CLINICAL TRIAL: CLINICAL TRIAL OF CEFTRIAXONE IN SUBJECTS WITH ALS

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。 本研究的具体目的是确定头孢曲松长期治疗的药代动力学和耐受性，并随后确定该治疗在ALS患者中的疗效。肌萎缩侧索硬化症是一种均匀进行性和致命性的神经退行性疾病，目前还没有已知的治疗方法。在一项扩大潜在治疗药物搜索范围的新尝试中，NINDS领导的一个合作小组在超过28种与各种神经退行性疾病相关的测试中，对1040种FDA批准的药物进行了体外筛选。几种头孢菌素类药物显示出提高ALS患者存活率的潜力。 这项研究的第一阶段和第二阶段将确定ALS的最佳剂量、安全性和初步疗效。60名患者(WFUBMC的8名)将被纳入I/II期研究，其中包括一组安慰剂和两组每天服用2克或4克头孢曲松的患者。将获得药代动力学信息和耐受性。基于这些数据，将评估是否可以给ALS患者提供安全剂量，以产生合理预期的生物效应的脑脊液水平。在60名患者完成至少4个月的治疗后，将决定是否继续进行第三阶段研究。这一阶段的试验将从40个地点额外招募540名患者(WFUBMC中的7名)。患者将随机服用安慰剂或头孢曲松，并每月跟踪观察安全性和有效性。主要的结果衡量标准将是两组人之间的存活率。

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 specific aims of this study are to determine the pharmacokinetics and tolerability of long term ceftriaxone treatment, and to subsequently determine the efficacy of this treatment in ALS patients. Amyotrophic lateral sclerosis is a uniformly progressive and fatal neurodegenerative disorder for which there is no known cure. In a novel attempt to widen the search for potential therapeutic agents, an NINDS led cooperative group performed an in-vitro screening program of 1040 FDA approved drugs in over 28 assays relevant to various neurodegenerative disorders. Several cephalosporins showed potential for improving survival in ALS patients. Phase 1 and 2 of this study will determine optimal dose, safety and preliminary efficacy in ALS. Sixty patients (8 at WFUBMC) will be enrolled into the phase I/II study, including a placebo group and two groups receiving either 2 or 4 grams of ceftriaxone daily. Both pharmacokinetic information and tolerability will be obtained. Based on these data, an assessment will be made as to whether a safe dose can be given to ALS patients that will produce CSF levels reasonably expected to produce a biologic effect. After 60 patients have completed at least 4 months of treatment, a decision whether to continue to a phase III study will be made. This phase of the trial will enroll an additional 540 patients (7 at WFUBMC) from 40 sites. The patients will be randomized to placebo or ceftriaxone and followed monthly for safety and efficacy. The main outcome measure will be survival between the two groups.