A Comparative Effectiveness Study of Positive Airway Pressure (PAP) Therapy, Dental Device, and Atomoxetine-Oxybutynin for Treatment of Obstructive Sleep Apnea in Adults

NCT07679282 | Not Yet Recruiting Phase 4 DMC FDA Drug FDA Device

• 1 other identifier: BPS-2024C2-37819
• Study Type: interventional
• Target: 2,400
• Locations: 1 country
• Sites: 4

Brief Summary

Researchers want to identify which treatments for obstructive sleep apnea (OSA) work best and are easiest for patients to use consistently. Eligible participants will be randomly assigned one of three OSA treatments: traditional PAP therapy, a dental device, or a combination of two FDA-approved medications (atomoxetine and oxybutynin) that are currently approved for other conditions. Over the course of one year, participants will attend two in-person visits and take part in four phone check-ins to complete surveys, report any side effects, and discuss how well they are following their assigned treatment.

Conditions

Obstructive Sleep Apnea (OSA)

Keywords

Sleep apnea treatments; Dental device for sleep; Positive airway pressure; Atomoxetine-oxybutynin; Comparative effectiveness

Outcome Measures

Primary Outcomes (1)

• Health-related quality of life

  To compare the effectiveness of positive airway pressure (PAP) therapy versus dental device versus atomoxetine-oxybutynin for key patient centered outcomes in improving health-related quality of life over 12 months, as assessed by the PROMIS-29 v2.0.

  At 12 months

Secondary Outcomes (7)

• OSA treatment effectiveness - Effective AHI score

  12 months

• OSA treatment effectiveness - PROMIS-Sleep Related Impairment 8a

  12 months

• Changes in systolic blood pressure

  12 months

• Changes in diastolic blood pressure

  12 months

• OSA treatment adherence

  12 months

Study Arms (3)

Positive airway pressure (PAP) therapy

ACTIVE COMPARATOR

Participants will use a PAP machine to treat their obstructive sleep apnea.

Device: Positive airway pressure (PAP) therapy

Dental device

ACTIVE COMPARATOR

Participants will use a sleep dental device to treat their obstructive sleep apnea.

Device: Sleep dental device

Medications - atomoxetine-oxybutynin

ACTIVE COMPARATOR

Participants will use the medication combination of atomoxetine-oxybutynin to treat their obstructive sleep apnea.

Drug: Atomoxetine-oxybutynin

Interventions

Positive airway pressure (PAP) therapy DEVICE

Positive airway pressure delivered via a nasal or face mask while a patient sleeps to keep the airways open.

Also known as: CPAP

Positive airway pressure (PAP) therapy

Sleep dental device DEVICE

An oral appliance worn during sleep to move the lower jaw forward, which tightens soft tissues and widens the airway to prevent sleep apnea.

Also known as: Mandibular advancement device (MAD)

Dental device

Atomoxetine-oxybutynin DRUG

The combination of two medications (atomoxetine-oxybutynin) can reduce obstructive sleep apnea by increasing upper airway muscle activity.

Medications - atomoxetine-oxybutynin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Obstructive sleep apnea (AHI \>/= 5 per hour), diagnosed in the past 6 months
• Two or more of the following symptoms: snoring, fragmented sleep, witnessed apneas, or daytime sleepiness
• Willingness/ability to use any of the 3 treatments for OSA (PAP, dental device, or atomoxetine-oxybutynin)
• Health insurance of any type

You may not qualify if:

• Prior treatment for OSA in past year
• Central sleep apnea or narcolepsy
• Contraindication for dental device (temporomandibular joint problems, severe periodontal disease, insufficient dentition)
• Heart failure with reduced ejection fraction of \</= 45%
• Active coronary artery disease (angina or infarction within 3 months of enrollment)
• Current untreated depression
• Untreated narrow angle glaucoma
• Untreated hypothyroidism
• Clinically significant gastric retention
• Clinically significant urinary retention
• History of liver disease
• Seizure disorder
• Pregnant or nursing, or plans to become pregnant within the year
• Concomitant medication use that is incompatible with atomoxetine or oxybutynin
• Participation in another clinical study with an investigational product

Sponsors & Collaborators

• Sairam Parthasarathy: lead
• Patient-Centered Outcomes Research Institute: collaborator
• University of Arizona: collaborator
• University of Maryland: collaborator
• University of Miami: collaborator
• Stanford University: collaborator

Study Sites (4)

Banner University Medical Center Tucson

Tucson, Arizona, 85719, United States

Location

Stanford Medical Center

Palo Alto, California, 94305, United States

Location

University of Miami Miller School of Medicine

Miami, Florida, 33136, United States

Location

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Related Publications (31)

• Aishah A, Loffler KA, Toson B, Mukherjee S, Adams RJ, Altree TJ, Ainge-Allen HW, Yee BJ, Grunstein RR, Carberry JC, Eckert DJ. One Month Dosing of Atomoxetine plus Oxybutynin in Obstructive Sleep Apnea: A Randomized, Placebo-controlled Trial. Ann Am Thorac Soc. 2023 Apr;20(4):584-595. doi: 10.1513/AnnalsATS.202206-492OC.

