Mechanisms of Upper Airway Obstruction (DISE-CAD)

Characterizing Mechanisms of Upper Airway Obstruction During Drug-Induced Sleep Endoscopy (DISE)

The current study is designed to examine underlying mechanisms of action of lingual muscles in the maintenance of airway patency during sleep. The investigators' major hypothesis is that specific tongue muscles are responsible for relieving upper airway obstruction during sleep.

Study Overview

• Status: Completed
• Conditions: Obstructive Sleep Apnea
• Intervention / Treatment: Device: Hypoglossal Nerve Stimulation

Detailed Description

Obstructive sleep apnea (OSA) is characterized by recurrent upper airway obstruction due to inadequate muscle tone during sleep leading to nocturnal hypercapnia, repeated oxyhemoglobin desaturations and arousals. Continuous positive airway pressure (CPAP) is the therapeutic mainstay for OSA, but adherence remains poor. The loss of motor input to the tongue during sleep has been implicated as a cause for upper airway collapse. Activation of tongue muscles with implanted hypoglossal nerve stimulators is an effective therapy for some OSA patients. Nevertheless, approximately 1/3 of OSA patients did not respond to hypoglossal nerve stimulation despite rigorous selection criteria, leaving large segments of CPAP intolerant patients at risk for OSA-related morbidity. Thus, there is a critical knowledge gap in the role of lingual muscle activity in the maintenance of airway patency.

The current study is designed to examine underlying mechanisms of action of lingual muscles in the maintenance of airway patency during sleep. The investigators' major hypothesis is that specific tongue muscles are responsible for relieving upper airway obstruction during sleep. To address this hypothesis, the investigators will (1) selectively stimulate specific lingual muscle groups (viz., protrudors and retractors) and measure effects on airway patency during Drug Induced Sleep Endoscopy (DISE). The investigators will (2) correlate responses in patency to alterations in tongue morphology (as assessed with ultrasound imaging). The investigators will (3) examine the impact of anatomic factors (e.g., the size of the maxillo-mandibular enclosure) on airway responses to stimulation. Patients will (4) undergo magnetic resonance imaging (MRI) determine the extent to which maxillo-mandibular size and tongue size and fat content compress pharyngeal structures. The investigators will (5) assess apnea severity and hypoglossal nerve stimulation with Inspire to measure response to therapy via split-night PSGs. The investigators will (6) examine digital morphometrics to quantify pharyngeal anatomy. A final goal is to (7) measure tongue force, as tongue force measurements may elucidate mechanisms of therapy response as related to neuromuscular control.

The study will contain two distinct pathways, Study A and Study B, in order to efficiently execute the protocol. Study A will focus primarily on measurements obtained as part of routine clinical care. Study B will focus on enhanced imaging and physiology techniques in patients using lingual muscle stimulation (Inspire).

Study A:

• To determine the contribution of defects in upper airway function to the pathogenesis of airway obstruction at specific sites of pharyngeal collapse by characterizing upper airway pressure-flow/area relationships during DISE.
• To determine the impact of jaw thrust and mouth closure maneuvers to functional determinants of upper airway obstruction at specific sites of pharyngeal collapse.
• To examine effects of maxillo-mandibular restriction and tongue size on upper airway functional properties during DISE.

Study B (In addition to the objectives for Study A):

• To assess effects of stimulating specific lingual muscles on upper airway patency during natural sleep and drug-induced sleep
• To assess whether craniofacial morphology predicts improvements in pharyngeal patency during sleep with stimulation.

• Study Type: Interventional
• Enrollment (Actual): 133
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Pennsylvania Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 22 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Study A Inclusion Criteria:

• Scheduled to undergo DISE as part of routine clinical standard of care.

Study B Inclusion Criteria:

• Adults (≥ 22yrs) willing and capable of providing informed consent
• Implanted with the MRI-conditional Inspire hypoglossal nerve stimulator (Model 3028 or later)
• Compliant with Inspire therapy (> 20 hours/week over 2+ weeks) as a standalone treatment for sleep-disordered breathing
• Inspire remote model 2500 or later.

