Clinical trial NCT02548754: Transcutaneous Electrical Vagus Nerve Stimulation to Suppress Atrial Fibrillation
Official title: TRanscutaneous Electrical vAgus Nerve sTimulation to Suppress Atrial Fibrillation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Atrial Fibrillation
Inflammation
Keywords: atrial fibrillation
neuromodulation
inflammation
Lead sponsor: University of Oklahoma
Sponsor class: OTHER
Collaborators: name: American Heart Association
First posted: 2015-09-14
Enrollment: 53
Sex: ALL
Minimum age (years): 21
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Atrial Fibrillation Burden
timeFrame: 6 months
Secondary outcomes:
measure: Markers of Inflammation
timeFrame: 6 months
measure: Markers of Inflammation
timeFrame: 6 months
Other outcomes:
Locations:
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
Study officials:
affiliation: University of Oklahoma
name: Stavros Stavrakis, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.