Characterizing Upper Airway Collapse to Guide Patient Selection for Oral Appliance Therapy for Obstructive Sleep Apnea

Study Overview
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Brief Summary
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Obstructive Sleep Apnea (OSA) is characterized by collapse of one or more pharyngeal structures during sleep (velum, tongue base, lateral walls, epiglottis). Structure-specific therapies for OSA have emerged as alternatives to positive airway pressure (PAP). Oral appliance (OA) therapy is increasingly being indicated for OSA treatment, although a complete response occurs in approximately 50% of patients. In general, OA devices are designed to maintain the mandible and/or tongue in a protruded posture during sleep, preventing upper airway obstruction. Limited studies in awake or sedated patients have demonstrated the effects of mandibular advancement on aspects of pharyngeal structure and function. The objective of the proposed research is to fully characterize upper airway collapse in OSA patients during natural sleep and use this information to understand why some patients appear to exhibit a large improvement in pharyngeal collapsibility whereas others do not.

Detailed Description
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OSA patients will undergo a baseline sleep endoscopy study to identify the site of pharyngeal collapse. Subsequently, they will undergo two clinical polysomnographies (PSGs) to measure the effect of an oral appliance (a site specific therapy) on upper airway collapsibility and sleep apnea severity. During the first hour of each clinical PSG, the passive pharyngeal collapsibility will be determined using the standard 5-breath continuous positive airway pressure (CPAP) drop method. During the remainder of the night, patients will be monitored to determine sleep apnea severity (apnea-hypopnea index). These measurements will allow the investigators to determine which pharyngeal collapsing site responds best (both in terms of collapsibility and AHI) to mandibular advancement with an oral appliance. Patients who have their own oral appliance will be recruited. In addition, patients without an oral appliance will be provided with a temporary oral appliance for the study.

Official Title
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Characterizing Site and Severity of Upper Airway Collapse to Guide Patient Selection for Oral Appliance Therapy for Obstructive Sleep Apnea

Conditions
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Sleep Apnea, Obstructive

Intervention / Treatment
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* Device: Oral appliance
* Device: BluePro oral appliance


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with Obstructive Sleep Apnea Exclusion Criteria: Any unstable cardiac condition (other than well controlled hypertension) or pulmonary problems. Any medication known to influence breathing, sleep/arousal or muscle physiology Concurrent sleep disorders (insomnia, narcolepsy, central sleep apnea or parasomnia) Claustrophobia Inability to sleep supine Periodontal disease and/or insufficient number of teeth Allergy to lidocaine or oxymetazoline hydrochloride For women: Pregnancy

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 70 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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control<br>No oral appliance (control) first, oral appliance (BluePro oral appliance or other device) second | |
| Experimental: Oral appliance<br>oral appliance (BluePro oral appliance or other device) first, no oral appliance (control) second | Device: Oral appliance<br>* Patients will bring their prescribed oral appliance.<br>Device: BluePro oral appliance<br>* Patients without a prescribed oral appliance will have a device provided for the duration of the study (BluePro, BlueSom; used for investigational purposes only). The device provided is a prefabricated thermoplastic customizable mandibular advancement splint.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in passive pharyngeal collapsibility (OA therapy minus control) | The passive pressure-flow relationship is characterized by the critical closing pressure (Pcrit) , and the ventilatory flow at atmospheric pressure ( V passive). Pcrit and V passive will be determined using the standard 5-breath CPAP drop method. The change in collapsibility will be compared across subgroups defined by the site of collapse measured using sleep-endoscopy. Patients will sleep supine for this measurement. | 3 nights | 
| Change in sleep apnea severity (AHI) | The change in apnea-hypopnea index (AHI, 3% desaturation or arousal criteria; OA therapy minus control) will be compared across subgroups defined by the site of collapse measured using sleep-endoscopy. Baseline collapsibility will be incorporated as a predictor of the change in AHI. | 2 nights | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in peak flow during sleep (OA therapy minus control) | During the portion of the night dedicated to measuring sleep apnea severity, peak flow will also be measured during sleep to quantify activated upper airway collapsibility. | 2 nights | 
| Objective sleep quality (OA therapy minus control) | Arousal index, one of the standard measures of sleep quality, will be assessed. | 2 nights | 
| Objective sleep quality (OA therapy minus control) | Proportion of sleep in Non rapid eyes movement ( NREM) stage 1,one of the standard measures of sleep quality, will be assessed. | 2 nights | 
| Subjective sleep quality (OA therapy minus control) | Patients will rate whether they slept better/worse/same with the OA vs control. | 2 nights |