- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04568369
Treatment of Post-concussion Syndrome With TMS: Using FNIRS as a Biomarker of Response
Functional Near Infrared Spectroscopy as a Biomarker of Response in Patients With Post-concussion Syndrome Treated With Transcranial Magnetic Stimulation
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.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Annually, up to 280,000 people in Canada and 42 million worldwide experience a mild traumatic brain injury (mTBI). In patients with mTBI, symptoms experienced following injury usually resolve within 3 months. However, up to 25% of patients will experience persistent post-concussion symptoms (PPCS), which can continue up to 1 year following injury. Common symptoms include headaches, dizziness, fatigue, irritability, depression, anxiety, emotional lability, concentration or memory difficulties, insomnia, and reduced alcohol tolerance (ICD-10 post-concussion syndrome diagnostic criteria). To date, there is no "cure" for PPCS and current treatment entails trial and error with behavior management, environmental modifications and medications. Consequently, there is a significant need for new approaches to symptom management in order to help improve functional impairment and disease burden, associated with PPCS. Transcranial magnetic stimulation (TMS) has been studied as an intervention for many mental health and neurological conditions, including major depression and migraines, and has shown initial promise for PPCS. We intend to study the efficacy of TMS for PPCS further in a randomized sham-controlled trial.
Mild traumatic injury is considered a risk factor in the development of post-traumatic stress disorder. As such, post-traumatic stress disorder and mild traumatic brain injury often co-occur and share similar symptoms, such as irritability, post-traumatic amnesia, sleep disturbances, concentration difficulties and cognitive processing deficits. Several studies have suggested the efficacy and safety of rTMS for the treatment of PTSD; however, a gap in the literature exists regarding treating comorbid post-traumatic stress disorder and PPCS following mild traumatic brain injury. To study potential differences in response to treatment between individuals experiencing PPCS with or without co-morbid post-traumatic stress disorder, we intend to measure PTSD symptoms for those with a clinical diagnosis of post-traumatic stress disorder. Tracking PTSD symptoms will allow insight into whether the presence of PTSD symptoms affects rTMS treatment outcomes in individuals experiencing PPCS.
RESEARCH QUESTIONS AND OBJECTIVES
The overall goal is to study the application of rTMS treatment to the left dorsal lateral prefrontal cortex (DLPFC) in patients with PPCS to improve overall symptom burden and to explore biomarkers of response, specifically functional near infrared spectroscopy (fNIRS).
Specifically the objectives are:
- Primary Objective: to determine changes in brain physiology associated with rTMS treatment as recorded by fNIRS.
- Secondary Objective: to determine whether patients with PPCS have significant improvement to a 20-day high frequency rTMS treatment protocol of the left DLPFC compared to patients with PPCS receiving a sham rTMS protocol as measured by the Rivermead post-concussion symptom questionnaire at 1 and 3 months post-treatment.
- Third Objective: To determine what exploratory outcomes such as quality of life, headaches, anxiety, depression, sleep, and somatic symptoms also improve with TMS treatment in individuals suffering with PPCS. Quality of life will be measured via the Quality of Life after Brain Injury questionnaire (QOLIBRI), headache intensity will be measured via the Headache intensity Test - 6 (HIT-6), feelings of depression will be measured via the Patient Health Questionnaire -9 (PHQ-9), anxiety via the Generalized Anxiety Disorder -7 (GAD-7), sleep via the Sleep and Concussion Questionnaire and somatic symptoms which are commonly present in functional neurological disorders via the SOMS-CD and Patient Health Questionnaire-15 (PHQ-15). Since Functional Neurological Disorder is often associated with past trauma, trauma history will be assessed via the Brief Trauma Questionnaire (BTQ) and the Life Stress Questionnaire (LSQ).
- To determine whether those with PPCS and PTSD respond differently to rTMS and what effect this has on their PTSD symptoms measured via the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) and the Montgomery-Asberg Depression Rating Scale. Participants with PTSD will be identified as those with scores higher than 33 in the PCL-5 and a clinical diagnosis of PTSD by a medical professional.
- To examine potential blood biomarkers of post-concussion syndrome and post-traumatic stress disorder.
METHODS
This study will be a double-blind, sham-controlled, concealed allocation, randomized clinical trial.
