Combined Transcranial Magnetic Stimulation and Therapy for mTBI Related Headaches

Study Overview
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Brief Summary
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This study will assess the combined effectiveness of repetitive transcranial magnetic stimulation (rTMS) and telehealth based therapy in helping manage mild traumatic brain injury (mTBI) related headaches. The investigators hypothesize that active rTMS combined with telehealth therapy will provide marked reduction in mTBI related headaches and symptoms in comparison to their placebo counterparts.

Detailed Description
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This study will be enrolling a total of 240 veterans or active military over a 4 year period at the VA San Diego Healthcare System (VASDHS). Participants will be randomized into one of four groups: Group A: active rTMS with telehealth headache management therapy Group B: active rTMS with telehealth headache education control Group C: sham rTMS with telehealth headache management therapy Group D: sham rTMS with telehealth headache education control Individual participation will consist of 19 visits to the VASDHS and 11 telehealth sessions over the course of 6-7 months. The in person visits will be divided into the following phases: PRE-TREATMENT ASSESSMENTS PHASE (weeks 1-2) which consists of Visit 1 (Screening Visit) and Visit 2 (Baseline Assessments with MRI scan); INDUCTION TREATMENT PHASE (weeks 3-4) consists of Visits 3-12 (10 weekday neuronavigation guided rTMS sessions at >24 and <72 hours apart); and POST-TREATMENT ASSESSMENTS AND MAINTENANCE TREATMENT PHASE (weeks 5-24) consists of 4 initial biweekly post-induction treatment assessments and maintenance treatments (Visits 13-16)) and two additional monthly post-induction assessments and maintenance treatments (Visits 17-18) and one final study visit (Visit 19). Eight weekly telehealth therapy/education sessions will be conducted from week 3 to 10 with additional three bolster sessions at 4 weeks apart. During the baseline and follow up visits, assessments will be conducted to evaluate headaches, neurobehavioral symptoms, depressive symptoms, post-concussion symptoms, and quality of life.

Official Title
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Combined Nonpharmacological Therapies for MTBI-Related Headaches

Conditions
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TBI (Traumatic Brain Injury), Headache, Depression

Intervention / Treatment
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* Device: Active rTMS
* Behavioral: Headache Management Therapy
* Device: Sham rTMS
* Behavioral: Headache Education Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Mild Traumatic Brain Injury (mTBI) Chronic headaches > 3 months after injury Aged 18-65 No prior TMS treatment Persistent Headaches with an intensity > 30 / 100 No history of daily headache prior to mTBI Exclusion Criteria: Pregnant Pacemaker or any metal in body that would prevent MRI History of dementia or major psychiatric disease, such as bipolar disorder or schizophrenia Presence of any other chronic neuropathic pain states History of seizure Pending litigation Can't understand English History of chronic headache like migraine prior to mTBI Evidence in chart of exacerbation of depressive/anxiety symptoms, active substance dependence, suicidal intent or attempt within previous month

