Managing Mild Traumatic Brain Injury Related Headaches With Repetitive Transcranial Magnetic Stimulation

NCT03314584 | Completed Results FDA Device

• 2 other identifiers: B2506-IH170053
• Study Type: interventional
• Target: 179
• Locations: 1 country
• Sites: 1

Brief Summary

Persistent headache is one of the most common debilitating symptoms in military personnel suffering from mild traumatic brain injury (MTBI). This study aims to assess the long-term effect of repetitive transcranial magnetic stimulation (rTMS) in managing MTBI related headaches for up to 2-3 months by comparing the treatment effect of active-rTMS to sham-rTMS.

Conditions

Traumatic Brain Injury (TBI)

Keywords

TBI; traumatic brain injury; transcranial magnetic stimulation; headache

Outcome Measures

Primary Outcomes (12)

• Number of Headache Days Per Week

  The outcome measure will be quantified through the headache diary log that tracks the intensity, frequency and duration of MTBI-headaches (MTBI-HA). Baseline data includes all logs from the start of the study until the start of treatment. Post-intervention data looked at the time between the 3-month follow-up and the previous visit.

  The measure will be assessed daily from baseline to the 3-month post-treatment follow up (treatment occurred for 2-5 weeks starting in week 3).

• Number of Days With Debilitating MTBI-headaches Per Week.

  The outcome measure will be quantified through the headache diary log that tracks the intensity, frequency and duration of MTBI-headaches (MTBI-HA). Baseline data includes all logs from the start of the study until the start of treatment. Post-intervention data looked at the time between the 3-month follow-up and the previous visit.

  The measure will be assessed daily from baseline to the 3-month post-treatment follow up (treatment occurred for 2-5 weeks starting in week 3).

• Duration of Debilitating MTBI-headaches (Hours).

  The outcome measure will be quantified through the headache diary log that tracks the intensity, frequency and duration of MTBI-headaches (MTBI-HA). Baseline data includes all logs from the start of the study until the start of treatment. Post-intervention data looked at the time between the 3-month follow-up and the previous visit.

  The measure will be assessed daily from baseline to the 3-month post-treatment follow up (treatments occurred for 2-5 weeks starting in week 3).

• Average Interference (0-10) of Headaches in Daily Activities.

  The outcome measure will be quantified through the headache diary log that tracks the intensity, frequency, duration, and interference of MTBI-headaches (MTBI-HA). A score of 0 for interference would indicate no interference in daily activities while a score of 10 would indicate complete interference (e.g. the subject could not get out of bed and go to work due to their pain). Baseline data includes all logs from the start of the study until the start of treatment. Post-intervention data looked at the time between the 3-month follow-up and the previous visit.

  The measure will be assessed daily from baseline to the 3-month post-treatment follow up (treatment occurred for 2-5 weeks starting in week 3).

• Baseline vs Post-Treatment HIT-6 Scores (36-78).

  The outcome measure is measuring headache impact on quality of life and will be quantified through the self-assessed Headache Impact Test (HIT-6). Each question ranges from 6-13 and the total score ranges from 36 to 78. The assessment indicates the effect that headaches have on normal daily life and ability to function with a higher score indicating more interference in daily life and function.

  The measure will be assessed every visit from baseline to the 3-month post-treatment follow up (treatment occurred for 2-5 weeks starting in week 3).

• Change From Baseline to Post-Treatment HDRS-17 Scores

  The outcome measure will be measuring depression scores and will be quantified through the administered Hamilton Scale for Depression. This contains 17 items to be rated (HDRS-17), but four other questions are not added to the total score and are used to provide additional clinical information. Each item on the questionnaire is scored on a 3 or 5 point scale, depending on the item, and the total score is compared to the corresponding descriptor. The total score ranges from 0 to 53 and is calculated from adding together the first 17 questions. A higher score indicated more severe depression.

  The measure will be assessed each visit from baseline to the 3-month post-treatment follow up (treatment occurred for 2-5 weeks starting in week 3).

• Connors Continuous Performance Test Score.

  The outcome measure quantified through the Connors continuous performance test will be sustained and selective attention. This is administered on a laptop and is automatically scored. Key performance indicators are reported as T-scores (mean of 50, SD = 10) and percentiles. T-scores are compared to the normative sample. Variability measure which looked at response speed consistency and indicated fluctuations in attention. A higher score indicated more fluctuations.