Clinical Assessments: Demographic information will be collected prior to starting the study including age, sex, education, headache history, concussion history, past medical history, medication use, and family medical history. Baseline questionnaires will be completed including Headache Impact Test - 6 (HIT-6), Rivermead PPCS questionnaire, British Columbia post-concussion symptom inventory (BC-PSI), quality of life after brain injury questionnaire (QOLIBRI), patient health questionnaire-9 (PHQ-9), generalized anxiety disorder scale-7 (GADS-7),the St. Louis University Mental examination Tool (SLUMS), the screening for somatoform symptoms questionnaire (SOMS-CD), the post traumatic stress disorder checklist for DSM-5 (PCL-5), the Brief Trauma Questionniare (BTQ), the Life Stress Questionnaire (LSQ), the Patient Health Questionnaire-15 (PHQ-15), and the Sleep and Concussion Questionnaire (SCQ). Those who are identified as having a PCL-5 score of greater than 33, in addition to a clinical diagnosis of post-traumatic stress disorder, will also complete the LEC-5, CAPS-5, MADRS and Columbia Suicide Severity Rating Scale. Patients will be reassessed at the completion of their rTMS treatment, and at 1 and 3 months post-treatment. The questionnaires that will be completed at all follow-up visits include the Rivermead PPCS questionnaire, the HIT-6, the BC-PSI, the QOLIBRI, the PHQ-9, the GAD-7, the PCL-5, the SLUMS, the SOMS-CD, the PHQ-15, and the Sleep and Concussion Questionnaire. For the Sleep and Concussion Questionnaire, the initial screening section will not be completed at follow-ups. Participants in the PTSD sub-group will also complete the MADRS, CAPS-5 and Columbia Suicide Severity Rating Scale at the 1 month and 3-month follow-up visits.
TMS Protocol: 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 inter-train interval of 45s. 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.
Imaging: Functional near infrared spectroscopy (fNIRS) measurements will be recorded at baseline, immediately following rTMS, and at one month and 3-month follow-ups post-rTMS to investigate changes in brain physiology associated with rTMS treatment. fNIRS data will be recorded over the frontoparietal cortex at a sampling rate of 3.91 Hz, using the TechEn fNIRS system (TechEn Inc., Milford, MA USA). Each recording will consist of a 5 min rest period, followed by a finger tapping exercise, and a graded working memory task, previously described by Hocke et al (2018). The fNIRS data will be processed and analyzed for task-evoked activation using an ordinary least squares method of general linear modeling, as implemented in the NIRS Brain AnalyzIR Toolbox.
Blood Samples: Blood samples will be collected from a certified phlebotomist at the Heritage Medical Research Clinic located in the Cal Wenzel Precision Health building at the Foothills Medical Centre Campus. Analysis will focus on blood biomarkers of inflammation and CNS injury.
Statistical Analysis: Outcome parameters within each specific group (rTMS, sham, sex, PTSD diagnosis) will be analyzed by a one-way repeated measures analysis of variance (RM-ANOVA).
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Chantel T Debert, MD MSc FRCPC CSCN
- Phone Number: (403) 944-4500
- Email: cdebert@ucalgary.ca
Study Contact Backup
- Name: Christina C Campbell, MSc
- Phone Number: 403-944-8649
- Email: tmsandfnirsstudy@ucalgary.ca
Study Locations
-
-
Alberta
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Calgary, Alberta, Canada, T2N2T9
- Recruiting
- Foothills Medical Centre
-
Contact:
- Chantel T Debert, MD MSc
- Phone Number: (403)944-4500
- Email: chantel.debert@ahs.ca
-
Contact:
- Alison J Wilson, BA BCom
- Phone Number: (403)944-8646
- Email: tmsandfnirsstudy@ucalgary.ca
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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. The medication will be maintained without intervention during the treatment study such as use of abortive headache medications (i.e. triptans, opioids, tricyclic antidepressants, anti-seizure medications).
