Multisite Advancement of Research on Chronic Posttraumatic Headache

Study Overview
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Brief Summary
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Posttraumatic headache (PTH) is a common and highly disabling consequence of traumatic brain injury (TBI) in U.S. military service members and veterans. Cognitive Behavioral Therapy for PTH has been shown to significantly improve disability outcomes in veterans with persistent PTH when delivered in-person. Telemedicine platforms can dramatically increase access to evidence-based care. However, whether CBT for PTH retains its effectiveness when delivered through a telemedicine platform has yet to be established. The purpose of this 3-arm randomized clinical trial is to compare Clinic-based Cognitive-Behavioral Therapy (CCBT) to Telemedicine-based Cognitive Behavioral Therapy (TCBT) and to treatment as usual (TAU) in 525 service members and veterans with chronic posttraumatic headaches (PTH) at 3 VA medical centers and 4 military treatment facilities across the U.S. Participants will be assessed for headache-related disability, headache experience, and psychiatric comorbidities across multiple time points.

Detailed Description
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Posttraumatic headache (PTH) is noticeably more common among military service members and veterans than among civilians, with an estimated 80-90% of veterans with TBI reporting new or exacerbated headaches. Unlike civilian PTH, military and veteran PTH is likely to become chronic and recalcitrant to most front-line interventions for primary headache (e.g., migraine, tension-type). Service members and veterans with PTH report significantly decreased productivity in work and home activities and high rates of military discharge and work absenteeism. Pharmacological treatments for chronic PTH have proven problematic (i.e., unwanted side effects; worsening of symptoms long term). However, prior to 2019, guidance for non-pharmacological treatment approaches for PTH was unclear. In 2019, the investigators completed a single-site randomized clinical trial comparing Clinic-based CBT for PTH to Treatment at Usual in 193 veterans with PTH. The study found that Clinic-based CBT for PTH led to a significant improvement in headache-related disability (as measured by the 6-Item Headache Impact Test; HIT-6) at follow-up. In contrast, headache disability scores for participants in the Treatment as Usual condition remained unchanged. COVID-19 pandemic led to widespread recognition of the need for distance-technology platforms to add meaningful infrastructure for extended service delivery without the limitations of in-office care. Telehealth-based care can decrease the cost and increase the convenience of treatment leading some to suggest that telehealth may eventually become a first option for treating patients. Given the potential impact of CBT for PTH to improve the functioning of service members and veterans with PTH following TBI, it is important to determine whether the results of the single-site trial can be replicated across diverse geographic regions and whether CBT for PTH retains its efficacy in improving headache-related disability when delivered through telemedicine platforms.

Official Title
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Project MARCH: Multisite Advancement of Research on Chronic Posttraumatic Headache

Conditions
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Posttraumatic Headache

