rTMS Treatment of Persistent Headache and Post Concussion Symptoms Attributed to Mild Traumatic Injury to the Head (TOPiCS-rTMS)
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ClinicalTrials.gov Identifier: NCT03691272 |
Recruitment Status :
Completed
First Posted : October 1, 2018
Last Update Posted : April 22, 2019
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Condition or disease | Intervention/treatment | Phase |
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Brain Injuries, Traumatic Concussion, Brain Headaches Chronic Headache Post-Traumatic Headache Mild Traumatic Brain Injury Transcranial Magnetic Stimulation | Device: rTMS - Real Air Film Coil Device: rTMS - Sham Coil | Phase 1 Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 20 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
Masking Description: | Participants will be randomized with a random number generator to receive either sham or rTMS. Allocation will be concealed through the use of sequentially numbered, sealed, opaque envelopes. |
Primary Purpose: | Treatment |
Official Title: | Treatment of Persistent Headache Attributed to Mild Traumatic Injury to the Head (PHATIH) in Patients With Persistent Post Concussion Symptoms (PPCS) Using Repetitive Transcranial Magnetic Stimulation (rTMS) |
Actual Study Start Date : | April 15, 2017 |
Actual Primary Completion Date : | September 30, 2018 |
Actual Study Completion Date : | January 30, 2019 |

Arm | Intervention/treatment |
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Experimental: rTMS- Real Air Film Coil
Patient MR brain scans will be loaded and processed using the Brainsight TMS neuronavigation software and stereotaxic data for localization of the TMS stimulation site will be determined through a co-registration method between the TMS coil position and the projected site on the MR brain scan. The DLPFC will be located through MNI coordinates (-48, 20, 34). Electromyography (EMG) electrodes will be attached to the right abductor digiti minimi (ADM) muscle. The resting motor threshold (RMT) is determined as the minimal stimulation intensity required to elicit motor-evoked response of 50 microvolts peak-to-peak amplitude in at least 5 out of 10 consecutive trials of the ADM (contralateral to stimulation).
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Device: rTMS - Real Air Film Coil
70% resting motor threshold amplitude; Frequency 10 Hz; 10 trains of 60 pulses/train (total of 600 pulses); Inter-train interval 45s.
Other Name: Repetitive Transcranial Magnetic Stimulation |
Sham Comparator: rTMS- Sham coil
The same procedure for determining RMT as described above will be employed for the Sham Arm. However, a sham coil will be used when the treatment over the left DLPFC is applied.
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Device: rTMS - Sham Coil
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. |
- Change in headache severity from baseline to 1 month post-treatment. [ Time Frame: Repeated measures: Baseline (0-2 weeks),1 month (6-8 weeks) ]Numeric Pain Rating Scale (NPRS): a tool to assess severity of pain, which is graded from 0-10 (11 points) with 0 defined as "no pain" and 10 as "worst possible pain".
- Change in headache frequency from baseline to 1 month post-treatment. [ Time Frame: Repeated measures: Baseline (0-2 weeks),1 month (6-8 weeks) ]Number of headaches/2 weeks
- Headache severity [ Time Frame: Repeated measures: Pre-treatment (0-2 weeks), During Treatment (2-4 weeks), Post-treatment (4-6 weeks), 1 Month (6-8 weeks), 3 Months (10-12 weeks), 6 Months (22-24 weeks) ]Numeric Pain Rating Scale (NPRS): a tool to assess severity of pain, which is graded from 0-10 (11 points) with 0 defined as "no pain" and 10 as "worst possible pain".
- Headache frequency [ Time Frame: Repeated measures: Pre-treatment (0-2 weeks), During Treatment (2-4 weeks), Post-treatment (4-6 weeks), 1 Month (6-8 weeks), 3 Months (10-12 weeks), 6 Months (22-24 weeks) ]Number of headaches/2 weeks
- Function [ Time Frame: Repeated measures: Pre-treatment (0-2 weeks), During Treatment (2-4 weeks), Post-treatment (4-6 weeks), 1 Month (6-8 weeks), 3 Months (10-12 weeks), 6 Months (22-24 weeks) ]Headache Impact Test (HIT-6): a global measure of headache impact. Addresses the 6 categories of headache impact including social, role, and cognitive functioning, vitality, psychological distress, and severity of headache pain. Each question is scored on a 5 point scale: never, rarely, sometimes, very often, and always. Total score can range from 36-78, with higher total score indicating greater impact.
