Apnea, Bariatric Surgery Versus Continuous Positive Airway Pressure (CPAP) Trial

Study Overview
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Brief Summary
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The purpose of this study is to assess the feasibility of conducting a comparative effectiveness study comparing a medical versus surgical approach to the initial management of obstructive sleep apnea (OSA) in the setting of obesity.

Detailed Description
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Obstructive sleep apnea (OSA) is one of the most common complications of obesity, resulting in excessive sleepiness and daytime functional impairment as well as acting 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 studies, 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. This trial will 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 35-45 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 CPAP 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.

Official Title
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A Randomized Trial of Bariatric Surgery for the Treatment of Sleep Apnea

Conditions
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Obstructive Sleep Apnea, Obesity

Intervention / Treatment
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* Procedure: Laparoscopic Gastric Banding
* Procedure: Continuous Positive Airway Pressure


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Severe sleep apnea with at least 1 referable symptom Obesity (BMI 35-45 kg/m2) Exclusion Criteria: Prior use of CPAP within the last two years or prior bariatric surgery Hypoxemia or hypercapnia Elevated peri-operative risk Drowsy driving in past year Unstable medical or psychiatric conditions

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Laparoscopic Gastric Banding<br> | Procedure: Laparoscopic Gastric Banding<br>* Those randomized to surgery would meet with the bariatric surgeon and the dietitian during the 3 month weight management period and based on insurance requirements, would undergo LGB surgery after 3 months of weight management. PAP therapy would be utilized for the 3 week peri-operative period (1 week prior to 2 weeks post-operatively) given evidence that this might reduce peri-operative respiratory complications. Routine surgical follow-up will occur 2 weeks post-operatively and then every 4-6 weeks to assess weight loss trajectory and adjust the band as needed.<br>|
| Active Comparator: Continuous Positive Airway Pressure<br> | Procedure: Continuous Positive Airway Pressure<br>* Participants randomized to the CPAP arm will undergo a CPAP titration within 2 weeks of enrollment unless a split-night study was already performed as part of their diagnostic polysomnogram (PSG) providing a reliable CPAP therapeutic pressure. As soon as an appropriate pressure is identified, CPAP therapy will begin with routinely scheduled follow-up visits to maximize CPAP adherence. All participants will be offered a 12 month supervised weight loss program in addition to OSA-specific therapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effective Apnea Hypopnea Index | The Effective Apnea Hypopnea Index (AHI) is the actual frequency of apneas and hypopneas per hour that the patient is exposed to. It is calculated as the AHI while on CPAP times the proportion of sleep time that CPAP was used plus the AHI off CPAP times the proportion of sleep time that CPAP is not used. | 9 months | 
| Epworth Sleepiness Score | The Epworth Sleepiness Scale results in scores ranging from 0-24, where scores of 0-10 indicate normal levels of sleepiness while 11-24 indicate excessive daytime sleepiness. | 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean 24-hour Systolic Blood Pressure |  | 9 months | 
| Insulin Resistance (HOMA Index) |  | 9 months | 
| Calgary Sleep Apnea Quality of Life Index | The Calgary Sleep Apnea Quality of Life Index results in scores ranging from 1-7, with higher scores indicating a higher quality of life. | 9 months | 
| Depression (Patient Health Questionnaire-9) | The PHQ-9 is scored from 0-27 with higher scores indicating more severe depression. | 9 months | 
| Direct Health Care Costs |  | 9 months | 
| Mean 24-hour Diastolic Blood Pressure |  | 9 months |