Atomoxetine and Oxybutynin in Obstructive Sleep Apnea

Study Overview
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Brief Summary
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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.

Official Title
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Effect of Atomoxetine and Oxybutynin on Phenotype Traits and OSA Severity

Conditions
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Obstructive Sleep Apnea (OSA)

Intervention / Treatment
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* Drug: Combination product of Atomoxetine and Oxybutynin
* Drug: Placebo, 2 tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criterion: - AHI > 20 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

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 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: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo 2 hours before bedtime | Drug: Placebo, 2 tablets<br>* Placebo 2 tablets 2 hours before sleep<br>|
| Active Comparator: Combination product of Atomoxetine and Oxybutynin<br>Combination product of Atomoxetine 80 mg and Oxybutynin 5 mg 2 hours before sleep | Drug: Combination product of Atomoxetine and Oxybutynin<br>* Combination product of Atomoxetine 80 mg and Oxybutynin 5 mg 2 hours before sleep<br>* Other names: Strattera + Ditropan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Apnea Hypopnea Index (AHI, Events/Hour of Sleep) | 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) | 1 night | 

Secondary Outcome Measures

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