tVNS Device for Atrial Fibrillation

Overseen By Natalia Wells-Serrano

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Oklahoma

Disqualifiers: Sick sinus syndrome, AV block, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

160 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a device called tVNS (Transcutaneous Electrical Nerve Stimulation Device) to determine its effectiveness for people with paroxysmal atrial fibrillation, a type of irregular heartbeat. The goal is to understand how tVNS affects heart rhythm and related body functions over six months. Participants will receive either active tVNS treatment or a placebo version to compare results. Individuals who have experienced paroxysmal atrial fibrillation might be suitable candidates, especially if this condition disrupts their daily activities. As an unphased trial, this study offers a chance to contribute to understanding a novel approach that could enhance daily life for those affected by this condition.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that this tVNS device is safe for patients with atrial fibrillation?

Research has shown that transcutaneous electrical nerve stimulation (tVNS) is generally safe for people. Most studies find that tVNS is well-tolerated, with few serious side effects reported. A review of multiple studies found tVNS to be a safe and practical treatment option. One study confirmed that the doses tested so far are safe for humans. These findings suggest that using a tVNS device does not cause significant negative effects, making it a promising choice for those considering participation in a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the transcutaneous electrical nerve stimulation (tVNS) device for atrial fibrillation because it offers a novel, non-invasive approach to managing the condition. Unlike current treatments, which often involve medication or invasive procedures, the tVNS device stimulates nerves through the skin to help regulate the heart's rhythm. This method could potentially reduce side effects associated with medications and provide a more accessible treatment option for patients. By targeting the nervous system, the tVNS device represents a fresh direction in treating atrial fibrillation, with the promise of improving patient comfort and outcomes.

What evidence suggests that this device is effective for atrial fibrillation?

Research has shown that transcutaneous electrical nerve stimulation (TENS) can help reduce atrial fibrillation (AF), a common heart rhythm problem. This trial will assign participants to either an active TENS stimulation group or an inactive (sham) TENS stimulation group. One study found that people using TENS spent less time in AF compared to those who received a sham treatment. Another study discovered that TENS reduced the frequency and duration of AF episodes over six months. TENS stimulates the vagus nerve, which helps control heart rhythm and can manage AF. Overall, early research suggests that TENS might be a useful tool for managing occasional AF episodes. ^{1 6 7 8 9}

Who Is on the Research Team?

Stavros Stavrakis, MD

Principal Investigator

University of Oklahoma

Are You a Good Fit for This Trial?

This trial is for individuals with paroxysmal atrial fibrillation, which means their heart occasionally beats irregularly. It's not for those with significant heart valve issues, severe kidney disease on dialysis, pregnant women, certain types of heart block without a pacemaker, history of vagotomy or frequent fainting spells due to vasovagal syncope, very weak hearts (ejection fraction <40%), or recent stroke or serious heart events.

Inclusion Criteria

I have episodes of irregular heartbeat.

I have episodes of irregular heartbeat.

Exclusion Criteria

I am on dialysis for end-stage kidney disease.

I have a serious heart valve problem.

Pregnancy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Optimization Phase

Patients with paroxysmal AF are randomized to a series of stimulation frequencies and intensities to define optimal effects and 'dosing' of tVNS.

5 minutes per session

Multiple sessions (in-person)

Treatment

Patients with paroxysmal AF not undergoing ablation are randomized to active or sham tVNS for 6 months using optimal parameters.

6 months

Daily sessions (self-administered)

Follow-up

Participants are monitored for safety and effectiveness after treatment using continuous monitoring with a smartwatch.

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Transcutaneous Electrical Nerve Stimulation Device

Trial Overview The study tests if tVNS—a non-invasive nerve stimulation—can improve the condition and reduce episodes over six months compared to fake (sham) treatment. Researchers will also look for physical and biochemical signs that show who benefits most from this therapy.

How Is the Trial Designed?

Group I: Active TENS Stimulation Active Control 1 Intervention

Group II: Inactive TENS Stimulation Placebo Group 1 Intervention

Transcutaneous Electrical Nerve Stimulation Device is already approved in United States, European Union for the following indications:

Approved in United States as Transcutaneous Vagal Stimulation for:

• Paroxysmal atrial fibrillation

Approved in European Union as Transcutaneous Vagal Stimulation for:

• Not specified in provided sources

Who Is Running the Clinical Trial?

University of Oklahoma

Lead Sponsor

Trials

484

Recruited

95,900+

Published Research Related to This Trial

Transcutaneous vagus nerve stimulation (tVNS) was found to significantly increase salivary alpha amylase (SAA) levels and reduce the decline of salivary cortisol in healthy participants, indicating a modulation of hormonal indices related to noradrenergic function.

However, tVNS did not show any significant effects on psychophysiological measures such as P3 amplitude or pupil size, suggesting that while it may influence hormonal responses, it does not impact certain cognitive or physiological indices in the same way.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The neuromodulatory and hormonal effects of transcutaneous vagus nerve stimulation as evidenced by salivary alpha amylase, salivary cortisol, pupil diameter, and the P3 event-related potential. Warren, CM., Tona, KD., Ouwerkerk, L., et al.[2019]

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]

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 of 199 horses undergoing transvenous electrical cardioversion (TVEC) for atrial fibrillation, the procedure had a high success rate of 94.4%, with mitral regurgitation and AF cycle length identified as key factors influencing success.

