Brain Stimulation for Post-Concussion Syndrome

Overseen By Kevin Bickart, MD/PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, Los Angeles

Disqualifiers: Neurologic deficits, Severe mental problems, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 15

Duration: 2 weeks

75 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this study is to investigate a new treatment for chronic symptoms after concussion or mild traumatic brain injury in people aged 18-65 years old. Chronic symptoms could include dizziness, headache, fatigue, brain fog, memory difficulty, sleep disruption, irritability, or anxiety that occurred or worsened after the injury. These symptoms can interfere with daily functioning, causing difficulty returning to physical activity, work, or school. Previous concussion therapies have not been personalized nor involved direct treatments to the brain itself. The treatment being tested in the present study is a noninvasive, personalized form of brain stimulation, called transcranial magnetic stimulation (TMS). The investigators intend to answer the questions: 1. Does personalized TMS improve brain connectivity after concussion? 2. Does personalized TMS improve avoidance behaviors and chronic concussive symptoms? 3. Do the improvements last up to 2 months post-treatment? 4. Are there predictors of treatment response, or who might respond the best? Participants will undergo 14 total visits to University of California Los Angeles (UCLA): 1. One for the baseline symptom assessments and magnetic resonance imaging (MRI) 2. Ten for TMS administration 3. Three for post-treatment symptom assessments and MRIs Participants will have a 66% chance of being assigned to an active TMS group and 33% chance of being assigned to a sham, or inactive, TMS group. The difference is that the active TMS is more likely to cause functional changes in the brain than the inactive TMS.

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 Personalized Brain Stimulation for post-concussion syndrome?

Research suggests that personalized repetitive magnetic stimulation (PrTMS), which adjusts stimulation based on brain activity patterns, improved symptoms in concussion patients. Although the study lacked a control group, it showed potential for improving brain function and symptoms in those with persistent concussion issues. ^{1 2 3 4 5}

Is brain stimulation safe for treating post-concussion syndrome?

Research on brain stimulation techniques like transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) suggests they are generally safe for humans, with studies focusing on their use for post-concussion symptoms showing they are well-tolerated. ^{2 3 4 6 7}

How is Personalized Brain Stimulation different from other treatments for post-concussion syndrome?

Personalized Brain Stimulation (PrTMS) is unique because it adjusts the frequency of magnetic pulses based on individual brain activity patterns measured by EEG (a test that records brain waves), making it tailored to each patient's needs. This approach aims to improve brain function by targeting specific areas, unlike standard treatments that do not offer this level of customization. ^{2 4 8 9 10}

Eligibility Criteria

This trial is for people aged 18-65 who've had a mild traumatic brain injury in the last year and are struggling with symptoms like dizziness, headaches, or memory issues. They should have significant post-concussive symptoms but no severe medical conditions, drug abuse history, previous TMS therapy, or MRI contraindications like pacemakers.

Inclusion Criteria

I score 20 or more on the Rivermead Post-Concussion Symptoms test.

I have had a mild brain injury in the last year.

I was between 18 and 65 years old when I had my mild traumatic brain injury.

Exclusion Criteria

I do not have severe health issues that could interfere with the study.

I have measurable issues with my nervous system.

Inability to speak and read English

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Assessment

Baseline symptom assessments and magnetic resonance imaging (MRI)

1 day

1 visit (in-person)

Treatment

Participants receive 10 days of transcranial magnetic stimulation (TMS) administration

2 weeks

10 visits (in-person)

Post-Treatment Assessment

Post-treatment symptom assessments and MRIs

1 week

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

Treatment Details

Interventions

• Personalized Brain Stimulation

Trial Overview The study tests personalized transcranial magnetic stimulation (TMS) to treat chronic concussion symptoms. Participants will visit UCLA for baseline assessments and MRIs, receive TMS over ten sessions, and then have follow-up assessments. Two-thirds will get active TMS believed to change brain function; one-third will get sham TMS.

Participant Groups

Group I: Active continuous theta-burst stimulation (cTBS) plus exposure Experimental Treatment 2 Interventions

10 days of active, continuous theta-burst stimulation (cTBS) will be delivered to a personalized region of the ventromedial prefrontal cortex (vmPFC) based on baseline brain circuit mapping for each individual participant.

Group II: Active Comparator continuous theta-burst stimulation (cTBS) plus exposure Active Control 2 Interventions

10 days of active, continuous theta-burst stimulation (cTBS) will be delivered to a personalized region of the ventromedial prefrontal cortex (vmPFC) based on baseline brain circuit mapping for each individual participant.

