Accelerated, Theta-burst Stimulation for the Treatment of Post-concussion Syndrome

NCT06031662 | Unknown

• 1 other identifier: 5821
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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.

Conditions

Post Concussion Syndrome

Outcome Measures

Primary Outcomes (3)

• Rivermead Post Concussion Symptoms Questionnaire

  RPQ, a validated measure of subjective global PCS symptoms.

  Baseline, change from baseline to immediately before the first iTBS treatment

• Rivermead Post Concussion Symptoms Questionnaire

  RPQ, a validated measure of subjective global PCS symptoms.

  5 days

• Rivermead Post Concussion Symptoms Questionnaire

  RPQ, a validated measure of subjective global PCS symptoms.

  1 month post-treatment

Secondary Outcomes (4)

• Montgomery-Åsberg Depression Rating Scale

  Baseline, post treatment day 5, and post treatment 1 month

• Repeatable Battery for the Assessment of Neuropsychological Status

  Baseline and post treatment 1 month

• The Behavior Rating Inventory of Executive Function

  Baseline, post treatment day 5, and post treatment 1 month

• Headache Impact Test

  Baseline and post treatment 1 month

Study Arms (2)

Treatment

EXPERIMENTAL

Device: Intermittent Theta-Burst Stimulation

Sham

SHAM COMPARATOR

Device: Sham Intermittent Theta-Burst Stimulation

Interventions

Intermittent Theta-Burst Stimulation DEVICE

Accelerated course of left dlPFC iTBS, consisting of 600 pulses/session, 50 minutes intersession interval, 8 session/day for 5 days) at 90% resting MT

Treatment

Sham Intermittent Theta-Burst Stimulation DEVICE

Magventure Active/Placebo B70 coil specifically designed for randomized clinical trials with TMS. This system uses electrodes placed on the scalp to provide stimulation mimicking the active treatment condition

Sham

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead

Study Sites (1)

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N3M5, Canada

RECRUITING

MeSH Terms

Conditions

Post-Concussion Syndrome

Condition Hierarchy (Ancestors)

Brain Concussion; Head Injuries, Closed; Craniocerebral Trauma; Trauma, Nervous System; Nervous System Diseases; Wounds and Injuries; Wounds, Nonpenetrating

Central Study Contacts

Sean Nestor, PhD, MD, FRCPC

CONTACT

416-480-4085; sean.nestor@sunnybrook.ca

Matthew Burke, MD, FRCPC

CONTACT

416-480-4216; matthew.burke@sunnybrook.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: clinician-investigator and interventional psychiatrist

Study Record Dates

• First Submitted: June 20, 2023
• First Posted: September 11, 2023
• Study Start: October 31, 2023
• Primary Completion: August 1, 2025
• Study Completion: August 1, 2025
• Last Updated: November 2, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)