Transcutaneous Auricular Vagus Nerve Stimulation for Depression

Overseen By David J Allison, PhD.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Lawson Health Research Institute

Must be taking: Depression medications

Disqualifiers: Autonomic dysreflexia, Cardiovascular disease, Epilepsy, others

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

Compensation: Varies

Number of Visits: 3

Duration: 30 days

44 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it requires that you are on a stable dose of depression medications. This suggests you may continue your current depression medication as long as the dose is stable.

What data supports the effectiveness of the treatment Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) for depression?

Research shows that taVNS can significantly reduce symptoms of depression, such as anxiety, sleep problems, and feelings of hopelessness. It is also considered effective for treatment-resistant depression, suggesting it may help when other treatments have not worked. ^{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, with only mild and temporary side effects like ear pain, headache, and tingling. Studies show no significant difference in the risk of adverse events between those receiving taVNS and those who do not, and there is no link between taVNS and severe adverse events. ^{5 6 7 8 9}

How is transcutaneous auricular vagus nerve stimulation (taVNS) different from other treatments for depression?

Transcutaneous auricular vagus nerve stimulation (taVNS) is unique because it involves stimulating the vagus nerve through the skin of the ear, which can help regulate mood by affecting brain regions involved in depression. Unlike traditional medications, taVNS is non-invasive and may also help with symptoms like anxiety and sleep disturbances. ^{1 2 3 4 5}

What is the purpose of this trial?

Spinal cord injury (SCI) has been shown to be associated with impairment to the autonomic nervous system in the form of reduced activity of a key nerve known as the vagus nerve. As the vagus nerve has an important role in regulating inflammation and is associated with depression, it may represent a key mechanism which contributes to chronic inflammation and depression following SCI. A technique known as transcutaneous auricular vagus nerve stimulation (taVNS) can stimulate the vagus nerve non-invasively through an electrode applied on the skin of the ear. This technique has been shown to effectively reduce inflammation and improve symptoms of depression in other populations without any serious adverse events. However, it has not been assessed in individuals with SCI. The primary objective of this study is to assess the efficacy of taVNS therapy for the treatment of inflammation and depression. Autonomic function as assessed by measures of heart rate variability (HRV) will also be assessed to quantify changes in vagal tone. The study will be conducted over a 2-year period, with 44 individuals with SCI and depression participating. Participants will be randomly assigned to receive either active taVNS or a placebo (sham) treatment over a 30-day period. The researchers will assess changes in depression symptoms, autonomic function (heart rate variability), and biomarkers related to inflammation at baseline and 30-days. Safety and adherence will also be evaluated to confirm the feasibility for long-term use. This study aims to explore a novel and non-invasive treatment strategy for depression in individuals with spinal cord injury. If taVNS is found to be safe, effective, and feasible for SCI patients, it could offer a simple, cost-effective way to address chronic inflammation and depression in this population.

Research Team

David J Allison, PhD.

Principal Investigator

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Eligibility Criteria

This trial is for adults with any level or severity of spinal cord injury (SCI) who show signs of mild to moderately severe depression. Participants must be on a stable dose of depression medications.

Inclusion Criteria

I have a spinal cord injury.

My depression is mild to moderately severe according to the PHQ-9.

My depression medication dose has been stable.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Assessment

In-person baseline visit to determine optimal taVNS stimulation parameters and train participants on instructions for use

1 day

1 visit (in-person)

Treatment

Participants receive either active or sham taVNS therapy for 30 days with daily 4-hour sessions

30 days

Twice weekly phone calls

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of HRV, depression, and inflammatory biomarkers

4 weeks

1 visit (in-person)

Treatment Details

Interventions

• Transcutaneous Auricular Vagus Nerve Stimulation (taVNS)

Trial Overview The study tests taVNS, a non-invasive method stimulating the vagus nerve through the ear to reduce inflammation and depression in SCI patients. It compares active taVNS against sham treatment over 30 days.

Participant Groups

Group I: Active taVNS Experimental Treatment 1 Intervention

Stimulation will target the auricular branch of the vagus nerve by applying stimulation to the cymba conchae region of the ear using the NEMOS® taVNS device (taVNS Technologies, Erlangen, Germany).

Group II: Sham taVNS Placebo Group 1 Intervention

Stimulation will target the ear lobe using the NEMOS® taVNS device (taVNS Technologies, Erlangen, Germany). Stimulation will be applied to the ear lobe in order to ensure participant feel the stimulation while avoiding activation of the vagus nerve.

Who Is Running the Clinical Trial?

Lawson Health Research Institute

Lead Sponsor

Trials

684

Recruited

432,000+

London Health Sciences Centre OR Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

668

Recruited

424,000+

London Health Sciences Centre Research Institute and Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

686

Recruited

427,000+

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

678

Recruited

421,000+

Findings from Research

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]

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]

Transcutaneous auricular vagus nerve stimulation (taVNS) significantly improved depressive behavior in rats, as evidenced by increased body weight and decreased immobility time in forced swimming tests after 21 days of treatment.

The mechanism of taVNS's effectiveness appears to involve the inhibition of the inflammatory response through the TLR4/MyD88 signaling pathway in the prefrontal cortex, suggesting a biological basis for its antidepressant effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of transcutaneous auricular vagus nerve stimulation on the expression of TLR4、MyD88、IL-18 protein in the prefrontal cortex of depression rats]. Wang, YF., Wang, Y., Zhang, Y., et al.[2022]

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 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]

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) 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]

References

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

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

2. 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]

3. China pubmed.ncbi.nlm.nih.gov

[Effect of transcutaneous auricular vagus nerve stimulation on the expression of TLR4、MyD88、IL-18 protein in the prefrontal cortex of depression rats]. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

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

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. 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]

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

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

8. England pubmed.ncbi.nlm.nih.gov

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

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

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