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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two innovative approaches to assist teenagers struggling with suicidal thoughts. One method stimulates the vagus nerve through the skin (transcutaneous vagus nerve stimulation, or tVNS) to help manage emotions. The other uses a smartphone app to inspire peer support and reduce loneliness. The researchers aim to determine if these digital tools can effectively reach and support more teens at a lower cost than current methods. Teens aged 13 to 17 who often feel isolated, have trouble managing emotions, or have engaged in self-harm might be a good fit. Participants need daily access to a smartphone and must attend meetings in South Bend, IN, or Rochester, NY. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could transform mental health support for teens.

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 prior data suggests that these interventions are safe for adolescents?

Research has shown that transcutaneous vagus nerve stimulation (tVNS), a key part of this trial, is generally safe for individuals without heart issues. Most participants find it easy to handle. The most common side effect is mild skin irritation where the device contacts the skin. A few individuals might experience headaches or a runny nose, but these are rare.

The peer-support smartphone app tested alongside tVNS aims to help young people connect with others and manage their emotions. While specific data on side effects from using the app is not available, it is intended as a helpful tool. Overall, both components of the trial treatment typically have mild and manageable side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for suicidal thoughts because they explore new ways to help adolescents through vagus nerve stimulation (tVNS) and innovative phone app technology. Unlike traditional treatments that often involve medication and therapy sessions, these approaches are non-invasive and can be self-administered at home, making them highly accessible. The tVNS treatment targets the vagus nerve, which plays a role in mood regulation, offering a fresh mechanism of action. Meanwhile, the accompanying phone app, MindTiles, is designed to enhance emotional coping and peer connection, which could help in building social support networks. This combination of technology and neuroscience offers a promising new avenue for managing suicidal thoughts, potentially leading to quicker and more personalized interventions.

What evidence suggests that this trial's treatments could be effective for reducing suicidal thoughts in adolescents?

Research has shown that using a device on the skin to stimulate the vagus nerve (tVNS) can help treat major depression by reducing depression levels and improving treatment response. This is crucial because depression often links to suicidal thoughts. In this trial, one group of participants will receive the tVNS Program, involving daily nerve stimulation sessions. Another group will use a specially designed phone app, which previous studies showed reduced suicide attempts by 58.3% among high-risk patients after hospital discharge. Additionally, some participants will receive a combination of tVNS and the phone app, potentially offering a two-part solution: tVNS aids in managing emotions, while the app helps build social connections, both key to reducing suicidal thoughts. ^{6 7 8 9 10}

Who Is on the Research Team?

Kristin Valentino, PhD

Principal Investigator

University of Notre Dame

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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 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 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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12561950/

Effectiveness of Mobile Applications for Suicide Prevention Thus, the effectiveness of mobile applications in reducing suicidality remains inconclusive with previous findings showing inconsistent outcomes ...

2. medicine.yale.edu medicine.yale.edu/news-article/yale-ohio-state-study-mobile-phone-app-reduced-suicidal-behavior-among-high-risk-patients/

Yale Study: Mobile Phone App Reduced Suicidal Behavior ... 8 in JAMA Network Open, found that the app, OTX-202, reduced the recurrence of post-discharge suicide attempts by 58.3% among patients who had ...

3. bmcpsychiatry.biomedcentral.com bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-017-1458-0

a systematic review and meta-analysis - BMC Psychiatry Online and mobile telephone applications ('apps') have the potential to improve the scalability of effective interventions for suicidal ideation and self-harm.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9573577/

The Effectiveness of Mobile Apps for Monitoring and ... The aim of this review is to identify original studies on mobile apps that target suicidal crises.

5. mental.jmir.org mental.jmir.org/2024/1/e55528/

Efficacy of BrighterSide, a Self-Guided App for Suicidal Ideation The primary outcome was severity and frequency of suicidal ideation, and secondary outcomes included psychological distress and functioning and ...

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

Safety of transcutaneous auricular vagus nerve stimulation ... The author concluded that transcutaneous vagus nerve stimulation is well tolerated and safe, with only mild side effects such as local skin ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11841445/

A pooled analysis of the side effects of non-invasive ... Stimulation did not result in any significant differences for the majority of the assessed side effects, including headaches, neck pain, neck ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30217648/

Safety and tolerability of Transcutaneous Vagus Nerve ... The most common side effects were: local skin irritation from electrode placement (240 participants, 18.2%), headache (47, 3.6%) and nasopharyngitis (23, 1.7%).

9. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X23019289

Meniere Disease treated with transcutaneous auricular ... Previous studies shown that taVNS have side-effects such as cough, dizziness [12,15,16,29,64], but all of which didn't appear in our 12 weeks treatment. However ...

10. alzdiscovery.org alzdiscovery.org/uploads/cognitive_vitality_media/Vagal_Nerve_Stimulation.pdf

Vagal nerve stimulation Safety: tVNS is generally considered safe for people without cardiac abnormalities, with stimulation site irritation as the most common side effect. Further ...