FOR-DMD:Double-blind randomized trial to optimize steroid regimen in Duchenne MD

FOR-DMD：优化 Duchenne MD 类固醇治疗方案的双盲随机试验

• 批准号: 8100212
• 负责人: Katherine Mary Dympna Bushby
• 金额: $ 150万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8100212
• 关键词: 3-Dimensional; Address; Adrenal Cortex Hormones; Adverse effects; Adverse event; Alternative Therapies; Ancillary Study; Award; Behavioral; Benefits and Risks; Cardiac; Caring; Child; Childhood; Client satisfaction; Clinical; Clinical Trials Design; Clinical Trials Unit; Clinical effectiveness; Collaborations; Cushingoid habitus; Data; Double-Blind Method; Duchenne muscular dystrophy; Educational workshop; Enrollment; Floor; Follow-Up Studies; Funding; Future; Generations; Goals; Grant; Health Personnel; International; Measures; Molecular; Multicenter Trials; Muscular Dystrophies; Netherlands; Neuromuscular Diseases; Outcome; Parents; Participant; Pathogenesis; Patients; Pharmaceutical Preparations; Phenotype; Predisposition; Prednisone; Prevention; Principal Investigator; Protocols documentation; Publishing; Quality of life; Randomized; Randomized Controlled Trials; Recruitment Activity; Regimen; Relative (related person); Research Personnel; Steroids; Study Subject; Testing; Time; Treatment Protocols; United States National Institutes of Health; Universities; Variant; Vital capacity; Work; aged; base; bone; boys; burden of illness; clinical practice; comparative effectiveness; comparative efficacy; deflazacort; dosage; effectiveness research; evidence base; evidence based guidelines; follow-up; genetic profiling; muscle strength; novel; primary outcome; professor; protein profiling; public health relevance; randomized trial; respiratory; response; satisfaction; secondary outcome; standard of care; treatment strategy; trial comparing

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：本申请提出了一项多中心试验，比较患有杜氏肌营养不良症的男孩的皮质类固醇长期治疗方案。皮质类固醇泼尼松在杜氏营养不良中具有18个月的优势，另一种皮质类固醇地夫可特也可能有益。由于对副作用和长期风险/获益的担忧，许多皮质类固醇方案已在使用中，导致实践中存在很大差异。鉴于《2008年比较效力研究法》，这项研究特别及时。拟定的随机对照试验将比较3种最广泛使用的皮质类固醇方案，以解决实用假设，即每日泼尼松和每日地夫可特在功能和父母满意度方面的获益大于间歇性（泼尼松）。主要统计分析将基于多变量（三维）结局（从地板上起身的时间、用力肺活量和治疗满意度）和零假设的总体检验，即皮质类固醇方案在三种结局中的任何一种方面均无差异，而替代方案则不同（在相同的方向上）对于所有3个结果变量，分别对三种皮质类固醇方案之间的三个成对比较中的每一个进行比较。次要假设指出，每日地夫可特的副作用特征优于每日泼尼松。该试验将300名4-7岁的男孩随机分配至0.75 mg/kg/d泼尼松; 0.9 mg/kg/d地夫可特;或0.75 mg/kg/d泼尼松10天，交替休息10天。次要结局变量将包括方案耐受性、其他定时功能检查、心脏功能、生活质量和不良事件特征。参与者将在2年内招募，并随访至少3年。研究方案包括治疗和预防杜氏营养不良和皮质类固醇的骨、心脏、呼吸、行为和库欣样并发症的标准化方案。本试验将通过在患者/父母对治疗满意度的背景下评估肌力获益，评估3种方案中哪一种是治疗杜氏营养不良的最佳方案。它将为长期（8-10年）研究皮质类固醇治疗方案的相对疗效和耐受性提供基础，主要结局变量为至停用阿托伐他汀的时间。辅助研究将探索研究受试者中不同表型和对皮质类固醇治疗反应的分子基础。 公共卫生相关性：这个项目将找到最佳的皮质类固醇治疗方案的男孩与杜氏肌营养不良症-最常见的形式的肌营养不良症和最常见的儿童神经肌肉疾病。这项试验的信息对所有治疗儿童的医疗保健提供者都很重要，对杜氏肌营养不良症的其他新治疗方法也很重要。