Electrical Nerve Stimulation for Depression

Recruiting at 2 trial locations

Overseen By Peter Colvonen

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Neurovalens Ltd.

Must be taking: SSRI/SNRI

Must not be taking: Recreational drugs, Antihistamines

Disqualifiers: Bipolar, Psychotic disorders, Substance use, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

170 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

No, you will not have to stop taking your current medications. Participants must stay on a stable dose of their current antidepressant medication (SSRI/SNRI) for the duration of the trial.

What data supports the effectiveness of the treatment Electrical Vestibular Nerve Stimulation (VeNS) for depression?

Research on vagus nerve stimulation (VNS), a similar nerve stimulation treatment, shows it can help people with severe depression who haven't responded to other treatments. Studies have found that VNS can improve depression symptoms and quality of life over time. ^{1 2 3 4 5}

Is electrical nerve stimulation safe for humans?

Studies on electrical vestibular nerve stimulation (VeNS) show it is generally safe for humans, with no reported side effects in a study involving stroke patients and no negative impact on hearing in long-term use. ^{6 7 8 9 10}

How is Electrical Vestibular Nerve Stimulation (VeNS) different from other treatments for depression?

Electrical Vestibular Nerve Stimulation (VeNS) is unique because it involves non-invasive electrical stimulation of the vestibular nerve, unlike Vagus Nerve Stimulation (VNS) which requires surgical implantation of a device. VeNS offers a potentially less invasive alternative for treating depression, focusing on modulating brain activity through external nerve stimulation. ^{4 5 11 12 13}

What is the purpose of this trial?

Trial title: A Randomized, Double Blind Sham Controlled Clinical Trial to Evaluate the Efficacy of Electrical Vestibular Nerve Stimulation (VeNS), Compared to a Sham Control for Treatment of Major Depressive Disorder (MDD) - Modius Mood Study The aim of this study: To better evaluate the efficacy of non-invasive electrical vestibular nerve stimulation (VeNS) as a method of treating major depressive disorder(MDD) , as compared to a sham control. Allocation: Randomized to either active device or control device usage. Endpoint classification: Efficacy Study Intervention Model: Parallel Assignment in 1:1 active to control allocation

Research Team

Peter Colvonen, MD

Principal Investigator

San Diego Healthcare System

Eligibility Criteria

This trial is for individuals with Major Depressive Disorder (MDD) who are seeking a new treatment option. Participants should not have other mental health conditions that could interfere with the study, and they must be willing to use either the active VeNS device or a sham (placebo) device as determined by chance.

Inclusion Criteria

Willingness to use a video calling platform for remote study visits

I agree not to make major lifestyle changes that could affect my mood during the study.

I have access to a digital device for study visits and questionnaires.

Exclusion Criteria

Diagnosis or history of bipolar disorder

History of severe tinnitus or vertigo

Risk of persistent self-harm or suicide as confirmed by the Columbia Suicide Severity Rating Scale (CSSRS)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants use the VeNS or sham device at home for 30 minutes per day

6 weeks

Baseline visit, home use

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Post-intervention visit

Treatment Details

Interventions

• Electrical Vestibular Nerve Stimulation (VeNS)

Trial Overview The study tests if an electrical vestibular nerve stimulation (VeNS) device can help treat depression compared to a sham device. Participants will be randomly assigned to receive either the real VeNS treatment or a placebo, in equal numbers, over a period of 10 weeks.

Participant Groups

Group I: Active VeNS Experimental Treatment 1 Intervention

The active device utilizes a technology termed vestibular nerve stimulation (VeNS). The device will be placed on the head in a manner analogous to headphones and will deliver a small electrical current to the skin behind the ears, over the mastoid processes. Participants will be advised to use the device at home for 30 minutes per day.

Group II: Sham VeNS Placebo Group 1 Intervention

The sham device looks identical to the active device and interacts with the app in a similar manner to the active device. The device will be placed on the head in a manner analogous to headphones with hydrogel electrodes placed over the mastoid processes. Participants will be advised to use the device at home for 30 minutes per day.

Who Is Running the Clinical Trial?

Neurovalens Ltd.

Lead Sponsor

Trials

18

Recruited

1,800+

Findings from Research

In a study of 15 patients with treatment-resistant depression, vagus nerve stimulation (VNS) significantly reduced depression scores over 12 months, with a mean Beck Depression Inventory score dropping from 37.8 to 24.6, indicating a positive treatment effect.

By the end of the year, 28.6% of patients showed a response to VNS, and 7.1% achieved remission, with side effects like hoarseness and nausea being common but not leading to treatment discontinuation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of vagus nerve stimulation for severe treatment-resistant major depression in clinical practice after FDA approval: outcomes at 1 year. Cristancho, P., Cristancho, MA., Baltuch, GH., et al.[2012]

Vagus nerve stimulation (VNS) is a promising treatment for treatment-resistant depression, showing a unique ability to maintain remission in patients with severe and chronic forms of depression, including both unipolar and bipolar types.

