Mechanisms of Upper Airway Obstruction

Obstructive Sleep Apnea Clinical Trial

— DISE-CAD  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04322097
• Other study ID #: 833511
• Status: Recruiting
• Phase: N/A
• Start date: June 3, 2020
• Est. completion date: April 2025

Study information

• Verified date: November 2023
• Source: University of Pennsylvania
• Contact: Everett Seay
• Phone: 2156158777
• Email: everett.seay[@]pennmedicine.upenn.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: April 2025
• Est. primary completion date: April 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 22 Years and older

Eligibility

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

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

Related Conditions & MeSH terms

• Airway Obstruction
• Obstructive Sleep Apnea
• Sleep Apnea, Obstructive

Intervention

Device:
• Lingual Muscle Stimulation
Tongue protrudor muscles will be stimulated

Other:
• Mandibular advancement
Outcome variables will be assess with and without mandibular advancement
• Postural maneuvers
Outcome variables will be measured with and without postural maneuvers
• Digital Morphometrics
A digital camera with laser pointers will be used to capture a series of craniofacial photographs (frontal, profile and neck extended) and intra-oral photographs (junction of the hard and soft palate, airway, or base of tongue).
• Tongue Force Exercise
The patient will place a small bulb behind their lower incisors and will press using their tongue as hard as possible for two seconds. This exercise will be repeated four times, with 30 seconds of rest in between each attempt. The patient will then be instructed to press and hold their tongue against the bulb as hard as possible for 35 seconds. This exercise will be repeated three times, with 2 minutes of rest in between each attempt.
• Magnetic resonance imaging (MRI)
The patient will undergo an MRI scan of the head and neck.
• Polysomnography (PSG) - Split Night
The patient will undergo a polysomnography (PSG). The PSG study will include monitoring of EEG, submental EMG, EOG, SpO2, tidal airflow, thoraco-abdominal efforts, and body position. The patient will spend half of the night at baseline (i.e. no intervention), and the second half with lingual muscle stimulation activated.

Locations

Country	Name	City	State
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
University of Pennsylvania

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Upper airway critical pressure (Pcrit)	Measurement of airway collapsibility (cmH2O)	Within 3 months of enrollment
Primary	Pharyngeal compliance	area/pressure in cm2 per cmH2O	Within 3 months of enrollment
Primary	Amax	Measurement of maximal pharyngeal cross-sectional area (in cm-squared)	Within 3 months of enrollment
Primary	Segmental Airway Resistances	Measurement of pharyngeal resistances upstream and downstream to site of collapse (cmH2O/l/s)	Within 3 months of enrollment
Secondary	Tongue Force	Measurements of maximal tongue force and fatigue	Within 3 months of enrollment
Secondary	Digital Morphometrics	Measurements of facial and oral airway dimensions	Within 3 months of enrollment