Study B Exclusion Criteria:

• MRI contraindications (claustrophobia, ferromagnetic implants/foreign bodies, etc.)
• Inspire Implant Model 3024
• Inspire Remote Model 3032
• Patients who have fallen asleep while during resulting in an accident or "near miss" accident within 1 year prior to device implantation.
• Inability to sleep in the supine position (by self-report)
• History of severe difficulty initiating or maintaining sleep in the laboratory
• Pregnant women

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Study A - Functional Phenotyping during DISE; Participants with diagnosed OSA undergo Drug-Induced Sleep Endoscopy (DISE) to characterize determinants of upper airway obstruction using CPAP and pharyngeal manometry. Jaw thrust and other positional maneuvers are performed during DISE as part of routine clinical standard of care.
Experimental: Study B - HGNS Responders; Participants with implanted Inspire HGNS devices undergo DISE and overnight polysomnography to assess upper airway responses with and without HGNS stimulation. CPAP titration is performed during DISE. Upper airway MRI and tongue force assessments are also conducted. Response was defined by a ≥ 50% reduction in AHI with stimulation.	Device: Hypoglossal Nerve Stimulation; On/off responses will be assessed both during Drug-Induced Sleep Endoscopy (DISE) and Polysomnography (PSG).
Experimental: Study B - HGNS Nonresponders; Participants with implanted Inspire HGNS devices undergo DISE and overnight polysomnography to assess upper airway responses with and without HGNS stimulation. CPAP titration is performed during DISE. Upper airway MRI and tongue force assessments are also conducted. Nonresponse was defined by a < 50% reduction in AHI with stimulation.	Device: Hypoglossal Nerve Stimulation; On/off responses will be assessed both during Drug-Induced Sleep Endoscopy (DISE) and Polysomnography (PSG).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharyngeal Critical Pressure (Pcrit)	Upper airway collapsibility (Pcrit, cmH₂O): Pressure at which the upper airway closes during inspiration, with a higher value indicating greater collapsibility. Pcrit less than zero indicates that the airway remains open. Pcrit greater than or equal to zero indicates that the airway is closed.	Collected during drug-induced sleep endoscopy (<1 day).
Pharyngeal Opening Pressure (PhOP)	Measurement of upper airway collapsibility (cmH2O)	Collected during drug-induced sleep endoscopy (<1 day).
Pharyngeal Compliance	Pressure-area relationships	Unable to be determined

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tongue Force	Measurements of maximal tongue force and fatigue	Within 3 months of enrollment
Digital Morphometrics	Measurements of facial and oral airway dimensions	Within 3 months of enrollment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tongue Force - Maximum	Tongue force was measured using the Iowa Oral Performance Instrument (IOPI) by recording the maximum pressure generated during a 2-second sustained tongue press against a bulb. Three trials were conducted and the average value was reported for all successful trials.	Assessed at a single visit
Tongue Force - Fatigue	Tongue fatigue was assessed by having participants apply maximum force to a pressure transducer and attempting to maintain this for 35 seconds. Data for each participant were reported as the time it takes for force to reduce by 67% of the maximum tongue force during each individual trial. Fatigue was reported as an average across up to 3 technically valid trials. Fatigue was determined by fitting a single term exponential curve to the pressure data starting at the maximal pressure (start period) and the pressure at the end of the trial.	Assessed at a single visit

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Investigators: Principal Investigator: Raj C Dedhia, MD, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): June 3, 2020
• Primary Completion (Actual): May 10, 2024
• Study Completion (Actual): May 10, 2024

Study Registration Dates

• First Submitted: March 19, 2020
• First Submitted That Met QC Criteria: March 23, 2020
• First Posted (Actual): March 26, 2020

Study Record Updates

• Last Update Posted (Actual): January 21, 2026
• Last Update Submitted That Met QC Criteria: January 16, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: compliance; drug-induced sleep endoscopy; pharynx; upper airway; collapsibility; hypoglossal stimulation
• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Wake Disorders; Apnea; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Apnea Syndromes; Behavior; Treatment Adherence and Compliance; Health Behavior; Patient Acceptance of Health Care; Sleep Apnea, Obstructive; Patient Compliance
• Other Study ID Numbers: 833511

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Information from the lingual muscle stimulation arm was shared with the National Sleep Research Resource.
• IPD Sharing Time Frame: As of July, 2025, all data has been transmitted to NSRR.
• IPD Sharing Access Criteria: See criteria at the URL below.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes