Investigation of the Effect of Unilateral Right, Unilateral Left and Bilateral Applications of Transcutaneous Auricular Vagus Nerve Stimulation on Autonomic Nervous System Activity in Healthy People

The vagus nerve is one of the main components of the parasympathetic nervous system, which oversees a wide variety of important bodily functions, including mood control, immune response, digestion, and heart rate. It is the tenth cranial nerve originating from the medulla oblongata in the central nervous system and is the longest cranial nerve. It starts from the medulla and progresses to the colon. It mainly innervates the thoracic and abdominal organs. It has an obvious effect on the autonomic nervous system, especially on parasympathetic activity. When the literature is examined, it has been proven by various studies that vagus nerve stimulation has effects on the regulation of the autonomic system. Vagus nerve stimulation with different methods has been investigated over the years and the effectiveness of several different methods has been proven. There are both invasive and non-invasive (transcutaneous) techniques for vagus nerve stimulation. The first experiments were developed on invasive applications, and then non-invasive applications began to emerge.

Today, the most used devices and stimulation models were approved by the FDA in the 1990s for use in patients with drug-resistant epilepsy. In the middle of the first decade of the 2000s, the FDA approved the use of these devices for drug-resistant depression. These application methods have therapeutic effects for a wide variety of conditions, including heart failure, obesity, migraine, Alzheimer's, inflammation, chronic pain, and tinnitus. Invasive intervention is not necessary to perform this procedure. Direct stimulation of afferent nerve fibers in the ear can produce a similar effect without surgical intervention. Non-invasive vagus nerve stimulation may affect human physiology and be a simple and inexpensive alternative to invasive vagus stimulation. It has been shown on different subjects that non-invasive stimulation of the tragus in the ear increases the activation in the parasympathetic system and decreases the sympathetic activity. This indicates that tragus stimulation may be a viable treatment for some disorders in which autonomic activity is compromised.

While the general mechanism has been explained in this way, there is no definite information in the literature about which ear from the right single ear, double ear or left single ear will be applied in Transcutaneous Auricular Vagus Nerve Stimulation applications. While specifying the application techniques, an objective scientific study about whether there is a difference between Unilateral Right, Unilateral Left and Bilateral Applications or which of them gives more effective results will be a guide for further studies. The purpose of the study, planning to carry out is to seek an answer to one of the questions that come to mind for standardization. The main question we seek to answer is whether there is a difference between Unilateral Right, Unilateral Left and Bilateral Applications while specifying the application techniques, or which of them gives more effective results. This studies main goal is to set up this study in order to seek answers about which application style will produce results and to provide a guide for further studies.

Study Overview

• Status: Not yet recruiting
• Conditions: Health, Subjective
• Intervention / Treatment: Device: Transcutaneous Auricular Vagus Nerve Stimulation

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Berkay Eren E. PEHLIVANOGLU, MSc, PhD(c); Phone Number: Tur 00905073337972; Email: fzt.berkayerenpehlivanoglu@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Volunteering to participate in the study
• Have signed the informed consent form
• The volunteer has no disease before or during the study
• Absence of menstrual cycle period in female volunteers
• The subject did not drink alcohol 24 hours before the study

Exclusion Criteria:

• Cases unwilling to continue the study.
• Having a respiratory disease and starting to use drugs
• Having a disease related to the cardiac system and starting to use drugs
• The presence of any chronic disease and the use of a drug related to it

