TRIAL OF MINOCYCLINE IN 400 SUBJECTS WITH ALS

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 我们将在本研究中检验的假设是二甲胺四环素减缓肌萎缩侧索硬化症（ALS）患者整体功能的进行性恶化。 主要结果测量是与服用安慰剂的患者相比，服用米诺环素的患者通过ALS功能评定量表（ALSFRS-R）检测的功能变化。该研究有80%的把握度检测患者ALSFRS-R评分随时间推移平均斜率降低18%或更高。次要结局指标是手动肌肉测试（MMT）、用力肺活量（FVC，预测百分比）、生活质量（QOL）和生存率的变化。 这是一项药物启动、多中心、III期、随机（1：1）、双盲、安慰剂对照试验。总研究长度为48个月：24个月用于患者招募，4个月的连续每月评估以确定每例患者的基线进展斜率，随后9个月的干预（二甲胺四环素或安慰剂），以及另外11个月的生存随访，数据分析和出版物的准备。受试者在13个月的参与期间接受每月评估。将在第4个月访视时进行随机化。在干预阶段的前3周（第5个月），受试者接受每天最多8片（400 mg）的递增剂量（如耐受），并每周进行电话联系。

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 hypothesis we will test in the current study is that minocycline slows the progressive deterioration of global function in patients with amyotrophic lateral sclerosis (ALS). The primary outcome measure is change in function as detected by the ALS Functional Rating Scale (ALSFRS-R) in patients taking minocycline compared to those taking placebo. The study is 80 % powered to detect an 18% or greater reduction in the average slope of patients' ALSFRS-R scores over time. The secondary outcome measures are changes in manual muscle testing (MMT), forced vital capacity (FVC, percent predicted), quality of life (QOL) and survival. This is an investigator-initiated, multi-center, phase III, randomized (1:1), double blind, placebo-controlled trial. The total study length is 48 months: Twenty-four months for patient recruitment, 4 months of serial monthly evaluations to determine baseline slopes of progression for each patient followed by 9 months of intervention (minocycline or placebo), and 11 additional months of survival follow-up, data analysis and preparation of publications. Subjects receive monthly evaluations during their 13 months of participation. Randomization will occur at the month 4 visit. During the first 3 weeks of the intervention phase (month 5) subjects receive an escalating dose of up to 8 pills (400 mg) per day as tolerated and have weekly phone contact.