Clinical trial NCT04322097: Mechanisms of Upper Airway Obstruction
Official title: Characterizing Mechanisms of Upper Airway Obstruction During Drug-Induced Sleep Endoscopy (DISE)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obstructive Sleep Apnea
Keywords: upper airway
pharynx
collapsibility
compliance
drug-induced sleep endoscopy
hypoglossal stimulation
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
First posted: 2020-03-26
Enrollment: 133
Sex: ALL
Minimum age (years): 22
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Upper airway critical pressure (Pcrit)
timeFrame: Within 3 months of enrollment
measure: Pharyngeal compliance
timeFrame: Within 3 months of enrollment
measure: Amax
timeFrame: Within 3 months of enrollment
measure: Segmental Airway Resistances
timeFrame: Within 3 months of enrollment
Secondary outcomes:
measure: Tongue Force
timeFrame: Within 3 months of enrollment
measure: Digital Morphometrics
timeFrame: Within 3 months of enrollment
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: Raj C Dedhia, MD
role: PRINCIPAL_INVESTIGATOR
References: