COMBINATION TRIAL IN ALS

ALS 联合试验

• 批准号: 7603375
• 负责人: ALAN PESTRONK
• 金额: $ 0.39万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2007-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7603375
• 关键词: Amyotrophic Lateral Sclerosis; Clinical Trials; Computer Retrieval of Information on Scientific Projects Database; Creatinine; Data; Databases; Disease; Disease Progression; Double-Blind Method; Drug Combinations; Enrollment; Evaluation; Funding; Futility; Grant; Institution; Laboratories; Minocycline; Natural History; Patients; Phase; Placebos; Probability; Procedures; Randomized; Rate; Research; Research Personnel; Resources; Source; Symptoms; Time; United States National Institutes of Health; Upper arm; Visit; celecoxib; design; placebo controlled study

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. This is an investigator-initiated, phase II, randomized, double-blind, controlled trial, which uses a simple and efficient design. We will employ up to 120 patients with ALS (60 per group) (FVC greater or equal to 60% predicted and symptom duration of less than 5 years). Patients will be randomized in pools of 60 to one of two arms: minocycline (100 mg BID)/creatinine (10g BID) or celecoxib (400 mg BID)/creatinine (10 g BID). Randomization will be stratified by center, and by disease rate of progression to assure an even distribution of treatment assignment within each stratum throughout the trial. After the first pool completes 6 monnths, the trial is stopped if the mean difference between the two arms is adequately large (defined as 0..75 times the SD); the combination inducing the smaller mean change in ALSFRS-R will be selected. If a combination provides 20% improvement in the mean change between groups, this stopping rule will conclude the trial in one pool with 67% probability. Otherwise, an additional 60 patients will be randomized. A maximum of two pools (120 patients) will be enrolled. We estimate a 4-month recruitment period 60 patients, requiring `10 months to complete each pool. Should the trial need two pools, it will take approximately 20 months to complete. Even if neither combination truly reduces the decline in ALSFRS-R by 20%, the selection procedure will still select the better combination with higher probability. Comparison to a natural history database from a recent clinical trial will be made to determine whether the selected combination is no worse than placebo (futility comparison). Subjects will meet El Escorial criteria for possible, laboratory supported probable, probable or definite ALS. They will receive monthly evaluations during their 6 months of participation. Randomization will occur at the baseline visit, and will be stratified by Center and by baseline rate of disease progression to assure an even distribution of subjects within each group throughout the trial. If one combination proves superior and non-futile, the data from this study will be used to design and implement a phase III placebo controlled trial of the selected drug combination.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这是一项由研究人员发起的II期随机、双盲、对照试验，采用了简单有效的设计。我们将雇用多达120名ALS患者(每组60名)(FVC大于或等于60%预测，症状持续时间少于5年)。患者将随机分为两组，每组60人：米诺环素(100毫克，每天2次)/肌酐(10克，每天2次)或塞来昔布(400毫克，每天2次)/肌酐(10克，每天2次)。随机化将按中心和疾病进展率分层，以确保在整个试验期间在每一层内均匀分配治疗分配。 在第一个池完成6个月后，如果两个臂之间的平均差异足够大(定义为0.75倍SD)，则停止试验；将选择导致ALSFRS-R平均变化较小的组合。如果组合在组之间的平均变化中提供了20%的改进，则该停止规则将以67%的概率结束在一个池中的试验。否则，另外60名患者将被随机分配。最多两个池(120名患者)将被纳入。我们估计4个月的招募周期为60名患者，需要10个月才能完成每个人才库。如果试验需要两个池，将需要大约20个月的时间才能完成。即使两个组合都没有真正将ALSFRS-R的降幅减少20%，选择程序仍将以更高的概率选择更好的组合。将与最近临床试验的自然病史数据库进行比较，以确定所选组合是否不比安慰剂更差(无效比较)。 受试者将符合实验室支持的可能的、可能的或确定的肌萎缩侧索硬化症的El Ecore标准。他们将在6个月的参与期间接受每月评估。随机化将在基线访问时进行，并将按中心和基线疾病进展速度分层，以确保受试者在整个试验期间在每组中均匀分布。如果一种组合被证明是好的和非徒劳的，这项研究的数据将被用于设计和实施所选药物组合的第三阶段安慰剂对照试验。