Trial Outcomes & Findings for Hypoglossal Nerve Stimulation on Cardiovascular Outcomes (NCT NCT03359096)
NCT ID: NCT03359096
Last Updated: 2023-03-30
Results Overview
Patients will undergo 24-hour ambulatory blood pressure testing (ABP) using a noninvasive, portable device. The monitor is programmed to record blood pressure every 30 minutes. The patient will be asked to record bedtime and wake time to corroborate the sleep and wake time from the recorder. Mean 24-hour systolic ambulatory blood pressure values will be calculated.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
63 participants
Primary outcome timeframe
Study Week 6, Day 1; study Week 11, Day 1
Results posted on
2023-03-30
Participant Flow
Participant milestones
| Measure |
Therapeutic HGNS, Then Subtherapeutic 'Sham' HGNS
Therapeutic Hypoglossal Nerve Stimulation (HGNS): Prior to enrollment in this study, the HGNS will have been implanted as part of clinical care, and a therapeutic voltage setting will have been determined via overnight sleep study The pulse generator, using technology from cardiac pacemakers, utilizes the signal from the pressure sensor for timing of stimulation to the tongue nerve. Patient will undergo activation of the implanted device one month post-operatively. A functional threshold (in volts) is obtained based on tongue motion during device stimulation. For the next month, the patient will have steadily increased stimulation strength by 0.1V every 2-3 nights within the preset range until the upper limit is reached.
Subtherapeutic 'Sham' HGNS: Sham threshold determination will be performed as follows. The patient will be in a reclined position with the mouth open while nasal breathing. Stimulation will be increased from 0.1V up by 0.1V until bulk tongue motion is detected without obvious protrusion. This process is repeated twice, and the average value is used to determine "sham-HGNS". The electrode configuration will remain consistent between the patient's therapeutic and sham thresholds.
|
Subtherapeutic 'Sham' HGNS, Then Therapeutic HGNS
Subtherapeutic 'Sham' HGNS: Sham threshold determination will be performed as follows. The patient will be in a reclined position with the mouth open while nasal breathing. Stimulation will be increased from 0.1V up by 0.1V until bulk tongue motion is detected without obvious protrusion. This process is repeated twice and the average value is used to determine "sham-HGNS". The electrode configuration will remain consistent between the patient's therapeutic and sham thresholds.
Therapeutic HGNS: Prior to enrollment in this study, the HGNS will have been implanted as part of clinical care, and a therapeutic voltage setting will have been determined via overnight sleep study The pulse generator, using technology from cardiac pacemakers, utilizes the signal from the pressure sensor for timing of stimulation to the tongue nerve. Patient will undergo activation of the implanted device one month post-operatively. A functional threshold (in volts) is obtained based on tongue motion during device stimulation. For the next month, the patient will have steadily increased stimulation strength by 0.1V every 2-3 nights within the preset range until the upper limit is reached.
|
|---|---|---|
|
HGNS Washout (1 Week)
STARTED
|
29
|
31
|
|
HGNS Washout (1 Week)
COMPLETED
|
29
|
31
|
|
HGNS Washout (1 Week)
NOT COMPLETED
|
0
|
0
|
|
First Intervention (4 Weeks)
STARTED
|
31
|
31
|
|
First Intervention (4 Weeks)
COMPLETED
|
29
|
31
|
|
First Intervention (4 Weeks)
NOT COMPLETED
|
2
|
0
|
|
Second Intervention (4 Weeks)
STARTED
|
29
|
31
|
|
Second Intervention (4 Weeks)
COMPLETED
|
29
|
31
|
|
Second Intervention (4 Weeks)
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
Therapeutic HGNS, Then Subtherapeutic 'Sham' HGNS
Therapeutic Hypoglossal Nerve Stimulation (HGNS): Prior to enrollment in this study, the HGNS will have been implanted as part of clinical care, and a therapeutic voltage setting will have been determined via overnight sleep study The pulse generator, using technology from cardiac pacemakers, utilizes the signal from the pressure sensor for timing of stimulation to the tongue nerve. Patient will undergo activation of the implanted device one month post-operatively. A functional threshold (in volts) is obtained based on tongue motion during device stimulation. For the next month, the patient will have steadily increased stimulation strength by 0.1V every 2-3 nights within the preset range until the upper limit is reached.
