NightWare Therapeutic Platform for improving Cardiovascular Health inAdults With Nightmares Associated with PTSD

项目摘要/摘要 创伤后应激障碍(PTSD)与加速衰老有关，并与 男性和女性早发性心血管疾病(CVD)。创伤后应激障碍与早产有关 血管老化(即大弹性动脉硬化和血管内皮功能障碍)和自主神经 功能障碍(例如，心脏迷走神经压力反射敏感性[CBRS]和心率变异性[HRV]降低)，关键 脑血管病发生的前驱因素。睡眠通过细胞和组织对心血管健康很重要 修复，自由基解毒，减少氧化应激和炎症。噩梦，一个中心特征 创伤后应激障碍是一种衰弱的疾病，可导致睡眠不足或失眠、白天嗜睡和 其他后遗症，最终在临床上造成严重的社会、职业和精神障碍 心血管功能。因此，应对噩梦相关的治疗策略和干预措施 创伤后应激障碍患者的睡眠障碍对改善睡眠质量、心血管疾病具有重要的临床意义 健康和未来与年龄相关的心血管疾病的风险。Nightware™数字治疗系统是一款新型智能手表 最近被FDA授予突破性设备名称的申请，用于治疗 患有创伤后应激障碍的成年人的噩梦。它使用机器学习来检测、跟踪和唤醒一个人 通过向智能手表发送振动触觉反馈来实现噩梦，并将个人从噩梦中唤醒 而不会被唤醒和打乱睡眠。在目前的R21中，我们提出了一种随机、双盲、 安慰剂(即假干预)对照的平行试验研究将为 NIGHTWARE数字化治疗系统改善成人高血压患者心血管健康状况的疗效 与创伤后应激障碍相关的噩梦。该R21的另一个目标将是获得探索性机械 了解哪些睡具可以改善心血管功能，特别是与睡眠质量、一氧化氮有关的功能 生物利用度、自由基产生、氧化应激和炎症。我们假设有6周的时间 夜间干预将改善血管老化的结果(例如，大弹性动脉硬化、血管 患有创伤后应激障碍相关噩梦的成年人的自主神经功能(CBRS，HRV)。这个 这项先导性研究的结果将为更大规模的随机临床试验提供基础 旨在确定夜总会作为一种安全有效的治疗策略的有效性 噩梦，促进健康的血管老化，自主神经功能，降低晚年患心血管疾病的风险 患有与创伤后应激障碍相关的噩梦的成年人。

PROJECT SUMMARY/ABSTRACT Post traumatic stress disorder (PTSD) is linked to accelerated aging and is associated with increased risk of early-onset cardiovascular disease (CVD) in both men and women. PTSD is associated with premature vascular aging (i.e., large elastic arterial stiffening and vascular endothelial dysfunction) and autonomic dysfunction (e.g., reduced cardiovagal baroreflex sensitivity [cBRS] and heart rate variability [HRV]), key antecedents in the development of CVD. Sleep is important for cardiovascular health via cellular and tissue repair, free radical detoxification and reducing oxidative stress and inflammation. Nightmares, a central feature of PTSD, are a debilitating condition that can lead to sleep deprivation or insomnia, daytime sleepiness and other sequala, that ultimately causes clinically significant distress and impairment in social, occupational and cardiovascular function. As such, therapeutic strategies and interventions that address nightmare-associated sleep disturbances in individuals with PTSD is clinically important for improving sleep quality, cardiovascular health and risk for future age-associated CVD. NightWare™ digital therapeutic system is a novel smart watch application that was recently granted Breakthrough Device designation by the FDA for the treatment of nightmares in adults with PTSD. It uses machine learning to detect, track and arouse an individual out of a nightmare by sending vibrotactile feedback to a smart watch, and arousing the individual out of the nightmare without awakening and disrupting sleep. In the present R21 we are proposing a randomized, double-blind, placebo (i.e., sham intervention) controlled parallel pilot study that will provide the first clinical evidence for the efficacy of the NightWare digital therapeutic system to improve cardiovascular health outcomes in adults with nightmares associated with PTSD. An additional goal of this R21 will be to obtain exploratory mechanistic insight by which NightWare improves cardiovascular function, specifically, related to sleep quality, nitric oxide bioavailability, free radical production, oxidative stress and inflammation. We hypothesize that 6 weeks of the NightWare intervention will improve outcomes of vascular aging (e.g., large elastic arterial stiffening, vascular endothelial dysfunction) and autonomic function (cBRS, HRV) in adults with PTSD-related nightmares. The results from this pilot investigation will provide the basis for a larger randomized clinical trial that would be conducted to establish the efficacy of NightWare as a safe and effective therapeutic strategy for treating nightmares, promoting healthy vascular aging, autonomic function and reducing the risk for CVD later in life in adults with nightmares associated with PTSD.