Efficacy of Continuous Positive Airway Pressure in Reducing Oxidative Stress in Individuals With Sleep Apnea

Study Overview
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Brief Summary
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Sleep-disordered breathing (SDB) is a condition in which a person experiences frequent breathing pauses during sleep, also known as sleep apnea. There is evidence that the recurrent sleep arousal and associated shortage of oxygen in the body may increase risk for cardiovascular disease (CVD). It is believed that treatment with continuous positive airway pressure (CPAP) may reduce certain risk factors for heart disease, including markers of inflammation and oxidative stress. This study will evaluate the effectiveness of CPAP in reducing CVD risk factors in people with SDB.

Detailed Description
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It is estimated that 18 million Americans are affected by SDB. SDB involves repeated sleep arousal caused by breathing difficulties. These frequent sleep disruptions may cause a person to experience daytime drowsiness, impaired mental functioning, and trouble concentrating or staying alert. SDB is also associated with an increased risk of certain cardiovascular diseases, such as high blood pressure and heart disease. Researchers believe that increased oxidative stress and inflammation associated with SDB may play a role in the physiologic pathway linking SDB and CVD. However, more information on the SDB-CVD relationship is needed to be able to identify risk factors for CVD and to discover the best means of treatment. CPAP, a current treatment for SDB, acts by delivering air through a mask during sleep. CPAP helps improve overnight breathing and quality of sleep and may, in turn, decrease oxidative stress and associated CVD risks. This study will compare the effectiveness of CPAP versus placebo CPAP in reducing CVD risk factors, such as oxidative stress markers, in people with SDB. Participation in this study will last between 2.5 and 4 months and will include four to five study visits. During the first study visit, participants will undergo a CPAP titration study, which will involve appropriate CPAP mask fitting and an overnight sleep test to determine the best CPAP pressure, as well as a lower placebo pressure, for each participant. Participants will also be provided educational information on diet, sleep, and the use of CPAP as a treatment for sleep apnea. After the titration study, participants will be asked to wear their fitted CPAP mask every night for the next 2 weeks, during which they will use the lower (placebo) pressure one week and use the higher pressure the other week. During this time, a technician will contact participants every 3 to 4 days to address any questions or problems with the CPAP equipment. One month later, participants who were able to tolerate and use CPAP most nights will attend Visit 2. This second visit will include an overnight sleep study without wearing the CPAP mask; blood and saliva collection; cheek brushing for genetic material; tests on diabetes, artery stiffness, and circulation; body fat measurements; and questionnaires. Participants will then be randomly assigned to use either the higher pressure CPAP or the lower pressure CPAP for 8 weeks. Visit 3 will occur 1 week after beginning CPAP treatment and will include a fasting blood test. During treatment, participants will be periodically contacted by a technician to check on equipment status. Upon completing treatment, participants will undergo repeat tests from Visit 2, except that they will wear the CPAP mask in the overnight sleep test. This fourth study visit will mark the completion of treatment for participants assigned to the lower pressure CPAP. Participants assigned to the higher pressure CPAP will be asked to use CPAP for 4 more weeks. These participants will return at the end of the 4 weeks for a final visit, which will include a repeat sleep study and other testing.

Official Title
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Oxidative Stress in Sleep Apnea and Cardiac Disease

Conditions
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Sleep Apnea Syndromes, Oxidative Stress, Cardiovascular Diseases

Intervention / Treatment
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* Device: Continuous Positive Airway Pressure (CPAP)
* Device: Sham CPAP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Moderate to severe sleep disordered breathing (SDB) (Apnea Hypopnea Index [AHI] greater than or equal to 15) diagnosed within the 2 months before study entry Able to participate in more than two overnight/daytime sleep and physiologic assessments over a 2.5-month period Exclusion Criteria: Current or planned use of specific sleep apnea treatments (e.g., CPAP, oral appliance) outside of the study Anticipated upper airway surgery or gastric bypass surgery in the 4 months after study completion Supplemental oxygen use Primary sleep disorder other than sleep apnea (e.g., periodic limb movement disorder) Severe chronic insomnia or circadian rhythm disorder with less than 4 hours of sleep per night, chronic problems falling asleep within 1 hour of bedtime, or chronic problems with early morning awakenings Unstable medical conditions (e.g., new onset or changing angina; heart attack or congestive heart failure exacerbation documented within the 6 months before study entry; high grade cardiac dysrhythmia/heart block; known unaddressed coronary artery disease by history, angina, stroke, or uncontrolled hypertension or diabetes mellitus; thyroid disorder; cirrhosis; a non-skin cancer diagnosed within the 2 years before study entry) Inadequately treated psychiatric disorders or compromised competence Daytime sleepiness with reports of sleepiness while driving or during other situations that would present a risk for the subject or public (e.g., operating heavy equipment) Alcohol abuse Pregnancy Use of oral corticosteroids

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Sham CPAP<br>Participants will receive sham continuous positive airway pressure (CPAP) for a 2 month period. Sham CPAP involves wearing a device that appears similar to a standard CPAP device, but administers a negligible pressure. Adherence will be tracked while the participant wears the device. | Device: Sham CPAP<br>* Participants will use the lower pressure CPAP every night for 8 weeks.<br>|
| Active Comparator: Treatment CPAP<br>Participants will receive continuous positive airway pressure for a 2 month period. The optimal treatment pressure will be identified during a titration study prior to trial enrollment. Adherence will be tracked while the participant wears the device. | Device: Continuous Positive Airway Pressure (CPAP)<br>* Participants will use the higher pressure CPAP, as determined by an in-laboratory attended titration study, every night for 12 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| F2-isoprostanes/Cr | Oxidative stress outcome, analyzed absolute change from baseline, with adjustment of baseline | Measured between baseline and after treatment | 
| Myeloperoxidase | Oxidative stress outcome, analyzed absolute change from baseline, with adjustment of baseline | Measured between baseline and after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Arterial BP, Evening | Blood pressure outcome, analyzed absolute change from baseline, with adjustment of baseline | Measured between baseline and after treatment | 
| Pulse Wave Velocity, Evening | Pulse wave analysis outcome, analyzed absolute change from baseline, with adjustment of baseline | Measured between baseline and after treatment | 
| IL-6 | Measures of inflammation outcome, analyzed absolute change from baseline, with adjustment of baseline | Measured between baseline and after treatment | 
| Mean Arterial BP, Morning | Blood pressure outcome, analyzed absolute change from baseline, with adjustment of baseline | Measured between baseline and after treatment | 
| sIL-6R | Measures of inflammation outcome, logarithm transformed before analysis due to skewed distribution, analyzed change of from baseline with adjustment of baseline. The least squares mean is transformed back to present the percent change from baseline. | Measured between baseline and after treatment | 
| Pulse Wave Velocity, Morning | Pulse wave analysis outcome, analyzed absolute change from baseline, with adjustment of baseline | Measured between Months 2 and 3 of treatment | 
| Augmentation Index, Evening | Pulse wave analysis outcome (a ratio of the augmentation of central aortic pressure by a reflected pulse wave, calculated from the blood pressure waveform), analyzed absolute change from baseline, with adjustment of baseline | Measured between Months 2 and 3 of treatment | 
| Augmentation Index, Morning | Pulse wave analysis outcome (a ratio of the augmentation of central aortic pressure by a reflected pulse wave, calculated from the blood pressure waveform), analyzed absolute change from baseline, with adjustment of baseline | Measured between Months 2 and 3 of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sleep-Disordered Breathing