Atrial Fibrillation, Inflammation
Conditions
Keywords
atrial fibrillation, neuromodulation, inflammation
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.
Interventions
DEVICEParasym device
Sponsors
American Heart Association
University of Oklahoma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 90 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Atrial Fibrillation Burden | 6 months | Percent time spent in atrial fibrillation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Markers of Inflammation | 6 months | Serum levels of tumor necrosis factor-alpha |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active Patients will receive 1 hour of active low level tragus stimulation daily for 6 months
Parasym device | 26 |
| Sham Patients will receive 1 hour of sham low level tragus stimulation daily for 6 months
Parasym device | 27 |
| Total | 53 |
Baseline characteristics
| Characteristic | Total | Sham | Active |
|---|---|---|---|
| AF burden | 2.5 % | 1 % | 4.5 % |
| Age, Continuous | 67 years STANDARD_DEVIATION 12 | 68 years STANDARD_DEVIATION 11 | 65 years STANDARD_DEVIATION 15 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 49 Participants | 24 Participants | 25 Participants |
| Sex: Female, Male Female | 29 Participants | 15 Participants | 14 Participants |
| Sex: Female, Male Male | 24 Participants | 12 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 26 | 2 / 27 |
| other Total, other adverse events | 0 / 26 | 0 / 27 |
| serious Total, serious adverse events | 0 / 26 | 0 / 27 |
Outcome results
Primary
Atrial Fibrillation Burden
Percent time spent in atrial fibrillation
Time frame: 6 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Active | Atrial Fibrillation Burden | 2 Percent time spent in atrial fibrillatio |
| Sham | Atrial Fibrillation Burden | 8.5 Percent time spent in atrial fibrillatio |
Secondary
Markers of Inflammation
Serum levels of tumor necrosis factor-alpha
Time frame: 6 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Active | Markers of Inflammation | 5.5 pg/ml |
| Sham | Markers of Inflammation | 5.4 pg/ml |
Secondary
Markers of Inflammation
Serum levels of inteleukin 6
Time frame: 6 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Active | Markers of Inflammation | 1.5 pg/ml |
| Sham | Markers of Inflammation | 2.3 pg/ml |