Brain Stimulation for Suicide Risk

(ENACTS Trial)

Overseen By Casey S Gilmore, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: VA Office of Research and Development

Disqualifiers: Cognitive impairment, Seizures, Eczema, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 11

Duration: 1 week

14 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a short-term treatment using a gentle brain treatment and exercises to help Veterans improve decision-making and reduce suicidal thoughts and behaviors.

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 this treatment for reducing suicide risk?

Research suggests that transcranial direct current stimulation (tDCS) may help with depression, which is often linked to suicide risk. Some studies show tDCS can improve mood and cognitive function in people with depression, potentially reducing factors that contribute to suicidal thoughts. ^{1 2 3 4 5}

Is transcranial direct current stimulation (tDCS) safe for humans?

Transcranial direct current stimulation (tDCS) is generally considered safe for humans, with no reports of serious adverse effects in over 33,200 sessions and 1,000 subjects, including vulnerable populations. Common mild side effects include itching, tingling, and headaches, but these are not significantly different from those experienced with placebo treatments. ^{6 7 8 9 10}

How is the treatment Active Transcranial Direct Current Stimulation (tDCS) different from other treatments for suicide risk?

Active Transcranial Direct Current Stimulation (tDCS) is unique because it is a non-invasive treatment that uses electrical currents to stimulate specific areas of the brain, which may help improve mood and reduce symptoms of depression. Unlike traditional treatments like medication or talk therapy, tDCS directly targets brain activity and can be administered at home, although safety concerns need to be addressed. ^{1 3 9 11 12}

Research Team

Casey S Gilmore, PhD

Principal Investigator

Minneapolis VA Health Care System, Minneapolis, MN

Eligibility Criteria

This trial is for veterans currently in the MVAHCS Inpatient Psychiatric Unit who are at high risk of suicide, either screened positive on the VA's risk evaluation or attempted suicide within the last year. Participants must be able to complete tasks and have a smartphone. Those with seizure history, metal in their head, severe skin conditions on the scalp, involuntary commitment, inability to consent, or significant cognitive impairment cannot join.

Inclusion Criteria

I can complete necessary medical procedures and tasks.

You have a high risk of attempting suicide based on a recent suicide attempt or positive VA Comprehensive Suicide Risk Evaluation (CSRE) screening.

currently admitted into the MVAHCS Inpatient Psychiatric Unit

Exclusion Criteria

have moderate/severe cognitive impairment as determined by the Mini-Mental State Examination (score 27)

do not have a smartphone or device running Android or Apple iOS with which to download the mPRO EMA app

I am able to understand and agree to the study's requirements.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive 10 sessions of cognitive training concurrent with either active or sham transcranial direct current stimulation over five days

1 week

10 sessions (in-person)

Follow-up

Participants are monitored for changes in impulsive behavior, executive function, and quality of life

2 months

Follow-up assessments at 1 week, 1 month, and 2 months

Treatment Details

Interventions

• Active Transcranial Direct Current Stimulation (tDCS)
• Sham Transcranial Direct Current Stimulation (tDCS)

Trial Overview The ENACTS study tests a five-day intervention combining transcranial direct current stimulation (tDCS) with executive function training for veterans at high suicide risk. The goal is to see if this can reduce future suicidal behavior and improve quality of life. Participants will receive either active tDCS or a sham (placebo) version as part of the study.

Participant Groups

Group I: Active tDCS Experimental Treatment 1 Intervention

Participants will receive 10 sessions of cognitive training concurrent with transcranial direct current stimulation (anode over left frontal cortex, cathode over right frontal cortex; 2 mAmps for 20 minutes).

Group II: Sham tDCS Placebo Group 1 Intervention

Participants will receive 10 sessions of cognitive training concurrent with sham tDCS. For sham tDCS, electrodes are placed at the same locations as for active tDCS, but current is ramped up for the initial 30 secs, then immediately ramped back down. This method mimics the initial physical sensation of stimulation, but there is no active current for the remainder of the session.

