Apnea Positive Pressure Long-Term Efficacy Study

BACKGROUND:

Nasal CPAP therapy is in widespread use as the primary treatment for OSAS, a sleep-related
breathing disorder affecting more than 15 million Americans. The therapeutic effectiveness of
CPAP in providing significant, stable, and long-term neurocognitive or other functional
benefits to patients with OSAS has not been systematically investigated.

DESIGN NARRATIVE:

The study is a randomized, blinded, sham-controlled, multi-center trial of CPAP therapy. The
principal aims of the study are: 1) to assess the long-term effectiveness of CPAP therapy on
neurocognitive function, mood, sleepiness, and quality of life by administering tests of
these indices to subjects randomly assigned to active or sham CPAP; 2) to identify specific
neurocognitive deficits associated with OSAS in a large, heterogeneous subject population; 3)
to determine which deficits in neurocognitive function in OSAS subjects are reversible and
most sensitive to the effects of CPAP; 4) to develop a composite multivariate outcome measure
from the results of this study that can be used to assess the clinical effectiveness of CPAP
in improving neurocognitive function, mood, sleepiness, and quality of life; and 5) to use
functional magnetic resonance imaging to compare cortical activation before and after CPAP
therapy, and to assess whether this change is associated with improvement in specific
neurocognitive task performance. The primary endpoint of the study is the effect of six
months of CPAP treatment on neurocognitive function. A total of 1100 subjects (550 per
treatment group) will be enrolled from the patient populations at five sites (Stanford
University; University of Arizona; Brigham and Women's Hospital; Massachusetts; St. Luke's
Hospital, Missouri; St. Mary Medical Center, Washington).

Inclusion Criteria:

- Male or female adults age 18 years or older with a diagnosis of OSAS using clinical
criteria defined by the study protocol

- Study participation may require seven or more laboratory visits over six months

Exclusion Criteria:

- Prior treatment for OSAS with continuous positive airway pressure or surgery

- Potential sleep apnea complications that may affect the health or safety of the
participant, including low blood oxygen, recent near-miss or prior automobile accident
due to sleepiness, congestive heart failure, history of angina, coronary artery
disease, myocardial infarction or stroke, cardiac rhythm disturbance, and chronic
neurological disorders affecting neurocognitive abilities or daily function

- The use of hypnotics, anxiolytics, sedating antidepressants, anticonvulsants, sedating
antihistamines, stimulants or other medications likely to affect neurocognitive
function and/or alertness

- Respiratory disease requiring medications (unless on stable medications for 2 months)

- Cancer, unless in remission for greater than one year and not taking exclusionary
medications

- Self-reported renal failure

- Pregnancy anytime during a subject's participation

- Psychiatric illness, as defined by a DSM-IV diagnosis, except for depression or mild
anxiety

- Narcolepsy, idiopathic hypersomnolence, DSM-IV chronic insomnia, restless legs
syndrome, or rapid eye movement (REM) behavior disorder

- Current use of diurnal or nocturnal supplemental oxygen

- Significant vision, hearing, or coordination problems

- Difficulty understanding or speaking English

- Currently working night or rotating shifts

- Consumption of more than 10 caffeinated beverages per day (approximately 1,000 mg per
day)

- Smokers whose habit interferes with the overnight polysomnogram or with the battery of
testing during the day

- Consumption of more than 2 alcoholic beverages per day

- Any illicit drug usage or marijuana usage more than once a week

- Any individual in the household currently on CPAP or on CPAP in the past

- A score of 26 or less on the Mini Mental State Examination (MMSE)