Orexin Receptor Antagonism, a New Sleep-Enabling Paradigm: A Proof-of-Concept Clinical Trial
Orexin Receptor Antagonism, a New Sleep-Enabling Paradigm: A Proof-of-Concept Clinical Trial
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DOI：
10.1038/clpt.2011.370
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发表时间：
2012-06-01
影响因子：
6.7
通讯作者：
Dingemanse, J.
中科院分区：
文献类型：
--
作者：
Hoever, P.;Dorffner, G.;Dingemanse, J.
食欲素系统是睡眠和觉醒的关键调节器。在一项多中心、双盲、随机、安慰剂对照、双向交叉研究中，161 名原发性失眠患者连续阶段接受 400、200、100 或 50 mg 的双食欲素受体拮抗剂阿莫乐生，或每隔 1 周在治疗夜接受安慰剂。主要终点是通过多导睡眠图测量的睡眠效率（SE）；次要终点是持续睡眠的客观潜伏期（LPS）、入睡后觉醒（WASO）、安全性和耐受性。在 SE、LPS 和 WASO 上观察到剂量依赖性阿莫司特效应。与安慰剂相比，阿莫司特 400 mg 后 SE 显着改善（平均治疗效果 14.4%；P < 0.001）。与安慰剂相比，400 mg 剂量组 LPS（-18 分钟（P = 0.02））和 WASO（-54 分钟（P < 0.001））显着降低。不良事件的发生率与剂量相关。 Almorexant 持续且剂量依赖性地改善睡眠变量。食欲素系统可能为原发性失眠提供一种新的治疗方法。
The orexin system is a key regulator of sleep and wakefulness. In a multicenter, double-blind, randomized, placebo-controlled, two-way crossover study, 161 primary insomnia patients received either the dual orexin receptor antagonist almorexant, at 400, 200, 100, or 50 mg in consecutive stages, or placebo on treatment nights at 1-week intervals. The primary end point was sleep efficiency (SE) measured by polysomnography; secondary end points were objective latency to persistent sleep (LPS), wake after sleep onset (WASO), safety, and tolerability. Dose-dependent almorexant effects were observed on SE, LPS, and WASO. SE improved significantly after almorexant 400 mg vs. placebo (mean treatment effect 14.4%; P < 0.001). LPS (-18 min (P = 0.02)) and WASO (-54 min (P < 0.001)) decreased significantly at 400 mg vs. placebo. Adverse-event incidence was dose-related. Almorexant consistently and dose-dependently improved sleep variables. The orexin system may offer a new treatment approach for primary insomnia.