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）是帕金森病（PD）最严重的一些表现。 睡眠和警觉性紊乱是最常见的 NMS，这些方面的 PD 影响高达 90%。 导致患者生活质量下降、情绪和认知受损，并增加发生事故的风险； 导致发病率和死亡率增加 导致 NMS 的机制和治疗尚不清楚。 选择仍然有限。内源性人体昼夜节律系统在调节睡眠和睡眠方面发挥着关键作用。 我们的试点临床试验表明，通过环境光刺激可以最有效地同步。 每日两次强光疗法 (LT) 对 PD 患者睡眠和警觉性的有益影响。 已经揭示了 LT 对 PD 的类似有益作用，虽然 LT 的这些结果令人鼓舞，但剂量方面。 LT 在转化为临床实践之前需要进一步研究。 该项目旨在研究 LT 给药的一个核心方面：LT 的给药频率。 影响 LT 的依从性和耐受性以及临床效果。在我们提出的工作中，研究对象为 144 名 PD 患者。 自我报告睡眠受损的患者将被随机分配接受 (i) 亮白 LT (BWLT)，每天两次（早上） (ii) BWLT 每天一次（仅晚上），(iii) BWLT 每周一次（仅晚上），以及 (iv) 暗红色 LT (DRLT) 每天两次（早上和晚上），每次一小时，持续八周，使用市售的 结果将包括安全性以及睡眠、警觉性、疲劳、运动和非运动的测量。 在整个研究过程中，参与者将持续佩戴腕部活动记录仪。 监测睡眠-觉醒模式，并记录每日睡眠日记和 LT 暴露记录。 利用比较选择设计来确定每日剂量的 BWLT 是否可以改善 PD 患者的睡眠 足以推进 III 期疗效试验，如果是的话，推进目标 2 的剂量频率。 将 (i) 评估每周一次 BWLT 是否是适当但相对于两次的较低负担控制条件 每日 DRLT；(ii) 评估每日 BWLT 对 PD 疲劳的影响；以及 (iii) 确定患者是否坚持治疗； 探索性分析将评估每日 BWLT 对总体 PD 症状严重程度、运动和功能的影响。 非运动症状、睡眠、生活质量、情绪和认知的客观测量。 从长远来看，该项目解决了开发针对睡眠障碍和其他 NMS 的新疗法的需求 短期内，该项目将为 LT 的未来 III 期临床试验奠定基础。 确定 BWLT 的最佳频率和适当的控制条件，该项目响应于。 最近 (2014) NINDS PD 研究中概述了临床研究的几个最优先领域 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) 促进对大脑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紊乱的预防、诊断和治疗。