Vagus Nerve Stimulation for Suicidal Thoughts

Recruiting at 1 trial location

Overseen By Cheryl Lee, MS

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: University of Notre Dame

Disqualifiers: Autism, Schizophrenia, Seizures, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

200 Participants Needed

Trial Summary

What is the purpose of this trial?

Suicidal thoughts, suicide attempts, and suicide are increasingly common in adolescence. Current face-to-face prevention approaches are of limited effectiveness, rely on extensive resources, and are at odds with adolescents' digital preferences. We will evaluate two unconventional but promising interventions delivered to 13- to 17-year-olds: transcutaneous vagus nerve stimulation to target emotion dysregulation, and a peer-support smartphone app to combat social isolation. If effective, these digitally-delivered interventions could reach far more adolescents at far lower cost than current approaches.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Vagus Nerve Stimulation for Suicidal Thoughts?

Research shows that transcutaneous vagus nerve stimulation (tVNS) is a non-invasive method that has been effective in treating conditions like depression and epilepsy. It is considered safe and has the potential to be used at home, making it accessible for various neuropsychiatric disorders. ^{1 2 3 4 5}

Is transcutaneous vagus nerve stimulation (tVNS) safe for humans?

Transcutaneous vagus nerve stimulation (tVNS) is generally considered safe, with mild and temporary side effects like ear pain, headache, and tingling. Studies show no significant risk of severe adverse events, making it a feasible option for clinical use. ^{5 6 7 8 9}

How is the treatment for suicidal thoughts using vagus nerve stimulation different from other treatments?

This treatment is unique because it uses a non-invasive method called transcutaneous vagus nerve stimulation (tVNS), which stimulates the vagus nerve through the skin, often at the ear, using a device. Unlike traditional invasive methods, tVNS is safer and more tolerable, and it is being explored for its potential to help with a wide range of conditions, including depression and anxiety, by modulating brain activity. ^{2 3 5 9 10}

Research Team

Kristin Valentino, PhD

Principal Investigator

University of Notre Dame

Eligibility Criteria

This trial is for adolescents aged 13-17 who often feel impulsive or have trouble managing their emotions. They may feel very lonely, use alcohol or drugs, and must be able to meet in person in South Bend, IN or Rochester, NY. It's specifically for those who've hurt themselves on purpose multiple times without intending suicide.

Inclusion Criteria

You use alcohol or other drugs.

You have intentionally hurt yourself multiple times in the past, or at least once in the past year.

You must be able to attend meetings in person in either South Bend, IN or Rochester, NY.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily transcutaneous vagus nerve stimulation and/or use a peer-support smartphone app for 30 days

4 weeks

Daily self-administered sessions

Follow-up

Participants are monitored for changes in self-injurious thoughts and behaviors, emotion dysregulation, and social connection

1 year

Post-treatment and one-year follow-up assessments

Treatment Details

Interventions

• Enhanced Treatment as Usual
• Phone App Program
• tVNS and Phone App Program
• tVns Program

Trial Overview The study tests two approaches: a noninvasive nerve stimulation therapy (tVNS) and a peer-support smartphone app. The tVNS aims to help with emotional control while the app addresses loneliness. These are compared against enhanced usual care to see if they can reduce suicidal behaviors more effectively.

Participant Groups

Group I: tVNS and Phone App Program Experimental Treatment 1 Intervention

Adolescents will self-administer 30-minute tVNS (i.e., nerve stimulation) sessions daily for 30 days. Adolescents will also use a specially designed phone app (MindTiles) to communicate with a peer to help them cope with emotions, and to foster connection with peers to establish social connections. They will receive a daily text message on their phone to remind them about their session. In addition, they will answer a 2-3 minute self-report survey on their current thoughts, feelings, and behaviors once a day for 30 days. They will receive a text message with a link to Qualtrics, a secure online platform where they will complete the survey.

Group II: tVNS Program + Control app Experimental Treatment 1 Intervention

Adolescents will self-administer 30-minute tVNS (i.e., nerve stimulation) sessions daily for 30 days. They will receive a daily text message on their phone to remind them about their session. They will have access to MindTiles where they will complete daily puzzles on their own. In addition, they will answer a 2-3 minute self-report survey on their current thoughts, feelings, and behaviors once a day for 30 days. They will receive a text message with a link to Qualtrics, a secure online platform where they will complete the survey.

Group III: Phone App Program + Sham tVNS Experimental Treatment 1 Intervention

Adolescents will use a specially designed phone app (MindTiles) to communicate with peer to help them cope with emotions, and to foster connection with peers to establish social connections. In addition, they will answer a 2-3 minute self-report survey on their current thoughts, feelings, and behaviors once a day for 30 days. They will receive a text message with a link to Qualtrics, a secure online platform where they will complete the survey. Adolescents will also self-administer 30-minute sham tVNS (i.e., nerve stimulation) sessions daily for 30 days; these sessions will include no actual stimulation.

Group IV: Sham tVNS + Control App Placebo Group 1 Intervention

Adolescents will self-administer 30-minute sham tVNS (i.e., nerve stimulation) sessions daily for 30 days; these sessions will include no actual stimulation.They will receive a daily text message on their phone to remind them about their session. They will also have access to MindTiles where they will complete daily puzzles on their own. They will answer a 2-3 minute self-report survey on their current thoughts, feelings, and behaviors once a day for 30 days. They will receive a text message with a link to Qualtrics, a secure online platform where they will complete the survey.

Phone App Program is already approved in European Union, United States for the following indications:

Approved in European Union as tVNS for:

• Epilepsy
• Depression
• Anxiety
• Insomnia
• Pain

Approved in United States as tVNS for:

• Epilepsy
• Depression
• Migraines

Who Is Running the Clinical Trial?