Exclusion Criteria:
- Prior history of TMS therapy
- TMS-related contraindications (pacemaker, metallic implant)
- Other medical conditions such as structural brain disease, previous seizure, psychiatric disorders excluding depression, PTSD and anxiety (schizophrenia, bipolar disorder), liver or kidney disease, malignancy, uncontrolled hypertension or diabetes, and pregnancy.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment group
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.
|
See treatment arm description.
|
Sham Comparator: Sham group
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.
|
See treatment arm description.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Rivermead Post-Concussion Symptom Questionnaire (RPQ)
Time Frame: Baseline
|
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)
Time Frame: Within 1 week post-intervention
|
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)
Time Frame: 1-month post-intervention
|
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)
Time Frame: 3-months post-intervention
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Quality of Life After Brain Injury (QOLIBRI)
Time Frame: Baseline
|
Assesses quality of life.
Total possible score ranges between 0-100, with higher scores indicative of better outcomes.
|
Baseline
|
Quality of Life After Brain Injury (QOLIBRI)
Time Frame: Within 1 week post-intervention
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Assesses quality of life.
Total possible score ranges between 0-100, with higher scores indicative of better outcomes.
|
Within 1 week post-intervention
|
Quality of Life After Brain Injury (QOLIBRI)
Time Frame: 1-month post-intervention
|
Assesses quality of life.
Total possible score ranges between 0-100, with higher scores indicative of better outcomes.
|
1-month post-intervention
|
Quality of Life After Brain Injury (QOLIBRI)
Time Frame: 3-months post-intervention
|
Assesses quality of life.
Total possible score ranges between 0-100, with higher scores indicative of better outcomes.
|
3-months post-intervention
|
Headache Impact Test (HIT-6)
Time Frame: Baseline
|
Assesses headache intensity.
Total possible score ranges from 36-78, with higher scores indicative of worse outcomes.
|
Baseline
|
Headache Impact Test (HIT-6)
Time Frame: Within 1 week post-intervention
|
Assesses headache intensity.
Total possible score ranges from 36-78, with higher scores indicative of worse outcomes.
|
Within 1 week post-intervention
|
Headache Impact Test (HIT-6)
Time Frame: 1-month post-intervention
|
Assesses headache intensity.
Total possible score ranges from 36-78, with higher scores indicative of worse outcomes.
|
1-month post-intervention
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Headache Impact Test (HIT-6)
Time Frame: 3-months post-intervention
|
Assesses headache intensity.
Total possible score ranges from 36-78, with higher scores indicative of worse outcomes.
|
3-months post-intervention
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Patient Health Questionnaire (PHQ-9)
Time Frame: Baseline
|
Assesses depressive symptoms.
Total possible score ranges from 0-27, with higher scores indicative of worse outcomes.
|
Baseline
|
Patient Health Questionnaire (PHQ-9)
Time Frame: Within 1 week post-intervention
|
Assesses depressive symptoms.
Total possible score ranges from 0-27, with higher scores indicative of worse outcomes.
|
Within 1 week post-intervention
|
Patient Health Questionnaire (PHQ-9)
Time Frame: 1-month post-intervention
|
Assesses depressive symptoms.
Total possible score ranges from 0-27, with higher scores indicative of worse outcomes.
|
1-month post-intervention
|
Patient Health Questionnaire (PHQ-9)
Time Frame: 3-months post-intervention
|
Assesses depressive symptoms.
Total possible score ranges from 0-27, with higher scores indicative of worse outcomes.
|
3-months post-intervention
|
Generalized Anxiety Disorder-7 (GAD-7)
Time Frame: Baseline
|
Assesses feelings of anxiety.
Total possible score ranges from 0-21, with higher scores indicative of worse outcomes.
|
Baseline
|
Generalized Anxiety Disorder-7 (GAD-7)
Time Frame: Within 1 week post-intervention
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Assesses feelings of anxiety.
Total possible score ranges from 0-21, with higher scores indicative of worse outcomes.
|
Within 1 week post-intervention
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Generalized Anxiety Disorder-7 (GAD-7)
Time Frame: 1-month post-intervention
|
Assesses feelings of anxiety.
Total possible score ranges from 0-21, with higher scores indicative of worse outcomes.
|
1-month post-intervention
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Generalized Anxiety Disorder-7 (GAD-7)
Time Frame: 3-months post-intervention
|
Assesses feelings of anxiety.
Total possible score ranges from 0-21, with higher scores indicative of worse outcomes.
