Weekly Prednisolone for Duchenne Muscular Dystrophy

Recruiting in Palo Alto (17 mi)

+4 other locations

Overseen by Anne Connolly, MD

Age: < 18

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: Anne M. Connolly

Must not be taking: Glucocorticosteroids

Disqualifiers: None

No Placebo Group

Prior Safety Data

Approved in 5 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing if a lower dose of steroids given once a week is as effective as a higher dose for infants and young boys with Duchenne muscular dystrophy. The goal is to see if the lower dose can reduce muscle damage while causing fewer side effects, like weight gain. The study will measure improvements in motor skills over time. Prednisolone has been shown to improve strength in Duchenne dystrophy, but high doses are associated with significant side effects.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have been treated with glucocorticosteroids before joining.

What evidence supports the effectiveness of the drug prednisolone for treating Duchenne Muscular Dystrophy?

Research shows that low-dose prednisolone can have beneficial effects in Duchenne Muscular Dystrophy without significant side effects. Additionally, studies suggest that prednisolone may help preserve muscle function and delay the loss of physical abilities in patients. ^{1 2 3 4 5}

Is weekly prednisolone safe for humans?

Prednisolone, used in treating Duchenne muscular dystrophy, has shown some side effects like increased appetite, weight gain, and irritability, but these are generally manageable with dietary control and monitoring. Long-term studies suggest it is safe with careful use, although more research is needed to fully understand its long-term effects. ^{1 2 5 6 7}

How does the drug prednisolone differ from other treatments for Duchenne Muscular Dystrophy?

Prednisolone is unique because it is used in low-dose, intermittent schedules, such as weekly or monthly cycles, which can help preserve muscle function with fewer side effects compared to continuous use. This approach is different from other treatments that may not use such specific dosing schedules. ^{1 2 3 4 8}

Research Team

Anne Connolly, MD

Principal Investigator

Nationwide Children's Hospital

Eligibility Criteria

This trial is for young children from 1 month to 30 months old who show signs of Duchenne Muscular Dystrophy (DMD) on physical exams, have high levels of an enzyme called creatine kinase in their blood, and a genetic mutation known to cause DMD. Children previously treated with glucocorticosteroids can't participate.

Inclusion Criteria

I am between 1 month and 30 months old.

I have Duchenne muscular dystrophy with high creatine kinase levels and a confirmed genetic mutation.

Exclusion Criteria

I have been treated with steroids before.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 5mg/kg/week of prednisolone to assess efficacy and side effects

24 months

Regular visits for assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Prednisolone (Corticosteroid)

Trial Overview The study is testing if a lower weekly dose of the corticosteroid Prednisolone (5mg/kg) is as effective as the standard higher dose (10mg/kg) for treating symptoms of Duchenne Muscular Dystrophy in infants.

Participant Groups

Group I: Experimental Experimental Treatment 1 Intervention

This is a one-arm study and the group of subjects are all experimental and will receive drug.

Prednisolone is already approved in Canada, Japan for the following indications:

Approved in Canada as Prednisolone for:

• Asthma
• Rheumatoid arthritis
• Crohn's disease
• Ulcerative colitis
• Multiple sclerosis
• Polymyalgia rheumatica
• Giant cell arteritis

Approved in Japan as Prednisolone for:

• Asthma
• Rheumatoid arthritis
• Crohn's disease
• Ulcerative colitis
• Multiple sclerosis
• Polymyalgia rheumatica
• Giant cell arteritis

Who Is Running the Clinical Trial?