Subtherapeutic 'Sham' HGNS: Sham threshold determination will be performed as follows. The patient will be in a reclined position with the mouth open while nasal breathing. Stimulation will be increased from 0.1V up by 0.1V until bulk tongue motion is detected without obvious protrusion. This process is repeated twice, and the average value is used to determine "sham-HGNS". The electrode configuration will remain consistent between the patient's therapeutic and sham thresholds.
|
Subtherapeutic 'Sham' HGNS, Then Therapeutic HGNS
Subtherapeutic 'Sham' HGNS: Sham threshold determination will be performed as follows. The patient will be in a reclined position with the mouth open while nasal breathing. Stimulation will be increased from 0.1V up by 0.1V until bulk tongue motion is detected without obvious protrusion. This process is repeated twice and the average value is used to determine "sham-HGNS". The electrode configuration will remain consistent between the patient's therapeutic and sham thresholds.
Therapeutic HGNS: Prior to enrollment in this study, the HGNS will have been implanted as part of clinical care, and a therapeutic voltage setting will have been determined via overnight sleep study The pulse generator, using technology from cardiac pacemakers, utilizes the signal from the pressure sensor for timing of stimulation to the tongue nerve. Patient will undergo activation of the implanted device one month post-operatively. A functional threshold (in volts) is obtained based on tongue motion during device stimulation. For the next month, the patient will have steadily increased stimulation strength by 0.1V every 2-3 nights within the preset range until the upper limit is reached.
|
|---|---|---|
|
HGNS Washout (1 Week)
Withdrawal by Subject
|
0
|
1
|
|
First Intervention (4 Weeks)
Death
|
1
|
0
|
|
First Intervention (4 Weeks)
Physician Decision
|
1
|
0
|
Baseline Characteristics
Hypoglossal Nerve Stimulation on Cardiovascular Outcomes
Baseline characteristics by cohort
| Measure |
Therapeutic HGNS, Then Subtherapeutic 'Sham' HGNS
n=29 Participants
Therapeutic Hypoglossal Nerve Stimulation (HGNS): Prior to enrollment in this study, the HGNS will have been implanted as part of clinical care, and a therapeutic voltage setting will have been determined via overnight sleep study The pulse generator, using technology from cardiac pacemakers, utilizes the signal from the pressure sensor for timing of stimulation to the tongue nerve. Patient will undergo activation of the implanted device one month post-operatively. A functional threshold (in volts) is obtained based on tongue motion during device stimulation. For the next month, the patient will have steadily increased stimulation strength by 0.1V every 2-3 nights within the preset range until the upper limit is reached.
Subtherapeutic 'Sham' HGNS: Sham threshold determination will be performed as follows. The patient will be in a reclined position with the mouth open while nasal breathing. Stimulation will be increased from 0.1V up by 0.1V until bulk tongue motion is detected without obvious protrusion. This process is repeated twice, and the average value is used to determine "sham-HGNS". The electrode configuration will remain consistent between the patient's therapeutic and sham thresholds.
\*The trial's total enrollment was 63 patients; however, 3 patients were consented \& enrolled but did not complete the entirety of study procedures. One patient was consented and enrolled but withdrew prior to intervention assignment, and two patients withdrew prior to crossover.
|
Subtherapeutic 'Sham' HGNS, Therapeutic HGNS
n=31 Participants
Subtherapeutic 'Sham' HGNS: Sham threshold determination will be performed as follows. The patient will be in a reclined position with the mouth open while nasal breathing. Stimulation will be increased from 0.1V up by 0.1V until bulk tongue motion is detected without obvious protrusion. This process is repeated twice and the average value is used to determine "sham-HGNS". The electrode configuration will remain consistent between the patient's therapeutic and sham thresholds.
Therapeutic HGNS: Prior to enrollment in this study, the HGNS will have been implanted as part of clinical care, and a therapeutic voltage setting will have been determined via overnight sleep study The pulse generator, using technology from cardiac pacemakers, utilizes the signal from the pressure sensor for timing of stimulation to the tongue nerve. Patient will undergo activation of the implanted device one month post-operatively. A functional threshold (in volts) is obtained based on tongue motion during device stimulation. For the next month, the patient will have steadily increased stimulation strength by 0.1V every 2-3 nights within the preset range until the upper limit is reached.
