rTMS Treatment of Persistent Headache and Post Concussion Symptoms Attributed to Mild Traumatic Injury to the Head

Headache Clinical Trial

— TOPiCS-rTMS  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03691272
• Other study ID #: 16-2377
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: April 15, 2017
• Est. completion date: January 30, 2019

Study information

• Verified date: September 2018
• Source: University of Calgary
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objective of this study is to investigate the treatment effect of repetitive transcranial magnetic stimulation in patients with a history of both persistent post-traumatic headache and post-concussion symptoms. In this double-blind, sham-controlled, concealed allocation, randomized clinical trial, 20 patients aged 18-65 yrs will be recruited from the Calgary Brain Injury Program (CBIP) and the Calgary Headache Assessment and Management Program (CHAMP) / Calgary Chronic Pain Centre, Calgary, Alberta, Canada. Patients will engage in a two-week rTMS treatment protocol (10 treatments) and will be followed for 6 months after therapy.

Description:

Demographic information will be collected two weeks prior to starting the study including age, sex, education, headache history, concussion history, past medical history, medication use, and family medical history. Headache history will be collected including frequency, severity, medication-use, type of headache, associated symptoms (i.e. neck pain, photophobia, phonophobia, nausea, vomiting) and headache triggers. Baseline questionnaires will be completed including headache intensity scale - 6 (HIT-6), Rivermead PPCS questionnaire, British Columbia post-concussion symptom inventory (BC-PSI), Montreal cognitive assessment (MoCA), quality of life after brain injury questionnaire (QOLIBRI), patient health questionnaire-9 (PHQ-9), generalized anxiety disorder scale-7 (GADS-7) and the post traumatic stress disorder checklist for DSM-5 (PCL-5). Patients will keep a two-week baseline headache diary before treatment, 2 weeks during treatment, 2 weeks following rTMS, and for 2 weeks at the 1, 3, and 6 month follow up assessments (total of 12 weeks). Patients will be reassessed at the completion of their rTMS treatment (day 14), and at 1, 3, and 6 months post-treatment. The questionnaires including: HIT-6, Rivermead PPCS questionnaire, PC-PSI, QOLIBRI, PHQ-9 and GAD-7 will be completed at all follow up visits.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: January 30, 2019
• Est. primary completion date: September 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Brain Concussion
• Brain Injuries
• Brain Injuries, Traumatic
• Concussion, Brain
• Craniocerebral Trauma
• Headache
• Headaches Chronic
• Mild Traumatic Brain Injury
• Post-Concussion Syndrome
• Post-Traumatic Headache
• Transcranial Magnetic Stimulation
• Wounds and Injuries

Intervention

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.
• 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.

Locations

Country	Name	City	State
Canada	University Of Calgary	Calgary	Alberta

Sponsors (2)

Lead Sponsor	Collaborator
University of Calgary	Hotchkiss Brain Institute, University of Calgary

Country where clinical trial is conducted

Canada, 

References & Publications (23)

Ashbaugh AR, Houle-Johnson S, Herbert C, El-Hage W, Brunet A. Psychometric Validation of the English and French Versions of the Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5). PLoS One. 2016 Oct 10;11(10):e0161645. doi: 10.1371/journal.pone.0161645. eCollection 2016. — View Citation

Eyres S, Carey A, Gilworth G, Neumann V, Tennant A. Construct validity and reliability of the Rivermead Post-Concussion Symptoms Questionnaire. Clin Rehabil. 2005 Dec;19(8):878-87. — View Citation

Fann JR, Bombardier CH, Dikmen S, Esselman P, Warms CA, Pelzer E, Rau H, Temkin N. Validity of the Patient Health Questionnaire-9 in assessing depression following traumatic brain injury. J Head Trauma Rehabil. 2005 Nov-Dec;20(6):501-11. — View Citation

Hjermstad MJ, Fayers PM, Haugen DF, Caraceni A, Hanks GW, Loge JH, Fainsinger R, Aass N, Kaasa S; European Palliative Care Research Collaborative (EPCRC). Studies comparing Numerical Rating Scales, Verbal Rating Scales, and Visual Analogue Scales for assessment of pain intensity in adults: a systematic literature review. J Pain Symptom Manage. 2011 Jun;41(6):1073-93. doi: 10.1016/j.jpainsymman.2010.08.016. Review. — View Citation

Iverson GL, Brooks BL, Ashton VL, Lange RT. Interview versus questionnaire symptom reporting in people with the postconcussion syndrome. J Head Trauma Rehabil. 2010 Jan-Feb;25(1):23-30. doi: 10.1097/HTR.0b013e3181b4b6ab. — View Citation

Iverson GL, Lange RT. Examination of "postconcussion-like" symptoms in a healthy sample. Appl Neuropsychol. 2003;10(3):137-44. — View Citation

Jacobson NS, Truax P. Clinical significance: a statistical approach to defining meaningful change in psychotherapy research. J Consult Clin Psychol. 1991 Feb;59(1):12-9. — View Citation

Kashluba S, Casey JE, Paniak C. Evaluating the utility of ICD-10 diagnostic criteria for postconcussion syndrome following mild traumatic brain injury. J Int Neuropsychol Soc. 2006 Jan;12(1):111-8. — View Citation

