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

Cardiovascular Diseases Clinical Trial

— SASS  

Official title:

Oxidative Stress in Sleep Apnea and Cardiac Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00607893
• Other study ID #: 562
• Secondary ID: K23HL079114
• Status: Completed
• Phase: N/A
• First received: January 25, 2008
• Last updated: July 21, 2014
• Start date: September 2006
• Est. completion date: July 2011

Study information

• Verified date: July 2014
• Source: Case Western Reserve University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 149
• Est. completion date: July 2011
• Est. primary completion date: July 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 20 Years to 75 Years

Eligibility

Inclusion Criteria:

• Moderate to severe 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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Apnea
• Cardiovascular Diseases
• Oxidative Stress
• Sleep Apnea Syndromes

Intervention

Device:
• Continuous Positive Airway Pressure (CPAP)
Participants will use the higher pressure CPAP, as determined by an in-laboratory attended titration study, every night for 12 weeks.
• Sham CPAP
Participants will use the lower pressure CPAP every night for 8 weeks.

Locations

Country	Name	City	State
United States	University Hospitals Case Medical Center	Cleveland	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Case Western Reserve University	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. Epub 2006 Jan 19. — View 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. Epub 2006 Aug 23. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Oxidative stress		Measured between Months 2 and 3 of treatment	No
Secondary	Blood pressure		Measured between Months 2 and 3 of treatment	No
Secondary	Pulse wave analysis		Measured between Months 2 and 3 of treatment	No
Secondary	Measures of inflammation		Measured between Months 2 and 3 of treatment	No
Secondary	Salivary cortisol		Measured between Months 2 and 3 of treatment	No
Secondary	Insulin resistance		Measured between Months 2 and 3 of treatment	No