Intervention / Treatment
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* Behavioral: Cognitive Behavioral Therapy for Posttraumatic Headache
* Other: Treatment as Usual
* Other: Telemedicine-based Cognitive Behavioral Therapy (TCBT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Any veteran or active duty service member (age 18 to 70 years) with mTBI whose headache began or exacerbated within 3 months of a head or neck injury. Headache meets ICHD-3 A5.2.2.1 criterion for delayed-onset persistent headache attributable to mild TBI and PTH is ongoing at enrollment (most recent headache within the past 2 weeks). At least moderate to severe headache-related disability based on a HIT-6 score greater than 50. Participant is stable on headache medication at baseline assessment (i.e., no changes in medication prescriptions in the past 4 weeks; this includes botulinum toxin injections and devices like Cefaly). Participant has a phone were they can receive reminders and complete the on-line Sleep Diaries. To participate in telemedicine study arm, participants must: Have access to high-speed internet or 4G/5G phone service and be able to connect from a location that affords privacy. Have phone or computer equipment to run the virtual video connect platform OR be willing to use study-provided equipment for the duration of the study. Exclusion Criteria: Participant reports a significant change in headache symptoms within 4 weeks of screening or has another secondary headache that may account for symptoms. Participant has medication overuse headache based on Structured Diagnostic Headache Interview-Revised (Brief Version; SDIH-R) and clinical judgment. Participant is unable to read or speak English at a 6th grade level. Participant has a psychiatric problem that warrants immediate treatment as indicated in the electronic health record, flagged study during testing, or confirmed by a clinician through screening or review of clinical notes. Participant demonstrates significant cognitive impairment that could impact treatment adherence/benefit.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Clinic-based Cognitive Behavioral Therapy (CCBT)<br>CCBT provides CBT for posttraumatic headache through 8 face-to-face, in-clinic sessions. | Behavioral: Cognitive Behavioral Therapy for Posttraumatic Headache<br>* CBT for Posttraumatic Headaches consists of 8 sessions of cognitive behavioral therapy that focus on (1) discussions and exercises that increase awareness of what may be related to headaches, (2) relaxation techniques to manage physiological stress, and (3) problem-solving techniques to manage common stressors. Sessions are delivered weekly and can last between 45 to 75 minutes based on clinical content and patient response to the material.<br>* Other names: CCBT;|
| Active Comparator: Telemedicine-based Cognitive Behavioral Therapy (TCBT)<br>TCBT provides 8-sessions of CBT for posttraumatic headache using telemedicine technology rather than attending in-office sessions. Additionally, TCBT includes instructions for each session specific to the mechanics of a telehealth encounter (e.g., asking participant for name, location, and accessible phone number for location in case of technical failure or crisis). All TCBT participants must be enrolled at the MTF or VA from which they were recruited, and the treatment facility will be notified that they are receiving TCBT in case a crisis arises and needs to be managed by the site. | Other: Telemedicine-based Cognitive Behavioral Therapy (TCBT)<br>* Participants assigned to TCBT will receive 8 sessions of cognitive behavioral therapy using telemedicine rather than face-to face office visits.<br>|
| Active Comparator: Treatment As Usual<br>Participants will continue to engage in clinical care as usual for 8 weeks. Research staff will call the TAU participants weekly to assess for adverse events. Research staff at each site will be trained on standardized assessment of usual care activities using forms adapted from our single-site trial. | Other: Treatment as Usual<br>* Participants will continue to engage in medical care as usual for 8 weeks.<br>* Other names: TAU or TPU;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Headache Impact Test (HIT-6) | Headache-disability as measured by the Headache Impact Test. The HIT-6 is a 6-item measure of headache-disability. The measure uses a 5-point Likert scale to rate the frequency that the respondent experiences headache-relate disability across six domains of functioning. Total scores range from 36 to 78 with higher scores representing a higher level of headache-relate disability. | Baseline to 3-month follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Standardized Headache Diary | Headache frequency, duration and intensity will be assessed using a smartphone-based daily headache self-monitoring diary developed by the HCoE. During treatment, participants will record their headache intensity twice daily, using a 0 to 10 scale, to assess: (a) days per week with a headache (ranging from 0 to 7); (b) weekly headache frequency (range from 0 to 10); (c) headache duration (>= 0 hours); and (d) average peak headache intensity (range from 0 to 10). | Baseline to 3-month follow-up | 
| Change in Patient Health Questionnaire-9 | Total score on the Patient Health Questionnaire-9 (PHQ-9). The PHQ-9 is 9-item, self-report screener for current depressive symptoms. Each item is rated on a frequency scale ranging from 0 (Not at all) to 3 (Nearly Every day). The measure provides a total severity score that ranges from 0 to 27, with higher scores representing more severe depressive symptoms. | Baseline to 3-month follow-up | 
| Change in Generalized Anxiety Disorder Screener-7 | Total score on the Generalized Anxiety Disorder Screener (GAD-7): The GAD-7 is 7-item, self-report screener for current anxiety symptoms. Each item is rated on a frequency scale ranging from 0 (Not at all) to 3 (Nearly Every day). The measure provides a total severity score that ranges from 0 to 21, with higher scores representing more severe anxiety symptoms. | Baseline to 3-month follow-up | 
| Change in PTSD Checklist-5 | Scale measurements by the PTSD CheckList-5 (PCL-5). The PCL-5 is a 20-item, self-report measure of PTSD symptoms experienced in the past month. Each item is rated on a severity scale ranging from 0 (Not at all) to 4 (Extremely). The measure provides a total severity score that ranges from 0 to 80, with higher scores representing more PTSD symptoms. | Baseline to 3-month follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Military Service Members, Chronic Pain, Headaches, Cognitive Behavioral Therapy, Telehealth, Veterans