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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Post Concussion Syndrome
• Intervention / Treatment: Device: Intermittent Theta-Burst Stimulation; Device: Sham Intermittent Theta-Burst Stimulation

• Study Type: Interventional
• Enrollment (Estimated): 26
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sean Nestor, PhD, MD, FRCPC; Phone Number: 416-480-4085; Email: sean.nestor@sunnybrook.ca
• Study Contact Backup: Name: Matthew Burke, MD, FRCPC; Phone Number: 416-480-4216; Email: matthew.burke@sunnybrook.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N3M5
      • Recruiting
      • Sunnybrook Health Sciences Centre
      • Contact: Sean Nestor, PhD MD FRCPC; Phone Number: 416-480-4085; Email: sean.nestor@sunnybrook.ca
      • Principal Investigator: Sean Nestor, PhD MD FRCPC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment	Device: Intermittent Theta-Burst Stimulation; 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
Sham Comparator: Sham	Device: Sham Intermittent Theta-Burst Stimulation; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Montgomery-Åsberg Depression Rating Scale	Montgomery-Åsberg Depression Rating Scale is a widely used clinician-rated measure of depressive severity	Baseline, post treatment day 5, and post treatment 1 month
Repeatable Battery for the Assessment of Neuropsychological Status	RBANS is a brief, individually administered battery to measure cognitive decline or improvement	Baseline and post treatment 1 month
The Behavior Rating Inventory of Executive Function	BRIEF-A is a standardized measure that captures views of an adult's executive functions or self-regulation in his or her everyday environment.	Baseline, post treatment day 5, and post treatment 1 month
Headache Impact Test	HIT is a tool used to measure the impact headaches have on your ability to function on the job, at school, at home and in social situations.	Baseline and post treatment 1 month

Collaborators and Investigators

• Sponsor: Sunnybrook Health Sciences Centre

Study record dates

Study Major Dates

• Study Start (Actual): October 31, 2023
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: June 20, 2023
• First Submitted That Met QC Criteria: September 7, 2023
• First Posted (Actual): September 11, 2023

Study Record Updates

• Last Update Posted (Actual): November 2, 2023
• Last Update Submitted That Met QC Criteria: October 31, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Wounds and Injuries; Disease; Craniocerebral Trauma; Trauma, Nervous System; Brain Concussion; Head Injuries, Closed; Wounds, Nonpenetrating; Syndrome; Post-Concussion Syndrome
• Other Study ID Numbers: 5821

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No