Combined Upper-airway and Breathing Control Therapies for Obstructive Sleep Apnea

NCT ID: NCT03189173

Last Updated: 2025-05-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

41 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-09-06

Study Completion Date

2023-05-01

Brief Summary

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The current study combines two treatments for obstructive sleep apnea (OSA), oral appliances and supplemental inspired oxygen. The following aims will be tested:

Aim 1. To determine whether supplemental inspired oxygen further reduces OSA severity (apnea-hypopnea index) in patients using an oral appliance.

Aim 2. To determine whether baseline OSA phenotypes can predict the efficacy of oral appliances versus supplemental oxygen versus both treatments in combination. We will test whether responders to oral appliances have distinct pathophysiological characteristics compared with oxygen responders.

Detailed Description

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Pre-specified primary analysis for Aim 1 is the change in AHI with combination treatment versus oral appliance alone (%reduction versus placebo; including hypopnea events without desaturation/arousals).

Aim 2 seeks to identify subgroups of patients that have the greatest reduction in AHI (responders) with each treatment (post-hoc). We will use baseline physiological measures of the four traits causing OSA (collapsibility, responsiveness, loop gain, arousal threshold) to determine which characteristics predict responses to each intervention (leave-one-out support vector machine modeling). Clinical measures of the same traits will be estimated from the placebo night to confirm that responses can be predicted with clinically-available data. We will also test whether responders to oral appliances have a greater response to oxygen than oral appliance non-responders (and vice-versa), to address whether responders to both treatments are similar or different.

Conditions

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Obstructive Sleep Apnea

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SINGLE_GROUP

Subjects will receive mandibular advancement, supplemental oxygen, mandibular advancement plus supplemental oxygen, and no treatment in randomized order. On nights without supplemental oxygen, subjects will be administered sham (air, single blinded). Oral appliance use will not be masked.
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Outcome Assessors
Supplemental oxygen versus air assignment nights will be blinded to participants, but will be known by the investigator. Oral appliances will be "open label".

Study Groups

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Combo, Mad, Sham, Oxygen

Order of interventions: Combo, Mad, Sham, Oxygen

Group Type EXPERIMENTAL

Oral appliance

Intervention Type DEVICE

An oral appliance (dental mouthpiece) will be used to improve upper airway patency. Patients who do not have their own custom dental oral appliance (various brands, commonly Herbst/Somnomed) will be provided with a device (BluePro, BlueSom) for the duration of the study.

Patients will also be administered sham (room air) at 4 L/min via nasal cannula.

Oxygen

Intervention Type DRUG

Supplemental oxygen will be delivered at 4 L/min via nasal cannula to improve ventilatory control stability.

Oral appliance plus oxygen

Intervention Type OTHER

Both treatments will be administered simultaneously.

No treatment

Intervention Type OTHER

Subjects will not wear an oral appliance, and will be administered sham (room air) at 4 L/min via nasal cannula.

Combo, Oxygen, Mad, Sham

Order of interventions: Combo, Oxygen, Mad, Sham

Group Type EXPERIMENTAL

Oral appliance

Intervention Type DEVICE

An oral appliance (dental mouthpiece) will be used to improve upper airway patency. Patients who do not have their own custom dental oral appliance (various brands, commonly Herbst/Somnomed) will be provided with a device (BluePro, BlueSom) for the duration of the study.

Patients will also be administered sham (room air) at 4 L/min via nasal cannula.

Oxygen

Intervention Type DRUG

Supplemental oxygen will be delivered at 4 L/min via nasal cannula to improve ventilatory control stability.

Oral appliance plus oxygen

Intervention Type OTHER

Both treatments will be administered simultaneously.

No treatment

Intervention Type OTHER

Subjects will not wear an oral appliance, and will be administered sham (room air) at 4 L/min via nasal cannula.

Combo, Oxygen, Sham, MAD

Order of interventions: Combo, Oxygen, Sham, MAD

Group Type EXPERIMENTAL

Oral appliance

Intervention Type DEVICE

An oral appliance (dental mouthpiece) will be used to improve upper airway patency. Patients who do not have their own custom dental oral appliance (various brands, commonly Herbst/Somnomed) will be provided with a device (BluePro, BlueSom) for the duration of the study.

Patients will also be administered sham (room air) at 4 L/min via nasal cannula.

Oxygen

Intervention Type DRUG

Supplemental oxygen will be delivered at 4 L/min via nasal cannula to improve ventilatory control stability.

Oral appliance plus oxygen

Intervention Type OTHER

Both treatments will be administered simultaneously.

