Continuous Positive Airway Pressure to Improve Milder Obstructive Sleep Apnea

Study Overview
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Brief Summary
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The purpose of this study is to determine whether functional status improves in individuals with milder obstructive sleep apnea (OSA) following continuous positive airway pressure (CPAP) treatment.

Detailed Description
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BACKGROUND: OSA is characterized as mild, moderate, or severe, according to the number of respiratory disturbances per hour of sleep (RDI), as defined by the American Academy of Sleep Medicine. CPAP is the primary treatment for sleep apnea. The column of pressure delivered to the upper airway by this device immediately eliminates the respiratory disturbances when it is applied. There is evidence from randomized controlled studies that CPAP also improves functional status, and the key manifestation of OSA, including excessive daytime sleepiness, in individuals with severe OSI (i.e., RDI greater than 30). However, there has been limited research exploring improvement in functional status in individuals with less severe OSA (i.e., those with mild OSA and RDI of 5-15 or moderate OSA and RDI of 16-30). The large placebo effect that has been reported in controlled studies of OSA-associated functional outcomes mandates the need for a placebo in studies evaluating the true impact of this treatment. Results from the three randomized controlled studies in milder OSA that have examined this issue have been equivocal, principally because of serious methodological limitations. It remains unclear whether CPAP treatment improves daily functioning in those with milder OSA (RDI 5-30). This is a critical issue as this level of disease severity represents the largest segment of OSA and comprises 15% of the U.S. population. DESIGN NARRATIVE: Using Granger's model of functional assessment, this study will examine whether functional status improves in participants with milder OSA following CPAP treatment. The study will employ a randomized, placebo-controlled, parallel study design, and will use a sham CPAP device as the placebo in participants with significant daytime sleepiness. The study will test the hypothesis that the change in functional status (measured by the Functional Outcomes of Sleep Questionnaire) after 8 weeks of treatment will be greater for participants treated with active CPAP compared to the placebo. Secondary aims of the study include examining whether CPAP also improves daytime sleepiness, and determining whether CPAP can reduce nocturnal blood pressure to lower the risk for stroke and hypertension linked to OSA.

Official Title
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Impact of CPAP on Functional Outcomes in Milder Obstructive Sleep Apnea (CATNAP)

Conditions
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Lung Diseases, Sleep Apnea Syndromes, Hypertension

Intervention / Treatment
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* Device: Continuous Positive Airway Pressure (CPAP) Treatment
* Device: Sham CPAP device - CPAP device with pressure delivered <1 cm H20


