offering a more holistic approach. Researchers are eager to see if these changes lead to improved quality of life and better long-term outcomes for patients.

What evidence suggests that this trial's treatments could be effective for Duchenne muscular dystrophy?

Studies have shown that prednisone, a type of steroid, can help slow muscle damage in boys with Duchenne muscular dystrophy (DMD). In this trial, participants will join different treatment arms to evaluate the effectiveness of prednisone and exercise. One arm will receive prednisone twice a week; research suggests this schedule might offer similar benefits to daily dosing but with fewer side effects. Another arm will combine twice-weekly prednisone with structured, supervised, and home-based exercise training. Additionally, an arm will include participants on daily glucocorticoids undergoing exercise training. Exercise, especially when done at home, is safe and might improve strength and function in boys with DMD. While researchers continue to explore all the benefits of exercise, early findings suggest it could complement steroid treatment. Together, these treatments aim to maintain muscle strength and slow disease progression. ^{1 2 3 5 6}

Who Is on the Research Team?

Tanja Taivassalo, MD

Principal Investigator

University of Florida

Are You a Good Fit for This Trial?

Boys aged 5 to 9 with confirmed Duchenne muscular dystrophy (DMD) who can walk at least 100 meters and climb stairs without help. They must not have been on steroids for the past six months or be on a stable steroid regimen if participating in different parts of the trial. Those with unstable medical conditions, severe heart issues, behavioral problems that affect testing cooperation, or other muscle-impacting diseases cannot join.

Inclusion Criteria

I have been diagnosed with DMD based on tests and physical exams.

I am between 5 and 9 years old.

I have been on a stable daily medication regimen for 6 months.

Exclusion Criteria

Contraindication to an MR examination

I do not have unstable health issues like heart problems.

I have a condition that affects my muscle function or metabolism.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive twice weekly prednisone for 12 months, with some participants also undergoing structured exercise training

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• In-home Exercise Training
• Prednisone

Trial Overview The study is testing low dose prednisone given twice weekly combined with exercise training against the standard daily prednisone treatment for DMD. The goal is to see if this new approach slows disease progression and improves muscle strength without causing significant side effects.

How Is the Trial Designed?

Group I: Daily Glucocorticoid (GC) Active Control 1 Intervention

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.

Group II: Twice weekly glucocorticoid with or without exercise Active Control 1 Intervention

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.

Group III: Daily glucocorticoid with exercise Active Control 3 Interventions

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

Prednisone is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Prednisone for:

• Allergic reactions
• Asthma
• Blood disorders
• Cancer
• Eye problems
• Immune system disorders
• Inflammatory conditions
• Multiple sclerosis
• Organ transplantation
• Rheumatoid arthritis
• Skin conditions

Approved in European Union as Prednisone for:

• Allergic reactions
• Asthma
• Blood disorders
• Cancer
• Eye problems
• Immune system disorders
• Inflammatory conditions
• Multiple sclerosis
• Organ transplantation
• Rheumatoid arthritis
• Skin conditions

Approved in Canada as Prednisone for:

• Allergic reactions
• Asthma
• Blood disorders
• Cancer
• Eye problems
• Immune system disorders
• Inflammatory conditions
• Multiple sclerosis
• Organ transplantation
• Rheumatoid arthritis
• Skin conditions

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

U.S. Army Medical Research and Development Command

Collaborator

Trials

296

Recruited

249,000+

Published Research Related to This Trial

In a study of 13 boys aged 6-14 with Duchenne muscular dystrophy (DMD), tamoxifen was found to be safe with only mild side effects, such as gynecomastia in 4 patients, while they continued their corticosteroid treatment.

Tamoxifen treatment helped preserve motor and respiratory function in these boys over 3 years, contrasting with significant deterioration in age-matched controls who only received corticosteroids, suggesting potential benefits for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and clinical outcome of tamoxifen in Duchenne muscular dystrophy. Tsabari, R., Simchovitz, E., Lavi, E., et al.[2022]

In a six-month trial involving 103 boys with Duchenne's muscular dystrophy, both doses of prednisone (0.75 mg/kg and 1.5 mg/kg) significantly improved muscle strength and function compared to placebo, with peak improvements observed by three months.

Despite the benefits in muscle function, some patients still required mobility aids, and side effects like weight gain and excessive hair growth were noted, indicating the need for further research on long-term corticosteroid use and its mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, double-blind six-month trial of prednisone in Duchenne's muscular dystrophy. Mendell, JR., Moxley, RT., Griggs, RC., et al.[2022]

In a study of 20 pediatric patients with Duchenne muscular dystrophy, those who received corticosteroid treatment (deflazacort) experienced stabilization in muscular strength and functional performance, while untreated patients showed progressive worsening.

Corticosteroid treatment led to improved muscular balance in 70% of patients, although only 2% showed significant functional improvement, indicating that while steroids can help stabilize the disease, they may not prevent loss of independent gait, which occurred at similar ages in both treated and untreated groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effects of corticosteroids in the management of Duchenne muscular dystrophy: our experience]. Rafia, S., Pascual-Pascual, SI., Martínez-Granero, MA., et al.[2018]

Prednisone and deflazacort are currently the most promising corticosteroids for providing temporary functional improvement in boys with Duchenne muscular dystrophy, a severe childhood condition that leads to loss of mobility and early death.

While there is no definitive cure for Duchenne muscular dystrophy yet, using these corticosteroids along with careful dietary management and monitoring for side effects is recommended as the best interim treatment strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Corticosteroids in Duchenne muscular dystrophy: a reappraisal. Wong, BL., Christopher, C.[2017]

A clinical trial is underway involving 300 boys aged 4-7 with Duchenne muscular dystrophy (DMD) to compare the effectiveness and side effects of three corticosteroid regimens: daily prednisone, daily deflazacort, and intermittent prednisone.

