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

描述（由申请人提供）： 阻塞性睡眠呼吸暂停综合征（OSA）患者中有30-50%会出现失眠症状。失眠与OSA的普遍共同发生可能不仅有助于增加疾病负担，还可能代表对OSA治疗依从性的实质性障碍。OSA中的胰岛素抵抗通常被视为OSA的结果（并且在现有的临床护理指南中如此规定）。在原发性失眠症患者中，睡眠启动和睡眠维持问题的发生率相同。相反，在OSA患者中，研究人员收集的初步数据表明，睡眠维持性失眠更为明显，CPAP治疗可能改善睡眠维持性失眠，但不能改善睡眠起始性失眠。这就产生了一个基本假设，即OSA患者的失眠是一种异质性疾病，在某些情况下可能是直接由于OSA，而在其他情况下，它是独立的OSA。因此，研究人员提出了一项对照临床干预试验，使用持续气道正压通气+接触控制（CPAP+CC）臂，假CPAP +CC臂和CPAP+认知行为疗法治疗失眠（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（这可能是由于OSA），而不是睡眠启动失眠（这通常可能是独立的OSA），以及CBT是否提供额外的好处。由于在开放标签失眠研究中可能发生显著的安慰剂效应，因此纳入假CPAP成分是检验这一假设的创新和必要组成部分。与项目公告的目标一致，拟定的研究设计是一项包含108名受试者的初步临床试验，其中54名受试者有睡眠启动症状，54名受试者有睡眠维持症状，这些受试者将被随机分配至CPAP+CC、假CPAP+CC或CPAP+CBT（双盲）组，从而创建6个组（每组18名受试者）。研究目的包括评估CPAP、假CPAP和CPAP+CBT对失眠严重程度、日间结局（主观和客观）和客观测量的CPAP依从性的影响。拟议的试点研究是有效治疗OSA失眠症状的长期目标的关键第一步，并将实现计划公告中概述的几个关键目标：1）确定CPAP，假CPAP和CPAP+CBT在OSA失眠患者中的可行性; 2）评估对研究干预的依从性，以及3）确定研究参数和协变量，用于未来确定性多地点研究的样本量估计;将特别强调年龄、性别和种族等协变量的作用。该提案具有重大的公共卫生影响，因为它代表了对OSA失眠的新观点，挑战了现有的临床范式，将识别独立于OSA的失眠与OSA引起的失眠的特征，并最终通过识别需要靶向失眠治疗的患者来改善患者对CPAP治疗的依从性，这些患者将补充其CPAP治疗。

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.