iTBS for Concussion-Related Impulsivity and Suicidal Thoughts

Overseen by Alexandra L Aaronson, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: VA Office of Research and Development

Disqualifiers: Epilepsy, Claustrophobia, Substance use disorder, others

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

The investigators hope to develop a treatment for suicidal ideation (SI), impulsivity and functional impairments (such as difficulties in social and work settings) that occur after a mild traumatic brain injury (mTBI). These conditions have been shown to be linked. The investigators are using a high-powered magnetic pulse, called intermittent theta burst stimulation (iTBS) applied to the head to see if it can improve these symptoms. The high-powered magnetic pulse causes certain cells in the brain to activate, which seems to strengthen connections between parts of the brain. The purpose of this research is to gather early information on the safety and effectiveness of iTBS provided to the front of the head for impulsivity, SI and functional deficits after mTBI. The investigators plan to use the data collected in this study to develop larger studies in the future. iTBS is FDA approved, but not for these specific symptoms, or in the specific location the investigators are placing it. The investigators are testing to see if its effective for the above conditions when applied to the front of the head.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications.

What data supports the idea that iTBS for Concussion-Related Impulsivity and Suicidal Thoughts is an effective treatment?

The available research shows that iTBS can significantly reduce suicidal thoughts in people with depression. In one study, patients who received iTBS experienced a noticeable decrease in suicide risk, which lasted up to a month. This suggests that iTBS might be effective in reducing suicidal thoughts, even in those who do not respond to other depression treatments. However, the decrease in suicide risk was not directly linked to whether the patients received real or fake (sham) stimulation, indicating that more research is needed to confirm these findings. ^{1 2 3 4 5}

What safety data exists for iTBS treatment?

The safety of intermittent theta burst stimulation (iTBS) has been evaluated in several studies. In a randomized, sham-controlled trial with therapy-resistant depressed patients, iTBS was found to be safe and well-tolerated, with no worsening of suicidal ideation observed. Another study on bipolar depression reported no adverse events, indicating the safety and tolerability of iTBS. Overall, these studies suggest that iTBS is a safe treatment option, though further research is recommended. ^{1 2 4 6 7}

Is the treatment Intermittent Theta Burst Stimulation (iTBS) a promising treatment for impulsivity and suicidal thoughts related to concussions?

Yes, Intermittent Theta Burst Stimulation (iTBS) is a promising treatment. Research shows it can reduce suicidal thoughts and improve mood in people with depression, which suggests it might help with impulsivity and suicidal thoughts related to concussions as well. ^{1 2 3 4 5}

Research Team

Alexandra L Aaronson, MD

Principal Investigator

Edward Hines Jr. VA Hospital, Hines, IL

Eligibility Criteria

This trial is for veterans aged 22-65 with mild traumatic brain injury (mTBI) who experience impulsivity and suicidal thoughts. Participants must have a history of impulsivity or score high on an urgency scale, and have had recent suicidal ideation. They cannot join if they have epilepsy, MRI contraindications like claustrophobia or metal implants, severe TBI history, unstable medical conditions, recent major surgery, pregnancy, active substance abuse issues, non-traumatic neuroinjury history or current psychosis.

Inclusion Criteria

Can read and speak English

Has a history of impulsivity documented in the medical chart and/or a score of >20 on the UPPS-P negative urgency impulsivity subscale

I am between 22 and 65 years old.

Exclusion Criteria

Has an active substance use disorder per the DSM-V criteria

I had major surgery less than 12 weeks ago.

Has a history of moderate to severe TBI

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intermittent theta burst stimulation (iTBS) to the frontal pole for impulsivity and suicidal ideation

2 weeks

5 treatment sessions per week

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Intermittent Theta Burst Stimulation (Behavioural Intervention)

Trial Overview The study tests intermittent theta burst stimulation (iTBS), which uses magnetic pulses to activate brain cells in hopes of improving symptoms from mTBI such as impulsivity and suicidal thoughts. While iTBS is FDA approved for other uses, it's not yet approved for these specific symptoms when applied to the front of the head.

Participant Groups

Group I: active iTBS Active Control 1 Intervention

Subjects receiving active iTBS treatment

Group II: placebo iTBS Placebo Group 1 Intervention

Subjects receiving placebo (sham) iTBS treatment

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Dr. Grant Huang

VA Office of Research and Development

Acting Chief Research and Development Officer

PhD in Medical Psychology and Master of Public Health from the Uniformed Services University of Health Sciences

Dr. Erica M. Scavella

VA Office of Research and Development

Chief Medical Officer since 2022

MD from University of Massachusetts School of Medicine

Findings from Research

In a study involving 81 participants with major depressive disorder, accelerated intermittent theta burst stimulation (iTBS) significantly reduced suicidality and depressive symptoms over a 6-week period, indicating its potential as an effective treatment.

