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

NCT ID: NCT06031662

Last Updated: 2023-11-02

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-10-31
• Study Completion Date: 2025-08-01

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Treatment

Group Type: EXPERIMENTAL

Intermittent Theta-Burst Stimulation

Intervention Type: 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

Sham

Group Type: SHAM_COMPARATOR

Sham Intermittent Theta-Burst Stimulation

Intervention Type: 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

Interventions

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

Intervention Type: 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

Intervention Type: DEVICE

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

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sunnybrook Health Sciences Centre

OTHER

Sponsor Role: lead

Responsible Party

Dr. Sean Michael Nestor

clinician-investigator and interventional psychiatrist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Sean Nestor, PhD, MD, FRCPC

Role: CONTACT

sean.nestor@sunnybrook.ca

416-480-4085

Matthew Burke, MD, FRCPC

Role: CONTACT

matthew.burke@sunnybrook.ca

416-480-4216

Facility Contacts

Sean Nestor, PhD MD FRCPC

Role: primary

sean.nestor@sunnybrook.ca

416-480-4085

Other Identifiers

5821

Identifier Type: -

Identifier Source: org_study_id