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3-months post-intervention
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Screening for Somatoform Symptoms-7 (SOMS-7 CD Sub-scale)
Time Frame: Baseline
|
Evaluates somatic symptoms.
Total possible score ranges from 0-56, with higher scores indicative of worse outcomes.
|
Baseline
|
Screening for Somatoform Symptoms-7 (SOMS-7 CD Sub-scale)
Time Frame: Within 1 week post-intervention
|
Evaluates somatic symptoms.
Total possible score ranges from 0-56, with higher scores indicative of worse outcomes.
|
Within 1 week post-intervention
|
Screening for Somatoform Symptoms-7 (SOMS-7 CD Sub-scale)
Time Frame: 1-month post-intervention
|
Evaluates somatic symptoms.
Total possible score ranges from 0-56, with higher scores indicative of worse outcomes.
|
1-month post-intervention
|
Screening for Somatoform Symptoms-7 (SOMS-7 CD Sub-scale)
Time Frame: 3-months post-intervention
|
Evaluates somatic symptoms.
Total possible score ranges from 0-56, with higher scores indicative of worse outcomes.
|
3-months post-intervention
|
Saint Louis University Mental Status Examination (SLUMS)
Time Frame: Baseline
|
Assesses for mild cognitive impairment.
Total possible score ranges from 0 to 30, with higher scores indicative of better outcomes.
|
Baseline
|
Saint Louis University Mental Status Examination (SLUMS)
Time Frame: Within 1 week post-intervention
|
Assesses for mild cognitive impairment.
Total possible score ranges from 0 to 30, with higher scores indicative of better outcomes.
|
Within 1 week post-intervention
|
Saint Louis University Mental Status Examination (SLUMS)
Time Frame: 1-month post-intervention
|
Assesses for mild cognitive impairment.
Total possible score ranges from 0 to 30, with higher scores indicative of better outcomes.
|
1-month post-intervention
|
Saint Louis University Mental Status Examination (SLUMS)
Time Frame: 3-months post-intervention
|
Assesses for mild cognitive impairment.
Total possible score ranges from 0 to 30, with higher scores indicative of better outcomes.
|
3-months post-intervention
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British Columbia Post-concussion Symptom Inventory
Time Frame: Baseline
|
Assesses the frequency and intensity of post-concussion symptoms.
Total possible score ranges from 3-67, with higher scores indicative of worse outcomes.
|
Baseline
|
British Columbia Post-concussion Symptom Inventory
Time Frame: Within 1 week post-intervention
|
Assesses the frequency and intensity of post-concussion symptoms.
Total possible score ranges from 3-67, with higher scores indicative of worse outcomes.
|
Within 1 week post-intervention
|
British Columbia Post-concussion Symptom Inventory
Time Frame: 1-month post-intervention
|
Assesses the frequency and intensity of post-concussion symptoms.
Total possible score ranges from 3-67, with higher scores indicative of worse outcomes.
|
1-month post-intervention
|
British Columbia Post-concussion Symptom Inventory
Time Frame: 3-months post-intervention
|
Assesses the frequency and intensity of post-concussion symptoms.
Total possible score ranges from 3-67, with higher scores indicative of worse outcomes.
|
3-months post-intervention
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Post-traumatic Stress Disorder Checklist for DSM-5 (PCL-5)
Time Frame: Baseline
|
Assesses PTSD symptoms.
Total possible score ranges from 0-80, with higher scores indicative of worse outcomes.
|
Baseline
|
Post-traumatic Stress Disorder Checklist for DSM-5 (PCL-5)
Time Frame: Within 1 week post-intervention
|
Assesses PTSD symptoms.
Total possible score ranges from 0-80, with higher scores indicative of worse outcomes.
|
Within 1 week post-intervention
|
Post-traumatic Stress Disorder Checklist for DSM-5 (PCL-5)
Time Frame: 1-month post-intervention
|
Assesses PTSD symptoms.
Total possible score ranges from 0-80, with higher scores indicative of worse outcomes.
|
1-month post-intervention
|
Post-traumatic Stress Disorder Checklist for DSM-5 (PCL-5)
Time Frame: 3-months post-intervention
|
Assesses PTSD symptoms.
