Electrical Nerve Stimulation for Depression

Not yet 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of a new treatment called Electrical Vestibular Nerve Stimulation (VeNS) for individuals with major depressive disorder (MDD). Participants will use a device similar to headphones that delivers a gentle electrical current behind the ears for 30 minutes daily. The study compares the effects of the active device with a sham (fake) device. Individuals who have been on the same antidepressant medication for at least a year and continue to experience depression might be suitable candidates for this trial. As an unphased trial, this study provides a unique opportunity to explore innovative treatment options for depression.

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 prior data suggests that this method is safe for treating major depressive disorder?

Research has shown that electrical vestibular nerve stimulation (VeNS) is generally safe for people. In previous studies, participants used VeNS devices for 30 minutes a day, five days a week, and reported no serious side effects. This suggests that the treatment is safe for most individuals.

Instead of causing discomfort, VeNS appears to help with issues like depression, insomnia, and anxiety. For instance, one study found that after eight weeks, people using VeNS showed noticeable improvements in their depression and sleep problems compared to those using a placebo device. This suggests that the treatment is not only safe but also potentially effective.

Overall, while every treatment carries some risk, current evidence suggests that VeNS is a safe option for those considering joining a clinical trial for depression. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for depression revolve around medication like SSRIs or therapy sessions, which can take weeks to show results. In contrast, Electrical Vestibular Nerve Stimulation (VeNS) offers a unique approach by delivering a small electrical current behind the ears, directly targeting the vestibular nerves. This method is non-invasive and could potentially offer quicker relief from depressive symptoms by influencing brain activity in a novel way. Researchers are excited about VeNS because it might provide a more immediate and accessible option for individuals struggling with depression, offering hope for those who haven't found success with traditional treatments.

What evidence suggests that electrical vestibular nerve stimulation (VeNS) is effective for major depressive disorder (MDD)?

Research has shown that Electrical Vestibular Nerve Stimulation (VeNS) can help treat major depressive disorder (MDD). In this trial, participants will join either an active VeNS group or a sham VeNS group. Previous studies found that using VeNS for eight weeks led to noticeable improvement in depression symptoms. Participants who used VeNS for 30 minutes a day, five days a week, reported feeling better and less anxious. Some also experienced improved sleep. Overall, VeNS appears to be a promising non-invasive treatment for depression. ^{1 2 3 4 6}

Who Is on the Research Team?

Peter Colvonen, MD

Principal Investigator

San Diego Healthcare System

Are You a Good Fit for This Trial?

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

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

Diagnosis or history of bipolar disorder

History of severe tinnitus or vertigo

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40691899/

A randomized, double-blind, sham controlled clinical trial to ... Conclusion: VeNS, when delivered over 8-weeks, appears to have a clinically meaningful benefit as an intervention for major depressive disorder.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165032725013916

A randomized, double-blind, sham controlled clinical trial to ... VeNS for 30 min, five days per week, significantly improved Major Depressive Disorder, insomnia severity, anxiety and QoL.

3. academic.oup.com academic.oup.com/sleep/article/48/Supplement_1/A527/8134973

1222 Electrical Vestibular Nerve Stimulation (VeNS) for ... The findings suggest that VeNS not only offers a significant reduction in depressive symptoms but also has a clinically meaningful impact on improving insomnia.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06051864

Study Details | NCT06051864 | Electrical Vestibular Nerve ... The aim of this study: To better evaluate the efficacy of non-invasive electrical vestibular nerve stimulation (VeNS) as a method of treating Depression, as ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X24000925

Repeated electrical vestibular nerve stimulation (VeNS ... Repeated VeNS with below parameters improved insomnia severity and fatigue. · Stimulation was effective when provided for 30 min daily for five days per week.

6. brainstimjrnl.com brainstimjrnl.com/article/S1935-861X(24)00092-5/fulltext

Repeated electrical vestibular nerve stimulation (VeNS) ... After 4 weeks, mean ISI score reduction was 2.26 greater in the VeNS treatment group than the sham group (p = 0.002). In the per protocol ...