Transcutaneous Electrical Vagus Nerve Stimulation to Suppress Atrial Fibrillation

NCT02548754 | Completed Results DMC

• 2 other identifiers: RSRCH13516015MCPRP25790001
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

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

Keywords

atrial fibrillation; neuromodulation; inflammation

Outcome Measures

Primary Outcomes (1)

• Atrial Fibrillation Burden

  Percent time spent in atrial fibrillation

  6 months

Secondary Outcomes (2)

• Markers of Inflammation

  6 months

• Markers of Inflammation

  6 months

Study Arms (2)

Active

EXPERIMENTAL

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

Device: Parasym device

Sham

SHAM COMPARATOR

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

Device: Parasym device

Interventions

Parasym device DEVICE

Active; Sham

Eligibility Criteria

• Age: 21 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients older than 21 year old
• Paroxysmal AF

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Oklahoma: lead
• American Heart Association: collaborator

Study Sites (1)

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Related Publications (1)

• 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.

  PMID: 32192678 DERIVED

MeSH Terms

Conditions

Atrial Fibrillation; Inflammation

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr. Stavros Stavrakis
• Organization: University of Oklahoma Health Sciences Center

stavros-stavrakis@ouhsc.edu

4052714742

Study Officials

• Stavros Stavrakis, MD

  University of Oklahoma

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2015
• First Posted: September 14, 2015
• Study Start: December 1, 2016
• Primary Completion: May 1, 2019
• Study Completion: March 1, 2020
• Last Updated: February 16, 2022
• Results First Posted: April 24, 2020

Record last verified: 2022-01

Locations

US (1)