Mechanisms of Upper Airway Obstruction

Not Applicable

Completed

• Conditions: Obstructive Sleep Apnea
• Interventions: Device: Lingual Muscle Stimulation; Other: Mandibular advancement; Other: Postural maneuvers; Other: Digital Morphometrics; Other: Tongue Force Exercise; Other: Magnetic resonance imaging (MRI); Other: Polysomnography (PSG) - Split Night

• Registration Number: NCT04322097
• Lead Sponsor: University of Pennsylvania

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).

\*As of 6/11/2021, the target recruitment for Study A was completed\*

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 Timeline

• Study First Submitted: 2020-03-19
• Study First Submitted QC: 2020-03-23
• Study First Posted: 2020-03-26
• Study Start: 2020-06-03
• Primary Completion: 2024-05-10
• Study Completion: 2024-05-10
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-03
• Last Update Posted: 2025-01-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 133

Inclusion Criteria

• Adults (≥ 22yrs)
• 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

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Exclusion Criteria

• MRI contraindications (claustrophobia, ferromagnetic implants, foreign bodies, etc)
• Inspire Implant Model 3024
• Inspire Remote Model 3032
• Patients who have fallen asleep while driving 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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Lingual Muscle Stimulation Patients	Digital Morphometrics	DISE
Lingual Muscle Stimulation Patients	Polysomnography (PSG) - Split Night	DISE
Lingual Muscle Stimulation Patients	Lingual Muscle Stimulation	DISE
Lingual Muscle Stimulation Patients	Postural maneuvers	DISE
Lingual Muscle Stimulation Patients	Magnetic resonance imaging (MRI)	DISE
Lingual Muscle Stimulation Patients	Mandibular advancement	DISE
Lingual Muscle Stimulation Patients	Tongue Force Exercise	DISE

Primary Outcome Measures

Name	Time	Method
Amax	Within 3 months of enrollment	Measurement of maximal pharyngeal cross-sectional area (in cm-squared)
Pharyngeal compliance	Within 3 months of enrollment	area/pressure in cm2 per cmH2O
Upper airway critical pressure (Pcrit)	Within 3 months of enrollment	Measurement of airway collapsibility (cmH2O)
Segmental Airway Resistances	Within 3 months of enrollment	Measurement of pharyngeal resistances upstream and downstream to site of collapse (cmH2O/l/s)

Secondary Outcome Measures

Name	Time	Method
Digital Morphometrics	Within 3 months of enrollment	Measurements of facial and oral airway dimensions
Tongue Force	Within 3 months of enrollment	Measurements of maximal tongue force and fatigue

Trial Locations

Locations (1)

Hospital of the University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States