This application requests continued funding for the data management and biostatistical support for an international multicenter clinical trial comparing three different corticosteroid (CS) regimens for the treatment of Duchenne muscular dystrophy (DMD). This is a companion application to that of Kate Bushby, M.D. from the University of Newcastle (UK) and Robert C. Griggs, M.D. from the University of Rochester (USA) entitled ?FOR-DMD: Double-Blind Randomized Trial to Optimize Steroid Regimens in Duchenne MD.? The primary aim of this project is to conduct an international multicenter, randomized, double-blind, controlled trial in which 225 children with DMD between the ages of 4 and 7 will be randomized to receive either daily prednisone (0.75 mg/kg), daily deflazacort (0.90 mg/kg), or intermittent (10 days on, 10 days off) prednisone (0.75 mg/kg) and followed for a minimum of three years. The primary outcome variable will be three-dimensional and will consist of (1) time to stand from lying (log-transformed), (2) forced vital capacity, and (3) subject/parent global satisfaction with treatment, all averaged over all post-baseline visits during the three-year follow-up period. The trial will address the pragmatic hypothesis that daily prednisone and daily deflazacort will be of greater benefit in terms of function and subject/parent satisfaction than intermittent CS (prednisone) given over a three-year period. Currently, 174 participants (77%) are enrolled in the trial and recruitment is expected to be completed by September 2016.
The specific aims of our application are (1) To provide data management for the trial including: implementation of web-based randomization and enrollment procedures, internet-facilitated entry of all study data into a standardized relational database, training of site personnel in the use of web-based applications for randomization and data entry, generation and resolution of data queries, monitoring of important study events, and maintenance of an appropriately secured and compliant network/database environment; and (2) To provide biostatistical support for the trial including: refinement and implementation of the statistical analysis plan to address the specific aims of the trial; implementation of an interim monitoring plan that will allow modification or termination of the study on the basis of early evidence of safety concerns, in conjunction with the NINDS-appointed Data and Safety Monitoring Board (DSMB); and preparation of open- and closed-session reports for the DSMB.
This trial is specifically designed to address the problems that have been raised as clinically relevant obstacles to establishing standards of practice in Duchenne muscular dystrophy (DMD), namely the lack of guidance on the relative efficacy and risks of different corticosteroid regimens and, in particular, the lack of long-term data. The current trial will generate practical guidance on the use of corticosteroids in DMD for immediate transfer into the clinic.
| 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 |
| Statland, Jeffrey M; Tawil, Rabi (2016) Facioscapulohumeral Muscular Dystrophy. Continuum (Minneap Minn) 22:1916-1931 |
| de Greef, J C; Lemmers, R J L F; Camano, P et al. (2010) Clinical features of facioscapulohumeral muscular dystrophy 2. Neurology 75:1548-54 |
