TaVNS for Healthcare Worker Anxiety

(fMRIVNS Trial)

Overseen By Nancy A Wintering

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Thomas Jefferson University

Must not be taking: Antidepressants, Antipsychotics, Anxiolytics, others

Disqualifiers: Epilepsy, Seizures, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a health device called Transauricular Vagal Nerve Stimulation (TaVNS) to determine its effectiveness in reducing anxiety and stress in healthcare workers. Researchers will use special brain scans to examine how the device impacts brain activity and stress levels. Healthcare workers in Philadelphia who feel anxious or stressed and have a smartphone for use with the device can participate. As an unphased trial, this study provides healthcare workers the chance to contribute to innovative research that could enhance stress management techniques.

Will I have to stop taking my current medications?

You may need to stop taking certain medications that affect brain function, like antidepressants or sedatives, as determined by the study's principal investigator. However, if you're on a stable dose of other medications for at least 3 months, you might be able to continue them during the trial.

What prior data suggests that the TaVNS device is safe for healthcare workers?

Research has shown that Transcutaneous Auricular Vagal Nerve Stimulation (TaVNS) is generally safe. Studies have found that it typically causes only mild and temporary side effects, such as ear pain or a slight headache, which are neither long-lasting nor serious. TaVNS has approval for use in some areas, indicating a strong safety record. In summary, for those considering joining a trial with this device, evidence suggests it is well-tolerated by most people. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about TaVNS (Transcutaneous Auricular Vagal Nerve Stimulation) because it offers a unique, non-invasive way to address anxiety in healthcare workers. Unlike standard treatments like medication or therapy, which can take weeks to show effects and may have side effects, TaVNS uses gentle electrical stimulation of the vagal nerve through the ear to potentially bring about faster relief. This novel delivery method could help reduce symptoms of anxiety without the need for pharmaceuticals, making it an attractive option for those looking for alternatives to traditional treatments.

What evidence suggests that the TaVNS device is effective for reducing anxiety in healthcare workers?

Studies have shown that Transcutaneous Auricular Vagal Nerve Stimulation (TaVNS) can effectively reduce anxiety. In this trial, some participants will receive the TaVNS intervention, which research indicates lowers anxiety and improves sleep quality among healthcare workers. Animal studies found that TaVNS reduces anxiety-like behaviors by activating certain brain pathways. These findings suggest that TaVNS might help healthcare workers manage stress and distress. Overall, TaVNS is a promising tool for addressing anxiety in various groups, including those in high-stress jobs like healthcare. ^{1 4 6 7 8}

Who Is on the Research Team?

Andrew B Newberg

Principal Investigator

Department of Integrative Medicine and Nutritional Sciences

Are You a Good Fit for This Trial?

This trial is for health care workers over 21 years old in Philadelphia experiencing distress, with stable health conditions like controlled hypertension or diabetes. They must be able to consent and follow the study protocol, have a smartphone compatible with Neuvana 2.0, and not be on brain-affecting drugs. Pregnant women can't participate.

Inclusion Criteria

I feel very distressed, scoring at least a 6 out of 10, and have physical reactions to stressful memories.

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

I am not taking any medications that could affect my brain, as confirmed by a doctor.

Exclusion Criteria

Pregnancy or breastfeeding

I am on medication that could affect my brain's blood flow, as decided by the study leader.

I have epilepsy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Evaluation

Subjects receive an initial evaluation using symptom questionnaires and physiological measures

1 week

1 visit (in-person)

Treatment

Participants are randomized to either the 3-month TaVNS program or the 3-month waitlist group

12 weeks

Monthly follow-up visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Substudy

Subgroup of participants undergo fMRI scans to evaluate brain function changes with TaVNS

1 day

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Neuvana 2.0 Transcutaneous Auricular Vagal Nerve Stimulation (TaVNS)
• Waitlist Control

Trial Overview The study tests if TaVNS (a non-invasive earbud device) reduces anxiety and changes brain function in distressed health care workers using fMRI scans. A subgroup of healthy controls will also use TaVNS to compare brain activity changes.

How Is the Trial Designed?

Group I: Healthy Controls: Group II and III Experimental Treatment 2 Interventions

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.

Group II: Transcutaneous Auricular Vagal Nerve Stimulation Intervention Group Distressed Healthcare Workers Active Control 1 Intervention

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.

Group III: Waitlist Control Distressed Healthcare Workers Delayed TaVNS Group Active Control 1 Intervention

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.

Neuvana 2.0 Transcutaneous Auricular Vagal Nerve Stimulation (TaVNS) is already approved in European Union, United States for the following indications:

Approved in European Union as TaVNS for:

• Epilepsy
• Depression
• Anxiety
• Chronic pain

Approved in United States as TaVNS for:

• Depression
• Anxiety

Who Is Running the Clinical Trial?

