Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05172765 |
| Other study ID # |
13786 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
September 14, 2022 |
| Est. completion date |
May 29, 2026 |
Study information
| Verified date |
March 2024 |
| Source |
University of Oklahoma |
| Contact |
Natalia Wells-Serrano |
| Phone |
405-271-4742 |
| Email |
Natalia-WellsSerrano[@]ouhsc.edu |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
This proposal aims to determine the effects of tVNS on autonomic tone, atrial substrate and
neuromodulators in patients with paroxysmal atrial fibrillation (AF), investigate the chronic
effects of optimal tVNS on AF burden in patients with paroxysmal AF over a 6-month period,
compared with sham stimulation, and identify physiological and biochemical markers of
response to chronic tVNS.
Description:
This proposal aims to 1. To determine the effects of tVNS on autonomic tone, atrial substrate
and neuromodulators in patients with paroxysmal atrial fibrillation (AF), 2. Investigate the
chronic effects of optimal tVNS on AF burden in patients with paroxysmal AF over a 6-month
period, compared with sham stimulation, and 3. To identify physiological and biochemical
markers of response to chronic tVNS. For Aim 1, patients with paroxysmal AF will be
randomized to a series of stimulation frequencies (5Hz, 10Hz, 20Hz) and intensities (50%
below, and 1mA lower than, the discomfort threshold, respectively) in a cross-over design, to
define optimal effects and 'dosing' of tVNS. Heart rate variability, a marker of autonomic
tone and PWA, will be derived from 5-minute ECG. A subgroup of these patients, who present to
the Electrophysiology laboratory for AF ablation, will be randomized to active or sham tVNS,
using the optimal parameters determined above, for 5 minutes prior to any ablation, under
baseline conditions, during isoproterenol or atropine infusion, and their combination. PWA
will be estimated based on a 5-min ECG. The level of NPY will be measured from peripheral
vein and coronary sinus samples. In this this Aim we will determine the optimal parameters
for tVNS, and if the response to tVNS is dependent on the underlying autonomic tone. For Aim
2, Patients with paroxysmal AF not undergoing ablation, will be randomized to active tVNS (1
hour or 30 minutes, daily) or sham tVNS (1 hour daily) for 6 months, using the optimal tVNS
parameters determined in Aim 1. AF burden will be monitored continuously using a smartwatch.
In addition, all patients will receive a short trial of acute tVNS at baseline. This Aim will
determine the minimum duration of tVNS needed to achieve a decrease in AF burden. Patients
participating in the clinical trial described in Aim 2, will comprise the population of Aim
3. The hypothesis is that patients who respond acutely to tVNS at baseline, as assessed by
PWA, are more likely to benefit from chronic tVNS therapy. Blood samples will be collected
from patients participating in Aim 2, and their NPY levels and metabolomic profile will be
correlated with AF burden. The results of these studies will first, provide insights into the
effects of tVNS on autonomic tone, AF substrate and neuromodulators, and second, permit
optimization of tVNS using PWA, NPY and metabolomic biomarkers to reduce AF burden of
afflicted patients. By introducing an optimized tVNS treatment protocol, results from our
proposed studies have the potential to overturn the current scientific paradigm for treatment
of AF, and thus, lead to major improvements in health care delivery.
