Transcranial Magnetic StimulationNCT04568369
Treatment of Post-concussion Syndrome With TMS: Using FNIRS as a Biomarker of Response
A study testing rTMS in people with Transcranial Magnetic Stimulation and Functional Near-Infrared Spectroscopy, run by University of Calgary at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Transcranial Magnetic Stimulation, Functional Near-Infrared Spectroscopy, Post-Concussion Syndrome
- What is being tested?
- rTMS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 91 participants
- Where
- 1 siteCanada
- Study dates
- 2 May 2020to Mar 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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).
- Conditions
- Transcranial Magnetic Stimulation, Functional Near-Infrared Spectroscopy, Post-Concussion Syndrome, Concussion, Mild Traumatic Brain Injury, Post-traumatic Stress Disorder
- Being tested
- rTMS
- Medical subject headings
- Post-Concussion Syndrome, Brain Concussion, Stress Disorders, Post-Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rTMSDevice
See treatment arm description.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Device: rTMS |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 3-months post-intervention
Secondary outcomes (60)
Quality of Life After Brain Injury (QOLIBRI)
Assesses quality of life. Total possible score ranges between 0-100, with higher scores indicative of better outcomes.
Measured: Baseline
Quality of Life After Brain Injury (QOLIBRI)
Assesses quality of life. Total possible score ranges between 0-100, with higher scores indicative of better outcomes.
Measured: Within 1 week post-intervention
Quality of Life After Brain Injury (QOLIBRI)
Assesses quality of life. Total possible score ranges between 0-100, with higher scores indicative of better outcomes.
Measured: 1-month post-intervention
Quality of Life After Brain Injury (QOLIBRI)
Assesses quality of life. Total possible score ranges between 0-100, with higher scores indicative of better outcomes.
Measured: 3-months post-intervention
Headache Impact Test (HIT-6)
Assesses headache intensity. Total possible score ranges from 36-78, with higher scores indicative of worse outcomes.
Measured: Baseline
Headache Impact Test (HIT-6)
Assesses headache intensity. Total possible score ranges from 36-78, with higher scores indicative of worse outcomes.
Measured: Within 1 week post-intervention
Headache Impact Test (HIT-6)
Assesses headache intensity. Total possible score ranges from 36-78, with higher scores indicative of worse outcomes.
Measured: 1-month post-intervention
Headache Impact Test (HIT-6)
Assesses headache intensity. Total possible score ranges from 36-78, with higher scores indicative of worse outcomes.
Measured: 3-months post-intervention
Patient Health Questionnaire (PHQ-9)
Assesses depressive symptoms. Total possible score ranges from 0-27, with higher scores indicative of worse outcomes.
Measured: Baseline
Patient Health Questionnaire (PHQ-9)
Assesses depressive symptoms. Total possible score ranges from 0-27, with higher scores indicative of worse outcomes.
Measured: Within 1 week post-intervention
Patient Health Questionnaire (PHQ-9)
Assesses depressive symptoms. Total possible score ranges from 0-27, with higher scores indicative of worse outcomes.
Measured: 1-month post-intervention
Patient Health Questionnaire (PHQ-9)
Assesses depressive symptoms. Total possible score ranges from 0-27, with higher scores indicative of worse outcomes.
Measured: 3-months post-intervention
Generalized Anxiety Disorder-7 (GAD-7)
Assesses feelings of anxiety. Total possible score ranges from 0-21, with higher scores indicative of worse outcomes.
Measured: Baseline
Generalized Anxiety Disorder-7 (GAD-7)
Assesses feelings of anxiety. Total possible score ranges from 0-21, with higher scores indicative of worse outcomes.
Measured: Within 1 week post-intervention
Generalized Anxiety Disorder-7 (GAD-7)
Assesses feelings of anxiety. Total possible score ranges from 0-21, with higher scores indicative of worse outcomes.
Measured: 1-month post-intervention
Generalized Anxiety Disorder-7 (GAD-7)
Assesses feelings of anxiety. Total possible score ranges from 0-21, with higher scores indicative of worse outcomes.
