Variable Dead Space Rebreathing Device to Treat Sleep Apnea

Obstructive sleep apnea (OSA) needs to be treated with devices that will be utilized with
greater compliance by patients than is currently the case with positive airway pressure. To
this end, the investigators recently showed that increased inspired CO2 via rebreathing was
effective in reducing most obstructive and central apneas in OSA patients. Then, the
investigator's University of Wisconsin (UW) team of bioengineers, physiologists, and sleep
physicians built a novel variable dead space rebreathe device—with no added positive
pressure—which monitors breath by breath ventilation and automatically adjusts the rebreathe
dead space volume to add or subtract the level of inspired CO2 depending on the degree of
sleep disordered breathing. This approach provides the minimum effective CO2 dose needed in
individual OSA patients to stabilize central respiratory motor output and to recruit upper
airway dilator muscles, thereby treating obstructive and central apneas. The investigators
propose to determine the effectiveness of this "Smart CO2" treatment as well as its effects
on sleep state stability, sleep quality, and blood pressure in 10 moderate to severe OSA
patients studied over several nights. The investigators expect the findings from the proposed
study to be sufficient to determine if the "Smart CO2" treatment is a viable approach to OSA
treatment worthy of testing in a clinical trial.

Inclusion Criteria:

1. Age 18-75 years old, inclusive

2. Moderate to severe OSA (Apnea hypopnea index [AHI] >15 events/hr of sleep, having >50%
obstructive apneic pattern)

3. Newly diagnosed OSA, or have either refused to or have not tolerated PAP treatment, or
are currently using Positive Airway Pressure (PAP) and are willing to hold it during
the night of sleep study visits.

4. Willing and able to provide consent to 5 laboratory visits with 4 full nights of sleep
study.

5. Self report of still having sleep apnea since the last sleep test (if diagnosis was
greater than a year prior).

Exclusion Criteria:

1. BMI >45 kg/m2

2. AHI<15 events/hour on the first night of sleep testing in our research laboratory
(Visit 2)

3. Cigarette smoking of 1 pack per day or more within 6 months of screening;

4. Diagnosed heart failure or coronary artery disease.

5. Diagnosed cerebrovascular disease, Transient Ischemic Attack (TIA) or stroke.

6. Diagnosed asthma or chronic obstructive pulmonary disease with significant airways
obstruction (FEVI/Forced Vital Capacity <65%)

7. End-stage hepatic or renal disease

8. Significant daytime sleepiness in subjects who have risky occupations or life-style
(for example, working in the transportation industry, history of motor vehicle crash,
occupation that requires vigilance for safety or performance)

9. Pregnancy (assessed on urine test at V1 in females with childbearing potential)

10. Clinically significant arrhythmia/dysrhythmias on the clinical diagnostic
polysomnography (per medical record) or on research polysomnography conducted at V2

11. Established diagnosis of neuromuscular disease (e.g., Parkinsonism, multiple
sclerosis, syringomyelia, transverse myelitis, amyotrophic lateral sclerosis,
poliomyelitis, Eaton-Lambert, Guillain-Barre, myasthenia gravis, myotonic dystrophy,
mononeuritis multiplex, in the setting of polymyositis/dermatomyositis or severe
cervical spine disease)

12. Any current use of benzodiazepines, opioids, or barbiturates

13. Any medical or psychiatric condition which in the opinion of the medical director
interferes with the subject's ability to enroll or to continue in the study (once
enrolled)

14. Veteran, cared for in the VA system