\*The trial's total enrollment was 63 patients; however, 3 patients were consented \& enrolled but did not complete the entirety of study procedures. One patient was consented and enrolled but withdrew prior to intervention assignment, and two patients withdrew prior to crossover.
|
Total
n=60 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
67.6 years
STANDARD_DEVIATION 7.5 • n=5 Participants
|
67.1 years
STANDARD_DEVIATION 11.8 • n=7 Participants
|
67.3 years
STANDARD_DEVIATION 9.9 • n=5 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
38 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
26 Participants
n=5 Participants
|
29 Participants
n=7 Participants
|
55 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Body Mass Index (BMI)
|
29.6 kg/m^2
STANDARD_DEVIATION 4.9 • n=5 Participants
|
27.9 kg/m^2
STANDARD_DEVIATION 4.2 • n=7 Participants
|
28.7 kg/m^2
STANDARD_DEVIATION 4.6 • n=5 Participants
|
|
Pre-Implant Apnea-Hypopnea Index (AHI)
|
34.4 events/hour
STANDARD_DEVIATION 15.0 • n=5 Participants
|
31.9 events/hour
STANDARD_DEVIATION 14.9 • n=7 Participants
|
33.1 events/hour
STANDARD_DEVIATION 14.9 • n=5 Participants
|
PRIMARY outcome
Timeframe: Study Week 6, Day 1; study Week 11, Day 1Patients will undergo 24-hour ambulatory blood pressure testing (ABP) using a noninvasive, portable device. The monitor is programmed to record blood pressure every 30 minutes. The patient will be asked to record bedtime and wake time to corroborate the sleep and wake time from the recorder. Mean 24-hour systolic ambulatory blood pressure values will be calculated.
Outcome measures
| Measure |
Therapeutic HGNS
n=60 Participants
Therapeutic Hypoglossal Nerve Stimulation (HGNS). Prior to enrollment in this study, the HGNS will have been implanted as part of clinical care, and a therapeutic voltage setting will have been determined via overnight sleep study.
Therapeutic HGNS: Prior to enrollment in this study, the HGNS will have been implanted as part of clinical care, and a therapeutic voltage setting will have been determined via overnight sleep study The pulse generator, using technology from cardiac pacemakers, utilizes the signal from the pressure sensor for timing of stimulation to the tongue nerve. Patient will undergo activation of the implanted device one month post-operatively. A functional threshold (in volts) is obtained based on tongue motion during device stimulation. For the next month, the patient will have steadily increased stimulation strength by 0.1V every 2-3 nights within the preset range until the upper limit is reached.
|
Subtherapeutic 'Sham' HGNS
n=60 Participants
Sham threshold determination will be performed as follows. The patient will be in a reclined position with the mouth open while nasal breathing. Stimulation will be increased from 0.1V up by 0.1V until bulk tongue motion is detected without obvious protrusion. This process is repeated twice and the average value is used to determine "sham-HGNS". The electrode configuration will remain consistent between the patient's therapeutic and sham thresholds.
Subtherapeutic 'Sham' HGNS: Sham threshold determination will be performed as follows. The patient will be in a reclined position with the mouth open while nasal breathing. Stimulation will be increased from 0.1V up by 0.1V until bulk tongue motion is detected without obvious protrusion. This process is repeated twice and the average value is used to determine "sham-HGNS". The electrode configuration will remain consistent between the patient's therapeutic and sham thresholds
|
|---|---|---|
|
Mean 24-Hour Systolic Ambulatory Blood Pressure Values
|
122.8 mmHg
Standard Deviation 11.8
|
123.0 mmHg
Standard Deviation 10.8
|
SECONDARY outcome
Timeframe: Study Week 6, Day 1; study Week 11, Day 1Patients will undergo 24-hour ambulatory blood pressure testing (ABP) using a noninvasive, portable device. The monitor is programmed to record blood pressure every 30 minutes. The patient will be asked to record bedtime and wake time to corroborate the sleep and wake time from the recorder. Mean 24-hour diastolic ambulatory blood pressure values will be calculated.
Outcome measures
| Measure |
Therapeutic HGNS
n=60 Participants
Therapeutic Hypoglossal Nerve Stimulation (HGNS). Prior to enrollment in this study, the HGNS will have been implanted as part of clinical care, and a therapeutic voltage setting will have been determined via overnight sleep study.
Therapeutic HGNS: Prior to enrollment in this study, the HGNS will have been implanted as part of clinical care, and a therapeutic voltage setting will have been determined via overnight sleep study The pulse generator, using technology from cardiac pacemakers, utilizes the signal from the pressure sensor for timing of stimulation to the tongue nerve. Patient will undergo activation of the implanted device one month post-operatively. A functional threshold (in volts) is obtained based on tongue motion during device stimulation. For the next month, the patient will have steadily increased stimulation strength by 0.1V every 2-3 nights within the preset range until the upper limit is reached.
|
Subtherapeutic 'Sham' HGNS
n=60 Participants
Sham threshold determination will be performed as follows. The patient will be in a reclined position with the mouth open while nasal breathing. Stimulation will be increased from 0.1V up by 0.1V until bulk tongue motion is detected without obvious protrusion. This process is repeated twice and the average value is used to determine "sham-HGNS". The electrode configuration will remain consistent between the patient's therapeutic and sham thresholds.
