Theta-Burst Stimulation for Post-Concussion Syndrome

Overseen By Erica S Reyvas, BA

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Sunnybrook Health Sciences Centre

Must not be taking: Anticonvulsants, Antiepileptics, Benzodiazepines

Disqualifiers: Seizure disorder, Substance dependence, Pregnancy, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 5 days

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment using intermittent theta-burst stimulation (iTBS), a non-invasive brain stimulation technique, to alleviate symptoms of post-concussion syndrome (PCS). Researchers aim to determine if iTBS is safe and effective in reducing PCS symptoms such as headaches, dizziness, and difficulties with memory or concentration. The trial seeks participants who have experienced a head injury resulting in issues like loss of consciousness and have had PCS symptoms for 3 to 24 months. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research that could enhance PCS treatment options.

Will I have to stop taking my current medications?

The trial requires that you stop taking any anticonvulsant or antiepileptic medications, and you cannot take more than 2 mg of lorazepam (or its equivalent) daily.

What prior data suggests that intermittent theta-burst stimulation is safe for treating post-concussion syndrome?

Research has shown that Intermittent Theta-Burst Stimulation (iTBS) is generally safe. Studies indicate a low risk of seizures during iTBS, with fewer than 3 out of 100,000 sessions resulting in one, making seizures a rare side effect. iTBS is a non-invasive method used to stimulate the brain and has been applied in treating conditions like depression and brain injuries. In these cases, it has improved thinking and movement abilities. These findings suggest that iTBS is well-tolerated and can be a safe option for those considering this treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for post-concussion syndrome, like rest, medication for symptoms, and cognitive therapy, focus on managing symptoms rather than addressing the underlying brain activity. However, intermittent theta-burst stimulation (iTBS) is unique because it uses a non-invasive technique called repetitive transcranial magnetic stimulation (rTMS) to directly stimulate brain activity. This method targets specific brain areas with magnetic pulses, potentially improving brain function and reducing symptoms. Researchers are excited about iTBS because it could offer faster relief and a more direct approach to healing the brain compared to traditional treatments.

What evidence suggests that intermittent theta-burst stimulation is effective for post-concussion syndrome?

Research suggests that Intermittent Theta-Burst Stimulation (iTBS) can improve thinking and movement in conditions like traumatic brain injury. This method uses quick, non-invasive pulses to potentially alter brain activity. Studies have shown that iTBS can influence the brain's ability to adapt and change, sometimes more effectively than longer sessions of other brain stimulation types. Although research on its effects for post-concussion syndrome is still developing, these findings are promising for its potential benefits. Participants in this trial will receive accelerated iTBS as an experimental treatment for post-concussion syndrome. ^{1 4 5 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals with post-concussion syndrome, which means they have lingering symptoms like headaches or dizziness after a head injury. Participants should be diagnosed with PCS to qualify.

Inclusion Criteria

My communication issues are not due to my health condition.

Able to provide informed consent and comply with the study protocol

My symptoms have lasted more than 3 months but less than 2 years.

Exclusion Criteria

I have a history of seizures, not counting childhood febrile seizures.

I take more than 2 mg of lorazepam daily or any anticonvulsant.

Substance dependence within the last 6 months

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive accelerated intermittent theta-burst stimulation (iTBS) repetitive transcranial magnetic stimulation (rTMS) for treating post-concussive syndrome

5 days

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment using various assessments

1 month

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Intermittent Theta-Burst Stimulation

Trial Overview

The study is testing intermittent theta-burst stimulation (iTBS), a non-invasive brain stimulation technique, to see if it can help relieve symptoms of post-concussion syndrome and improve brain function.

How Is the Trial Designed?

Group I: Accelerated Intermittent Theta-Burst Stimulation Experimental Treatment 1 Intervention

Non-invasive brain stimulation technique, accelerated intermittent theta-burst stimulation (iTBS) repetitive transcranial magnetic stimulation (rTMS), for treating post- concussive syndrome (PCS) in persons with mild traumatic brain injury

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

Approved in United States as Intermittent Theta-Burst Stimulation for:

• Treatment-resistant depression
• Research use for post-concussion syndrome

Approved in European Union as Intermittent Theta-Burst Stimulation for:

• Treatment-resistant depression
• Research use for various neurological conditions

Approved in Canada as Intermittent Theta-Burst Stimulation for:

• Treatment-resistant depression
• Research use for post-concussion syndrome and other neurological conditions

Who Is Running the Clinical Trial?

Sunnybrook Health Sciences Centre

Lead Sponsor

Trials

693

Recruited

1,569,000+

Published Research Related to This Trial

Combining intermittent theta burst stimulation (iTBS) with cognitive training significantly improved cognitive function and upper limb performance in post-stroke cognitive impairment (PSCI) patients compared to cognitive training alone, as shown by increased scores on various cognitive assessments and functional tests.

The study found that improvements in cognitive scores (MMSE/MoCA) were significantly correlated with enhanced gait parameters, indicating that iTBS may not only aid cognitive recovery but also positively influence physical rehabilitation outcomes in PSCI patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent theta burst stimulation combined with cognitive training improves cognitive dysfunction and physical dysfunction in patients with post-stroke cognitive impairment. Yu, H., Shu, X., Zhou, Y., et al.[2023]

Theta burst stimulation (TBS) is a promising technique for altering brain excitability, with a review of studies showing that adverse events were mostly mild and occurred in only 5% of subjects, indicating a generally safe profile.

