CLINICAL TRIAL: CLINICAL TRIAL OF CEFTRIAXONE IN SUBJECTS WITH ALS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 本研究的具体目的是确定长期头孢曲松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进行性的致命性神经退行性疾病，目前尚无治愈方法。在一项扩大潜在治疗药物搜索的新尝试中，NINDS领导的合作小组在超过28项与各种神经退行性疾病相关的试验中对1040种FDA批准的药物进行了体外筛选。几种头孢菌素显示出改善ALS患者生存率的潜力。 本研究的1期和2期将确定ALS的最佳剂量、安全性和初步疗效。60例患者（8例在WFUBMC）将入组I/II期研究，包括安慰剂组和每天接受2克或4克头孢曲松的两组。 将获得药代动力学信息和耐受性。 根据这些数据，将评估是否可以向ALS患者给予安全剂量，该剂量将产生合理预期产生生物效应的CSF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III期研究。 本试验阶段将从40个研究中心额外入组540例患者（7例在WFUBMC）。 患者将被随机分配至安慰剂组或头孢曲松组，每月随访一次，以评估安全性和疗效。 主要的结局指标是两组之间的生存率。

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.