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

NCT03189173 | Completed Phase 2 FDA Drug FDA Device

• 3 other identifiers: 2017P00103715SDG25890059R01HL128658
• Study Type: interventional
• Target: 41
• Locations: 2 countries
• Sites: 2

Brief Summary

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.

Conditions

Obstructive Sleep Apnea

Keywords

Obstructive Sleep Apnea; Ventilatory Control Instability; Complex Sleep Apnea

Outcome Measures

Primary Outcomes (1)

• Change in apnea hypopnea index (AHI), percent of baseline.

  Primary test is difference between combination therapy and oral appliance

  Single night

Secondary Outcomes (4)

• Change in frequency of arousals, percent of baseline.

  Single night

• Patient reported sleep quality (visual analog scale)

  Single night

• Morning minus evening systolic blood pressure

  Single night

• Morning minus evening diastolic blood pressure

  Single night

Study Arms (20)

Combo, Mad, Sham, Oxygen

EXPERIMENTAL

Order of interventions: Combo, Mad, Sham, Oxygen

Device: Oral appliance; Drug: Oxygen; Other: Oral appliance plus oxygen; Other: No treatment

Combo, Oxygen, Mad, Sham

EXPERIMENTAL

Order of interventions: Combo, Oxygen, Mad, Sham

Device: Oral appliance; Drug: Oxygen; Other: Oral appliance plus oxygen; Other: No treatment

Combo, Oxygen, Sham, MAD

EXPERIMENTAL

Order of interventions: Combo, Oxygen, Sham, MAD

Device: Oral appliance; Drug: Oxygen; Other: Oral appliance plus oxygen; Other: No treatment

Combo, Sham, Mad, Oxygen

EXPERIMENTAL

Order of interventions: Combo, Sham, Mad, Oxygen

Device: Oral appliance; Drug: Oxygen; Other: Oral appliance plus oxygen; Other: No treatment

Combo, Sham, Oxygen, MAD

EXPERIMENTAL

Order of interventions: Combo, Sham, Oxygen, MAD

Device: Oral appliance; Drug: Oxygen; Other: Oral appliance plus oxygen; Other: No treatment

MAD, Combo, Oxygen, Sham

EXPERIMENTAL

Order of interventions: MAD, Combo, Oxygen, Sham

Device: Oral appliance; Drug: Oxygen; Other: Oral appliance plus oxygen; Other: No treatment

MAD, Combo, Sham, Oxygen

EXPERIMENTAL

Order of interventions: MAD, Combo, Sham, Oxygen

Device: Oral appliance; Drug: Oxygen; Other: Oral appliance plus oxygen; Other: No treatment

MAD, Oxygen, Combo, Sham

EXPERIMENTAL

Order of interventions: MAD, Oxygen, Combo, Sham

Device: Oral appliance; Drug: Oxygen; Other: Oral appliance plus oxygen; Other: No treatment

MAD, Oxygen, Sham, Combo

EXPERIMENTAL

Order of interventions: MAD, Oxygen, Sham, Combo

Device: Oral appliance; Drug: Oxygen; Other: Oral appliance plus oxygen; Other: No treatment

MAD, Sham, Combo, Oxygen

EXPERIMENTAL

Order of interventions: MAD, Sham, Combo, Oxygen

Device: Oral appliance; Drug: Oxygen; Other: Oral appliance plus oxygen; Other: No treatment

MAD, Sham, Oxygen, Combo

EXPERIMENTAL

Order of interventions: MAD, Sham, Oxygen, Combo

Device: Oral appliance; Drug: Oxygen; Other: Oral appliance plus oxygen; Other: No treatment

Oxygen, Combo, Sham, MAD

EXPERIMENTAL

Order of interventions: Oxygen, Combo, Sham, MAD

Device: Oral appliance; Drug: Oxygen; Other: Oral appliance plus oxygen; Other: No treatment

Oxygen, MAD, Sham, Combo

EXPERIMENTAL

Order of interventions: Oxygen, MAD, Sham, Combo

Device: Oral appliance; Drug: Oxygen; Other: Oral appliance plus oxygen; Other: No treatment

Oxygen, Sham, Combo, MAD

EXPERIMENTAL

Order of interventions: Oxygen, Sham, Combo, MAD

Device: Oral appliance; Drug: Oxygen; Other: Oral appliance plus oxygen; Other: No treatment

Oxygen, Sham, MAD, Combo

EXPERIMENTAL

Order of interventions: Oxygen, Sham, MAD, Combo

Device: Oral appliance; Drug: Oxygen; Other: Oral appliance plus oxygen; Other: No treatment