Active Transcranial Direct Current Stimulation (tDCS) is already approved in United States, European Union for the following indications:

Approved in United States as Transcranial Direct Current Stimulation for:

• Treatment-resistant depression
• Chronic pain
• Cognitive enhancement
• Research purposes including suicide prevention

Approved in European Union as Transcranial Direct Current Stimulation for:

• Treatment-resistant depression
• Chronic pain
• Cognitive enhancement
• Research purposes including neurological and psychiatric conditions

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Findings from Research

Transcranial direct current stimulation (tDCS) did not cause cognitive deficits in 243 patients with major depressive disorder over 10 weeks, indicating it is a safe non-pharmacological treatment option.

Patients receiving tDCS showed improved verbal fluency compared to those on placebo, suggesting that tDCS may enhance certain cognitive functions in individuals who respond positively to the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive changes after tDCS and escitalopram treatment in major depressive disorder: Results from the placebo-controlled ELECT-TDCS trial. Moreno, ML., Goerigk, SA., Bertola, L., et al.[2022]

Transcranial direct current stimulation (tDCS) effectively targets and modulates depression-related brain areas, specifically the left dorsolateral prefrontal cortex (DLPFC), as confirmed by significant changes in cerebral blood flow and induced magnetic fields during treatment in a study of 66 depressed participants.

High-definition (HD) tDCS showed stronger effects on brain network modulation compared to conventional tDCS, and while both active treatments improved symptoms of anhedonia, there were no significant differences in overall depression scores between the two stimulation methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In-vivo imaging of targeting and modulation of depression-relevant circuitry by transcranial direct current stimulation: a randomized clinical trial. Jog, MS., Kim, E., Anderson, C., et al.[2021]

Transcranial direct current stimulation (tDCS) showed significant antidepressant effects in a study of 64 participants with depression, with improved mood after active treatment compared to sham treatment.

While tDCS was generally safe, there was a cautionary note regarding mood switching in individuals with bipolar disorder, as one participant experienced hypomania after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation for depression: 3-week, randomised, sham-controlled trial. Loo, CK., Alonzo, A., Martin, D., et al.[2022]

In a study involving 120 patients with moderate to severe major depressive disorder, the combination of transcranial direct current stimulation (tDCS) and sertraline significantly improved depression scores compared to sertraline alone, tDCS alone, and placebo, indicating enhanced treatment efficacy.

Both tDCS and sertraline showed similar safety profiles, with common side effects, but tDCS was associated with more scalp redness. Notably, there were some episodes of mania or hypomania, particularly in the combined treatment group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The sertraline vs. electrical current therapy for treating depression clinical study: results from a factorial, randomized, controlled trial. Brunoni, AR., Valiengo, L., Baccaro, A., et al.[2022]

Transcranial direct current stimulation (tDCS) was found to be significantly more effective than sham treatment in reducing depression severity, with a moderate effect size (Hedges' g=0.743) based on a meta-analysis of 6 randomized controlled trials involving 176 participants.

The study highlights the need for larger and more representative trials to better evaluate the efficacy of tDCS in treating major depression, as the current analysis was limited by the small number of studies and their sample sizes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation in the treatment of major depression: a meta-analysis. Kalu, UG., Sexton, CE., Loo, CK., et al.[2021]

Transcranial Direct Current Stimulation (tDCS) has been shown to be safe, with no reports of Serious Adverse Effects or irreversible injuries across over 33,200 sessions involving more than 1,000 subjects, including vulnerable populations.

Safety assessments indicate that the current densities used in conventional tDCS (≤4 milliamperes) are significantly lower than those that could potentially cause brain injury, suggesting that tDCS protocols are well within safe limits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. Bikson, M., Grossman, P., Thomas, C., et al.[2022]

Transcranial Direct Current Stimulation (tDCS) is generally considered safe, but there are concerns that it could lead to significant negative effects in healthy individuals.

The scientific community needs to be alerted about the potential risks of tDCS, emphasizing the importance of protecting healthy volunteers from possible harm.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of transcranial direct current stimulation in healthy participants. Boccard-Binet, S., Sen, A.[2021]

Transcranial direct current stimulation (tDCS) has been found to be safe for use in humans, with no severe complications reported in studies involving both adults and children when applied at intensities of 4 mA or less for up to 60 minutes.

