Pharyngeal Muscle Control Mechanisms of Atomoxetine-plus-oxybutynin in Obstructive Sleep Apnea

• Status: Not yet recruiting
• Trial end date: 2024-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Current therapies available for obstructive sleep apnea (OSA) have varying degrees of efficacy due to the complex nature of the disorder. A reduction in pharyngeal muscle activity characterizes OSA, and recent research has shown that combining atomoxetine and oxybutynin improves OSA severity. Thus this may be a viable treatment option. However, the specific effects of these agents alone and in combination on pharyngeal muscle activity remain unknown. The current study will look at the impact of each drug on pharyngeal muscles to gain insight into the mechanisms of this combination.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Brigham and Women's Hospital
• Treatments: Atomoxetine Hydrochloride; Oxybutynin

Criteria

Inclusion Criteria:

• diagnosed OSA (AHI≥15 events/h reported in PSG performed within one year) or Suspected OSA (snoring, sleepiness, witness apneas, other clinical symptoms)

• not using CPAP (>1 week)

Exclusion Criteria:

• Any uncontrolled medical condition

• Current use of the medications under investigation

• Use of medications expected to stimulate or depress respiration (including opioids, barbiturates, doxapram, almitrine, theophylline, 4-hydroxybutanoic acid).

• Current use of SNRIs/SSRIs or anticholinergic medications.

• Conditions likely to affect obstructive sleep apnea physiology: neuromuscular disease or other major neurological disorder, heart failure (also below), or any other unstable major medical condition.

• Respiratory disorders other than sleep disordered breathing:

chronic hypoventilation/hypoxemia (awake SaO2 < 92% by oximetry) due to chronic obstructive pulmonary disease or other respiratory conditions.

• Other sleep disorders: periodic limb movements (periodic limb movement arousal index > 10/hr), narcolepsy, or parasomnias.

• Contraindications for atomoxetine and oxybutynin, including:

• hypersensitivity to atomoxetine or oxybutynin (angioedema or urticaria)

• pheochromocytoma

• use of monoamine oxidase inhibitors

• diagnosed benign prostatic hypertrophy, urinary retention

• suspected benign prostatic hypertrophy / urinary retention based on a positive answer to either of the following questions:

• "During the last month, when urinating, have you had the sensation of not emptying your bladder completely more often than 1 out of 5 times?"

• "During the last month, have you had a weak urinary stream more often than 1 out of 5 times?

• untreated narrow angle glaucoma

• bipolar disorder, mania, psychosis

• history of major depressive disorder (age<24).

• history of attempted suicide or suicidal ideation within one year prior to screening

• clinically significant constipation, gastric retention

• pre-existing seizure disorders

• clinically-significant kidney disorders (eGFR<60 ml/min/1.73m2)

• clinically-significant liver disorders

• clinically-significant cardiovascular conditions

• severe hypertension (SBP>180 mmHg or DBP>110 mmHg measured at baseline)

• cardiomyopathy (LVEF<50%) or heart failure

• advanced atherosclerosis

• history of cerebrovascular events

• history of cardiac arrhythmias e.g., atrial fibrillation, QT prolongation

• other serious cardiac conditions that would raise the consequences of an increase in blood pressure or heart rate

• myasthenia gravis

• pregnancy/breast-feeding

• Allergy to lidocaine

• Use of oral anti-coagulants

• Claustrophobia

• Pregnancy or nursing