Despite its safety, TBS carries a theoretical higher risk of seizures compared to other stimulation methods, necessitating cautious application and further research into its dosing parameters to better understand seizure risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of theta burst transcranial magnetic stimulation: a systematic review of the literature. Oberman, L., Edwards, D., Eldaief, M., et al.[2022]

Intermittent theta-burst stimulation (iTBS) significantly improves hand function in stroke patients, particularly in those with higher baseline motor function and the presence of motor-evoked potentials (MEPs).

The study of 72 stroke patients showed that those with MEPs and better grip strength (Group A) had the greatest improvement in motor function, suggesting that iTBS effectiveness can be predicted by these factors, allowing for more tailored neurostimulation strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Corticospinal integrity and motor impairment predict outcomes after excitatory repetitive transcranial magnetic stimulation: a preliminary study. Lai, CJ., Wang, CP., Tsai, PY., et al.[2016]

Intermittent theta-burst stimulation (iTBS) shows promise as a targeted treatment for cognitive and psychosocial deficits following traumatic brain injury (TBI), potentially enhancing recovery when combined with behavioral interventions like cognitive rehabilitation and psychotherapy.

This review suggests that iTBS could lead to consistent functional gains in TBI patients, and future research may explore its application in other complex neuropsychiatric conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

rTMS/iTBS and Cognitive Rehabilitation for Deficits Associated With TBI and PTSD: A Theoretical Framework and Review. Lindsey, A., Ellison, RL., Herrold, AA., et al.[2023]

Theta burst stimulation (TBS) appears to be safe and tolerable for children and adolescents, with reported adverse events mostly being mild, such as headaches, similar to those seen in adults.

Despite the promising safety profile, there is a lack of long-term studies on TBS in younger populations, highlighting the need for further research to better understand its effects and potential risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review of the Safety and Tolerability of Theta Burst Stimulation in Children and Adolescents. Elmaghraby, R., Sun, Q., Ozger, C., et al.[2023]

A study involving 30 patients recovering from mild traumatic brain injury (mTBI) and 26 matched controls found that one session of intermittent theta burst stimulation (iTBS) did not significantly change neurophysiological activity or cognitive performance, as measured by EEG and working memory tests.

The results indicate that iTBS may not be an effective intervention for enhancing brain recovery after mTBI, suggesting that further research is needed to explore its potential effects before considering it for therapeutic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigation of neurobiological responses to theta burst stimulation during recovery from mild traumatic brain injury (mTBI). Coyle, HL., Bailey, NW., Ponsford, J., et al.[2023]

In a study involving 46 veterans with PTSD, those who received 4 weeks of active intermittent theta burst stimulation (iTBS) had significantly better long-term outcomes, with a mean relapse time of 296 days compared to 182 days for those who received only 2 weeks of active treatment.

The study suggests that greater exposure to active iTBS is associated with reduced clinical relapse rates and that neuroimaging of brain connectivity may help predict long-term treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

One-year clinical outcomes following theta burst stimulation for post-traumatic stress disorder. Petrosino, NJ., Wout-Frank, MV'., Aiken, E., et al.[2021]

In a study involving 36 multiple sclerosis patients, intermittent theta burst stimulation (iTBS) significantly improved manual dexterity, as shown by faster completion times in the nine-hole peg test and increased performance in the Box and Block Test.

However, iTBS did not have a significant impact on hand motor imagery abilities, indicating that while it can enhance physical tasks, it may not affect cognitive aspects of motor function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Intermittent Theta Burst Stimulation on Manual Dexterity and Motor Imagery in Patients with Multiple Sclerosis: A Quasi-Experimental Controlled Study. Azin, M., Zangiabadi, N., Iranmanesh, F., et al.[2020]

Intermittent theta-burst stimulation (iTBS) may enhance cognitive function compared to control conditions, but results vary widely across studies due to methodological differences and small sample sizes (often less than 30 participants).

The meta-analysis highlights the need for standardization in iTBS application, as factors like stimulation location significantly affect outcomes, while the type of cognitive task does not contribute to variability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review and meta-analysis of the efficacy of intermittent theta burst stimulation (iTBS) on cognitive enhancement. Pabst, A., Proksch, S., Médé, B., et al.[2022]

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 frontal lobe showed significant improvements in language abilities for participants with post-stroke aphasia, as evidenced by moderate to large effect sizes on tests like the Boston Naming Test and Semantic Fluency Test.

The study, involving 36 participants over 3 weeks, demonstrated that iTBS not only enhanced language function but also led to increased brain activation and connectivity, suggesting that this treatment may promote cortical plasticity in the brain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent Theta Burst Stimulation (iTBS) for Treatment of Chronic Post-Stroke Aphasia: Results of a Pilot Randomized, Double-Blind, Sham-Controlled Trial. Szaflarski, JP., Nenert, R., Allendorfer, JB., et al.[2021]

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Theta-Burst Stimulation for Post-Concussion Syndrome

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Theta Burst Stimulation TMS Treatment: A Patient's Guide

For iTBS, current estimates suggest that fewer than 3 patients experience a seizure per 100,000 sessions. Seizures are more likely in patients ...