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

Inflammation Clinical Trial

Official title:

Inflammatory Response to Sleep Apnea in Obese Subjects: The Cardiovascular Effects of Obstructive Sleep Apnea (COSA) Study

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00371293
• Other study ID #: 442
• Secondary ID: R01HL080076-01A1
• Status: Active, not recruiting
• Phase: N/A
• First received: September 1, 2006
• Last updated: June 13, 2012
• Start date: September 2006
• Est. completion date: August 2012

Study information

• Verified date: June 2012
• Source: University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 181
• Est. completion date: August 2012
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Apnea
• Inflammation
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive

Intervention

Behavioral:
• Weight Loss Program
Participants in the weight loss program will receive weekly dietary counseling and will be encouraged to decrease caloric intake and increase physical activity.

Device:
• CPAP therapy
Participants receiving CPAP therapy will use a CPAP machine each night while they sleep.

Locations

Country	Name	City	State
United States	Philadelphia Veterans Affairs Medical Center	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
University of Pennsylvania	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Inflammation		Measured at Week 24	No
Secondary	Insulin resistance		Measured at Week 24	No
Secondary	HDL cholesterol levels		Measured at Week 24	No
Secondary	Triglyceride levels		Measured at Week 24	No
Secondary	LDL cholesterol levels		Measured at Week 24	No