Obstructive Sleep ApneaPhase 1/2NCT07577661
Combination Upper-Airway Electrical and Pharmacological Stimulation for Obstructive Sleep Apnea
A Phase 1/2 study testing Combination device and drug: Unilateral hypoglossal nerve stimulation & atomoxetine-plus-oxybutynin (HGNS+AtoOxy), Unilateral hypoglossal nerve stimulation (HGNS), active comparator condition and Atomoxetine-plus-oxybutynin (80/5 mg) (AtoOxy), active comparator condition in people with Obstructive Sleep Apnea and Sleep-disordered Breathing, run by Brigham and Women's Hospital at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 79 years
- Conditions the study is for
- Obstructive Sleep Apnea, Sleep-disordered Breathing
- What is being tested?
- Combination device and drug: Unilateral hypoglossal nerve stimulation & atomoxetine-plus-oxybutynin (HGNS+AtoOxy), Unilateral hypoglossal nerve stimulation (HGNS), active comparator condition and Atomoxetine-plus-oxybutynin (80/5 mg) (AtoOxy), active comparator condition
- Type of treatment
- Pill or oral medicine, Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Sep 2026to 1 Sep 2028
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 79 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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.
Show all 35Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Dillon Gilbertson, BASc, 617-732-6488, dgilbertson@bwh.harvard.edu
Natalie Lawrence, BASc, 7817076558, nvlawrence@bwh.harvard.edu
About this study
Official title: Combination Upper-Airway Electrical and Pharmacological Stimulation for Obstructive Sleep Apnea: A Randomized-Controlled Trial.
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.
Read more
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.
Read the detailed description
Residual obstructive sleep apnea (OSA) is common among patients treated with hypoglossal nerve stimulation (HGNS), reflecting incomplete correction of underlying pathophysiological traits. In addition to upper airway collapsibility, non-anatomical factors such as a low arousal threshold may contribute to persistent disease despite HGNS therapy. Pharmacologic modulation of these traits represents a potential strategy to enhance treatment efficacy.
Atomoxetine (a norepinephrine re-uptake inhibitor) and oxybutynin (an anti-muscarinic agent) have been shown to increase upper airway muscle tone and raise the arousal threshold, leading to reductions in OSA severity in prior studies. However, their combined effect when added to ongoing HGNS therapy has not been systematically evaluated.
This study is a randomized, placebo-controlled, crossover trial designed to assess the acute effects of combined pharmacologic and electrical stimulation on OSA severity. Participants with OSA who are already implanted with HGNS, or pending clinical implantation, will be enrolled in a four-period randomized placebo-controlled cross-over trial assessing HGNS+AtoOxy, HGNS alone (plus placebo), AtoOxy alone (HGNS device off), and placebo (HGNS device off).
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.
Polysomnographic measurements will be also be used to explore mechanisms underlying response, including the interaction between pharmacologically modifiable traits and HGNS-mediated airway stabilization. Additional analyses will evaluate whether baseline physiological characteristics predict treatment response, with the goal of informing personalized treatment strategies for patients with residual OSA. Patient-reported outcomes, including sleepiness, sleep-related quality of life, fatigue, and treatment satisfaction, will also be assessed to evaluate the broader clinical impact of the combination intervention.