Total possible score ranges from 0-80, with higher scores indicative of worse outcomes.
|
3-months post-intervention
|
Patient Health Questionnaire-15 (PHQ-15)
Time Frame: Baseline
|
Assesses somatic symptoms.
Total possible score ranges from 0-30, with higher scores indicative of worse outcomes.
|
Baseline
|
Patient Health Questionnaire-15 (PHQ-15)
Time Frame: Within 1 week post-intervention
|
Assesses somatic symptoms.
Total possible score ranges from 0-30, with higher scores indicative of worse outcomes.
|
Within 1 week post-intervention
|
Patient Health Questionnaire-15 (PHQ-15)
Time Frame: 1-month post-intervention
|
Assesses somatic symptoms.
Total possible score ranges from 0-30, with higher scores indicative of worse outcomes.
|
1-month post-intervention
|
Patient Health Questionnaire-15 (PHQ-15)
Time Frame: 3-months post-intervention
|
Assesses somatic symptoms.
Total possible score ranges from 0-30, with higher scores indicative of worse outcomes.
|
3-months post-intervention
|
Sleep and Concussion Questionnaire
Time Frame: Baseline
|
Assesses sleep changes following mTBI.
Total possible score ranges from 0-36, with higher scores indicative of worse outcomes.
|
Baseline
|
Sleep and Concussion Questionnaire
Time Frame: Within 1 week post-intervention
|
Assesses sleep changes following mTBI.
Total possible score ranges from 0-36, with higher scores indicative of worse outcomes.
|
Within 1 week post-intervention
|
Sleep and Concussion Questionnaire
Time Frame: 1-month post-intervention
|
Assesses sleep changes following mTBI.
Total possible score ranges from 0-36, with higher scores indicative of worse outcomes.
|
1-month post-intervention
|
Sleep and Concussion Questionnaire
Time Frame: 3-months post-intervention
|
Assesses sleep changes following mTBI.
Total possible score ranges from 0-36, with higher scores indicative of worse outcomes.
|
3-months post-intervention
|
Brief Trauma Questionnaire
Time Frame: Baseline
|
Assesses trauma history in a YES/NO format.
|
Baseline
|
Brief Trauma Questionnaire
Time Frame: Within 1 week post-intervention
|
Assesses trauma history in a YES/NO format.
|
Within 1 week post-intervention
|
Brief Trauma Questionnaire
Time Frame: 1-month post-intervention
|
Assesses trauma history in a YES/NO format.
|
1-month post-intervention
|
Brief Trauma Questionnaire
Time Frame: 3-months post-intervention
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Assesses trauma history in a YES/NO format.
|
3-months post-intervention
|
Life Stress Questionnaire
Time Frame: Baseline
|
Assesses significant life stressors in the past 2 years.
Total possible score ranges from 0-1645, with higher scores indicative of worse outcomes.
|
Baseline
|
Life Stress Questionnaire
Time Frame: Within 1 week post-intervention
|
Assesses significant life stressors in the past 2 years.
Total possible score ranges from 0-1645, with higher scores indicative of worse outcomes.
|
Within 1 week post-intervention
|
Life Stress Questionnaire
Time Frame: 1-month post-intervention
|
Assesses significant life stressors in the past 2 years.
Total possible score ranges from 0-1645, with higher scores indicative of worse outcomes.
|
1-month post-intervention
|
Life Stress Questionnaire
Time Frame: 3-months post-intervention
|
Assesses significant life stressors in the past 2 years.
Total possible score ranges from 0-1645, with higher scores indicative of worse outcomes.
|
3-months post-intervention
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Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)
Time Frame: Baseline
|
Assesses PTSD symptoms over the past week.
Total possible symptom severity score ranges from 0-80, with higher scores indicative of worse outcomes.
|
Baseline
|
Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)
Time Frame: Within 1 week post-intervention
|
Assesses PTSD symptoms over the past week.
Total possible symptom severity score ranges from 0-80 with higher scores indicative of worse outcomes.
|
Within 1 week post-intervention
|
Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)
Time Frame: 1-month post-intervention
|
Assesses PTSD symptoms over the past week.
Total possible symptom severity score ranges from 0-80 with higher scores indicative of worse outcomes.
|
1-month post-intervention
|
Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)
Time Frame: 3-months post-intervention
|
Assesses PTSD symptoms over the past week.