Thomas Jefferson University

Lead Sponsor

Trials

475

Recruited

189,000+

Published Research Related to This Trial

The study demonstrated that remote supervised administration of transcutaneous auricular vagus nerve stimulation (taVNS) at home is feasible for 12 patients with autism spectrum disorder (ASD), achieving an 88.5% completion rate over 132 sessions.

Initial results indicated improvements in anxiety and sleep measures after 2 weeks of treatment, suggesting potential efficacy that warrants further investigation in larger trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Remotely supervised at-home delivery of taVNS for autism spectrum disorder: feasibility and initial efficacy. Black, B., Hunter, S., Cottrell, H., et al.[2023]

Transcutaneous auricular vagus nerve stimulation (taVNS) is a safe and effective neuromodulation therapy for a variety of conditions, including epilepsy, depression, and anxiety, indicating its broad therapeutic potential.

Despite its effectiveness, there is currently no standardization among taVNS devices, and further research is needed to clarify the relationship between stimulation parameters and therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous auricular vagus nerve stimulators: a review of past, present, and future devices. Wang, L., Wang, Y., Wang, Y., et al.[2022]

Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive and cost-effective method for modulating the vagus nerve, making it a promising alternative to traditional surgical vagus nerve stimulation.

taVNS allows for easy and safe administration, with considerations for proper electrode placement and individual dosing based on perception thresholds, which enhances its potential for treating various central and peripheral diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Laboratory Administration of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS): Technique, Targeting, and Considerations. Badran, BW., Yu, AB., Adair, D., et al.[2020]

Transcutaneous auricular vagus nerve stimulation (TaVNS) effectively normalized gastric dysrhythmias in healthy individuals during a water-load test, indicating its potential as a treatment for gastric symptoms.

The study found that TaVNS at 40 Hz improved heart rate variability and reduced bloating, suggesting it positively influences both parasympathetic and sympathetic nervous system pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous Auricular Vagus Nerve Stimulation Normalizes Induced Gastric Myoelectrical Dysrhythmias in Controls Assessed by Body-Surface Gastric Mapping. Du, P., Maharjan, A., Calder, S., et al.[2023]

Transcutaneous auricular vagus nerve stimulation (taVNS) is generally safe, with a low incidence of mild and transient adverse effects, such as ear pain, headache, and tingling, reported in only 24.86% of the studies analyzed.

In a systematic review of 177 studies involving 6322 subjects, there was no significant difference in the risk of adverse events between taVNS and control groups, indicating that taVNS is a feasible option for clinical intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic review and meta-analysis. Kim, AY., Marduy, A., de Melo, PS., et al.[2023]

Transcutaneous auricular vagus nerve stimulation (taVNS) significantly improves depression symptoms, as evidenced by reduced scores on the Hamilton Depression Scale in a review of 12 studies involving 838 participants.

taVNS shows comparable response rates to traditional antidepressants and has fewer side effects, suggesting it could be a safe alternative or complementary treatment for depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of transcutaneous auricular vagus nerve stimulation in the treatment of depressive disorder: A systematic review and meta-analysis of randomized controlled trials. Tan, C., Qiao, M., Ma, Y., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05132881

Effect of (TaVNS) on Anxiety and Brain Function in ... 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 ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38143418/

Effect of vagus nerve stimulation (taVNS) on anxiety and ... Conclusion: The findings suggest that taVNS may be an effective intervention for addressing anxiety and sleep issues in geriatric medical professionals. These ...

3. researchgate.net researchgate.net/publication/376779316_Effect_of_vagus_nerve_stimulation_taVNS_on_anxiety_and_sleep_disturbances_among_elderly_health_care_workers_in_post_Covid19_pandemic

Effect of vagus nerve stimulation (taVNS) on anxiety and ... Results ... The study's outcomes suggest that transcutaneous auricular vagal nerve stimulation is effective in alleviating anxiety and enhancing sleep quality.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12375034/

Transcutaneous auricular vagus nerve stimulation alleviates ... Our findings substantiate that taVNS significantly mitigates anxiety-like behaviors in PTSD-like male mice via activating specific glutamatergic ...

5. frontiersin.org frontiersin.org/journals/human-neuroscience/articles/10.3389/fnhum.2025.1539416/full

A pooled analysis of the side effects of non-invasive ... Effects of transcutaneous auricular vagus nerve stimulation (taVNS) on the processing and recognition of emotional and neutral faces [ ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9772204/

Safety of transcutaneous auricular vagus nerve stimulation ... Although the general impression is that taVNS is a safe technique with only mild and transient adverse effects (AEs), human data on safety and ...

7. withpower.com withpower.com/trial/phase-anxiety-disorders-3-2021-33197

TaVNS for Healthcare Worker Anxiety (fMRIVNS Trial) Transcutaneous auricular vagus nerve stimulation (taVNS) is generally safe, with a low incidence of mild and transient adverse effects, such as ear pain, ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06258590

Study Details | NCT06258590 | taVNS for Anxiety in ASD This pilot trial will be an open-label investigation of the safety and feasibility of transcutaneous auricular vagus nerve stimulation (taVNS) as a ...