Accelerated, Theta-burst Stimulation for the Treatment of Post-concussion Syndrome - Open-label Pilot Study

Image-guided, Accelerated, Theta-burst Stimulation for the Treatment of Post-concussion Syndrome - Open-label Pilot Study

The current study aims to better understand the efficacy of intermittent theta-burst stimulation (iTBS) treatment in patients diagnosed with post-concussion syndrome (PCS) and to explore changes in brain networks after undergoing iTBS to assess its safety and feasibility in treating PCS.

Study Overview

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

Detailed Description

This open-label pilot study aims to investigate the potential of a 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 (mTBI). PCS is characterized by symptoms like cognitive impairment, mood dysregulation, fatigue, and headaches, with limited treatment options. Previous research has indicated brain network dysfunction in mTBI patients and suggested the potential of conventional once daily high frequency rTMS for treating PCS symptoms. Our proposal builds on these findings by utilizing the expertise and resources of Sunnybrook's Harquail Centre for Neuromodulation, which has extensive experience in delivering rTMS and theta-burst stimulation for treatment-resistant depression. This pilot study will implement an accelerated iTBS rTMS protocol, offering shorter treatment duration, as well as MRI-guided stimulation for precise targeting. The investigators will also explore changes in brain function following rTMS using a technique called functional magnetic resonance imaging. The investigators ultimately aim to understand how iTBS may alter the post-concussive brain and the extent to which these changes may improve PCS.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sean M Nestor, MD; Phone Number: 416-480-4085; Email: sean.nestor@sunnybrook.ca
• Study Contact Backup: Name: Erica S Reyvas, BA; Phone Number: 416-480-4053; Email: erica.reyvas@sri.utoronto.ca

Study Locations

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

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 24 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: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Accelerated Intermittent Theta-Burst Stimulation; 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	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 motor threshold (MT)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rivermead Post-Concussion Symptoms Questionnaire	A validated measure of subjective global PCS symptoms	Baseline, immediately before the first iTBS treatment
Rivermead Post-Concussion Symptoms Questionnaire	A validated measure of subjective global PCS symptoms	5 days
Rivermead Post-Concussion Symptoms Questionnaire	A validated measure of subjective global PCS symptoms	1 month post-treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Montgomery-Asberg Depression Rating Scale	Montgomery-Åsberg Depression Rating Scale is a widely used clinician-rated measure of depressive severity	Baseline, post treatment day 5, and Study endpoint
Repeatable Battery for the Assessment of Neuropsychological Status	Repeatable Battery for the Assessment of Neuropsychological Status 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	The Behavior Rating Inventory of Executive Function-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	Headache Impact Test is a tool used to measure the impact headaches have on one's 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): April 29, 2024
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: May 1, 2024
• First Submitted That Met QC Criteria: May 1, 2024
• First Posted (Actual): May 3, 2024

Study Record Updates

• Last Update Posted (Actual): May 8, 2024
• Last Update Submitted That Met QC Criteria: May 6, 2024
• Last Verified: May 1, 2024

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: 6160

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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