Clinical trial NCT00607893: Efficacy of Continuous Positive Airway Pressure in Reducing Oxidative Stress in Individuals With Sleep Apnea
Official title: Oxidative Stress in Sleep Apnea and Cardiac Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Sleep Apnea Syndromes
Oxidative Stress
Cardiovascular Diseases
Keywords: Sleep-Disordered Breathing
Lead sponsor: Case Western Reserve University
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2008-02-06
Enrollment: 153
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: F2-isoprostanes/Cr
timeFrame: Measured between baseline and after treatment
measure: Myeloperoxidase
timeFrame: Measured between baseline and after treatment
Secondary outcomes:
measure: Mean Arterial BP, Evening
timeFrame: Measured between baseline and after treatment
measure: Pulse Wave Velocity, Evening
timeFrame: Measured between baseline and after treatment
measure: IL-6
timeFrame: Measured between baseline and after treatment
measure: Mean Arterial BP, Morning
timeFrame: Measured between baseline and after treatment
measure: sIL-6R
timeFrame: Measured between baseline and after treatment
measure: Pulse Wave Velocity, Morning
timeFrame: Measured between Months 2 and 3 of treatment
measure: Augmentation Index, Evening
timeFrame: Measured between Months 2 and 3 of treatment
measure: Augmentation Index, Morning
timeFrame: Measured between Months 2 and 3 of treatment
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
Study officials:
affiliation: University Hospitals Cleveland Medical Center
name: Reena Mehra, MD, MS
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.