MINOCYCLINE STUDY IN ALS PATIENTS

ALS 患者的米诺环素研究

• 批准号: 7377204
• 负责人: ALAN PESTRONK
• 金额: $ 2.37万
• 依托单位: WASHINGTON UNIVERSITY
• 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/7377204
• 关键词: MINOCYCLINE; STUDY; ALS; PATIENTS

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. The project will be a phase III, multicenter, IRB-approved, randomized, double-blind, placebo-controlled study of minocycline in 400 subjects with ALS treated for 9 months. The total length of the study is 48 months, including 24 months for recruitment, 4 months of serial monthly evaluations to determine baseline rates of deterioration for each subject, followed by 9 months on study medication and 11 months of survival follow-up, data analysis and preparation of publications. Subjects will undergo dose escalation during the first 3 weeks of the 9-month intervention period. The primary outcome measure is the change in slope of intr-subject ALSFRS-R scores. Secondary outcome measures include changes in disease progression rate as measured by manual muscle testing (MMT), pulmonary function (th rate of decline of forced vital capacity, precent predicted), QOL and survival (mortality combined with initiation of mechanical ventilation). There will be two arms with subjects randomized at month 4: after the 4 month lead in period; Group 1 (200 subjects) will receive placebo (identical to active drug) during the 9 month intervention period; Gtoup 2 (200 subjects) will receive minocycline starting at 100 mg twice daily and increasing each week by 50 mg twice daily until maximum tolerated dose or 200 mg twice daily dose is reached. Weekly phone contact will be made with subjects during the 3 weeks of the dose titration phase. The study medication will be dispensed every 4 weeks. Subject will undergo serial monthly outpatient evaluations and analysis of laboratory and adverse events. The 9 month treatment period was chosen as sufficient to demonstrate effects of treatment in slowing the progression of ALS, and to ensure that the majority of subjects complete the study. A mixed linear effect model will be used to measure the drug effect for each endpoint.

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。该项目将是一项III期、多中心、IRB批准、随机、双盲、安慰剂对照的米诺环素试验，对象为400名ALS患者，治疗时间为9个月。这项研究的总时间为48个月，包括24个月的征聘、4个月的连续月度评价以确定每个受试者的基线恶化速度、9个月的研究药物治疗和11个月的生存跟踪、数据分析和编写出版物。受试者将在9个月干预期的前3周内进行剂量递增。主要的结果衡量标准是受试者ALSFRS-R评分斜率的变化。次要结果指标包括通过手动肌肉测试(MMT)测量的疾病进展率、肺功能(用力肺活量下降的比率，预测的百分比)、生活质量和存活率(死亡率和开始机械呼吸)的变化。将有两组受试者在第4个月随机分组：在4个月的先导期后；第1组(200名受试者)将在9个月的干预期内接受安慰剂(与活性药物相同)；第2组(200名受试者)将接受米诺环素，从100毫克开始，每天两次，每周增加50毫克，每天两次，直到达到最大耐受量或200毫克每天两次。每周将在剂量滴定阶段的3周内与受试者进行电话联系。研究用药将每4周分发一次。受试者将接受每月一系列的门诊评估以及实验室和不良事件的分析。选择9个月的治疗周期足以证明治疗在减缓ALS进展方面的效果，并确保大多数受试者完成研究。将使用混合线性效应模型来衡量每个终点的药物效应。