- Being tested
- 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
- Keywords
- Obstructive sleep apnea, Pharmacotherapy, Hypoglossal nerve stimulation, Oxybutynin, Atomoxetine
- Medical subject headings
- Sleep Apnea, Obstructive, Sleep Apnea Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Combination device and drug: Unilateral hypoglossal nerve stimulation & atomoxetine-plus-oxybutynin (HGNS+AtoOxy)Other
Also called 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 conditionDevice
Also called HGNS
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 conditionDrug
Also called AtoOxy
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 conditionDrug
Also called Placebo
Matching placebo capsules administered orally at bedtime. HGNS device off
| Study group | Role | What they receive |
|---|---|---|
| Sequence 1 | Other | 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. Receives: Other: Combination device and drug: Unilateral hypoglossal nerve stimulation & atomoxetine-plus-oxybutynin (HGNS+AtoOxy); Device: Unilateral hypoglossal nerve stimulation (HGNS), active comparator condition; Drug: Atomoxetine-plus-oxybutynin (80/5 mg) (AtoOxy), active comparator condition; Drug: Placebo; placebo comparator condition |
| Sequence 2 | Other | 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. Receives: Other: Combination device and drug: Unilateral hypoglossal nerve stimulation & atomoxetine-plus-oxybutynin (HGNS+AtoOxy); Device: Unilateral hypoglossal nerve stimulation (HGNS), active comparator condition; Drug: Atomoxetine-plus-oxybutynin (80/5 mg) (AtoOxy), active comparator condition; Drug: Placebo; placebo comparator condition |
| Sequence 3 | Other | 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. Receives: Other: Combination device and drug: Unilateral hypoglossal nerve stimulation & atomoxetine-plus-oxybutynin (HGNS+AtoOxy); Device: Unilateral hypoglossal nerve stimulation (HGNS), active comparator condition; Drug: Atomoxetine-plus-oxybutynin (80/5 mg) (AtoOxy), active comparator condition; Drug: Placebo; placebo comparator condition |
| Sequence 4 | Other | 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. Receives: Other: Combination device and drug: Unilateral hypoglossal nerve stimulation & atomoxetine-plus-oxybutynin (HGNS+AtoOxy); Device: Unilateral hypoglossal nerve stimulation (HGNS), active comparator condition; Drug: Atomoxetine-plus-oxybutynin (80/5 mg) (AtoOxy), active comparator condition; Drug: Placebo; placebo comparator condition |
What is being measured
The primary outcome is the main question the study is designed to answer.
Apnea-Hypopnea Index
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.
Measured: 2 Weeks
Secondary outcomes (2)
Hypoxic Burden
Hypoxic burden, defined as the area under the oxygen desaturation curve associated with respiratory events multiplied by event frequency, measured during overnight polysomnography.
Quantitative outcome variable: percent change (symmetrized) from baseline.
Measured: 2 Weeks
Visual Analog Scale for Sleep Quality
Self-reported sleep quality measured using a visual analog scale. Quantitative outcome variable: absolute change from baseline. Range: 0-10 (higher values indicate greater sleep quality).
Measured: 2 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2026
- Study start1 Sep 2026
- Primary completion1 Sep 2028 (estimated)
- Study completion1 Sep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for Obstructive Sleep ApneaStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Randomized, double-blind (medication), crossover trial with four treatment conditions: hypoglossal nerve stimulation (HGNS) alone, pharmacotherapy alone (atomoxetine plus oxybutynin), combination therapy (HGNS plus pharmacotherapy), and placebo (HGNS off). Each participant undergoes four 2-week treatment periods with 1-week washout intervals between periods. Treatment order is randomized.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Scott Aaron Sands, Brigham and Women's Hospital
- Investigators
- Scott A Sands, PhD, Principal investigator, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07577661
- Sponsor's protocol ID
- 2026P000970
- Status last verified
- Sep 2026
- First submitted
- 27 Apr 2026
- Last updated
- 21 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- Undecided
Publications
Edwards BA, Sands SA, Eckert DJ, White DP, Butler JP, Owens RL, Malhotra A, Wellman A. Acetazolamide improves loop gain but not the other physiological traits causing obstructive sleep apnoea. J Physiol. 2012 Mar 1;590(5):1199-211. doi: 10.1113/jphysiol.2011.223925. Epub 2012 Jan 4.
PubMed 22219335Sands SA, Terrill PI, Edwards BA, Taranto Montemurro L, Azarbarzin A, Marques M, de Melo CM, Loring SH, Butler JP, White DP, Wellman A. Quantifying the Arousal Threshold Using Polysomnography in Obstructive Sleep Apnea. Sleep. 2018 Jan 1;41(1):zsx183. doi: 10.1093/sleep/zsx183.