  The measure will be assessed every visit from baseline to the 3-month post-treatment follow up (treatment occurred for 2-5 weeks starting in week 3).

• Brief Pain Inventory Global Score.

  The outcome will measure global pain through the brief pain inventory assessment. Pain will be recorded at it's worst, it's best and on average over the previous 24 hours on a 0 to 10 scale These scores are reflected in questions 3-6 of the assessment and will be averaged together to give an overall average pain level score with a higher value reflecting more pain. Then the pain's impact on general activity, mood, walking ability, normal work, relationships, sleep and enjoyment of life will be measured on a 0 to 10 scale and averaged for an overall pain score. These scores are reflected in question 9a-g and will be averaged together to give an overall average pain interference level with a higher value indicating more interference in daily life.

  The measure will be assessed every visit from baseline to the 3-month post-treatment follow up (treatment occurred for 2-5 weeks starting in week 3).

• Hopkins Verbal Learning Test (HVLT-R) Total Scores

  The Hopkins Verbal Learning Test (HVLT-R) will be used to measure memory. In this assessment, 12 words are taught and subjects are tasked to recall those words in three difference trials. When scoring the HVLT-R, the number of words recalled are summed to calculate a total recall score which ranges from 0-36 with higher values indicating more words being recalled.

  The measure will be assessed every visit from baseline to the 3-month post-treatment follow up (treatment occurred for 2-5 weeks starting in week 3).

• Stroop Test Score

  The Stroop test was administered to assess cognitive functioning performance. In the test, the participant must demonstrate inhibition of cognitive interference by naming the color of the colored word instead of the word itself based on the observation that normal individuals can read words much faster than they can identify and name colors. This follows two other trials where the participant just reads the words aloud and another trial of the participant just identifying the color of a series of x's. Each trial, the participant was given 45 second to identify as many colors as they could. There is no maximum score for this assessment. This assessment is scored by the number of items they were able to correctly read out rather than on a T-score. A higher score indicated higher cognitive functioning.

  The measure will be assessed every visit from baseline to the 3-month post-treatment follow up (treatment occurred for 2-5 weeks starting in week 3).

• Average Intensity of Persistent Headaches.

  The outcome measure will be quantified through the headache diary log that tracks the intensity, frequency and duration of MTBI-headaches (MTBI-HA). Intensity was rated on a scale of 0-10 with 0 indicating no pain and 10 indicating the worst pain they have experienced. Baseline data includes all logs from the start of the study until the start of treatment. Post-intervention data looked at the time between the 3-month follow-up and the previous visit.

  The measure will be assessed daily from baseline to the 3-month post-treatment follow up (treatment occurred for 2-5 weeks starting in week 3).

• Average Intensity of Debilitating Headaches.

  The outcome measure will be quantified through the headache diary log that tracks the intensity, frequency and duration of MTBI-headaches (MTBI-HA). Intensity was rated on a scale of 0-10 with 0 indicating no pain and 10 indicating the worst pain they have experience. Baseline data includes all logs from the start of the study until the start of treatment. Post-intervention data looked at the time between the 3-month follow-up and the previous visit.

  The measure will be assessed daily from baseline to the 3-month post-treatment follow up (treatment occurred for 2-5 weeks starting in week 3).

Secondary Outcomes (1)

• Significant T-Values for Connectivity Between Regions.

  Subjects will have 2 functional magnetic imaging scans, at baseline and then at the 1-week post treatment follow-up.

Study Arms (2)

Transcranial Magnetic Stimulation

EXPERIMENTAL

Active-repetitive transcranial magnetic stimulation (rTMS) at the left motor cortex.

Device: Transcranial Magnetic Stimulation; Diagnostic Test: Magnetic resonance imaging (MRI)

Sham Transcranial Magnetic Stimulation

SHAM COMPARATOR

Sham rTMS will consist of the same parameters as active, however, the subject will not receive the actual magnetic stimulation to the left motor cortex.

