Mechanisms of Upper Airway Obstruction

NCT ID: NCT04322097

Last Updated: 2026-01-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 133 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-03
• Study Completion Date: 2024-05-10

Brief Summary

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.

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.

Conditions

Obstructive Sleep Apnea

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

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.

Group Type: EXPERIMENTAL

Hypoglossal Nerve Stimulation

Intervention Type: DEVICE

On/off responses will be assessed both during Drug-Induced Sleep Endoscopy (DISE) and Polysomnography (PSG).

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.

Group Type: EXPERIMENTAL

Hypoglossal Nerve Stimulation

Intervention Type: DEVICE

On/off responses will be assessed both during Drug-Induced Sleep Endoscopy (DISE) and Polysomnography (PSG).

Interventions

Hypoglossal Nerve Stimulation

On/off responses will be assessed both during Drug-Induced Sleep Endoscopy (DISE) and Polysomnography (PSG).

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

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

• 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.

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

• Minimum Eligible Age: 22 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Raj Dedhia, MD

Associate Professor, Director, Division of Sleep Surgery

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Raj C Dedhia, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Locations

Pennsylvania Hospital

Philadelphia, Pennsylvania, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

833511

Identifier Type: -

Identifier Source: org_study_id