Enhancing Precision Sleep Medicine in traumatic Brain Injury: Examining the feasibility of Home-Based Measurement of Circadian Timing

加强创伤性脑损伤的精准睡眠医学：检验家庭昼夜节律测量的可行性

• 批准号: 10700406
• 负责人: Daniel James Reis
• 金额: --
• 依托单位: VA EASTERN COLORADO HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10700406
• 关键词: Address; Behavioral; Biological; Brain region; Chronotherapy; Circadian Dysregulation; Circadian Rhythms; Circadian desynchrony; Clinical; Cognitive Therapy; Collection; Data; Detection; Development; Devices; Disease; Ensure; Etiology; Evidence based treatment; Fatigue; Goals; Health; Healthcare; Home; Home environment; Hormones; Hour; Human; Information Systems; Injury; Intervention; Interview; Label; Laboratories; Light; Link; Longitudinal Studies; Measurement; Measures; Medicine; Melatonin; Mental Depression; Methods; Mission; Pain; Participant; Patient Outcomes Assessments; Patients; Personal Satisfaction; Phase; Population; Post-Traumatic Stress Disorders; Process; Production; Productivity; Provider; Quality of life; Recording of previous events; Recovery; Recovery of Function; Reporting; Research; Risk; Saliva; Salivary; Sampling; Schedule; Shipping; Sleep; Sleep disturbances; Sleeplessness; Spinal cord injury; Stroke; System; Testing; Time; Traumatic Brain Injury; Traumatic Brain Injury recovery; Veterans; Wrist; actigraphy; arm; chronic pain; circadian; circadian pacemaker; comorbidity; cost; design; diaries; disability; disability risk; evidence base; experience; falls; feasibility testing; functional disability; functional improvement; functional independence; functional outcomes; improved; mathematical model; novel; patient population; peer; personalized medicine; psychologic; psychosocial; rehabilitation research; rehabilitation science; rehabilitative care; research and development; saliva sample; severe mental illness; sleep onset; sleep regulation; standard care; standard measure; targeted treatment; tool

Veterans with traumatic brain injury (TBI) frequently experience insomnia, which is linked with delayed TBI recovery, more severe functional impairment, and exacerbation of disabling TBI sequelae such as depression, chronic pain, and fatigue. Current research suggests that TBI can impact numerous systems involved in sleep regulation, suggesting that insomnia may manifest from various etiologies and that a “one-size-fits-all” approach to treatment is likely inadequate. As such, it is necessary to differentiate Veterans who may benefit from standard evidence-based treatments, such as Cognitive Behavior Therapy for Insomnia, from those who may require enhanced treatments targeting specific underlying mechanisms. An emerging body of evidence has established a link between circadian rhythm disruption and post-TBI insomnia. A mismatch between circadian and desired sleep timing (i.e., “circadian misalignment”) is common following TBI, as evidenced by perturbations of key circadian rhythms involved in sleep regulation (e.g., melatonin production), as well as the manifestation of circadian rhythm sleep-wake disorders. Importantly, circadian-driven sleep disturbances require specialized treatments that target circadian rhythms (i.e., “chronotherapies”), such as timed sleep windows or enhanced light exposure, as standard treatment approaches can fail to address or even exacerbate the underlying circadian misalignment. Thus, circadian misalignment represents a novel and modifiable treatment target and has the potential to improve functional outcomes in Veterans with TBI and insomnia. Detection of circadian misalignment and optimal use of chronotherapies require the ability to measure circadian phase (i.e., timing of the central circadian clock). However, current sleep medicine in TBI is hampered by a lack of pragmatic options for measuring circadian phase. This is because laboratory dim light melatonin onset (DLMO), the gold standard measure of circadian phase, is time and cost prohibitive, requiring specialized sample (e.g., saliva) collection facilities and placing substantial burden on the patient. Recently, novel methods of DLMO measurement have been developed that may enhance the accessibility and practicality of circadian phase assessment, although, as of yet, they have not been used in Veterans with TBI. The proposed single-arm, longitudinal study seeks to evaluate the feasibility of two methods of measuring DLMO in the home environment of Veterans with TBI and insomnia: 1) direct measurement of self-collected salivary melatonin; and 2) indirect estimation of DLMO using activity and light- exposure data collected through actigraphy. Additionally, this study seeks to explore the relationships between circadian misalignment, sleep disturbance, and functional impairment in Veterans with TBI. The specific aims of this study are to: Aim 1) evaluate the feasibility of two methods of home DLMO measurement (i.e., self-collected salivary melatonin and actigraphy data) in Veterans with TBI and insomnia; and Aim 2) examine associations between circadian misalignment (i.e., the difference in timing between DLMO and attempted sleep onset), sleep disturbance, and functional impairment. Veterans with TBI and insomnia will be asked to wear a wrist-based actigraphy device for one week, which will collect data on light exposure and sleep-wake states. They will then be asked to self-collect seven hourly saliva samples under dim light conditions in their own home and mail them to a testing facility using a provided pre-paid shipping label. Saliva samples will be used to directly measure DLMO and actigraphy data will be used to indirectly estimate DLMO using established mathematical models of the human circadian pacemaker. Evaluating the feasibility of home DLMO measurement is a crucial first step for enhancing precision sleep medicine for Veterans with TBI and insomnia. Findings will inform the development and testing of tailored sleep interventions for use with this patient population.

脑外伤的退伍军人（TBI）经常出现失眠，这与TBI延迟有关 恢复，更严重的功能障碍以及禁用TBI后遗症的加剧，例如抑郁症， 慢性疼痛和疲劳。当前的研究表明，TBI会影响涉及睡眠的众多系统 调节，表明失眠可能来自各种病因，并且“一定程度合适” 治疗方法可能不足。因此，有必要区分可能受益的退伍军人 从标准的基于证据的治疗（例如失眠的认知行为疗法）来看 可能需要增强针对特定潜在机制的治疗方法。 新兴的证据已经建立了昼夜节律破坏与tbi之间的联系 失眠。常见的 在TBI之后，这是由参与睡眠调节的关键昼夜节律的扰动所证明的（例如， 褪黑激素的产生），以及昼夜节律睡眠效果的表现。重要的是， 昼夜节律的睡眠障碍需要针对昼夜节律的专门治疗（即 “计时疗法”），例如定时睡眠窗或增强的光曝光，作为标准处理 方法可能无法解决甚至加剧基本的昼夜节律错位。那， 昼夜节律未对准代表了一个新颖且可修改的治疗靶标，并且有可能 改善TBI和失眠的退伍军人的功能结果。 检测昼夜节律未对准和最佳使用时间疗法需要测量的能力 昼夜节律阶段（即中央昼夜节律的时机）。但是，当前TBI的睡眠药物是 由于缺乏测量昼夜节律的务实选择而阻碍了。这是因为实验室昏暗 光褪黑激素发作（DLMO）是昼夜节律的黄金标准测量，是时间和成本的， 需要专门的样本（例如唾液）收集设施，并对患者进行大量燃烧。 最近，已经开发了新颖的DLMO测量方法，可以增强可访问性和 昼夜评估的实用性，尽管迄今为止，它们尚未用于TBI的退伍军人。 拟议的单臂纵向研究旨在评估两种方法的可行性 在使用TBI和失眠的退伍军人的家庭环境中测量DLMO：1）直接测量 自我收集的唾液褪黑激素； 2）使用活性和光的DLMO间接估计 通过行为摄影收集的暴露数据。此外，本研究旨在探索关系 TBI退伍军人的昼夜节律错位，睡眠障碍和功能障碍之间。 这项研究的具体目的是：目标1）评估两种家庭DLMO方法的可行性 TBI和失眠的退伍军人中的测量（即自我收集的唾液褪黑激素和行动摄影数据）； 目标2）检查昼夜节律未对准之间的关联（即， DLMO和尝试的睡眠发作），睡眠障碍和功能障碍。有TBI的退伍军人 失眠症将被要求佩戴基于腕部的表观摄影设备一周，该设备将在灯光下收集数据 暴露和睡眠效果状态。然后，他们将被要求自我收集七个小时的唾液样本 在自己的家中轻度条件，并使用提供的预付运输标签将其邮寄到测试设施中。 唾液样品将用于直接测量DLMO，并且行动图数据将用于间接估计 DLMO使用人类昼夜节律起搏器的既定数学模型。评估可行性 家庭DLMO测量是增强退伍军人精确睡眠药物的关键第一步 有TBI和失眠。调查结果将为量身定制的睡眠干预措施的开发和测试提供信息 与该患者人群一起使用。