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.
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.24689
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.15101112
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.12379
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.
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 was able to walk on my own during my first visit.
I have not received any gastric cancer treatment before.
Exclusion Criteria
I do not have unstable health issues like heart problems.
I have a condition that affects my muscle function or metabolism.
I have a condition that affects my development or movement.
I have a health condition that changes rapidly.
Treatment Details
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.
3Treatment groups
Active Control
Group I: Daily Glucocorticoid (GC)Active Control1 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 exerciseActive Control1 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 exerciseActive Control3 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
Find a clinic near you
Research locations nearbySelect from list below to view details:
University of FloridaGainesville, FL
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Who is running the clinical trial?
University of FloridaLead Sponsor
U.S. Army Medical Research and Development CommandCollaborator
References
Steroids in Duchenne muscular dystrophy--deflazacort trial. [2019]We conducted a double blind controlled trial in 28 Duchenne muscular dystrophy (DMD) patients with Deflazacort (DF), an oxazoline derivative of prednisolone which reduces its side-effects. Myometric muscle strength measurements, Scott Score and timed tests showed statistically significant improvement for the treated group (P less than 0.05). Side-effects after 9 months of treatment included mild cushingoid appearance in four patients (28%) and moderate in only one (7%), increased appetite in seven (50%), increased body hair in four (28%), irritability and hyperactivity in three (21%). Increased body weight was not prominent and was controlled with dietary measures. No patient had to be withdrawn from medication. More research and long-term follow-up are needed in order to establish the mechanism of improvement and the consequences of long-term steroid administration in DMD. In this regard DF appears as an alternative to prednisone preserving its benefits but with fewer side-effects.
Prednisone in Duchenne dystrophy. A randomized, controlled trial defining the time course and dose response. Clinical Investigation of Duchenne Dystrophy Group. [2019]A randomized, controlled trial of daily prednisone was conducted in 99 boys (aged 5 to 15 years) with Duchenne dystrophy to define the time course of improvement and the dose response to treatment. Prednisone at 0.3 mg/kg (n = 33), prednisone at 0.75 mg/kg (n = 34), and placebo (n = 32) were administered for 6 months. Patients were examined using manual muscle and myometry testing, timed functional testing, pulmonary function testing, and laboratory measurements at 10 days, 1 month, 2 months, 3 months, and 6 months of treatment. Boys treated with prednisone had stronger average muscle strength scores, than did boys treated with placebo as early as 10 days after starting therapy. At the 3-month visit, the boys in the group given 0.75 mg/kg of prednisone were significantly stronger than those in the group given 0.3 mg/kg of prednisone, indicating a dose response. At 6 months, significant side effects occurred in the group treated with 0.75 mg/kg of prednisone, including weight gain, cushingoid appearance, and excessive hari growth. Only weight gain was observed in the group taking prednisone at a dose of 0.3 mg/kg. Importantly, no side effects were evident at 10 days or 1 month of treatment, despite improvement in muscle strength and function. We conclude that prednisone produces a rapid increase in muscle strength in patients with Duchenne dystrophy and that this improvement is maximal at a prednisone dosage of 0.75 mg/kg or less.
Randomized, double-blind six-month trial of prednisone in Duchenne's muscular dystrophy. [2022]We performed a randomized, double-blind, controlled six-month trial of prednisone in 103 boys with Duchenne's muscular dystrophy (age, 5 to 15 years). The patients were assigned to one of three regimens: prednisone, 0.75 mg per kilogram of body weight per day (n = 33); prednisone, 1.5 mg per kilogram per day (n = 34); or placebo (n = 36). The groups were initially comparable in all measures of muscle function. Both prednisone groups had significant improvement of similar degree in the summary scores of muscle strength and function. Improvement began as early as one month and peaked by three months. At six months the high-dose prednisone group, as compared with the placebo group, had improvement in the time needed to rise from a supine to a standing position (3.4 vs. 6.2 seconds), to walk 9 m (7.0 vs. 9.7 seconds), and to climb four stairs (4.0 vs. 7.1 seconds), in lifting a weight (2.1 vs. 1.2 kg), and in forced vital capacity (1.7 vs. 1.5 liters) (P less than 0.001 for all comparisons). There was an increase in urinary creatinine excretion (261 vs. 190 mg per 24 hours), which suggested an increase in total muscle mass. However, the prednisone-treated patients who had required long-leg braces (n = 5) or wheelchairs (n = 11) continued to require them. The most frequent side effects were weight gain, cushingoid appearance, and excessive hair growth. We conclude from this six-month study that prednisone improves the strength and function of patients with Duchenne's muscular dystrophy. However, further research is required to identify the mechanisms responsible for these improvements and to determine whether prolonged treatment with corticosteroids may be warranted despite their side effects.
