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）最严重的致残表现之一。