Treatment of Post-concussion Syndrome With TMS: Using FNIRS as a Biomarker of Response

NCT04568369 | Unknown

• 1 other identifier: 19-1552
• Study Type: interventional
• Target: 91
• Locations: 1 country
• Sites: 1

Brief Summary

Every year, approximately 2 million people in the United States and 280,000 in Canada experience a mild traumatic brain injury/concussion. In patients with concussion, symptoms experienced following injury usually get better within 3 months. However, approximately 5-25% of people will experience symptoms beyond the 3 month period, characterized by persistent headaches, fatigue, insomnia, anxiety, depression, and thinking or concentration problems, which contribute to significant functional impairment. Chronic headache is the most common symptom following concussions. They can last beyond 5 years following injury, significantly impacting daily activities. To date, post-concussion symptoms have no known "cure". One potential approach to treating post-concussion symptoms may involve using drug-free interventions, such as neuromodulation therapy. This has the goal of restoring normal brain activity. Repetitive transcranial magnetic stimulation (rTMS) is one method currently being explored as a treatment option. TMS is a procedure where brain electrical activity is influenced by a magnetic field. Numerous studies using rTMS to treat other disorders, such as dementia, stroke, cerebral palsy, addictions, depression and anxiety, have shown much promise. The primary objective of this study is to determine whether rTMS treatment can significantly improve persistent post-concussion symptoms. A secondary objective is to explore the relationship between potential changes in brain function and clinical markers associated with rTMS treatment and how functional near-infrared spectroscopy (fNIRS), a neuroimaging technology, may be used to assess rTMS-treatment response.

Conditions

Transcranial Magnetic Stimulation; Functional Near-Infrared Spectroscopy; Post-Concussion Syndrome; Concussion; Mild Traumatic Brain Injury; Post-traumatic Stress Disorder

Outcome Measures

Primary Outcomes (4)

• Rivermead Post-Concussion Symptom Questionnaire (RPQ)

  Assesses the severity of 16 commonly experienced PCS symptoms. Participants are instructed to rate the extent to which they have suffered from each of the listed symptoms in the past 24 hours, as compared to pre-injury levels, using a scale of 0 ("not experienced at all") to 4 ("a severe problem"). The RPQ has been demonstrated as a valid measure of PPCS with a minimal clinically important difference (MCID) of 4.5 points. It is advised to analyze this assessment as two separate scales (RPQ-13 and RRQ-3). The RPQ-3 has a total possible score of 0-12, with higher scores indicative of worse outcomes. The RPQ-13 has a total possible score of 0-52, with higher scores indicative of worse outcomes. Using these sub-scales, the instrument has good test-retest reliability and external construct validity. This questionnaire probes the separate cognitive, emotional and somatic components of PPCS.

  Baseline

• Rivermead Post-Concussion Symptom Questionnaire (RPQ)

  Assesses the severity of 16 commonly experienced PCS symptoms. Participants are instructed to rate the extent to which they have suffered from each of the listed symptoms in the past 24 hours, as compared to pre-injury levels, using a scale of 0 ("not experienced at all") to 4 ("a severe problem"). The RPQ has been demonstrated as a valid measure of PPCS with a minimal clinically important difference (MCID) of 4.5 points. It is advised to analyze this assessment as two separate scales (RPQ-13 and RRQ-3). The RPQ-3 has a total possible score of 0-12, with higher scores indicative of worse outcomes. The RPQ-13 has a total possible score of 0-52, with higher scores indicative of worse outcomes. Using these sub-scales, the instrument has good test-retest reliability and external construct validity. This questionnaire probes the separate cognitive, emotional and somatic components of PPCS.

  Within 1 week post-intervention

• Rivermead Post-Concussion Symptom Questionnaire (RPQ)

  Assesses the severity of 16 commonly experienced PCS symptoms. Participants are instructed to rate the extent to which they have suffered from each of the listed symptoms in the past 24 hours, as compared to pre-injury levels, using a scale of 0 ("not experienced at all") to 4 ("a severe problem"). The RPQ has been demonstrated as a valid measure of PPCS with a minimal clinically important difference (MCID) of 4.5 points. It is advised to analyze this assessment as two separate scales (RPQ-13 and RRQ-3). The RPQ-3 has a total possible score of 0-12, with higher scores indicative of worse outcomes. The RPQ-13 has a total possible score of 0-52, with higher scores indicative of worse outcomes. Using these sub-scales, the instrument has good test-retest reliability and external construct validity. This questionnaire probes the separate cognitive, emotional and somatic components of PPCS.

