NCT07577661 · Brigham and Women's Hospital
Combination Upper-Airway Electrical and Pharmacological Stimulation for Obstructive Sleep Apnea
What this study is about
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.
View original scientific 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
OTHER
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.
DEVICE
Unilateral hypoglossal nerve stimulation (HGNS), active comparator condition
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.
DRUG
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
DRUG
Placebo; placebo comparator condition
Matching placebo capsules administered orally at bedtime. HGNS device off
Primary outcome measures
Apnea-Hypopnea Index
Time frame: 2 Weeks
Apnea-hypopnea index (AHI), defined as the number of apneas and hypopneas per hour of sleep, measured by overnight polysomnography at the end of each treatment period. Quantitative outcome variable: percent change (symmetrized) from baseline.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
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:
- "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?
- 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
Where
- Boston, Massachusetts
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Sep 21, 2026 · Source of record for eligibility and locations