The Effect of Different Low-Level Tragus Stimulation Parameters On Autonomic Nervous System Function

NCT04682704 | Recruiting DMC FDA Device

• 1 other identifier: 12708
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

Low level transcutaneous vagus nerve stimulation (LLTS) involves delivery of electrical impulses transcutaneously at the auricular branch of vagus nerve and it has been shown to have anti-inflammatory and anti-arrhythmic effects. In previous studies from our laboratory, we found that LLTS significantly suppressed atrial fibrillation (AF) inducibility and decreased AF duration. The anti-arrhythmic effects of LLTS were similar to those delivered to the cervical VN trunk. LLTS for just one hour significantly shortened the AF duration and decreased inflammatory cytokines. We have also shown that LLTS leads to favorable heart rate variability (HRV) changes and cardiac mechanics in patients with diastolic dysfunction. These results support the use of LLTS as a novel non-pharmacological, non-ablative treatment modality for AF and possibly other inflammatory conditions. However, the optimal stimulation parameters of LLTS remain to be determined. In this study, we aim to examine the effect of 2 different frequencies (5Hz and 20Hz) and 2 different amplitudes (50% below the pain threshold and 1mA below the pain threshold) of LLTS on heart rate variability with deep breathing (HRVdb), mental arithmetic stress test (MAST), frequency domain measures of heart rate variability (HRV) and brain stem evoked potentials (BSEVP) in healthy volunteers and patients with AF or heart failure with preserved ejection fraction (HFpEF). HRV is a marker of vagus nerve activity and can be easily measured by software calculating the distance between consecutive R waves on the ECG. BSEVP are a surrogate for the central projections of the vagus nerve. Patients will be randomized into 4 groups in a 2x2 factorial design. LLTS will be delivered through a transcutaneous electrical nerve stimulation (TENS) device for 15 minutes. HRVdb, HRV and BSEVP will be measured before and after LLTS and compared.

Conditions

Atrial Fibrillation; Heart Failure, Diastolic

Outcome Measures

Primary Outcomes (2)

• Heart rate variability

  Heart rate variability is a marker of vagus nerve activity and can be easily measured by PC-based ECG software calculating the distance between consecutive R waves on the ECG. Both time domain \[standard deviation of normal-to-normal intervals (SDNN), root mean square of successive differences of the normal-to-normal intervals (RMSSD)\] and frequency domain \[low frequency (LF; 0.04-0.15 Hz), high frequency (HF; 0.15-0.4 Hz), and LF/HF ratio\] measures will be analyzed.

  15 minutes

• Mental arithmetic stress test

  Mental arithmetic stress test is a measure of sympathetic activity and will be performed by asking the patient to consistently subtract 7 from 500 for a period of 2 minutes. Blood pressure will be measured before and after the test, before and during stimulation and the maximum blood pressure during the test will be the outcome of interest.

  15 minutes

Study Arms (4)

Frequency 20Hz; amplitude 1mA below discomfort threshold

EXPERIMENTAL

Patients will receive tragus stimulation for 15 minutes using the following settings: Frequency 20Hz; amplitude 1mA below discomfort threshold. Continuous ECG will be recorded to assess heart rate variability.

Device: Parasym

Frequency 5Hz; amplitude 1mA below discomfort threshold

ACTIVE COMPARATOR

Patients will receive tragus stimulation for 15 minutes using the following settings: Frequency 5Hz; amplitude 1mA below discomfort threshold. Continuous ECG will be recorded to assess heart rate variability.

Device: Parasym

Frequency 20Hz; amplitude 50% below discomfort threshold

ACTIVE COMPARATOR

Patients will receive tragus stimulation for 15 minutes using the following settings: Frequency 20Hz; amplitude 50% below discomfort threshold. Continuous ECG will be recorded to assess heart rate variability.

Device: Parasym

Frequency 5Hz; amplitude 50% below discomfort threshold

ACTIVE COMPARATOR

Patients will receive tragus stimulation for 15 minutes using the following settings: Frequency 5Hz; amplitude 50% below discomfort threshold. Continuous ECG will be recorded to assess heart rate variability.

Device: Parasym

Interventions

Parasym DEVICE

Tragus stimulation

Frequency 20Hz; amplitude 1mA below discomfort threshold; Frequency 20Hz; amplitude 50% below discomfort threshold; Frequency 5Hz; amplitude 1mA below discomfort threshold; Frequency 5Hz; amplitude 50% below discomfort threshold

Eligibility Criteria

• Age: 21 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients older than 21 year old
• Healthy volunteers free from diagnosis of AF, heart failure, coronary artery disease or diseases that affect the autonomic nervous system.
• Patients with Paroxysmal Atrial Fibrillation
• Patients with Heart Failure with Preserved Ejection Fraction (HFpEF)

You may not qualify if:

• Recent (\<6 months) stroke
• Recent (\<6 months) myocardial infarction
• Heart failure (NYHA class III or IV)
• Left ventricular ejection fraction \<50%
• Recurrent vaso-vagal syncopal episodes
• Unilateral or bilateral vagotomy
• Pregnancy or breast feeding
• Uncontrolled diabetes or hypertension
• Inability or unwillingness to understand and/or sign informed consent
• Any serious disease that affects autonomic nervous system function
• Any medications that affect autonomic nervous system function

Sponsors & Collaborators

• University of Oklahoma: lead

Study Sites (1)

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

MeSH Terms

Conditions

Atrial Fibrillation; Heart Failure, Diastolic

Condition Hierarchy (Ancestors)

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

Study Officials

• Stavros Stavrakis, MD, PhD

  University of Oklahoma

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Karrie Meeks

CONTACT

4052714742; karrie-meeks@ouhsc.edu

Study Design

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

Study Record Dates

• First Submitted: December 8, 2020
• First Posted: December 24, 2020
• Study Start: November 30, 2021
• Primary Completion: October 1, 2024
• Study Completion: February 1, 2025
• Last Updated: February 21, 2024

Record last verified: 2024-02

Locations

US (1)