Sustained Auricular Nerve Stimulation for PVC Suppression

NCT07093034 | Enrolling By Invitation DMC FDA Device

• 1 other identifier: 812185
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

Non-invasive vagus nerve stimulation has been clinically tested for the treatment cardiac arrhythmias. However, prior studies have shown mixed results-possibly in part due to inadequate stimulation duration. Therefore, we have designed an investigator-initiated early feasibility study to evaluate safety, tolerability, and compliance with prolonged, nocturnal auricular nerve stimulation using the Parasym device.

Conditions

Premature Ventricular Complexes; PVC - Premature Ventricular Contraction; Auricular Vagus Nerve Stimulation

Keywords

auricular vagus nerve stimulation; parasym; premature ventricular contractions (PVCs); Non-invasive neuromodulation; Cardiac arrhythmia; autonomic nervous system modulation; Trancutaneous electrical stimulation; Randomized controlled trial; heart rate variability; feasibility study

Outcome Measures

Primary Outcomes (4)

• Safety

  The occurrence of adverse events (AEs) throughout the study.

  10 weeks (duration of entire study)

• Tolerability

  Participants will rate tolerability of wearing the device at night at multiple pre-specified time points throughout the study

  10 weeks

• Quality of Life

  Participants will rate quality of life at multiple pre-specified time points throughout the study

  10 weeks

• Feasibility

  Participants will rate ease of wearing the device at night at multiple pre-specified time points throughout the study

  10 weeks

Secondary Outcomes (1)

• PVC burden

  10 weeks

Other Outcomes (2)

• PVC Burden stratified by timing

  10 weeks

• Heart rate variability (HRV)

  10 weeks

Study Arms (2)

Arm 1: Active stimulation followed by crossover to Sham stimulation

EXPERIMENTAL

Device: Extended nocturnal use of auricular vagus nerve stimulator device

Arm 2: Sham stimulation followed by crossover to Active stimulation

EXPERIMENTAL

Device: Extended nocturnal use of auricular vagus nerve stimulator device

Interventions

Extended nocturnal use of auricular vagus nerve stimulator device DEVICE

Patients will wear the ParasymTM device with an ear clip on the tragus that provides stimulation at sub-detection threshold.

Arm 1: Active stimulation followed by crossover to Sham stimulation; Arm 2: Sham stimulation followed by crossover to Active stimulation

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years
• PVC burden ≥ 5% documented on an event monitor or implanted cardiac device
• Provide written informed consent
• Willingness to comply with all study procedures
• Availability for the duration of the study (10 weeks)

You may not qualify if:

• Unwilling or unable to provide informed consent for oneself
• Last available left ventricular ejection fraction \< 20%
• NYHA Class IV symptoms
• Acute coronary syndrome within two weeks of randomization
• Active pregnancy or breastfeeding
• Intention to become pregnant
• Statement Regarding Equitable Selection:

Sponsors & Collaborators

• University of California, San Diego: lead
• Parasym Ltd.: collaborator
• Zywie Healthcare: collaborator

Study Sites (1)

UC San Diego Health System

La Jolla, California, 92037, United States

Location

Related Publications (13)

• Kim AY, Marduy A, de Melo PS, Gianlorenco AC, Kim CK, Choi H, Song JJ, Fregni F. Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic review and meta-analysis. Sci Rep. 2022 Dec 21;12(1):22055. doi: 10.1038/s41598-022-25864-1.

  PMID: 36543841 RESULT

• Gentile F, Giannoni A, Navari A, Degl'Innocenti E, Emdin M, Passino C. Acute right-sided transcutaneous vagus nerve stimulation improves cardio-vagal baroreflex gain in patients with chronic heart failure. Clin Auton Res. 2025 Feb;35(1):75-85. doi: 10.1007/s10286-024-01074-9. Epub 2024 Oct 14.

  PMID: 39402309 RESULT

• Hua K, Cummings M, Bernatik M, Brinkhaus B, Usichenko T, Dietzel J. Cardiovascular effects of auricular stimulation -a systematic review and meta-analysis of randomized controlled clinical trials. Front Neurosci. 2023 Sep 1;17:1227858. doi: 10.3389/fnins.2023.1227858. eCollection 2023.

  PMID: 37727325 RESULT

• Frangos E, Ellrich J, Komisaruk BR. Non-invasive Access to the Vagus Nerve Central Projections via Electrical Stimulation of the External Ear: fMRI Evidence in Humans. Brain Stimul. 2015 May-Jun;8(3):624-36. doi: 10.1016/j.brs.2014.11.018. Epub 2014 Dec 6.

