Healthy Brain Ageing Program, The University of Sydney School of Psychology, Sydney, New South Wales, Australia.
Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia.
BMJ Open. 2021 Feb 10;11(2):e041500. doi: 10.1136/bmjopen-2020-041500.
Melatonin has multiple proposed therapeutic benefits including antioxidant properties, synchronisation of the circadian system and lowering of blood pressure. In this protocol, we outline a randomised controlled trial to assess the feasibility, acceptability and tolerability of higher dose (25 mg) melatonin to target brain oxidative stress and sleep disturbance in older adults with mild cognitive impairment (MCI).
The study design is a randomised double-blind, placebo-controlled, parallel group trial. Forty individuals with MCI will be recruited from the Healthy Brain Ageing Clinic, University of Sydney and from the community, and randomised to receive either 25 mg oral melatonin or placebo nightly for 12 weeks. The primary outcomes are feasibility of recruitment, acceptability of intervention and adherence to trial medication at 12 weeks. Secondary outcomes will include the effect of melatonin on brain oxidative stress as measured by magnetic resonance spectroscopy, blood pressure, blood biomarkers, mood, cognition and sleep. Outcomes will be collected at 6 and 12 weeks. The results of this feasibility trial will inform a future conclusive randomised controlled trial to specifically test the efficacy of melatonin on modifiable risk factors of dementia, as well as cognition and brain function. This will be the first trial to investigate the effect of melatonin in the population with MCI in this way, with the future aim of using this approach to reduce progression to dementia.
This protocol has been approved by the Sydney Local Health District Ethics Committee (X18-0077). This randomised controlled trial will be conducted in compliance with the protocol published in the registry, the International Conference for Harmonisation on Good Clinical Practice and all other applicable regulatory requirements. The findings of the trial will be disseminated via conferences, publications and media, as applicable. Participants will be informed of results of the study at the conclusion of the trial. Eligible authors will include investigators who are involved in the conception and design of the study, the conduct of the trial, the analysis of the results, and reporting and presentation of study findings.
Australian and New Zealand Clinical Trials Registry (ANZCTRN 12619000876190).
V.8 15 October 2020.
褪黑素具有多种治疗益处，包括抗氧化特性、调节生物钟系统和降低血压。在本方案中，我们概述了一项随机对照试验，以评估较高剂量（25mg）褪黑素靶向治疗轻度认知障碍（MCI）老年人脑氧化应激和睡眠障碍的可行性、可接受性和耐受性。
该研究设计为随机、双盲、安慰剂对照、平行组试验。将从悉尼大学健康大脑衰老诊所和社区招募 40 名 MCI 患者，并将其随机分为每晚接受 25mg 口服褪黑素或安慰剂治疗 12 周。主要结局是招募的可行性、干预措施的可接受性和 12 周时对试验药物的依从性。次要结局将包括褪黑素对磁共振波谱测量的脑氧化应激、血压、血液生物标志物、情绪、认知和睡眠的影响。结果将在 6 周和 12 周收集。这项可行性试验的结果将为未来专门测试褪黑素对痴呆可改变风险因素以及认知和大脑功能的疗效的结论性随机对照试验提供信息。这将是第一项以这种方式在 MCI 人群中研究褪黑素作用的试验，未来的目标是使用这种方法来降低向痴呆的进展。
本方案已获得悉尼地方卫生区伦理委员会（X18-0077）的批准。这项随机对照试验将按照在注册处公布的方案、国际协调会议关于良好临床实践的指导原则以及所有其他适用的监管要求进行。试验结果将通过会议、出版物和媒体（如适用）进行传播。试验结束时，将告知参与者研究结果。合格作者将包括参与研究构思和设计、试验进行、结果分析以及报告和呈现研究结果的研究人员。
澳大利亚和新西兰临床试验注册（ANZCTRN 12619000876190）。
V.8 2020 年 10 月 15 日。
