Academic Primary Care, Institute of Applied Health Sciences, Aberdeen, UK
Department of Anaesthesia, Aberdeen Royal Infirmary, NHS Grampian, Aberdeen, UK.
BMJ Open. 2020 Mar 16;10(3):e034443. doi: 10.1136/bmjopen-2019-034443.
Chronic pain is prevalent, and approximately half of patients with chronic pain experience sleep disturbance. Exogenous melatonin is licensed to treat primary insomnia and there is some evidence for analgesic effects of melatonin.The aim of this study is to investigate the effects of oral melatonin (as Circadin) 2 mg at night in adults with severe non-malignant pain of at least 3 months' duration.
We will conduct a randomised double-blind placebo-controlled cross-over study. The primary outcome is sleep disturbance. Secondary outcomes are pain intensity, actigraphy, fatigue, reaction time testing, serum melatonin and endogenous opioid peptide levels along with patient views about study participation.We aim to recruit 60 patients with severe chronic pain (average pain intensity ≥7 on the Brief Pain Inventory (BPI)) from a tertiary referral pain clinic in Northeast Scotland. Participants will be randomised to receive melatonin (as modified release Circadin) 2 mg daily for 6 weeks or placebo, followed by a 4-week washout period, then 6 weeks treatment with the treatment they did not receive. Participants will complete the Verran Snyder-Halpern Sleep Scale, Pittsburgh Sleep Quality Index, Pain and Sleep Questionnaire 3-item index, BPI and psychomotor vigilance reaction time testing at 6 points over 20 weeks. Actigraphy watches will be used to provide objective measures of sleep duration and latency and other sleep measures and will prompt patients to report contemporaneous pain and fatigue scores daily.Cross-over analyses will include tests for effects of treatment, period, treatment-period interaction (carryover effect) and sequence. Within-patient effects and longitudinal data will be analysed using mixed linear models, accounting for potential confounders.
Approved by Office for Research Ethics Committees Northern Ireland, reference 19/NI/0007. Results will be published in peer-reviewed journals and will be presented at national and international conferences.
ISRCTN12861060.
慢性疼痛很常见，大约一半的慢性疼痛患者都有睡眠障碍。外源性褪黑素已获许可用于治疗原发性失眠，并且有一些关于褪黑素的镇痛作用的证据。本研究旨在调查夜间口服 2 毫克褪黑素（作为 Circadin）对至少持续 3 个月的严重非恶性疼痛的成年人的影响。
我们将进行一项随机、双盲、安慰剂对照交叉研究。主要结局是睡眠障碍。次要结局是疼痛强度、活动记录仪、疲劳、反应时间测试、血清褪黑素和内源性阿片肽水平以及患者对研究参与的看法。我们的目标是从苏格兰东北部的一家三级转诊疼痛诊所招募 60 名患有严重慢性疼痛（平均疼痛强度≥Brief Pain Inventory（BPI）的 7）的患者。参与者将随机接受褪黑素（作为改良释放的 Circadin）2 毫克，每天一次，持续 6 周，或安慰剂，然后进行 4 周洗脱期，然后再接受 6 周未接受的治疗。参与者将在 20 周内完成 6 个时间点的 Verran Snyder-Halpern 睡眠量表、匹兹堡睡眠质量指数、疼痛和睡眠问卷 3 项指数、BPI 和精神运动警觉性反应时间测试。活动记录仪手表将用于提供睡眠持续时间和潜伏期以及其他睡眠测量的客观指标，并提示患者每天报告同时的疼痛和疲劳评分。交叉分析将包括治疗、周期、治疗-周期相互作用（交叉效应）和序列的效果测试。使用混合线性模型对患者内效应和纵向数据进行分析，同时考虑潜在的混杂因素。
经北爱尔兰研究伦理委员会办公室批准，参考号 19/NI/0007。结果将发表在同行评议的期刊上，并将在国内和国际会议上进行展示。
ISRCTN12861060。