Subtherapeutic 'Sham' HGNS: Sham threshold determination will be performed as follows. The patient will be in a reclined position with the mouth open while nasal breathing. Stimulation will be increased from 0.1V up by 0.1V until bulk tongue motion is detected without obvious protrusion. This process is repeated twice and the average value is used to determine "sham-HGNS". The electrode configuration will remain consistent between the patient's therapeutic and sham thresholds
|
|---|---|---|
|
Mean 24-Hour Diastolic Ambulatory Blood Pressure Values
|
71.9 mmHg
Standard Deviation 7.8
|
72.1 mmHg
Standard Deviation 7.0
|
SECONDARY outcome
Timeframe: Study Week 6, Day 1; study Week 11, Day 1Patients will undergo ambulatory blood pressure testing (ABP) using a noninvasive, portable device. The patient will be asked to record bedtime and wake time to corroborate the sleep and wake time from the recorder. Mean sleep systolic and diastolic ambulatory blood pressure values will be calculated.
Outcome measures
| Measure |
Therapeutic HGNS
n=60 Participants
Therapeutic Hypoglossal Nerve Stimulation (HGNS). Prior to enrollment in this study, the HGNS will have been implanted as part of clinical care, and a therapeutic voltage setting will have been determined via overnight sleep study.
Therapeutic HGNS: Prior to enrollment in this study, the HGNS will have been implanted as part of clinical care, and a therapeutic voltage setting will have been determined via overnight sleep study The pulse generator, using technology from cardiac pacemakers, utilizes the signal from the pressure sensor for timing of stimulation to the tongue nerve. Patient will undergo activation of the implanted device one month post-operatively. A functional threshold (in volts) is obtained based on tongue motion during device stimulation. For the next month, the patient will have steadily increased stimulation strength by 0.1V every 2-3 nights within the preset range until the upper limit is reached.
|
Subtherapeutic 'Sham' HGNS
n=60 Participants
Sham threshold determination will be performed as follows. The patient will be in a reclined position with the mouth open while nasal breathing. Stimulation will be increased from 0.1V up by 0.1V until bulk tongue motion is detected without obvious protrusion. This process is repeated twice and the average value is used to determine "sham-HGNS". The electrode configuration will remain consistent between the patient's therapeutic and sham thresholds.
Subtherapeutic 'Sham' HGNS: Sham threshold determination will be performed as follows. The patient will be in a reclined position with the mouth open while nasal breathing. Stimulation will be increased from 0.1V up by 0.1V until bulk tongue motion is detected without obvious protrusion. This process is repeated twice and the average value is used to determine "sham-HGNS". The electrode configuration will remain consistent between the patient's therapeutic and sham thresholds
|
|---|---|---|
|
Mean Nocturnal Systolic and Diastolic Ambulatory Blood Pressure Values
SLEEP systolic blood pressure
|
115.0 mmHg
Standard Deviation 14.6
|
114.8 mmHg
Standard Deviation 14.0
|
|
Mean Nocturnal Systolic and Diastolic Ambulatory Blood Pressure Values
SLEEP diastolic blood pressure
|
65.8 mmHg
Standard Deviation 9.1
|
66.3 mmHg
Standard Deviation 8.7
|
SECONDARY outcome
Timeframe: Study Week 6, Day 2; Study Week 11, Day 2Population: MSNA was only performed on 7 patients at Emory University, prior to the trial being transferred to the University of Pennsylvania. For MSNA performed during Therapeutic HGNS arm, 3 patients did not have analyzable MSNA data. For MSNA performed during subtherapeutic 'Sham' HGNS arm, 2 patients did not have analyzable MSNA data.
The peroneal nerve will be located with transcutaneous stimulation and a tungsten microelectrode will be inserted into the nerve, and a reference electrode will be inserted 1-2 cm from the recording electrode. Nerve signals will be preamplified, amplified, filtered, rectified, and integrated to obtain a mean voltage display of sympathetic nerve activity that is recorded. Muscle sympathetic bursts will be identified by visual inspection and expressed as burst frequency (bursts per minute). MSNA was only performed on 7 patients at Emory University, prior to the trial being transferred to the University of Pennsylvania. This is due to there being no research collaborators available at the University of Pennsylvania to capture MSNA as part of this trial. There is insufficient data gathered to make meaningful claims regarding this outcome measure.
Outcome measures
| Measure |
Therapeutic HGNS
n=4 Participants
Therapeutic Hypoglossal Nerve Stimulation (HGNS). Prior to enrollment in this study, the HGNS will have been implanted as part of clinical care, and a therapeutic voltage setting will have been determined via overnight sleep study.
