Trial Outcomes & Findings for Mechanisms of Upper Airway Obstruction (NCT NCT04322097)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

133 participants

Primary outcome timeframe

Collected during drug-induced sleep endoscopy (<1 day).

Results posted on

2026-01-21

Participant Flow

Participant milestones

Participant milestones
Measure	Study A - Functional Phenotyping During DISE 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.	Study B - Hypoglossal Nerve Stimulation (HGNS) Patients 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 imaging and tongue force assessments are also conducted.
Overall Study STARTED	100	33
Overall Study COMPLETED	100	32
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Three participants in study A did not have baseline sleep studies available for review.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Study A - Functional Phenotyping During DISE n=100 Participants 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.	Study B - HGNS Responders n=13 Participants Therapy response is defined as a ≥ 50% reduction in baseline AHI with HGNS, measured during overnight polysomnography.	Study B - HGNS Nonresponders n=19 Participants Therapy response is defined as a \< 50% reduction in baseline AHI with HGNS, measured during overnight polysomnography.	Total n=132 Participants Total of all reporting groups
Age, Continuous	54.9 years STANDARD_DEVIATION 14.3 • n=100 Participants	62.4 years STANDARD_DEVIATION 10.5 • n=13 Participants	66.2 years STANDARD_DEVIATION 7.2 • n=19 Participants	57.2 years STANDARD_DEVIATION 13.8 • n=132 Participants
Sex: Female, Male Female	23 Participants n=100 Participants	10 Participants n=13 Participants	9 Participants n=19 Participants	42 Participants n=132 Participants
Sex: Female, Male Male	77 Participants n=100 Participants	3 Participants n=13 Participants	10 Participants n=19 Participants	90 Participants n=132 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=100 Participants	0 Participants n=13 Participants	1 Participants n=19 Participants	2 Participants n=132 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	94 Participants n=100 Participants	13 Participants n=13 Participants	18 Participants n=19 Participants	125 Participants n=132 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	5 Participants n=100 Participants	0 Participants n=13 Participants	0 Participants n=19 Participants	5 Participants n=132 Participants
Apnea-Hypopnea Index (AHI)	31.2 events/hr STANDARD_DEVIATION 21.1 • n=97 Participants • Three participants in study A did not have baseline sleep studies available for review.	37.5 events/hr STANDARD_DEVIATION 30.0 • n=13 Participants • Three participants in study A did not have baseline sleep studies available for review.	40.1 events/hr STANDARD_DEVIATION 19.5 • n=19 Participants • Three participants in study A did not have baseline sleep studies available for review.	33.2 events/hr STANDARD_DEVIATION 22.0 • n=129 Participants • Three participants in study A did not have baseline sleep studies available for review.
BMI	29.6 kg/m^2 STANDARD_DEVIATION 4.8 • n=99 Participants • One participant in study A did not have BMI data collected.	26.6 kg/m^2 STANDARD_DEVIATION 3.0 • n=13 Participants • One participant in study A did not have BMI data collected.	29.3 kg/m^2 STANDARD_DEVIATION 3.7 • n=19 Participants • One participant in study A did not have BMI data collected.	29.3 kg/m^2 STANDARD_DEVIATION 4.6 • n=131 Participants • One participant in study A did not have BMI data collected.

PRIMARY outcome

Timeframe: Collected during drug-induced sleep endoscopy (<1 day).

Population: Pcrit was unable to be measured in 20 patients (study A) and 2 patients (study B) due to technical issues and protocol deviations.

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.

Outcome measures

Outcome measures
Measure	Study A - Functional Phenotyping During DISE n=80 Participants 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.	Study B - HGNS Responders n=12 Participants Therapy response is defined as a ≥ 50% reduction in baseline AHI with HGNS, measured during overnight polysomnography.	Study B - HGNS Nonresponders n=18 Participants Therapy response is defined as a \< 50% reduction in baseline AHI with HGNS, measured during overnight polysomnography.
Pharyngeal Critical Pressure (Pcrit)	1.26 cm H2O Standard Deviation 3.29	-1.42 cm H2O Standard Deviation 4.36	-1.06 cm H2O Standard Deviation 2.62

PRIMARY outcome

Timeframe: Collected during drug-induced sleep endoscopy (<1 day).

