Theta-Burst Stimulation for Post-Concussion Syndrome

Overseen By Matthew Burke, MD, FRCPC

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 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 10

Duration: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for post-concussion syndrome, a condition that can cause headaches, dizziness, and memory problems after a head injury. The treatment uses theta-burst stimulation, a quick and targeted brain stimulation method, to determine if it can improve symptoms faster than traditional methods. The trial includes both a real treatment group and a placebo group to measure results effectively. Individuals who have experienced a concussion with symptoms like headaches and memory troubles for 3 to 12 months might be suitable for this study. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could lead to new treatment options.

Will I have to stop taking my current medications?

The trial requires that you stop taking any antiepileptic medications and limits lorazepam to no more than 2 mg daily (or its equivalent in other benzodiazepines). If you are taking these medications, you may need to adjust or stop them to participate.

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

Research has shown that intermittent theta-burst stimulation (iTBS) is generally safe and well-tolerated. Studies have found that iTBS can improve symptoms in conditions like PTSD without major side effects, especially compared to conventional repetitive transcranial magnetic stimulation (rTMS).

One study reported no seizures in 90 healthy children and 40 pediatric patients after iTBS treatment, suggesting its safety. Additionally, the FDA recently approved a faster version of iTBS for treating depression, indicating confidence in its safety for that condition.

Overall, while more research is needed specifically for post-concussion syndrome, current evidence suggests that iTBS remains safe and well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Theta-burst stimulation is unique because it uses rapid, short bursts of magnetic energy to stimulate specific areas of the brain. Unlike traditional treatments for post-concussion syndrome, which often include medication and cognitive therapy, this technique directly targets brain activity with precision. Researchers are excited about this treatment because it promises quicker symptom relief without the need for drugs, potentially offering a non-invasive alternative to help those who don't respond well to standard therapies.

What evidence suggests that accelerated theta-burst stimulation might be an effective treatment for post-concussion syndrome?

Research shows that accelerated intermittent theta-burst stimulation (iTBS) might improve symptoms in people with post-concussion syndrome (PCS). iTBS, a type of brain stimulation, works quickly and may help the brain change and adapt, similar to traditional methods. Some studies have found it effective for treating depression and post-traumatic stress disorder (PTSD), suggesting it could also benefit those with PCS. In this trial, participants will receive either the iTBS treatment or a sham comparator. Unlike regular treatments, iTBS sessions take only a few minutes and can be completed in just one week. Recent advancements allow doctors to target specific brain areas, enhancing treatment precision. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-60 who've had a head injury leading to loss of consciousness or memory issues, with symptoms like headaches and dizziness starting within 4 weeks of the injury and lasting 3-12 months. Participants must be able to consent and follow the study plan but can't join if they have major brain damage, history of seizures (except childhood febrile seizures), are pregnant, on certain medications, or involved in personal injury lawsuits.

Inclusion Criteria

I experience at least three symptoms like headache, dizziness, or fatigue.

My symptoms started within 4 weeks after a head injury.

I have had a head injury that caused me to lose consciousness or forget things.

Exclusion Criteria

I am currently on medication for epilepsy.

Ferromagnetic, non-removable metallic implants from above the clavicle with the exception of dental work

Active personal injury litigation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive accelerated iTBS rTMS treatment targeting the left dorsolateral prefrontal cortex over 8-10 sessions within a 5-day interval

1 week

8-10 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Accelerated, Theta-burst Stimulation

Trial Overview The trial tests an advanced form of brain stimulation called intermittent Theta-Burst Stimulation (iTBS) against a sham treatment. iTBS aims to improve neural plasticity using rapid bursts mimicking natural brain patterns. It's delivered over five days instead of six weeks like older methods. The technology also allows targeting specific brain areas implicated in Post-Concussion Syndrome using MRI guidance.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 1 Intervention

Group II: Sham Placebo Group 1 Intervention

Accelerated, Theta-burst Stimulation is already approved in United States for the following indications:

Approved in United States as rTMS for:

• Treatment-resistant depression

Who Is Running the Clinical Trial?

Sunnybrook Health Sciences Centre

Lead Sponsor

Trials

693

Recruited

1,569,000+

Published Research Related to This Trial

Theta-burst stimulation (TBS) was found to be safe for children, with no serious adverse events reported among 40 participants aged under 18, including those with Tourette syndrome and typically developing children.

Only 11.6% of participants experienced mild, self-limited side effects, such as finger twitching and headaches, indicating that TBS is well tolerated in this age group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of theta-burst transcranial magnetic stimulation in children. Wu, SW., Shahana, N., Huddleston, DA., et al.[2012]

In a study involving 300 patients with treatment-resistant depression, accelerated bilateral theta burst stimulation (TBS) was found to be effective and safe, with a treatment response rate of 43.7% and a remission rate of 28.2%.

The study revealed no significant differences in efficacy between different TBS intensities or when compared to traditional unilateral 10 Hz rTMS, indicating that the accelerated TBS does not provide faster antidepressant effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated theta burst stimulation for the treatment of depression: A randomised controlled trial. Chen, L., Thomas, EHX., Kaewpijit, P., et al.[2022]

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]

A study involving 50 veterans with PTSD showed that intermittent theta-burst stimulation (iTBS) significantly improved social and occupational functioning after 2 weeks, indicating its potential efficacy as a treatment for PTSD.

