TaVNS for Healthcare Worker Anxiety

(fMRIVNS Trial)

Overseen By Andrew B Newberg, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Thomas Jefferson University

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

Disqualifiers: Epilepsy, Seizures, Pregnancy, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial aims to see if a device that sends mild electrical signals to the ears can reduce stress and anxiety in healthcare workers. Researchers will use brain scans to observe changes in brain activity while using the device. The study focuses on healthcare workers in Philadelphia who are experiencing high levels of distress. This method has been researched and applied as a non-invasive treatment for various conditions over the past two decades.

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 data supports the effectiveness of the treatment Neuvana 2.0 Transcutaneous Auricular Vagal Nerve Stimulation (TaVNS) for anxiety?

Research shows that transcutaneous auricular vagus nerve stimulation (taVNS) is safe and effective for treating anxiety and other conditions like depression and insomnia. This non-invasive treatment is appealing because it is inexpensive and portable, making it a promising option for managing anxiety in healthcare workers. ^{1 2 3 4 5}

Is transcutaneous auricular vagus nerve stimulation (taVNS) safe for humans?

Transcutaneous auricular vagus nerve stimulation (taVNS) is generally considered safe for humans, with only mild and temporary side effects like ear pain, headache, and tingling. There is no evidence of a causal relationship between taVNS and severe adverse events. ^{1 2 4 5 6}

How is the treatment Neuvana 2.0 TaVNS different from other treatments for anxiety?

Neuvana 2.0 TaVNS is unique because it is a non-invasive, portable device that stimulates the vagus nerve through the ear, unlike traditional anxiety treatments that often involve medication or therapy. This method is appealing as it is safe, inexpensive, and can be used at home, reducing the need for frequent clinic visits. ^{2 3 4 5 6}

Research Team

Andrew B Newberg

Principal Investigator

Department of Integrative Medicine and Nutritional Sciences

Eligibility Criteria

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.

Trial Timeline

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)

Treatment Details

Interventions

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

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.

Participant Groups

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.

Who Is Running the Clinical Trial?

Thomas Jefferson University

Lead Sponsor

Trials

475

Recruited

189,000+

Findings from Research

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) 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) 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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic review and meta-analysis. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Transcutaneous auricular vagus nerve stimulators: a review of past, present, and future devices. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Laboratory Administration of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS): Technique, Targeting, and Considerations. [2020]

4. Netherlands 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. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Transcutaneous Auricular Vagus Nerve Stimulation Normalizes Induced Gastric Myoelectrical Dysrhythmias in Controls Assessed by Body-Surface Gastric Mapping. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Remotely supervised at-home delivery of taVNS for autism spectrum disorder: feasibility and initial efficacy. [2023]