Therapeutic HGNS: Prior to enrollment in this study, the HGNS will have been implanted as part of clinical care, and a therapeutic voltage setting will have been determined via overnight sleep study The pulse generator, using technology from cardiac pacemakers, utilizes the signal from the pressure sensor for timing of stimulation to the tongue nerve. Patient will undergo activation of the implanted device one month post-operatively. A functional threshold (in volts) is obtained based on tongue motion during device stimulation. For the next month, the patient will have steadily increased stimulation strength by 0.1V every 2-3 nights within the preset range until the upper limit is reached.
|
Subtherapeutic 'Sham' HGNS
n=5 Participants
Sham threshold determination will be performed as follows. The patient will be in a reclined position with the mouth open while nasal breathing. Stimulation will be increased from 0.1V up by 0.1V until bulk tongue motion is detected without obvious protrusion. This process is repeated twice and the average value is used to determine "sham-HGNS". The electrode configuration will remain consistent between the patient's therapeutic and sham thresholds.
Subtherapeutic 'Sham' HGNS: Sham threshold determination will be performed as follows. The patient will be in a reclined position with the mouth open while nasal breathing. Stimulation will be increased from 0.1V up by 0.1V until bulk tongue motion is detected without obvious protrusion. This process is repeated twice and the average value is used to determine "sham-HGNS". The electrode configuration will remain consistent between the patient's therapeutic and sham thresholds
|
|---|---|---|
|
Mean Muscle Sympathetic Nerve Activity (MSNA) Frequency (Bursts/Minute)
|
20.2 bursts/minute
Standard Deviation 10.6
|
17.6 bursts/minute
Standard Deviation 5.8
|
SECONDARY outcome
Timeframe: Study Week 6, Day 2; Study Week 11, Day 2Population: MSNA was only performed on 7 patients at Emory University, prior to the trial being transferred to the University of Pennsylvania. For MSNA performed during Therapeutic HGNS arm, 3 patients did not have analyzable MSNA data. For MSNA performed during subtherapeutic 'Sham' HGNS arm, 2 patients did not have analyzable MSNA data.
The peroneal nerve will be located with transcutaneous stimulation and a tungsten microelectrode will be inserted into the nerve, and a reference electrode will be inserted 1-2 cm from the recording electrode. Nerve signals will be preamplified, amplified, filtered, rectified, and integrated to obtain tonal activity (units/minute). MSNA was only performed on 7 patients at Emory University, prior to the trial being transferred to the University of Pennsylvania. This is due to there being no research collaborators available at the University of Pennsylvania to capture MSNA as part of this trial. There is insufficient data gathered to make meaningful claims regarding this outcome measure.
Outcome measures
| Measure |
Therapeutic HGNS
n=4 Participants
Therapeutic Hypoglossal Nerve Stimulation (HGNS). Prior to enrollment in this study, the HGNS will have been implanted as part of clinical care, and a therapeutic voltage setting will have been determined via overnight sleep study.
Therapeutic HGNS: Prior to enrollment in this study, the HGNS will have been implanted as part of clinical care, and a therapeutic voltage setting will have been determined via overnight sleep study The pulse generator, using technology from cardiac pacemakers, utilizes the signal from the pressure sensor for timing of stimulation to the tongue nerve. Patient will undergo activation of the implanted device one month post-operatively. A functional threshold (in volts) is obtained based on tongue motion during device stimulation. For the next month, the patient will have steadily increased stimulation strength by 0.1V every 2-3 nights within the preset range until the upper limit is reached.
|
Subtherapeutic 'Sham' HGNS
n=5 Participants
Sham threshold determination will be performed as follows. The patient will be in a reclined position with the mouth open while nasal breathing. Stimulation will be increased from 0.1V up by 0.1V until bulk tongue motion is detected without obvious protrusion. This process is repeated twice and the average value is used to determine "sham-HGNS". The electrode configuration will remain consistent between the patient's therapeutic and sham thresholds.
Subtherapeutic 'Sham' HGNS: Sham threshold determination will be performed as follows. The patient will be in a reclined position with the mouth open while nasal breathing. Stimulation will be increased from 0.1V up by 0.1V until bulk tongue motion is detected without obvious protrusion. This process is repeated twice and the average value is used to determine "sham-HGNS". The electrode configuration will remain consistent between the patient's therapeutic and sham thresholds
|
|---|---|---|
|
Mean Muscle Sympathetic Nerve Activity (MSNA) Tonal Activity (Units/Minute)
|
29.6 units/minute
Standard Deviation 15.1
|
7.0 units/minute
Standard Deviation 23.9
|
SECONDARY outcome
Timeframe: Study Week 6, Day 2; Study Week 11, Day 2Population: Due to COVID-19 related resource constraints and/or poor signal quality acquisition, several PEP measurements were not included for analysis.
