Brain Stimulation for Concussion

Traumatic Brain Injury Clinical Trial

Official title:

Neurometabolic Effects of Theta-burst Treatment in Mild Traumatic Brain Injury

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05889117
• Other study ID #: 23-110
• Status: Recruiting
• Phase: N/A
• Start date: October 30, 2023
• Est. completion date: December 2024

Study information

• Verified date: March 2024
• Source: The Mind Research Network
• Contact: Jody Roberts, MS
• Phone: 505-272-5028
• Email: jroberts[@]mrn.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this clinical trial is to test a new type of magnetic brain stimulation in patients with persistent post-concussive symptoms. Participants will undergo detailed MRI scans before and after 30 treatment sessions (of 3-10 minutes each). The main questions the study aims to answer are:

• Will this new type of treatment result in fewer symptoms and better daily functioning?

• What are the effects of this treatment on brain functioning?

Description:

Repetitive transcranial magnetic stimulation (rTMS) seems a promising treatment option for patients with persistent post-concussive symptoms (PPCS). Traditional rTMS sessions are relatively long in duration and can be exhaustive for patients with PPCS. Intermittent theta-burst stimulation (iTBS) is a newer and more rapid form of rTMS, which only takes up to 10 minutes per session. However, little is known about the effects of iTBS in patients with PPCS. Furthermore, there is a pressing need for methods that reliably measure the effects of TMS treatments in-vivo. Using diffusion magnetic resonance spectroscopy (dMRS) changes in neural and glial cell morphology can be quantified, which makes it possible to disentangle neurometabolic changes related to neural injury and neuroinflammation, two key elements in the pathophysiology of mTBI.

In the current study, 15 patients with chronic (>3 months after mTBI) PPCS will undergo a total of 30 iTBS sessions. After a baseline scan, patients will enter a 2-week control waitlist period. Following the waitlist control, a pre-treatment scan is acquired, followed by the stimulation sessions, and final post-treatment scan. The scanning protocol includes T1 and T2 imaging, dMRS, multi-shell diffusion MRI (dMRI), as well as a demanding executive function fMRI task, and resting-state fMRI (rs-fMRI). A comprehensive battery of clinical tests will be administered at all time points, which includes cognitive testing, self-report of symptoms and emotional distress. Long-term outcome is determined three months after start of the study.

Specific study aims are:

Aim 1: To determine the effects of a precision-medicine iTBS guided approach applied to the left dorsolateral prefrontal cortex (DLPFC) on clinical recovery in patients with PPCS relative to waitlist control.

Aim 2: To determine the neurometabolic effects of iTBS in both the left and right DLPFC as measured with dMRS in patients with PPS, and to untangle differential effects on pathophysiological processes (e.g., neural plasticity vs. anti-inflammatory effects).

Aim 3: To determine the relationship of these neurometabolic effects and the integrity of major frontoparietal white matter tracts (as measured with dMRI), as well as activation and functional connectivity of key large-scale cognitive and emotional networks (i.e., executive, default mode, and salience network), measured using task-based and resting-state fMRI.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 64 Years

Eligibility

Inclusion Criteria:

• Adult age at inclusion 18-64 years.

• mTBI as defined by an altered mental status at time of injury, and LOC of max 30 min, GCS 13-15 (after 30 min), and PTA max 24 hrs.

• Persistent post-traumatic symptoms in chronic phase (>3 months post-injury).

Exclusion Criteria:

• History of developmental, neurological (e.g., epilepsy) or serious mental health disorders (e.g., schizophrenia, bipolar disorder) prior to TBI onset.

• History of a previous substance use disorder except for alcohol, or a currently active substance use disorder (within last 6 months.)

• Contraindications for MRI (e.g., any implanted ferromagnetic materials, claustrophobia, pregnancy) or iTBS (e.g., history of seizures).

Related Conditions & MeSH terms

• Brain Injuries
• Brain Injuries, Traumatic
• Magnetic Resonance Imaging
• Neuropsychological Tests
• Post-Concussion Syndrome
• Transcranial Magnetic Stimulation
• Traumatic Brain Injury

Intervention

Device:
• Intermittent theta-burst treatment (iTBS) using MagPro Transcranial Magnetic Stimulator (manufacturer: Magventure)
3-10 minute sessions of brain stimulation applied to the left dorsolateral prefrontal cortex, up to 10 sessions a day, 30 sessions in total, planned within 2 weeks.

Locations

Country	Name	City	State
United States	The Mind Research Network	Albuquerque	New Mexico

Sponsors (2)

Lead Sponsor	Collaborator
The Mind Research Network	University of New Mexico

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Post-concussive symptoms	Rivermead post concussion symptoms questionnaire (16 items, rated 0-4, higher number indicating more symptoms, max score of 64; decrease of the score means improvement of symptoms)	Post-treatment (after completion of all sessions, at ~4 weeks), and at 3 months after start of the study for the individual participant. Data will be reported at the conclusion of the study for all participants.
Primary	Neurometabolite diffusion related to neuronal function and inflammation	As measured with diffusion MRS (diffusion of neurometabolites computed as the apparent diffusion coefficient (ADC)).	Post-treatment for the individual participant (~4 weeks). Data will be reported at the conclusion of the study for all participants.
Secondary	Cognitive functioning	Neuropsychological test scores (attention measured using Stroop interference test: T scores, 0-100, higher scores indicating better performance; processing speed measured using the Symbol search test, also T-scores). Increase in score means clinical improvement.	Post-treatment for the individual participant (~4 weeks). Data will be reported at the conclusion of the study for all participants.
Secondary	Functional outcome	Glasgow Outcome Scale Extended (range 1-8, 1=dead, 8=complete recovery; increase in score means clinical improvement).	At 3 months after start of the study for the individual participant. Data will be reported at the conclusion of the study for all participants.
Secondary	Brain network functioning	As measured with advanced MRI (e.g., improvement on the multimodal attention task can be reflected by a change in percent signal change in the dorsolateral prefrontal cortices of the executive network, which can be either an increase or decrease).	Post-treatment for the individual participant (~ 4 weeks). Data will be reported at the conclusion of the study for all participants.