NCT03691272

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
20

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Apr 2017

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 15, 2017

Completed
1.4 years until next milestone

First Submitted

Initial submission to the registry

September 26, 2018

Completed
4 days until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 30, 2018

Completed
1 day until next milestone

First Posted

Study publicly available on registry

October 1, 2018

Completed
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

January 30, 2019

Completed
Last Updated

April 22, 2019

Status Verified

September 1, 2018

Enrollment Period

1.5 years

First QC Date

September 26, 2018

Last Update Submit

April 18, 2019

Conditions

Brain Injuries, TraumaticConcussion, BrainHeadaches ChronicHeadachePost-Traumatic HeadacheMild Traumatic Brain InjuryTranscranial Magnetic Stimulation

Outcome Measures

Primary Outcomes (2)

  • 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)

  • 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 Outcomes (10)

  • Headache severity

    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 frequency

    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)

  • Function

    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)

  • Depression

    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)

  • Anxiety

    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)

  • +5 more secondary outcomes

Study Arms (2)

rTMS- Real Air Film Coil

EXPERIMENTAL

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).

Device: rTMS - Real Air Film Coil

rTMS- Sham coil

SHAM COMPARATOR

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.

Device: rTMS - Sham Coil

Interventions

rTMS - Real Air Film CoilDEVICE

70% resting motor threshold amplitude; Frequency 10 Hz; 10 trains of 60 pulses/train (total of 600 pulses); Inter-train interval 45s.

Also known as: Repetitive Transcranial Magnetic Stimulation
rTMS- Real Air Film Coil
rTMS - Sham CoilDEVICE

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.

rTMS- Sham coil

Eligibility Criteria

Age16 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University Of Calgary

Calgary, Alberta, T2N 4Z6, Canada

Location

Related Publications (24)

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    PMID: 23963471BACKGROUND

  • 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.

    PMID: 19680134BACKGROUND

  • Iverson GL, Lange RT. Examination of "postconcussion-like" symptoms in a healthy sample. Appl Neuropsychol. 2003;10(3):137-44. doi: 10.1207/S15324826AN1003_02.

    PMID: 12890639BACKGROUND

  • 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. doi: 10.1037//0022-006x.59.1.12.

    PMID: 2002127BACKGROUND

  • 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. doi: 10.1191/0269215505cr905oa.

    PMID: 16323387BACKGROUND

  • Lannsjo M, Borg J, Bjorklund 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.

    PMID: 22031345BACKGROUND

  • 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. doi: 10.1007/BF00868811.

    PMID: 8551320BACKGROUND

  • 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.

    PMID: 27723815BACKGROUND

  • Spitzer RL, Kroenke K, Williams JB, Lowe B. A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med. 2006 May 22;166(10):1092-7. doi: 10.1001/archinte.166.10.1092.

    PMID: 16717171BACKGROUND

  • Lowe B, Schenkel I, Carney-Doebbeling C, Gobel C. Responsiveness of the PHQ-9 to Psychopharmacological Depression Treatment. Psychosomatics. 2006 Jan-Feb;47(1):62-7. doi: 10.1176/appi.psy.47.1.62.

    PMID: 16384809BACKGROUND

  • 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. doi: 10.1097/00001199-200511000-00003.

    PMID: 16304487BACKGROUND

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

    BACKGROUND

  • Nasreddine ZS, Phillips NA, Bedirian 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. doi: 10.1111/j.1532-5415.2005.53221.x.

    PMID: 15817019BACKGROUND

  • 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.

    PMID: 24045573BACKGROUND

  • 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.

    PMID: 25080874BACKGROUND

  • 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.

    PMID: 20819842BACKGROUND

  • Kosinski M, Bayliss MS, Bjorner JB, Ware JE Jr, Garber WH, Batenhorst A, Cady R, Dahlof 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. doi: 10.1023/a:1026119331193.

    PMID: 14651415BACKGROUND

  • von Steinbuchel N, Wilson L, Gibbons H, Hawthorne G, Hofer 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.

    PMID: 20210602BACKGROUND

  • 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.

    PMID: 25794219BACKGROUND

  • 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.

    PMID: 21621130BACKGROUND

  • 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.

    PMID: 20722715BACKGROUND

  • 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. doi: 10.1017/S1355617706060036.

    PMID: 16433950BACKGROUND

  • 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/>.

    BACKGROUND

  • Stilling J, Paxman E, Mercier L, Gan LS, Wang M, Amoozegar F, Dukelow SP, Monchi O, Debert C. Treatment of Persistent Post-Traumatic Headache and Post-Concussion Symptoms Using Repetitive Transcranial Magnetic Stimulation: A Pilot, Double-Blind, Randomized Controlled Trial. J Neurotrauma. 2020 Jan 15;37(2):312-323. doi: 10.1089/neu.2019.6692. Epub 2019 Nov 8.

    PMID: 31530227DERIVED

MeSH Terms

Conditions

Brain Injuries, TraumaticBrain ConcussionHeadache DisordersHeadachePost-Traumatic Headache

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Brain InjuriesBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesCraniocerebral TraumaTrauma, Nervous SystemWounds and InjuriesHead Injuries, ClosedWounds, NonpenetratingPainNeurologic ManifestationsSigns and SymptomsPathological Conditions, Signs and SymptomsHeadache Disorders, Secondary

Intervention Hierarchy (Ancestors)

Magnetic Field TherapyTherapeutics

Study Officials

  • Chantel Debert, MD MSc FRCPC

    University of Calgary

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
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.
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 26, 2018

First Posted

October 1, 2018

Study Start

April 15, 2017

Primary Completion

September 30, 2018

Study Completion

January 30, 2019

Last Updated

April 22, 2019

Record last verified: 2018-09

Locations

CA(1)