目的:目前不宁腿综合征(RLS)的治疗指南推荐使用非多巴胺能药物开始治疗。鉴于食欲素在RLS病理生理学中的潜在作用,我们表演了一个飞行员,概念验证研究,以调查suvorexant的治疗效果,双重食欲素受体拮抗剂(DORA),特发性RLS患者的睡眠和感觉/运动症状。
方法:这是一个随机的,双盲,交叉和安慰剂对照研究。纳入标准是诊断为特发性RLS,国际RLS研究组严重程度评定量表(IRLS)评分>15分,并且在晚上9点前没有明显的RLS症状。从任何先前的中枢神经系统(CNS)活性药物中清除后,患者被随机分为两组,分别接受suvorexant或安慰剂,连续两个2周的治疗期.在第一周期间,以10mg/天的固定剂量在晚上9点进行治疗。和20毫克在第二周。主要和共同主要终点是睡眠发作后醒来(WASO)和总睡眠时间(TST),分别,而IRLS等级量表评分,多次建议固定试验(m-SIT),周期性肢体运动(PLM)是次要终点。使用IRLS和临床总体改善(CGI)量表每周测量RLS严重程度。在每个治疗阶段结束时,在晚上8点至午夜之间进行m-SIT,然后进行睡眠研究。
结果:共有41名参与者被随机分组,其中40人完成了这项研究。与安慰剂相比,suvorexant治疗可显着改善RLS症状(根据IRLS总分,CGI,和m-SIT),睡眠期间的PLM,和PLM与唤醒。在过去未接触多巴胺能药物的患者中,RLS症状的改善更大。睡眠结构也随着TST的显著变化而改善,WASO,睡眠发作潜伏期,睡眠效率,非快速眼动阶段1(N1)%,非快速眼动阶段2(N2)%,和快速眼动(REM)%。苏沃雷生在RLS中耐受性良好,很少和轻微的不良事件。
结论:我们的研究结果为DORA在改善RLS患者睡眠和感觉及运动症状方面的疗效提供了第一个证据。鉴于食欲素在疼痛和感觉加工中的作用,讨论了潜在的作用机制。
方法:该研究提供了支持Suvorexant治疗RLS伴睡眠障碍患者的II类证据。
背景:EudraCT#:2017-004580-12。
Current treatment guidelines for restless legs syndrome (RLS) recommend treatment be initiated with non-dopaminergic drugs. Given the potential role of orexins in the pathophysiology of RLS, we performed a pilot, proof-of-concept
study to investigate the therapeutic effects of suvorexant, a dual orexin receptor antagonist (DORA), on sleep and sensory/motor symptoms in individuals with idiopathic RLS.
This was a randomized, double-blind, crossover and placebo-controlled
study. Inclusion criteria were diagnosis with idiopathic RLS, an International RLS
Study Group Severity Rating Scale (IRLS) score > 15, and the absence of significant RLS symptoms before 9 pm. Following washout from any previous central nervous system (CNS)-active drugs, patients were randomized to receive either suvorexant or placebo for two consecutive 2-week treatment periods. Treatment was administered at 9 pm at a fixed dose of 10 mg/day during the first week, and 20 mg during the second week. Primary and coprimary endpoints were wake after sleep onset (WASO) and total sleep time (TST), respectively, while IRLS rating scale score, multiple suggested immobilization tests (m-SIT), and periodic limb movements (PLMs) were secondary endpoints. RLS severity was measured weekly using the IRLS and Clinical Global Improvement (CGI) scales. m-SIT were also performed between 8 pm and midnight at the end of each treatment phase and were followed by a sleep study.
A total of 41 participants were randomized, 40 of whom completed the
study. Compared with placebo, treatment with suvorexant significantly improved RLS symptoms (according to IRLS total score, CGI, and the m-SIT), PLM during sleep, and PLM with arousal. Improvement of RLS symptoms was greater in those who had not been exposed to dopaminergic agents in the past. Sleep architecture also improved with significant changes in TST, WASO, sleep onset latency, sleep efficiency, non rapid-eye movement stage 1 (N1) %, non rapid-eye movement stage 2 (N2) %, and rapid eye movement (REM) %. Suvorexant was well tolerated in RLS, with few and mild adverse events.
Our results provide the first proof of evidence of the therapeutic efficacy of DORAs in improving sleep and sensory and motor symptoms in RLS. Given orexin\'s role in pain and sensory processing, potential mechanisms of action are discussed.
The
study provides class II evidence supporting the therapeutic efficacy of suvorexant in patients with RLS with sleep disturbance.
EudraCT#: 2017-004580-12.