Understanding the sleep apnea/insomnia interaction: a CPAP/sham-CPAP trial

描述(由申请人提供)： 高达30%-50%的阻塞性睡眠呼吸暂停(OSA)患者会出现失眠症状。普遍存在的失眠和阻塞性睡眠呼吸暂停综合征可能不仅会增加疾病负担，还可能对阻塞性睡眠呼吸暂停综合征的治疗坚持造成实质性的障碍。阻塞性睡眠呼吸暂停综合征的失眠通常被认为是阻塞性睡眠呼吸暂停综合症的结果(现有的临床护理指南中对此有明确规定)。在“原发性失眠”患者中，睡眠启动问题和睡眠维持问题的发生率相同。相比之下，研究调查人员收集的初步数据表明，在阻塞性睡眠呼吸暂停综合征患者中，睡眠维持性失眠更为明显，CPAP治疗可能会改善睡眠维持性，但不会改善睡眠启动失眠。这提出了OSA患者失眠是一种异质性障碍的基本假设，在某些情况下可能直接由OSA引起，而在其他情况下它是独立于OSA的。因此，研究人员建议进行一项对照临床干预试验，使用持续正压+接触控制(CPAP+CC)组、假CPAP+CC组和CPAP+失眠认知行为疗法(CPAP+CBT)组，以评估OSA治疗对失眠的影响程度，这些影响是否仅限于睡眠维持性失眠(很可能是由OSA引起的)，而不是睡眠启动失眠(通常可能是独立于OSA)，以及CBT是否提供额外的好处。纳入Sham-CPAP成分是检验这一假说的一个创新和必要的成分，因为在开放标签失眠研究中可能出现显著的安慰剂效应。与计划公告的目标一致，拟议的研究设计是一项针对108名受试者的试点临床试验，其中54名有睡眠启动症状，54名有睡眠维持症状，他们将被随机分为CPAP+CC、Sham-CPAP+CC或CPAP+CBT(双盲)，从而创建六组(每组18名受试者)。这项研究的目的包括评估CPAP、假CPAP和CPAP+CBT对失眠严重程度、白天结果(主观和客观)和客观测量的CPAP依从性的影响。拟议的试验性研究是有效治疗阻塞性睡眠呼吸暂停综合征失眠症状的长期目标的关键的第一步，将实现计划公告中概述的几个关键目标：1)确定CPAP、SHAM-CPAP和CPAP+CBT在阻塞性睡眠呼吸暂停综合征失眠患者中的可行性；2)评估对研究干预的遵守情况；3)确定研究参数和协变量，用于未来确定的多地点研究的样本量估计；将特别强调协变量的作用，如年龄、性别和种族。这项提案具有重大的公共卫生影响，因为它代表了一种挑战现有临床范式的关于OSA失眠的新视角，将确定与OSA无关的失眠与OSA引起的失眠的特征，并可能通过确定哪些患者需要进行定向失眠治疗来补充他们的CPAP治疗，最终提高患者对CPAP治疗的依从性。

DESCRIPTION (provided by applicant): Insomnia symptoms occur in up to 30-50% of obstructive sleep apnea (OSA) patients. The prevalent co- occurrence of insomnia with OSA may not only serve to increase illness burden, it may also represent a substantial impediment to OSA treatment adherence. Insomnia in OSA has generally been viewed as a consequence of OSA (and is so specified in the existing clinical care guidelines). In patients with 'Primary Insomnia', sleep initiation and sleep maintenance problems occur with equal prevalence. In contrast, in patients with OSA, preliminary data gathered by the study investigators suggest that sleep maintenance insomnia is more pronounced and that CPAP treatment may ameliorate sleep maintenance but not sleep initiation insomnia. This gives rise to the primary hypothesis that insomnia in OSA patients is a heterogenous disorder which in some cases may be directly due to the OSA, while in others it is independent of the OSA. Accordingly, the investigators propose a controlled clinical intervention trial using a continuous positive airway pressure+contact control (CPAP+CC) arm, a sham-CPAP+CC arm and a CPAP+cognitive behavioral therapy for insomnia (CPAP+CBT) arm to assess the extent to which OSA treatment affects insomnia, whether these effects are limited to sleep maintenance insomnia (which is likely to be due to OSA) as opposed to sleep initiation insomnia (which may generally be independent of OSA), and whether CBT provides additional benefit. Inclusion of a sham-CPAP component is an innovative and essential component in testing this hypothesis because of the significant placebo effects that can occur in open-label insomnia research. Consistent with the goals of the Program Announcement, the proposed study design is a pilot clinical trial of 108 subjects, 54 with sleep initiation symptoms and 54 wih sleep maintenance symptoms, who will be randomized to CPAP+CC, sham- CPAP+CC, or CPAP+CBT (double-blind), thus creating six groups (18 subjects per group). The study aims include assessing CPAP, sham-CPAP, and CPAP+CBT effects on insomnia severity, daytime outcomes (both subjective and objective) and objectively measured CPAP adherence. The proposed pilot study is a crucial first step in the long-term objective of effectively treating insomnia symptoms in OSA and would accomplish several key goals as outlined in the program announcement: 1) Determine the feasibility of CPAP, sham-CPAP, and CPAP+CBT in OSA patients with insomnia; 2) Assess adherence to the study intervention and 3) Identify study parameters and covariates for sample size estimates for a future definitive multi-site study; particular emphasis will be placed on the role of covariates such as age, gender and race. The proposal has significant public health ramifications in that it represents a novel perspective on insomnia in OSA that challenges existing clinical paradigms, will identify characteristics of insomnia independent from OSA versus insomnia due to OSA, and could ultimately improve patient adherence to CPAP therapy by identifying patients who warrant targeted insomnia therapy that will supplement their CPAP therapy.