The intervention was found to be safe, with no serious adverse events reported, and showed particularly pronounced anti-suicidal effects in individuals with higher risk profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suicidality and relief of depressive symptoms with intermittent theta burst stimulation in a sham-controlled randomized clinical trial. Wilkening, J., Witteler, F., Goya-Maldonado, R.[2023]

Accelerated intermittent theta burst stimulation (TBS) was found to be safe and well tolerated in 12 suicidal therapy-resistant depressed patients, showing a significant decrease in suicidal ideation over time.

However, the reduction in suicidal thoughts was not definitively linked to the active TBS treatment compared to sham stimulation, indicating that further research is needed to confirm its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The acute effects of accelerated repetitive Transcranial Magnetic Stimulation on suicide risk in unipolar depression: preliminary results. Desmyter, S., Duprat, R., Baeken, C., et al.[2022]

In a clinical trial involving patients with treatment-resistant depression, both 10 Hz repetitive transcranial magnetic stimulation (rTMS) and intermittent theta-burst stimulation (iTBS) effectively reduced suicidality, with remission rates of 43.7% and 49.1% respectively, showing no significant difference between the two methods.

There was a strong correlation between reductions in suicidality and overall depression severity, indicating that improvements in suicidal thoughts were linked to greater decreases in depressive symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of high frequency versus theta-burst repetitive transcranial magnetic stimulation on suicidality in patients with treatment-resistant depression. Mehta, S., Downar, J., Mulsant, BH., et al.[2023]

Accelerated intermittent Theta Burst Stimulation (iTBS) was found to be safe and well tolerated in a study of 50 treatment-resistant depressed patients, with no worsening of suicidal ideation observed during the treatment.

The study showed a significant decrease in suicide risk, as measured by the Beck Scale of Suicide Ideation, lasting up to one month after treatment, regardless of whether patients received active or sham stimulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated Intermittent Theta Burst Stimulation for Suicide Risk in Therapy-Resistant Depressed Patients: A Randomized, Sham-Controlled Trial. Desmyter, S., Duprat, R., Baeken, C., et al.[2020]

In a randomized, double-blind trial involving 56 patients, intermittent theta burst stimulation (iTBS) over the dorsomedial prefrontal cortex showed a significant reduction in negative symptoms for patients with depression, but not for those with schizophrenia.

The treatment was generally safe and well-tolerated, with serious adverse events occurring only in the sham group, indicating that iTBS may be a promising intervention for depressive symptoms in certain patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dorsomedial prefrontal theta burst stimulation to treat anhedonia, avolition, and blunted affect in schizophrenia or depression - a randomized controlled trial. Bodén, R., Bengtsson, J., Thörnblom, E., et al.[2021]

In a study of 26 patients with bipolar depression, active intermittent theta burst stimulation (iTBS) showed a high response rate of 72% and a remission rate of 42%, indicating its potential efficacy in treating this condition.

No adverse events were reported, demonstrating that iTBS is safe and well-tolerated, but further research with larger sample sizes is needed to confirm its superiority over sham treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Twice-daily neuronavigated intermittent theta burst stimulation for bipolar depression: A Randomized Sham-Controlled Pilot Study. Bulteau, S., Beynel, L., Marendaz, C., et al.[2020]

Intermittent theta burst stimulation (iTBS) applied to the left dorsolateral prefrontal cortex significantly reduced suicidal ideation and depressive symptoms in adolescents with major depressive disorder over a 2-week treatment period involving 10 sessions.

The study involved 45 participants, and those with higher initial depression and suicidal ideation scores experienced greater improvements, suggesting that iTBS is particularly effective for more severely affected individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of intermittent theta burst stimulation on suicidal ideation and depressive symptoms in adolescent depression with suicide attempt: A randomized sham-controlled study. Zhao, Y., He, Z., Luo, W., et al.[2023]

References

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

Suicidality and relief of depressive symptoms with intermittent theta burst stimulation in a sham-controlled randomized clinical trial. [2023]

2. Croatia pubmed.ncbi.nlm.nih.gov

The acute effects of accelerated repetitive Transcranial Magnetic Stimulation on suicide risk in unipolar depression: preliminary results. [2022]

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

Effect of high frequency versus theta-burst repetitive transcranial magnetic stimulation on suicidality in patients with treatment-resistant depression. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Accelerated Intermittent Theta Burst Stimulation for Suicide Risk in Therapy-Resistant Depressed Patients: A Randomized, Sham-Controlled Trial. [2020]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Dorsomedial prefrontal theta burst stimulation to treat anhedonia, avolition, and blunted affect in schizophrenia or depression - a randomized controlled trial. [2021]

6. France pubmed.ncbi.nlm.nih.gov

Twice-daily neuronavigated intermittent theta burst stimulation for bipolar depression: A Randomized Sham-Controlled Pilot Study. [2020]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Effect of intermittent theta burst stimulation on suicidal ideation and depressive symptoms in adolescent depression with suicide attempt: A randomized sham-controlled study. [2023]