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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Obstructive Sleep Apnea
• Intervention / Treatment: Device: Oral appliance; Drug: Oxygen; Other: Oral appliance plus oxygen; Other: No treatment

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Scott A Sands, PhD; Phone Number: 6172780911; Email: sasands@bwh.harvard.edu
• Study Contact Backup: Name: Lauren Hess; Phone Number: 6177328976; Email: lhess1@bwh.harvard.edu

Study Locations

• Australia
  • Victoria
    • Notting Hill, Victoria, Australia, 3168
      • Sleep and Circadian Medicine Laboratory, BASE Facility, Monash University
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: All patients; Patients will receive all four interventions in randomized order. Note: Data will not be analyzed separately for the 16 cross-over combinations of intervention order: Interventions: Oral appliance | Oral appliance plus oxygen | Oxygen | No treatment

Device: 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.; Other Names: Mandibular advancement device; Drug: Oxygen; Supplemental oxygen will be delivered at 4 L/min via nasal cannula to improve ventilatory control stability.; Other Names: Supplemental inspired oxygen; Other: Oral appliance plus oxygen; Both treatments will be administered simultaneously.; Other Names: Combination therapy; Other: No treatment; Subjects will not wear an oral appliance, and will be administered sham (room air) at 4 L/min via nasal cannula.; Other Names: Sham

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in apnea hypopnea index (AHI), percent of baseline.	Primary test is difference between combination therapy and oral appliance	Single night

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in frequency of arousals, percent of baseline.	Primary test is difference between combination therapy and oral appliance	Single night
Patient reported sleep quality (better/same/worse)	Primary test is difference between combination therapy and oral appliance	Single night
Morning minus evening systolic blood pressure	Primary test is difference between combination therapy and oral appliance	Single night
Morning minus evening diastolic blood pressure	Primary test is difference between combination therapy and oral appliance	Single night

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Monash University; American Heart Association; Heart Foundation of Australia
• Investigators: Principal Investigator: Scott A Sands, PhD, Brigham and Women's Hospital; Principal Investigator: Bradley A Edwards, PhD, Monash University

Study record dates

Study Major Dates

• Study Start (Actual): September 6, 2017
• Primary Completion (Estimated): December 1, 2023
• Study Completion (Estimated): December 1, 2023

Study Registration Dates

• First Submitted: June 14, 2017
• First Submitted That Met QC Criteria: June 14, 2017
• First Posted (Actual): June 16, 2017

Study Record Updates

• Last Update Posted (Actual): July 13, 2023
• Last Update Submitted That Met QC Criteria: July 12, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Obstructive Sleep Apnea; Ventilatory Control Instability; Complex Sleep Apnea
• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Signs and Symptoms, Respiratory; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Apnea
• Other Study ID Numbers: 2017P001037; 15SDG25890059 (Other Grant/Funding Number: American Heart Association); R01HL128658 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Fully-deidentified subject data will be shared via an online repository.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No