taVNS for Atrial Fibrillation

Overseen By Harald M Stauss, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Burrell College of Osteopathic Medicine

Must be taking: Anticoagulants

Disqualifiers: Pregnancy, Epilepsy, Vestibulocochlear issues, 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: 3

Duration: 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a new treatment called taVNS (Transcutaneous Auricular Vagus Nerve Stimulation), which applies a small electric current to the left ear, can lower heart rates in people with persistent atrial fibrillation (a type of irregular heartbeat). Participants will use the treatment at home for 30 minutes each day over two weeks while wearing a heart monitor. One week will involve the actual treatment, and the other will use a non-active version to compare results. Ideal participants are those managing persistent atrial fibrillation and currently on blood thinners. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research and potentially benefit from an innovative treatment.

Will I have to stop taking my current medications?

The trial requires that participants stay on their anti-coagulation medication throughout the study.

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

Research has shown that transcutaneous auricular vagus nerve stimulation (taVNS) is generally safe. Most people tolerate it well. Mild skin irritation, the most common side effect, occurs in about 18% of users. This irritation is usually not serious and resolves on its own. Overall, taVNS has proven safe for users. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about taVNS for atrial fibrillation because it offers a non-invasive approach that differs from traditional treatments like medications or invasive procedures such as ablation. Unlike these options, taVNS uses transcutaneous electrical stimulation to target the vagus nerve through the skin, potentially helping to regulate heart rhythm without the need for drugs or surgery. This method not only reduces the risk of side effects associated with medication but also provides a more accessible, easy-to-use option for patients. With a short daily administration time of just 30 minutes, taVNS could offer quicker and easier symptom management for those with atrial fibrillation.

What evidence suggests that taVNS is effective for atrial fibrillation?

This trial will compare active transcutaneous auricular vagus nerve stimulation (taVNS) with a sham intervention for people with atrial fibrillation (AF), a condition where the heart beats irregularly. Research has shown that stimulating the vagus nerve through the skin of the ear, known as taVNS, can help people with AF. Studies have found that using low-level stimulation on the tragus, a part of the ear, significantly reduces the time a person experiences AF compared to sham treatments. This suggests that taVNS might lessen the impact of AF on a person. While some research did not find a significant change in heart rate, other studies emphasize that taVNS is safe and could be beneficial. Overall, taVNS shows promise for reducing AF symptoms. ^{1 4 6 7 8}

Who Is on the Research Team?

Harald M Stauss, MD, PhD

Principal Investigator

Burrell College of Osteopathic Medicine

Are You a Good Fit for This Trial?

This trial is for adults over 18 with persistent atrial fibrillation who are on anticoagulation therapy. It's not suitable for pregnant individuals, those under 18, or anyone with a history of vestibulocochlear nerve issues like hearing loss or epilepsy.

Inclusion Criteria

I have ongoing irregular heartbeats.

I am taking blood thinners and will continue during the study.

Exclusion Criteria

I am not taking blood thinners.

I am under 18 years old.

I have epilepsy or a history of it.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants self-administer taVNS or sham-taVNS for 30 minutes daily for two weeks, with continuous ECG monitoring.

2 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• taVNS

Trial Overview The study tests if non-invasive ear stimulation (taVNS) can reduce heart rate in patients with persistent atrial fibrillation. Participants will self-administer taVNS daily and have their heart activity monitored to see if there's a difference in heart rate reduction.

How Is the Trial Designed?

Group I: Active Intervention Active Control 1 Intervention

Participants will self-administer active taVNS for 30 min per day for 7 days.

Group II: Sham Intervention Placebo Group 1 Intervention

Participants will self-administer sham-taVNS for 30 min per day for 7 days.

taVNS is already approved in United States, European Union for the following indications:

Approved in United States as Transcutaneous Auricular Vagus Nerve Stimulation for:

• Epilepsy
• Depression
• Obesity

Approved in European Union as Transcutaneous Auricular Vagus Nerve Stimulation for:

• Epilepsy
• Depression

Who Is Running the Clinical Trial?

Burrell College of Osteopathic Medicine

Lead Sponsor

Trials

6

Recruited

330+

Published Research Related to This Trial

Acupuncture at the auricular branch of the vagus nerve (ABVN) significantly reduced heart rate by approximately 4%-6% and increased heart rate variability (HRV) as measured by SDNN by about 19% in a study of 24 healthy male volunteers.

These results suggest that ABVN acupuncture may activate the parasympathetic nervous system, although the overall effects on other HRV parameters were modest and warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acupuncture at the auricular branch of the vagus nerve enhances heart rate variability in humans: An exploratory study. Boehmer, AA., Georgopoulos, S., Nagel, J., et al.[2022]

Noninvasive transcutaneous stimulation of the auricular branch of the vagus nerve (AB-VNS) significantly reduces spontaneous ventricular arrhythmias in beagle dogs after myocardial infarction, indicating its potential as an antiarrhythmic treatment.

