Plan forTrial to find Optimum Steroid Regimen in Duchenne Muscular Dystrophy

寻找杜氏肌营养不良症最佳类固醇治疗方案的试验计划

• 批准号: 7114207
• 负责人: Robert C Griggs
• 金额: $ 21.78万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-15 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7114207
• 关键词: child rearing; corticosteroids; parents; satisfaction

DESCRIPTION (provided by applicant): This application proposes to plan a multicenter trial 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 different regimens have been developed because of concerns regarding side effects and long-term risk/benefit, resulting in great inconsistency of practice. Defining the optimum regimen is a stated NIH priority; this proposal has been developed in response to PA-05-038 (Muscular Dystrophy- pathogenesis and therapy). The proposed randomized controlled trial will compare 3 corticosteroid regimens to address the pragmatic hypothesis that daily corticosteroid (prednisone or deflazacort) will be of greater benefit in terms of function and patient/parent satisfaction than intermittent corticosteroid (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 a global test 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) with regard to at least one of the outcomes. We also hypothesize 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, caregiver burden, 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, behavioral, and cushingoid complications of Duchenne dystrophy and corticosteroids. Planning phase activities include establishing data management/communication and patient monitoring strategies; test/retest reliability assessment; preparation of operations manual; translation of assessment tools; confirming the achievability of recruitment targets; and finalizing details of drug distribution and plans for data and safety monitoring. This trial will assess which of the 3 regimens is optimum for treatment of Duchenne dystrophy and provide novel information on longer-term corticosteroid side effects. 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. Lay Summary: This project will plan a study to determine the best dosage and schedule of treatment for use of corticosteroids in Duchenne muscular dystrophy and will help to standardize approaches to prevent complications of Duchenne dystrophy and its corticosteroid treatment.

描述(申请人提供)：本申请计划对患有Duchenne肌营养不良症的男孩进行一项皮质类固醇的多中心试验。皮质类固醇激素泼尼松对Duchenne营养不良患者的体力有18个月的益处，另一种皮质类固醇药物呋喃西林也可能是有益的。出于对副作用和长期风险/益处的担忧，已经开发了许多不同的方案，导致实践中存在极大的不一致。确定最佳方案是美国国立卫生研究院规定的优先事项；这项建议是为了响应PA-05-038(肌营养不良症-发病机制和治疗)而制定的。这项拟议的随机对照试验将对3种皮质类固醇方案进行比较，以解决每日皮质类固醇(泼尼松或呋喃西林)在功能和患者/父母满意度方面比间歇性皮质类固醇(泼尼松)更有益处的实用假设。初步的统计分析将基于多变量(3维)结果(起跳时间、用力肺活量和治疗满意度)和对无效假设的全局检验，即皮质类固醇方案在三种结果中的任何一种与替代方案在至少一种结果上不同(在同一方向上)。我们还假设，与每日服用泼尼松相比，每日服用地塞米松会有更好的副作用。这项试验将随机选择300名4-7岁的男孩，分别服用0.75 mg/kg/d的泼尼松、0.9 mg/kg/d的呋喃西林或0.75 mg/kg/d的泼尼松，为期10天，期间休息10天。次要结果变量将包括方案耐受性、其他计时功能测试、心功能、生活质量、照顾者负担和不良事件概况。参与者将在两年内被招募，并被跟踪至少三年。研究方案包括治疗和预防Duchenne营养不良症和皮质类固醇所致的骨、心脏、行为和库辛戈德并发症的标准化方案。规划阶段的活动包括建立数据管理/通信和病人监测战略；测试/再测试可靠性评估；编写操作手册；翻译评估工具；确认招募目标的实现情况；最后确定药品分配细节以及数据和安全监测计划。这项试验将评估3种方案中哪一种是治疗Duchenne营养不良的最佳方案，并提供有关皮质类固醇长期副作用的新信息。这将为长期(8-10年)研究糖皮质激素方案的相对有效性和耐受性提供依据，主要结果变量为失去下地行走的时间。本项目将计划进行一项研究，以确定使用皮质类固醇治疗Duchenne肌营养不良症的最佳剂量和治疗方案，并将有助于标准化预防Duchenne肌营养不良症并发症及其皮质类固醇治疗的方法。