A randomized trial of bariatric surgery for the treatment of sleep apnea

描述(申请人提供)：阻塞性睡眠呼吸暂停(OSA)是肥胖最常见的并发症之一，导致过度嗜睡和日间功能障碍。此外，反复暴露于间歇性低氧血症似乎与肥胖在高血压、胰岛素抵抗、糖尿病、心血管疾病和中风的易感性方面具有协同作用。目前治疗中重度OSA的一线治疗，鼻腔持续正压(CPAP)非常有效，但往往耐受性不佳，导致许多患者的依从率较低。减肥手术已经被批准用于治疗OSA合并肥胖症患者，在小病例系列中，似乎产生了实质性的改善。然而，还没有直接比较减肥手术和标准CPAP治疗的试验，以指导临床医生和患者选择最合适的一线治疗。我们建议进行一项试验性研究，以解决可行性和安全性，并估计随后的第三阶段试验的效果大小。我们将从两个大型临床睡眠计划中招募80名患有严重阻塞性睡眠呼吸暂停综合征和病态肥胖(体重指数为35-40公斤/平方米)的患者，这两个计划共同照顾范围广泛和人口统计多样化的阻塞性睡眠呼吸暂停患者群体。在建立患者和医生的平衡后，受试者将被随机分成CPAP试验或腹腔镜胃束带试验，作为OSA的一线治疗。主要的结果衡量标准将是在理想和现实生活条件下(即在阻塞性睡眠呼吸暂停组中，分别在受控环境中使用CPAP与在通常的家庭环境中使用处方疗法时)OSA严重程度的改善，这将允许对相对疗效和有效性进行评估。将在9个月后对结果进行评估，以量化每种治疗策略的早期有效性，并证明在未来使用这两种药物进行更大规模的长期试验时的临床均衡性。进一步的随访将在18个月后在40名患者的子组中进行，以确定在减肥手臂体重接近平台点时的后续研究的效果大小。次要结果将包括与患者相关的结果，包括嗜睡、生活质量和卫生服务利用指数。此外，还将评估与炎症、胰岛素抵抗、血脂、血压和动脉僵硬相关的生物标志物的变化，以及与BMI和OSA变化的关系，以确定未来试验的有希望的结果指标。将收集所有科目的已发生成本，以便确定成本效益分析所需的参数。这项初步研究将是首次对阻塞性睡眠呼吸暂停综合征的内科和外科治疗进行对照比较，此外，还将提供必要的数据，为随后的长期多中心比较有效性研究开发最佳研究设计，以便更好地了解减肥手术在阻塞性睡眠呼吸暂停综合征的治疗中可能起到的潜在作用。 与公共健康相关：睡眠呼吸暂停是肥胖最常见的并发症之一，涉及睡眠时呼吸暂停。目前，最常见的睡眠呼吸暂停治疗方法是持续气道正压治疗(CPAP)，它包括一个戴在鼻子上的口罩和一个在压力下吹气的鼓风机。虽然CPAP在保持喉咙畅通方面是有效的，但它通常会让人感到不舒服，因此许多患者很难定期使用。减肥或减肥手术已被证明在减肥方面有效，正因为如此，也可能在治疗睡眠呼吸暂停方面有效。在这项研究中，我们将进行一项试验，比较CPAP和减肥手术治疗严重睡眠呼吸暂停和病态肥胖患者的能力。

DESCRIPTION (provided by applicant): Obstructive sleep apnea (OSA) is one of the most common complications of obesity, resulting in excessive sleepiness and daytime functional impairment. In addition, the recurrent exposure to intermittent hypoxemia appears to act synergistically with obesity in predisposing to hypertension, insulin resistance, diabetes, cardiovascular disease, and stroke. The current first line treatment for moderate to severe OSA, nasal continuous positive airway pressure (CPAP) is extremely effective but is often not well tolerated, leading to low adherence rates in many patients. Bariatric surgery has been approved as treatment for OSA in patients with co-morbid obesity and in small case series, appears to produce substantial improvements. However, no trials directly comparing bariatric procedures with standard CPAP treatment yet exist to guide clinicians and patients in choosing the most appropriate first line treatment. We propose to conduct a pilot study to address the feasibility and safety, and estimate the effect sizes for a subsequent Phase 3 trial. We will recruit 80 patients with severe OSA and morbid obesity (body mass index, BMI, of 35-40 kg/m2) from two large clinical sleep programs that together care for a wide spectrum and demographically diverse group of OSA patients. After establishing patient and physician equipoise, subjects will be randomized to a trial of CPAP or laparoscopic gastric banding as first line treatment for OSA. The primary outcome measures will be improvement in OSA severity under both ideal and real life conditions (i.e., in the OSA arm, while using CPAP in a controlled environment vs. while using prescribed therapy in the usual home environment, respectively), which will allow for assessments of both comparative efficacy and effectiveness. Outcomes will be assessed at 9 months to quantify the early effectiveness of each treatment strategy as well as to demonstrate clinical equipoise in conducting a future larger long term trial using these two arms. Further follow-up will occur at 18 months in a subset of 40 patients to determine effect sizes for the subsequent study at a point where the bariatric arm has neared a plateau in weight. Secondary outcomes will include patient-related outcomes including sleepiness, quality of life, and an index of health service utilization. In addition, changes in biomarkers related to inflammation, insulin resistance, lipids, blood pressure, and arterial stiffness will be assessed in each group, and in relationship to changes in BMI and OSA, to identify promising outcome measures for future trials. Incurred costs will be collected in all subjects in order to establish the parameters needed for a cost effectiveness analysis. This pilot study will represent the first controlled comparison of medical and surgical treatments for OSA and in addition, will provide the necessary data to develop the optimal study design for a subsequent long term multi-center comparative effectiveness study to better understand the potential role that bariatric surgery may offer in the management of OSA. PUBLIC HEALTH RELEVANCE: Sleep apnea, which involves breathing stoppages during sleep, is one of the most common complications of obesity. Currently the most common treatment for sleep apnea is continuous positive airway pressure (CPAP) which consists of a mask applied to the nose and a blower that blows air under pressure. While CPAP is effective at keeping the throat open, it is often uncomfortable and so difficult for many patients to use on a regular basis. Bariatric or weight loss surgery has been shown to be effective at producing weight loss and because of this, may also be effective at curing sleep apnea. In this study, we will conduct a trial comparing the ability of CPAP and bariatric surgery to treat sleep apnea in patients who have severe sleep apnea and morbid obesity.