taVNS + TMS for Depression

Overseen By Mark George

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Medical University of South Carolina

Must be taking: Antidepressants

Disqualifiers: Neurological disorders, Dementia, Head trauma, others

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

Compensation: Varies

Number of Visits: 9

Duration: 2 weeks

24 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a combined treatment for depression using electrical signals to a nerve in the ear and magnetic stimulation of the brain. It aims to see if this combination is more effective than either treatment alone. The study involves people with depression and uses methods that can help improve mood. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive procedure that stimulates electrical activity in the brain and has been found effective for treating depression.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you have a cervical VNS device, you will continue using it as part of the study.

What data supports the effectiveness of the treatment taVNS + TMS for Depression?

Research shows that transcutaneous auricular vagus nerve stimulation (taVNS) can help reduce symptoms of depression, including anxiety and sleep problems, and has been effective in treatment-resistant cases. Although the combination with transcranial magnetic stimulation (TMS) is not directly studied, taVNS alone has shown promise in improving mood and brain function in people with depression. ^{1 2 3 4 5}

Is taVNS safe for humans?

Transcutaneous auricular vagus nerve stimulation (taVNS) is generally considered safe for humans, with mild and temporary side effects like ear pain, headache, and tingling. There is no evidence of severe adverse events directly caused by taVNS. ^{1 2 5 6 7}

How is the taVNS + TMS treatment for depression different from other treatments?

The taVNS + TMS treatment for depression is unique because it combines two non-invasive techniques: taVNS, which stimulates the vagus nerve through the ear to modulate brain activity and mood, and TMS, which uses magnetic fields to stimulate nerve cells in the brain. This combination aims to enhance the therapeutic effects by targeting different mechanisms involved in depression. ^{1 3 5 8 9}

Research Team

Mark George, MD

Principal Investigator

Medical University of South Carolina

Eligibility Criteria

This trial is for adults aged 18-75 with severe depression, who haven't improved with talk therapy and have tried at least two antidepressants without success. It's also open to those already using cervical VNS. Participants must be able to consent, speak English, and not be pregnant or at high risk of suicide.

Inclusion Criteria

I am receiving VNS for my neck or have tried two antidepressants without success.

I can speak, read, and write in English.

Able to provide informed consent

Exclusion Criteria

History of major head trauma

I need a legal guardian to make decisions for me due to cognitive issues.

Current active suicidal intent or plan, prior attempt within the last 6 months, or who in the judgment of the investigator would be at elevated risk for suicide will be excluded

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Participants receive either VNS treatment alone, TMS treatment alone, or both at the same time over 6 treatment days

2 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 calls (virtual)

Treatment Details

Interventions

• taVNS
• TMS

Trial Overview The study tests a combined depression treatment involving ear nerve stimulation (taVNS) and brain magnetic stimulation (TMS), separately or together. Over six sessions at the MUSC campus in Charleston, treatments are randomized across different days to assess which combination might best alleviate symptoms.

Participant Groups

Group I: Vagus Nerve Stimulation (VNS) only Experimental Treatment 1 Intervention

Group II: Transcranial Magnetic Stimulation (TMS) only Experimental Treatment 1 Intervention

Group III: Synchronized VNS and TMS Experimental Treatment 2 Interventions

taVNS is already approved in United States, European Union for the following indications:

Approved in United States as Transcutaneous Auricular Vagus Nerve Stimulation for:

• Epilepsy
• Depression
• Obesity

Approved in European Union as Transcutaneous Auricular Vagus Nerve Stimulation for:

• Epilepsy
• Depression

Who Is Running the Clinical Trial?

Medical University of South Carolina

Lead Sponsor

Trials

994

Recruited

7,408,000+

Findings from Research

Transcutaneous auricular vagus nerve stimulation (taVNS) has been shown to effectively modulate brain activity in patients with treatment-resistant depression (TRD), as evidenced by significant changes in brain regions such as the medial orbital frontal cortex after just 30 minutes of stimulation.

The study utilized rest-state functional magnetic resonance imaging (rs-fMRI) with 40 TRD patients and 40 healthy controls, revealing that taVNS may alter functional connectivity in key cortical areas, suggesting potential neural mechanisms for its therapeutic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous auricular vagus nerve immediate stimulation treatment for treatment-resistant depression: A functional magnetic resonance imaging study. Ma, Y., Wang, Z., He, J., et al.[2022]

Transcutaneous auricular vagus nerve stimulation (taVNS) significantly reduced depression symptoms in patients with major depressive disorder, outperforming sham treatments in multiple depression scales, including the 24-item HAMD and Self-Rating Depression Scale.

