Recruiting

Phase 1

Phase 2

AtoOxy & HGNSCombination Upper-Airway Electrical and Pharmacological Stimulation for Obstructive Sleep Apnea

Sponsor:

Brigham and Women's Hospital

Code:

NCT07577661

Conditions

Obstructive Sleep Apnea

Sleep-disordered Breathing

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

Combination device and drug: Unilateral hypoglossal nerve stimulation & atomoxetine-plus-oxybutynin (HGNS+AtoOxy)

Unilateral hypoglossal nerve stimulation (HGNS), active comparator condition

Atomoxetine-plus-oxybutynin (80/5 mg) (AtoOxy), active comparator condition

Placebo; placebo comparator condition

Study Details

Brief summary:

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.

Conditions

Obstructive Sleep Apnea

Sleep-disordered Breathing

Study ID

NCT07577661

Start date

Sep 1, 2026

Status verified date

Sep, 2026

Completion date

Sep 1, 2028

Anticipated

Primary completion date

Sep 1, 2028

Anticipated

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

24 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

other: Sequence 1

HGNS+AtoOxy -> Placebo -> HGNS -> AtoOxy

Each participant receives all four treatment conditions ("periods") in randomized order; outcomes are analyzed as within-subject comparisons, not between sequence arms.

other: Sequence 2

HGNS -> AtoOxy -> HGNS+AtoOxy -> Placebo

Each participant receives all four treatment conditions ("periods") in randomized order; outcomes are analyzed as within-subject comparisons, not between sequence arms.

other: Sequence 3

AtoOxy -> HGNS -> Placebo -> HGNS+AtoOxy

Each participant receives all four treatment conditions ("periods") in randomized order; outcomes are analyzed as within-subject comparisons, not between sequence arms.

other: Sequence 4

Placebo -> HGNS+AtoOxy -> AtoOxy -> HGNS

Each participant receives all four treatment conditions ("periods") in randomized order; outcomes are analyzed as within-subject comparisons, not between sequence arms.

Interventions

Combination device and drug: Unilateral hypoglossal nerve stimulation & atomoxetine-plus-oxybutynin (HGNS+AtoOxy)

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

Atomoxetine-plus-oxybutynin (80/5 mg) (AtoOxy), active comparator condition

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

Matching placebo capsules administered orally at bedtime. HGNS device off

Primary outcome measure

Apnea-Hypopnea Index [ Time Frame: 2 Weeks ]

Central Contacts and Locations

Central contacts

Daniel P Vena, PhD

617-852-0719 dvena@bwh.harvard.edu

Dillon Gilbertson, BASc

617-732-6488 dgilbertson@bwh.harvard.edu

Locations

Brigham and Women's Hospital

Recruiting

Boston, Massachusetts, United States, 02115

Contacts

Dillon Gilbertson, BASc

617-732-6488 dgilbertson@bwh.harvard.edu

Natalie Lawrence, BASc

7817076558 nvlawrence@bwh.harvard.edu

More Information

Sponsor

Brigham and Women's Hospital

Last update posted

Sep 21, 2026

Last verified

Sep, 2026

Keywords

Obstructive sleep apnea
Pharmacotherapy
Hypoglossal nerve stimulation
Oxybutynin
Atomoxetine

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-24. This information was provided to ClinicalTrials.gov by Brigham and Women's Hospital on 2026-09-21. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.