Total possible symptom severity score ranges from 0-80 with higher scores indicative of worse outcomes.
|
3-months post-intervention
|
Montgomery-Asberg Depression Rating Scale
Time Frame: Baseline
|
Semi-structured interview to assess depression symptoms.
Total possible score ranges from 0-60, with higher scores indicative of worse outcomes.
|
Baseline
|
Montgomery-Asberg Depression Rating Scale
Time Frame: Within 1 week post-intervention
|
Semi-structured interview to assess depression symptoms.
Total possible score ranges from 0-60, with higher scores indicative of worse outcomes.
|
Within 1 week post-intervention
|
Montgomery-Asberg Depression Rating Scale
Time Frame: 1-month post-intervention
|
Semi-structured interview to assess depression symptoms.
Total possible score ranges from 0-60, with higher scores indicative of worse outcomes.
|
1-month post-intervention
|
Montgomery-Asberg Depression Rating Scale
Time Frame: 3-months post-intervention
|
Semi-structured interview to assess depression symptoms.
Total possible score ranges from 0-60, with higher scores indicative of worse outcomes.
|
3-months post-intervention
|
Columbia Suicide Severity Rating Scale
Time Frame: Baseline
|
Screening tool for suicidal ideation and behavior
|
Baseline
|
Columbia Suicide Severity Rating Scale
Time Frame: Within 1 week post-intervention
|
Screening tool for suicidal ideation and behavior
|
Within 1 week post-intervention
|
Columbia Suicide Severity Rating Scale
Time Frame: 1-month post-intervention
|
Screening tool for suicidal ideation and behavior
|
1-month post-intervention
|
Columbia Suicide Severity Rating Scale
Time Frame: 3-months post-intervention
|
Screening tool for suicidal ideation and behavior
|
3-months post-intervention
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Functional near infrared spectroscopy
Time Frame: Baseline
|
Functional near infrared spectroscopy (fNIRS) will used as a tool to determine TMS response
|
Baseline
|
Functional near infrared spectroscopy
Time Frame: Within 1 week post-intervention
|
Functional near infrared spectroscopy (fNIRS) will used as a tool to determine TMS response
|
Within 1 week post-intervention
|
Functional near infrared spectroscopy
Time Frame: 1-month post-intervention
|
Functional near infrared spectroscopy (fNIRS) will used as a tool to determine TMS response
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1-month post-intervention
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Functional near infrared spectroscopy
Time Frame: 3-months post-intervention
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Functional near infrared spectroscopy (fNIRS) will used as a tool to determine TMS response
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3-months post-intervention
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Chantel T Debert, MD MSc FRCPC CSCN, University of Calgary
Publications and helpful links
General Publications
- Harmon KG, Drezner JA, Gammons M, Guskiewicz KM, Halstead M, Herring SA, Kutcher JS, Pana A, Putukian M, Roberts WO. American Medical Society for Sports Medicine position statement: concussion in sport. Br J Sports Med. 2013 Jan;47(1):15-26. doi: 10.1136/bjsports-2012-091941. Erratum In: Br J Sports Med. 2013 Feb;47(3):184.
- Maas AIR, Menon DK, Adelson PD, Andelic N, Bell MJ, Belli A, Bragge P, Brazinova A, Buki A, Chesnut RM, Citerio G, Coburn M, Cooper DJ, Crowder AT, Czeiter E, Czosnyka M, Diaz-Arrastia R, Dreier JP, Duhaime AC, Ercole A, van Essen TA, Feigin VL, Gao G, Giacino J, Gonzalez-Lara LE, Gruen RL, Gupta D, Hartings JA, Hill S, Jiang JY, Ketharanathan N, Kompanje EJO, Lanyon L, Laureys S, Lecky F, Levin H, Lingsma HF, Maegele M, Majdan M, Manley G, Marsteller J, Mascia L, McFadyen C, Mondello S, Newcombe V, Palotie A, Parizel PM, Peul W, Piercy J, Polinder S, Puybasset L, Rasmussen TE, Rossaint R, Smielewski P, Soderberg J, Stanworth SJ, Stein MB, von Steinbuchel N, Stewart W, Steyerberg EW, Stocchetti N, Synnot A, Te Ao B, Tenovuo O, Theadom A, Tibboel D, Videtta W, Wang KKW, Williams WH, Wilson L, Yaffe K; InTBIR Participants and Investigators. Traumatic brain injury: integrated approaches to improve prevention, clinical care, and research. Lancet Neurol. 2017 Dec;16(12):987-1048. doi: 10.1016/S1474-4422(17)30371-X. Epub 2017 Nov 6. No abstract available.