A patient will be fitted with Impedance Cardiography (ICG) Noninvasive Cardiac Output Module that will record the ECG (Electrocardiogram) and the ICG (Impedance cardiography) continuously during a 10-minute period. PEP will be calculated as the average interval (milliseconds) from the onset of left ventricular depolarization, reflected by the Q-wave onset in the ECG to the opening of the aortic valve, reflected by the B-point in the ICG signal. A significant difference in PEP to be a 10 millisecond increase from baseline.
Outcome measures
| Measure |
Therapeutic HGNS
n=51 Participants
Therapeutic Hypoglossal Nerve Stimulation (HGNS). Prior to enrollment in this study, the HGNS will have been implanted as part of clinical care, and a therapeutic voltage setting will have been determined via overnight sleep study.
Therapeutic HGNS: Prior to enrollment in this study, the HGNS will have been implanted as part of clinical care, and a therapeutic voltage setting will have been determined via overnight sleep study The pulse generator, using technology from cardiac pacemakers, utilizes the signal from the pressure sensor for timing of stimulation to the tongue nerve. Patient will undergo activation of the implanted device one month post-operatively. A functional threshold (in volts) is obtained based on tongue motion during device stimulation. For the next month, the patient will have steadily increased stimulation strength by 0.1V every 2-3 nights within the preset range until the upper limit is reached.
|
Subtherapeutic 'Sham' HGNS
n=50 Participants
Sham threshold determination will be performed as follows. The patient will be in a reclined position with the mouth open while nasal breathing. Stimulation will be increased from 0.1V up by 0.1V until bulk tongue motion is detected without obvious protrusion. This process is repeated twice and the average value is used to determine "sham-HGNS". The electrode configuration will remain consistent between the patient's therapeutic and sham thresholds.
Subtherapeutic 'Sham' HGNS: Sham threshold determination will be performed as follows. The patient will be in a reclined position with the mouth open while nasal breathing. Stimulation will be increased from 0.1V up by 0.1V until bulk tongue motion is detected without obvious protrusion. This process is repeated twice and the average value is used to determine "sham-HGNS". The electrode configuration will remain consistent between the patient's therapeutic and sham thresholds
|
|---|---|---|
|
Mean Pre-Ejection Period (PEP)
|
105.7 milliseconds
Standard Deviation 16.5
|
105.4 milliseconds
Standard Deviation 16.8
|
SECONDARY outcome
Timeframe: Study Week 6, Day 2; Study Week 11, Day 2Population: Due to COVID-19 related resource constraints and/or poor signal quality acquisition, several FMD measurements were not included for analysis.
The brachial artery of the nondominant arm will be imaged using a high-resolution ultrasound transducer. A blood pressure cuff on the forearm will be inflated to suprasystolic pressures to produce 5 min of ischemia. On cuff deflation, imaging will be performed to measure FMD. Brachial artery FMD will be calculated as (post-ischemia diameter - baseline diameter) / (baseline diameter) x 100.
Outcome measures
| Measure |
Therapeutic HGNS
n=43 Participants
Therapeutic Hypoglossal Nerve Stimulation (HGNS). Prior to enrollment in this study, the HGNS will have been implanted as part of clinical care, and a therapeutic voltage setting will have been determined via overnight sleep study.
Therapeutic HGNS: Prior to enrollment in this study, the HGNS will have been implanted as part of clinical care, and a therapeutic voltage setting will have been determined via overnight sleep study The pulse generator, using technology from cardiac pacemakers, utilizes the signal from the pressure sensor for timing of stimulation to the tongue nerve. Patient will undergo activation of the implanted device one month post-operatively. A functional threshold (in volts) is obtained based on tongue motion during device stimulation. For the next month, the patient will have steadily increased stimulation strength by 0.1V every 2-3 nights within the preset range until the upper limit is reached.
|
Subtherapeutic 'Sham' HGNS
n=42 Participants
Sham threshold determination will be performed as follows. The patient will be in a reclined position with the mouth open while nasal breathing. Stimulation will be increased from 0.1V up by 0.1V until bulk tongue motion is detected without obvious protrusion. This process is repeated twice and the average value is used to determine "sham-HGNS". The electrode configuration will remain consistent between the patient's therapeutic and sham thresholds.
