Trial of celecoxib in amyotrophic lateral sclerosis
Trial of celecoxib in amyotrophic lateral sclerosis
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DOI：
10.1002/ana.20903
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发表时间：
2006-07-01
影响因子：
11.2
通讯作者：
Drachman, Daniel B.
中科院分区：
文献类型：
--
作者：
Cudkowicz, Merit E.;Shefner, Jeremy M.;Drachman, Daniel B.
目的：塞来昔布是一种环氧合酶-2抑制剂，临床前试验证明其对肌萎缩侧索硬化症（ALS）患者是有益的，为了确定塞来昔布长期治疗是否安全有效，进行了一项双盲、安慰剂对照的临床试验。300名ALS患者随机（2：1）接受塞来昔布（800 mg/天）或安慰剂治疗12个月。主要结果测量是上肢运动功能的变化率，通过最大随意等长收缩强度测量。次要终点包括安全性，生存率，脑脊液前列腺素E水平的变化，以及腿部和握力，肺活量，ALS功能评定量表修订版，和运动单位数量estimates.Results：塞来昔布没有减缓肌肉力量，肺活量，运动单位数量估计，ALS功能评定量表修订版的下降速度，或影响生存率。塞来昔布耐受性良好，与不良事件发生频率增加无关。脑脊液中的前列腺素E水平在基线时没有升高，也没有随着治疗而下降。解释：在所研究的剂量下，塞来昔布对ALS研究受试者没有有益的影响，并且是安全的。在脑脊液中未证实塞来昔布的生物学效应。不需要进一步研究塞来昔布800 mg/天治疗ALS。
Objective: To determine whether chronic treatment with celecoxib, a cyclooxygenase-2 inhibitor that has been shown to be beneficial in preclinical testing, is safe and effective in amyotrophic lateral sclerosis (ALS).Methods: A double-blind, placebo-controlled, clinical trial was conducted. Three hundred research subjects with ALS were randomized (2:1) to receive celecoxib (800mg/day) or placebo for 12 months. The primary outcome measure was the rate of change in upper extremity motor function measured by the maximum voluntary isometric contraction strength. Secondary end points included safety, survival, change in cerebrospinal fluid prostaglandin E, levels, and changes in the rate of decline of leg and grip strength, vital capacity, ALS Functional Rating Scale-Revised, and motor unit number estimates.Results: Celecoxib did not slow the decline in muscle strength, vital capacity, motor unit number estimates, ALS Functional Rating Scale-Revised, or affect survival. Celecoxib was well tolerated and was not associated with an increased frequency of adverse events. Prostaglandin E, levels in cerebrospinal fluid were not elevated at baseline and did not decline with treatment.Interpretation: At the dosage studied, celecoxib did not have a beneficial effect on research subjects with ALS, and it was safe. A biological effect of celecoxib was not demonstrated in the cerebrospinal fluid. Further studies of celecoxib at a dosage of 800mg/day in ALS are not warranted.