iTBS for Concussion-Related Impulsivity and Suicidal Thoughts

Overseen By Ibuola Kale

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: VA Office of Research and Development

Disqualifiers: Epilepsy, Claustrophobia, Substance use disorder, others

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

Compensation: Varies

Number of Visits: 5

Duration: 2 weeks

55 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called intermittent theta burst stimulation (iTBS), a high-powered magnetic pulse, to determine its effectiveness in addressing impulsivity, suicidal thoughts, and everyday difficulties following a mild traumatic brain injury (mTBI). The study aims to assess whether applying iTBS to the front of the head can improve these symptoms. Participants will receive either active iTBS or a placebo (inactive version) for comparison. Suitable candidates have experienced a mild brain injury, exhibit impulsive behavior, and have had recent suicidal thoughts. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative treatment.

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 prior data suggests that this technique is safe for treating impulsivity and suicidal thoughts after mTBI?

Research has shown that intermittent theta burst stimulation (iTBS) is generally safe for people. Studies have found that daily iTBS applied to certain brain areas can reduce suicidal thoughts and depression without causing major side effects. One study found that iTBS was safe and well-tolerated in a small group of patients with severe depression.

The FDA has already approved iTBS for treating depression, indicating a good safety record, although not specifically for the conditions studied in this trial. The current research aims to determine if using iTBS on the front of the head can help with impulsivity and suicidal thoughts after a mild brain injury. While this treatment is still in early testing for these specific issues, past findings suggest it is generally well-tolerated. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Intermittent Theta Burst Stimulation (iTBS) for concussion-related impulsivity and suicidal thoughts because it offers a novel approach to treatment through non-invasive brain stimulation. Unlike traditional methods that often rely on medication or cognitive therapy, iTBS uses targeted magnetic pulses to modulate brain activity, potentially providing quicker and more precise relief. This technique harnesses the brain's plasticity, aiming to improve symptoms by directly influencing neural circuits associated with impulsivity and mood regulation. The potential for rapid improvement and the non-invasive nature of iTBS make it an appealing alternative to standard treatment options.

What evidence suggests that iTBS is effective for impulsivity and suicidal thoughts after mTBI?

Research has shown that intermittent theta burst stimulation (iTBS) can help reduce suicidal thoughts. One study found that iTBS significantly lowered suicidal feelings in people with major depression. This treatment uses magnetic pulses to stimulate brain cells, strengthening brain connections. These changes can improve symptoms like impulsiveness and suicidal thoughts. Although the FDA has approved iTBS for other conditions, this trial tests it for these specific symptoms after a mild traumatic brain injury (mTBI). Participants in this trial will receive either active iTBS or placebo (sham) iTBS. Early results suggest that iTBS might be helpful, but more research is needed to confirm its effectiveness. ^{3 4 5 6 7}

Who Is on the Research Team?

Alexandra L Aaronson, MD

Principal Investigator

Edward Hines Jr. VA Hospital, Hines, IL

Are You a Good Fit for This Trial?

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

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.

I have been diagnosed with a mild traumatic brain injury according to the SACA scale.

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Intermittent Theta Burst Stimulation

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.

How Is the Trial Designed?

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

Intermittent Theta Burst Stimulation is already approved in United States, European Union for the following indications:

Approved in United States as iTBS for:

• Treatment-resistant depression

Approved in European Union as iTBS for:

• Treatment-resistant depression

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Published Research Related to This Trial

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 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 (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]

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]

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]

Citations

1. withpower.com withpower.com/trial/phase-1-mild-traumatic-brain-injury-mtbi-3-2023-a1743

iTBS for Concussion-Related Impulsivity and Suicidal ... In a study involving 81 participants with major depressive disorder, accelerated intermittent theta burst stimulation (iTBS) significantly reduced suicidality ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05647044

Study Details | NCT05647044 | Frontal iTBS for Impulsivity ... TMS induces neuroplasticity, leading to changes that have the potential to improve neurorehabilitation outcomes. TMS is effective for treating post-TBI ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165032723000770

Effect of intermittent theta burst stimulation on suicidal ... Intermittent theta burst stimulation (iTBS) is a safe, effective brain stimulation treatment for alleviating suicidal ideation in adults with ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11043680/

Effect of novel accelerated intermittent theta burst ... Similar results have been observed in our study, where 20 Hz aiTBS therapy improved SI, depressive symptoms and hopelessness, with no serious ...

5. nature.com nature.com/articles/s41380-025-03183-x

Intermittent theta burst stimulation for non-suicidal self ... In this study, we hypothesized that iTBS stimulation would be feasible and effective in reducing NSSI symptoms, suicidal ideation, and ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36682694/

Effect of intermittent theta burst stimulation on suicidal ... The current study suggested that daily iTBS of the left DLPFC for 2 weeks could effectively and safely alleviate suicidal ideation and mitigate depression in ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006322325013563

Efficacy and Safety of Accelerated Intermittent Theta-burst ... While 10-session daily accelerated intermittent theta burst stimulation (a-iTBS) is effective in adults, its duration and safety limit its use ...