Vagal Nerve Stimulation for the Treatment of Persistent AF

Study Overview
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Brief Summary
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The goal of this clinical trial is to answer the question whether a transcutaneous stimulation of a certain nerve (Nervus vagus) with a dedicated device reduces the recurrence of the heart rhythm disorder atrial fibrillation. Participants will receive a dedicated nerval stimulation device and will treat themselves on a daily basis for at least an hour per day. Treatment will last for 3 months. Researchers will compare this group with a similar group that uses an ineffective device. Both researcher and patients will be blinded so they do not know which device they will be using.

Detailed Description
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This study is an investigator-initiated, monocentric, randomised, controlled and blinded trial. Patients with persistent atrial fibrillation and planned electrical cardioversion will be included. The participants are randomised to one of two groups - the verum-group or the sham-group. Both groups receive a dedicated stimulation device that stimulates transcutaneously the Ramus auricularis of the Nervus vagus at the area of the Tragus. The verum-group will receive an effective stimulation and the sham-group an ineffective one. The aim of this trial is to evaluate whether this stimulation could reduce the recurrence of atrial fibrillation or not. Therefore daily stimulation of at least one hour will be performed for overall three months. After that period the stimulation will be withdrawn and both groups will be compared. Then, after another three months without stimulation both groups will be compared again to evaluate if a potential effect of the initial stimulation persists.

Official Title
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Transcutaneous Vagal Nerve Stimulation for the Treatment of Persistent Atrial Fibrillation (VAST-AF): a Randomized, Controlled, Blinded, Monocentric, Clinical Trial

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Device: Vagal stimulation with the device tVNS from tVNS Technologies GmbH
* Device: Sham stimulation with the device tVNS from tVNS Technologies GmbH


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Persistent atrial fibrillation Planned electric cardioversion Sufficient oral anticoagulation for at least four weeks or Absence of thrombus in transoesophageal echocardiography Oral anticoagulation possible Able to sign informed consent Estimated life expectancy >1 year Exclusion Criteria: Permanent atrial fibrillation Ablation therapy of supraventricular arrhythmias in the past Missing anticoagulation respective missing rule out of thrombus Inability to treat with oral anticoagulation Latent or manifest hyperthyroidism Acute infection with relevant clinical signs (temp > 38°C, significant elevated C-reactive protein or white blood cells) Inability to sign informed consent Preexisting pacemaker or implantable cardioverter defibrillator Recent vagal stimulation for other causes Recent intolerance of transcutaneous vagal stimulation Estimated life expectancy <1 year Acute coronary syndrome Haemodynamic instability Valvular atrial fibrillation Pregnancy

Ages Eligible for Study
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Minimum Age: 18 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Verum group<br>Verum group - active vagal stimulation with the stimulation device tVNS from tVNS Technologies GmbH. The stimulation is performed with an ear-electrode at the Tragus. Minimal stimulation duration is 1 hour per day for 3 months. | Device: Vagal stimulation with the device tVNS from tVNS Technologies GmbH<br>* The tVNS device is used to stimulate the Ramus auricularis of the Nervus vagus with a dedicated ear electrode for at least one hour per day on a daily basis. Stimulation frequency is 20Hz, pulsewidth is 200µs and amplitude is determined individually.<br>|
| Sham Comparator: Sham group<br>Sham group with ineffective vagal stimulation. Same stimulation procedure like in the verum group with the stimulation device tVNS from tVNS Technologies GmbH. The stimulation is performed with an ear-electrode at the Tragus, too. Minimal stimulation duration is 1 hour per day for 3 months, but with a non conducting ear electrode. | Device: Sham stimulation with the device tVNS from tVNS Technologies GmbH<br>* The tVNS device is used to stimulate the Ramus auricularis of the Nervus vagus with a dedicated ear electrode for at least one hour per day on a daily basis. In this case to perform a sham stimulation a non conducting ear electrode is used. The device is set to the same settings with a frequency of 20Hz, a pulsewidth of 200µs and an amplitude that is determined individually.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence of atrial fibrillation | Defined as an episode of atrial fibrillation >30 seconds that is detected with ECG, holter-ECG or wearable (i.e. Apple Watch). ECGs are performed during follow-up visits or could be conducted by an other hospital or during an ambulatory medical contact. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of symptoms due to atrial fibrillation | Assessed with the Atrial Fibrillation Severity Scale: AFSS V2 | 6 months | 
| Significant alterations of parameters of the autonomous nervous system | Different parameters of the autonomous nervous system like heart rate variability and heart rate turbulence etc. are analyzed via ECG | 6 months | 
| Delay in recurrence of atrial fibrillation due to vagal stimulation | Comparison of the time interval to the first recurrence of atrial fibrillation between both groups | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atrial Fibrillation, Vagal stimulation, Transcutaneous nerve stimulation, Autonomic nervous system, parasympathetic nervous system