No treatment

Intervention Type OTHER

Subjects will not wear an oral appliance, and will be administered sham (room air) at 4 L/min via nasal cannula.

Combo, Sham, Mad, Oxygen

Order of interventions: Combo, Sham, Mad, Oxygen

Group Type EXPERIMENTAL

Oral appliance

Intervention Type DEVICE

An oral appliance (dental mouthpiece) will be used to improve upper airway patency. Patients who do not have their own custom dental oral appliance (various brands, commonly Herbst/Somnomed) will be provided with a device (BluePro, BlueSom) for the duration of the study.

Patients will also be administered sham (room air) at 4 L/min via nasal cannula.

Oxygen

Intervention Type DRUG

Supplemental oxygen will be delivered at 4 L/min via nasal cannula to improve ventilatory control stability.

Oral appliance plus oxygen

Intervention Type OTHER

Both treatments will be administered simultaneously.

No treatment

Intervention Type OTHER

Subjects will not wear an oral appliance, and will be administered sham (room air) at 4 L/min via nasal cannula.

Combo, Sham, Oxygen, MAD

Order of interventions: Combo, Sham, Oxygen, MAD

Group Type EXPERIMENTAL

Oral appliance

Intervention Type DEVICE

An oral appliance (dental mouthpiece) will be used to improve upper airway patency. Patients who do not have their own custom dental oral appliance (various brands, commonly Herbst/Somnomed) will be provided with a device (BluePro, BlueSom) for the duration of the study.

Patients will also be administered sham (room air) at 4 L/min via nasal cannula.

Oxygen

Intervention Type DRUG

Supplemental oxygen will be delivered at 4 L/min via nasal cannula to improve ventilatory control stability.

Oral appliance plus oxygen

Intervention Type OTHER

Both treatments will be administered simultaneously.

No treatment

Intervention Type OTHER

Subjects will not wear an oral appliance, and will be administered sham (room air) at 4 L/min via nasal cannula.

MAD, Combo, Oxygen, Sham

Order of interventions: MAD, Combo, Oxygen, Sham

Group Type EXPERIMENTAL

Oral appliance

Intervention Type DEVICE

An oral appliance (dental mouthpiece) will be used to improve upper airway patency. Patients who do not have their own custom dental oral appliance (various brands, commonly Herbst/Somnomed) will be provided with a device (BluePro, BlueSom) for the duration of the study.

Patients will also be administered sham (room air) at 4 L/min via nasal cannula.

Oxygen

Intervention Type DRUG

Supplemental oxygen will be delivered at 4 L/min via nasal cannula to improve ventilatory control stability.

Oral appliance plus oxygen

Intervention Type OTHER

Both treatments will be administered simultaneously.

No treatment

Intervention Type OTHER

Subjects will not wear an oral appliance, and will be administered sham (room air) at 4 L/min via nasal cannula.

MAD, Combo, Sham, Oxygen

Order of interventions: MAD, Combo, Sham, Oxygen

Group Type EXPERIMENTAL

Oral appliance

Intervention Type DEVICE

An oral appliance (dental mouthpiece) will be used to improve upper airway patency. Patients who do not have their own custom dental oral appliance (various brands, commonly Herbst/Somnomed) will be provided with a device (BluePro, BlueSom) for the duration of the study.

Patients will also be administered sham (room air) at 4 L/min via nasal cannula.

Oxygen

Intervention Type DRUG

Supplemental oxygen will be delivered at 4 L/min via nasal cannula to improve ventilatory control stability.

Oral appliance plus oxygen

Intervention Type OTHER

Both treatments will be administered simultaneously.

No treatment

Intervention Type OTHER

Subjects will not wear an oral appliance, and will be administered sham (room air) at 4 L/min via nasal cannula.

MAD, Oxygen, Combo, Sham

Order of interventions: MAD, Oxygen, Combo, Sham

Group Type EXPERIMENTAL

Oral appliance

Intervention Type DEVICE

An oral appliance (dental mouthpiece) will be used to improve upper airway patency. Patients who do not have their own custom dental oral appliance (various brands, commonly Herbst/Somnomed) will be provided with a device (BluePro, BlueSom) for the duration of the study.

Patients will also be administered sham (room air) at 4 L/min via nasal cannula.

Oxygen

Intervention Type DRUG

Supplemental oxygen will be delivered at 4 L/min via nasal cannula to improve ventilatory control stability.

Oral appliance plus oxygen

Intervention Type OTHER

Both treatments will be administered simultaneously.

No treatment

Intervention Type OTHER

Subjects will not wear an oral appliance, and will be administered sham (room air) at 4 L/min via nasal cannula.

