Development of a Strength Training Protocol in Duchenne Muscular Dystrophy

杜氏肌营养不良症力量训练方案的制定

• 批准号: 8771672
• 负责人: Donovan J Lott
• 金额: $ 19.8万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-19 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8771672
• 关键词: 9 year old; Address; Analog Pain Scale; Area; Becker Muscular Dystrophy; Cessation of life; Child; Clinical; Consent; Creatine Kinase; Data; Development; Dose; Duchenne muscular dystrophy; Dystrophin; Exercise; Flexor; Goals; Guidelines; Heart Rate; Home environment; Human; Intervention; Intervention Studies; Investigation; Isometric Contraction; Isometric Exercise; Joints; Knee; Link; Literature; Magnetic Resonance Imaging; Maintenance; Measures; Monitor; Muscle; Muscle Weakness; Muscle function; Muscular Dystrophies; Neuromuscular Diseases; Outcome Measure; Output; Parents; Patients; Physical activity; Pilot Projects; Protocols documentation; Public Health; Recommendation; Recreation; Recruitment Activity; Research; Resistance; Rodent Model; Safety; Self-Help Devices; Serum; Staging; Structural Protein; Swimming; Testing; Therapeutic; Thigh structure; Time; Torque; Training; Variant; Visual Analogue Pain Scale; Walking; Weight; Work; base; boys; clinical practice; design; experience; human subject; innovation; muscle form; muscular dystrophy mouse model; patient population; programs; public health relevance; research clinical testing; response; strength training; time interval; wasting

DESCRIPTION (provided by applicant): Duchenne muscular dystrophy (DMD) is a debilitating neuromuscular disease that causes muscle breakdown, weakness, and eventual death. Over the last 40 years parents have received little guidance on the potential of exercise as a therapeutic strategy to maintain muscle function. It is well known that high intensity exercise and eccentric contractions can result in muscle damage in dystrophic muscle, yet the absence of muscle loading will conversely result in muscle wasting. Recent research in rodent models and milder forms of muscular dystrophy supports earlier studies that resistance exercise may have beneficial effects for maintenance of muscle mass in dystrophic muscle. However, careful and systematic investigation into the safety and feasibility of resistance exercise is needed to consider its implementation in boys with DMD. The overall objective of this pilot study is to assess whether a mild to moderate-intensity strengthening exercise program can be safely implemented in boys with DMD. In Aim 1 we will determine the dose response and safety of mild to moderate-intensity isometric resistance exercise in children with DMD. Twelve ambulatory boys with DMD will participate in an isometric exercise dosing protocol, in which the load is progressively increased. In this early proof of concept pilot study, two large muscle groups will be studied: the knee extensors and the knee flexors. T2 weighted magnetic resonance imaging (MRI) of the thigh muscles will be used to monitor evidence of muscle damage at each intensity level and determine a safe exercise range. Other safety measures will include a verbal pain analog scale, clinical examination, and serum creatine kinase (CK) levels. In Aim 2 we will implement a pilot intervention study to examine the feasibility and safety of a 12 week in-home isometric strengthening program in children with DMD. In this study, 10 boys with DMD will complete a progressive exercise program using the parameters and dose identified in Aim 1. Assessment of strength and safety will be performed at regular time intervals throughout the study. Ten boys with DMD not participating in an exercise intervention will be tested at similar time intervals and serve as controls. The data from this pilot study will serve to perform the power analysis needed to design an appropriately powered clinical intervention study. This innovative application may have significant public health implications as it sets the stage for the development of guidelines for exercise parameters in patients with DMD.

描述（由申请人提供）：杜氏肌营养不良症（DMD）是一种使人衰弱的神经肌肉疾病，可导致肌肉衰竭、虚弱和最终死亡。在过去的40年里，父母几乎没有得到关于运动作为维持肌肉功能的治疗策略的指导。众所周知，高强度运动和离心收缩可导致营养不良肌肉的肌肉损伤，而缺乏肌肉负荷将反过来导致肌肉萎缩。最近对啮齿动物模型和轻度肌营养不良症的研究支持了早期的研究，即阻力运动可能对维持营养不良肌肉的肌肉质量具有有益作用。然而，需要对抗阻运动的安全性和可行性进行仔细和系统的调查，才能考虑在患有DMD的男孩中实施抗阻运动。这项初步研究的总体目标是评估轻度至中度强度的强化运动计划是否可以安全地实施于DMD男孩。在目标1中，我们将确定轻度至中度强度等长阻力运动对DMD儿童的剂量反应和安全性。12名患有DMD的非卧床男孩将参加等长运动给药方案，其中负荷逐渐增加。在这个概念初步研究的早期证明中，将研究两个大的肌肉群：膝伸肌和膝屈肌。大腿肌肉的T2加权磁共振成像（MRI）将用于监测每个强度水平下肌肉损伤的证据，并确定安全的运动范围。其他安全性指标将包括语言疼痛模拟量表、临床检查和血清肌酸激酶（CK）水平。在目的2方面，我们会进行一项试验性的干预研究，以探讨12 一周的家庭等长肌力训练计划。在这项研究中，10名DMD男孩将使用目标1中确定的参数和剂量完成渐进式运动计划。在整个研究期间，将定期进行规格和安全性评估。10名没有参加运动干预的DMD男孩将在类似的时间间隔进行测试，并作为对照。本初步研究的数据将用于进行设计适当把握度的临床干预研究所需的把握度分析。这一创新应用可能具有重大的公共卫生意义，因为它为 制定DMD患者运动参数指南。