Effect of (TaVNS) on Anxiety and Brain Function in Distressed Health Care Workers

NCT05132881 | Active Not Recruiting

• 1 other identifier: 221D.069
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research is to measure alterations in anxiety and brain activity associated with the use of an approved health device called Transauricular Vagal Nerve Stimulation (TaVNS) in distressed persons who work in a health care and distressed healthcare workers in the the Philadelphia, PA region. The Investigators will be using functional magnetic resonance imaging (or fMRI) to measure changes in each subject's brain function during the use of VNS. This study is designed to allow researchers to understand the changes in cerebral (brain) activity that occur when a subject uses VNS. Thus, the primary goal of the proposed study is to evaluate the ability of the TaVNS system to reduce distress and change neurophysiology among health care providers. The Investigators, hypothesize that using the TaVNS device will help reduce distress in individuals. In order to understand the mechanisms of change that occur while using the VNS study, the Investigators have added a substudy of participants who do not experience high levels of distress to evaluate the effects of the functional changes that may occur in the brain while using the TaVNS device. In addition to the primary aims of the overalll study to assess distress in workers while enrolled in a TaVNS program, a subgroup of 50 subjects will undergo functional magnetic resonance imaging (fMRI) while using the VNS device to assess the changes in the brain including neurophysiological effects of TaVNS. The goal of this substudy is to observe the changes in the brain while using the TaVNS earbuds in the MRI to increase our understanding of the mechanisms and processing involved while using TaVNS. In this substudy, which is amendment version 3.0, the investigators have increased the number of persons to include 50 subjects who will use the device in the MRI to evaluate the neural processes and cerebral blood flow while using TaVNS.

Conditions

Anxiety; Distress, Emotional; Effects of Vibration; Healthy

Keywords

Vagal Nerve Stimulation; Distressed Workers; Work-related Stress; Magnetic Resonance Imaging (MRI); Functional Magnetic Resonance Imaging (fMRI); Healthy Controls

Outcome Measures

Primary Outcomes (13)

• Subjective Units of Distress Survey

  The Subjective Units of Distress Survey (SUDS) is a way for participants to communicate how much distress they are currently feeling using a 0 to 10 scale with zero corresponding to a relaxed state without distress and ten corresponding to extreme distress filled with panic, tension, fear, and anxiety.

  Screening Measure Subjects will be evaluated at baseline.

• Subjective Units of Distress Survey

  The Subjective Units of Distress Survey (SUDS) is a way for participants to communicate how much distress they are currently feeling using a 0 to 10 scale with zero corresponding to a relaxed state without distress and ten corresponding to extreme distress filled with panic, tension, fear, and anxiety.

  Change from baseline and after using the TaVNS system approximately 90 days (~3 months)] .

• Subjective Units of Distress Survey

  The Subjective Units of Distress Survey (SUDS) is a way for participants to communicate how much distress they are currently feeling using a 0 to 10 scale with zero corresponding to a relaxed state without distress and ten corresponding to extreme distress filled with panic, tension, fear, and anxiety.

  Evaluate at baseline to evaluate distress for healthy controls in Group III

• Heart Rate Variability for Active and Waitlist

  Heart rate variability (HRV) is the physiological phenomenon of the variation in the time interval between consecutive heartbeats in milliseconds.

  Screening Measure Subjects will be evaluated at baseline

• Heart Rate Variability for Active and Waitlist

  Heart rate variability (HRV) is the physiological phenomenon of the variation in the time interval between consecutive heartbeats in milliseconds.

  Change from baseline and after using the TaVNS system approximately 90 days (~3 months)] .

• Galvanic Skin Resistance (GSR) for Active and Waitlist

  To measure changes in sweat gland activity, which reflect the intensity of participants' emotional state

  Screening Measure Subjects will be evaluated at baseline

• Galvanic Skin Resistance (GSR) for Active and Waitlist

  To measure changes in sweat gland activity, which reflect the intensity of participants' emotional state

  Change from baseline and after using the TaVNS System approximately 90 days (~3 months)]

• Functional magnetic resonance imaging (fMRI) in all groups

  This scan will be used to assess functional connectivity, tractography, and brain volume

  Subjects will be evaluated at baseline

• Functional magnetic resonance imaging (fMRI) in Active and Waitlist Groups

  This scan will be used to assess functional connectivity, tractography, and brain volume

  Change from baseline and after using the TaVNS system approximately 90 days (~3 months)] .

• Blood Oxygen Level Dependent Imaging scan in all groups

  Blood Oxygen Level Dependent Imaging (BOLD) scan analysis, used to observe different areas of the brain or other organs, which are found to be active at any given time.