- Depression [ Time Frame: Repeated measures: Pre-treatment (0-2 weeks), During Treatment (2-4 weeks), Post-treatment (4-6 weeks), 1 Month (6-8 weeks), 3 Months (10-12 weeks), 6 Months (22-24 weeks) ]Patient Health Questionnaire - 9 (PHQ-9): a 9 item tool used to assess the presence and severity of depressive symptoms. Each item is rated based on the frequency of occurrence in the past two weeks and is graded on a 0-3 scale (0=not at all, 1= several days, 3= nearly every day). Finally, one question rates how difficult problems have made completing tasks at home, doing work, and getting along with people. This is graded on a 4 point scale from not difficult at all to extremely difficult. Total score is calculated out of 27, with a values indicating severity of depression (i.e. 0-4= none to mild, 5-9 = mild, 10-14 = moderate, 15-19 = moderately severe, and 20-27 = very severe).
- Anxiety [ Time Frame: Repeated measures: Pre-treatment (0-2 weeks), During Treatment (2-4 weeks), Post-treatment (4-6 weeks), 1 Month (6-8 weeks), 3 Months (10-12 weeks), 6 Months (22-24 weeks) ]Generalized Anxiety Disorder (GAD-7): a 7-item tool where similar to the PHQ-9, each item is rated on frequency over a 2 week period based on a 0-3 scale (0=not at all, 1= several days, 3= nearly every day). Total score GAD-7 total score ranges from 0 to 21, with scores indicating severity of anxiety (i.e. 0-5= mild, 6-10 = moderate, 11-15 = moderately severe, 16-21 = very severe).
- Post-traumatic Stress Disorder [ Time Frame: Repeated measures: Pre-treatment (0-2 weeks), During Treatment (2-4 weeks), Post-treatment (4-6 weeks), 1 Month (6-8 weeks), 3 Months (10-12 weeks), 6 Months (22-24 weeks) ]PTSD Checklist for DSM-5 (PCL-5): is a paper and pencil self-report measure, which rates the severity of PTSD symptoms over the past month. It is composed of 4 subscales, and is a total of 20 items long. Each item corresponds to the 20 criteria for PTSD defined in the DSM-5.
- Cognition [ Time Frame: Repeated measures: Pre-treatment (0-2 weeks), During Treatment (2-4 weeks), Post-treatment (4-6 weeks), 1 Month (6-8 weeks), 3 Months (10-12 weeks), 6 Months (22-24 weeks) ]Montreal Cognitive Assessment (MoCA):a paper and pencil global cognitive assessment tool which measures 7 neurocognitive domains including visuospatial/executive function, naming, memory, attention, language, abstraction and orientation. It is composed of 16 items and scored out of 30 points.
- Quality of Life (QoL): QOLIBRI [ Time Frame: Repeated measures: Pre-treatment (0-2 weeks), During Treatment (2-4 weeks), Post-treatment (4-6 weeks), 1 Month (6-8 weeks), 3 Months (10-12 weeks), 6 Months (22-24 weeks) ]The QOLIBRI is a health-related quality of life instrument developed specifically for patients who have experienced a traumatic brain injury. It has 6 subscales and a total of 37 items. The tool is divided into two sections. The first addresses satisfaction with health related quality of life, characterized by cognition, self, autonomy in daily life, and social aspects. These are reported on a 1-5 scale with 1 defined as "not at all satisfied" and 5 as "very satisfied". The second section is related to "feeing bothered by" emotions and physical problems. They are again scored from 1-5, however 1 is defined as "very bothered" and 5 as "not bothered at all". The score from all subscales are totaled, and then divided by the number of responses. This gives a mean score, which can range from 1-5. Next, 1 is subtracted from the mean and then multiplied by 25 to produce a score on the 0-100 scale (0=worst possible quality of life, 100= best possible quality of life).
