Transcutaneous Electrical Vagus Nerve Stimulation to Suppress Atrial Fibrillation

NCT ID: NCT02548754

Last Updated: 2022-02-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 53 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-12-31
• Study Completion Date: 2020-03-31

Brief Summary

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.

Conditions

Atrial Fibrillation; Inflammation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Active

Patients will receive 1 hour of active low level tragus stimulation daily for 6 months

Group Type: EXPERIMENTAL

Parasym device

Intervention Type: DEVICE

Sham

Patients will receive 1 hour of sham low level tragus stimulation daily for 6 months

Group Type: SHAM_COMPARATOR

Parasym device

Intervention Type: DEVICE

Interventions

Parasym device

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

1. Male and female patients older than 21 year old

2. Paroxysmal AF

Exclusion Criteria

1. Left ventricular dysfunction (Left ventricular ejection fraction <40%)

2. Significant valvular disorder (i.e., prosthetic valve or hemodynamically relevant valvular diseases)

3. Recent (<6 months) stroke or myocardial infarction

4. Severe heart failure (NYHA IV)

5. Left atrial dilatation (>55mm)

6. Recurrent vaso-vagal syncopal episodes

7. Unilateral or bilateral vagotomy

8. Pregnancy or breast feeding

9. Sick sinus syndrome, 2nd or 3rd degree AV block, bifascicular block or prolonged (PR>300ms) 1st degree AV block.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

American Heart Association

OTHER

Sponsor Role: collaborator

University of Oklahoma

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stavros Stavrakis, MD

Role: PRINCIPAL_INVESTIGATOR

University of Oklahoma

Locations

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Countries

United States

References

Stavrakis S, Stoner JA, Humphrey MB, Morris L, Filiberti A, Reynolds JC, Elkholey K, Javed I, Twidale N, Riha P, Varahan S, Scherlag BJ, Jackman WM, Dasari TW, Po SS. TREAT AF (Transcutaneous Electrical Vagus Nerve Stimulation to Suppress Atrial Fibrillation): A Randomized Clinical Trial. JACC Clin Electrophysiol. 2020 Mar;6(3):282-291. doi: 10.1016/j.jacep.2019.11.008. Epub 2020 Jan 29.

Reference Type: DERIVED

PMID: 32192678 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

15MCPRP25790001

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

RSRCH135160

Identifier Type: -

Identifier Source: org_study_id