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Newly diagnosed with OSA on overnight polysomnogram (PSG) with RDI between 5 and 30 Score of greater than 11 on the Epworth Sleepiness Scale (ESS) on two administrations of the instrument (performed at prescreening and screening), each completed on a different day to avoid sporadic values and confirm the presence of excessive daytime sleepiness Stable medical history and no change in medications, including hypertension medications, in the 3 months prior to study entry Stable psychiatric history and no change in psychotropic medications in the 3 months prior to study entry Has access to a telephone Exclusion Criteria Diagnosis of another sleep disorder in addition to OSA based on PSG, e.g., periodic limb movement disorder (greater than 10 limb movements per hour of sleep with arousal); central sleep apnea (greater than 5 or more central apneas); insomnia; sleep hypoventilation syndrome; or narcolepsy Previous treatment for sleep apnea with nasal CPAP, oral appliance, home oxygen therapy, uvulopalatopharyngoplasty, tracheotomy, or other surgery for OSA Oxygen or bi-level CPAP required for treatment of OSA Unable to return for study instructions or follow-up testing Medically unstable condition (e.g., heart attack, congestive heart failure, Cheyne-Stokes breathing, unstable angina, uncontrolled thyroid disease, unstable diabetes, depression or psychosis, ventricular arrhythmias, cirrhosis, or recently diagnosed cancer) in the 3 months prior to study entry Regular use (greater than 3 times per week) of sedative, hypnotic, or alerting medications (such as Modafinil) in the 3 months prior to study entry Chronic nasal congestion that would prevent the use of a nasal mask, in the 3 months prior to study entry History of automobile accidents due to excessive daytime sleepiness Employed in transportation-related safety sensitive occupation such as an airline pilot, truck driver, or train engineer Night shift worker regularly experiencing jet lag, or a history of irregular work schedules in the 6 months prior to study entry Regular use of alcohol as determined by answering yes to one or more of the questions on the CAGE questionnaire (i.e., alcohol dependent) Recent or recurring history of substance abuse leading to tolerance or dependence Pregnant; women must either be postmenopausal or confirmed not pregnant by a urine pregnancy test Unable to perform study tests, e.g., inability to communicate verbally; inability to write and read in English; less than a 5th grade reading level (evaluated using Flesch-Kincaid assessment); visual impairment; hearing impairment; cognitive impairment (e.g., previous head injury); or upper extremity motor deficit (e.g., previous stroke or spinal cord injury) Residing with an individual who is currently using CPAP treatment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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 |
| --- | --- |
| Active Comparator: Active Treatment<br>Continuous Positive Airway Pressure Treatment | Device: Continuous Positive Airway Pressure (CPAP) Treatment<br>* CPAP device used at night<br>* Other names: Positive Airway Pressure;|
| Placebo Comparator: Sham/Placebo Treatment<br>Ineffective sham continuous positive airway pressure device with leak in interface to <1.0 cm H2O and resistance in motor to simulate normal operating noise and no compensation for leak. | Device: Sham CPAP device - CPAP device with pressure delivered <1 cm H20<br>* Sham CPAP device used at night<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Score of the Functional Outcomes of Sleep Questionnaire at Baseline and Week 8 Treatment | The primary endpoint is change after 8 weeks of treatment from baseline value (controlling for baseline value) in the 30-item Functional Outcomes of Sleep Questionnaire (FOSQ) that will be used to test the primary study hypothesis that patients with milder OSA (RDI 5-30) on active treatment will demonstrate greater mean change for the Total score from baseline to 8 weeks treatment. The FOSQ is designed to assess the impact of excessive sleepiness on functional status. The instrument has established content validity, test-retest reliability (r= 0.91), and internal consistency (alpha = 0.96). The scale ranges from 5 - 20 with normal functional status being a value greater than 17. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Score From Baseline to 8 Weeks Treatment Epworth Sleepiness Scale | Change in the score from baseline to 8 weeks treatment, controlling for baseline in the self-rated 8 item measure of daytime sleepiness with a range from 0 - 24. Lower values indicting less daytime sleepiness | Measured at Baseline and Week 8 of treatment in ITT sample | 
| Change in Mean Arterial Daytime Pressure at Baseline and Week 8 Treatment | Change in mean arterial pressure (MAP) value from baseline to 8 weeks treatment, controlling for baseline, measured by 48 hours ambulatory blood pressure device - Space Laboratories | Measured at Baseline and Week 8 treatment in the ITT sample | 
| Change in the Score From Baseline to 8 Weeks Treatment Measured by the Profile of Mood States | Change in the score from baseline to 8 weeks treatment, controlling for baseline, in the POMS is a reliable and valid measure of mood states that consists of 65 adjectives on which subjects' rate themselves as they feel today using a five-point scale. There are six mood or affective states on this test derived through factor analysis: Tension-Anxiety (score range 0-36), Depression-Dejection (score range 0 - 60), Anger-Hostility (score range 0-48), Vigor-Activity (score range 0-32), Fatigue-Inertia (score range 0-28), and Confusion-Bewilderment (score range 0-28). There is also a summary Total Mood Disturbance (TMD) score that gives a Total estimate of affective state score range 0-200). Higher scores indicate greater disability. | Measured at Baseline and Week 8 treatment in the ITT sample | 
| Change in the Number of Lapses From Baseline to 8 Weeks Treatment on the Psychomotor Vigilance Task (PVT) - Total Lapses in 20 Minute Test | Change in the score from baseline to 8 weeks treatment, controlling for baseline, in the PVT is an objective assessment of sleepiness and measures decrements in neurobehavioral performance due to sleepiness, i.e., ability to sustain attention and respond in a timely manner to salient signals.(7) The PVT yields five highly informative metrics on the capacity for sustained attention and vigilance performance: frequency of lapses, duration of lapse domain, optimum response time, vigilance decrement function, false response frequency. We applied this conceptually valid, relatively short duration, reliable task with known psychometric properties and minimal practice/learning curves to document attentional lapses (response times > 500 msec) in performance. | Baseline and 8 weeks of treatment in the ITT sample | 
| Change in the Score From Baseline to 8 Weeks Treatment on the SF36 - Physical | Change in the score from baseline to 8 weeks treatment, controlling for baseline, in the SF-36 is a 36-item questionnaire that assesses eight health concepts: physical functioning, bodily pain, role limitations due to physical problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions. Higher scores indicate greater disability with a range of scores from 0-100. | Baseline and Week 8 of treatment in ITT sample. | 
| Change in the Score From Baseline to 8 Weeks Treatment SF-36 Mental Component | Change in the score from baseline to 8 weeks treatment, controlling for baseline, in the SF-36 is a 36-item questionnaire that assesses eight health concepts: physical functioning, bodily pain, role limitations due to physical problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions. Higher scores indicate greater disability with a range of scores from 0-100. | Baseline and after 8 weeks of treatment in ITT sample |