An interventional study of Hypoglossal Nerve Stimulation in Obstructive Sleep Apnea, sponsored by University of Pennsylvania. Completed at 1 site in United States. Open to participants aged 22 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-01-21.
Sponsored by University of Pennsylvania · Not applicable, Interventional, and Basic science
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.
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:
Study B (In addition to the objectives for Study A):
2,198 studies on the registry are indexed under Sleep Apnea, Obstructive; 469 are open to participants now.
This study's enrollment of 133 is above the median of 53 across 1,448 interventional studies indexed under Sleep Apnea, Obstructive.
Browse Sleep Apnea, Obstructive studies →University of Pennsylvania is the lead sponsor of 1,635 studies on the registry; 239 are open to participants now.
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Study A Inclusion Criteria:
Study B Inclusion Criteria:
Study B Exclusion Criteria:
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.
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.
Device: Hypoglossal Nerve Stimulation
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.
Device: Hypoglossal Nerve Stimulation
On/off responses will be assessed both during Drug-Induced Sleep Endoscopy (DISE) and Polysomnography (PSG).
Pharyngeal Critical Pressure (Pcrit)
Upper airway collapsibility (Pcrit, cmH₂O): Pressure at which the upper airway closes during inspiration, with a higher value indicating greater collapsibility. Pcrit less than zero indicates that the airway remains open. Pcrit greater than or equal to zero indicates that the airway is closed.
Time frame: Collected during drug-induced sleep endoscopy (<1 day).
Pharyngeal Opening Pressure (PhOP)
Measurement of upper airway collapsibility (cmH2O)
Time frame: Collected during drug-induced sleep endoscopy (<1 day).
Pharyngeal Compliance
Pressure-area relationships
Time frame: Unable to be determined
Tongue Force - Maximum
Tongue force was measured using the Iowa Oral Performance Instrument (IOPI) by recording the maximum pressure generated during a 2-second sustained tongue press against a bulb. Three trials were conducted and the average value was reported for all successful trials.
Time frame: Assessed at a single visit
Tongue Force - Fatigue
Tongue fatigue was assessed by having participants apply maximum force to a pressure transducer and attempting to maintain this for 35 seconds. Data for each participant were reported as the time it takes for force to reduce by 67% of the maximum tongue force during each individual trial. Fatigue was reported as an average across up to 3 technically valid trials. Fatigue was determined by fitting a single term exponential curve to the pressure data starting at the maximal pressure (start period) and the pressure at the end of the trial.
Time frame: Assessed at a single visit
| Milestone | Study A - Functional Phenotyping During DISE | Study B - Hypoglossal Nerve Stimulation (HGNS) Patients |
|---|---|---|
| Started | 100 | 33 |
| Completed | 100 | 32 |
| Not completed | 0 | 1 |
Upper airway collapsibility (Pcrit, cmH₂O): Pressure at which the upper airway closes during inspiration, with a higher value indicating greater collapsibility. Pcrit less than zero indicates that the airway remains open. Pcrit greater than or equal to zero indicates that the airway is closed.
| cm H2O | Study A - Functional Phenotyping During DISE | Study B - HGNS Responders | Study B - HGNS Nonresponders |
|---|---|---|---|
| Pharyngeal Critical Pressure (Pcrit) | 1.26 ± 3.29 | -1.42 ± 4.36 | -1.06 ± 2.62 |
Measurement of upper airway collapsibility (cmH2O)
| cm H2O | Study A - Functional Phenotyping During DISE | Study B - HGNS Responders | Study B - HGNS Nonresponders |
|---|---|---|---|
| Pharyngeal Opening Pressure (PhOP) | 7.99 ± 3.45 | 7.33 ± 3.60 | 7.44 ± 4.08 |
Pressure-area relationships
No measurements were reported for this outcome.
