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The Effect of Different Low-Level Tragus Stimulation Parameters On Autonomic Nervous System Function (LLT-SPANS)

Primary Purpose

Atrial Fibrillation, Heart Failure, Diastolic

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Parasym
Sponsored by
University of Oklahoma
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Atrial Fibrillation

Eligibility Criteria

21 Years - 90 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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

Sites / Locations

  • University of Oklahoma Health Sciences CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Active Comparator

Active Comparator

Active Comparator

Arm Label

Frequency 20Hz; amplitude 1mA below discomfort threshold

Frequency 5Hz; amplitude 1mA below discomfort threshold

Frequency 20Hz; amplitude 50% below discomfort threshold

Frequency 5Hz; amplitude 50% below discomfort threshold

Arm Description

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

Full Information

First Posted
December 8, 2020
Last Updated
May 8, 2023
Sponsor
University of Oklahoma
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1. Study Identification

Unique Protocol Identification Number
NCT04682704
Brief Title
The Effect of Different Low-Level Tragus Stimulation Parameters On Autonomic Nervous System Function
Acronym
LLT-SPANS
Official Title
The Effect of Different Low-Level Tragus Stimulation Parameters On Autonomic Nervous System Function
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 30, 2021 (Actual)
Primary Completion Date
October 2023 (Anticipated)
Study Completion Date
February 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Oklahoma

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atrial Fibrillation, Heart Failure, Diastolic

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
90 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Frequency 20Hz; amplitude 1mA below discomfort threshold
Arm Type
Experimental
Arm Description
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.
Arm Title
Frequency 5Hz; amplitude 1mA below discomfort threshold
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Frequency 20Hz; amplitude 50% below discomfort threshold
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Frequency 5Hz; amplitude 50% below discomfort threshold
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
Parasym
Intervention Description
Tragus stimulation
Primary Outcome Measure Information:
Title
Heart rate variability
Description
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.
Time Frame
15 minutes
Title
Mental arithmetic stress test
Description
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.
Time Frame
15 minutes

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 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) Exclusion Criteria: 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Karrie Meeks
Phone
4052714742
Email
karrie-meeks@ouhsc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stavros Stavrakis, MD, PhD
Organizational Affiliation
University of Oklahoma
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Oklahoma Health Sciences Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Brittany Karfonta, RN
Phone
405-271-2229
Email
brittany-karfonta@ouhsc.edu
First Name & Middle Initial & Last Name & Degree
Karrie Meeks, CCRP
Phone
405-271-2229
Email
karrie-meeks@ouhsc.edu
First Name & Middle Initial & Last Name & Degree
Stavros Stavrakis, MD, PhD

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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

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