  PMID: 25573069 RESULT

• Stavrakis S, Stoner JA, Humphrey MB, Morris L, Filiberti A, Reynolds JC, Elkholey K, Javed I, Twidale N, Riha P, Varahan S, Scherlag BJ, Jackman WM, Dasari TW, Po SS. TREAT AF (Transcutaneous Electrical Vagus Nerve Stimulation to Suppress Atrial Fibrillation): A Randomized Clinical Trial. JACC Clin Electrophysiol. 2020 Mar;6(3):282-291. doi: 10.1016/j.jacep.2019.11.008. Epub 2020 Jan 29.

  PMID: 32192678 RESULT

• Stavrakis S, Chakraborty P, Farhat K, Whyte S, Morris L, Abideen Asad ZU, Karfonta B, Anjum J, Matlock HG, Cai X, Yu X. Noninvasive Vagus Nerve Stimulation in Postural Tachycardia Syndrome: A Randomized Clinical Trial. JACC Clin Electrophysiol. 2024 Feb;10(2):346-355. doi: 10.1016/j.jacep.2023.10.015. Epub 2023 Nov 22.

  PMID: 37999672 RESULT

• Chakraborty P, Farhat K, Morris L, Whyte S, Yu X, Stavrakis S. Non-invasive Vagus Nerve Simulation in Postural Orthostatic Tachycardia Syndrome. Arrhythm Electrophysiol Rev. 2023 Dec 13;12:e31. doi: 10.15420/aer.2023.20. eCollection 2023.

  PMID: 38173801 RESULT

• Premchand RK, Sharma K, Mittal S, Monteiro R, Dixit S, Libbus I, DiCarlo LA, Ardell JL, Rector TS, Amurthur B, KenKnight BH, Anand IS. Autonomic regulation therapy via left or right cervical vagus nerve stimulation in patients with chronic heart failure: results of the ANTHEM-HF trial. J Card Fail. 2014 Nov;20(11):808-16. doi: 10.1016/j.cardfail.2014.08.009. Epub 2014 Sep 1.

  PMID: 25187002 RESULT

• Gold MR, Van Veldhuisen DJ, Hauptman PJ, Borggrefe M, Kubo SH, Lieberman RA, Milasinovic G, Berman BJ, Djordjevic S, Neelagaru S, Schwartz PJ, Starling RC, Mann DL. Vagus Nerve Stimulation for the Treatment of Heart Failure: The INOVATE-HF Trial. J Am Coll Cardiol. 2016 Jul 12;68(2):149-58. doi: 10.1016/j.jacc.2016.03.525. Epub 2016 Apr 4.

  PMID: 27058909 RESULT

• Zannad F, De Ferrari GM, Tuinenburg AE, Wright D, Brugada J, Butter C, Klein H, Stolen C, Meyer S, Stein KM, Ramuzat A, Schubert B, Daum D, Neuzil P, Botman C, Castel MA, D'Onofrio A, Solomon SD, Wold N, Ruble SB. Chronic vagal stimulation for the treatment of low ejection fraction heart failure: results of the NEural Cardiac TherApy foR Heart Failure (NECTAR-HF) randomized controlled trial. Eur Heart J. 2015 Feb 14;36(7):425-33. doi: 10.1093/eurheartj/ehu345. Epub 2014 Aug 31.

  PMID: 25176942 RESULT

• De Ferrari GM, Crijns HJ, Borggrefe M, Milasinovic G, Smid J, Zabel M, Gavazzi A, Sanzo A, Dennert R, Kuschyk J, Raspopovic S, Klein H, Swedberg K, Schwartz PJ; CardioFit Multicenter Trial Investigators. Chronic vagus nerve stimulation: a new and promising therapeutic approach for chronic heart failure. Eur Heart J. 2011 Apr;32(7):847-55. doi: 10.1093/eurheartj/ehq391. Epub 2010 Oct 28.

  PMID: 21030409 RESULT

• Li M, Zheng C, Sato T, Kawada T, Sugimachi M, Sunagawa K. Vagal nerve stimulation markedly improves long-term survival after chronic heart failure in rats. Circulation. 2004 Jan 6;109(1):120-4. doi: 10.1161/01.CIR.0000105721.71640.DA. Epub 2003 Dec 8.

  PMID: 14662714 RESULT

• Eckberg DL, Drabinsky M, Braunwald E. Defective cardiac parasympathetic control in patients with heart disease. N Engl J Med. 1971 Oct 14;285(16):877-83. doi: 10.1056/NEJM197110142851602. No abstract available.

  PMID: 4398792 RESULT

MeSH Terms

Conditions

Ventricular Premature Complexes; Arrhythmias, Cardiac

Condition Hierarchy (Ancestors)

Cardiac Complexes, Premature; Heart Diseases; Cardiovascular Diseases; Cardiac Conduction System Disease; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: July 14, 2025
• First Posted: July 30, 2025
• Study Start: July 1, 2025
• Primary Completion: March 1, 2026
• Study Completion (Estimated): May 31, 2026
• Last Updated: October 16, 2025

Record last verified: 2025-08

Locations

US (1)