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

February 18, 2017 updated by: Julio A. Chirinos, University of Pennsylvania

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

181

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19014
        • University of Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19014
        • Philadelphia Veterans Affairs Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 1
Participants will receive CPAP therapy.
Device: CPAP therapy
Participants receiving CPAP therapy will use a CPAP machine each night while they sleep.
Active Comparator: 2
Participants will take part in a weight loss program.
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.
Experimental: 3
Participants will receive CPAP therapy and take part in a weight loss program.
Device: CPAP therapy
Participants receiving CPAP therapy will use a CPAP machine each night while they sleep.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Inflammation
Time Frame: Measured at Baseline and Week 24
Measured at Baseline and Week 24

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Insulin Resistance (Insulin Sensitivity Index, x10-4/Min-1/μU/ml)
Time Frame: 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.
Measured at Baseline and Week 24
Change in LDL Cholesterol Levels
Time Frame: Measured at Baseline and Week 24
Measured at Baseline and Week 24
Change in Triglyceride Levels
Time Frame: Measured at Baseline and Week 24
Measured at Baseline and Week 24
Change in HDL Cholesterol Levels
Time Frame: Measured at Baseline and Week 24
Measured at Baseline and Week 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Pennsylvania

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

  • Principal Investigator: Julio A. Chirinos, MD, University of Pennsylvania, Philadelphia Veterans Affairs Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2006

Primary Completion (Actual)

September 1, 2012

Study Completion (Actual)

December 1, 2013

Study Registration Dates

First Submitted

September 1, 2006

First Submitted That Met QC Criteria

September 1, 2006

First Posted (Estimate)

September 4, 2006

Study Record Updates

Last Update Posted (Actual)

April 5, 2017

Last Update Submitted That Met QC Criteria

February 18, 2017

Last Verified

February 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 442
  • R01HL080076-01A1 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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