One month after treatment, iTBS demonstrated significant reductions in both clinician- and self-rated PTSD symptoms, as well as improvements in depression and functioning, suggesting that iTBS could be a promising new approach for managing PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Theta-Burst Transcranial Magnetic Stimulation for Posttraumatic Stress Disorder. Philip, NS., Barredo, J., Aiken, E., et al.[2020]

Intermittent theta-burst stimulation (iTBS) and high-frequency rTMS (HF-rTMS) show similar efficacy in treating treatment-resistant depression (TRD), with response rates of 48.0% for iTBS and 45.5% for HF-rTMS based on two high-quality randomized controlled trials involving 474 participants.

Both iTBS and HF-rTMS have comparable safety profiles, with similar rates of discontinuation and adverse events, such as headaches, indicating that iTBS is a safe alternative to HF-rTMS for patients with TRD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of intermittent theta burst stimulation versus high-frequency repetitive transcranial magnetic stimulation for patients with treatment-resistant depression: a systematic review. Lan, XJ., Yang, XH., Qin, ZJ., et al.[2023]

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]

The study found that continuous theta-burst stimulation (cTBS) can effectively reduce cortical excitability, but its effects show limited reproducibility across sessions, indicating variability in its impact.

Among the neurophysiological markers assessed, the modulation of corticospinal excitability measured 5 minutes after cTBS was the most consistent, suggesting it could be a reliable measure for future research on cTBS effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reproducibility of the effects of theta burst stimulation on motor cortical plasticity in healthy participants. Vernet, M., Bashir, S., Yoo, WK., et al.[2022]

A 25-year-old man with chronic traumatic brain injury showed significant improvements in balance and motor function after three weeks of cerebellar intermittent theta burst stimulation (iTBS) combined with neurorehabilitation, as measured by various assessments including the Fugl-Meyer Assessment and Berg Balance Scale.

The results indicated notable enhancements in balance performance (+10.72%), motor recovery (+3.00%), step length (+3.4 cm), and walking speed (+0.04 m/sec), suggesting that combining rTMS with rehabilitation can effectively aid recovery in TBI patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical effects of non-invasive cerebellar magnetic stimulation treatment combined with neuromotor rehabilitation in traumatic brain injury. A single case study. Martino Cinnera, A., Bonnì, S., Iosa, M., et al.[2022]

Intermittent theta burst stimulation (iTBS) is as effective as standard high-frequency (10 Hz) rTMS for treating treatment-resistant depression, showing non-inferiority in improving depression scores over 4-6 weeks in a study with 414 participants.

Both iTBS and 10 Hz rTMS had similar safety profiles and dropout rates, with headaches being the most common side effect, indicating that iTBS can be a viable alternative that allows for more patients to be treated in a shorter time without losing effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial. Blumberger, DM., Vila-Rodriguez, F., Thorpe, KE., et al.[2022]

Monophasic intermittent theta-burst stimulation (iTBS) was found to induce significantly greater increases in motor corticospinal excitability compared to biphasic iTBS, based on a study involving 30 healthy volunteers.

The study suggests that monophasic iTBS may have a stronger potential for functional impact in clinical applications, as it demonstrated a more pronounced physiological effect on motor neuron activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of pulse shape in theta-burst stimulation: Monophasic vs biphasic TMS. Wendt, K., Sorkhabi, MM., Stagg, CJ., 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]

This study aims to develop and assess a combined intervention of intermittent theta burst stimulation (iTBS) and yoga for military veterans with mild traumatic brain injury (mTBI) and chronic pain, focusing on feasibility and acceptability.

The intervention will be conducted over 6 weeks with 20 participants, and it is expected to provide preliminary evidence of safety and effectiveness in improving quality of life, function, and pain management for these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of a Combined Neuromodulation and Yoga Intervention for Mild Traumatic Brain Injury and Chronic Pain: Protocol for an Open-label Pilot Trial. Krese, KA., Donnelly, KZ., Etingen, B., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07211919

Study Details | NCT07211919 | Accelerated Transcranial ... This study looks at the effects of accelerated intermittent theta burst stimulation (aiTBS) on patients with chronic and acute post-concussion ...

2. medrxiv.org medrxiv.org/content/10.1101/2025.10.08.25336734v1

Functional MRI Guided Accelerated Intermittent Theta Burst ... This exploratory study aims to examine the feasibility and efficacy of a rapid, accelerated intermittent theta burst stimulation (iTBS) TMS ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0165178123004833

Effects of intermittent theta-burst transcranial magnetic ... ITBS, with a shorter treatment duration, can effectively improve the symptoms of PTSD, with no significant difference in effect from that of rTMS.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06398665

Accelerated, Theta-burst Stimulation for the Treatment of ... The current study aims to better understand the efficacy of intermittent theta-burst stimulation (iTBS) treatment in patients diagnosed with post-concussion ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12202228/

Adaptive trial for the treatment of depressive symptoms ... Adaptive trial for the treatment of depressive symptoms associated with concussion using accelerated intermittent theta burst stimulation (ADEPT): ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7664843/

Use of Repetitive Transcranial Magnetic Stimulation in the ... A Pilot Investigation of Repetitive Transcranial Magnetic Stimulation for Post-Traumatic Brain Injury Depression: Safety, Tolerability, and Efficacy. J ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7732158/

Transcranial Magnetic Stimulation (TMS) Safety with ... Allen et al 2017 identified no seizures after reviewing three theta-burst studies in 90 healthy children and 40 pediatric patients with CNS ...