  Subject will be evaluated at baseline

• Blood Oxygen Level Dependent Imaging scan in Active and Waitlist Groups

  Blood Oxygen Level Dependent Imaging (BOLD) scan fMRI analysis, used to observe different areas of the brain or other organs, which are found to be active at any given time.

  Change from baseline and after using the TaVNS System approximately 90 days (~3 months)]

• Arterial spin labeling scan in all groups

  Arterial spin labeling (ASL) scan fMRI analysis, used to quantify cerebral blood perfusion by labelling blood water as it flows throughout the brain.

  Subjects will be evaluated at baseline

• Arterial spin labeling scan in Active and Waitlist Groups

  Arterial spin labeling (ASL) scan fMRI analysis used to quantify cerebral blood perfusion by labelling blood water as it flows throughout the brain.

  Change from baseline and after using the TaVNS System approximately 90 days (~3 months)]

Secondary Outcomes (18)

• The Maslach Burnout Scale

  Subjects will be evaluated at baseline with questionnaires.

• The Maslach Burnout Scale

  Subjects will be evaluated at approximately three months follow up with questionnaires.

• The Maslach Burnout Scale

  Subjects will be evaluated approximately six months follow up with questionnaires.

• Patient Health Questionnaire

  Subjects will be evaluated at baseline with questionnaires.

• Patient Health Questionnaire

  Subjects will be evaluated at approximately three months follow up with questionnaires.

Study Arms (3)

Transcutaneous Auricular Vagal Nerve Stimulation Intervention Group Distressed Healthcare Workers

ACTIVE COMPARATOR

Two subgroups will be included in fMRI in the Active Comparator Group where scans performed during the initial evaluation period (pre) and at 3 months (post). Subgroup I of 30 subjects will undergo fMRI scans that will include structural imaging and functional imaging with Blood Oxygen Level Dependent Imaging (BOLD) scan and two arterial spin labeling (ASL) scans. This same imaging protocol, which takes a total of about 45 minutes, will be performed initially and then after the 3 month TaVNS program or the waitlist period. All scans will be co-registered and comparable slices of the cerebral cortex will be examined. Subgroup II will consist of 10 study subjects all receiving the TaVNS program who will undergo fMRI initially and then again at 3 months. This group will be scanned while wearing the TaVNS system (a special one that can be used in the MRI environment) and the fMRI will be used to evaluate the direct effects of the TaVNS while turned on and off in the scanner.

Other: Neuvana 2.0 Transcutaneous Auricular Vagal Nerve Stimulation (TaVNS)

Waitlist Control Distressed Healthcare Workers Delayed TaVNS Group

ACTIVE COMPARATOR

After baseline and 3 month imaging is completed. The waitlist control subgroups will be included in fMRI scans performed during the initial evaluation period (pre) and at 3 months (post). Subgroup I of 30 subjects will undergo fMRI scans that will include structural imaging and functional imaging with Blood Oxygen Level Dependent (BOLD) scan and two arterial spin labeling (ASL) scans. a typical morning waking up). This same imaging protocol, will be performed initially and then after the 3 month waitlist period. All scans will be co-registered and comparable slices of the cerebral cortex will be examined. After the waitlist imaging is completed the subjects will be offered the TaVNS health device.

Other: Waitlist Control

Healthy Controls: Group II and III

OTHER

The Investigators will also plan to recruit 10 healthy controls with no reports of psychological distress (i.e. less than 2 on the SUDS). These 10 healthy controls will have the TaVNS placed while receiving two fMRI scans approximately 3 months apart. These control subjects will be used to compare the subgroup of study subjects to ensure that any changes are not associated with test-retest effects.the Investigators also plan to recruit 50 additional healthy controls with no reports of psychological distress (i.e. less than 2 on the SUDS.) These 50 controls will have the TaVNS placed while receiving one fMRI scan sequence in one day while wearing a non-metalllic set of the TaVNS ear buds to evaluate the effects of the functional changes that may occur in the brain while using the TaVNS device.

Other: Healthy Controls: Substudy Group III; Other: Distressed Workers: Subgroup II

Interventions

Neuvana 2.0 Transcutaneous Auricular Vagal Nerve Stimulation (TaVNS) OTHER

The intervention administered is the TaVNS program and the fMRI scans to evaluate changes in the brain. The TaVNS program consists of placing ear buds from the device into each ear. They are initially sprayed once with a small amount of saline that is also provided as part of the TaVNS materials. Once the ear buds are placed in each ear, the test subject will start a preprogramed session of vibrations that will stimulate the vagus nerve. The session will last for 15 minutes and then the subject will take the ear buds out and clean them. They will use the TaVNS program once a day for 3 months.