MAD, Oxygen, Sham, Combo

Order of interventions: MAD, Oxygen, Sham, Combo

Group Type EXPERIMENTAL

Oral appliance

Intervention Type DEVICE

An oral appliance (dental mouthpiece) will be used to improve upper airway patency. Patients who do not have their own custom dental oral appliance (various brands, commonly Herbst/Somnomed) will be provided with a device (BluePro, BlueSom) for the duration of the study.

Patients will also be administered sham (room air) at 4 L/min via nasal cannula.

Oxygen

Intervention Type DRUG

Supplemental oxygen will be delivered at 4 L/min via nasal cannula to improve ventilatory control stability.

Oral appliance plus oxygen

Intervention Type OTHER

Both treatments will be administered simultaneously.

No treatment

Intervention Type OTHER

Subjects will not wear an oral appliance, and will be administered sham (room air) at 4 L/min via nasal cannula.

MAD, Sham, Combo, Oxygen

Order of interventions: MAD, Sham, Combo, Oxygen

Group Type EXPERIMENTAL

Oral appliance

Intervention Type DEVICE

An oral appliance (dental mouthpiece) will be used to improve upper airway patency. Patients who do not have their own custom dental oral appliance (various brands, commonly Herbst/Somnomed) will be provided with a device (BluePro, BlueSom) for the duration of the study.

Patients will also be administered sham (room air) at 4 L/min via nasal cannula.

Oxygen

Intervention Type DRUG

Supplemental oxygen will be delivered at 4 L/min via nasal cannula to improve ventilatory control stability.

Oral appliance plus oxygen

Intervention Type OTHER

Both treatments will be administered simultaneously.

No treatment

Intervention Type OTHER

Subjects will not wear an oral appliance, and will be administered sham (room air) at 4 L/min via nasal cannula.

MAD, Sham, Oxygen, Combo

Order of interventions: MAD, Sham, Oxygen, Combo

Group Type EXPERIMENTAL

Oral appliance

Intervention Type DEVICE

An oral appliance (dental mouthpiece) will be used to improve upper airway patency. Patients who do not have their own custom dental oral appliance (various brands, commonly Herbst/Somnomed) will be provided with a device (BluePro, BlueSom) for the duration of the study.

Patients will also be administered sham (room air) at 4 L/min via nasal cannula.

Oxygen

Intervention Type DRUG

Supplemental oxygen will be delivered at 4 L/min via nasal cannula to improve ventilatory control stability.

Oral appliance plus oxygen

Intervention Type OTHER

Both treatments will be administered simultaneously.

No treatment

Intervention Type OTHER

Subjects will not wear an oral appliance, and will be administered sham (room air) at 4 L/min via nasal cannula.

Oxygen, Combo, Sham, MAD

Order of interventions: Oxygen, Combo, Sham, MAD

Group Type EXPERIMENTAL

Oral appliance

Intervention Type DEVICE

An oral appliance (dental mouthpiece) will be used to improve upper airway patency. Patients who do not have their own custom dental oral appliance (various brands, commonly Herbst/Somnomed) will be provided with a device (BluePro, BlueSom) for the duration of the study.

Patients will also be administered sham (room air) at 4 L/min via nasal cannula.

Oxygen

Intervention Type DRUG

Supplemental oxygen will be delivered at 4 L/min via nasal cannula to improve ventilatory control stability.

Oral appliance plus oxygen

Intervention Type OTHER

Both treatments will be administered simultaneously.

No treatment

Intervention Type OTHER

Subjects will not wear an oral appliance, and will be administered sham (room air) at 4 L/min via nasal cannula.

Oxygen, MAD, Sham, Combo

Order of interventions: Oxygen, MAD, Sham, Combo

Group Type EXPERIMENTAL

Oral appliance

Intervention Type DEVICE

An oral appliance (dental mouthpiece) will be used to improve upper airway patency. Patients who do not have their own custom dental oral appliance (various brands, commonly Herbst/Somnomed) will be provided with a device (BluePro, BlueSom) for the duration of the study.

Patients will also be administered sham (room air) at 4 L/min via nasal cannula.

Oxygen

Intervention Type DRUG

Supplemental oxygen will be delivered at 4 L/min via nasal cannula to improve ventilatory control stability.

Oral appliance plus oxygen

Intervention Type OTHER

Both treatments will be administered simultaneously.

No treatment

Intervention Type OTHER

Subjects will not wear an oral appliance, and will be administered sham (room air) at 4 L/min via nasal cannula.