- Hunt C, Zanetti K, Kirkham B, Michalak A, Masanic C, Vaidyanath C, Bhalerao S, Cusimano MD, Baker A, Ouchterlony D. Identification of hidden health utilization services and costs in adults awaiting tertiary care following mild traumatic brain injury in Toronto, Ontario, Canada. Concussion. 2016 Aug 8;1(4):CNC21. doi: 10.2217/cnc-2016-0009. eCollection 2016 Dec.
- Hendrikse J, Kandola A, Coxon J, Rogasch N, Yucel M. Combining aerobic exercise and repetitive transcranial magnetic stimulation to improve brain function in health and disease. Neurosci Biobehav Rev. 2017 Dec;83:11-20. doi: 10.1016/j.neubiorev.2017.09.023. Epub 2017 Sep 23.
- Daoud H, Alharfi I, Alhelali I, Charyk Stewart T, Qasem H, Fraser DD. Brain injury biomarkers as outcome predictors in pediatric severe traumatic brain injury. Neurocrit Care. 2014 Jun;20(3):427-35. doi: 10.1007/s12028-013-9879-1.
- Mychasiuk R, Hehar H, Ma I, Kolb B, Esser MJ. The development of lasting impairments: a mild pediatric brain injury alters gene expression, dendritic morphology, and synaptic connectivity in the prefrontal cortex of rats. Neuroscience. 2015 Mar 12;288:145-55. doi: 10.1016/j.neuroscience.2014.12.034. Epub 2014 Dec 30.
- Henry LC, Tremblay S, Boulanger Y, Ellemberg D, Lassonde M. Neurometabolic changes in the acute phase after sports concussions correlate with symptom severity. J Neurotrauma. 2010 Jan;27(1):65-76. doi: 10.1089/neu.2009.0962.
- Liu G, Feng D, Wang J, Zhang H, Peng Z, Cai M, Yang J, Zhang R, Wang H, Wu S, Tan Q. rTMS Ameliorates PTSD Symptoms in Rats by Enhancing Glutamate Transmission and Synaptic Plasticity in the ACC via the PTEN/Akt Signalling Pathway. Mol Neurobiol. 2018 May;55(5):3946-3958. doi: 10.1007/s12035-017-0602-7. Epub 2017 May 26.
- Lewis CP, Port JD, Frye MA, Vande Voort JL, Ameis SH, Husain MM, Daskalakis ZJ, Croarkin PE. An Exploratory Study of Spectroscopic Glutamatergic Correlates of Cortical Excitability in Depressed Adolescents. Front Neural Circuits. 2016 Nov 29;10:98. doi: 10.3389/fncir.2016.00098. eCollection 2016.
- Yang XR, Kirton A, Wilkes TC, Pradhan S, Liu I, Jaworska N, Damji O, Keess J, Langevin LM, Rajapakse T, Lebel RM, Sembo M, Fife M, MacMaster FP. Glutamate alterations associated with transcranial magnetic stimulation in youth depression: a case series. J ECT. 2014 Sep;30(3):242-7. doi: 10.1097/YCT.0000000000000094.
- Covassin T, Elbin RJ 3rd, Larson E, Kontos AP. Sex and age differences in depression and baseline sport-related concussion neurocognitive performance and symptoms. Clin J Sport Med. 2012 Mar;22(2):98-104. doi: 10.1097/JSM.0b013e31823403d2.