The study aims to establish a standardized corticosteroid treatment for DMD, which is crucial since corticosteroids are currently the only documented treatment that improves strength and function in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Developing standardized corticosteroid treatment for Duchenne muscular dystrophy. Guglieri, M., Bushby, K., McDermott, MP., et al.[2018]

In a study of 99 boys aged 5 to 15 with Duchenne dystrophy, daily prednisone treatment led to significant improvements in muscle strength as early as 10 days, with the most effective dose being 0.75 mg/kg after 3 months.

While prednisone was effective in increasing muscle strength, the higher dose of 0.75 mg/kg resulted in notable side effects after 6 months, including weight gain and changes in appearance, whereas the lower dose of 0.3 mg/kg had fewer side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prednisone in Duchenne dystrophy. A randomized, controlled trial defining the time course and dose response. Clinical Investigation of Duchenne Dystrophy Group. Griggs, RC., Moxley, RT., Mendell, JR., et al.[2019]

Corticosteroids, particularly prednisone/prednisolone and deflazacort, have been shown to stabilize muscle strength in children with Duchenne muscular dystrophy (DMD), allowing some to remain able to walk longer than expected based on natural history data.

While both steroids are similarly effective, deflazacort may have a better side-effect profile, causing less weight gain, and long-term treatment with corticosteroids appears to reduce the frequency of complications such as respiratory insufficiency and cardiac symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of corticosteroids in muscular dystrophy: a critical appraisal. Angelini, C.[2022]

Deflazacort treatment in boys with Duchenne muscular dystrophy (DMD) significantly delayed the loss of walking ability and improved pulmonary function compared to untreated boys, with treated boys maintaining better functional vital capacity at 15 years (88% vs. 39%).

While deflazacort was associated with the development of asymptomatic cataracts in 10 out of 30 boys, other side effects like hypertension and infections were not more common than in untreated boys, indicating a relatively favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deflazacort treatment of Duchenne muscular dystrophy. Biggar, WD., Gingras, M., Fehlings, DL., et al.[2014]

Deflazacort, approved for Duchenne muscular dystrophy (DMD) in 2017, shows similar or slower rates of functional decline compared to prednisone/prednisolone, based on evidence from various clinical studies.

While deflazacort has a better safety profile regarding weight gain and behavioral side effects, it may have more negative impacts on bone health, growth, and cataract development compared to prednisone/prednisolone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing Deflazacort and Prednisone in Duchenne Muscular Dystrophy. Biggar, WD., Skalsky, A., McDonald, CM.[2022]

In a study of 99 boys with Duchenne dystrophy, prednisone at a dose of 0.75 mg/kg/d was found to significantly improve muscle strength and increase muscle mass by 36% over 18 months.

Azathioprine, when added to the treatment, did not provide any additional benefits, suggesting that the positive effects of prednisone are not related to its immunosuppressive properties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duchenne dystrophy: randomized, controlled trial of prednisone (18 months) and azathioprine (12 months) Griggs, RC., Moxley, RT., Mendell, JR., et al.[2019]

In a double-blind trial involving 28 patients with Duchenne muscular dystrophy, Deflazacort (DF) showed statistically significant improvements in muscle strength and function compared to a placebo, indicating its efficacy as a treatment option.

While some mild side effects were observed, such as increased appetite and a cushingoid appearance in a few patients, no one had to stop taking the medication, suggesting that DF may have a better safety profile than traditional steroids like prednisone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Steroids in Duchenne muscular dystrophy--deflazacort trial. Mesa, LE., Dubrovsky, AL., Corderi, J., et al.[2019]

Long-term corticosteroid treatment (over 3 years) in patients with Duchenne muscular dystrophy provides significant benefits, including prolonging ambulation by 2 to 5 years and improving overall neuromuscular function without major side effects.

Corticosteroids also reduce the need for spinal stabilization surgery, enhance cardiopulmonary function, delay the requirement for noninvasive ventilation, and improve both survival rates and quality of life for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Change in natural history of Duchenne muscular dystrophy with long-term corticosteroid treatment: implications for management. Moxley, RT., Pandya, S., Ciafaloni, E., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9254904/

Safety, Feasibility, and Efficacy of Strengthening Exercise ... An in-home, mild-moderate intensity leg exercise program is safe with potential to positively impact both strength and function in ambulatory boys with DMD.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8862644/

EXERCISE TRAINING IN DUCHENNE MUSCULAR ... Exercise training may be beneficial in Duchenne muscular dystrophy, but the evidence remains uncertain. Further research is needed on exercise training.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02421523

Strength Training in Duchenne Muscular Dystrophy 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 ...

4. pedneur.com pedneur.com/article/S0887-8994(23)00456-3/abstract

Family Involvement and at-Home Physical Therapy on ... Our results suggest that complementing conventional treatment with at-home treatment in which the family is involved maintains better motor function, in ...

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1002/mus.27137

Safety, feasibility, and efficacy of strengthening exercise in ... An in-home, mild–moderate intensity leg exercise program is safe with potential to positively impact both strength and function in ambulatory ...

6. journals.lww.com journals.lww.com/10.1249/01.mss.0000563145.66107.56

Safety And Feasibility Of Strength Training In Patients... CONCLUSION: This in-home, 12-week supervised strength training program was safe, feasible, and improved strength and function in boys with DMD.