This application proposes a multicenter trial comparing long-term regimens of corticosteroids in boys with Duchenne muscular dystrophy. The corticosteroid prednisone is of established 18 months benefit to strength in Duchenne dystrophy, and another corticosteroid, deflazacort, may also be of benefit. Many corticosteroid regimens have been in use because of concerns regarding side effects and long-term risk/benefit, resulting in great variations in practice. The study is particularly timely in view of the """"""""Comparative Effectiveness Research Act of 2008"""""""". The proposed randomized controlled trial will compare the 3 most widely used corticosteroid regimens to address the pragmatic hypothesis that both daily prednisone and daily deflazacort will be of greater benefit in terms of function and parent satisfaction than intermittent (prednisone). The primary statistical analysis will be based on a multivariate (3-dimensional) outcome (time to rise from the floor, forced vital capacity, and treatment satisfaction) and global tests of the null hypothesis that the corticosteroid regimens do not differ with regard to any of the three outcomes vs the alternative that they differ (in the same direction) for all 3 outcome variables, performed separately for each of the three pair-wise comparisons among the three corticosteroid regimens. A secondary hypothesis states that daily deflazacort will have a preferable side effect profile to that of daily prednisone. The trial will randomize 300 boys aged 4-7 years to 0.75 mg/kg/d prednisone;0.9 mg/kg/d deflazacort;or 0.75 mg/kg/d prednisone for 10 days alternating with 10 days off. Secondary outcome variables will include regimen tolerance, other timed function tests;cardiac function, quality of life, and adverse event profile. Participants will be recruited over a 2 year period and followed for at least 3 years. The study protocol includes standardized regimens for treatment and prevention of bone, cardiac, respiratory, behavioral, and cushingoid complications of Duchenne dystrophy and corticosteroids. This trial will assess which of the 3 regimens is optimum for treatment of Duchenne dystrophy by assessing benefits to muscle strength in the context of patient/parent satisfaction with treatment. It will provide the basis for the long-term (8-10 year) study of the relative efficacy and tolerability of corticosteroid regimens with the primary outcome variable of time to loss of ambulation. Ancillary studies will explore the molecular basis for differing phenotypes and responses to corticosteroid treatment in study subjects.

Public Health Relevance

This project will find the optimum corticosteroid regimen for treatment of boys with Duchenne muscular dystrophy --- the commonest form of muscular dystrophy and the commonest childhood neuromuscular disease. Information from this trial will be of importance to all health care providers treating children and is essential for other novel treatments being explored in Duchenne muscular dystrophy.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project--Cooperative Agreements (U01)
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National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
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Cordell, Janice
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University of Rochester
Schools of Dentistry
United States
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Crow, Rebecca A; Hart, Kimberly A; McDermott, Michael P et al. (2018) A checklist for clinical trials in rare disease: obstacles and anticipatory actions-lessons learned from the FOR-DMD trial. Trials 19:291
Guglieri, Michela; Bushby, Kate; McDermott, Michael P et al. (2017) Developing standardized corticosteroid treatment for Duchenne muscular dystrophy. Contemp Clin Trials 58:34-39
Ke, Qing; Zhang, Li; He, Chaying et al. (2016) China's shift from population control to population quality: Implications for neurology. Neurology 87:e85-8
Hoffman, Eric P; Reeves, Erica; Damsker, Jesse et al. (2012) Novel approaches to corticosteroid treatment in Duchenne muscular dystrophy. Phys Med Rehabil Clin N Am 23:821-8