Sham, Combo, MAD, Oxygen

EXPERIMENTAL

Order of interventions: Sham, Combo, MAD, Oxygen

Device: Oral appliance; Drug: Oxygen; Other: Oral appliance plus oxygen; Other: No treatment

Sham, MAD, Combo, Oxygen

EXPERIMENTAL

Order of interventions: Sham, MAD, Combo, Oxygen

Device: Oral appliance; Drug: Oxygen; Other: Oral appliance plus oxygen; Other: No treatment

Sham, MAD, Oxygen, Combo

EXPERIMENTAL

Order of interventions: Sham, MAD, Oxygen, Combo

Device: Oral appliance; Drug: Oxygen; Other: Oral appliance plus oxygen; Other: No treatment

Sham, Oxygen, Combo, MAD

EXPERIMENTAL

Order of interventions: Sham, Oxygen, Combo, MAD

Device: Oral appliance; Drug: Oxygen; Other: Oral appliance plus oxygen; Other: No treatment

Sham, Oxygen, MAD, Combo

EXPERIMENTAL

Order of interventions: Sham, Oxygen, MAD, Combo

Device: Oral appliance; Drug: Oxygen; Other: Oral appliance plus oxygen; Other: No treatment

Interventions

Oral appliance 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.

Also known as: Mandibular advancement device

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Oxygen DRUG

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

Also known as: Supplemental inspired oxygen

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Oral appliance plus oxygen OTHER

Both treatments will be administered simultaneously.

Also known as: Combination therapy

Combo, Mad, Sham, Oxygen; Combo, Oxygen, Mad, Sham; Combo, Oxygen, Sham, MAD; Combo, Sham, Mad, Oxygen; Combo, Sham, Oxygen, MAD; MAD, Combo, Oxygen, Sham; MAD, Combo, Sham, Oxygen; MAD, Oxygen, Combo, Sham; MAD, Oxygen, Sham, Combo; MAD, Sham, Combo, Oxygen; MAD, Sham, Oxygen, Combo; Oxygen, Combo, Sham, MAD; Oxygen, MAD, Sham, Combo; Oxygen, Sham, Combo, MAD; Oxygen, Sham, MAD, Combo; Sham, Combo, MAD, Oxygen; Sham, MAD, Combo, Oxygen; Sham, MAD, Oxygen, Combo; Sham, Oxygen, Combo, MAD; Sham, Oxygen, MAD, Combo

No treatment OTHER

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

Also known as: Sham

Combo, Mad, Sham, Oxygen; Combo, Oxygen, Mad, Sham; Combo, Oxygen, Sham, MAD; Combo, Sham, Mad, Oxygen; Combo, Sham, Oxygen, MAD; MAD, Combo, Oxygen, Sham; MAD, Combo, Sham, Oxygen; MAD, Oxygen, Combo, Sham; MAD, Oxygen, Sham, Combo; MAD, Sham, Combo, Oxygen; MAD, Sham, Oxygen, Combo; Oxygen, Combo, Sham, MAD; Oxygen, MAD, Sham, Combo; Oxygen, Sham, Combo, MAD; Oxygen, Sham, MAD, Combo; Sham, Combo, MAD, Oxygen; Sham, MAD, Combo, Oxygen; Sham, MAD, Oxygen, Combo; Sham, Oxygen, Combo, MAD; Sham, Oxygen, MAD, Combo

Eligibility Criteria

• Age: 21 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosed OSA or suspected OSA based on snoring

You may not qualify if:

• 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

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• Monash University: collaborator
• American Heart Association: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Heart Foundation of Australia: collaborator

Study Sites (2)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Sleep and Circadian Medicine Laboratory, BASE Facility, Monash University

Notting Hill, Victoria, 3168, Australia

Location

Related Publications (1)

• 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.

  PMID: 39688178 DERIVED

MeSH Terms

Conditions

Sleep Apnea, Obstructive; Sleep Apnea Syndromes

Interventions

Occlusal Splints; Oxygen; Combined Modality Therapy; salicylhydroxamic acid

Condition Hierarchy (Ancestors)

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; Chalcogens; Elements; Inorganic Chemicals; Gases; Therapeutics

Study Officials

• Scott A Sands, PhD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

• Bradley A Edwards, PhD

  Monash University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Supplemental oxygen versus air assignment nights will be blinded to participants, but will be known by the investigator. Oral appliances will be "open label".
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Physiologist / Instructor in Medicine

Model Details: 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.

Study Record Dates

• First Submitted: June 14, 2017
• First Posted: June 16, 2017
• Study Start: September 6, 2017
• Primary Completion: May 1, 2023
• Study Completion: May 1, 2023
• Last Updated: May 4, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Time Frame: 6 months after publication

Locations

US (1); AU (1)