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

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

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.

Study Overview

• Status: Completed
• Conditions: Sleep Apnea, Obstructive
• Intervention / Treatment: Device: Oral appliance; Device: BluePro oral appliance

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; No oral appliance (control) first, oral appliance (BluePro oral appliance or other device) second
Experimental: Oral appliance; oral appliance (BluePro oral appliance or other device) first, no oral appliance (control) second	Device: Oral appliance; Patients will bring their prescribed oral appliance.; Device: BluePro oral appliance; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Investigators: Principal Investigator: David A Wellman, PhD, Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 14, 2015
• Primary Completion (Actual): May 1, 2018
• Study Completion (Actual): November 1, 2018

Study Registration Dates

• First Submitted: June 30, 2015
• First Submitted That Met QC Criteria: July 2, 2015
• First Posted (Estimate): July 3, 2015

Study Record Updates

• Last Update Posted (Actual): March 9, 2022
• Last Update Submitted That Met QC Criteria: February 23, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• 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: 2012P000957

Drug and device information, study documents

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