Atomoxetine and Oxybutynin in Obstructive Sleep Apnea


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.

Full Title of Study: “Effect of Atomoxetine and Oxybutynin on Phenotype Traits and OSA Severity”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Crossover Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: December 2017


  • Drug: Combination product of Atomoxetine and Oxybutynin
    • Combination product of Atomoxetine 80 mg and Oxybutynin 5 mg 2 hours before sleep
  • Drug: Placebo, 2 tablets
    • Placebo 2 tablets 2 hours before sleep

Arms, Groups and Cohorts

  • Placebo Comparator: Placebo
    • Placebo 2 hours before bedtime
  • Active Comparator: Combination product of Atomoxetine and Oxybutynin
    • Combination product of Atomoxetine 80 mg and Oxybutynin 5 mg 2 hours before sleep

Clinical Trial Outcome Measures

Primary Measures

  • Apnea Hypopnea Index (AHI, Events/Hour of Sleep)
    • Time Frame: 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 Measures

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

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 21 Years

Maximum Age: 65 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Brigham and Women’s Hospital
  • Provider of Information About this Clinical Study
    • Principal Investigator: David Andrew Wellman, Assistant Professor of Medicine – Harvard Medical School – Brigham and Women’s Hospital

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