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1st Group; With the vagustim device, the application will be made first from the left ear. Then, a 48-hour break will be taken and the application will be made from the right ear. Then, the application will be performed on both ears with a 48-hour break.	Device: Transcutaneous Auricular Vagus Nerve Stimulation; Vagus nerve stimulation will be applied with the Vagustim device for 20 (10+10) minutes, with a biphasic frequency, a frequency of 10 Hz, a pulse width of 300 μs in Modulation mode, and a constant current intensity where the participant feels the current comfortably.
Experimental: 2nd Group; With the vagustim device, the application will be made first from the left ear. Then, a 48-hour break will be made and the application will be made from both ears. Then, the application will be performed on the right ear with a break for 48 hours.	Device: Transcutaneous Auricular Vagus Nerve Stimulation; Vagus nerve stimulation will be applied with the Vagustim device for 20 (10+10) minutes, with a biphasic frequency, a frequency of 10 Hz, a pulse width of 300 μs in Modulation mode, and a constant current intensity where the participant feels the current comfortably.
Experimental: 3rd Group; With the vagustim device, the application will be made first from the right ear. Then, a 48-hour break will be taken and the application will be made from the left ear. Then, the application will be performed on both ears with a 48-hour break.	Device: Transcutaneous Auricular Vagus Nerve Stimulation; Vagus nerve stimulation will be applied with the Vagustim device for 20 (10+10) minutes, with a biphasic frequency, a frequency of 10 Hz, a pulse width of 300 μs in Modulation mode, and a constant current intensity where the participant feels the current comfortably.
Experimental: 4th Group; With the vagustim device, the application will be made first from the right ear. Then, a 48-hour break will be made and the application will be made from both ears. Then, the application will be performed on the left ear with a break for 48 hours.	Device: Transcutaneous Auricular Vagus Nerve Stimulation; Vagus nerve stimulation will be applied with the Vagustim device for 20 (10+10) minutes, with a biphasic frequency, a frequency of 10 Hz, a pulse width of 300 μs in Modulation mode, and a constant current intensity where the participant feels the current comfortably.
Experimental: 5th Group; With the vagustim device, the application will be made from both ears first. Then, a 48-hour break will be made and the application will be made from the left ear. Then, the application will be performed on the right ear with a break for 48 hours.	Device: Transcutaneous Auricular Vagus Nerve Stimulation; Vagus nerve stimulation will be applied with the Vagustim device for 20 (10+10) minutes, with a biphasic frequency, a frequency of 10 Hz, a pulse width of 300 μs in Modulation mode, and a constant current intensity where the participant feels the current comfortably.
Experimental: 6th Group; With the vagustim device, the application will be made from both ears first. Then, a 48-hour break will be made and the application will be made from the right ear. Then, the application will be performed on the left ear with a break for 48 hours.	Device: Transcutaneous Auricular Vagus Nerve Stimulation; Vagus nerve stimulation will be applied with the Vagustim device for 20 (10+10) minutes, with a biphasic frequency, a frequency of 10 Hz, a pulse width of 300 μs in Modulation mode, and a constant current intensity where the participant feels the current comfortably.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heart Rate	Omron Hem 7321 E M6 device will be used to measure heart rate	Up to 1 week
Systolic and Diastolic Blood Pressure	Omron Hem 7321 E M6 device will be used to measure Systolic and Diastolic Blood Pressure	Up to 1 week
Evaluation of Galvanic Skin Resistance	Bogazici University GSR device will be used to measure Galvanic Skin Resistance	Up to 1 week
Heart Rate Variability	Elite HRV device will be used to measure Heart Rate Variability	Up to 1 week

Collaborators and Investigators

• Sponsor: Bahçeşehir University

Study record dates

Study Major Dates

• Study Start (Anticipated): July 15, 2022
• Primary Completion (Anticipated): August 30, 2022
• Study Completion (Anticipated): September 15, 2022

Study Registration Dates

• First Submitted: April 26, 2022
• First Submitted That Met QC Criteria: May 6, 2022
• First Posted (Actual): May 11, 2022

Study Record Updates

• Last Update Posted (Actual): June 15, 2022
• Last Update Submitted That Met QC Criteria: June 14, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: transcutaneous auricular vagus nerve stimulation; vagus nerve stimulation; vagus nerve
• Other Study ID Numbers: BahcesehirU_B.Pehlivanoglu001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No