Group III: Inactive/Sham continuous theta-burst stimulation (cTBS) plus exposure Placebo Group 2 Interventions

10 days of inactive, or sham, continuous theta-burst stimulation (cTBS) will be delivered to a personalized region of the ventromedial prefrontal cortex (vmPFC) based on baseline brain circuit mapping for each individual participant.

Who Is Running the Clinical Trial?

University of California, Los Angeles

Lead Sponsor

Trials

1,594

Recruited

10,430,000+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Findings from Research

A study involving 25 patients aged 12-20 with post-concussion syndrome showed that a multimodal physical therapy approach significantly reduced symptoms, as indicated by a decrease in the Post-Concussion Symptom Scale scores from an average of 18.2 to 9.1 after treatment.

The therapy also improved physical performance, with a 23% increase in maximum symptom-free heart rate during exercise and a 52% reduction in balance errors, demonstrating both safety and efficacy in managing post-concussion symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multimodal impairment-based physical therapy for the treatment of patients with post-concussion syndrome: A retrospective analysis on safety and feasibility. Grabowski, P., Wilson, J., Walker, A., et al.[2022]

Repetitive transcranial magnetic stimulation (rTMS) shows promising preliminary results in treating post-concussive symptoms, particularly for depression and headaches, based on a systematic review of 11 studies involving small pilot samples.

While rTMS demonstrated positive outcomes in some studies, the overall methodological diversity and small sample sizes highlight the need for further research to confirm its efficacy in larger populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Magnetic Stimulation for the Treatment of Concussion: A Systematic Review. Mollica, A., Safavifar, F., Fralick, M., et al.[2022]

Transcranial direct current stimulation (tDCS) showed promising early efficacy in improving working memory performance in youth with cognitive persistent post-concussion symptoms, particularly on a dual task working memory test.

The study found that participants tolerated tDCS well, with the active tDCS group reporting fewer strong symptoms compared to the sham group, suggesting it could be a feasible adjunct to behavioral therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of transcranial direct current stimulation on cognitive performance in youth with persistent cognitive symptoms following concussion: a controlled pilot study. Quinn de Launay, K., Cheung, ST., Riggs, L., et al.[2022]

A personalized rTMS (PrTMS) protocol was tested on 185 patients with persistent concussion symptoms over approximately 6 weeks, showing improvements in concussion-related indices and normalization of EEG measures, suggesting potential changes in neurotransmitter and cognitive function.

While the results are promising, indicating that PrTMS may be a viable treatment option for concussion, the study lacked a control group and did not account for several variables, highlighting the need for further research to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary Observations of Personalized Repetitive Magnetic Stimulation (PrTMS) Guided by EEG Spectra for Concussion. Makale, MT., Nybo, C., Keifer, J., et al.[2023]

Brain stimulation techniques, particularly transcranial direct current stimulation, show promise in promoting recovery from traumatic brain injury (TBI), especially in chronic phases, but evidence for acute phase efficacy and safety is still limited.

Most current brain stimulation interventions are non-targeted and lack sufficient clinical trials, highlighting the need for larger, well-designed studies to better understand their potential benefits in enhancing neuroplasticity and functional outcomes after TBI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical utility of brain stimulation modalities following traumatic brain injury: current evidence. Li, S., Zaninotto, AL., Neville, IS., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Multimodal impairment-based physical therapy for the treatment of patients with post-concussion syndrome: A retrospective analysis on safety and feasibility. [2022]

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

Transcranial Magnetic Stimulation for the Treatment of Concussion: A Systematic Review. [2022]

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

The effect of transcranial direct current stimulation on cognitive performance in youth with persistent cognitive symptoms following concussion: a controlled pilot study. [2022]

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

Preliminary Observations of Personalized Repetitive Magnetic Stimulation (PrTMS) Guided by EEG Spectra for Concussion. [2023]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Clinical utility of brain stimulation modalities following traumatic brain injury: current evidence. [2022]

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

Post concussion syndrome. [2022]

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

Cognitive-behavioral prevention of postconcussion syndrome in at-risk patients: a pilot randomized controlled trial. [2018]

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

Individualized Connectome-Targeted Transcranial Magnetic Stimulation for Neuropsychiatric Sequelae of Repetitive Traumatic Brain Injury in a Retired NFL Player. [2022]

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

Corticomotor correlates of somatosensory reaction time and variability in individuals with post concussion symptoms. [2021]

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

Regional personalized electrodes to select transcranial current stimulation target. [2021]