  1-month post-intervention

• Rivermead Post-Concussion Symptom Questionnaire (RPQ)

  Assesses the severity of 16 commonly experienced PCS symptoms. Participants are instructed to rate the extent to which they have suffered from each of the listed symptoms in the past 24 hours, as compared to pre-injury levels, using a scale of 0 ("not experienced at all") to 4 ("a severe problem"). The RPQ has been demonstrated as a valid measure of PPCS with a minimal clinically important difference (MCID) of 4.5 points. It is advised to analyze this assessment as two separate scales (RPQ-13 and RRQ-3). The RPQ-3 has a total possible score of 0-12, with higher scores indicative of worse outcomes. The RPQ-13 has a total possible score of 0-52, with higher scores indicative of worse outcomes. Using these sub-scales, the instrument has good test-retest reliability and external construct validity. This questionnaire probes the separate cognitive, emotional and somatic components of PPCS.

  3-months post-intervention

Secondary Outcomes (60)

• Quality of Life After Brain Injury (QOLIBRI)

  Baseline

• Quality of Life After Brain Injury (QOLIBRI)

  Within 1 week post-intervention

• Quality of Life After Brain Injury (QOLIBRI)

  1-month post-intervention

• Quality of Life After Brain Injury (QOLIBRI)

  3-months post-intervention

• Headache Impact Test (HIT-6)

  Baseline

Other Outcomes (4)

• Functional near infrared spectroscopy

  Baseline

• Functional near infrared spectroscopy

  Within 1 week post-intervention

• Functional near infrared spectroscopy

  1-month post-intervention

Study Arms (2)

Treatment group

EXPERIMENTAL

Patients will engage in a four-week treatment protocol (20 treatments). This was chosen as it is the midpoint between typical depression and migraine protocol durations. A standardized atlas brain with Montreal neurologic institute (MNI) coordinates will be used for navigation. The DLPFC will be located through MNI coordinates (-50, 30, 36). The intensity of the rTMS will be 100-120% of resting motor threshold amplitude, with a frequency of 10 Hz, 10 trains of 60 pulses/train (total of 600 pulses) and an inter-train interval of 45s.

Device: rTMS

Sham group

SHAM COMPARATOR

In the sham condition, a sham coil will be applied to the scalp after the resting motor threshold is determined. Patients will be able to hear the sound and feel the vibration of sham coil, but will not experience any effective stimulation. Previous sham studies have demonstrated efficacy of the blinding method.

Device: rTMS

Interventions

rTMS DEVICE

See treatment arm description.

Sham group; Treatment group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of persistent post-concussion syndrome based on the ICD-10 criteria. This diagnosis should be given to the patient from a clinical practitioner.
• Concussion in the past 5 years attributed to current symptoms.
• Age 18-75 yrs.
• Current pharmacologic management can remain stable throughout the protocol such as use of abortive headache medications (i.e. triptans, opioids, tricyclic antidepressants, anti-seizure medications).

You may not qualify if:

• Prior history of TMS therapy
• TMS-related contraindications (pacemaker, metallic implant)
• Other medical conditions such as structural brain disease, previous seizures, psychiatric disorders excluding depression, PTSD and anxiety (schizophrenia, bipolar disorder), liver or kidney disease, malignancy, uncontrolled hypertension or diabetes, and pregnancy.

Sponsors & Collaborators

• University of Calgary: lead

Study Sites (1)

Foothills Medical Centre

Calgary, Alberta, T2N2T9, Canada

Location

Related Publications (21)

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MeSH Terms

Conditions

Post-Concussion Syndrome; Brain Concussion; Stress Disorders, Post-Traumatic

Condition Hierarchy (Ancestors)

Head Injuries, Closed; Craniocerebral Trauma; Trauma, Nervous System; Nervous System Diseases; Wounds and Injuries; Wounds, Nonpenetrating; Brain Injuries, Traumatic; Brain Injuries; Brain Diseases; Central Nervous System Diseases; Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Study Officials

• Chantel T Debert, MD MSc FRCPC CSCN

  University of Calgary

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Patients will be randomized with a random number generator to receive either sham or rTMS. The research assistant administering the fNIRS and PTSD assessments, will be blinded to the treatment allocations. Once the study is completed, patients and all study personnel will be unblinded. Subjects in the sham group will be given the opportunity to cross over to the treatment group.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study will be a double-blind, sham-controlled, concealed allocation, randomized, cross over clinical trial.

Study Record Dates

• First Submitted: September 4, 2020
• First Posted: September 29, 2020
• Study Start: May 2, 2020
• Primary Completion: March 1, 2024
• Study Completion: March 1, 2024
• Last Updated: November 24, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)