PubMed 29228393Sands SA, Edwards BA, Terrill PI, Taranto-Montemurro L, Azarbarzin A, Marques M, Hess LB, White DP, Wellman A. Phenotyping Pharyngeal Pathophysiology using Polysomnography in Patients with Obstructive Sleep Apnea. Am J Respir Crit Care Med. 2018 May 1;197(9):1187-1197. doi: 10.1164/rccm.201707-1435OC.
PubMed 29327943Terrill PI, Edwards BA, Nemati S, Butler JP, Owens RL, Eckert DJ, White DP, Malhotra A, Wellman A, Sands SA. Quantifying the ventilatory control contribution to sleep apnoea using polysomnography. Eur Respir J. 2015 Feb;45(2):408-18. doi: 10.1183/09031936.00062914. Epub 2014 Oct 16.
PubMed 25323235Sands SA, Edwards BA, Terrill PI, Butler JP, Owens RL, Taranto-Montemurro L, Azarbarzin A, Marques M, Hess LB, Smales ET, de Melo CM, White DP, Malhotra A, Wellman A. Identifying obstructive sleep apnoea patients responsive to supplemental oxygen therapy. Eur Respir J. 2018 Sep 27;52(3):1800674. doi: 10.1183/13993003.00674-2018. Print 2018 Sep.
PubMed 30139771Pepperell JC, Maskell NA, Jones DR, Langford-Wiley BA, Crosthwaite N, Stradling JR, Davies RJ. A randomized controlled trial of adaptive ventilation for Cheyne-Stokes breathing in heart failure. Am J Respir Crit Care Med. 2003 Nov 1;168(9):1109-14. doi: 10.1164/rccm.200212-1476OC. Epub 2003 Aug 19.
PubMed 12928310Pepperell JC, Ramdassingh-Dow S, Crosthwaite N, Mullins R, Jenkinson C, Stradling JR, Davies RJ. Ambulatory blood pressure after therapeutic and subtherapeutic nasal continuous positive airway pressure for obstructive sleep apnoea: a randomised parallel trial. Lancet. 2002 Jan 19;359(9302):204-10. doi: 10.1016/S0140-6736(02)07445-7.
PubMed 11812555Ryan CM, Usui K, Floras JS, Bradley TD. Effect of continuous positive airway pressure on ventricular ectopy in heart failure patients with obstructive sleep apnoea. Thorax. 2005 Sep;60(9):781-5. doi: 10.1136/thx.2005.040972. Epub 2005 Jun 30.
PubMed 15994252Gold AR, Schwartz AR, Bleecker ER, Smith PL. The effect of chronic nocturnal oxygen administration upon sleep apnea. Am Rev Respir Dis. 1986 Nov;134(5):925-9. doi: 10.1164/arrd.1986.134.5.925.
PubMed 3096178Azarbarzin A, Sands SA, Stone KL, Taranto-Montemurro L, Messineo L, Terrill PI, Ancoli-Israel S, Ensrud K, Purcell S, White DP, Redline S, Wellman A. The hypoxic burden of sleep apnoea predicts cardiovascular disease-related mortality: the Osteoporotic Fractures in Men Study and the Sleep Heart Health Study. Eur Heart J. 2019 Apr 7;40(14):1149-1157. doi: 10.1093/eurheartj/ehy624.
PubMed 30376054Taylor KS, Murai H, Millar PJ, Haruki N, Kimmerly DS, Morris BL, Tomlinson G, Bradley TD, Floras JS. Arousal From Sleep and Sympathetic Excitation During Wakefulness. Hypertension. 2016 Dec;68(6):1467-1474. doi: 10.1161/HYPERTENSIONAHA.116.08212. Epub 2016 Oct 3.
PubMed 27698070Winslow DH, Bowden CH, DiDonato KP, McCullough PA. A randomized, double-blind, placebo-controlled study of an oral, extended-release formulation of phentermine/topiramate for the treatment of obstructive sleep apnea in obese adults. Sleep. 2012 Nov 1;35(11):1529-39. doi: 10.5665/sleep.2204.
PubMed 23115402Phillips CL, Grunstein RR, Darendeliler MA, Mihailidou AS, Srinivasan VK, Yee BJ, Marks GB, Cistulli PA. Health outcomes of continuous positive airway pressure versus oral appliance treatment for obstructive sleep apnea: a randomized controlled trial. Am J Respir Crit Care Med. 2013 Apr 15;187(8):879-87. doi: 10.1164/rccm.201212-2223OC.
