NCT07577661

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.

Trial Health

63
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
24

participants targeted

Target at P25-P50 for phase_1

Timeline
18mo left

Started Jun 2026

Geographic Reach
1 country

1 active site

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 27, 2026

Completed
14 days until next milestone

First Posted

Study publicly available on registry

May 11, 2026

Completed
21 days until next milestone

Study Start

First participant enrolled

June 1, 2026

Expected
1.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2027

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2027

Last Updated

May 11, 2026

Status Verified

May 1, 2026

Enrollment Period

1.5 years

First QC Date

April 27, 2026

Last Update Submit

May 4, 2026

Conditions

Obstructive Sleep ApneaSleep-disordered Breathing

Keywords

Obstructive sleep apneaPharmacotherapyHypoglossal nerve stimulationOxybutyninAtomoxetine

Outcome Measures

Primary Outcomes (1)

  • 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.

    2 Weeks

Secondary Outcomes (2)

  • Hypoxic Burden

    2 Weeks

  • Visual Analog Scale for Sleep Quality

    2 Weeks

Other Outcomes (6)

  • Epworth Sleepiness Scale (ESS)

    2 Weeks

  • Visual Analog Scale for Treatment Satisfaction

    2 Weeks

  • Sleep Apnea Quality of Life Index (SAQLI)

    2 Weeks

  • +3 more other outcomes

Study Arms (4)

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.

Other: Combination device and drug: Unilateral hypoglossal nerve stimulation & atomoxetine-plus-oxybutynin (HGNS+AtoOxy)Device: Unilateral hypoglossal nerve stimulation (HGNS), active comparator conditionDrug: Atomoxetine-plus-oxybutynin (80/5 mg) (AtoOxy), active comparator conditionDrug: 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.

Other: Combination device and drug: Unilateral hypoglossal nerve stimulation & atomoxetine-plus-oxybutynin (HGNS+AtoOxy)Device: Unilateral hypoglossal nerve stimulation (HGNS), active comparator conditionDrug: Atomoxetine-plus-oxybutynin (80/5 mg) (AtoOxy), active comparator conditionDrug: 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.

Other: Combination device and drug: Unilateral hypoglossal nerve stimulation & atomoxetine-plus-oxybutynin (HGNS+AtoOxy)Device: Unilateral hypoglossal nerve stimulation (HGNS), active comparator conditionDrug: Atomoxetine-plus-oxybutynin (80/5 mg) (AtoOxy), active comparator conditionDrug: 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.

Other: Combination device and drug: Unilateral hypoglossal nerve stimulation & atomoxetine-plus-oxybutynin (HGNS+AtoOxy)Device: Unilateral hypoglossal nerve stimulation (HGNS), active comparator conditionDrug: Atomoxetine-plus-oxybutynin (80/5 mg) (AtoOxy), active comparator conditionDrug: Placebo; placebo comparator condition

Interventions

Unilateral hypoglossal nerve stimulation (HGNS), active comparator conditionDEVICE

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.

Also known as: HGNS
Sequence 1Sequence 2Sequence 3Sequence 4
Placebo; placebo comparator conditionDRUG

Matching placebo capsules administered orally at bedtime. HGNS device off

Also known as: Placebo
Sequence 1Sequence 2Sequence 3Sequence 4
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.

Also known as: HGNS+AtoOxy
Sequence 1Sequence 2Sequence 3Sequence 4
Atomoxetine-plus-oxybutynin (80/5 mg) (AtoOxy), active comparator conditionDRUG

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

Also known as: AtoOxy
Sequence 1Sequence 2Sequence 3Sequence 4

Eligibility Criteria

Age18 Years - 79 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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).

You may not qualify if:

  • 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
  • +20 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Related Publications (14)

  • 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.

    PMID: 22219335BACKGROUND

  • Sands 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.

    PMID: 29228393BACKGROUND

  • Sands 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.

    PMID: 29327943BACKGROUND

  • Terrill 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.

    PMID: 25323235BACKGROUND

  • Sands 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.

    PMID: 30139771BACKGROUND

  • Pepperell 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.

    PMID: 12928310BACKGROUND

  • Pepperell 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.

    PMID: 11812555BACKGROUND

  • Ryan 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.

    PMID: 15994252BACKGROUND

  • Gold 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.

    PMID: 3096178BACKGROUND

  • Azarbarzin 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.

    PMID: 30376054BACKGROUND

  • Taylor 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.

    PMID: 27698070BACKGROUND

  • Winslow 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.

    PMID: 23115402BACKGROUND

  • Phillips 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.

    PMID: 23413266BACKGROUND

  • Strollo 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.

    PMID: 24401051BACKGROUND

MeSH Terms

Conditions

Sleep Apnea, ObstructiveSleep Apnea Syndromes

Condition Hierarchy (Ancestors)

ApneaRespiration DisordersRespiratory Tract DiseasesSleep Disorders, IntrinsicDyssomniasSleep Wake DisordersNervous System Diseases

Study Officials

  • Scott A Sands, PhD

    Brigham and Women's Hospital

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Daniel P Vena, PhD

CONTACT

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

Dillon Gilbertson, BASc

CONTACT

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

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
Medication (atomoxetine plus oxybutynin vs placebo) is double-blinded to participants, investigators, and outcomes assessors. Hypoglossal nerve stimulation (HGNS) cannot be blinded, as device activation status must be known to study staff and participants. Randomization procedures are designed to maintain blinding of medication assignment while allowing appropriate administration of HGNS.
Purpose
TREATMENT
Intervention Model
CROSSOVER
Model Details: 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.
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Associate Professor

Study Record Dates

First Submitted

April 27, 2026

First Posted

May 11, 2026

Study Start (Estimated)

June 1, 2026

Primary Completion (Estimated)

December 1, 2027

Study Completion (Estimated)

December 1, 2027

Last Updated

May 11, 2026

Record last verified: 2026-05

Locations

US(1)