  PMID: 36538809 BACKGROUND

• Taranto-Montemurro L, Messineo L, Sands SA, Azarbarzin A, Marques M, Edwards BA, Eckert DJ, White DP, Wellman A. The Combination of Atomoxetine and Oxybutynin Greatly Reduces Obstructive Sleep Apnea Severity. A Randomized, Placebo-controlled, Double-Blind Crossover Trial. Am J Respir Crit Care Med. 2019 May 15;199(10):1267-1276. doi: 10.1164/rccm.201808-1493OC.

  PMID: 30395486 BACKGROUND

• Schweitzer PK, Maynard JP, Wylie PE, Emsellem HA, Sands SA. Efficacy of atomoxetine plus oxybutynin in the treatment of obstructive sleep apnea with moderate pharyngeal collapsibility. Sleep Breath. 2023 May;27(2):495-503. doi: 10.1007/s11325-022-02634-x. Epub 2022 May 13.

  PMID: 35551600 BACKGROUND

• Rosenberg R, Abaluck B, Thein S. Combination of atomoxetine with the novel antimuscarinic aroxybutynin improves mild to moderate OSA. J Clin Sleep Med. 2022 Dec 1;18(12):2837-2844. doi: 10.5664/jcsm.10250.

  PMID: 35975547 BACKGROUND

• Kinouchi T, Terada J, Sakao S, Koshikawa K, Sasaki T, Sugiyama A, Sato S, Sakuma N, Abe M, Shikano K, Hayama N, Shiko Y, Ozawa Y, Ikeda S, Suzuki T, Tatsumi K. Effects of the combination of atomoxetine and oxybutynin in Japanese patients with obstructive sleep apnoea: A randomized controlled crossover trial. Respirology. 2023 Mar;28(3):273-280. doi: 10.1111/resp.14383. Epub 2022 Oct 2.

  PMID: 36184258 BACKGROUND

• Chen TY, Chung CH, Chang HA, Kao YC, Chang SY, Kuo TBJ, Yang CCH, Chien WC, Tzeng NS. Long-term atomoxetine-oxybutynin combination use may be beneficial for the prevention of obstructive sleep apnea. Sci Rep. 2021 Jun 15;11(1):12526. doi: 10.1038/s41598-021-91988-5.

  PMID: 34131226 BACKGROUND

• Schwartz M, Acosta L, Hung YL, Padilla M, Enciso R. Effects of CPAP and mandibular advancement device treatment in obstructive sleep apnea patients: a systematic review and meta-analysis. Sleep Breath. 2018 Sep;22(3):555-568. doi: 10.1007/s11325-017-1590-6. Epub 2017 Nov 11.

  PMID: 29129030 BACKGROUND

• Ramar K, Dort LC, Katz SG, Lettieri CJ, Harrod CG, Thomas SM, Chervin RD. Clinical Practice Guideline for the Treatment of Obstructive Sleep Apnea and Snoring with Oral Appliance Therapy: An Update for 2015. J Clin Sleep Med. 2015 Jul 15;11(7):773-827. doi: 10.5664/jcsm.4858.

  PMID: 26094920 BACKGROUND

• Chan AS, Lee RW, Cistulli PA. Dental appliance treatment for obstructive sleep apnea. Chest. 2007 Aug;132(2):693-9. doi: 10.1378/chest.06-2038.

  PMID: 17699143 BACKGROUND

• Marin JM, Carrizo SJ, Vicente E, Agusti AG. Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet. 2005 Mar 19-25;365(9464):1046-53. doi: 10.1016/S0140-6736(05)71141-7.

  PMID: 15781100 BACKGROUND

• Martinez-Garcia MA, Campos-Rodriguez F, Catalan-Serra P, Soler-Cataluna JJ, Almeida-Gonzalez C, De la Cruz Moron I, Duran-Cantolla J, Montserrat JM. Cardiovascular mortality in obstructive sleep apnea in the elderly: role of long-term continuous positive airway pressure treatment: a prospective observational study. Am J Respir Crit Care Med. 2012 Nov 1;186(9):909-16. doi: 10.1164/rccm.201203-0448OC. Epub 2012 Sep 13.

