A Dose Selection Trial of Light Therapy for Impaired Sleep in Parkinson's Disease

光疗法治疗帕金森病睡眠障碍的剂量选择试验

• 批准号: 10012951
• 负责人: Aleksandar Videnovic
• 金额: $ 215.64万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-15 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10012951
• 关键词: Accidents; Address; Adherence; Adverse event; Affect; Area; Biological Rhythm; Brain; Chronic; Circadian Rhythms; Clinical; Clinical Research; Clinical Trials; Cognition; Consensus; Development; Diagnosis; Disease; Dopa; Dose; Etiology; Fatigue; Foundations; Frequencies; Functional disorder; Future; Goals; Hour; Human; Hypothalamic structure; Impairment; Individual; Intervention; Intervention Studies; Lead; Light; Measures; Medical; Medicine; Modality; Moods; Morbidity - disease rate; Motor; National Institute of Neurological Disorders and Stroke; Neurodegenerative Disorders; Outcome; Parkinson Disease; Participant; Patient Self-Report; Patients; Pattern; Phase; Phase III Clinical Trials; Phototherapy; Polysomnography; Population; Prevention; Property; Psyche structure; Quality of life; Randomized; Records; Reporting; Research; Resistance; Risk; Role; Safety; Selection Criteria; Severities; Sleep; Sleep Disorders; Sleep disturbances; Stimulus; Symptoms; System; Translations; United States National Institutes of Health; Work; Wrist; actigraphy; alertness; associated symptom; base; circadian; clinical effect; clinical practice; comparative; design; diaries; effective therapy; efficacy clinical trial; efficacy trial; improved; improved functioning; light effects; meetings; mortality; non-motor symptom; novel; sleep quality; sleep regulation; suprachiasmatic nucleus; therapeutic target; trial design

Non-motor symptoms (NMS) are some of the most disabling manifestations of Parkinson’s disease (PD). Disrupted sleep and alertness are among the most common NMS. These aspects of PD affect as many as 90% of patients; contribute to poor quality of life, impaired mood and cognition, and increased risk for accidents; and lead to increased morbidity and mortality. Mechanisms leading to NMS are not well understood and treatment options remain limited. The endogenous human circadian system has a critical role in the regulation of sleep and alertness and is most effectively synchronized by environmental light stimuli. Our pilot clinical trial suggested beneficial effects of twice-daily bright light therapy (LT) on sleep and alertness in PD. Several other recent studies have revealed similar beneficial effects of LT in PD. While these outcomes of LT are encouraging, dosing aspects of LT require further study before translation to clinical practice. This project aims to investigate one central aspect of dosing of LT: the frequency of LT. Dose frequency will influence adherence and tolerability as well as the clinical effect of LT. In our proposed work, 144 PD patients with impaired sleep by self-report will be randomized to receive (i) bright-white LT (BWLT) twice daily (morning and evening), (ii) BWLT once daily (evening only), (iii) BWLT once weekly (evening only), and (iv) dim-red LT (DRLT) twice daily (morning and evening) in one-hour blocks for eight weeks using a commercially available lightbox. Outcomes will include safety, and measures of sleep, alertness, fatigue, motor and non-motor symptoms, and quality of life. Throughout the study, participants will wear a wrist actigraph for continuous monitoring of sleep-wake patterns, and keep daily sleep diaries and records of their LT exposure. Aim 1 will utilize a comparative selection design to determine whether either daily dose of BWLT improves sleep in PD sufficiently to carry forward into a phase III efficacy trial and, if so, which dose frequency to carry forward. Aim 2 will (i) assess whether once-weekly BWLT is an appropriate but lower burden control condition relative to twice- daily DRLT; (ii) estimate the effect of daily BWLT on fatigue in PD; and (iii) determine whether patients adhere to LT. Exploratory analyses will estimate the effect of daily BWLT on overall PD symptom severity, motor and non-motor symptoms, objective measures of sleep, quality of life, mood, and cognition. Long-term, this project addresses the need to develop novel treatments for impaired sleep and other NMS associated with PD. Short-term, the project will provide a foundation for a future phase III clinical trial of LT by determining the optimal frequency of BWLT and the appropriate control condition. This project is responsive to several highest priority areas for clinical research outlined in the most recent (2014) NINDS PD Research Consensus Meeting and in the 2011 NIH Sleep Disorders Research Plan: (i) to develop effective treatments for non-motor features of PD; (ii) to advance the understanding of sleep and circadian functions in both the brain and body; and (iii) to improve prevention, diagnosis, and treatment of sleep and circadian disorders.

非运动症状（NMS）是帕金森氏病（PD）最残疾的表现。 睡眠和机敏性破坏是最常见的NM。 PD的这些方面影响多达90％ 患者；促进生活质量差，情绪和认知受损以及发生事故风险的增加；和 导致发病率和死亡率增加。导致NMS的机制尚不清楚和治疗 选项仍然有限。内源性人类昼夜节律系统在睡眠调节和 机敏性，最有效地通过环境光刺激同步。我们的飞行员临床试验建议 每天两次明亮光治疗（LT）对PD的睡眠和机敏性的有益影响。其他最近的研究 LT在PD中揭示了类似的有益作用。尽管LT的这些结果令人鼓舞，但给药方面 LT需要在转化为临床实践之前进一步研究。 该项目旨在研究LT剂量的一个核心：LT的频率。剂量频率会 影响LT的依从性和耐受性以及LT的临床作用。在我们建议的工作中，有144名PD患者 由于自我报告的睡眠受损，每天两次都会随机接收（i）亮白色LT（BWLT） （ii）BWLT每天一次（仅傍晚），（iii）BWLT每周一次（仅晚上）和（iv）昏暗的LT （DRLT）每天两次（早上甚至）在一个小时的街区中使用市售的街区八周 灯箱。结果将包括安全性和睡眠，机敏性，疲劳，电动机和非运动的措施 症状和生活质量。通过这项研究，参与者将戴上腕部动作图 监视睡眠效果图案，并保留每日睡眠日记及其LT暴露的记录。目标1意志 利用比较选择设计来确定BWLT每日剂量是否改善PD的睡眠 足以进行III期有效试验，如果是，则可以进行剂量频率。目标2 （i）评估每周一次的BWLT是否是适当但相对于两次的燃烧控制条件 每日DRLT； （ii）估计每日BWLT对PD疲劳的影响； （iii）确定患者是否遵守 到LT。探索性分析将估算每日BWLT对总体PD症状严重程度，运动和 非运动症状，睡眠的客观度量，生活质量，情绪和认知。 长期，该项目解决了为睡眠受损和其他NMS开发新型治疗方法的需求 与PD相关。短期，该项目将为LT的未来III期临床试验提供基础 确定BWLT的最佳频率和适当的控制条件。这个项目对 最近（2014年）Ninds PD研究中概述的临床研究的几个最高优先领域 共识会议和2011年NIH睡眠障碍研究计划：（i）开发有效的治疗方法 PD的非运动特征； （ii）提高对大脑的睡眠和昼夜节律功能的理解 和身体； （iii）改善睡眠和昼夜节律疾病的预防，诊断和治疗。