PubMed 23413266Strollo PJ Jr, Soose RJ, Maurer JT, de Vries N, Cornelius J, Froymovich O, Hanson RD, Padhya TA, Steward DL, Gillespie MB, Woodson BT, Van de Heyning PH, Goetting MG, Vanderveken OM, Feldman N, Knaack L, Strohl KP; STAR Trial Group. Upper-airway stimulation for obstructive sleep apnea. N Engl J Med. 2014 Jan 9;370(2):139-49. doi: 10.1056/NEJMoa1308659.
PubMed 24401051
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combination Upper-Airway Electrical and Pharmacological Stimulation for Obstructive Sleep Apnea: A Randomized-Controlled Trial.
- ClinicalTrials.gov ID
- NCT07577661
- Acronym / sponsor ID
- 2026P000970
- Keywords
- Obstructive sleep apnea, Pharmacotherapy, Hypoglossal nerve stimulation, Oxybutynin, Atomoxetine
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Study start
- 1 Sep 2026 (actual)
- Primary completion
- 1 Sep 2028 (estimated)
- Study completion
- 1 Sep 2028 (estimated)
- First posted
- 11 May 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Residual obstructive sleep apnea (OSA) is common among patients treated with hypoglossal nerve stimulation (HGNS), reflecting incomplete correction of underlying pathophysiological traits. In addition to upper airway collapsibility, non-anatomical factors such as a low arousal threshold may contribute to persistent disease despite HGNS therapy. Pharmacologic modulation of these traits represents a potential strategy to enhance treatment efficacy.
Atomoxetine (a norepinephrine re-uptake inhibitor) and oxybutynin (an anti-muscarinic agent) have been shown to increase upper airway muscle tone and raise the arousal threshold, leading to reductions in OSA severity in prior studies. However, their combined effect when added to ongoing HGNS therapy has not been systematically evaluated.
This study is a randomized, placebo-controlled, crossover trial designed to assess the acute effects of combined pharmacologic and electrical stimulation on OSA severity. Participants with OSA who are already implanted with HGNS, or pending clinical implantation, will be enrolled in a four-period randomized placebo-controlled cross-over trial assessing HGNS+AtoOxy, HGNS alone (plus placebo), AtoOxy alone (HGNS device off), and placebo (HGNS device off).
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.
Polysomnographic measurements will be also be used to explore mechanisms underlying response, including the interaction between pharmacologically modifiable traits and HGNS-mediated airway stabilization. Additional analyses will evaluate whether baseline physiological characteristics predict treatment response, with the goal of informing personalized treatment strategies for patients with residual OSA. Patient-reported outcomes, including sleepiness, sleep-related quality of life, fatigue, and treatment satisfaction, will also be assessed to evaluate the broader clinical impact of the combination intervention.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- Randomized, double-blind (medication), crossover trial with four treatment conditions: hypoglossal nerve stimulation (HGNS) alone, pharmacotherapy alone (atomoxetine plus oxybutynin), combination therapy (HGNS plus pharmacotherapy), and placebo (HGNS off). Each participant undergoes four 2-week treatment periods with 1-week washout intervals between periods. Treatment order is randomized.
