RECRUITING Phase 1 / Phase 2 ClinicalTrials.gov

Combination Upper-Airway Electrical and Pharmacological Stimulation for Obstructive Sleep Apnea

Sponsor: Brigham and Women's Hospital • ClinicalTrials.gov ID: NCT07577661

Registry updated: 2026-09-21

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Description

Obstructive sleep apnea (OSA) is a common condition in which the airway repeatedly collapses during sleep, leading to poor sleep quality and reduced oxygen levels. Hypoglossal nerve stimulation (HGNS) is an approved treatment that uses a small implanted device to stimulate the genioglossus muscle and keep the airway open. However, some patients continue to have OSA despite using HGNS. Atomoxetine and oxybutynin, "AtoOxy", is a promising pharmacologcal therapy under investigation that has been shown to activate pharyngeal muscles-in particular non-genioglossus muscles--but appears more efficacious in some patients than others. This study will test whether the combination of AtoOxy and HGNS can further improve breathing during sleep compared to either monotherapy alone. Participants with OSA and an HGNS device will be randomized to receive, in random order: HGNS+AtoOxy, HGNS alone (plus placebo), AtoOxy alone (HGNS device off), and placebo (HGNS device off), in a cross-over trial. The main goal is to determine whether the combined treatment reduces the number of breathing events during sleep; the primary outcome test will compare HGNS+AtoOxy versus HGNS alone. The effect of each intervention versus placebo will also be presented. The study will also examine how individual patient characteristics influence response to treatment.

Interventions

Combination device and drug: Unilateral hypoglossal nerve stimulation & atomoxetine-plus-oxybutynin (HGNS+AtoOxy) (Other)
Electrical stimulation of the hypoglossal nerve using an implanted device (Inspire Medical Systems) to activate upper airway dilator muscles during sleep at prescribed therapeutic settings. Atomoxetine 80 mg administered orally at bedtime. Oxybutynin 5 mg administered orally at bedtime. Dose escalation with half-dose for initial 3 nights followed by full dose.
Unilateral hypoglossal nerve stimulation (HGNS), active comparator condition (Device)
Electrical stimulation of the hypoglossal nerve using an implanted device (Inspire Medical Systems) to activate upper airway dilator muscles during sleep at prescribed therapeutic settings. Matching placebo capsules administered orally at bedtime.
Atomoxetine-plus-oxybutynin (80/5 mg) (AtoOxy), active comparator condition (Drug)
Atomoxetine 80 mg administered orally at bedtime. Oxybutynin 5 mg administered orally at bedtime. Dose escalation with half-dose for initial 3 nights followed by full dose. HGNS device off
Placebo; placebo comparator condition (Drug)
Matching placebo capsules administered orally at bedtime. HGNS device off

Eligibility criteria

Inclusion Criteria for Enrolment: * Ages 18 - 79 years * Diagnosed OSA * Implantation of a hypoglossal nerve stimulation device (HGNS, Inspire Medical) or scheduled for implantation (implantation required for randomization) * Willingness to withhold HGNS while testing therapies (up to 6 weeks with HGNS off \[with/without pharmacotherapy\] to assess benefits of HGNS therapy). Exclusion Criteria: * Any uncontrolled medical condition * Current use of the medications under investigation. * Issues relating to short-term withdrawal of HGNS therapy * Excluded: Occupational driving (truck drivers, fork-lift operation, taxi/uber drivers) * Excluded: History of traffic accidents attributable to sleepiness or fatigue (\<2 years). * Use of SNRIs/SSRIs or anticholinergic medications during the study. * 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: narcolepsy, parasomnias. Insomnia * 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: 1. "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?" 2. "During the last month, have you had a weak urinary stream more often than 1 out of 5 times? * known untreated narrow angle glaucoma * known bipolar disorder, mania, psychosis * known history of major depressive disorder (age\<24). * known history of attempted suicide or suicidal ideation within one year prior to screening * known clinically significant constipation, gastric retention * known pre-existing seizure disorders * known clinically-significant kidney disorders (eGFR\<60 ml/min/1.73m2) * known clinically-significant liver disorders * known clinically-significant cardiovascular conditions * moderate-to-severe hypertension (SBP\>160 mmHg or DBP\>100 mmHg measured at baseline; average of evening and morning measures) * known cardiomyopathy (LVEF\<50%) or heart failure * known advanced atherosclerosis * recent cerebrovascular events (within 2 years) * recent history of cardiac arrhythmias e.g., atrial fibrillation, QT prolongation (within 2 years) * other serious cardiac conditions that would raise the consequences of an increase in blood pressure or heart rate * myasthenia gravis * pregnancy/breast-feeding

Conditions

Obstructive Sleep Apnea Sleep-disordered Breathing

Locations

Brigham and Women's Hospital — Boston, Massachusetts, United States

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Official Source

Data sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

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