Non-invasive Vagal Stimulation for Premature Ventricular Contractions

((NoVa-PVC) Trial)

Recruiting at 1 trial location

Overseen By Kristie Coleman, RN

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Northwell Health

Disqualifiers: Heart failure, Valve disease, Pregnancy, Thyroid issues, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 20 days

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a device that uses low-level tragus stimulation, a non-invasive technique, to reduce premature ventricular contractions (PVCs), which are disruptive extra heartbeats. The study compares the effects of real stimulation with a sham version to assess the treatment's effectiveness. It targets individuals with frequent PVCs who find standard medications like beta blockers ineffective or intolerable. Participants should have a noticeable PVC burden and should not have certain heart conditions, such as severe heart failure or structural heart disease. As an unphased trial, this study provides an opportunity to explore a new treatment option for those seeking alternatives to standard medications.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants should be intolerant to or unwilling to take certain heart medications, or that these medications have been ineffective for them.

What prior data suggests that this device is safe for treating premature ventricular contractions?

Research has shown that Low-Level Tragus Stimulation (LLTS) is very safe. It has been used for a long time to treat epilepsy, establishing a strong safety record. Although this trial focuses on treating premature ventricular contractions (PVCs), the treatment is likely safe. While detailed safety data from this trial is not yet available, the long history of using similar methods for conditions like epilepsy supports the idea that LLTS could be well-tolerated with minimal risk. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about low-level tragus stimulation for treating premature ventricular contractions because it offers a non-invasive approach that directly targets the nervous system. Most standard treatments involve medications like beta-blockers or calcium channel blockers, which can have systemic side effects. In contrast, this technique uses vagal stimulation, specifically targeting the ear's tragus to modulate heart activity without the need for drugs. This method could potentially provide faster relief and fewer side effects, making it a promising alternative to traditional medication-based therapies.

What evidence suggests that low-level tragus stimulation is effective for premature ventricular contractions?

Research has shown that low-level tragus stimulation (LLTS), which participants in this trial may receive, can help reduce premature ventricular contractions (PVCs), or extra heartbeats. One study significantly lowered PVCs from 12.8% to 9.9% with LLTS, compared to a sham treatment. Another study found similar results, reducing PVCs from 10.5% to 8.59% with LLTS. These findings suggest that LLTS could be a useful treatment for individuals who frequently experience PVCs and have not found relief with other medical treatments. Participants in this trial may also receive a sham procedure for comparison. ^{1 5 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 with frequent premature ventricular complexes (PVCs) who can't or don't want to use certain heart medications. It's not for those with severe heart failure, valve disease, pregnant/nursing women, people with specific cardiac devices or metallic/electronic implants, thyroid issues, renal dialysis patients, certain types of heart block or autonomic dysfunction.

Inclusion Criteria

I have frequent or noticeable skipped heartbeats.

Beta blockers and calcium channel blockers don't work for me or I choose not to take them.

Exclusion Criteria

I have severe heart failure or serious heart valve problems.

I have had surgery on the nerves of my cervix.

My skin on the tragus is broken or cracked.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Monitoring

Participants receive a cardiac event monitor for baseline data collection

28 days

1 visit (in-person) for device setup

Treatment

Participants receive either LLTS or sham-stimulation for 10 days, followed by a crossover to the alternate treatment for another 10 days

20 days

Daily sessions (self-administered)

Wash-out

An 8-day wash-out period between the two treatment phases

8 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

28 days

What Are the Treatments Tested in This Trial?

Interventions

• Low-level Tragus Stimulation
• Parasym Device
• Sham Device

Trial Overview The study tests a non-invasive device called Parasym against a sham (fake) device to see if it helps reduce PVCs by stimulating the ear's tragus. Participants are randomly chosen to receive either the real treatment or a placebo in this controlled trial.

How Is the Trial Designed?

Group I: Active Experimental Treatment 1 Intervention

Patients will receive 1 hour of active low level tragus stimulation daily for 10 days.

Group II: Sham Placebo Group 1 Intervention

Patients will receive 1 hour of sham low level tragus stimulation daily for 10 days.

Who Is Running the Clinical Trial?

Northwell Health

Lead Sponsor

Trials

481

Recruited

470,000+

University of Oklahoma

Collaborator

Trials

484

Recruited

95,900+

Published Research Related to This Trial

In a study involving 24 patients with diastolic dysfunction, low-level transcutaneous vagus nerve stimulation (LLTS) significantly improved left ventricular function, as indicated by a 1.8% increase in global longitudinal strain compared to sham stimulation.

LLTS also positively affected heart rate variability, suggesting it enhances autonomic tone, which may contribute to better cardiac mechanics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autonomic Neuromodulation Acutely Ameliorates Left Ventricular Strain in Humans. Tran, N., Asad, Z., Elkholey, K., et al.[2020]

Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive and cost-effective method for modulating the vagus nerve, making it a promising alternative to traditional surgical vagus nerve stimulation.

taVNS allows for easy and safe administration, with considerations for proper electrode placement and individual dosing based on perception thresholds, which enhances its potential for treating various central and peripheral diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Laboratory Administration of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS): Technique, Targeting, and Considerations. Badran, BW., Yu, AB., Adair, D., et al.[2020]

Low-level tragus stimulation (LLTS) is a promising non-invasive treatment that has shown potential benefits in managing various cardiovascular conditions, including atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF).

