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

Study Overview
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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.

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

Conditions
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Obstructive Sleep Apnea

Intervention / Treatment
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* Device: Oral appliance
* Drug: Oxygen
* Other: Oral appliance plus oxygen
* Other: No treatment


Participation Criteria
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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

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: All patients<br>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<br>* 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.<br>* Other names: Mandibular advancement device;Drug: Oxygen<br>* Supplemental oxygen will be delivered at 4 L/min via nasal cannula to improve ventilatory control stability.<br>* Other names: Supplemental inspired oxygen;Other: Oral appliance plus oxygen<br>* Both treatments will be administered simultaneously.<br>* Other names: Combination therapy;Other: No treatment<br>* Subjects will not wear an oral appliance, and will be administered sham (room air) at 4 L/min via nasal cannula.<br>* Other names: Sham;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Complex Sleep Apnea, Obstructive Sleep Apnea, Ventilatory Control Instability