Measured: 3-months post-intervention
Screening for Somatoform Symptoms-7 (SOMS-7 CD Sub-scale)
Evaluates somatic symptoms. Total possible score ranges from 0-56, with higher scores indicative of worse outcomes.
Measured: Baseline
Screening for Somatoform Symptoms-7 (SOMS-7 CD Sub-scale)
Evaluates somatic symptoms. Total possible score ranges from 0-56, with higher scores indicative of worse outcomes.
Measured: Within 1 week post-intervention
Screening for Somatoform Symptoms-7 (SOMS-7 CD Sub-scale)
Evaluates somatic symptoms. Total possible score ranges from 0-56, with higher scores indicative of worse outcomes.
Measured: 1-month post-intervention
Screening for Somatoform Symptoms-7 (SOMS-7 CD Sub-scale)
Evaluates somatic symptoms. Total possible score ranges from 0-56, with higher scores indicative of worse outcomes.
Measured: 3-months post-intervention
Saint Louis University Mental Status Examination (SLUMS)
Assesses for mild cognitive impairment. Total possible score ranges from 0 to 30, with higher scores indicative of better outcomes.
Measured: Baseline
Saint Louis University Mental Status Examination (SLUMS)
Assesses for mild cognitive impairment. Total possible score ranges from 0 to 30, with higher scores indicative of better outcomes.
Measured: Within 1 week post-intervention
Saint Louis University Mental Status Examination (SLUMS)
Assesses for mild cognitive impairment. Total possible score ranges from 0 to 30, with higher scores indicative of better outcomes.
Measured: 1-month post-intervention
Saint Louis University Mental Status Examination (SLUMS)
Assesses for mild cognitive impairment. Total possible score ranges from 0 to 30, with higher scores indicative of better outcomes.
Measured: 3-months post-intervention
British Columbia Post-concussion Symptom Inventory
Assesses the frequency and intensity of post-concussion symptoms. Total possible score ranges from 3-67, with higher scores indicative of worse outcomes.
Measured: Baseline
British Columbia Post-concussion Symptom Inventory
Assesses the frequency and intensity of post-concussion symptoms. Total possible score ranges from 3-67, with higher scores indicative of worse outcomes.
Measured: Within 1 week post-intervention
British Columbia Post-concussion Symptom Inventory
Assesses the frequency and intensity of post-concussion symptoms. Total possible score ranges from 3-67, with higher scores indicative of worse outcomes.
Measured: 1-month post-intervention
British Columbia Post-concussion Symptom Inventory
Assesses the frequency and intensity of post-concussion symptoms. Total possible score ranges from 3-67, with higher scores indicative of worse outcomes.
Measured: 3-months post-intervention
Post-traumatic Stress Disorder Checklist for DSM-5 (PCL-5)
Assesses PTSD symptoms. Total possible score ranges from 0-80, with higher scores indicative of worse outcomes.
Measured: Baseline
Post-traumatic Stress Disorder Checklist for DSM-5 (PCL-5)
Assesses PTSD symptoms. Total possible score ranges from 0-80, with higher scores indicative of worse outcomes.
Measured: Within 1 week post-intervention
Post-traumatic Stress Disorder Checklist for DSM-5 (PCL-5)
Assesses PTSD symptoms. Total possible score ranges from 0-80, with higher scores indicative of worse outcomes.
Measured: 1-month post-intervention
Post-traumatic Stress Disorder Checklist for DSM-5 (PCL-5)
Assesses PTSD symptoms. Total possible score ranges from 0-80, with higher scores indicative of worse outcomes.
Measured: 3-months post-intervention
Patient Health Questionnaire-15 (PHQ-15)
Assesses somatic symptoms. Total possible score ranges from 0-30, with higher scores indicative of worse outcomes.
Measured: Baseline
Patient Health Questionnaire-15 (PHQ-15)
Assesses somatic symptoms. Total possible score ranges from 0-30, with higher scores indicative of worse outcomes.
