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长期皮质类固醇治疗方案。皮质类固醇泼尼松已被证实可在 18 个月内对杜氏营养不良症患者的力量有益，另一种皮质类固醇地夫可特也可能有益。由于担心副作用和长期风险/效益，许多皮质类固醇治疗方案已被使用，导致实践中存在很大差异。鉴于“2008年比较有效性研究法案”的出台，这项研究显得尤为及时。拟议的随机对照试验将比较 3 种最广泛使用的皮质类固醇治疗方案，以解决以下实用假设：每日泼尼松和每日地夫可特在功能和家长满意度方面比间歇性（泼尼松）具有更大的益处。主要统计分析将基于多变量（3 维）结果（从地板上起身的时间、用力肺活量和治疗满意度）以及对原假设的全局测试，即皮质类固醇治疗方案在三个结果中的任何一个上都没有差异，而替代方案则在所有 3 个结果变量上都存在差异（方向相同），对三个结果变量中的三个成对比较中的每一个分别进行 皮质类固醇治疗方案。第二个假设指出，每日服用地夫可特比每日服用泼尼松具有更好的副作用。该试验将随机将 300 名 4-7 岁男孩随机分组，接受 0.75 毫克/公斤/天的泼尼松治疗； 0.9毫克/公斤/天地夫可特；或 0.75 mg/kg/d 泼尼松，连续 10 天，间歇 10 天。次要结果变量将包括方案耐受性、其他定时功能测试；心脏功能、生活质量和不良事件概况。参与者将在 2 年的时间内招募并跟踪至少 3 年。该研究方案包括治疗和预防杜氏营养不良的骨骼、心脏、呼吸、行为和库欣样并发症和皮质类固醇的标准化方案。该试验将通过评估患者/家长对治疗的满意度对肌肉力量的益处，来评估 3 种治疗方案中哪一种最适合治疗杜氏营养不良。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以及主要结果变量即丧失行走能力的时间提供基础。辅助研究将探讨研究对象不同表型和对皮质类固醇治疗反应的分子基础。 公共健康相关性：该项目将找到治疗患有杜氏肌营养不良症（最常见的肌营养不良症和最常见的儿童神经肌肉疾病）男孩的最佳皮质类固醇治疗方案。该试验的信息对于所有治疗儿童的医疗保健提供者都很重要，并且对于正在探索杜氏肌营养不良症的其他新疗法至关重要。