Combined Upper-airway and Breathing Control Therapies for Obstructive Sleep Apnea

Pre-specified primary analysis for Aim 1 is the change in AHI with combination treatment
versus oral appliance alone (%reduction versus placebo; including hypopnea events without
desaturation/arousals).

Aim 2 seeks to identify subgroups of patients that have the greatest reduction in AHI
(responders) with each treatment (post-hoc). We will use baseline physiological measures of
the four traits causing OSA (collapsibility, responsiveness, loop gain, arousal threshold) to
determine which characteristics predict responses to each intervention (leave-one-out support
vector machine modeling). Clinical measures of the same traits will be estimated from the
placebo night to confirm that responses can be predicted with clinically-available data. We
will also test whether responders to oral appliances have a greater response to oxygen than
oral appliance non-responders (and vice-versa), to address whether responders to both
treatments are similar or different.

Inclusion Criteria:

- Diagnosed OSA or suspected OSA based on snoring

Exclusion Criteria:

- Severe co-morbidities (cardiovascular, renal, lung disease, neurological), including:

Congestive heart failure, Neurological conditions that may affect sleep or breathing (e.g.
neuromuscular diseases e.g. myasthenia gravis; neurodegenerative diseases e.g.
Alzheimer's/Parkinson's)

- Medications that will substantially affect respiration, including opioids,
barbiturates, theophylline, doxapram, acetazolamide, pseudoephedrine

- Claustrophobia

- Insomnia and other non-respiratory sleep disorders

- Inability to sleep supine

- Contraindications to oral appliances, including insufficient teeth to support the
device, periodontal problems inducing tooth mobility, active temporomandibular joint
disorder

- Allergy to lidocaine or oxymetazoline HCl