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（由申请人提供）： 本申请建议计划在Duchenne型肌营养不良症男孩中进行皮质类固醇多中心试验。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，已经开发了许多不同的方案，导致实践的极大不一致。确定最佳方案是NIH的优先事项;该建议是根据PA-05-038（肌营养不良-发病机制和治疗）制定的。拟定的随机对照试验将比较3种糖皮质激素治疗方案，以解决以下实用假设：每日糖皮质激素（泼尼松或地夫可特）在功能和患者/家长满意度方面的获益大于间歇性糖皮质激素（泼尼松）。主要统计分析将基于多变量（三维）结果（从地板上站起来的时间、用力肺活量和治疗满意度）和零假设的全局检验，即皮质类固醇方案在三种结果中的任何一种方面都没有差异，而替代方案是它们在至少一种结果方面存在差异（方向相同）。我们还假设每日地夫可特的副作用优于每日泼尼松。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、护理人员负担和不良事件特征。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、行为和库欣样并发症的标准化方案。计划阶段的活动包括建立数据管理/沟通和患者监测策略;测试/重新测试可靠性评估;编写操作手册;翻译评估工具;确认招募目标的可接受性;以及最终确定药物分发的细节以及数据和安全性监测计划。本试验将评估3种方案中哪一种是治疗杜氏营养不良的最佳方案，并提供有关长期皮质类固醇副作用的新信息。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。概述：该项目将计划进行一项研究，以确定使用皮质类固醇治疗杜氏肌营养不良症的最佳剂量和治疗时间表，并将有助于标准化方法，以预防杜氏肌营养不良症及其皮质类固醇治疗的并发症。