Population: PhOP could not be obtained in 16 subjects (14 in study A, 2 for study B) due to technical issues or protocol deviations.

Measurement of upper airway collapsibility (cmH2O)

Outcome measures

Outcome measures
Measure	Study A - Functional Phenotyping During DISE n=86 Participants 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.	Study B - HGNS Responders n=12 Participants Therapy response is defined as a ≥ 50% reduction in baseline AHI with HGNS, measured during overnight polysomnography.	Study B - HGNS Nonresponders n=18 Participants Therapy response is defined as a \< 50% reduction in baseline AHI with HGNS, measured during overnight polysomnography.
Pharyngeal Opening Pressure (PhOP)	7.99 cm H2O Standard Deviation 3.45	7.33 cm H2O Standard Deviation 3.60	7.44 cm H2O Standard Deviation 4.08

PRIMARY outcome

Timeframe: Unable to be determined

Population: Pharyngeal compliance was not analyzed from any participant due to the inability to reliably identify and standardize airway dimensions following data acquisition. Although data acquisition was performed, measurement values were not collected. Calibration was unsuccessful, and the variability in anatomical landmarks prevented a reproducible method. No valid outcome data were generated. There are no plans to further validate the measurement procedure or to analyze these data in the future.

Pressure-area relationships

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Assessed at a single visit

Population: Tongue force was only conducted during study B.

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.

Outcome measures

Outcome measures
Measure	Study A - Functional Phenotyping During DISE 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.	Study B - HGNS Responders n=10 Participants Therapy response is defined as a ≥ 50% reduction in baseline AHI with HGNS, measured during overnight polysomnography.	Study B - HGNS Nonresponders n=12 Participants Therapy response is defined as a \< 50% reduction in baseline AHI with HGNS, measured during overnight polysomnography.
Tongue Force - Maximum	—	38.0 kPa Standard Deviation 18.8	47.4 kPa Standard Deviation 10.9

OTHER_PRE_SPECIFIED outcome

Timeframe: Assessed at a single visit

Population: Tongue fatigue was assessed during study B only.

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.

Outcome measures

Outcome measures
Measure	Study A - Functional Phenotyping During DISE 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.	Study B - HGNS Responders n=10 Participants Therapy response is defined as a ≥ 50% reduction in baseline AHI with HGNS, measured during overnight polysomnography.	Study B - HGNS Nonresponders n=13 Participants Therapy response is defined as a \< 50% reduction in baseline AHI with HGNS, measured during overnight polysomnography.
Tongue Force - Fatigue	—	11.1 seconds Standard Deviation 9.5	17.1 seconds Standard Deviation 12.7

POST_HOC outcome

Timeframe: Assessed at a single visit

Population: MRI was performed on participants in study B only, per protocol.

Soft palate volume measured via MRI.

Outcome measures

Outcome measures
Measure	Study A - Functional Phenotyping During DISE 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.	Study B - HGNS Responders n=13 Participants Therapy response is defined as a ≥ 50% reduction in baseline AHI with HGNS, measured during overnight polysomnography.	Study B - HGNS Nonresponders n=18 Participants Therapy response is defined as a \< 50% reduction in baseline AHI with HGNS, measured during overnight polysomnography.
Soft Palate Volume	—	9011.37 mm^3 Standard Deviation 1904.12	11094.10 mm^3 Standard Deviation 2721.72

POST_HOC outcome

Timeframe: Assessed at a single visit

Population: MRI was performed on participants in study B only, per protocol.

Tongue volume measured via MRI

Outcome measures

Outcome measures
Measure	Study A - Functional Phenotyping During DISE 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.	Study B - HGNS Responders n=13 Participants Therapy response is defined as a ≥ 50% reduction in baseline AHI with HGNS, measured during overnight polysomnography.	Study B - HGNS Nonresponders n=18 Participants Therapy response is defined as a \< 50% reduction in baseline AHI with HGNS, measured during overnight polysomnography.
Tongue Volume	—	85131.9 mm^3 Standard Deviation 16334.92	85322.08 mm^3 Standard Deviation 12149.09

Adverse Events

Study A - Functional Phenotyping During DISE

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Study B - Hypoglossal Nerve Stimulation (HGNS) Patients

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Raj Dedhia, MD

University of Pennsylvania

Phone: 2158293720

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place