The Effects of Obesity and Obstructive Sleep Apnea on Inflammation and Heart Disease

Not Applicable

Completed

Conditions: Inflammation
Sleep Apnea Syndromes

Interventions: Device: CPAP therapy
Behavioral: Weight Loss Program

Registration Number: NCT00371293

Lead Sponsor: University of Pennsylvania

Brief Summary: Obstructive sleep apnea (OSA) is a serious sleep disorder in which a person's breathing is restricted during sleep. Obese individuals with OSA are at an increased risk of inflammation and heart conditions, but it is unknown whether this risk is related to the effects of OSA or obesity. This study will evaluate whether OSA or obesity plays the primary role in inflammation related to heart disease. The study will also determine the independent effects of OSA and obesity on insulin resistance and blood vessel function.

Detailed Description: OSA is a common sleep disorder that is characterized by a brief collapse of the upper airway during sleep. This blockage prevents air from flowing properly into the lungs and causes pauses in breathing. If left untreated, OSA can cause high blood pressure, memory problems, weight gain, impotency, and headaches. It is also associated with an increased risk of inflammation-related heart conditions. Obesity is common among individuals with OSA and it may also be associated with inflammation. It is not known, however, whether the increased risk of heart problems is caused primarily by the inflammatory effects of OSA or obesity.

The most common treatment for OSA is continuous positive airway pressure (CPAP) therapy, in which a mask is worn over the nose during sleep. Air flows through the mask to maintain a level of pressure that keeps the throat open. The most common treatment for obesity is weight loss. This study will determine the primary cause of heart-related inflammation by evaluating the individual and combined effects of CPAP therapy and a weight loss program in treating obese individuals with OSA. The study will also determine the independent effects of these therapies on insulin resistance and blood vessel function (arterial stiffness, central arterial pressures).

This study will enroll obese individuals with moderate to severe OSA for a total of 24 weeks. Potential participants will first take part in an overnight sleep study at the University of Pennsylvania sleep lab. Sensors will monitor body functions during the night, including brain and muscle activity, eye movement, heart rate, breathing effort, air flow, and blood oxygen levels. Eligible participants will then be randomly assigned to CPAP therapy, a weight loss program, or a combination of the two. Participants in the weight loss program will receive weekly dietary counseling and will be encouraged to decrease caloric intake and increase physical activity. Participants receiving CPAP therapy will use a CPAP machine each night while they sleep. Study visits for all participants will occur at baseline and Weeks 6, 12, and 24. Blood will be collected to measure levels of triglycerides, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and levels of C-reactive protein (CRP), which is an inflammation biomarker. Insulin resistance will be evaluated using a glucose tolerance test, and blood vessel function will be evaluated using a brachial artery reactivity test in which artery size and blood flow will be measured with an ultrasound.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 181

Inclusion Criteria

Moderate to severe OSA (as defined by an apnea-hypopnea index [AHI] score greater than 15 events per hour)
Body mass index greater than 30 kg/m
Baseline CRP greater than 1.0 mg/dL

Exclusion Criteria

Predominant central sleep apnea
Type 1 Diabetes
Type 2 Diabetes associated with either: (a) unstable anti-diabetic therapy (anti-diabetic medication changes within past 3 months); (b) Hemoglobin A1C levels > 7%; (c) Inability to perform home blood glucose monitoring (fingerstick checks).
Requires use of supplemental oxygen
Acute coronary syndrome or stroke in the 3 months prior to study entry
A high-risk occupation or motor vehicle driving record, as defined by a score of 10 points or higher on an occupational and driving habits questionnaire
Blood pressure greater than 160/95 mm Hg (may be re-screened after blood pressure control is obtained)
Active infection, cancer, or chronic inflammatory disorder
Use of systemic steroids
Currently on an unstable dose of statin therapy (participants taking statins must be on a stable dose for at least 8 weeks prior to study entry)
Simultaneous use of peroxisome proliferator-activated receptor (PPAR)-alpha (e.g., gemfibrozil, fenofibrate) or PPAR-gamma (e.g., rosiglitazone, pioglitazone)
Consumes more than 14 alcoholic drinks per week
History of surgery in the 3 months prior to study entry
Sustained ventricular or supraventricular tachycardia greater than 30 seconds during overnight sleep study
Known left ventricular ejection fraction less than 30% or decompensated congestive heart failure requiring hospitalization in the year prior to study entry
Any episode of decompensated respiratory function requiring hospitalization in the year prior to study entry
Severe restless leg syndrome or chronic pain syndrome that gives rise to frequent awakenings at night, as determined during the overnight sleep study (individuals may still be enrolled if these sleep-disrupting disorders can be resolved prior to study entry)
Pregnant or likely to become pregnant (i.e., pre-menopausal and not using a form of birth control)
Severe depression, as defined by a score of 29 or higher on the Beck Depression Index, or suicidal ideation
Serious medical or psychological condition that may compromise the participant's safety or successful participation in the study, in the opinion of the investigator

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	CPAP therapy	Participants will receive CPAP therapy.
3	CPAP therapy	Participants will receive CPAP therapy and take part in a weight loss program.
2	Weight Loss Program	Participants will take part in a weight loss program.
3	Weight Loss Program	Participants will receive CPAP therapy and take part in a weight loss program.

Primary Outcome Measures

Name	Time	Method
Inflammation	Measured at Baseline and Week 24

Secondary Outcome Measures

Name	Time	Method
Change in Insulin Resistance (Insulin Sensitivity Index, x10-4/Min-1/μU/ml)	Measured at Baseline and Week 24	Assessed using the frequently sampled intravenous glucose tolerance test (FSIGTT) which evaluates blood glucose and insulin levels. Insulin sensitivity is estimated using the Bergman's minimal model.
Change in LDL Cholesterol Levels	Measured at Baseline and Week 24
Change in Triglyceride Levels	Measured at Baseline and Week 24
Change in HDL Cholesterol Levels	Measured at Baseline and Week 24

Trial Locations

Locations (2): Philadelphia Veterans Affairs Medical Center
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Philadelphia, Pennsylvania, United States
University of Pennsylvania
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Philadelphia, Pennsylvania, United States