Clinical trial NCT06031662: Accelerated, Theta-burst Stimulation for the Treatment of Post-concussion Syndrome
Official title: Image-guided, Accelerated, Theta-burst Stimulation for the Treatment of Post-concussion Syndrome
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Post Concussion Syndrome
Lead sponsor: Sunnybrook Health Sciences Centre
Sponsor class: OTHER
First posted: 2023-09-11
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: TMS has been safely and reliably delivered at the Harquail Centre for over 5 years, with a primary focus on conventional rTMS protocols for treatment-resistant depression. Recently, the investgator team has gained the capability to deliver sham-controlled intermittent theta-burst stimulation (iTBS) rTMS. Unlike conventional high frequency rTMS, which was used in the previous sham-controlled rTMS PCS pilot study, iTBS is a patterned form of stimulation that recapitulates endogenous activity patterns of neural circuits pairing gamma frequency (50Hz) burst pulses coupled in a theta frequency rhythm (5Hz).12 iTBS delivers 600 pulses in just over 3 minutes with similar or greater effects on neural plasticity compared to conventional rTMS (taking over 30-45 minutes) and similar tolerability and efficacy in trials of depression. Furthermore, novel accelerated iTBS protocols stimulating the left dorsolateral prefrontal cortex (dlPFC) over 8-10 treatments, 50 minutes apart over a 5 day interval has recently demonstrated robust efficacy in depression and received recent FDA approval. Thus, accelerated iTBS can be delivered in a single week of treatment compared to 6 weeks with conventional rTMS methods. Finally, the investigators recently acquired the technology to integrate MRI neuroimage-guided stimulation, which would allow to target specific brain regions/networks implicated in PCS at high spatial resolution. No studies to date have investigated image-guided accelerated iTBS rTMS for the treatment of PCS.


Eligibility criteria: Inclusion Criteria:

* Documented evidence of head trauma sufficiently severe to result in loss of consciousness, post-traumatic amnesia and/or acute altered mental status.
* At least three symptoms including headache, dizziness, fatigue, irritability, insomnia, memory difficulties, concentration difficulties, mood dysregulation.
* Onset of symptoms within 4 weeks following the head trauma.
* Age 18-60, inclusive.
* Persistence of PCS symptoms for at least 3 months but less than 12 months
* Able to provide informed consent and comply with the study protocol
* Patients will not be excluded solely on the basis of communication (i.e., non-English speaking) unless they have exclusion criteria that is the cause of the communication difficulties.

Exclusion Criteria:

* Evidence of major structural neuroimaging abnormalities (e.g., intracranial hemorrhage, skull fracture or a large intracranial lesion)
* History of prior rTMS therapy,
* Contraindications to MRI (e.g., pacemaker, metallic implants etc.).
* Ferromagnetic, non-removable metallic implants from above the clavicle with the exception of dental work.
* Active personal injury litigation
* History of seizure disorder, not including febrile seizures in childhood
* Substance dependence within the last 6 months
* Pregnant
* Currently taking more than lorazepam 2 mg daily (or benzodiazepine equivalent) or any dose of an anticonvulsant (due to the potential to reduce rTMS efficacy)
* Currently taking an antiepileptic medication
* Mild and major comorbid medical conditions (as determined by investigators - e.g., neurological diseases, uncontrolled hypertension or diabetes, malignancy)
* A major comorbid psychiatric disorder (as determined by investigators - e.g., schizophrenia or bipolar disorder) and/or psychosis at the time of study enrollment

Primary outcomes:
measure: Rivermead Post Concussion Symptoms Questionnaire
timeFrame: Baseline, change from baseline to immediately before the first iTBS treatment
measure: Rivermead Post Concussion Symptoms Questionnaire
timeFrame: 5 days
measure: Rivermead Post Concussion Symptoms Questionnaire
timeFrame: 1 month post-treatment
Secondary outcomes:
measure: Montgomery-Åsberg Depression Rating Scale
timeFrame: Baseline, post treatment day 5, and post treatment 1 month
measure: Repeatable Battery for the Assessment of Neuropsychological Status
timeFrame: Baseline and post treatment 1 month
measure: The Behavior Rating Inventory of Executive Function
timeFrame: Baseline, post treatment day 5, and post treatment 1 month
measure: Headache Impact Test
timeFrame: Baseline and post treatment 1 month
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
Study officials:
References: