taVNS + TMS for Depression

Recruiting in Palo Alto (17 mi)

Overseen by Mark George, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Medical University of South Carolina

Must be taking: Antidepressants

Disqualifiers: Neurological disorders, Dementia, Head trauma, others

No Placebo Group

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 between 18 and 75 years old.

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

I can speak, read, and write in English.

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

Trial 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 (Behavioural Intervention)
• TMS (Behavioural Intervention)

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Medical University of South Carolina Institute of Psychiatry Charleston, SC

Who Is Running the Clinical Trial?

Medical University of South Carolina

Lead Sponsor

Trials

994

Patients Recruited

7,408,000+

Findings from Research

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 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]