Managing Mild Traumatic Brain Injury Related Headaches With Repetitive Transcranial Magnetic Stimulation
- Conditions
- Traumatic Brain Injury (TBI)
- Registration Number
- NCT03314584
- Lead Sponsor
- VA Office of Research and Development
- 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.
- Detailed Description
Headache is one of the most common debilitating chronic pain conditions in either active or retired military personnel with MTBI. This high prevalence of persistent chronic headache is often associated with neuropsychological dysfunction in mood, attention, and memory, which casts a profound negative impact on patients' quality of life and increases stress in their caregivers. Unfortunately, as witnessed by the investigators in their clinical practices, conventional pharmacological treatments for MTBI related headache (MTBI-HA) has not been shown to be effective and drugs such as narcotics contain many long-term untoward psychosomatic and abusive side effects. This calls for an urgent need in developing alternate and innovative long-term headache management strategies for this rapidly increasing patient population.
Coinciding with other published treatment protocols related to traumatic brain injury and pain, this initial clinical evidence provides compelling support for the current proposal aiming to assess the effect of a longer duration of rTMS protocol in managing MTBI-HA for up to 10 weeks after the initiation of the treatment. Given existing treatment options for MTBI-HA are limited, validating such a non-pharmacological and non-invasive treatment option will significantly enhance the capability of the VA healthcare system in caring for this rapidly increasing patient population.
1. PRE-TREATMENT PHASE (weeks 1-2) consists of Visit 1 (Screening Visit) and Visit 2 (Pre-treatment Assessments);
2. TREAMENT PHASE (week 3-4) consists of Visits 3-12 (Neuronavigation guided rTMS consisting of 10 weekday treatments at \>24 and \< 72 hours apart, weekends excluded, maximum 5 weeks for treatment completion) rTMS will take place in Building 23 Room 105 at the VASDHS; and
3. POST-TREATMENT PHASE (week 5-14) consists of two initial weekly visits (Visits 13\&14) and two additional biweekly visits (Visits 15\&16) and one monthly visit (Visit 17).
Brain anatomical and functional MRI will be performed within 72 hours after Visits 2 and 13. Subjects will be required to fill out headache diary between assessment visits. Headache assessments along with quality of life, mood and functions assessments will be carried out at Visits 1,2, and 13--17. This frequency of treatment and duration of follow-up is in line with recently published rTMS articles related to TBI, headache and pain, and also in accordance with the 3-month post treatment initiation follow-up guideline/recommendation.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 179
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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:
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any loss of consciousness
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any loss of memory for events immediately before or after the accident
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any alteration in mental state at the time of the accident, e.g.:
- feeling dazed
- disoriented
- confused)
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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
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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:
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- injury to the head
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- regaining of consciousness following the injury
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- discontinuation of medication(s) that impairs the ability to sense or report headache following the injury
- D. Headache persists for >3 mo after injury to the head
- E. Not better accounted for by another ICHD-3 diagnosis
Additional Inclusion Criteria:
- no prior experience of TMS treatment
- average persistent headache intensity more than 30 on the 0-100 mechanical visual analog scale(M-VAS) at the screening visit (visit 1) and average persistent headache intensity score greater than 3/10 on a numerical rating scale (NRS) reported in the headache diary (between visits 1&2)
- no history of daily persistent headache prior to the MTBI incidence
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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
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history of pacemaker implant
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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
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history of dementia, major psychiatric or life threatening diseases
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presence of any other chronic neuropathic pain states;
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history of seizure
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pending litigation
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lack of ability to understand the experimental protocol and to adequately communicate in English
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history of chronic headache diagnoses such migraine, tension or cluster headaches prior to the incidence of MTBI.
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history of chronic headache prior to the MTBI incidence at a frequency more than once a month lasting more than one hour.
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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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Primary Outcome Measures
Name Time Method Number of Headache Days Per Week 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). 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.
Number of Days With Debilitating MTBI-headaches Per Week. 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). 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.
Duration of Debilitating MTBI-headaches (Hours). 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). 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.
Average Interference (0-10) of Headaches in Daily Activities. 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). 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.
Baseline vs Post-Treatment HIT-6 Scores (36-78). 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). 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.
Change From Baseline to Post-Treatment HDRS-17 Scores 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). 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.
Connors Continuous Performance Test Score. 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). 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.
Brief Pain Inventory Global Score. 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). 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.
Hopkins Verbal Learning Test (HVLT-R) Total Scores 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). 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.
Stroop Test Score 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). 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.
Average Intensity of Debilitating Headaches. 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). 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.
Average Intensity of Persistent Headaches. 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). 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.
- Secondary Outcome Measures
Name Time Method 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. Resting state functional magnetic imaging scans and subsequent processing using CONN Toolbox were used to determine T-values. ROIs (region of interest) where determined and compared to other ROIs to assess connectivity between regions. Value of "0" indicated no significant connectivity between regions (p\<0.01). The sign of the value indicated directionality of connectivity. Larger absolute values of the T-value indicated stronger connectivity.
Trial Locations
- Locations (1)
VA San Diego Healthcare System, San Diego, CA
🇺🇸San Diego, California, United States
VA San Diego Healthcare System, San Diego, CA🇺🇸San Diego, California, United States