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Interventional Model Description: Each participant will be randomized into one of 4 groups. Blocked randomization will be used with random block size of 4 or 8. Participants will be randomized to study groups in a 1:1:1:1 ratio.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active rTMS with telehealth headache management therapy<br>Participants receive both active rTMS treatment at the left dorsolateral prefrontal cortex and therapy for headache management | Device: Active rTMS<br>* Active rTMS will be given at the left dorsolateral prefrontal cortex with a double blind TMS coil.<br>Behavioral: Headache Management Therapy<br>* Therapy will be provided on headache management.<br>|
| Other: Active rTMS with telehealth headache education control<br>Participants receive active rTMS treatment at the left dorsolateral prefrontal cortex and headache education | Device: Active rTMS<br>* Active rTMS will be given at the left dorsolateral prefrontal cortex with a double blind TMS coil.<br>Behavioral: Headache Education Control<br>* In the control, educational sessions on headaches will be provided.<br>|
| Other: Sham rTMS with telehealth headache management therapy<br>Participants receive sham rTMS treatment at the left dorsolateral prefrontal cortex and therapy for headache management | Behavioral: Headache Management Therapy<br>* Therapy will be provided on headache management.<br>Device: Sham rTMS<br>* Sham rTMS will be given at the left dorsolateral prefrontal cortex. All parameters of the treatment will appear identical to the active treatment, with only the rTMS coil used to administer the treatment flipped 180 degrees to prevent stimulation.<br>|
| Sham Comparator: Sham rTMS with telehealth headache education control<br>Participants receive sham rTMS treatment at the left dorsolateral prefrontal cortex and headache education | Device: Sham rTMS<br>* Sham rTMS will be given at the left dorsolateral prefrontal cortex. All parameters of the treatment will appear identical to the active treatment, with only the rTMS coil used to administer the treatment flipped 180 degrees to prevent stimulation.<br>Behavioral: Headache Education Control<br>* In the control, educational sessions on headaches will be provided.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intensity of Persistent Headaches | Assesses the intensity of persistent headaches, from a scale of 0, being no pain, to 10, being worst possible pain. | Change from baseline to 2-, 4-, 6-, 8-, 12-, 16-, and 20-weeks follow up visit | 
| Intensity of Debilitating Headaches | Assesses the intensity of debilitating headaches, from a scale of 0, being no pain, to 10, being worst possible pain. | Change from baseline to 2-, 4-, 6-, 8-, 12-, 16-, and 20-weeks follow up visit | 
| Persistent Headache Frequency | Assesses the frequency per week of persistent headaches | Change from baseline to 2-, 4-, 6-, 8-, 12-, 16-, and 20-weeks follow up visit | 
| Debilitating Headache Frequency | Assesses the frequency per week of debilitating headaches | Change from baseline to 2-, 4-, 6-, 8-, 12-, 16-, and 20-weeks follow up visit | 
| Debilitating Headache Interference | Assesses the interference of debilitating headaches for activities of daily living, from 0, being no interference, to 10, being worst possible interference. | Change from baseline to 2-, 4-, 6-, 8-, 12-, 16-, and 20-weeks follow up visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Headache Impact Test | Measures the impact of headache on an individual's ability to function at work, school, home, and/or social situations. Each item is measured from never, rarely, sometimes, very often, or always, with scores of 6, 8, 10, 11, and 13 respectively. A higher score correlates to a greater negative impact of headaches on quality of life. | Change from baseline to 2-, 4-, 6-, 8-, 12-, 16-, and 20-weeks follow up visit | 
| Neurobehavioral Symptom Inventory | Assesses the severity of symptoms in the following areas: somatic, cognitive, affective, and sensory. Each item ranges from 0-4 with a higher score indicating a worse outcome. | Change from baseline to 2-, 4-, 6-, 8-, 12-, 16-, and 20-weeks follow up visit | 
| Hamilton Rating Scale for Depression | Rates the severity of symptoms observed in depression such as low mood, insomnia, agitation, anxiety and weight loss. Scores range from 0 to 53, with a higher score indicating a larger degree of depression. | Change from baseline to 2-, 4-, 6-, 8-, 12-, 16-, and 20-weeks follow up visit | 
| Rivermead Post-Concussion Symptoms Questionnaire | Assesses somatic, cognitive, and emotional symptoms experiences after traumatic brain injury. Each item ranges from 0-4, with a higher score indicating a worse outcome. | Change from baseline to 2-, 4-, 6-, 8-, 12-, 16-, and 20-weeks follow up visit | 
| Short Form Health Survey-36 | Measures health status and quality of life in regards to eight main areas: vitality, physical functioning, bodily pain, health perceptions, physical, emotional, and social role functioning and mental health. Each item is scored on a 0 to 100 range, with a higher score indicating a worse outcome. | Change from baseline to 2-, 4-, 6-, 8-, 12-, 16-, and 20-weeks follow up visit | 
| Short-Form NEURO-QoL | Assesses quality of life related to neurological disorders. Each item ranges from 1-5, with a higher score indicating a worse outcome. | Change from baseline to 2-, 4-, 6-, 8-, 12-, 16-, and 20-weeks follow up visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rTMS, transcranial magnetic stimulation, therapy