Clinical trial NCT04909528: LLTS to Treat Premature Ventricular Contractions
Official title: Transcutaneous Electrical Vagus Nerve Stimulation to Suppress Premature Ventricular Contractions
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Premature Ventricular Contraction
Keywords: Premature Ventricular Contraction
Low-level Tragus Stimulation
autonomic nerve modulation
Lead sponsor: The First Affiliated Hospital with Nanjing Medical University
Sponsor class: OTHER
Collaborators: name: University of Oklahoma
name: The Affiliated Hospital of Xuzhou Medical University
name: Wuxi No. 2 People's Hospital
name: The First People's Hospital of Changzhou
name: Second Affiliated Hospital of Nantong University
name: Affiliated Hospital of Nantong University
name: Geriatric Hospital of Nanjing Medical University
name: First Affiliated Hospital of Wannan Medical College
name: Jiangsu Taizhou People's Hospital
First posted: 2021-06-01
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This randomized control trial is designed to explore the effect of low-level tragus stimulation in patients with frequent premature ventricular contractions.

Detailed description: Background Premature ventricular contraction (PVC), also known as premature ventricular beat, is one of the most common symptomatic arrhythmias in clinical practice. PVCs may cause serious harm to patients as follow: 1. PVCs with considerable load can increase the incidence of cardiomyopathy; 2. Some recurrent malignant arrhythmias, such as ventricular tachycardia and ventricular fibrillation, can be induced by PVCs; 3. cardiac resynchronization therapy-pacing/defibrillator non-responders may be due to frequent PVCs, which reduce the proportion of biventricular pacing; 4. For structural heart disease patients, PVCs may make their damaged heart function further deteriorated. At present, the clinical treatment of PVCs is still based on drugs, such as beta-blockers, mexiletine, propafenone, etc., and their effectiveness varies greatly among individuals. The status of catheter ablation in the treatment of ventricular premature beats continuous improvement, but this is an invasive operation and relatively expensive, which limits its wide application in clinical practice. Recent studies have shown that the autonomic nervous system plays an important role in the occurrence and maintenance of ventricular arrhythmia. Relevant studies have confirmed that the onset of ventricular arrhythmia is related to sympathetic nerve excitement. Moreover, inhibiting sympathetic nerve activity, including anesthesia, sympathetic nerve block, sympathetic nerve denervation, etc., can effectively reduce the onset and burden of ventricular arrhythmia. On the other hand, in patients with myocardial ischemia-related ventricular arrhythmia, atrial arrhythmia, and heart failure, the safety and effectiveness of the treatment of vagus nerve stimulation have also been verified. Low-level tragus stimulation (LLTS) is an emerging method of regulating autonomic nerves. Functional cardiac magnetic resonance studies have confirmed that by stimulating the auricle branch of the vagus nerve distributed in the tragus of the outer ear, the central projection of the vagus nerve in the brainstem and other higher centers can be activated. It is worth noting that LLTS has been used in clinical practice to treat tinnitus and epilepsy. Moreover, recent studies have confirmed that LLTS can reduce sympathetic nerve activity, inhibit inflammatory factors, and reduce the atrial fibrillation burden in patients with paroxysmal atrial fibrillation.

Aim of the Study The current trial is designed to explore the effect of low-level tragus stimulation in patients with frequent premature ventricular contractions.

Study Design This is a randomized, prospective, parallel, single-blind multicenter design. The enrollment target for this investigation is 100 patients. Patients are randomized in a 1:1 fashion into one of the investigation arms: active and sham LLTS group. Active LLTSs are performed using a transcutaneous vagus nerve stimulation device (Parasym device, Parasym Health, London, United Kingdom) with an ear clip attached to the tragus of the right ear. In the sham group, the clips are attached to the ear lobe and regarded as effectless to vagus nerve. At baseline, 3 months, and 6 months, patients underwent noninvasive continuous ECG monitoring for 10 days to evaluate their PVC burden (deﬁned as the percentage of premature ventricular beats in total heart beats) using an adhesive continuous ECG patch. Heart rate variability, quality of life, skin sympathetic nerve activity and serum cytokine measurement are evaluated at baseline and follow-up.

Eligibility criteria: Inclusion Criteria:

* Age \>18, \<80 of age
* Symptomatic PVCs refractory to ≥1 antiarrhythmic drugs (including β-blockers and calcium-channel blockers).
* PVC burden ≥ 10%, with or without prior ablation
* Arrhythmias originated from any focus (foci) in the right ventricular or left ventricular.

Exclusion Criteria:

* Left ventricular ejection fraction (LVEF) \< 45% unless proven to be PVC-mediated cardiomyopathy (history of improving LVEF by \>15% when PVC burden was reduced by pharmacological agents or ablation)
* EF continues to decrease in the past 4 months regardless of the etiology
* Unwilling to continue current pharmacological therapy during the study period
* Severe heart failure with New York Heart Association Class ≥ III
* Ventricular arrhythmias attributed to underlying structural heart disease, known myocardial scar or myocarditis
* Change of anti-arrhythmic drug dosing, including β-blockers and calcium channel blockers, within 2 months prior to enrollment
* \< 3 months after prior unsuccessful ablation:
* Patients on amiodarone
* Patients with known thyroid issues, on renal-dialysis
* life expectancy of \< 12 months
* Sustained ventricular tachycardia

Primary outcomes:
measure: PVC burden
timeFrame: 3 months follow-up
measure: PVC burden
timeFrame: 6 months follow-up
Secondary outcomes:
measure: Questionnaire to score severity of symptoms and quality of life
timeFrame: 3 months and 6 months follow-up
measure: Serum cytokine marker
timeFrame: 3 months and 6 months follow-up
measure: Serum cytokine marker
timeFrame: 3 months and 6 months follow-up
measure: Skin sympathetic nerve activity
timeFrame: 3 months and 6 months follow-up
measure: Treatment compliance
timeFrame: 3 months and 6 months follow-up
measure: Number of participants with adverse effects
timeFrame: 3 months and 6 months follow-up
measure: Heart rate variability
timeFrame: 3 months and 6 months follow-up
Other outcomes:
Locations:
city: Nanjing
country: China
facility: The First Affiliated Hospital of Nanjing Medical University
state: Jiangsu
Study officials:
References: