A Randomized, Double-blind, Placebo-Controlled Study of Latrepirdine in Patients With Mild to Moderate Huntington Disease
A Randomized, Double-blind, Placebo-Controlled Study of Latrepirdine in Patients With Mild to Moderate Huntington Disease
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DOI：
10.1001/2013.jamaneurol.382
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发表时间：
2013-01-01
期刊：
影响因子：
29
通讯作者：
Miyasaki, Janis
中科院分区：
文献类型：
--
作者：
Kieburtz, Karl;Landwehrmeyer, Georg B.;Miyasaki, Janis
背景资料：Latrepirdine是一种口服实验性小分子，最初是作为抗组胺药开发的，随后被证明可以稳定线粒体膜和功能，这可能在亨廷顿病中受损。目的：确定Latrepirdine对轻度至中度亨廷顿病患者认知和整体功能的影响。设计：随机、双盲、安慰剂对照研究。设置：患者：403名轻度至中度亨廷顿病和基线认知障碍患者（简易精神状态检查评分，10-26）。干预：拉曲匹定（20 mg）与匹配的安慰剂口服给药，每日3次，持续26周。主要结果测量：共同主要结局指标为认知（通过简易精神状态检查评分从基线至第26周的变化测量）和第26周时的整体功能（通过基于临床医生访谈的变化印象测量），加上护理人员访谈，范围为1（显著改善）至7（显著恶化）。次要疗效结果的措施包括行为，日常功能，运动功能，和safety.Results：在小型精神状态检查评分的平均变化，随机分配到latrepirdine（1.5分改善）的参与者之间没有显着差异，随机分配到安慰剂（1.3分改善）（P= 0.39）。同样，随机分配至拉曲匹定组的患者与安慰剂组相比，基于临床医生访谈的变化印象的分布加上护理人员访谈没有显著差异（P= 0.84）。在次要疗效结局指标上未检测到显著的治疗效应。不良事件的发生率在随机分配到拉曲匹定组（68.5%）和安慰剂组（68.0%）之间相似。结论：在轻度至中度亨廷顿舞蹈症和认知障碍患者中，拉曲匹定治疗6个月是安全的，耐受性良好，但相对于安慰剂，并没有改善认知或整体功能。clinicaltrials.gov 2013;70（1）：25-33。2012年10月29日在线发布。doi：10.1001/2013.jamaneurol.382
Background: Latrepirdine is an orally administered experimental small molecule that was initially developed as an antihistamine and subsequently was shown to stabilize mitochondrial membranes and function, which might be impaired in Huntington disease.Objective: To determine the effect of latrepirdine on cognition and global function in patients with mild to moderate Huntington disease.Design: Randomized, double-blind, placebo-controlled study.Setting: Sixty-four research centers in Australia, Europe, and North America.Patients: Four hundred three patients with mild to moderate Huntington disease and baseline cognitive impairment (Mini-Mental State Examination score, 10-26).Intervention: Latrepirdine (20 mg) vs matching placebo administered orally 3 times daily for 26 weeks.Main Outcome Measures: The co-primary outcome measures were cognition as measured by the change in Mini-Mental State Examination score from baseline to week 26 and global function at week 26 as measured by the Clinician Interview-Based Impression of Change, plus carer interview, which ranges from 1 (marked improvement) to 7 (marked worsening). Secondary efficacy outcome measures included behavior, daily function, motor function, and safety.Results: The mean change in Mini-Mental State Examination score among participants randomized to latrepirdine (1.5-point improvement) did not differ significantly from that among participants randomized to placebo (1.3-point improvement) (P=.39). Similarly, the distribution of the Clinician Interview-Based Impression of Change, plus carer interview did not differ significantly among those randomized to latrepirdine compared with placebo (P=.84). No significant treatment effects were detected on the secondary efficacy outcome measures. The incidence of adverse events was similar between those randomized to latrepirdine (68.5%) and placebo (68.0%).Conclusion: In patients with mild to moderate Huntington disease and cognitive impairment, treatment with latrepirdine for 6 months was safe and well tolerated but did not improve cognition or global function relative to placebo.Trial Registration: clinicaltrials.gov Identifier: NCT00920946 JAMA Neurol. 2013;70(1):25-33. Published online October 29, 2012. doi:10.1001/2013.jamaneurol.382