Measured: Within 1 week post-intervention
Patient Health Questionnaire-15 (PHQ-15)
Assesses somatic symptoms. Total possible score ranges from 0-30, with higher scores indicative of worse outcomes.
Measured: 1-month post-intervention
Patient Health Questionnaire-15 (PHQ-15)
Assesses somatic symptoms. Total possible score ranges from 0-30, with higher scores indicative of worse outcomes.
Measured: 3-months post-intervention
Sleep and Concussion Questionnaire
Assesses sleep changes following mTBI. Total possible score ranges from 0-36, with higher scores indicative of worse outcomes.
Measured: Baseline
Sleep and Concussion Questionnaire
Assesses sleep changes following mTBI. Total possible score ranges from 0-36, with higher scores indicative of worse outcomes.
Measured: Within 1 week post-intervention
Sleep and Concussion Questionnaire
Assesses sleep changes following mTBI. Total possible score ranges from 0-36, with higher scores indicative of worse outcomes.
Measured: 1-month post-intervention
Sleep and Concussion Questionnaire
Assesses sleep changes following mTBI. Total possible score ranges from 0-36, with higher scores indicative of worse outcomes.
Measured: 3-months post-intervention
Brief Trauma Questionnaire
Assesses trauma history in a YES/NO format.
Measured: Baseline
Brief Trauma Questionnaire
Assesses trauma history in a YES/NO format.
Measured: Within 1 week post-intervention
Brief Trauma Questionnaire
Assesses trauma history in a YES/NO format.
Measured: 1-month post-intervention
Brief Trauma Questionnaire
Assesses trauma history in a YES/NO format.
Measured: 3-months post-intervention
Life Stress Questionnaire
Assesses significant life stressors in the past 2 years. Total possible score ranges from 0-1645, with higher scores indicative of worse outcomes.
Measured: Baseline
Life Stress Questionnaire
Assesses significant life stressors in the past 2 years. Total possible score ranges from 0-1645, with higher scores indicative of worse outcomes.
Measured: Within 1 week post-intervention
Life Stress Questionnaire
Assesses significant life stressors in the past 2 years. Total possible score ranges from 0-1645, with higher scores indicative of worse outcomes.
Measured: 1-month post-intervention
Life Stress Questionnaire
Assesses significant life stressors in the past 2 years. Total possible score ranges from 0-1645, with higher scores indicative of worse outcomes.
Measured: 3-months post-intervention
Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)
Assesses PTSD symptoms over the past week. Total possible symptom severity score ranges from 0-80, with higher scores indicative of worse outcomes.
Measured: Baseline
Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)
Assesses PTSD symptoms over the past week. Total possible symptom severity score ranges from 0-80 with higher scores indicative of worse outcomes.
Measured: Within 1 week post-intervention
Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)
Assesses PTSD symptoms over the past week. Total possible symptom severity score ranges from 0-80 with higher scores indicative of worse outcomes.
Measured: 1-month post-intervention
Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)
Assesses PTSD symptoms over the past week. Total possible symptom severity score ranges from 0-80 with higher scores indicative of worse outcomes.
Measured: 3-months post-intervention
Montgomery-Asberg Depression Rating Scale
Semi-structured interview to assess depression symptoms. Total possible score ranges from 0-60, with higher scores indicative of worse outcomes.
Measured: Baseline
Montgomery-Asberg Depression Rating Scale
Semi-structured interview to assess depression symptoms. Total possible score ranges from 0-60, with higher scores indicative of worse outcomes.
Measured: Within 1 week post-intervention
Montgomery-Asberg Depression Rating Scale
Semi-structured interview to assess depression symptoms. Total possible score ranges from 0-60, with higher scores indicative of worse outcomes.
Measured: 1-month post-intervention
Montgomery-Asberg Depression Rating Scale
Semi-structured interview to assess depression symptoms. Total possible score ranges from 0-60, with higher scores indicative of worse outcomes.
