Biomarker-Guided Optimization of Transcutaneous Vagal Stimulation for Atrial (BiG tVNS-AF)

NCT ID: NCT05172765

Last Updated: 2024-03-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 160 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-09-14
• Study Completion Date: 2026-05-29

Brief 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.

Detailed 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.

Conditions

Paroxysmal Atrial Fibrillation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Active TENS Stimulation

Group Type: ACTIVE_COMPARATOR

Transcutaneous Electrical Nerve Stimulation Device

Intervention Type: DEVICE

Low-level, electrical stimulation of the outer ear (LLTS), using a transcutaneous electrical nerve stimulation (TENS) device.

Inactive TENS Stimulation

Group Type: SHAM_COMPARATOR

Transcutaneous Electrical Nerve Stimulation Device

Intervention Type: DEVICE

Low-level, electrical stimulation of the outer ear (LLTS), using a transcutaneous electrical nerve stimulation (TENS) device.

Interventions

Transcutaneous Electrical Nerve Stimulation Device

Low-level, electrical stimulation of the outer ear (LLTS), using a transcutaneous electrical nerve stimulation (TENS) device.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

1. Paroxysmal atrial fibrillation

Exclusion Criteria

1. Sick sinus syndrome

2. 2nd and 3rd degree AV block (without pacemaker), bifascicular block or prolonged (PR>300ms) 1st degree AV block

3. History of vagotomy

4. Recurrent vasovagal syncope

5. Left ventricular ejection fraction < 40%

6. Significant valvular disorder (i.e., prosthetic valve or hemodynamic significant valvular diseases)

7. Recent stroke (< 3 months)

8. Myocardial infarction or hospitalization for heart failure (< 3 months)

9. Severe heart failure (NYHA Class IV)

10. End stage kidney disease on dialysis

11. Pregnancy

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

Sponsors

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

Site Status: RECRUITING

Countries

United States

Central Contacts

Natalia Wells-Serrano

Role: CONTACT

Natalia-WellsSerrano@ouhsc.edu

405-271-4742

Facility Contacts

Stavros Stavrakis, MD

Role: primary

Stavros-Stavrakis@ouhsc.edu

405-271-9696

Other Identifiers

13786

Identifier Type: -

Identifier Source: org_study_id