Animal studies indicate that the electrical current used in tDCS is significantly lower than the threshold that could cause permanent changes to brain tissue, suggesting a strong safety profile for this neurorehabilitation method.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Transcranial Direct Current Stimulation in Neurorehabilitation. Ko, MH.[2023]

Transcranial direct current stimulation (tDCS) is shown to be as safe and acceptable as sham treatment in patients with major depressive disorder (MDD), with dropout rates of 8.8% for active tDCS and 12% for sham, indicating no significant difference.

The study analyzed data from 6 randomized clinical trials, revealing that while adverse event rates were slightly higher in the active tDCS group (73.5%) compared to sham (68.3%), the difference was not statistically significant, suggesting that tDCS is well-tolerated in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and acceptability of transcranial direct current stimulation for the acute treatment of major depressive episodes: Analysis of individual patient data. Moffa, AH., Brunoni, AR., Fregni, F., et al.[2019]

Transcranial direct current stimulation (tDCS) is generally considered safe, with mild and transient adverse effects reported in clinical trials, but the frequency and relationship of these effects with clinical variables remain unclear due to selective reporting bias.

Out of 209 studies reviewed, 117 mentioned adverse effects, with common issues like itching and tingling reported more frequently in the active tDCS group, although these differences were not statistically significant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review on reporting and assessment of adverse effects associated with transcranial direct current stimulation. Brunoni, AR., Amadera, J., Berbel, B., et al.[2022]

A randomized controlled trial (HomeDC) on the use of transcranial direct current stimulation (tDCS) at home for major depressive disorder was prematurely terminated due to safety concerns, specifically skin lesions in patients, highlighting the need for better safety monitoring.

Although the study showed significant reductions in depression scales over time, active tDCS did not demonstrate superior efficacy compared to sham tDCS, indicating that further high-quality research is necessary to explore the potential of tDCS for treating depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TDCS at home for depressive disorders: an updated systematic review and lessons learned from a prematurely terminated randomized controlled pilot study. Kumpf, U., Palm, U., Eder, J., et al.[2023]

Transcranial direct current stimulation (tDCS) is being tested as a safe and noninvasive treatment for patients with ultraresistant major depressive disorder (MDD) in a trial involving 60 participants, aiming to improve depressive symptoms compared to a sham treatment.

The study will assess various outcomes, including changes in depression ratings and cognitive function, over 30 sessions of stimulation, with the goal of determining the efficacy of tDCS in patients who have not responded to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Neurostimulation of the Brain in Depression Trial: Protocol for a Randomized Controlled Trial of Transcranial Direct Current Stimulation in Treatment-Resistant Depression. Suleman, R., Tucker, BV., Dursun, SM., et al.[2021]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Cognitive changes after tDCS and escitalopram treatment in major depressive disorder: Results from the placebo-controlled ELECT-TDCS trial. [2022]

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

In-vivo imaging of targeting and modulation of depression-relevant circuitry by transcranial direct current stimulation: a randomized clinical trial. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation for depression: 3-week, randomised, sham-controlled trial. [2022]

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

The sertraline vs. electrical current therapy for treating depression clinical study: results from a factorial, randomized, controlled trial. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation in the treatment of major depression: a meta-analysis. [2021]

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

Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. [2022]

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

Safety of transcranial direct current stimulation in healthy participants. [2021]

8. Korea (South) pubmed.ncbi.nlm.nih.gov

Safety of Transcranial Direct Current Stimulation in Neurorehabilitation. [2023]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and acceptability of transcranial direct current stimulation for the acute treatment of major depressive episodes: Analysis of individual patient data. [2019]

10. England pubmed.ncbi.nlm.nih.gov

A systematic review on reporting and assessment of adverse effects associated with transcranial direct current stimulation. [2022]

11. Germany pubmed.ncbi.nlm.nih.gov

TDCS at home for depressive disorders: an updated systematic review and lessons learned from a prematurely terminated randomized controlled pilot study. [2023]

12. Canada pubmed.ncbi.nlm.nih.gov

The Neurostimulation of the Brain in Depression Trial: Protocol for a Randomized Controlled Trial of Transcranial Direct Current Stimulation in Treatment-Resistant Depression. [2021]