  PMID: 22983957 BACKGROUND

• Platt AB, Field SH, Asch DA, Chen Z, Patel NP, Gupta R, Roche DF, Gurubhagavatula I, Christie JD, Kuna ST. Neighborhood of residence is associated with daily adherence to CPAP therapy. Sleep. 2009 Jun;32(6):799-806. doi: 10.1093/sleep/32.6.799.

  PMID: 19544757 BACKGROUND

• Bakker JP, O'Keeffe KM, Neill AM, Campbell AJ. Ethnic disparities in CPAP adherence in New Zealand: effects of socioeconomic status, health literacy and self-efficacy. Sleep. 2011 Nov 1;34(11):1595-603. doi: 10.5665/sleep.1404.

  PMID: 22043130 BACKGROUND

• Billings ME, Auckley D, Benca R, Foldvary-Schaefer N, Iber C, Redline S, Rosen CL, Zee P, Kapur VK. Race and residential socioeconomics as predictors of CPAP adherence. Sleep. 2011 Dec 1;34(12):1653-8. doi: 10.5665/sleep.1428.

  PMID: 22131602 BACKGROUND

• McEvoy RD, Antic NA, Heeley E, Luo Y, Ou Q, Zhang X, Mediano O, Chen R, Drager LF, Liu Z, Chen G, Du B, McArdle N, Mukherjee S, Tripathi M, Billot L, Li Q, Lorenzi-Filho G, Barbe F, Redline S, Wang J, Arima H, Neal B, White DP, Grunstein RR, Zhong N, Anderson CS; SAVE Investigators and Coordinators. CPAP for Prevention of Cardiovascular Events in Obstructive Sleep Apnea. N Engl J Med. 2016 Sep 8;375(10):919-31. doi: 10.1056/NEJMoa1606599. Epub 2016 Aug 28.

  PMID: 27571048 BACKGROUND

• Redline S, Yenokyan G, Gottlieb DJ, Shahar E, O'Connor GT, Resnick HE, Diener-West M, Sanders MH, Wolf PA, Geraghty EM, Ali T, Lebowitz M, Punjabi NM. Obstructive sleep apnea-hypopnea and incident stroke: the sleep heart health study. Am J Respir Crit Care Med. 2010 Jul 15;182(2):269-77. doi: 10.1164/rccm.200911-1746OC. Epub 2010 Mar 25.

  PMID: 20339144 BACKGROUND

• Mulgrew AT, Nasvadi G, Butt A, Cheema R, Fox N, Fleetham JA, Ryan CF, Cooper P, Ayas NT. Risk and severity of motor vehicle crashes in patients with obstructive sleep apnoea/hypopnoea. Thorax. 2008 Jun;63(6):536-41. doi: 10.1136/thx.2007.085464. Epub 2008 Jan 30.

  PMID: 18234904 BACKGROUND

• Teran-Santos J, Jimenez-Gomez A, Cordero-Guevara J. The association between sleep apnea and the risk of traffic accidents. Cooperative Group Burgos-Santander. N Engl J Med. 1999 Mar 18;340(11):847-51. doi: 10.1056/NEJM199903183401104.

  PMID: 10080847 BACKGROUND

• Gami AS, Howard DE, Olson EJ, Somers VK. Day-night pattern of sudden death in obstructive sleep apnea. N Engl J Med. 2005 Mar 24;352(12):1206-14. doi: 10.1056/NEJMoa041832.

  PMID: 15788497 BACKGROUND

• Punjabi NM, Caffo BS, Goodwin JL, Gottlieb DJ, Newman AB, O'Connor GT, Rapoport DM, Redline S, Resnick HE, Robbins JA, Shahar E, Unruh ML, Samet JM. Sleep-disordered breathing and mortality: a prospective cohort study. PLoS Med. 2009 Aug;6(8):e1000132. doi: 10.1371/journal.pmed.1000132. Epub 2009 Aug 18.

  PMID: 19688045 BACKGROUND

• Weaver TE. Outcome measurement in sleep medicine practice and research. Part 1: assessment of symptoms, subjective and objective daytime sleepiness, health-related quality of life and functional status. Sleep Med Rev. 2001 Apr;5(2):103-128. doi: 10.1053/smrv.2001.0152.