Subtherapeutic 'Sham' HGNS: Sham threshold determination will be performed as follows. The patient will be in a reclined position with the mouth open while nasal breathing. Stimulation will be increased from 0.1V up by 0.1V until bulk tongue motion is detected without obvious protrusion. This process is repeated twice and the average value is used to determine "sham-HGNS". The electrode configuration will remain consistent between the patient's therapeutic and sham thresholds
|
|---|---|---|
|
Mean Flow-mediated Dilation (FMD)
|
6.65 % of dilation from baseline
Standard Deviation 4.38
|
6.79 % of dilation from baseline
Standard Deviation 5.03
|
SECONDARY outcome
Timeframe: Study Week 6, Day 2; Study Week 11, Day 2Population: For PAS performed during Therapeutic HGNS arm, 2 patients did not have analyzable PAS data.
Following a rest period of 10 minutes with subjects in a supine position in a quiet, temperature-controlled room, blood pressure will be measured 3 times at 5-minute intervals by an automatic device. The standard metric of peripheral arterial stiffness (PAS) is carotid-femoral pulse wave velocity (PWV), which will be estimated using the Sphygmocor device® (Atcor Medical, Sydney, Australia). PAS was only captured on 21 patients at Emory University and the University of Pennsylvania. This is due to our cardiovascular research collaborators at the University of Pennsylvania indicating they would no longer be able to support our research study due to their own COVID-19 related resource constraints. There is insufficient data gathered to make meaningful claims regarding this outcome measure. PAS is reported as changes in pulse wave velocity, with a meters/second unit measure.
Outcome measures
| Measure |
Therapeutic HGNS
n=19 Participants
Therapeutic Hypoglossal Nerve Stimulation (HGNS). Prior to enrollment in this study, the HGNS will have been implanted as part of clinical care, and a therapeutic voltage setting will have been determined via overnight sleep study.
Therapeutic HGNS: Prior to enrollment in this study, the HGNS will have been implanted as part of clinical care, and a therapeutic voltage setting will have been determined via overnight sleep study The pulse generator, using technology from cardiac pacemakers, utilizes the signal from the pressure sensor for timing of stimulation to the tongue nerve. Patient will undergo activation of the implanted device one month post-operatively. A functional threshold (in volts) is obtained based on tongue motion during device stimulation. For the next month, the patient will have steadily increased stimulation strength by 0.1V every 2-3 nights within the preset range until the upper limit is reached.
|
Subtherapeutic 'Sham' HGNS
n=21 Participants
Sham threshold determination will be performed as follows. The patient will be in a reclined position with the mouth open while nasal breathing. Stimulation will be increased from 0.1V up by 0.1V until bulk tongue motion is detected without obvious protrusion. This process is repeated twice and the average value is used to determine "sham-HGNS". The electrode configuration will remain consistent between the patient's therapeutic and sham thresholds.
Subtherapeutic 'Sham' HGNS: Sham threshold determination will be performed as follows. The patient will be in a reclined position with the mouth open while nasal breathing. Stimulation will be increased from 0.1V up by 0.1V until bulk tongue motion is detected without obvious protrusion. This process is repeated twice and the average value is used to determine "sham-HGNS". The electrode configuration will remain consistent between the patient's therapeutic and sham thresholds
|
|---|---|---|
|
Mean Peripheral Arterial Stiffness (PAS)
|
11.1 meters/second
Standard Deviation 6.2
|
9.8 meters/second
Standard Deviation 2.8
|
SECONDARY outcome
Timeframe: Study Week 6, Day 2; Study Week 11, Day 2Population: PVT was only captured on 43 patients following the trial's transfer from Emory University to the University of Pennsylvania. This was due to a new collaboration between the Department of Otorhinolaryngology \& the Department of Psychiatry to investigate changes in cognitive status for obstructive sleep apnea patients being treated with HGNS.
Patients will perform the neurobehavioral test on a specially calibrated (for timing precision) and designated laptop in a quiet room in the outpatient setting. Each patient will perform a unique version of the psychomotor vigilance test to assess psychomotor speed. The trial's protocol was amended to begin capturing neurobehavioral measures like the PVT at the University of Pennsylvania, as part of a new collaboration with research collaborators in the Department of Psychiatry. PVT is a validated instrument to capture attention, and response time on this cognitive test is reported as reciprocal milliseconds or 1/milliseconds.
Outcome measures
| Measure |
Therapeutic HGNS
n=43 Participants
Therapeutic Hypoglossal Nerve Stimulation (HGNS). Prior to enrollment in this study, the HGNS will have been implanted as part of clinical care, and a therapeutic voltage setting will have been determined via overnight sleep study.