Duchenne dystrophy: randomized, controlled trial of prednisone (18 months) and azathioprine (12 months) [2019]Prednisone has been shown to improve strength in Duchenne dystrophy. Azathioprine often benefits corticosteroid-responsive diseases and can reduce the dose of prednisone needed. The present study reports a randomized, controlled trial of prednisone and azathioprine designed to assess the longer-term effects of prednisone and to determine whether azathioprine alone, or in combination with prednisone, improves strength. Ninety-nine boys (aged five to 15 years) with Duchenne dystrophy were randomized to one of three groups: (I) placebo; (II) prednisone 0.3 mg/kg/d; or (III) prednisone 0.75 mg/kg/d. After 6 months, azathioprine 2 to 2.5 mg/kg/d was added in groups I and II and placebo added in group III. The study showed that the beneficial effect of prednisone (0.75 mg/kg/d) is maintained for at least 18 months and is associated with a 36% increase in muscle mass. There was weight gain, growth retardation, and other side effects. Azathioprine did not have a beneficial effect. This study suggests that prednisone's beneficial effect is not due to immunosuppression.
Deflazacort treatment of Duchenne muscular dystrophy. [2014]We report the long-term effects on muscle strength and side effects with deflazacort in Duchenne muscular dystrophy (DMD).
Corticosteroids in Duchenne muscular dystrophy: a reappraisal. [2017]Duchenne muscular dystrophy is the most common and most severe form of childhood muscular dystrophies, resulting in early loss of ambulation between the ages of 7 and 13 years and death in the teens and twenties. Despite the phenomenal advances made in the understanding of the molecular genetics of the disease, no definitive cure has been found. Of all of the therapeutic drugs studied in Duchenne muscular dystrophy, only prednisone seems to have the potential for providing interim functional improvement for boys with Duchenne muscular dystrophy while they wait for a cure with gene or cell therapy. There is still no consensus regarding recommending corticosteroids as standard therapy for boys. This is an evidence-based review of all of the studies of corticosteroids (prednisone, deflazacort, and oxandrolone) in Duchenne muscular dystrophy. From this review, it is clear that until a definitive treatment for Duchenne muscular dystrophy is available, the use of deflazacort and prednisone with judicious dietary control and close clinical monitoring for side effects seems the best intervention for interim preservation of function in such a common devastating disorder of young growing boys.
[Effects of corticosteroids in the management of Duchenne muscular dystrophy: our experience]. [2018]Objective To evaluate the clinical course in patients with Duchenne muscular dystrophy admitted to our department who received corticosteroid treatment and to compare their course with that in patients who did not receive corticosteroid treatment.Patients and methodsWe performed a retrospective study of 20 pediatric patients with a diagnosis of Duchenne muscular dystrophy who were offered corticosteroid treatment: 10 patients received deflazacort and 10 refused the treatment. The MRC muscular strength scale and Vignos' functional scale were used to evaluate clinical course, which was compared in both groups.ResultsUntreated patients showed progressive worsening. Corticosteroid-treated patients showed disease stabilization both in muscular strength and functional performance. In addition, muscular balance improved in 70 % of these patients, but only 2 % showed functional improvement. The positive effect of steroid treatment had a mean duration of 12 months. Loss of independent gait occurred at similar ages in both groups (10.3 vs. 10.5 years). The results of Achilles' tendon surgery were poor.ConclusionsCorticosteroids produced clinical stabilization and improved muscular strength. Functional improvement was not significant, including loss of gait, probably because this loss also depends on an increase in joint contracture. Good coordination among multiprofessional teams is essential to achieve optimal results.
The role of corticosteroids in muscular dystrophy: a critical appraisal. [2022]Over the years various steroid trials have been conducted in Duchenne muscular dystrophy (DMD). In children who are still able to walk as well as in those who are wheelchair-bound, corticosteroids have been found to stabilize muscle strength for a period of time. Controlled clinical observations have shown that some boys remain ambulatory for years longer than reported in natural history data. The two main steroids used are prednisone/prednisolone and deflazacort. They are probably equally effective in stabilizing muscle strength but may have different side-effect profiles; for instance, deflazacort causes less weight gain. The exact mechanism by which steroids slow the dystrophic process is under investigation. DMD children treated long term also seem to develop other complications of the condition less frequently. For instance, they develop respiratory insufficiency later and have fewer cardiac symptoms. The therapeutic value of corticosteroids is limited, but these drugs represent the best treatment option currently available.