Preliminary clinical studies suggest that LLTS may improve heart function and reduce arrhythmias by positively influencing the balance between the sympathetic and parasympathetic nervous systems, although further research and larger trials are needed to confirm these effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-invasive Low-level Tragus Stimulation in Cardiovascular Diseases. Jiang, Y., Po, SS., Amil, F., et al.[2020]

In a study involving 26 patients with ischemic cardiomyopathy and heart failure, acute low-level tragus stimulation (LLTS) was found to significantly increase the T-wave alternans (TWA) burden during sinus rhythm, indicating a potential risk for ventricular tachy-arrhythmias.

The study demonstrated that the increase in TWA burden was heart-rate dependent, particularly during right atrial pacing at 100 bpm, suggesting that LLTS may not have the desired anti-arrhythmic effects in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microvolt T-Wave Alternans Is Modulated by Acute Low-Level Tragus Stimulation in Patients With Ischemic Cardiomyopathy and Heart Failure. Kulkarni, K., Stavrakis, S., Elkholey, K., et al.[2021]

Chronic low-level tragus stimulation (LLTS) significantly reduced the burden of paroxysmal atrial fibrillation (AF) by 85% over 6 months compared to a sham control, indicating its potential as an effective treatment option.

The active LLTS group also showed a significant 23% reduction in tumor necrosis factor-alpha levels and improved heart rate variability, with no reported side effects, suggesting both safety and efficacy in managing AF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TREAT AF (Transcutaneous Electrical Vagus Nerve Stimulation to Suppress Atrial Fibrillation): A Randomized Clinical Trial. Stavrakis, S., Stoner, JA., Humphrey, MB., et al.[2021]

In a study involving 10 patients undergoing coronary artery bypass grafting, low-level vagus nerve stimulation through the tragus (tLLVNS) significantly increased unipolar potential voltage, indicating enhanced atrial electrophysiological properties.

Some patients experienced additional benefits during tLLVNS, such as reduced total activation time and changes in sinoatrial node exit sites, suggesting potential antiarrhythmic effects that could help in preventing atrial fibrillation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insights Into the Effects of Low-Level Vagus Nerve Stimulation on Atrial Electrophysiology: Towards Patient-Tailored Cardiac Neuromodulation. Kharbanda, RK., Ramdat Misier, NL., van Schie, MS., et al.[2023]

Vagus nerve stimulation (VNS) is effective for treating refractory epilepsy and depression, but traditional methods involve surgical implantation, which carries risks such as infection and bradycardia.

New non-invasive VNS systems eliminate the need for surgery, improving safety and tolerability, and allowing patients to administer stimulation on demand, potentially expanding its use in various medical conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgically implanted and non-invasive vagus nerve stimulation: a review of efficacy, safety and tolerability. Ben-Menachem, E., Revesz, D., Simon, BJ., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40392172/

A Crossover, Randomized Clinical Trial (NoVa-PVC) Conclusions: LLTS effectively reduced PVC burden in patients with symptomatic PVCs refractory to medical therapy, highlighting its potential as an adjuvant ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2405500X25002646

Transcutaneous Electrical Vagus Nerve Stimulation to ... We found that LLTS resulted in a significant reduction of the PVC burden compared with sham stimulation (10.5% [IQR: 14.4%] vs 8.59% [IQR: 8.45%]; P = 0.021) ( ...

3. heartrhythmjournal.com heartrhythmjournal.com/article/S1547-5271(25)02140-X/fulltext

PO-07-209 TRANSCUTANEOUS ELECTRICAL VAGUS ... LLTS significantly reduced PVC burden compared to sham stimulation [12.8 ± 10.9% vs 9.9 ± 8.3%, p=0.021). No significant differences in heart rate variability ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37872628/

Transcutaneous electrical vagus nerve stimulation to ... Transcutaneous electrical vagus nerve stimulation to suppress premature ventricular complexes (TREAT PVC): study protocol for a multi-center, ...

5. jacc.org jacc.org/doi/abs/10.1016/j.jacep.2025.04.011

A Crossover, Randomized Clinical Trial (NoVa-PVC) The median baseline PVC burden was 12.00% (IQR: 11.4%). LLTS significantly reduced the median PVC burden by 13.4% compared with sham stimulation (10.5% [IQR: ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10591365/

Transcutaneous electrical vagus nerve stimulation to suppress ... The present study will be a prospective multicenter, double-blind, randomized, controlled trial to assess the antiarrhythmic effects of LLTS on frequent PVCs.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT07026695

Transcutaneous Vagus Nerve Stimulation for Ventricular ... This is called Low-Level Tragus Stimulation (LLTS). Because it has been used for epilepsy for decades, we have evidence of a very high safety profile and ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11285463/

Efficacy and safety of transcutaneous auricular vagus nerve ... The TASC-V trial will help to reveal the efficacy and safety of taVNS for frequent PVCs, offering new clinical evidence for the clinical practice.