- McCrory P, Meeuwisse WH, Aubry M, Cantu RC, Dvorak J, Echemendia RJ, Engebretsen L, Johnston KM, Kutcher JS, Raftery M, Sills A, Benson BW, Davis GA, Ellenbogen R, Guskiewicz KM, Herring SA, Iverson GL, Jordan BD, Kissick J, McCrea M, McIntosh AS, Maddocks DL, Makdissi M, Purcell L, Putukian M, Schneider K, Tator CH, Turner M. Consensus statement on concussion in sport--the 4th International Conference on Concussion in Sport held in Zurich, November 2012. PM R. 2013 Apr;5(4):255-79. doi: 10.1016/j.pmrj.2013.02.012. Epub 2013 Feb 27. No abstract available.
- Covassin T, Elbin RJ, Harris W, Parker T, Kontos A. The role of age and sex in symptoms, neurocognitive performance, and postural stability in athletes after concussion. Am J Sports Med. 2012 Jun;40(6):1303-12. doi: 10.1177/0363546512444554. Epub 2012 Apr 26.
- Scholkmann F, Kleiser S, Metz AJ, Zimmermann R, Mata Pavia J, Wolf U, Wolf M. A review on continuous wave functional near-infrared spectroscopy and imaging instrumentation and methodology. Neuroimage. 2014 Jan 15;85 Pt 1:6-27. doi: 10.1016/j.neuroimage.2013.05.004. Epub 2013 May 16.
- Kleinschmidt A, Obrig H, Requardt M, Merboldt KD, Dirnagl U, Villringer A, Frahm J. Simultaneous recording of cerebral blood oxygenation changes during human brain activation by magnetic resonance imaging and near-infrared spectroscopy. J Cereb Blood Flow Metab. 1996 Sep;16(5):817-26. doi: 10.1097/00004647-199609000-00006.
- Hocke LM, Duszynski CC, Debert CT, Dleikan D, Dunn JF. Reduced Functional Connectivity in Adults with Persistent Post-Concussion Symptoms: A Functional Near-Infrared Spectroscopy Study. J Neurotrauma. 2018 Jun 1;35(11):1224-1232. doi: 10.1089/neu.2017.5365. Epub 2018 Mar 23.
- Santosa H, Fishburn F, Zhai X, Huppert TJ. Investigation of the sensitivity-specificity of canonical- and deconvolution-based linear models in evoked functional near-infrared spectroscopy. Neurophotonics. 2019 Apr;6(2):025009. doi: 10.1117/1.NPh.6.2.025009. Epub 2019 May 30.
- Huppert TJ, Diamond SG, Franceschini MA, Boas DA. HomER: a review of time-series analysis methods for near-infrared spectroscopy of the brain. Appl Opt. 2009 Apr 1;48(10):D280-98. doi: 10.1364/ao.48.00d280.
- Kontos AP, Huppert TJ, Beluk NH, Elbin RJ, Henry LC, French J, Dakan SM, Collins MW. Brain activation during neurocognitive testing using functional near-infrared spectroscopy in patients following concussion compared to healthy controls. Brain Imaging Behav. 2014 Dec;8(4):621-34. doi: 10.1007/s11682-014-9289-9.
- Wu Z, Mazzola CA, Catania L, Owoeye O, Yaramothu C, Alvarez T, Gao Y, Li X. Altered cortical activation and connectivity patterns for visual attention processing in young adults post-traumatic brain injury: A functional near infrared spectroscopy study. CNS Neurosci Ther. 2018 Jun;24(6):539-548. doi: 10.1111/cns.12811. Epub 2018 Jan 22.
- du Plessis S, Oni IK, Lapointe AP, Campbell C, Dunn JF, Debert CT. Treatment of Persistent Postconcussion Syndrome With Repetitive Transcranial Magnetic Stimulation Using Functional Near-Infrared Spectroscopy as a Biomarker of Response: Protocol for a Randomized Controlled Clinical Trial. JMIR Res Protoc. 2022 Mar 22;11(3):e31308. doi: 10.2196/31308.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Mental Disorders
- Pathologic Processes
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Wounds and Injuries
- Disease
- Craniocerebral Trauma
- Trauma, Nervous System
- Trauma and Stressor Related Disorders
- Head Injuries, Closed
- Wounds, Nonpenetrating
- Syndrome
- Brain Injuries
- Stress Disorders, Traumatic
- Stress Disorders, Post-Traumatic
- Brain Injuries, Traumatic
- Post-Concussion Syndrome
- Brain Concussion
Other Study ID Numbers
- 19-1552
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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