  PMID: 12531049 BACKGROUND

• Yaggi HK, Concato J, Kernan WN, Lichtman JH, Brass LM, Mohsenin V. Obstructive sleep apnea as a risk factor for stroke and death. N Engl J Med. 2005 Nov 10;353(19):2034-41. doi: 10.1056/NEJMoa043104.

  PMID: 16282178 BACKGROUND

• Yumino D, Wang H, Floras JS, Newton GE, Mak S, Ruttanaumpawan P, Parker JD, Bradley TD. Relationship between sleep apnoea and mortality in patients with ischaemic heart failure. Heart. 2009 May;95(10):819-24. doi: 10.1136/hrt.2008.160952. Epub 2009 Jan 8.

  PMID: 19131443 BACKGROUND

• Leung RS, Bradley TD. Sleep apnea and cardiovascular disease. Am J Respir Crit Care Med. 2001 Dec 15;164(12):2147-65. doi: 10.1164/ajrccm.164.12.2107045. No abstract available.

  PMID: 11751180 BACKGROUND

• Peker Y, Carlson J, Hedner J. Increased incidence of coronary artery disease in sleep apnoea: a long-term follow-up. Eur Respir J. 2006 Sep;28(3):596-602. doi: 10.1183/09031936.06.00107805. Epub 2006 Apr 26.

  PMID: 16641120 BACKGROUND

• Nieto FJ, Young TB, Lind BK, Shahar E, Samet JM, Redline S, D'Agostino RB, Newman AB, Lebowitz MD, Pickering TG. Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study. Sleep Heart Health Study. JAMA. 2000 Apr 12;283(14):1829-36. doi: 10.1001/jama.283.14.1829.

  PMID: 10770144 BACKGROUND

• Peppard PE, Young T, Palta M, Skatrud J. Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med. 2000 May 11;342(19):1378-84. doi: 10.1056/NEJM200005113421901.

  PMID: 10805822 BACKGROUND

• Marin JM, Agusti A, Villar I, Forner M, Nieto D, Carrizo SJ, Barbe F, Vicente E, Wei Y, Nieto FJ, Jelic S. Association between treated and untreated obstructive sleep apnea and risk of hypertension. JAMA. 2012 May 23;307(20):2169-76. doi: 10.1001/jama.2012.3418.

  PMID: 22618924 BACKGROUND

• Punjabi NM. The epidemiology of adult obstructive sleep apnea. Proc Am Thorac Soc. 2008 Feb 15;5(2):136-43. doi: 10.1513/pats.200709-155MG.

  PMID: 18250205 BACKGROUND

• May AM, Patel SR, Yamauchi M, Verma TK, Weaver TE, Chai-Coetzer CL, Thornton JD, Ewart G, Showers T, Ayas NT, Parthasarathy S, Mehra R, Billings ME. Moving toward Equitable Care for Sleep Apnea in the United States: Positive Airway Pressure Adherence Thresholds: An Official American Thoracic Society Policy Statement. Am J Respir Crit Care Med. 2023 Feb 1;207(3):244-254. doi: 10.1164/rccm.202210-1846ST.

  PMID: 36722719 BACKGROUND

• Weaver TE, Grunstein RR. Adherence to continuous positive airway pressure therapy: the challenge to effective treatment. Proc Am Thorac Soc. 2008 Feb 15;5(2):173-8. doi: 10.1513/pats.200708-119MG.

  PMID: 18250209 BACKGROUND

MeSH Terms

Conditions

Sleep Apnea, Obstructive

Interventions

Therapeutics; Occlusal Splints

Condition Hierarchy (Ancestors)

Sleep Apnea Syndromes; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Orthotic Devices; Orthopedic Equipment; Surgical Equipment; Equipment and Supplies

Study Officials

• Sairam Parthasarathy, MD

  University of Arizona

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Heidi Erickson, BSN, RN

CONTACT

1-520-626-5287; herickso@arizona.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator, Professor of Medicine

Model Details: Participants will be randomized to receive 1 of 3 possible OSA treatments - positive airway pressure (PAP) therapy, dental device, or medication treatment with atomoxetine-oxybutynin.

Study Record Dates

• First Submitted: June 4, 2026
• First Posted: July 1, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): March 1, 2030
• Study Completion (Estimated): May 1, 2032
• Last Updated: July 1, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: One year after the primary paper has been accepted and secondary paper has been submitted. Data will be available for as long as Dr. Parthasarathy is with the University of Arizona.
• Access Criteria: Researchers that contact the primary PI (S. Parthasarathy, MD) with a proposal to use the data and complete a data use agreement with the University of Arizona.

Locations

US (4)