| Arm | Type | Receives |
|---|---|---|
| Sequence 1 | Other | Other: Combination device and drug: Unilateral hypoglossal nerve stimulation & atomoxetine-plus-oxybutynin (HGNS+AtoOxy), Device: Unilateral hypoglossal nerve stimulation (HGNS), active comparator condition, Drug: Atomoxetine-plus-oxybutynin (80/5 mg) (AtoOxy), active comparator condition, Drug: Placebo; placebo comparator conditionHGNS+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. |
| Sequence 2 | Other | Other: Combination device and drug: Unilateral hypoglossal nerve stimulation & atomoxetine-plus-oxybutynin (HGNS+AtoOxy), Device: Unilateral hypoglossal nerve stimulation (HGNS), active comparator condition, Drug: Atomoxetine-plus-oxybutynin (80/5 mg) (AtoOxy), active comparator condition, Drug: Placebo; placebo comparator conditionHGNS -> 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. |
| Sequence 3 | Other | Other: Combination device and drug: Unilateral hypoglossal nerve stimulation & atomoxetine-plus-oxybutynin (HGNS+AtoOxy), Device: Unilateral hypoglossal nerve stimulation (HGNS), active comparator condition, Drug: Atomoxetine-plus-oxybutynin (80/5 mg) (AtoOxy), active comparator condition, Drug: Placebo; placebo comparator conditionAtoOxy -> 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. |
| Sequence 4 | Other | Other: Combination device and drug: Unilateral hypoglossal nerve stimulation & atomoxetine-plus-oxybutynin (HGNS+AtoOxy), Device: Unilateral hypoglossal nerve stimulation (HGNS), active comparator condition, Drug: Atomoxetine-plus-oxybutynin (80/5 mg) (AtoOxy), active comparator condition, Drug: Placebo; placebo comparator conditionPlacebo -> 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. |
Who may qualify
- Ages
- 18 to 79 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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).
Key exclusion criteria (35 listed)
- Any uncontrolled medical condition
- Current use of the medications under investigation.
- Issues relating to short-term withdrawal of HGNS therapy
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Combination device and drug: Unilateral hypoglossal nerve stimulation & atomoxetine-plus-oxybutynin (HGNS+AtoOxy)Also: HGNS+AtoOxyElectrical 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. | Other | Sequence 1, Sequence 2, Sequence 3, Sequence 4 |
| Unilateral hypoglossal nerve stimulation (HGNS), active comparator conditionAlso: HGNSElectrical 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. | Device | Sequence 1, Sequence 2, Sequence 3, Sequence 4 |
| Atomoxetine-plus-oxybutynin (80/5 mg) (AtoOxy), active comparator conditionAlso: AtoOxyAtomoxetine 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 | Sequence 1, Sequence 2, Sequence 3, Sequence 4 |
| Placebo; placebo comparator conditionAlso: PlaceboMatching placebo capsules administered orally at bedtime. HGNS device off | Drug | Sequence 1, Sequence 2, Sequence 3, Sequence 4 |
Primary outcome
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.
2 secondary outcomes
Hypoxic Burden
Time frame: 2 Weeks
Visual Analog Scale for Sleep Quality
Time frame: 2 Weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2026.
- Background: PubMed 22219335Edwards BA, Sands SA, Eckert DJ, White DP, Butler JP, Owens RL, Malhotra A, Wellman A. Acetazolamide improves loop gain but not the other physiological traits causing obstructive sleep apnoea. J Physiol. 2012 Mar 1;590(5):1199-211. doi: 10.1113/jphysiol.2011.223925. Epub 2012 Jan 4.
- Background: PubMed 29228393Sands SA, Terrill PI, Edwards BA, Taranto Montemurro L, Azarbarzin A, Marques M, de Melo CM, Loring SH, Butler JP, White DP, Wellman A. Quantifying the Arousal Threshold Using Polysomnography in Obstructive Sleep Apnea. Sleep. 2018 Jan 1;41(1):zsx183. doi: 10.1093/sleep/zsx183.
- Background: PubMed 29327943Sands SA, Edwards BA, Terrill PI, Taranto-Montemurro L, Azarbarzin A, Marques M, Hess LB, White DP, Wellman A. Phenotyping Pharyngeal Pathophysiology using Polysomnography in Patients with Obstructive Sleep Apnea. Am J Respir Crit Care Med. 2018 May 1;197(9):1187-1197. doi: 10.1164/rccm.201707-1435OC.
- Background: PubMed 25323235Terrill PI, Edwards BA, Nemati S, Butler JP, Owens RL, Eckert DJ, White DP, Malhotra A, Wellman A, Sands SA. Quantifying the ventilatory control contribution to sleep apnoea using polysomnography. Eur Respir J. 2015 Feb;45(2):408-18. doi: 10.1183/09031936.00062914. Epub 2014 Oct 16.
