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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL106410-04
Application #
8386593
Study Section
Special Emphasis Panel (ZDK1-GRB-N (M2))
Program Officer
Bonds, Denise
Project Start
2010-08-14
Project End
2014-11-30
Budget Start
2012-12-01
Budget End
2014-11-30
Support Year
4
Fiscal Year
2013
Total Cost
$928,623
Indirect Cost
$393,975
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115