Hypoglossal Nerve Stimulation on Cardiovascular Outcomes

Not Applicable

Completed

• Conditions: Obstructive Sleep Apnea
• Interventions: Device: Therapeutic HGNS; Device: Subtherapeutic 'Sham' HGNS

• Registration Number: NCT03359096
• Lead Sponsor: University of Pennsylvania

Brief Summary

A new, well-tolerated treatment for obstructive sleep apnea - tongue stimulation - is a device which opens the airway during sleep and can provide treatment for patients unable to use the mask and hose treatment. The study will evaluate the effect of this new treatment on blood pressure and heart-related measures to see if it lowers patients' risk of heart problems.

Detailed Description

Obstructive sleep apnea, repetitive airway blockage during sleep, affects 1 in 10 Americans. If left untreated, it results in decreased quality of life and increased risk of heart problems. Only half of these people are able to use the main treatment, continuous positive airway pressure (CPAP) therapy, which involves wearing a mask and hose at night. A new, well-tolerated treatment - tongue stimulation - is a device which opens the airway during sleep and can provide treatment for patients unable to use the mask and hose treatment. The study will evaluate the effect of this new treatment on blood pressure and heart-related measures to see if it lowers patients' risk of heart problems.

Study Timeline

• Study First Submitted: 2017-11-27
• Study First Submitted QC: 2017-11-30
• Study First Posted: 2017-12-02
• Study Start: 2017-12-13
• Primary Completion: 2022-01-21
• Study Completion: 2022-01-21
• Results First Submitted: 2022-11-09
• Status Verified: 2023-03
• Results First Submitted QC: 2023-03-29
• Last Update Submitted: 2023-03-29
• Results First Posted: 2023-03-30
• Last Update Posted: 2023-03-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 63

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Therapeutic HGNS	Therapeutic 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.
Subtherapeutic 'Sham' 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.

Primary Outcome Measures

Name	Time	Method
Mean 24-Hour Systolic Ambulatory Blood Pressure Values	Study Week 6, Day 1; study Week 11, Day 1	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.

Secondary Outcome Measures

Name	Time	Method
Mean Peripheral Arterial Stiffness (PAS)	Study Week 6, Day 2; Study Week 11, Day 2	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.
Mean 24-Hour Diastolic Ambulatory Blood Pressure Values	Study Week 6, Day 1; study Week 11, Day 1	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 diastolic ambulatory blood pressure values will be calculated.
Mean Muscle Sympathetic Nerve Activity (MSNA) Frequency (Bursts/Minute)	Study Week 6, Day 2; Study Week 11, Day 2	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.
Mean Muscle Sympathetic Nerve Activity (MSNA) Tonal Activity (Units/Minute)	Study Week 6, Day 2; Study Week 11, Day 2	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.
Mean Pre-Ejection Period (PEP)	Study Week 6, Day 2; Study Week 11, Day 2	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.
Mean Flow-mediated Dilation (FMD)	Study Week 6, Day 2; Study Week 11, Day 2	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.
Mean Nocturnal Systolic and Diastolic Ambulatory Blood Pressure Values	Study Week 6, Day 1; study Week 11, Day 1	Patients 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.
Mean Psychomotor Vigilance Test (PVT) Reciprocal Reaction Time	Study Week 6, Day 2; Study Week 11, Day 2	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.
Mean Digit Symbol Substitution Test (DSST) Reaction Time	Study Week 6, Day 2; Study Week 11, Day 2	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.

Trial Locations

Locations (1)

Hospital of the University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States