- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00607893
Efficacy of Continuous Positive Airway Pressure in Reducing Oxidative Stress in Individuals With Sleep Apnea (SASS)
Oxidative Stress in Sleep Apnea and Cardiac Disease
Study Overview
Status
Intervention / Treatment
Detailed Description
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.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Ohio
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Cleveland, Ohio, United States, 44106
- University Hospitals Case Medical Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Sham Comparator: Sham CPAP
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.
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Participants will use the lower pressure CPAP every night for 8 weeks.
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Active Comparator: Treatment CPAP
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.
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Participants will use the higher pressure CPAP, as determined by an in-laboratory attended titration study, every night for 12 weeks.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
F2-isoprostanes/Cr
Time Frame: Measured between baseline and after treatment
|
Oxidative stress outcome, analyzed absolute change from baseline, with adjustment of baseline
|
Measured between baseline and after treatment
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Myeloperoxidase
Time Frame: Measured between baseline and after treatment
|
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
Time Frame: Measured between baseline and after treatment
|
Blood pressure outcome, analyzed absolute change from baseline, with adjustment of baseline
|
Measured between baseline and after treatment
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Pulse Wave Velocity, Evening
Time Frame: Measured between baseline and after treatment
|
Pulse wave analysis outcome, analyzed absolute change from baseline, with adjustment of baseline
|
Measured between baseline and after treatment
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IL-6
Time Frame: Measured between baseline and after treatment
|
Measures of inflammation outcome, analyzed absolute change from baseline, with adjustment of baseline
|
Measured between baseline and after treatment
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Mean Arterial BP, Morning
Time Frame: Measured between baseline and after treatment
|
Blood pressure outcome, analyzed absolute change from baseline, with adjustment of baseline
|
Measured between baseline and after treatment
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sIL-6R
Time Frame: Measured between baseline and after treatment
|
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
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Pulse Wave Velocity, Morning
Time Frame: Measured between Months 2 and 3 of treatment
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Pulse wave analysis outcome, analyzed absolute change from baseline, with adjustment of baseline
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Measured between Months 2 and 3 of treatment
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Augmentation Index, Evening
Time Frame: Measured between Months 2 and 3 of treatment
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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
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Measured between Months 2 and 3 of treatment
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Augmentation Index, Morning
Time Frame: Measured between Months 2 and 3 of treatment
|
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
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Reena Mehra, MD, MS, University Hospitals Cleveland Medical Center
Publications and helpful links
General Publications
- Mehra R, Storfer-Isser A, Kirchner HL, Johnson N, Jenny N, Tracy RP, Redline S. Soluble interleukin 6 receptor: A novel marker of moderate to severe sleep-related breathing disorder. Arch Intern Med. 2006 Sep 18;166(16):1725-31. doi: 10.1001/archinte.166.16.1725.
- Mehra R, Principe-Rodriguez K, Kirchner HL, Strohl KP. Sleep apnea in acute coronary syndrome: high prevalence but low impact on 6-month outcome. Sleep Med. 2006 Sep;7(6):521-8. doi: 10.1016/j.sleep.2006.03.012. Epub 2006 Aug 23.
- Mehra R, Benjamin EJ, Shahar E, Gottlieb DJ, Nawabit R, Kirchner HL, Sahadevan J, Redline S; Sleep Heart Health Study. Association of nocturnal arrhythmias with sleep-disordered breathing: The Sleep Heart Health Study. Am J Respir Crit Care Med. 2006 Apr 15;173(8):910-6. doi: 10.1164/rccm.200509-1442OC. Epub 2006 Jan 19.
- May AM, Wang L, Strohl KP, Walia H, Hazen SL, Mehra R. Sex-Specific Differential Responses of Circulating Biomarkers in Obstructive Sleep Apnea Treatment. A Post Hoc Analysis of a Randomized Controlled Trial. Ann Am Thorac Soc. 2020 May;17(5):605-613. doi: 10.1513/AnnalsATS.201908-593OC.
- May AM, Gharibeh T, Wang L, Hurley A, Walia H, Strohl KP, Mehra R. CPAP Adherence Predictors in a Randomized Trial of Moderate-to-Severe OSA Enriched With Women and Minorities. Chest. 2018 Sep;154(3):567-578. doi: 10.1016/j.chest.2018.04.010. Epub 2018 Apr 21.
- DeMartino T, Ghoul RE, Wang L, Bena J, Hazen SL, Tracy R, Patel SR, Auckley D, Mehra R. Oxidative Stress and Inflammation Differentially Elevated in Objective Versus Habitual Subjective Reduced Sleep Duration in Obstructive Sleep Apnea. Sleep. 2016 Jul 1;39(7):1361-9. doi: 10.5665/sleep.5964.
- Paz Y Mar HL, Hazen SL, Tracy RP, Strohl KP, Auckley D, Bena J, Wang L, Walia HK, Patel SR, Mehra R. Effect of Continuous Positive Airway Pressure on Cardiovascular Biomarkers: The Sleep Apnea Stress Randomized Controlled Trial. Chest. 2016 Jul;150(1):80-90. doi: 10.1016/j.chest.2016.03.002. Epub 2016 Mar 18.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 562
- K23HL079114 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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