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

This study has been completed.
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Julio A. Chirinos, University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT00371293
First received: September 1, 2006
Last updated: February 18, 2017
Last verified: February 2017
  Purpose
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.

Condition Intervention
Sleep Apnea Syndromes
Inflammation
Behavioral: Weight Loss Program
Device: CPAP therapy

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: Inflammatory Response to Sleep Apnea in Obese Subjects: The Cardiovascular Effects of Obstructive Sleep Apnea (COSA) Study

Resource links provided by NLM:


Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:
  • Inflammation [ Time Frame: Measured at Baseline and Week 24 ]

Secondary Outcome Measures:
  • 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.

  • Change in LDL Cholesterol Levels [ Time Frame: Measured at Baseline and Week 24 ]
  • Change in Triglyceride Levels [ Time Frame: Measured at Baseline and Week 24 ]
  • Change in HDL Cholesterol Levels [ Time Frame: Measured at Baseline and Week 24 ]

Enrollment: 181
Study Start Date: September 2006
Study Completion Date: December 2013
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00371293

Locations
United States, Pennsylvania
Philadelphia Veterans Affairs Medical Center
Philadelphia, Pennsylvania, United States, 19014
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19014
Sponsors and Collaborators
University of Pennsylvania
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Principal Investigator: Julio A. Chirinos, MD University of Pennsylvania, Philadelphia Veterans Affairs Medical Center
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Julio A. Chirinos, MD, PhD, University of Pennsylvania
ClinicalTrials.gov Identifier: NCT00371293     History of Changes
Other Study ID Numbers: 442
R01HL080076-01A1 ( US NIH Grant/Contract Award Number )
Study First Received: September 1, 2006
Results First Received: December 4, 2014
Last Updated: February 18, 2017

Keywords provided by University of Pennsylvania:
Sleep Apnea
C-Reactive Protein
Obesity
Insulin Resistance
Arterial stiffness

Additional relevant MeSH terms:
Sleep Apnea Syndromes
Sleep Apnea, Obstructive
Inflammation
Apnea
Pathologic Processes
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Wake Disorders
Nervous System Diseases

ClinicalTrials.gov processed this record on April 21, 2017