The study, which included 4 trials with a total of 222 participants, found no significant adverse effects associated with taVNS, suggesting it is a safe alternative treatment for depression, although further research with larger sample sizes is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous auricular vagus nerve stimulation in treating major depressive disorder: A systematic review and meta-analysis. Wu, C., Liu, P., Fu, H., et al.[2022]

Transcutaneous auricular vagus nerve stimulation (taVNS) has shown significant potential in reducing multiple symptoms of depression, including anxiety, sleep disturbances, and hopelessness, based on clinical studies and re-analysis of the Hamilton Depression Scale.

The proposed mechanisms of action for taVNS include modulating brain activity related to mood regulation, inhibiting neuro-inflammation, promoting neurogenesis in the hippocampus, and influencing the microbiome-brain-gut axis, highlighting its multifaceted approach to treating depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treating Depression with Transcutaneous Auricular Vagus Nerve Stimulation: State of the Art and Future Perspectives. Kong, J., Fang, J., Park, J., et al.[2020]

Transcutaneous vagus nerve stimulation (taVNS) was assessed in a pilot study of 5 patients with treatment-resistant depression, showing substantial improvement in mental state for 2 participants after 12 weeks of treatment.

While taVNS is a non-invasive method that avoids surgical risks, 3 patients dropped out due to difficulties in using the device, highlighting a potential barrier to its broader application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of transcutaneous auricular vagus nerve stimulation (taVNS) in the treatment of drug-resistant depression - a pilot study, presentation of five clinical cases. Kaczmarczyk, M., Antosik-Wójcińska, A., Dominiak, M., et al.[2021]

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) 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]

This study will evaluate the efficacy of transcutaneous auricular vagus nerve stimulation (taVNS) in treating mild to moderate depression in adolescents aged 12-16, involving 120 participants in a randomized controlled trial comparing taVNS to sertraline, a common antidepressant.

The research will also explore the underlying neural mechanisms of taVNS using advanced MRI techniques, aiming to provide insights into how this non-invasive treatment can effectively alleviate depression symptoms without the severe side effects often associated with medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and brain mechanism of transcutaneous auricular vagus nerve stimulation for adolescents with mild to moderate depression: Study protocol for a randomized controlled trial. Xiao, X., Hou, X., Zhang, Z., et al.[2022]

This study will investigate the effects of transcutaneous auricular vagus nerve stimulation (taVNS) on 15 patients with a minimally conscious state, using five different frequencies (1, 10, 25, 50, and 100 Hz) to determine the optimal stimulation parameters.

The goal is to achieve stable improvements in consciousness levels in patients with disorders of consciousness by optimizing the taVNS neuromodulation technique, with results measured through the coma recovery scale-revised (CRS-R) and resting EEG assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing the modulation paradigm of transcutaneous auricular vagus nerve stimulation in patients with disorders of consciousness: A prospective exploratory pilot study protocol. Zhai, W., Jiao, H., Zhuang, Y., et al.[2023]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Transcutaneous auricular vagus nerve immediate stimulation treatment for treatment-resistant depression: A functional magnetic resonance imaging study. [2022]

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

Transcutaneous auricular vagus nerve stimulation in treating major depressive disorder: A systematic review and meta-analysis. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Treating Depression with Transcutaneous Auricular Vagus Nerve Stimulation: State of the Art and Future Perspectives. [2020]

4. Poland pubmed.ncbi.nlm.nih.gov

Use of transcutaneous auricular vagus nerve stimulation (taVNS) in the treatment of drug-resistant depression - a pilot study, presentation of five clinical cases. [2021]

5. 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]

6. England pubmed.ncbi.nlm.nih.gov

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

7. England pubmed.ncbi.nlm.nih.gov

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

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

Efficacy and brain mechanism of transcutaneous auricular vagus nerve stimulation for adolescents with mild to moderate depression: Study protocol for a randomized controlled trial. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Optimizing the modulation paradigm of transcutaneous auricular vagus nerve stimulation in patients with disorders of consciousness: A prospective exploratory pilot study protocol. [2023]