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

Primary Purpose

Sleep Apnea Syndromes, Inflammation

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Weight Loss Program
CPAP therapy
Sponsored by
University of Pennsylvania
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sleep Apnea Syndromes focused on measuring Sleep Apnea, C-Reactive Protein, Obesity, Insulin Resistance, Arterial stiffness

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Philadelphia Veterans Affairs Medical Center
  • University of Pennsylvania

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Experimental

Arm Label

1

2

3

Arm Description

Participants will receive CPAP therapy.

Participants will take part in a weight loss program.

Participants will receive CPAP therapy and take part in a weight loss program.

Outcomes

Primary Outcome Measures

Inflammation

Secondary Outcome Measures

Change in Insulin Resistance (Insulin Sensitivity Index, x10-4/Min-1/μU/ml)
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
Change in Triglyceride Levels
Change in HDL Cholesterol Levels

Full Information

First Posted
September 1, 2006
Last Updated
February 18, 2017
Sponsor
University of Pennsylvania
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
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1. Study Identification

Unique Protocol Identification Number
NCT00371293
Brief Title
The Effects of Obesity and Obstructive Sleep Apnea on Inflammation and Heart Disease
Official Title
Inflammatory Response to Sleep Apnea in Obese Subjects: The Cardiovascular Effects of Obstructive Sleep Apnea (COSA) Study
Study Type
Interventional

2. Study Status

Record Verification Date
February 2017
Overall Recruitment Status
Completed
Study Start Date
September 2006 (undefined)
Primary Completion Date
September 2012 (Actual)
Study Completion Date
December 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Pennsylvania
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sleep Apnea Syndromes, Inflammation
Keywords
Sleep Apnea, C-Reactive Protein, Obesity, Insulin Resistance, Arterial stiffness

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
181 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Active Comparator
Arm Description
Participants will receive CPAP therapy.
Arm Title
2
Arm Type
Active Comparator
Arm Description
Participants will take part in a weight loss program.
Arm Title
3
Arm Type
Experimental
Arm Description
Participants will receive CPAP therapy and take part in a weight loss program.
Intervention Type
Behavioral
Intervention Name(s)
Weight Loss Program
Intervention Description
Participants in the weight loss program will receive weekly dietary counseling and will be encouraged to decrease caloric intake and increase physical activity.
Intervention Type
Device
Intervention Name(s)
CPAP therapy
Intervention Description
Participants receiving CPAP therapy will use a CPAP machine each night while they sleep.
Primary Outcome Measure Information:
Title
Inflammation
Time Frame
Measured at Baseline and Week 24
Secondary Outcome Measure Information:
Title
Change in Insulin Resistance (Insulin Sensitivity Index, x10-4/Min-1/μU/ml)
Description
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.
Time Frame
Measured at Baseline and Week 24
Title
Change in LDL Cholesterol Levels
Time Frame
Measured at Baseline and Week 24
Title
Change in Triglyceride Levels
Time Frame
Measured at Baseline and Week 24
Title
Change in HDL Cholesterol Levels
Time Frame
Measured at Baseline and Week 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Julio A. Chirinos, MD
Organizational Affiliation
University of Pennsylvania, Philadelphia Veterans Affairs Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Philadelphia Veterans Affairs Medical Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19014
Country
United States
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19014
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
29038203
Citation
Jain S, Gurubhagavatula I, Townsend R, Kuna ST, Teff K, Wadden TA, Chittams J, Hanlon AL, Maislin G, Saif H, Broderick P, Ahmad Z, Pack AI, Chirinos JA. Effect of CPAP, Weight Loss, or CPAP Plus Weight Loss on Central Hemodynamics and Arterial Stiffness. Hypertension. 2017 Dec;70(6):1283-1290. doi: 10.1161/HYPERTENSIONAHA.117.09392. Epub 2017 Oct 16.
Results Reference
derived
PubMed Identifier
24918371
Citation
Chirinos JA, Gurubhagavatula I, Teff K, Rader DJ, Wadden TA, Townsend R, Foster GD, Maislin G, Saif H, Broderick P, Chittams J, Hanlon AL, Pack AI. CPAP, weight loss, or both for obstructive sleep apnea. N Engl J Med. 2014 Jun 12;370(24):2265-75. doi: 10.1056/NEJMoa1306187.
Results Reference
derived

Learn more about this trial

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

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