University of Notre Dame

Lead Sponsor

Trials

36

Recruited

60,000+

University of Wisconsin, Madison

Collaborator

Trials

1,249

Recruited

3,255,000+

University of Rochester

Collaborator

Trials

883

Recruited

555,000+

Findings from Research

Transcutaneous vagus nerve stimulation (tVNS) significantly reduced depression symptoms in patients with mild to moderate major depressive disorder (MDD), as evidenced by a notable decrease in Hamilton Depression Rating Scale scores after one month of treatment.

tVNS was found to modulate functional connectivity in the brain's default mode network, indicating potential mechanisms through which it may exert its antidepressant effects, particularly by altering connectivity with regions like the anterior insula and parahippocampus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous Vagus Nerve Stimulation Modulates Default Mode Network in Major Depressive Disorder. Fang, J., Rong, P., Hong, Y., et al.[2022]

Transcutaneous vagus nerve stimulation (tVNS) was found to significantly increase salivary alpha amylase (SAA) levels and reduce the decline of salivary cortisol in healthy participants, indicating a modulation of hormonal indices related to noradrenergic function.

However, tVNS did not show any significant effects on psychophysiological measures such as P3 amplitude or pupil size, suggesting that while it may influence hormonal responses, it does not impact certain cognitive or physiological indices in the same way.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The neuromodulatory and hormonal effects of transcutaneous vagus nerve stimulation as evidenced by salivary alpha amylase, salivary cortisol, pupil diameter, and the P3 event-related potential. Warren, CM., Tona, KD., Ouwerkerk, L., et al.[2019]

Transcutaneous vagus nerve stimulation (tVNS) is a promising non-invasive alternative to traditional vagus nerve stimulation (VNS) for treating conditions like epilepsy and depression, which can be invasive and have side effects.

There is ongoing research into the best stimulation parameters and sites for tVNS, particularly focusing on stimulation at the outer ear, to optimize its therapeutic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous vagus nerve stimulation and the realm of its therapeutic hopes and physiologic enigmas. Hilz, MJ., Bolz, A.[2022]

Vagus nerve stimulation (VNS) is an FDA-approved treatment for epilepsy, morbid obesity, and treatment-resistant depression, but it is often underutilized due to high costs and the need for surgical implantation.

The development of transcutaneous auricular VNS (taVNS) offers a promising noninvasive alternative that could provide a safe, at-home treatment option for various neuropsychiatric disorders, with ongoing trials like the RECOVER trial evaluating its efficacy in treatment-resistant depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Future Is Noninvasive: A Brief Review of the Evolution and Clinical Utility of Vagus Nerve Stimulation. Badran, BW., Austelle, CW.[2023]

Transcutaneous vagus nerve stimulation (tVNS) shows promise for treating various conditions in pediatric patients, but current studies lack specific protocols and justification for its use in this age group, as none of the 15 identified studies focused exclusively on children.

There are no dedicated tVNS devices for pediatric use, and existing studies do not adequately address neurodevelopmental considerations, highlighting the need for more research on age-appropriate stimulation parameters and protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous Auricular Vagus Nerve Stimulation in Pediatric Patients: A Systematic Review of Clinical Treatment Protocols and Stimulation Parameters. Sigrist, C., Torki, B., Bolz, LO., 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) 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 a safe and well-tolerated method for treating conditions like drug-resistant epilepsy, but a recent randomized double-blind trial found no significant difference in outcomes between high- and low-stimulation groups.

The most common side effect of taVNS is a tingling sensation or pain at the stimulation site, and while it shows promise, further research is needed to fully understand its efficacy and to potentially gain approval for insurance coverage in Japan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical Application of Transcutaneous Auricular Vagus Nerve Stimulation]. Yamamoto, T.[2022]

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]

A pilot study involving 24 patients with chronic tinnitus demonstrated that transcutaneous vagus nerve stimulation (tVNS) is a feasible and generally safe treatment method, with only two adverse cardiac events reported, which were unlikely linked to the device.

Preliminary data suggest that tVNS does not cause arrhythmic effects in patients without known heart conditions, indicating its potential safety for cardiac function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous vagus nerve stimulation: retrospective assessment of cardiac safety in a pilot study. Kreuzer, PM., Landgrebe, M., Husser, O., et al.[2022]

References

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

Transcutaneous Vagus Nerve Stimulation Modulates Default Mode Network in Major Depressive Disorder. [2022]

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

The neuromodulatory and hormonal effects of transcutaneous vagus nerve stimulation as evidenced by salivary alpha amylase, salivary cortisol, pupil diameter, and the P3 event-related potential. [2019]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Transcutaneous vagus nerve stimulation and the realm of its therapeutic hopes and physiologic enigmas. [2022]

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

The Future Is Noninvasive: A Brief Review of the Evolution and Clinical Utility of Vagus Nerve Stimulation. [2023]

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

Transcutaneous Auricular Vagus Nerve Stimulation in Pediatric Patients: A Systematic Review of Clinical Treatment Protocols and Stimulation Parameters. [2023]

6. England pubmed.ncbi.nlm.nih.gov

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

7. 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]

8. Japan pubmed.ncbi.nlm.nih.gov

[Clinical Application of Transcutaneous Auricular Vagus Nerve Stimulation]. [2022]

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

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

10. Switzerland pubmed.ncbi.nlm.nih.gov

Transcutaneous vagus nerve stimulation: retrospective assessment of cardiac safety in a pilot study. [2022]