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: 10208984
• 负责人: Aleksandar Videnovic
• 金额: $ 164.9万
• 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 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10208984
• 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; poor sleep; 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）的一些最致残的表现。 睡眠中断和警觉性是最常见的NMS。PD的这些方面影响多达90% 导致生活质量差、情绪和认知受损，并增加事故风险;以及 导致发病率和死亡率增加。导致NMS的机制尚未得到很好的理解， 选择仍然有限。内源性人类昼夜节律系统在调节睡眠和呼吸中具有关键作用。 警觉性，并且通过环境光刺激最有效地同步。我们的初步临床试验表明 每天两次明亮光疗法（LT）对PD患者的睡眠和警觉性的有益影响。最近的几项研究 已经揭示了LT在PD中的类似有益效果。虽然LT的这些结果令人鼓舞，但剂量方面 在临床应用前需要进一步研究。 本项目旨在研究LT给药的一个核心方面：LT的频率。 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， 通过自我报告睡眠受损的患者将随机接受（i）亮白LT（BWLT），每天两次（早晨 （ii）BWLT每日一次（仅晚上），（iii）BWLT每周一次（仅晚上），和（iv）暗红LT （DRLT），每天两次（早晨和晚上），每次一小时，持续八周，使用市售的 灯箱。结果将包括安全性，睡眠，警觉性，疲劳，运动和非运动的措施 症状和生活质量。在整个研究过程中，参与者将佩戴腕关节活动记录仪， 监测睡眠-觉醒模式，并保持每日睡眠日记和LT暴露记录。目标1将 利用比较选择设计来确定BWLT的任一日剂量是否改善PD患者的睡眠 足以转入III期疗效试验，以及如果是，应转入何种剂量频率。目的2 将（i）评估每周一次的BWLT是否是一种适当的但相对于两次更低的负担控制条件- 每日DRLT;（ii）估计每日BWLT对PD中疲劳的影响;以及（iii）确定患者是否遵守 探索性分析将评估每日BWLT对总体PD症状严重程度、运动和 非运动症状、睡眠的客观测量、生活质量、情绪和认知。 从长远来看，该项目解决了开发睡眠受损和其他NMS新疗法的需求。 与PD有关。短期内，该项目将为未来的LT III期临床试验提供基础， 确定最佳的压载水冷却频率和合适的控制条件。该项目是响应 最新（2014年）NINDS PD研究中概述的临床研究的几个最高优先级领域 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）促进对大脑中睡眠和昼夜节律功能的理解 以及（iii）改善对睡眠和昼夜节律紊乱的预防、诊断和治疗。