AB-VNS enhances ventricular electrical stability and reduces ventricular interstitial fibrosis, although it does not improve overall cardiac function or reverse structural changes in the heart after 4 weeks of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation reduces ventricular arrhythmias and increases ventricular electrical stability. Nasi-Er, BG., Wenhui, Z., HuaXin, S., et al.[2019]

Transcutaneous auricular vagus nerve stimulation (taVNS) significantly improves depression symptoms, as evidenced by reduced scores on the Hamilton Depression Scale in a review of 12 studies involving 838 participants.

taVNS shows comparable response rates to traditional antidepressants and has fewer side effects, suggesting it could be a safe alternative or complementary treatment for depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of transcutaneous auricular vagus nerve stimulation in the treatment of depressive disorder: A systematic review and meta-analysis of randomized controlled trials. Tan, C., Qiao, M., Ma, Y., et al.[2023]

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]

Transcutaneous auricular Vagus Nerve Stimulation (taVNS) can be optimized by varying electrode designs, which significantly affects the sensitivity and selectivity of nerve activation in different regions of the ear, as shown through a detailed anatomical model and finite element analysis.

The study found that smaller electrodes increase the electric field strength for a given current, allowing for more targeted stimulation of specific ear regions, which is crucial for enhancing the efficacy of taVNS in clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-resolution computational modeling of the current flow in the outer ear during transcutaneous auricular Vagus Nerve Stimulation (taVNS). Kreisberg, E., Esmaeilpour, Z., Adair, D., et al.[2023]

Transcutaneous auricular vagus nerve stimulation (taVNS) is a safe and well-tolerated method for treating conditions like drug-resistant epilepsy, but a recent randomized double-blind trial found no significant difference in outcomes between high- and low-stimulation groups.

The most common side effect of taVNS is a tingling sensation or pain at the stimulation site, and while it shows promise, further research is needed to fully understand its efficacy and to potentially gain approval for insurance coverage in Japan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical Application of Transcutaneous Auricular Vagus Nerve Stimulation]. Yamamoto, T.[2022]

Transcutaneous auricular vagus nerve stimulation (TaVNS) effectively normalized gastric dysrhythmias in healthy individuals during a water-load test, indicating its potential as a treatment for gastric symptoms.

The study found that TaVNS at 40 Hz improved heart rate variability and reduced bloating, suggesting it positively influences both parasympathetic and sympathetic nervous system pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous Auricular Vagus Nerve Stimulation Normalizes Induced Gastric Myoelectrical Dysrhythmias in Controls Assessed by Body-Surface Gastric Mapping. Du, P., Maharjan, A., Calder, S., et al.[2023]

A systematic review of 261 studies revealed significant confusion in the nomenclature for transcutaneous stimulation of the auricular branch of the vagus nerve (ABVN), with 67 full and 27 abbreviated terms identified, highlighting the need for standardization.

The most commonly used terms were 'transcutaneous vagus nerve stimulation' and 'tVNS', but there was no consistent one-to-one relationship between full and abbreviated names, indicating a lack of uniformity in terminology across different research teams.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toward Diverse or Standardized: A Systematic Review Identifying Transcutaneous Stimulation of Auricular Branch of the Vagus Nerve in Nomenclature. Wang, Y., Li, L., Li, S., et al.[2023]

Transcutaneous auricular vagus nerve stimulation (taVNS) is generally safe, with a low incidence of mild and transient adverse effects, such as ear pain, headache, and tingling, reported in only 24.86% of the studies analyzed.

In a systematic review of 177 studies involving 6322 subjects, there was no significant difference in the risk of adverse events between taVNS and control groups, indicating that taVNS is a feasible option for clinical intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic review and meta-analysis. Kim, AY., Marduy, A., de Melo, PS., et al.[2023]

Citations

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

TRanscutaneous Electrical vAgus nerve sTimulation to ... Noninvasive neuromodulation using low level tragus stimulation (LLTS) significantly decreased atrial fibrillation (AF) burden and decreased tumor necrosis ...

2. 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 ...

3. elifesciences.org elifesciences.org/reviewed-preprints/100088v1/reviews

The effect of transcutaneous auricular vagus nerve ... The results showed that repetitive taVNS did not significantly alter heart rate, corrected QT interval, blood pressure, or intracranial pressure ...

4. 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 ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02548754

NCT02548754 | Transcutaneous Electrical Vagus Nerve ... These investigations will establish the first evidence of the long-term effects of LLTS on AF suppression in patients with paroxysmal AF and may provide the ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12061502/

Effects of Transcutaneous Auricular Vagus Nerve Stimulation ... After exclusion of an outlier, data of 15 participants were analyzed. In tests with taVNS, HR was significantly reduced at maximum exercise (136.0±9.7 vs. 132.0 ...

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

Safety and tolerability of Transcutaneous Vagus Nerve ... tVNS has been safe and well tolerated by research participants to date. · The most common side effect of tVNS was skin irritation (in 18.2%). · 35 (2.6%) tVNS ...

8. bmccomplementmedtherapies.biomedcentral.com bmccomplementmedtherapies.biomedcentral.com/articles/10.1186/s12906-024-04568-1

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.