Atomoxetine and Oxybutynin in Obstructive Sleep Apnea

Phase 1

Completed

Interventions: Drug: Placebo, 2 tablets
Drug: Combination product of Atomoxetine and Oxybutynin

Brief Summary: Obstructive sleep apnea (OSA) is common and has major health implications but treatment options are limited. OSA patients show a marked reduction in upper airway (UA) dilator muscle activity at sleep onset and this phenomenon leads to increased collapsibility of UA compared to normal subjects. Until recently, the search for medicines to activate pharyngeal muscles in sleeping humans has been discouraging. However, exciting new animal research has shown that drugs with noradrenergic and antimuscarinic effects can restore pharyngeal muscle activity to waking levels. In this protocol the investigators will test the effect of atomoxetine (a norepinephrine reuptake inhibitor) and oxybutynin (an antimuscarinic drug) administered together on OSA phenotype traits and OSA severity during sleep.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Any medical condition other than well controlled hypertension.
Any medication known to influence breathing, sleep/arousal or muscle physiology.
Claustrophobia.
Inability to sleep supine.
Allergy to lidocaine, Oxymetazoline HCl, atomoxetine/oxybutynin.
Individuals with underlying cardiac disease, such as arrhythmias.
Individuals taking psychiatric medications, such as atomoxetine, or any of the studied medications for medical care.
History of seizures
For women: Pregnancy.
History of panic disorder / hyperventilation syndrome / Attention deficit-hyperactivity disorder (ADHD) / autism

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo, 2 tablets	Placebo 2 hours before bedtime
Combination product of Atomoxetine and Oxybutynin	Combination product of Atomoxetine and Oxybutynin	Combination product of Atomoxetine 80 mg and Oxybutynin 5 mg 2 hours before sleep

Primary Outcome Measures

Name	Time	Method
Apnea Hypopnea Index (AHI, Events/Hour of Sleep)	1 night	Based on previous studies the investigators anticipate that Atomoxetine and Oxybutynin will reduce AHI more effectively in subjects with moderate sleep apnea, mildly obese (BMI\<32), Vpassive \> 50% of Veupnea (ventilation during eupneic ventilatory drive), low muscle compensation (Vactive - Vpassive \<1 L/min)

Secondary Outcome Measures

Name	Time	Method
Genioglossus Muscle Responsiveness to Increased Ventilatory Drive (Esophageal Pressure Swings)	1 night	For genioglossus muscle responsiveness, data will be expressed as change in electromyography of genioglossus (GG EMG) for cmH2O change in esophageal pressure.