Oxygen, Sham, Combo, MAD

Order of interventions: Oxygen, Sham, Combo, MAD

Group Type EXPERIMENTAL

Oral appliance

Intervention Type DEVICE

An oral appliance (dental mouthpiece) will be used to improve upper airway patency. Patients who do not have their own custom dental oral appliance (various brands, commonly Herbst/Somnomed) will be provided with a device (BluePro, BlueSom) for the duration of the study.

Patients will also be administered sham (room air) at 4 L/min via nasal cannula.

Oxygen

Intervention Type DRUG

Supplemental oxygen will be delivered at 4 L/min via nasal cannula to improve ventilatory control stability.

Oral appliance plus oxygen

Intervention Type OTHER

Both treatments will be administered simultaneously.

No treatment

Intervention Type OTHER

Subjects will not wear an oral appliance, and will be administered sham (room air) at 4 L/min via nasal cannula.

Oxygen, Sham, MAD, Combo

Order of interventions: Oxygen, Sham, MAD, Combo

Group Type EXPERIMENTAL

Oral appliance

Intervention Type DEVICE

An oral appliance (dental mouthpiece) will be used to improve upper airway patency. Patients who do not have their own custom dental oral appliance (various brands, commonly Herbst/Somnomed) will be provided with a device (BluePro, BlueSom) for the duration of the study.

Patients will also be administered sham (room air) at 4 L/min via nasal cannula.

Oxygen

Intervention Type DRUG

Supplemental oxygen will be delivered at 4 L/min via nasal cannula to improve ventilatory control stability.

Oral appliance plus oxygen

Intervention Type OTHER

Both treatments will be administered simultaneously.

No treatment

Intervention Type OTHER

Subjects will not wear an oral appliance, and will be administered sham (room air) at 4 L/min via nasal cannula.

Sham, Combo, MAD, Oxygen

Order of interventions: Sham, Combo, MAD, Oxygen

Group Type EXPERIMENTAL

Oral appliance

Intervention Type DEVICE

An oral appliance (dental mouthpiece) will be used to improve upper airway patency. Patients who do not have their own custom dental oral appliance (various brands, commonly Herbst/Somnomed) will be provided with a device (BluePro, BlueSom) for the duration of the study.

Patients will also be administered sham (room air) at 4 L/min via nasal cannula.

Oxygen

Intervention Type DRUG

Supplemental oxygen will be delivered at 4 L/min via nasal cannula to improve ventilatory control stability.

Oral appliance plus oxygen

Intervention Type OTHER

Both treatments will be administered simultaneously.

No treatment

Intervention Type OTHER

Subjects will not wear an oral appliance, and will be administered sham (room air) at 4 L/min via nasal cannula.

Sham, MAD, Combo, Oxygen

Order of interventions: Sham, MAD, Combo, Oxygen

Group Type EXPERIMENTAL

Oral appliance

Intervention Type DEVICE

An oral appliance (dental mouthpiece) will be used to improve upper airway patency. Patients who do not have their own custom dental oral appliance (various brands, commonly Herbst/Somnomed) will be provided with a device (BluePro, BlueSom) for the duration of the study.

Patients will also be administered sham (room air) at 4 L/min via nasal cannula.

Oxygen

Intervention Type DRUG

Supplemental oxygen will be delivered at 4 L/min via nasal cannula to improve ventilatory control stability.

Oral appliance plus oxygen

Intervention Type OTHER

Both treatments will be administered simultaneously.

No treatment

Intervention Type OTHER

Subjects will not wear an oral appliance, and will be administered sham (room air) at 4 L/min via nasal cannula.

Sham, MAD, Oxygen, Combo

Order of interventions: Sham, MAD, Oxygen, Combo

Group Type EXPERIMENTAL

Oral appliance

Intervention Type DEVICE

An oral appliance (dental mouthpiece) will be used to improve upper airway patency. Patients who do not have their own custom dental oral appliance (various brands, commonly Herbst/Somnomed) will be provided with a device (BluePro, BlueSom) for the duration of the study.

Patients will also be administered sham (room air) at 4 L/min via nasal cannula.

Oxygen

Intervention Type DRUG

Supplemental oxygen will be delivered at 4 L/min via nasal cannula to improve ventilatory control stability.

Oral appliance plus oxygen

Intervention Type OTHER

Both treatments will be administered simultaneously.

No treatment

Intervention Type OTHER

Subjects will not wear an oral appliance, and will be administered sham (room air) at 4 L/min via nasal cannula.

