CLINICAL PILOT TRIAL OF CREATINE IN AMYOTROPHIC LATERAL SCLEROSIS (ALS)

肌酸治疗肌萎缩侧索硬化症 (ALS) 的临床试点试验

• 批准号: 7378171
• 负责人: CARLAYNE E JACKSON
• 金额: $ 1.16万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7378171
• 关键词: CLINICAL; PILOT; TRIAL; CREATINE; AMYOTROPHIC

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a progressive, degenerative disease of the voluntary motor system resulting in generalized muscle weakness, dysphagia, dysarthria, and eventual respiratory failure. It has been hypothesized that in ALS there may be involvement of oxidative free radical damage and impaired mitochondrial energy metabolism that could in turn lead to excitotoxic cell death. Creatine, an agent that improves mitochondrial function, has been shown to be neuroprotective in animal models of ALS and Huntington's disease. The objective of this project is to determine whether creatine slows disease progression in patients with ALS. The specific aims of this proposal are to: (1) Determine whether treatment with creatine results in an acute increase in muscle strength and whether that effect is sustained with chronic therapy; (2) Determine whether chronic treatment with creatine will slow by 35% the progressive deterioration of motor and pulmonary function in patients with ALS; and (3) Determine whether administration of loading doses of creatine followed by chronic treatment is safe in patients with ALS. RESEARCH PLAN AND METHODS: This is a phase 2, double-blind, placebo-controlled, randomized, multi-center safety and efficacy study of creatine in 200 subjects with ALS. Each center will recruit approximately 20 patients. Patients will be randomized to receive treatment with creatine (10 grams/d for 5 days followed by 5 grams/d for duration of study) vs. placebo. The patients will be evaluated weekly for the first 3 weeks, monthly for 3 months, and then bimonthly until the completion of the study. Patients will then be offered participation in an open-label study until the data from the blinded portion of the study can be analyzed. The primary outcome measure is change in disease progression rate as measured by the maximum voluntary isometric contraction (MVIC) strength of eight arm muscle groups (bilateral shoulder and elbow flexion and extension). Secondary endpoints include the rate of decline of forced vital capacity (FVC, percent predicted), manual muscle strength, grip strength, the change in the ALS functional rating scale (ALSFRS-R) and the SF-12 (quality of life instrument), the safety and tolerability of creatine, and survival.

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。目的：肌萎缩性侧索硬化症（ALS）是一种进行性、退行性随意运动系统疾病，可导致全身肌肉无力、吞咽困难、构音障碍和最终的呼吸衰竭。据推测，ALS可能涉及氧化自由基损伤和线粒体能量代谢受损，从而导致兴奋性毒性细胞死亡。肌酸是一种改善线粒体功能的物质，在ALS和亨廷顿氏病的动物模型中被证明具有神经保护作用。该项目的目的是确定肌酸是否减缓ALS患者的疾病进展。本建议的具体目的是：(1)确定肌酸治疗是否会导致肌肉力量的急性增加，以及慢性治疗是否会持续这种效果；(2)确定慢性肌酸治疗是否会使ALS患者运动和肺功能的进行性恶化减缓35%；(3)确定肌酸负荷剂量后进行慢性治疗对ALS患者是否安全。研究计划和方法：这是一项2期、双盲、安慰剂对照、随机、多中心的肌酸在200名ALS患者中的安全性和有效性研究。每个中心将招募大约20名患者。患者将随机接受肌酸治疗（10克/天，持续5天，随后5克/天，持续研究期间）和安慰剂。患者前3周每周评估一次，3个月每月评估一次，然后每两个月评估一次，直到研究完成。然后，患者将被邀请参加一项开放标签研究，直到该研究的盲法部分的数据可以被分析。主要结局指标是疾病进展率的变化，通过8个手臂肌肉群（双侧肩膀和肘关节屈伸）的最大自主等距收缩（MVIC）强度来测量。次要终点包括用力肺活量下降率（FVC，预测百分比）、手肌力、握力、ALS功能评定量表（ALSFRS-R）和SF-12（生活质量指标）的变化、肌酸的安全性和耐受性以及生存率。