Measured: 3-months post-intervention
Columbia Suicide Severity Rating Scale
Screening tool for suicidal ideation and behavior
Measured: Baseline
Columbia Suicide Severity Rating Scale
Screening tool for suicidal ideation and behavior
Measured: Within 1 week post-intervention
Columbia Suicide Severity Rating Scale
Screening tool for suicidal ideation and behavior
Measured: 1-month post-intervention
Columbia Suicide Severity Rating Scale
Screening tool for suicidal ideation and behavior
Measured: 3-months post-intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Sep 2020
- Study start2 May 2020
- Primary completionMar 2024 (estimated)
- Study completionMar 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (21)Papers the sponsor has linked to this study.
- Other trials for Transcranial Magnetic StimulationStudies of the same condition, open and under way.
- More trials run by University of CalgaryThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- This study will be a double-blind, sham-controlled, concealed allocation, randomized, cross over clinical trial.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 91 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Calgary
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Chantel T Debert, MD MSc FRCPC CSCN, Principal investigator, University of Calgary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04568369
- Sponsor's protocol ID
- 19-1552
- Status last verified
- Nov 2023
- First submitted
- 4 Sep 2020
- Last updated
- 24 Nov 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 29122524Hunt 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.
PubMed 30202563Hendrikse 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.
PubMed 28951250Daoud 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.
PubMed 23943317Mychasiuk 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.
PubMed 25555930Henry 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.
PubMed 19761385Liu 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.
PubMed 28550530Lewis 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.
PubMed 27965544Yang 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.
PubMed 24820947Covassin 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.
PubMed 22246342Harmon 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.
PubMed 23243113McCrory 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.
PubMed 23466418Covassin 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.
PubMed 22539534Scholkmann 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.
PubMed 23684868Kleinschmidt 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.
PubMed 8784226
Study at a glance
From the registry record, last updated by the sponsor on 24 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Functional Near Infrared Spectroscopy as a Biomarker of Response in Patients With Post-concussion Syndrome Treated With Transcranial Magnetic Stimulation
- ClinicalTrials.gov ID
- NCT04568369
- Acronym / sponsor ID
- 19-1552
- Conditions
- Transcranial Magnetic Stimulation, Functional Near-Infrared Spectroscopy, Post-Concussion Syndrome, Concussion, Mild Traumatic Brain Injury, Post-traumatic Stress Disorder
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 91 participants (actual)
- Lead sponsor
- University of CalgaryUniversity, hospital or other
- Study start
- 2 May 2020 (actual)
- Primary completion
- Mar 2024 (estimated)
- Study completion
- Mar 2024 (estimated)
- First posted
- 29 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- This study will be a double-blind, sham-controlled, concealed allocation, randomized, cross over clinical trial.
| Arm | Type | Receives |
|---|---|---|
| Treatment group | Experimental | Device: rTMSPatients 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. |
| Sham group | Sham comparator | Device: rTMSIn 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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).
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| rTMSSee treatment arm description. | Device | Sham group, Treatment group |
Primary outcome
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.
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.
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.
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.