- Post-concussion Symptoms [ Time Frame: Repeated measures: Pre-treatment (0-2 weeks), During Treatment (2-4 weeks), Post-treatment (4-6 weeks), 1 Month (6-8 weeks), 3 Months (10-12 weeks), 6 Months (22-24 weeks) ]Rivermead Post-concussion Symptoms Questionnaire (RPQ): an instrument developed to assess the frequency and severity of 16 common post-concussion symptoms. On this paper and pencil tool, patients rate the extent to which their symptoms (compared to their pre-injury levels) have become more problematic over the past 24 hours using a rating scale from 0-4 (0=not experienced, 1=no more of a problem, 2=mild problem, 3=moderate problem, 4=severe problem). A total symptom score is calculated out of 64.
- Post-concussion Symptoms [ Time Frame: Repeated measures: Pre-treatment (0-2 weeks), During Treatment (2-4 weeks), Post-treatment (4-6 weeks), 1 Month (6-8 weeks), 3 Months (10-12 weeks), 6 Months (22-24 weeks) ]British Columbia Post-concussion symptom inventory (BC-PSI): a 16 item instrument, where 13 questions are used to assess the frequency and intensity of post-concussion symptoms as defined by ICD-10 criteria over the past two weeks (i.e. headaches, dizziness or light-headedness, nausea, fatigue, phonophobia, sadness, nervousness or tension, temper problems, poor concentration, memory problems, reading difficulty, and sleep disturbance). Severity is rated from 0-5 (6 point scale) where 0 is defined as "not at all" and 5 as "constantly". Intensity is also rated from 0-5, where 0 is defined as "not at all" and 5 as "very severe problem". The two items are then multiplied (frequency x intensity) for each item. This is subsequently converted to item total scores where: 0-1=0, 2-3=1, 4-6=2, 8-12=3, and ≥15=4. Scores from 1-2 signify mild symptoms and ≥3 moderate to severe symptoms, which can be considered clinically significant.

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Ages Eligible for Study: | 16 Years to 65 Years (Child, Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Diagnosis of a persistent headache attributed to traumatic injury to the head based on the ICHD-3 criteria
- Diagnosis of persistent post-concussion symptoms based on the ICD-10 criteria
- mTBI occurrence from 3 months to 5 years from study start date
Exclusion Criteria:
- Prior history of TMS therapy
- TMS-related contraindications (pacemaker, metallic implant)
- History of chronic headache (>15 days/month for 3 months) or migraine prior to most recent trauma
- Other medical conditions such as: structural brain disease, previous seizure, psychotic disorders (schizophrenia, bipolar disorder), liver or kidney disease, malignancy, uncontrolled hypertension or diabetes, and pregnancy

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03691272
Canada, Alberta | |
University Of Calgary | |
Calgary, Alberta, Canada, T2N 4Z6 |
Principal Investigator: | Chantel Debert, MD MSc FRCPC | University of Calgary |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | University of Calgary |
ClinicalTrials.gov Identifier: | NCT03691272 |
Other Study ID Numbers: |
16-2377 |
First Posted: | October 1, 2018 Key Record Dates |
Last Update Posted: | April 22, 2019 |
Last Verified: | September 2018 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Undecided |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | No |
Product Manufactured in and Exported from the U.S.: | No |
Brain Injuries Brain Injuries, Traumatic Brain Concussion Post-Traumatic Headache Post-Concussion Syndrome Craniocerebral Trauma Headache Wounds and Injuries Brain Diseases |
Central Nervous System Diseases Nervous System Diseases Trauma, Nervous System Pain Neurologic Manifestations Head Injuries, Closed Wounds, Nonpenetrating Headache Disorders, Secondary Headache Disorders |