Hypoglossal Nerve Stimulation on Cardiovascular Outcomes

NCT03359096 | Completed Results DMC FDA Device

• 1 other identifier: 834158
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

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.

Conditions

Obstructive Sleep Apnea

Keywords

Sleep apnea; Tongue stimulation; Cardiovascular function

Outcome Measures

Primary Outcomes (1)

• Mean 24-Hour Systolic Ambulatory Blood Pressure Values

  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.

  Study Week 6, Day 1; study Week 11, Day 1

Secondary Outcomes (9)

• Mean 24-Hour Diastolic Ambulatory Blood Pressure Values

  Study Week 6, Day 1; study Week 11, Day 1

• Mean Nocturnal Systolic and Diastolic Ambulatory Blood Pressure Values

  Study Week 6, Day 1; study Week 11, Day 1

• Mean Muscle Sympathetic Nerve Activity (MSNA) Frequency (Bursts/Minute)

  Study Week 6, Day 2; Study Week 11, Day 2

• Mean Muscle Sympathetic Nerve Activity (MSNA) Tonal Activity (Units/Minute)

  Study Week 6, Day 2; Study Week 11, Day 2

• Mean Pre-Ejection Period (PEP)

  Study Week 6, Day 2; Study Week 11, Day 2

Study Arms (2)

Therapeutic HGNS

EXPERIMENTAL

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.

Device: Therapeutic HGNS

Subtherapeutic 'Sham' HGNS

SHAM COMPARATOR

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.

Device: Subtherapeutic 'Sham' HGNS

Interventions

Therapeutic HGNS DEVICE

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.

Also known as: Hypoglossal Nerve Stimulation

Therapeutic HGNS

Subtherapeutic 'Sham' HGNS DEVICE

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

Also known as: Sham Hypoglossal Nerve Stimulation

Subtherapeutic 'Sham' HGNS

Eligibility Criteria

• Age: 22 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• As tolerating the therapeutic level during sleep can take time (weeks to months), all patients must be able to use the device at the therapeutic setting (\> 20 hours/week for \> 1 month) prior to enrollment, based on compliance data.
• All patients will be English-speaking and able to give written informed consent.

You may not qualify if:

• Inspire® remote Model 2500 or later is required. Patients with older remotes are not candidates due to limited adherence monitoring capabilities.
• Patients who have fallen asleep while driving resulting in accident or "near miss" accident within 1 year prior to HGNS implantation.
• Actively using positive airway pressure (PAP) therapy for treatment of OSA.
• Patients in whom the difference between sham and therapeutic voltages is less than 30% the therapeutic voltage.
• Pregnant women will be excluded.\*
• Women of childbearing potential must NOT be pregnant or plan on becoming pregnant. This study involves temporarily stopping treatment of obstructive sleep apnea, which may harm the fetus. If applicable, the patient will need to take a urine pregnancy test after enrollment (prior to washout #1), and again prior to washout #2.

Sponsors & Collaborators

• University of Pennsylvania: lead
• American Heart Association: collaborator
• American Academy of Sleep Medicine: collaborator

Study Sites (1)

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (2)

• Dedhia RC, Quyyumi AA, Park J, Shah AJ, Strollo PJ, Bliwise DL. Cardiovascular endpoints for obstructive sleep apnea with twelfth cranial nerve stimulation (CARDIOSA-12): Rationale and methods. Laryngoscope. 2018 Nov;128(11):2635-2643. doi: 10.1002/lary.27284. Epub 2018 Sep 8.

  PMID: 30194765 BACKGROUND

• Dedhia RC, Bliwise DL, Quyyumi AA, Thaler ER, Boon MS, Huntley CT, Seay EG, Tangutur A, Strollo PJ, Gurel N, Keenan BT. Hypoglossal Nerve Stimulation and Cardiovascular Outcomes for Patients With Obstructive Sleep Apnea: A Randomized Clinical Trial. JAMA Otolaryngol Head Neck Surg. 2024 Jan 1;150(1):39-48. doi: 10.1001/jamaoto.2023.3756.

  PMID: 38032624 DERIVED

MeSH Terms

Conditions

Sleep Apnea, Obstructive; Sleep Apnea Syndromes

Condition Hierarchy (Ancestors)

Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Limitations and Caveats

* partially therapeutic effect of sham HGNS * recruitment of patients with dramatic symptomatic improvement with HGNS was challenging as these patients declined to be without treatment for 6 out of 10 weeks * HGNS is appropriate for a select subset of OSA patients, limiting generalizability of study findings. * baseline AHI was obtained from patient medical records, other baseline outcome measurements (ABPM, PEP, FMD) were not obtained * excluded severely excessively sleepy OSA patients

Results Point of Contact

• Title: Raj C. Dedhia, MD, MSCR
• Organization: University of Pennsylvania

Raj.Dedhia@pennmedicine.upenn.edu

215-349-5009

Study Officials

• Raj C Dedhia, MD, MSCR

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Otorhinolaryngology: Head and Neck Surgery

Model Details: Washout Period 1 (Study Week 1): The patient will not use Hypoglossal Nerve Stimulation (HGNS) for 1 week. Randomization Visit (Study Week 2): The patient will be randomized to sub-therapeutic HGNS (sham) or therapeutic HGNS (treatment) for 28 days. Sympathetic and Vascular testing (Study Week 6). Washout Period 2 (Study Week 6-7): The patient will not use HGNS for 7 days. The patient will be switched to the other intervention arm (treatment to sham vs. sham to treatment) for 28 days. Sympathetic and Vascular testing (Study Week 11).

Study Record Dates

• First Submitted: November 27, 2017
• First Posted: December 2, 2017
• Study Start: December 13, 2017
• Primary Completion: January 21, 2022
• Study Completion: January 21, 2022
• Last Updated: March 30, 2023
• Results First Posted: March 30, 2023

Record last verified: 2023-03

Locations

US (1)