60 secondary outcomes
Quality of Life After Brain Injury (QOLIBRI)
Time frame: Baseline
Quality of Life After Brain Injury (QOLIBRI)
Time frame: Within 1 week post-intervention
Quality of Life After Brain Injury (QOLIBRI)
Time frame: 1-month post-intervention
Quality of Life After Brain Injury (QOLIBRI)
Time frame: 3-months post-intervention
Headache Impact Test (HIT-6)
Time frame: Baseline
Headache Impact Test (HIT-6)
Time frame: Within 1 week post-intervention
Headache Impact Test (HIT-6)
Time frame: 1-month post-intervention
Headache Impact Test (HIT-6)
Time frame: 3-months post-intervention
Patient Health Questionnaire (PHQ-9)
Time frame: Baseline
Patient Health Questionnaire (PHQ-9)
Time frame: Within 1 week post-intervention
Patient Health Questionnaire (PHQ-9)
Time frame: 1-month post-intervention
Patient Health Questionnaire (PHQ-9)
Time frame: 3-months post-intervention
Generalized Anxiety Disorder-7 (GAD-7)
Time frame: Baseline
Generalized Anxiety Disorder-7 (GAD-7)
Time frame: Within 1 week post-intervention
Generalized Anxiety Disorder-7 (GAD-7)
Time frame: 1-month post-intervention
Generalized Anxiety Disorder-7 (GAD-7)
Time frame: 3-months post-intervention
Screening for Somatoform Symptoms-7 (SOMS-7 CD Sub-scale)
Time frame: Baseline
Screening for Somatoform Symptoms-7 (SOMS-7 CD Sub-scale)
Time frame: Within 1 week post-intervention
Screening for Somatoform Symptoms-7 (SOMS-7 CD Sub-scale)
Time frame: 1-month post-intervention
Screening for Somatoform Symptoms-7 (SOMS-7 CD Sub-scale)
Time frame: 3-months post-intervention
Saint Louis University Mental Status Examination (SLUMS)
Time frame: Baseline
Saint Louis University Mental Status Examination (SLUMS)
Time frame: Within 1 week post-intervention
Saint Louis University Mental Status Examination (SLUMS)
Time frame: 1-month post-intervention
Saint Louis University Mental Status Examination (SLUMS)
Time frame: 3-months post-intervention
British Columbia Post-concussion Symptom Inventory
Time frame: Baseline
British Columbia Post-concussion Symptom Inventory
Time frame: Within 1 week post-intervention
British Columbia Post-concussion Symptom Inventory
Time frame: 1-month post-intervention
British Columbia Post-concussion Symptom Inventory
Time frame: 3-months post-intervention
Post-traumatic Stress Disorder Checklist for DSM-5 (PCL-5)
Time frame: Baseline
Post-traumatic Stress Disorder Checklist for DSM-5 (PCL-5)
Time frame: Within 1 week post-intervention
Post-traumatic Stress Disorder Checklist for DSM-5 (PCL-5)
Time frame: 1-month post-intervention
Post-traumatic Stress Disorder Checklist for DSM-5 (PCL-5)
Time frame: 3-months post-intervention
Patient Health Questionnaire-15 (PHQ-15)
Time frame: Baseline
Patient Health Questionnaire-15 (PHQ-15)
Time frame: Within 1 week post-intervention
Patient Health Questionnaire-15 (PHQ-15)
Time frame: 1-month post-intervention
Patient Health Questionnaire-15 (PHQ-15)
Time frame: 3-months post-intervention
Sleep and Concussion Questionnaire
Time frame: Baseline
Sleep and Concussion Questionnaire
Time frame: Within 1 week post-intervention
Sleep and Concussion Questionnaire
Time frame: 1-month post-intervention
Sleep and Concussion Questionnaire
Time frame: 3-months post-intervention
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Nov 2023.
- Background: PubMed 29122524Maas 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.
- Background: PubMed 30202563Hunt 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.
- Background: PubMed 28951250Hendrikse 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.
- Background: PubMed 23943317Daoud 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.
- Background: PubMed 25555930Mychasiuk 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.
- Background: PubMed 19761385Henry 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.
- Background: PubMed 28550530Liu 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.
- Background: PubMed 27965544Lewis 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.
- Background: PubMed 24820947Yang 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.
- Background: PubMed 22246342Covassin 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.
- Background: PubMed 23243113Harmon 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.
- Background: PubMed 23466418McCrory 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Chantel T Debert, MD MSc FRCPC CSCN principal investigator
University of Calgary
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing rTMS in people with Transcranial Magnetic Stimulation and Functional Near-Infrared Spectroscopy, run by University of Calgary at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 24 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rivermead Post-Concussion Symptom Questionnaire (RPQ) (time frame: Baseline). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04568369, which also lists 21 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Nov 2023.