DISE-CAD: Mechanisms of Upper Airway Obstruction

Sponsor

University of Pennsylvania (Other)

Overall Status

Recruiting

CT.gov ID

NCT04322097

Collaborator

(none)

100

Enrollment

Location

Arm

57.9

Anticipated Duration (Months)

1.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Condition or Disease	Intervention/Treatment	Phase
Obstructive Sleep Apnea	Device: Lingual Muscle Stimulation Diagnostic Test: Mandibular advancement Device: Postural maneuvers	N/A

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 also (2) correlate responses in patency to alterations in tongue morphology (as assessed with ultrasound imaging). A final goal is to (3) examine the impact of anatomic factors (e.g., the size of the maxillo-mandibular enclosure) on airway responses to stimulation.

Objectives (all primary and secondary objectives)

To assess effects of stimulating specific lingual muscles on upper airway patency during DISE and on tongue morphology.

The investigators hypothesize that stimulation will lead to improvements in upper airway patency during DISE when tongue protrudors are stimulated, and that concomitant stimulation of retractors will augment this response.

To correlate improvements in upper airway patency during sleep with stimulation to alterations in tongue shape and position when stimulating during DISE.

The investigators hypothesize that the restoration of airway patency during sleep will be associated with anterior tongue movement and preservation of tongue shape when stimulated during DISE.

To assess whether craniofacial morphology predicts improvements in pharyngeal patency during DISE with stimulation.

The investigators hypothesize that maxillo-mandibular restriction will be associated with diminished responses in airway patency to stimulation during DISE.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

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

Actual Study Start Date :

Jun 3, 2020

Anticipated Primary Completion Date :

Apr 1, 2025

Anticipated Study Completion Date :

Apr 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Other: DISE patients DISE	Device: Lingual Muscle Stimulation Tongue protrudor and retractor muscles will be stimulated separately and in combination Diagnostic Test: Mandibular advancement Outcome variables will be assess with and without mandibular advancement Device: Postural maneuvers Outcome variables will be measured with and without postural maneuvers

Arm

Intervention/Treatment

Other: DISE patients

DISE

Device: Lingual Muscle Stimulation

Tongue protrudor and retractor muscles will be stimulated separately and in combination

Diagnostic Test: Mandibular advancement

Outcome variables will be assess with and without mandibular advancement

Device: Postural maneuvers

Outcome variables will be measured with and without postural maneuvers

Outcome Measures

Primary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

22 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Adults (≥ 22yrs)
Moderate to severe obstructive sleep apnea (AHI ≥ 20)
No underlying cardiac disease

Exclusion Criteria:

Significant cardiac disease, unstable or recent cardiac events
Active pulmonary, liver, or renal disease
Uncontrolled hypertension (BP>160/100)
Neuromuscular disease
Major psychiatric disease
Lifestyle considerations by the use of excessive alcohol, tobacco, or drugs and involvement in shift work occupations that preclude study in the laboratory
Pregnancy
Anticoagulation therapy (e.g. Coumadin, Dabigatran)
MRI contraindications (claustrophobia, ferromagnetic implants/foreign bodies, etc.)