Change in natural history of Duchenne muscular dystrophy with long-term corticosteroid treatment: implications for management. [2022]In 2005, the American Academy of Neurology and the Child Neurology Society published a practice parameter, based primarily on studies that involved 6 to 18 months of treatment, indicating that prednisone has a beneficial effect on muscle strength and function in patients with Duchenne muscular dystrophy and recommended that corticosteroids be offered (prednisone 0.75 mg/kg/d and deflazacort 0.9 mg/kg/d) as treatment. Recent reports emphasize that longer term treatment with corticosteroids (greater than 3 years) produces important sustained benefits in neuromuscular function without causing major side effects. This review highlights these reports and indicates that long-term corticosteroid therapy (1) prolongs ambulation by 2 to 5 years, (2) reduces the need for spinal stabilization surgery, (3) improves cardiopulmonary function, (4) delays the need for noninvasive nasal ventilation, and (5) increases survival and the quality of life of patients with Duchenne muscular dystrophy. Educational, vocational, and other social counseling is now a vital part of management for Duchenne muscular dystrophy.
Developing standardized corticosteroid treatment for Duchenne muscular dystrophy. [2018]Despite corticosteroids being the only treatment documented to improve strength and function in boys with Duchenne muscular dystrophy (DMD) corticosteroid prescription is inconsistent and in some countries, corticosteroids are not prescribed. We are conducting a clinical trial that (1) compares the 3 most frequently prescribed corticosteroid regimes; (2) standardizes treatment of DMD complications; and (3) standardizes prevention of corticosteroid side effects. Investigators at 38 sites in 5 countries plan to recruit 300 boys aged 4-7 who are randomly assigned to one of three regimens: daily prednisone; daily deflazacort; or intermittent prednisone (10days on/10days off). Boys are followed for a minimum of 3years to assess the relative effectiveness and adverse event profiles of the different regimens. The primary outcome is a 3-dimensional variable consisting of log-transformed time to rise from the floor, forced vital capacity, and subject/parent satisfaction with treatment, each averaged over all post-baseline visits. The study protocol includes evidence- and consensus-based treatment of DMD complications and of corticosteroid side effects. This study seeks to establish a standard corticosteroid regimen for DMD. Since all new interventions for DMD are being developed as add-on therapies to corticosteroids, defining the optimum regimen is of importance for all new treatments.
Safety and clinical outcome of tamoxifen in Duchenne muscular dystrophy. [2022]Patients having Duchenne muscular dystrophy (DMD) are currently being treated with corticosteroids, which slow down disease progression at the expense of serious adverse effects. Tamoxifen is a pro-drug some of whose metabolites interact with the nuclear estrogen receptor, leading to anti-fibrotic and muscle-protective effects as has been demonstrated in a murine model of DMD. Here we report the results from a monocentric single arm prospective study in 13 ambulant boys aged 6-14 years with genetically confirmed DMD, aimed to assess the safety of tamoxifen and its impact on disease progression. Boys were treated for up to 3 years with 20 mg/day of oral tamoxifen, in addition to their ongoing corticosteroid treatment. For 8 of these patients, outcome was compared to an age- and performance-matched 12-month natural history dataset. The primary end point was the 6-minute walk test. Secondary end points were the NorthStar assessment, timed function tests, pulmonary function, the biomarker creatine phosphokinase and adverse effects. No adverse effects were noticed other than mild gynecomastia in 4 boys. Tamoxifen-treated patients retained motor and respiratory function, compared with a significant deterioration of age-matched historical control patients receiving corticosteroids only. These encouraging findings warrant a larger clinical trial to substantiate the use of tamoxifen in Duchenne muscular dystrophy.
Comparing Deflazacort and Prednisone in Duchenne Muscular Dystrophy. [2022]Deflazacort and prednisone/prednisolone are the current standard of care for patients with Duchenne muscular dystrophy (DMD) based on evidence that they improve muscle strength, improve timed motor function, delay loss of ambulation, improve pulmonary function, reduce the need for scoliosis surgery, delay onset of cardiomyopathy, and increase survival. Both have been used off-label for many years (choice dependent on patient preference, cost, and geographic location) before FDA approval of deflazacort for DMD in 2017. In this review, we compare deflazacort and prednisone/prednisolone in terms of their key pharmacological features, relative efficacy, and safety profiles in patients with DMD. Differentiating features include lipid solubility, pharmacokinetics, changes in gene expression profiles, affinity for the mineralocorticoid receptor, and impact on glucose metabolism. Evidence from randomized clinical trials, prospective studies, meta-analyses, and post-hoc analyses suggests that patients receiving deflazacort experience similar or slower rates of functional decline compared with those receiving prednisone/prednisolone. Regarding side effects, weight gain and behavior side effects appear to be greater with prednisone/prednisolone than with deflazacort, whereas bone health, growth parameters, and cataracts appear worse with deflazacort.