A randomized cross over trial of two treatments for OSA in Veterans with PTSD

描述（由申请人提供）： 阻塞性睡眠呼吸暂停（Obstructive sleep apnea，OSA）是一种常见的睡眠呼吸暂停疾病，由于间歇性缺氧和反复觉醒导致神经认知功能低下和器官系统功能障碍。反复的血流动力学应激与全身性高血压和心血管疾病的发病率增加有关。睡眠不足和睡眠中断对情绪、注意力、认知和行为都有类似的负面影响。在患有创伤后应激障碍（PTSD）的退伍军人中，睡眠紊乱会进一步恶化PTSD的认知行为表现，并导致不良的心理和身体健康结果。最近的流行病学研究在很大程度上支持PTSD患者与普通人群相比OSA发生率更高的相关性。用持续气道正压通气（CPAP）治疗潜在的阻塞性睡眠障碍，可恢复睡眠结构，减少白天嗜睡，减少噩梦的频率和强度。然而，坚持使用CPAP治疗在患有PTSD的退伍军人中并不理想。下颌前移装置（MAD）被认为是CPAP的非手术替代方案，并且在没有PTSD的OSA受试者中与CPAP进行头对头比较时是首选。然而，据我们所知，还没有研究评估MAD与CPAP在OSA合并PTSD患者中的临床疗效、依从性和睡眠质量。因此，我们假设MAD在治疗患有PTSD和OSA的退伍军人中有效治疗OSA方面不劣于CPAP。为此，我们建议进行一项可行性研究，使用12周的CPAP和MAD的随机交叉试验，在42名新诊断为OSA的PTSD门诊患者中进行为期2周的洗脱期。 本试验的主要终点是比较CPAP和MAD在患有PTSD和OSA的退伍军人中的治疗效果。次要终点旨在：1）比较使用CPAP与MAD治疗结束时埃普沃思嗜睡量表、SF-36和匹兹堡睡眠质量指数的变化，2）比较使用CPAP和MAD治疗患有OSA的PTSD患者的依从性和短期副作用，3）确定MDA成功应答的拟人、多导睡眠图和头影测量预测因子。四肢末端的评估包括对睡眠质量、日间嗜睡、生活质量和治疗副作用的评估。 将在每个治疗期结束时测量每种治疗的依从性。该试验的结果在确定患有PTSD和OSA的退伍军人中MAD与CPAP相比的疗效、耐受性和依从性方面至关重要。这项可行性研究将成为未来试验的基础，研究OSA的各种治疗方法对PTSD的治疗和进展的有效性。

DESCRIPTION (provided by applicant): Obstructive sleep apnea (OSA) is a prevalent disorder associated with poor neurocognitive performance and organ system dysfunction due to intermittent hypoxia and repeated arousals. The repetitive hemodynamic stresses are implicated in the increased incidence of systemic hypertension and cardiovascular diseases. Insufficient and disrupted sleep has similar negative impact on mood, attention, cognition, and behavior. In Veterans with post traumatic stress disorder (PTSD), the disturbed sleep can worsen further the cognitive-behavioral manifestations of PTSD and contributes to poor mental and physical health outcomes. Recent epidemiologic studies largely support the association of higher rates of OSA in patients with PTSD compared with the general population. Treatment of the underlying obstructive sleep disturbances with continuous positive airway pressure (CPAP) has resulted in restoration of sleep architecture, decrease daytime sleepiness, and reduction in nightmares frequency and intensity. However, adherence to treatment with CPAP is less than optimal in Veterans with PTSD. Mandibular advancing devices (MADs) are considered non surgical alternatives to CPAP and are preferred in a head to head comparison to CPAP in OSA subjects without PTSD. However, there has been no study to our knowledge that has assessed MAD in terms of clinical efficacy, compliance, and quality of sleep compared to CPAP in OSA patients with PTSD. Therefore, we hypothesize that MAD is not inferior to CPAP in treating OSA effectively in Veterans with PTSD and OSA. To that end, we propose to conduct a feasibility study using a randomized crossover trial of 12 weeks of CPAP and MAD in 42 consecutive outpatients with PTSD newly diagnosed with OSA separated by 2 weeks washout period. The primary endpoint of the trial is to compare the treatment efficacy of CPAP and MAD in Veterans with PTSD and OSA. Secondary endpoints aim at: 1) comparing change in the Epworth Sleepiness Scale, SF-36, and the Pittsburgh Sleep Quality Index at end of treatment following use of CPAP versus MAD, 2) comparing adherence and short-term side effects between using CPAP and MAD in PTSD patients with OSA, and 3) determining anthropomorphic, polysomnographic, and cephalometric predictors of successful MDA response. Assessments at the end of both limbs comprise evaluation of quality of sleep, daytime sleepiness, quality of life, and side effects of treatment. Compliance with each therapy will be measured at the end of each treatment period. The results of the trial are pivotal in determining the efficacy, tolerability, and adherence to MAD compared to CPAP in Veterans with PTSD and OSA. This feasibility study would form the basis of a future trial examining the effectiveness of various therapeutic modalities for OSA on PTSD symptomatology and progression.