Tongue force was measured using the Iowa Oral Performance Instrument (IOPI) by recording the maximum pressure generated during a 2-second sustained tongue press against a bulb. Three trials were conducted and the average value was reported for all successful trials.
| kPa | Study A - Functional Phenotyping During DISE | Study B - HGNS Responders | Study B - HGNS Nonresponders |
|---|---|---|---|
| Tongue Force - Maximum | — | 38.0 ± 18.8 | 47.4 ± 10.9 |
Tongue fatigue was assessed by having participants apply maximum force to a pressure transducer and attempting to maintain this for 35 seconds. Data for each participant were reported as the time it takes for force to reduce by 67% of the maximum tongue force during each individual trial. Fatigue was reported as an average across up to 3 technically valid trials. Fatigue was determined by fitting a single term exponential curve to the pressure data starting at the maximal pressure (start period) and the pressure at the end of the trial.
| seconds | Study A - Functional Phenotyping During DISE | Study B - HGNS Responders | Study B - HGNS Nonresponders |
|---|---|---|---|
| Tongue Force - Fatigue | — | 11.1 ± 9.5 | 17.1 ± 12.7 |
Soft palate volume measured via MRI.
| mm^3 | Study A - Functional Phenotyping During DISE | Study B - HGNS Responders | Study B - HGNS Nonresponders |
|---|---|---|---|
| Soft Palate Volume | — | 9011.37 ± 1904.12 | 11094.10 ± 2721.72 |
Tongue volume measured via MRI
| mm^3 | Study A - Functional Phenotyping During DISE | Study B - HGNS Responders | Study B - HGNS Nonresponders |
|---|---|---|---|
| Tongue Volume | — | 85131.9 ± 16334.92 | 85322.08 ± 12149.09 |
Collected over Data were collected over the course of active participation in the trial which lasted on average 7-14 days.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Study A - Functional Phenotyping During DISE | 0/100 (0%) | 0/100 (0%) | 0/100 (0%) |
| Study B - Hypoglossal Nerve Stimulation (HGNS) Patients | 0/32 (0%) | 0/32 (0%) | 0/32 (0%) |
| Age, Continuous(years) | Study A - Functional Phenotyping During DISE | Study B - HGNS Responders | Study B - HGNS Nonresponders | Total |
|---|---|---|---|---|
| Mean | 54.9 ± 14.3 | 62.4 ± 10.5 | 66.2 ± 7.2 | 57.2 ± 13.8 |
| Sex: Female, Male(Participants) | Study A - Functional Phenotyping During DISE | Study B - HGNS Responders | Study B - HGNS Nonresponders | Total |
|---|---|---|---|---|
| Female | 23 | 10 | 9 | 42 |
| Male | 77 | 3 | 10 | 90 |
| Ethnicity (NIH/OMB)(Participants) | Study A - Functional Phenotyping During DISE | Study B - HGNS Responders | Study B - HGNS Nonresponders | Total |
|---|---|---|---|---|
| Hispanic or Latino | 1 | 0 | 1 | 2 |
| Not Hispanic or Latino | 94 | 13 | 18 | 125 |
| Unknown or Not Reported | 5 | 0 | 0 | 5 |
| Apnea-Hypopnea Index (AHI)(events/hr) | Study A - Functional Phenotyping During DISE | Study B - HGNS Responders | Study B - HGNS Nonresponders | Total |
|---|---|---|---|---|
| Mean | 31.2 ± 21.1 | 37.5 ± 30.0 | 40.1 ± 19.5 | 33.2 ± 22.0 |
| BMI(kg/m^2) | Study A - Functional Phenotyping During DISE | Study B - HGNS Responders | Study B - HGNS Nonresponders | Total |
|---|---|---|---|---|
| Mean | 29.6 ± 4.8 | 26.6 ± 3.0 | 29.3 ± 3.7 | 29.3 ± 4.6 |
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Plan to share: Yes — Information from the lingual muscle stimulation arm was shared with the National Sleep Research Resource.
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