Combined Upper-airway and Breathing Control Therapies for Obstructive Sleep Apnea
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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 Design
Arms and Interventions
| 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:
Drug: Oxygen
Supplemental oxygen will be delivered at 4 L/min via nasal cannula to improve ventilatory control stability.
Other Names:
Other: Oral appliance plus oxygen
Both treatments will be administered simultaneously.
Other Names:
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:
|
Outcome Measures
Primary Outcome Measures
- Change in apnea hypopnea index (AHI), percent of baseline. [Single night]
Primary test is difference between combination therapy and oral appliance
Secondary Outcome Measures
- Change in frequency of arousals, percent of baseline. [Single night]
Primary test is difference between combination therapy and oral appliance
- Patient reported sleep quality (better/same/worse) [Single night]
Primary test is difference between combination therapy and oral appliance
- Morning minus evening systolic blood pressure [Single night]
Primary test is difference between combination therapy and oral appliance
- Morning minus evening diastolic blood pressure [Single night]
Primary test is difference between combination therapy and oral appliance
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Brigham and Women's Hospital | Boston | Massachusetts | United States | 02115 |
| 2 | Sleep and Circadian Medicine Laboratory, BASE Facility, Monash University | Notting Hill | Victoria | Australia | 3168 |
Sponsors and Collaborators
- Brigham and Women's Hospital
- Monash University
- American Heart Association
- National Heart, Lung, and Blood Institute (NHLBI)
- 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 Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2017P001037
- 15SDG25890059
- R01HL128658