The study also found a recurrence rate of 31.9%, with significant risk factors for recurrence including being a stallion, having mitral regurgitation, and longer duration of atrial fibrillation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transvenous electrical cardioversion of atrial fibrillation in horses: Horse and procedural factors correlated with success and recurrence. Vernemmen, I., Van Steenkiste, G., Dufourni, A., et al.[2022]

Transvenous electrical cardioversion (TVEC) is a promising alternative to quinidine salts for treating atrial fibrillation in horses, offering higher efficacy at lower energy levels.

The report provides detailed guidance on the TVEC technique, including potential complications and illustrated examples, making it a valuable resource for veterinarians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How to perform transvenous electrical cardioversion in horses with atrial fibrillation. McGurrin, MK., Physick-Sheard, PW., Kenney, DG.[2008]

Transcutaneous low-level vagus nerve stimulation (tVNS) in 15 male volunteers showed significant reductions in left ventricular contractility and output, indicating a potential for cardiac autonomic modulation.

While tVNS reduced heart workload, it also led to increased blood pressure and total peripheral resistance, suggesting a reflex response that needs further investigation to understand its therapeutic implications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular responses to low-level transcutaneous vagus nerve stimulation. Sinkovec, M., Trobec, R., Meglic, B.[2021]

The transvenous transseptal (TS) approach for transcatheter aortic valve replacement (TAVR) was successfully performed in 9 inoperable patients with significant contraindications for other access methods, demonstrating its feasibility as an option for patients with limited access.

At 6 months post-procedure, patients showed significant improvement in heart function (NYHA Class improved from 3.4 to 1.7) with no major complications such as cerebrovascular events or rehospitalizations, although some experienced major bleeding and acute kidney injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transseptal antegrade transcatheter aortic valve replacement for patients with no other access approach - a contemporary experience. Cohen, MG., Singh, V., Martinez, CA., et al.[2014]

A novel 2-stage low-voltage defibrillation protocol was developed, which first converts ventricular fibrillation (VF) into ventricular tachycardia (VT) using low-voltage stimuli, and then terminates VT, requiring significantly less energy than traditional methods.

The study demonstrated that applying low-voltage stimuli at specific rates (88% of the VF cycle length) effectively defibrillated VF, using only 0.58% of the energy needed for a single strong biphasic shock, highlighting a potential for safer and more efficient defibrillation techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Terminating ventricular tachyarrhythmias using far-field low-voltage stimuli: mechanisms and delivery protocols. Rantner, LJ., Tice, BM., Trayanova, NA.[2022]

Transcutaneous vagus nerve stimulation (tVNS) significantly reduced postural tachycardia in patients with POTS, showing a mean heart rate increase of 17.6 beats/min in the active group compared to 31.7 beats/min in the sham group after 2 months.

tVNS also led to lower levels of antiadrenergic autoantibodies and inflammatory cytokines, along with improved heart rate variability, indicating its potential as a safe and effective noninvasive treatment for POTS without any reported side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noninvasive Vagus Nerve Stimulation in Postural Tachycardia Syndrome: A Randomized Clinical Trial. Stavrakis, S., Chakraborty, P., Farhat, K., et al.[2023]

Transvenous electrical cardioversion (TVEC) is highly effective for treating atrial fibrillation in horses, achieving successful cardioversion in 71 out of 72 episodes with a mean energy of 165.43 J.

Factors such as age and sex influence the energy required for successful cardioversion, but the duration of arrhythmia prior to treatment does not affect the treatment outcome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transvenous electrical cardioversion of equine atrial fibrillation: patient factors and clinical results in 72 treatment episodes. McGurrin, MK., Physick-Sheard, PW., Kenney, DG.[2016]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7100921/

TRanscutaneous Electrical vAgus nerve sTimulation to ... Chronic, intermittent LLTS resulted in lower AF burden than sham control stimulation, supporting its use to treat paroxysmal AF in selected patients.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02548754

NCT02548754 | Transcutaneous Electrical Vagus Nerve ... The investigators hypothesize that intermittent (1 hour daily) LLTS for 6 months may result in long-term decrease of AF burden and suppression inflammatory ...

3. cureus.com cureus.com/articles/361702-efficacy-of-transcutaneous-vagus-nerve-stimulation-to-suppress-paroxysmal-atrial-fibrillation-a-systematic-review

Efficacy of Transcutaneous Vagus Nerve Stimulation to ... Results showed that LLTS significantly reduced AF burden, the time a patient spends in AF, compared to sham stimulation, with reductions of up ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0965229925001001

Clinical outcome of electrical transcutaneous auricular ... Low-level transcutaneous auricular vagus nerve stimulation (Ta-VNS) showed reduced occurrence of perioperative atrial fibrillation and demonstrated an ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12276761/

Efficacy of Transcutaneous Vagus Nerve Stimulation to ... The primary outcome of this systematic review is to evaluate the efficacy of arrhythmia suppression, including parameters such as the frequency ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4352201/

Low-level transcutaneous electrical vagus nerve stimulation ... Transcutaneous low-level tragus electrical stimulation (LLTS) suppresses atrial fibrillation (AF) in canines. We examined the antiarrhythmic and ...

7. nature.com nature.com/articles/s41598-022-25864-1

Safety of transcutaneous auricular vagus nerve stimulation ... This is the first systematic review and meta-analysis of transcutaneous auricular stimulation safety. Overall, taVNS is a safe and feasible option for clinical ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1935861X18302936

Safety and tolerability of Transcutaneous Vagus Nerve ... The available evidence to date suggests that tVNS is well tolerated in humans at the doses tested and is safe.

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7199464/

Critical Review of Transcutaneous Vagus Nerve Stimulation Low-level transcutaneous electrical vagus nerve stimulation suppresses atrial fibrillation. J. Am. Coll. Cardiol. 65, 867–875. 10.1016/j ...