Sham, Oxygen, Combo, MAD

Order of interventions: Sham, Oxygen, Combo, MAD

Group Type EXPERIMENTAL

Oral appliance

Intervention Type DEVICE

An oral appliance (dental mouthpiece) will be used to improve upper airway patency. Patients who do not have their own custom dental oral appliance (various brands, commonly Herbst/Somnomed) will be provided with a device (BluePro, BlueSom) for the duration of the study.

Patients will also be administered sham (room air) at 4 L/min via nasal cannula.

Oxygen

Intervention Type DRUG

Supplemental oxygen will be delivered at 4 L/min via nasal cannula to improve ventilatory control stability.

Oral appliance plus oxygen

Intervention Type OTHER

Both treatments will be administered simultaneously.

No treatment

Intervention Type OTHER

Subjects will not wear an oral appliance, and will be administered sham (room air) at 4 L/min via nasal cannula.

Sham, Oxygen, MAD, Combo

Order of interventions: Sham, Oxygen, MAD, Combo

Group Type EXPERIMENTAL

Oral appliance

Intervention Type DEVICE

An oral appliance (dental mouthpiece) will be used to improve upper airway patency. Patients who do not have their own custom dental oral appliance (various brands, commonly Herbst/Somnomed) will be provided with a device (BluePro, BlueSom) for the duration of the study.

Patients will also be administered sham (room air) at 4 L/min via nasal cannula.

Oxygen

Intervention Type DRUG

Supplemental oxygen will be delivered at 4 L/min via nasal cannula to improve ventilatory control stability.

Oral appliance plus oxygen

Intervention Type OTHER

Both treatments will be administered simultaneously.

No treatment

Intervention Type OTHER

Subjects will not wear an oral appliance, and will be administered sham (room air) at 4 L/min via nasal cannula.

Interventions

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Oral appliance

An oral appliance (dental mouthpiece) will be used to improve upper airway patency. Patients who do not have their own custom dental oral appliance (various brands, commonly Herbst/Somnomed) will be provided with a device (BluePro, BlueSom) for the duration of the study.

Patients will also be administered sham (room air) at 4 L/min via nasal cannula.

Intervention Type DEVICE

Oxygen

Supplemental oxygen will be delivered at 4 L/min via nasal cannula to improve ventilatory control stability.

Intervention Type DRUG

Oral appliance plus oxygen

Both treatments will be administered simultaneously.

Intervention Type OTHER

No treatment

Subjects will not wear an oral appliance, and will be administered sham (room air) at 4 L/min via nasal cannula.

Intervention Type OTHER

Other Intervention Names

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Mandibular advancement device Supplemental inspired oxygen Combination therapy Sham

Eligibility Criteria

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Inclusion Criteria

* Diagnosed OSA or suspected OSA based on snoring

Exclusion Criteria

* Severe co-morbidities (cardiovascular, renal, lung disease, neurological), including:

Congestive heart failure, Neurological conditions that may affect sleep or breathing (e.g. neuromuscular diseases e.g. myasthenia gravis; neurodegenerative diseases e.g. Alzheimer's/Parkinson's)

* Medications that will substantially affect respiration, including opioids, barbiturates, theophylline, doxapram, acetazolamide, pseudoephedrine
* Claustrophobia
* Insomnia and other non-respiratory sleep disorders
* Inability to sleep supine
* Contraindications to oral appliances, including insufficient teeth to support the device, periodontal problems inducing tooth mobility, active temporomandibular joint disorder
* Allergy to lidocaine or oxymetazoline HCl
Minimum Eligible Age

21 Years

Maximum Eligible Age

79 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Monash University

OTHER

Sponsor Role collaborator

American Heart Association

OTHER

Sponsor Role collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

Heart Foundation of Australia

UNKNOWN

Sponsor Role collaborator

Brigham and Women's Hospital

OTHER

Sponsor Role lead

Responsible Party

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Scott Aaron Sands

Associate Physiologist / Instructor in Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Scott A Sands, PhD

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Bradley A Edwards, PhD

Role: PRINCIPAL_INVESTIGATOR

Monash University

Locations

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Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status

Sleep and Circadian Medicine Laboratory, BASE Facility, Monash University

Notting Hill, Victoria, Australia

Site Status

Countries

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United States Australia

References

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Hynes DJ, Mann DL, Landry SA, Joosten SA, Edwards BA, Hamilton GS. Night-to-night variability in obstructive sleep apnea severity, the physiological endotypes, and the frequency of flow limitation. Sleep. 2025 Apr 11;48(4):zsae295. doi: 10.1093/sleep/zsae295.

Reference Type DERIVED
PMID: 39688178 (View on PubMed)

Other Identifiers

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15SDG25890059

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

R01HL128658

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2017P001037

Identifier Type: -

Identifier Source: org_study_id

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