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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a non-invasive treatment called transcutaneous auricular vagus nerve stimulation (taVNS) to reduce depression and inflammation in people with spinal cord injuries. The treatment uses a device that stimulates a nerve through the ear, potentially alleviating symptoms of depression. Participants will receive either the real treatment or a placebo over 30 days to assess improvements in their condition. It suits individuals with spinal cord injuries who have mild to moderate depression and are on a stable dose of depression medication. The goal is to find a simple and affordable way to manage depression and inflammation for these individuals. As an unphased trial, this study offers participants a unique opportunity to contribute to pioneering research aimed at improving quality of life through innovative treatment.

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 prior data suggests that this technique is safe for individuals with spinal cord injury?

Research has shown that using a device to gently stimulate a nerve in the ear, known as transcutaneous auricular vagus nerve stimulation (taVNS), is generally safe. Studies have found that taVNS can reduce symptoms of depression without causing serious side effects. While some individuals might experience mild and short-lived issues, these are uncommon.

In past studies, taVNS proved as effective as some antidepressant treatments and had a similar safety level. This indicates it works well for depression and is well-tolerated by most people. For other conditions, like chronic insomnia, taVNS also demonstrated good safety results.

The evidence suggests that taVNS is a safe option for treating depression, with minimal risk of side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about transcutaneous auricular vagus nerve stimulation (taVNS) for depression because it offers a non-invasive way to potentially improve mood by targeting the vagus nerve through the ear. Unlike standard depression treatments like antidepressants, which often work by altering brain chemistry, taVNS directly stimulates the nervous system, which can lead to mood improvements. This method is appealing because it avoids the systemic side effects common with medication and offers a novel approach by using the NEMOS® device to specifically target the auricular branch of the vagus nerve.

What evidence suggests that transcutaneous auricular vagus nerve stimulation is effective for depression in individuals with spinal cord injury?

Research has shown that transcutaneous auricular vagus nerve stimulation (taVNS) can reduce symptoms of depression. In this trial, participants will receive either active taVNS, which targets the auricular branch of the vagus nerve, or a sham taVNS, which targets the ear lobe without activating the vagus nerve. Studies have found that people using active taVNS experience significant improvements in depression compared to those receiving a sham treatment. This method is safe and effective, particularly for mild to moderate depression. Additionally, taVNS may help reduce inflammation, benefiting those with chronic inflammation. Overall, taVNS offers a promising, non-invasive option for managing depression symptoms. ^{1 2 6 7 8}

Who Is on the Research Team?

David J Allison, PhD.

Principal Investigator

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

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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) 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) 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) 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) 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]

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 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 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]

Citations

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Effect of transcutaneous auricular vagus nerve stimulation on ... After two weeks of treatment, the taVNS group showed significant improvement on the Beck Depression Inventory (BDI) as compared with the sham condition. However ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0165032723006857

The efficacy and safety of transcutaneous auricular vagus ... taVNS is an effective and safe method for mild to moderate depression. •. taVNS has significantly higher response rate than sham-taVNS.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37230264/

The efficacy and safety of transcutaneous auricular vagus ... taVNS could significantly improve depression and reduce Hamilton Depression Scale scores. Low to very low evidence showed that taVNS had higher ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1094715925000327

Accelerated Transcutaneous Auricular Vagus Nerve ... In this open label study, taVNS significantly decreased depression and anxiety symptoms in patients admitted to the inpatient unit.

5. jneuroinflammation.biomedcentral.com jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-020-01732-5

Neural networks and the anti-inflammatory effect of ... It has been postulated that acupuncture may achieve its treatment effects on MDD through suppression of vagal nerve inflammatory responses. Our ...

6. nature.com nature.com/articles/s41598-022-25864-1

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 ...

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Effectiveness and safety of transcutaneous auricular vagus ... Conclusion: Our study suggests that taVNS may effectively improve depressive symptoms in PWE. This may be an efficacious and safe treatment for ...

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Transcutaneous Auricular Vagus Nerve Stimulation for ... This randomized clinical trial investigates the efficacy and safety of transcutaneous auricular vagus nerve stimulation (taVNS) for chronic insomnia.