Transcutaneous Electrical Vagus Nerve Stimulation to Suppress Atrial Fibrillation

Study Overview
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Brief Summary
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Atrial fibrillation (AF) is the most common cardiac arrhythmia. In previous experimental studies, the investigators found that low-level vagus nerve (VN) stimulation (LLVNS), at voltages substantially below that which slowed the sinus rate, significantly suppressed AF inducibility and decreased AF duration. The investigators subsequently developed a non-invasive neuromodulatory therapy, in which LLVNS was delivered to the auricular branch of the VN located at the tragus, the anterior protuberance of the outer canine ear (low level tragus stimulation; LLTS). The anti-arrhythmic effects of LLTS were similar to those of LLVNS delivered to the cervical VN trunk. More recently, in a proof-of-concept study in humans, the investigators showed that in patients with drug-refractory AF undergoing AF ablation, LLTS for just one hour significantly shortened the AF duration and decreased inflammatory cytokines. The overall objective of this proposal is to translate in ambulatory patients with paroxysmal AF the results of previous studies showing acute suppression of AF and inflammation in anesthetized canines as well as humans, in order to examine the long-term therapeutic effects of this approach. The investigators hypothesize that intermittent (1 hour daily) LLTS for 6 months may result in long-term decrease of AF burden and suppression inflammatory cytokines in patients with paroxysmal AF. Patients will be randomized to either active or sham LLTS. LLTS will be delivered through a transcutaneous electrical nerve stimulation (TENS) device for 1 hour daily over a 6-month period. AF burden will be defined as the percent of time spent in AF over a 2-week period, assessed by noninvasive continuous ECG monitoring at baseline and at 6 months. In addition, blood samples will be collected from patients at baseline, and at 3 and 6 months, for cytokine measurement. 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 basis for a potential expansion of the therapeutic targets of this treatment modality beyond AF.

Official Title
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TRanscutaneous Electrical vAgus Nerve sTimulation to Suppress Atrial Fibrillation

Conditions
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Atrial Fibrillation, Inflammation

Intervention / Treatment
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* Device: Parasym device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients older than 21 year old Paroxysmal AF Exclusion Criteria: Left ventricular dysfunction (Left ventricular ejection fraction <40%) Significant valvular disorder (i.e., prosthetic valve or hemodynamically relevant valvular diseases) Recent (<6 months) stroke or myocardial infarction Severe heart failure (NYHA IV) Left atrial dilatation (>55mm) Recurrent vaso-vagal syncopal episodes Unilateral or bilateral vagotomy Pregnancy or breast feeding Sick sinus syndrome, 2nd or 3rd degree AV block, bifascicular block or prolonged (PR>300ms) 1st degree AV block.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active<br>Patients will receive 1 hour of active low level tragus stimulation daily for 6 months | Device: Parasym device<br> <br> |
| Sham Comparator: Sham<br>Patients will receive 1 hour of sham low level tragus stimulation daily for 6 months | Device: Parasym device<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Atrial Fibrillation Burden | Percent time spent in atrial fibrillation | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Markers of Inflammation | Serum levels of tumor necrosis factor-alpha | 6 months | 
| Markers of Inflammation | Serum levels of inteleukin 6 | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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atrial fibrillation, neuromodulation, inflammation