Despite its potential, VNS has not been widely adopted in clinical practice, particularly in France, due to factors such as a lack of awareness among psychiatrists about surgical options, previous methodological challenges in early trials, and the need for multidisciplinary teams for implementation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Vagus nerve stimulation and depression]. Senova, S., Rabu, C., Beaumont, S., et al.[2019]

Vagus nerve stimulation (VNS) is being explored as a treatment for major depression that does not respond to traditional medications, although its exact mechanism of action is still unclear.

This review examines preclinical studies of VNS in relation to two key theories of depression: the monoaminergic hypothesis, which focuses on neurotransmitters, and the neural plasticity hypothesis, which emphasizes the brain's ability to adapt and change.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The antidepressant mechanism of action of vagus nerve stimulation: Evidence from preclinical studies. Grimonprez, A., Raedt, R., Baeken, C., et al.[2021]

Invasive vagus nerve stimulation (VNS) is a long-term treatment option for chronic and treatment-resistant depression, showing a significant cumulative response rate of 67.6% after 5 years when combined with standard treatment, compared to 40.9% for standard treatment alone.

VNS is generally safe, with hoarseness being the most common side effect, and it may improve depression severity, quality of life, and cognitive function, potentially through mechanisms like increased monoaminergic transmission and anti-inflammatory effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Vagus Nerve Stimulation (VNS) in Depression]. Kavakbasi, E., Baune, BT.[2023]

In a study of 25 long-term users of electrical vestibular nerve stimulation (VeNS) over an average of 22 months, no adverse events or significant side effects were reported, indicating a strong safety profile for this treatment.

Formal audiometry tests showed no significant changes in hearing function among 18 users, suggesting that long-term VeNS does not negatively impact hearing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electrical vestibular nerve stimulation (VeNS): a follow-up safety assessment of long-term usage. McCulloch, E., Kumar Goothy, SS., McKeown, J.[2022]

Galvanic vestibular stimulation (GVS) applied for 30 minutes over 5 consecutive days was well-tolerated by a stroke patient, with no reported side effects during or after the sessions.

The study suggests that increasing the duration and frequency of GVS could lead to further improvements in stroke impairment, providing a foundation for larger studies on its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of repeated sessions of galvanic vestibular stimulation following stroke: a single-case study. Wilkinson, D., Zubko, O., Sakel, M.[2019]

Vagus Nerve Stimulation (VNS) has shown promising long-term antidepressant effects when combined with standard treatment in over 1100 patients with difficult-to-treat depression, particularly after 12 months of stimulation.

A recent randomized trial did not show immediate benefits from VNS, suggesting that longer treatment durations are necessary to fully assess its efficacy and that new metrics are needed to evaluate clinically meaningful improvements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Long and Winding Road of Vagus Nerve Stimulation: Challenges in Developing an Intervention for Difficult-to-Treat Mood Disorders. Sackeim, HA., Dibué, M., Bunker, MT., et al.[2022]

References

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

Effectiveness and safety of vagus nerve stimulation for severe treatment-resistant major depression in clinical practice after FDA approval: outcomes at 1 year. [2012]

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

Vagus Nerve Stimulation: Changing the Paradigm for Chronic Severe Depression? [2019]

3. France pubmed.ncbi.nlm.nih.gov

[Vagus nerve stimulation and depression]. [2019]

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

The antidepressant mechanism of action of vagus nerve stimulation: Evidence from preclinical studies. [2021]

5. Germany pubmed.ncbi.nlm.nih.gov

[Vagus Nerve Stimulation (VNS) in Depression]. [2023]

6. Germany pubmed.ncbi.nlm.nih.gov

Electrical vestibular nerve stimulation (VeNS): a follow-up safety assessment of long-term usage. [2022]

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

Safety of repeated sessions of galvanic vestibular stimulation following stroke: a single-case study. [2019]

8. Germany pubmed.ncbi.nlm.nih.gov

Modulation of sleep using electrical vestibular nerve stimulation prior to sleep onset: a pilot study. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Acceptability and feasibility of a vestibular nerve stimulation headset protocol in children with cerebral palsy. [2022]

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

Dominant parameter of galvanic vestibular stimulation for the non-associative learning processes. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Acute effect of vagus nerve stimulation (VNS) on brain function. [2021]

12. New Zealand pubmed.ncbi.nlm.nih.gov

The Long and Winding Road of Vagus Nerve Stimulation: Challenges in Developing an Intervention for Difficult-to-Treat Mood Disorders. [2022]

13. Germany pubmed.ncbi.nlm.nih.gov

[Vagus nerve stimulation for difficult to treat depression]. [2022]