King NS, Crawford S, Wenden FJ, Moss NE, Wade DT. The Rivermead Post Concussion Symptoms Questionnaire: a measure of symptoms commonly experienced after head injury and its reliability. J Neurol. 1995 Sep;242(9):587-92. — View Citation

Kjeldgaard D, Forchhammer H, Teasdale T, Jensen RH. Chronic post-traumatic headache after mild head injury: a descriptive study. Cephalalgia. 2014 Mar;34(3):191-200. doi: 10.1177/0333102413505236. Epub 2013 Sep 17. — View Citation

Kosinski M, Bayliss MS, Bjorner JB, Ware JE Jr, Garber WH, Batenhorst A, Cady R, Dahlöf CG, Dowson A, Tepper S. A six-item short-form survey for measuring headache impact: the HIT-6. Qual Life Res. 2003 Dec;12(8):963-74. — View Citation

Kumar, S., Jawahar, A., Shah, P. & Kumar, M. Montreal Cognitive Assessment, a screening tool for Mild Traumatic Brain Injury (P7.185). Neurology 84 (2015).

Lannsjö M, Borg J, Björklund G, Af Geijerstam JL, Lundgren-Nilsson A. Internal construct validity of the Rivermead Post-Concussion Symptoms Questionnaire. J Rehabil Med. 2011 Nov;43(11):997-1002. doi: 10.2340/16501977-0875. — View Citation

Lee JJ, Lee MK, Kim JE, Kim HZ, Park SH, Tae JH, Choi SS. Pain relief scale is more highly correlated with numerical rating scale than with visual analogue scale in chronic pain patients. Pain Physician. 2015 Mar-Apr;18(2):E195-200. — View Citation

Löwe B, Schenkel I, Carney-Doebbeling C, Göbel C. Responsiveness of the PHQ-9 to Psychopharmacological Depression Treatment. Psychosomatics. 2006 Jan-Feb;47(1):62-7. — View Citation

Misra UK, Kalita J, Bhoi SK. High-rate repetitive transcranial magnetic stimulation in migraine prophylaxis: a randomized, placebo-controlled study. J Neurol. 2013 Nov;260(11):2793-801. doi: 10.1007/s00415-013-7072-2. Epub 2013 Aug 21. — View Citation

Nasreddine ZS, Phillips NA, Bédirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005 Apr;53(4):695-9. — View Citation

Olesen, J. Section 5.2.2 Persistent headache attributed to mild traumatic injury to the head. IHS Classification ICHD-3 beta (2016). <https://www.ichd-3.org/5-headache-attributed-to-trauma-or-injury-to-the-head-andor-neck/5-2-persistent-headache-attributed-to-traumatic-injury-to-the-head/5-2-2-persistent-headache-attributed-to-mild-traumatic-injury-to-the-head/>.

Provost JS, Petrides M, Monchi O. Dissociating the role of the caudate nucleus and dorsolateral prefrontal cortex in the monitoring of events within human working memory. Eur J Neurosci. 2010 Sep;32(5):873-80. doi: 10.1111/j.1460-9568.2010.07333.x. Epub 2010 Aug 16. — View Citation

Rendas-Baum R, Yang M, Varon SF, Bloudek LM, DeGryse RE, Kosinski M. Validation of the Headache Impact Test (HIT-6) in patients with chronic migraine. Health Qual Life Outcomes. 2014 Aug 1;12:117. doi: 10.1186/s12955-014-0117-0. — View Citation

Spitzer RL, Kroenke K, Williams JB, Löwe B. A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med. 2006 May 22;166(10):1092-7. — View Citation

von Steinbüchel N, Wilson L, Gibbons H, Hawthorne G, Höfer S, Schmidt S, Bullinger M, Maas A, Neugebauer E, Powell J, von Wild K, Zitnay G, Bakx W, Christensen AL, Koskinen S, Formisano R, Saarajuri J, Sasse N, Truelle JL; QOLIBRI Task Force. Quality of Life after Brain Injury (QOLIBRI): scale validity and correlates of quality of life. J Neurotrauma. 2010 Jul;27(7):1157-65. doi: 10.1089/neu.2009.1077. — View Citation

Yang M, Rendas-Baum R, Varon SF, Kosinski M. Validation of the Headache Impact Test (HIT-6™) across episodic and chronic migraine. Cephalalgia. 2011 Feb;31(3):357-67. doi: 10.1177/0333102410379890. Epub 2010 Sep 6. — View Citation

* Note: There are 23 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in headache severity from baseline to 1 month post-treatment.	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".	Repeated measures: Baseline (0-2 weeks),1 month (6-8 weeks)
Primary	Change in headache frequency from baseline to 1 month post-treatment.	Number of headaches/2 weeks	Repeated measures: Baseline (0-2 weeks),1 month (6-8 weeks)
Secondary	Headache severity	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".	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)
Secondary	Headache frequency	Number of headaches/2 weeks	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)
Secondary	Function	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.	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)
Secondary	Depression	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).	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)
Secondary	Anxiety	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).	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)
Secondary	Post-traumatic Stress Disorder	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.	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)
Secondary	Cognition	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.	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)
Secondary	Quality of Life (QoL): QOLIBRI	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).	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)
Secondary	Post-concussion Symptoms	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.	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)
Secondary	Post-concussion Symptoms	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.	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)