Anne M. Connolly

Lead Sponsor

Trials

1

Recruited

30+

Muscular Dystrophy Association

Collaborator

Trials

38

Recruited

60,800+

University of Texas

Collaborator

Trials

193

Recruited

143,000+

Dr. Olukotun

University of Texas

Chief Medical Officer since 2020

MD from Albert Einstein College of Medicine

Dr. Jacqualyn A. Fouse

University of Texas

Chief Executive Officer since 2019

Ph.D. in Finance from the University of Texas at Arlington

Virginia Commonwealth University

Collaborator

Trials

732

Recruited

22,900,000+

Arturo Saavedra

Virginia Commonwealth University

Chief Medical Officer since 2022

MD, University of Texas Southwestern Medical School

Michael Rao

Virginia Commonwealth University

Chief Executive Officer since 2009

Ph.D. in Education Administration

Children's Hospital Medical Center, Cincinnati

Collaborator

Trials

844

Recruited

6,566,000+

Steve Davis

Children's Hospital Medical Center, Cincinnati

Chief Executive Officer since 2021

MD

Daniel Ostlie

Children's Hospital Medical Center, Cincinnati

Chief Medical Officer

MD from University of North Dakota

Ann & Robert H Lurie Children's Hospital of Chicago

Collaborator

Trials

275

Recruited

5,182,000+

Dr. Michael D. Kelleher

Ann & Robert H Lurie Children's Hospital of Chicago

Chief Medical Officer since 2012

MD from University of Chicago

Dr. Thomas Shanley

Ann & Robert H Lurie Children's Hospital of Chicago

Chief Executive Officer since 2019

MD from University of Chicago Pritzker School of Medicine

Findings from Research

A special program involving low-dose prednisolone (0.5 mg/kg per day, effectively 0.25 mg/kg daily due to alternate day dosing) was tested in a randomized double-blind trial with 50 patients suffering from Duchenne-Becker muscular dystrophy.

Preliminary results indicate beneficial effects from the treatment without significant side effects, suggesting that this low-dose regimen may be a safe and effective option for managing the condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The use of low doses of prednisolone for the treatment of patients with Duchenne-Becker myodystrophy]. Shakhovskaia, NI., Shishkin, SS., Skozobtseva, LF., et al.[2016]

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 5-year follow-up of two boys with Duchenne muscular dystrophy showed a remarkable response to a low-dosage, intermittent regimen of prednisolone, with one boy achieving complete remission of symptoms and the other maintaining significant improvement for nearly 5 years.

The treatment was well tolerated, with no signs of chronic prednisolone toxicity or bone demineralization, suggesting that this approach could be safe for long-term use in young children with the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Remission of clinical signs in early duchenne muscular dystrophy on intermittent low-dosage prednisolone therapy. Dubowitz, V., Kinali, M., Main, M., et al.[2019]

In a meta-analysis of clinical trials involving patients with nonsense mutation Duchenne muscular dystrophy, deflazacort showed significant improvements in physical function compared to prednisone/prednisolone, particularly in the 6-minute walk distance (6MWD) with a mean difference of 39.54 meters.

Deflazacort also demonstrated clinically meaningful enhancements in timed function tests, such as the 4-stair climb and descend, indicating its effectiveness in delaying the loss of physical milestones over 48 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meta-analyses of deflazacort versus prednisone/prednisolone in patients with nonsense mutation Duchenne muscular dystrophy. Shieh, PB., Elfring, G., Trifillis, P., et al.[2022]

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]

Deflazacort has been shown to significantly benefit boys with Duchenne muscular dystrophy by prolonging ambulation, preserving cardiac and respiratory function, reducing scoliosis, and improving overall survival, based on long-term data from two Canadian centers.

While effective, common side effects of deflazacort treatment include weight gain, decreased height, and cataract formation, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Canadian experience with long-term deflazacort treatment in Duchenne muscular dystrophy. McAdam, LC., Mayo, AL., Alman, BA., et al.[2021]

References

1. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[The use of low doses of prednisolone for the treatment of patients with Duchenne-Becker myodystrophy]. [2016]

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

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

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

Preserving function in Duchenne dystrophy with long-term pulse prednisone therapy. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Remission of clinical signs in early duchenne muscular dystrophy on intermittent low-dosage prednisolone therapy. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Meta-analyses of deflazacort versus prednisone/prednisolone in patients with nonsense mutation Duchenne muscular dystrophy. [2022]

6. England pubmed.ncbi.nlm.nih.gov

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

7. Italy pubmed.ncbi.nlm.nih.gov

The Canadian experience with long-term deflazacort treatment in Duchenne muscular dystrophy. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Low-dose prednisolone treatment in Duchenne and Becker muscular dystrophy. [2019]