Therapeutic HGNS: Prior to enrollment in this study, the HGNS will have been implanted as part of clinical care, and a therapeutic voltage setting will have been determined via overnight sleep study The pulse generator, using technology from cardiac pacemakers, utilizes the signal from the pressure sensor for timing of stimulation to the tongue nerve. Patient will undergo activation of the implanted device one month post-operatively. A functional threshold (in volts) is obtained based on tongue motion during device stimulation. For the next month, the patient will have steadily increased stimulation strength by 0.1V every 2-3 nights within the preset range until the upper limit is reached.
|
Subtherapeutic 'Sham' HGNS
n=43 Participants
Sham threshold determination will be performed as follows. The patient will be in a reclined position with the mouth open while nasal breathing. Stimulation will be increased from 0.1V up by 0.1V until bulk tongue motion is detected without obvious protrusion. This process is repeated twice and the average value is used to determine "sham-HGNS". The electrode configuration will remain consistent between the patient's therapeutic and sham thresholds.
Subtherapeutic 'Sham' HGNS: Sham threshold determination will be performed as follows. The patient will be in a reclined position with the mouth open while nasal breathing. Stimulation will be increased from 0.1V up by 0.1V until bulk tongue motion is detected without obvious protrusion. This process is repeated twice and the average value is used to determine "sham-HGNS". The electrode configuration will remain consistent between the patient's therapeutic and sham thresholds
|
|---|---|---|
|
Mean Psychomotor Vigilance Test (PVT) Reciprocal Reaction Time
|
4.01 1/milliseconds
Standard Deviation 0.47
|
3.97 1/milliseconds
Standard Deviation 0.51
|
SECONDARY outcome
Timeframe: Study Week 6, Day 2; Study Week 11, Day 2Population: DSST was only captured on 43 patients following the trial's transfer from Emory University to the University of Pennsylvania. This was due to a new collaboration between the Department of Otorhinolaryngology \& the Department of Psychiatry to investigate changes in cognitive status for obstructive sleep apnea patients being treated with HGNS.
Patients will perform the neurobehavioral test on a specially calibrated (for timing precision) and designated laptop in a quiet room in the outpatient setting. Each patient will perform a unique version of the digit symbol substitution test to assess processing speed. The trial's protocol was amended to begin capturing neurobehavioral measures like the DSST at the University of Pennsylvania, as part of a new collaboration with research collaborators in the Department of Psychiatry. DSST is a validated instrument to capture visual tracking and working memory, and response time on this cognitive test is reported in milliseconds.
Outcome measures
| Measure |
Therapeutic HGNS
n=43 Participants
Therapeutic Hypoglossal Nerve Stimulation (HGNS). Prior to enrollment in this study, the HGNS will have been implanted as part of clinical care, and a therapeutic voltage setting will have been determined via overnight sleep study.
Therapeutic HGNS: Prior to enrollment in this study, the HGNS will have been implanted as part of clinical care, and a therapeutic voltage setting will have been determined via overnight sleep study The pulse generator, using technology from cardiac pacemakers, utilizes the signal from the pressure sensor for timing of stimulation to the tongue nerve. Patient will undergo activation of the implanted device one month post-operatively. A functional threshold (in volts) is obtained based on tongue motion during device stimulation. For the next month, the patient will have steadily increased stimulation strength by 0.1V every 2-3 nights within the preset range until the upper limit is reached.
|
Subtherapeutic 'Sham' HGNS
n=43 Participants
Sham threshold determination will be performed as follows. The patient will be in a reclined position with the mouth open while nasal breathing. Stimulation will be increased from 0.1V up by 0.1V until bulk tongue motion is detected without obvious protrusion. This process is repeated twice and the average value is used to determine "sham-HGNS". The electrode configuration will remain consistent between the patient's therapeutic and sham thresholds.
Subtherapeutic 'Sham' HGNS: Sham threshold determination will be performed as follows. The patient will be in a reclined position with the mouth open while nasal breathing. Stimulation will be increased from 0.1V up by 0.1V until bulk tongue motion is detected without obvious protrusion. This process is repeated twice and the average value is used to determine "sham-HGNS". The electrode configuration will remain consistent between the patient's therapeutic and sham thresholds
|
|---|---|---|
|
Mean Digit Symbol Substitution Test (DSST) Reaction Time
|
1846.64 milliseconds
Standard Deviation 355.5
|
1893.57 milliseconds
Standard Deviation 428.1
|
Adverse Events
Therapeutic HGNS
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Subtherapeutic 'Sham' HGNS
Serious events: 0 serious events
Other events: 0 other events
Deaths: 1 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place