- Background: PubMed 30139771Sands SA, Edwards BA, Terrill PI, Butler JP, Owens RL, Taranto-Montemurro L, Azarbarzin A, Marques M, Hess LB, Smales ET, de Melo CM, White DP, Malhotra A, Wellman A. Identifying obstructive sleep apnoea patients responsive to supplemental oxygen therapy. Eur Respir J. 2018 Sep 27;52(3):1800674. doi: 10.1183/13993003.00674-2018. Print 2018 Sep.
- Background: PubMed 12928310Pepperell JC, Maskell NA, Jones DR, Langford-Wiley BA, Crosthwaite N, Stradling JR, Davies RJ. A randomized controlled trial of adaptive ventilation for Cheyne-Stokes breathing in heart failure. Am J Respir Crit Care Med. 2003 Nov 1;168(9):1109-14. doi: 10.1164/rccm.200212-1476OC. Epub 2003 Aug 19.
- Background: PubMed 11812555Pepperell JC, Ramdassingh-Dow S, Crosthwaite N, Mullins R, Jenkinson C, Stradling JR, Davies RJ. Ambulatory blood pressure after therapeutic and subtherapeutic nasal continuous positive airway pressure for obstructive sleep apnoea: a randomised parallel trial. Lancet. 2002 Jan 19;359(9302):204-10. doi: 10.1016/S0140-6736(02)07445-7.
- Background: PubMed 15994252Ryan CM, Usui K, Floras JS, Bradley TD. Effect of continuous positive airway pressure on ventricular ectopy in heart failure patients with obstructive sleep apnoea. Thorax. 2005 Sep;60(9):781-5. doi: 10.1136/thx.2005.040972. Epub 2005 Jun 30.
- Background: PubMed 3096178Gold AR, Schwartz AR, Bleecker ER, Smith PL. The effect of chronic nocturnal oxygen administration upon sleep apnea. Am Rev Respir Dis. 1986 Nov;134(5):925-9. doi: 10.1164/arrd.1986.134.5.925.
- Background: PubMed 30376054Azarbarzin A, Sands SA, Stone KL, Taranto-Montemurro L, Messineo L, Terrill PI, Ancoli-Israel S, Ensrud K, Purcell S, White DP, Redline S, Wellman A. The hypoxic burden of sleep apnoea predicts cardiovascular disease-related mortality: the Osteoporotic Fractures in Men Study and the Sleep Heart Health Study. Eur Heart J. 2019 Apr 7;40(14):1149-1157. doi: 10.1093/eurheartj/ehy624.
- Background: PubMed 27698070Taylor KS, Murai H, Millar PJ, Haruki N, Kimmerly DS, Morris BL, Tomlinson G, Bradley TD, Floras JS. Arousal From Sleep and Sympathetic Excitation During Wakefulness. Hypertension. 2016 Dec;68(6):1467-1474. doi: 10.1161/HYPERTENSIONAHA.116.08212. Epub 2016 Oct 3.
- Background: PubMed 23115402Winslow DH, Bowden CH, DiDonato KP, McCullough PA. A randomized, double-blind, placebo-controlled study of an oral, extended-release formulation of phentermine/topiramate for the treatment of obstructive sleep apnea in obese adults. Sleep. 2012 Nov 1;35(11):1529-39. doi: 10.5665/sleep.2204.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Scott A Sands, PhD principal investigator
Brigham and Women's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Combination device and drug: Unilateral hypoglossal nerve stimulation & atomoxetine-plus-oxybutynin (HGNS+AtoOxy), Unilateral hypoglossal nerve stimulation (HGNS), active comparator condition and Atomoxetine-plus-oxybutynin (80/5 mg) (AtoOxy), active comparator condition in people with Obstructive Sleep Apnea and Sleep-disordered Breathing, run by Brigham and Women's Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 21 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Daniel P Vena, PhD (617-852-0719, dvena@bwh.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Apnea-Hypopnea Index (time frame: 2 Weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07577661, which also lists 14 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2026; AzTrials last refreshed its copy on 26 Oct 2026.