Sleep and Neurology Department, Beau Soleil Clinic and EuroMov, Digital Health in Motion, University of Montpellier, Montpellier, France.
Sleep Disorders Unit, Pitié-Salpêtrière University Hospital, Paris, France.
Lancet Neurol. 2022 May;21(5):428-437. doi: 10.1016/S1474-4422(22)00085-0.
Insomnia is a frequent complaint of patients with Parkinson's disease, and it negatively affects quality of life. Drugs that improve both sleep and parkinsonism would be of major benefit to patients with Parkinson's disease-related insomnia. We aimed to test the safety and efficacy of subcutaneous night-time only apomorphine infusion in patients with Parkinson's disease and insomnia.
We did a randomised, multicentre, double-blind, placebo-controlled, crossover trial in 11 expert centres in Parkinson's disease and sleep centres in France. Participants aged 35-90 years with fluctuating Parkinson's disease and moderate to severe insomnia (Insomnia Severity Index score ≥15) were randomly assigned to either first receive night-time subcutaneous apomorphine (up to 5 mg/h) or matching placebo. Randomisation was done using a computer-generated plan in blocks of four, stratified by centre. This first intervention was followed by a 14-night washout period, then crossover to the other intervention. The treatment periods consisted of a 10-night titration phase followed by a 7-night fixed-dose phase. The dose was adjusted during the titration phase on the basis of a daily telephone call assessing sleep quality and treatment tolerability. The primary efficacy endpoint was the difference in Parkinson's disease sleep scale (PDSS) scores from the beginning to the end of each treatment period. Analysis was done on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, NCT02940912.
Between Jan 31, 2017, and Jan 29, 2021, 46 participants were enrolled. 25 (54%) patients were randomly assigned to receive apomorphine first and 21 (46%) patients to receive placebo first. Mean change in PDSS score was significantly greater with night-time apomorphine infusion (15·18 [SD 24·34]) compared with placebo (5·23 [21·52]; treatment effect 9·95 [95% CI 0·88-19·03]; p=0·041). Adverse events were reported in 25 (54%) participants during the apomorphine period and in 17 (37%) participants during the placebo period (p=0·16). Apomorphine was associated with more frequent dizziness than was placebo (seven [15%] vs 0; p=0·041).
Subcutaneous night-time only apomorphine infusion improved sleep disturbances according to difference on PDSS score, with an overall safety profile consistent with previous studies in Parkinson's disease. This treatment might be useful to manage sleep disturbances in patients with advanced Parkinson's disease and moderate to severe insomnia.
Orkyn and Aguettant Pharma.
For the French translation of the abstract see Supplementary Materials section.
失眠是帕金森病患者常见的主诉，会对生活质量产生负面影响。能同时改善睡眠和帕金森病症状的药物对帕金森病相关失眠患者将有重大益处。我们旨在测试夜间仅皮下给予阿扑吗啡对帕金森病伴失眠患者的安全性和疗效。
我们在法国的 11 个帕金森病专家中心和睡眠中心进行了一项随机、多中心、双盲、安慰剂对照、交叉试验。年龄在 35-90 岁、有波动型帕金森病且有中度至重度失眠（失眠严重程度指数评分≥15）的参与者被随机分配至首先接受夜间皮下阿扑吗啡（高达 5mg/h）或匹配安慰剂治疗。采用计算机生成的方案，按中心分层，以 4 人为一组进行随机分组。首次干预后进行 14 天的洗脱期，然后交叉至另一项干预。治疗期包括 10 天的滴定期和 7 天的固定剂量期。在滴定期，根据每日电话评估睡眠质量和治疗耐受性来调整剂量。主要疗效终点是从每个治疗期开始到结束时帕金森病睡眠量表（PDSS）评分的差异。采用意向治疗进行分析。本试验在 ClinicalTrials.gov 注册，编号为 NCT02940912。
在 2017 年 1 月 31 日至 2021 年 1 月 29 日期间，共纳入了 46 名参与者。25 名（54%）患者被随机分配至接受阿扑吗啡治疗，21 名（46%）患者接受安慰剂治疗。与安慰剂相比，夜间阿扑吗啡输注后 PDSS 评分的变化显著更大（15.18[24.34] vs 5.23[21.52]；治疗效果 9.95[95%CI 0.88-19.03]；p=0.041）。在阿扑吗啡治疗期间，有 25 名（54%）参与者和 17 名（37%）参与者报告了不良事件（p=0.16）。与安慰剂相比，阿扑吗啡更常引起头晕（7 名[15%] vs 0；p=0.041）。
夜间仅皮下给予阿扑吗啡可改善 PDSS 评分上的睡眠障碍，其总体安全性与帕金森病的先前研究一致。这种治疗方法可能对治疗晚期帕金森病伴中度至重度失眠的患者的睡眠障碍有用。
Orkyn 和 Aguettant Pharma。