Device: Sham Transcranial Magnetic Stimulation; Diagnostic Test: Magnetic resonance imaging (MRI)

Interventions

Transcranial Magnetic Stimulation DEVICE

Active-repetitive transcranial magnetic stimulation (rTMS) at the left motor cortex.

Transcranial Magnetic Stimulation

Sham Transcranial Magnetic Stimulation DEVICE

Sham rTMS will consist of the same parameters as active, however, the subject will not receive the actual magnetic stimulation to the left motor cortex due to the use of a double sided Active/Sham coil used specifically for research studies.

Sham Transcranial Magnetic Stimulation

Magnetic resonance imaging (MRI) DIAGNOSTIC_TEST

Brain imaging will be done via MRI prior to the first rTMS/Sham TMS session. Imaging will allow investigators to target specific areas in the brain.

Sham Transcranial Magnetic Stimulation; Transcranial Magnetic Stimulation

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The following diagnostic criteria for MTBI based on the 1993 American Congress of Rehabilitation Medicine and recent recommendation from the DOD, and the current diagnostic criteria adopted by the VASDHS TBI Clinic will be used for the study. A traumatically induced physiological disruption of brain function, as manifested by at least one of the following:
• any loss of consciousness
• any loss of memory for events immediately before or after the accident
• any alteration in mental state at the time of the accident, e.g.:
• feeling dazed
• disoriented
• confused)
• Focal neurologic deficit (s) that may or may not be transient but where the severity of the injury does not exceed the following:
• loss of consciousness of approximately 30 min or less
• after 30 min, an initial Glasgow Coma Scale score of 13-15
• post-traumatic amnesia not greater than 24 hrs
• In addition, the following established diagnostic criteria for " Persistent headache attributed to mild traumatic injury headache" based on the International Classification of Headache Disorder (ICHD-3) will be applied to the study subjects:
• A. Any headache fulfilling criteria C and D
• B. Traumatic injury to the head has occurred
• C. Headache is reported to have developed within 7 d after one of the following:

You may not qualify if:

• pregnancy; To be eligible for the study and to ensure no pregnancy risk, you will need to utilize contraception or practice abstinence until your study participation is completed
• history of pacemaker implant
• any ferromagnetic material in the brain or body that would prohibit the patients from having a brain MRI, e.g.:
• bullet fragment
• shrapnel
• device implant
• history of dementia, major psychiatric or life threatening diseases
• presence of any other chronic neuropathic pain states;
• history of seizure
• pending litigation
• lack of ability to understand the experimental protocol and to adequately communicate in English
• history of chronic headache diagnoses such migraine, tension or cluster headaches prior to the incidence of MTBI.
• history of chronic headache prior to the MTBI incidence at a frequency more than once a month lasting more than one hour.
• evidence in the chart of recent exacerbation of depressive or anxiety symptoms, active substance dependence, suicidal intent or attempt within the previous month, and/or current psychotic symptoms

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

VA San Diego Healthcare System, San Diego, CA

San Diego, California, 92161-0002, United States

Location

Related Publications (1)

• Leung A, Ho M, Vaninetti M, Krug P, Rutledge T, Lin L, Tsai A, Le L, Rimmele C, Lee R, Golshan S. Long-term Efficacy of Repetitive Transcranial Magnetic Stimulation at Motor Cortex for Mild Traumatic Brain Injury-Related Headaches. Neuromodulation. 2025 Oct 18:S1094-7159(25)01033-5. doi: 10.1016/j.neurom.2025.09.308. Online ahead of print.

  PMID: 41109991 DERIVED

MeSH Terms

Conditions

Brain Injuries, Traumatic; Headache

Interventions

Transcranial Magnetic Stimulation; Magnetic Resonance Imaging

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics; Tomography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis

Results Point of Contact

• Title: Dr. Albert Leung
• Organization: VAORD

ayleung@health.ucsd.edu

858-552-8585

Study Officials

• Albert Yick Leung, MD

  VA San Diego Healthcare System, San Diego, CA

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: This is a double-blinded study where only the statistician is aware of the randomization.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 4, 2017
• First Posted: October 19, 2017
• Study Start: January 1, 2018
• Primary Completion: September 30, 2023
• Study Completion: January 31, 2024
• Last Updated: August 7, 2025
• Results First Posted: August 7, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)