Steroids + Exercise for Duchenne Muscular Dystrophy

Recruiting in Palo Alto (17 mi)

Overseen by Tanja Taivassalo, MD

Age: < 18

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: University of Florida

No Placebo Group

Prior Safety Data

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing if giving a smaller amount of medication less frequently, along with exercise, can help boys with a muscle condition. The current frequent treatment has bad side effects, but this new method might work just as well without them. The medication has been shown to improve muscle strength in boys with this condition, but its frequent use is associated with significant side effects.

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.

What data supports the idea that Steroids + Exercise for Duchenne Muscular Dystrophy is an effective treatment?

The available research shows that using steroids like prednisone and deflazacort in combination with exercise can improve muscle strength and function in patients with Duchenne Muscular Dystrophy. For example, one study found that boys treated with prednisone showed significant improvements in muscle strength and function within just one month, and these improvements peaked by three months. Another study highlighted that long-term use of corticosteroids can prolong the ability to walk by 2 to 5 years and improve heart and lung function. While there are side effects like weight gain and increased body hair, the benefits in muscle strength and quality of life are significant. Compared to no treatment, steroids help stabilize the condition and improve muscle strength, even if they don't significantly improve overall function. ^{1 2 3 4 5}

What safety data exists for steroids and exercise in treating Duchenne Muscular Dystrophy?

Several studies have evaluated the safety of corticosteroids like prednisone and deflazacort in treating Duchenne Muscular Dystrophy (DMD). A trial with deflazacort showed improvements in muscle strength with side effects such as mild to moderate cushingoid appearance, increased appetite, body hair, irritability, and hyperactivity. Another study compared deflazacort and prednisone, noting that weight gain and behavioral side effects were more common with prednisone, while deflazacort had worse effects on bone health, growth, and cataracts. A large trial is also underway to standardize corticosteroid regimens and assess their safety profiles. Overall, while corticosteroids improve muscle function, they come with significant side effects that need careful management. ^{1 6 7 8 9}

Is the drug Prednisone a promising treatment for Duchenne Muscular Dystrophy?

Yes, Prednisone is a promising drug for Duchenne Muscular Dystrophy. It improves muscle strength and function, helps patients walk longer, reduces the need for surgeries, and enhances heart and lung health. It also increases survival and quality of life. ^{4 5 10 11 12}

Research Team

Tanja Taivassalo, MD

Principal Investigator

University of Florida

Eligibility Criteria

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.

Treatment Details

Interventions

• In-home Exercise Training (Behavioural Intervention)
• Prednisone (Corticosteroid)

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.

Participant Groups

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 Canada for the following indications:

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+

Dr. Stephen J. Motew

University of Florida

Chief Executive Officer since 2024

MD cum laude from the University of Illinois at Chicago School of Medicine, Master's in Healthcare Administration from the University of North Carolina at Chapel Hill

Dr. Timothy E. Morey

University of Florida

Chief Medical Officer since 2023

MD and Bachelor's from the University of Florida

U.S. Army Medical Research and Development Command

Collaborator

Trials

296

Recruited

249,000+

Findings from Research

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]

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]

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]

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]

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]

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 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 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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Steroids in Duchenne muscular dystrophy--deflazacort trial. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Randomized, double-blind six-month trial of prednisone in Duchenne's muscular dystrophy. [2022]

3. Spain pubmed.ncbi.nlm.nih.gov

[Effects of corticosteroids in the management of Duchenne muscular dystrophy: our experience]. [2018]

4. United States 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. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Change in natural history of Duchenne muscular dystrophy with long-term corticosteroid treatment: implications for management. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Deflazacort treatment of Duchenne muscular dystrophy. [2014]

7. United States pubmed.ncbi.nlm.nih.gov

Developing standardized corticosteroid treatment for Duchenne muscular dystrophy. [2018]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Comparing Deflazacort and Prednisone in Duchenne Muscular Dystrophy. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Safety and clinical outcome of tamoxifen in Duchenne muscular dystrophy. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Duchenne dystrophy: randomized, controlled trial of prednisone (18 months) and azathioprine (12 months) [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Corticosteroids in Duchenne muscular dystrophy: a reappraisal. [2017]

12. United States pubmed.ncbi.nlm.nih.gov

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