Also known as: Active TaVNS Program in Distressed Workers

Transcutaneous Auricular Vagal Nerve Stimulation Intervention Group Distressed Healthcare Workers

Waitlist Control OTHER

Baseline imaging and follow up imaging for comparison to the TaVNS health device group at approximately 3 months. The TaVNS intervention is offered after completion of the imaging.

Also known as: Waitlist Control Group of Distressed Workers

Waitlist Control Distressed Healthcare Workers Delayed TaVNS Group

Healthy Controls: Substudy Group III OTHER

fMRI Imaging to evaluate the effects of the functional changes that may occur in the brain while using the TaVNS device during one fMRI session.

Also known as: Controls without Distress for one fMRI imaging session while using the TaVNS health device

Healthy Controls: Group II and III

Distressed Workers: Subgroup II OTHER

Subgroup II of 10 subjects with distress(all receiving TaVNS) will undergo fMRI scans with the TaVNS system being turned on and off while in the scanner to observe for any immediate effects and to evaluate the effects of the functional changes that may occur in the brain while using the TaVNS device during one fMRI session.

Also known as: Distressed Workers for fMRI one fMRI imaging while using the TaVNS health device

Healthy Controls: Group II and III

Eligibility Criteria

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

You may qualify if:

• Healthy male and female persons who work in health care and health care workers (all races and ethnicity) \>21 years of age
• All subjects must have a smartphone device that can be used in conjunction the Neuvana 2.0
• Drug-free from medications that may affect brain physiology such that the imaging results will not be useful as determined by the PI.
• Able to understand and provide signed informed consent. Available and willing to be followed -up according to study protocol
• Female subjects of childbearing potential have a negative pregnancy test
• Subjects have no significant medical neurological or psychological disorders
• Stable health problems that should have no substantial effect on cerebral blood flow will be allowed (i.e. controlled hypertension, medication controlled diabetes).
• Current medications and supplements will be reviewed by the Principal Investigator or a designated physician or health practitioner. Subjects may take medications or supplements but should be on a stable dose regimen for at least 3 months. For those receiving TaVNS program, it is preferable that subjects remain on that dose for the full TaVNS program period (with the exception of having an adverse reaction in which the medication or supplement must be stopped).
• PI will evaluate each subject for any potential medical issues that might be a problem and will consult with the subject's primary care provider if there are any questions about it.
• Distress scored as at least a 6 or greater on the SUDS distress level from 1 to 10.
• Distressing recollection(s) that causes physiological reactivity (i.e., increased heart rate and/or increased skin conductance level - SCL), as described above.

You may not qualify if:

• Any medical conditions that may interfere with cerebral blood flow as determined by the PI.
• Currently taking medication that might affect cerebral blood flow as per the P.I. (i.e. antidepressants, antipsychotics, anxiolytics, benzodiazepines, sedatives, anti-seizure medications, but with the exception of those described above)
• Subject is unable or unwilling to lie still in the scanner (i.e. due to claustrophobia or weight)
• Subject has metal in their body or other reason that they cannot undergo magnetic resonance imaging.
• Previous brain surgery or intracranial abnormalities they may complicate interpretation of the brain scans (e.g., stroke, tumor, vascular abnormality).
• Pregnancy or breastfeeding
• Concurrent participation in another research protocol that might affect the outcome of this study.
• Use of a defibrillator or pacemaker or other implanted or metallic electronic device. Doing so could cause electric shock, burns, electrical interference, or death.
• Epilepsy
• History of Seizures
• Temporomandibular Joint Disorder, Bell's Palsy, impaired cranial nerve function, or facial pain.

Sponsors & Collaborators

• Thomas Jefferson University: lead

Study Sites (1)

Thomas Jefferson University, Marcus Institute of Integrative Health Centers

Philadelphia, Pennsylvania, 19107, United States

Location

MeSH Terms

Conditions

Anxiety Disorders; Occupational Stress

Condition Hierarchy (Ancestors)

Mental Disorders; Occupational Diseases; Stress, Psychological; Behavioral Symptoms; Behavior

Study Officials

• Andrew B Newberg

  Department of Integrative Medicine and Nutritional Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Department of Integrative Medicine and Nutritional Sciences; Professor, Department of Radiology

Model Details: Subjects will be assigned by randomization to place individuals into the TaVNS or wait-list groups using a permuted block design with a 1:1 ratio to the group assignments. Subjects will be assigned a study number that will be used on the research files. Each subject will be informed of their group assignment.

Study Record Dates

• First Submitted: October 21, 2021
• First Posted: November 24, 2021
• Study Start: April 1, 2021
• Primary Completion: November 20, 2025
• Study Completion: November 20, 2025
• Last Updated: September 17, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: Study scan report will be offered to the subject after subject completes study
• Access Criteria: Access only to authorized research staff and study participants

Locations

US (1)