Bright Light Therapy for Sleep Disturbance in Multiple Sclerosis

强光疗法治疗多发性硬化症的睡眠障碍

• 批准号: 9901968
• 负责人: Kathryn C. Fitzgerald
• 金额: $ 16.38万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-19 至 2022-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9901968
• 关键词: Adult; Affect; Biological; Biological Process; Cell physiology; Central Nervous System Diseases; Chronic; Circadian Rhythms; Data; Drowsiness; Effectiveness; Environment; Etiology; Fatigue; Functional disorder; Future; Glaucoma; Goals; Hour; Hypothalamic structure; Impairment; Inflammatory; Intervention; Intervention Studies; Investigation; Light; Measures; Mediating; Melatonin; Meta-Analysis; Morbidity - disease rate; Multiple Sclerosis; Nature; Neurodegenerative Disorders; Neurologic Dysfunctions; Outcome; Parkinson Disease; Patients; Pattern; Pharmaceutical Preparations; Pharmacological Treatment; Pharmacology; Phase; Photosensitivity; Phototherapy; Pilot Projects; Population; Prevalence; Quality of life; Rehabilitation therapy; Research Personnel; Research Support; Retinal Ganglion Cells; Risk; Role; Safety; Seasonal Affective Disorder; Sleep; Sleep Architecture; Sleep Disorders; Sleep Fragmentations; Sleep disturbances; Sleeplessness; Testing; Time; Variant; age related; candidate marker; circadian; circadian pacemaker; circadian regulation; cost; follow-up; high risk; improved; improved functioning; innovation; insight; light effects; macula; multiple sclerosis patient; nervous system disorder; novel; patient population; patient subsets; primary outcome; secondary outcome; sleep quality; sleep regulation; sound; suprachiasmatic nucleus

PROJECT SUMMARY Multiple sclerosis (MS), an inflammatory and neurodegenerative disorder of the central nervous system (CNS), is the most common cause of progressive neurologic dysfunction in early to middle adulthood. People with MS are a markedly high risk for sleep disturbance. Estimates of the lifetime prevalence of sleep disturbance in MS reach 50%; sleep disturbance is also associated with excess MS-associated morbidity and diminished quality of life. Despite the high burden of impaired sleep and its contribution to adverse MS outcomes, effective approaches to treat and ameliorate disturbed sleep in people with MS remain poorly understood. Current pharmacologic strategies offer predominantly short-term solutions and may not be ideal for the typically chronic and habitual nature of sleep disturbance in MS. Therefore, there is unmet need to develop safe and effective rehabilitative alternatives to mitigate sleep disturbance in MS. Prior research supports the use of timed bright light therapy (LT) as one such approach for insomnia and sleepiness in those with sleep disorders or other neurologic diseases. Yet, the safety and potential effectiveness of timed LT have yet to be tested in MS. The goal of the proposed study is to conduct a detailed intervention study testing if timed bright LT in people with MS is 1) safe (primary outcome) and 2) potentially effective for reducing sleep disturbance (specifically, reducing insomnia, fatigue and improving sleep efficiency, quantity and quality as secondary outcomes). Furthermore, our study will explore whether LT stimulates a novel subtype of retinal ganglion cells which are central to the regulation of circadian rhythms and sleep. Namely, this subtype, intrinsically photosensitive retinal ganglion cells (ipRGCs), serves as the origin of the retinohypothalamic tract, projects light information to the central circadian pacemaker in the hypothalamus, and, intriguingly, may be impaired in people with MS (as suggested by our preliminary data). Thus, results of these highly innovative exploratory analyses may suggest a candidate mechanism for the observed effect as well as a potential rehabilitative target for improving sleep in people with MS (or in a specific subset of patients). Collectively, this pilot will provide integral preliminary data to support future definitive trials of bright LT as safe, possibly efficacious approach for sleep disturbance in people with MS. Importantly, it will also provide key insight into a potentially intervenable biological target for sleep disturbance in a highly vulnerable patient population.

项目摘要 多发性硬化症（MS）是一种中枢神经系统（CNS）的炎性和神经退行性疾病， 是成年早期至中期进行性神经功能障碍的最常见原因。MS患者 有很高的睡眠障碍风险MS睡眠障碍终生患病率的估计 达到50%;睡眠障碍也与MS相关的发病率和质量下降有关。 生活尽管睡眠受损的负担很重，而且会导致MS的不良结局， 治疗和改善MS患者的睡眠障碍仍然知之甚少。当前药理学 策略主要提供短期的解决方案，对于典型的慢性和习惯性的 因此，对开发安全有效的康复药物的需求尚未得到满足。 缓解MS睡眠障碍的替代方案。先前的研究支持使用定时强光疗法 (LT)作为治疗睡眠障碍或其他神经系统疾病患者失眠和嗜睡的一种方法， 疾病然而，定时LT的安全性和潜在有效性尚未在MS中进行测试。 拟议的研究是进行一项详细的干预研究，测试MS患者的定时明亮LT是否安全 （主要结果）和2）潜在有效地减少睡眠障碍（具体地，减少失眠， 疲劳和改善睡眠效率、数量和质量作为次要结果）。此外，我们的研究将 探索LT是否刺激视网膜神经节细胞的一种新亚型，这种神经节细胞是调节 昼夜节律和睡眠。也就是说，这种亚型，固有光敏视网膜神经节细胞（ipRGC）， 作为视网膜下丘脑束的起源，将光信息投射到中央昼夜节律起搏器 在下丘脑，有趣的是，可能在MS患者中受损（正如我们的初步研究所建议的那样）。 数据）。因此，这些高度创新的探索性分析的结果可能表明， 观察到的效果以及改善MS患者睡眠的潜在康复目标（或在特定的 患者的子集）。总的来说，该试点将提供完整的初步数据，以支持未来的最终试验， 明亮的LT是治疗MS患者睡眠障碍的安全、可能有效的方法。重要的是， 提供了一个关键的洞察潜在的可干预的生物目标，睡眠障碍，在一个高度脆弱的 患者人群。