Clinical trial NCT05620719: Multisite Advancement of Research on Chronic Posttraumatic Headache
Official title: Project MARCH: Multisite Advancement of Research on Chronic Posttraumatic Headache
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Posttraumatic Headache
Keywords: Cognitive Behavioral Therapy
Telehealth
Veterans
Military Service Members
Chronic Pain
Headaches
Lead sponsor: The University of Texas Health Science Center at San Antonio
Sponsor class: OTHER
Collaborators: name: Brooke Army Medical Center
name: C.R.Darnall Army Medical Center
name: Desmond Doss Health Clinic, Schofield Barracks
name: Minneapolis Veterans Affairs Medical Center
name: South Texas Veterans Health Care System
name: VA Palo Alto Health Care System
name: Walter Reed National Military Medical Center
name: Harvard University
name: University of California, Los Angeles
name: United States Department of Defense
First posted: 2022-11-17
Enrollment: 525
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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 4 VA medical centers and 3 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: 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.

The study has four aims.

Aim 1: Determine the efficacy of Clinic-based Cognitive-Behavioral Therapy (CCBT; using our manualized intervention) and Telemedicine-Based Cognitive Behavioral Therapy (TCBT; using our manualized intervention) for posttraumatic headache (PTH) compared to treatment as usual (TAU) across seven geographically-dispersed treatment sites.

Hypothesis 1A: There will be significantly greater improvement in PTH disability (measured by the Headache Impact Test-6; HIT-6) at 3-month follow-up among service members and veterans in CCBT compared to TAU.

Hypothesis 1B: There will be significantly greater improvement in PTH disability (measured by the HIT-6) at 3-month follow-up for service members/veterans who participate in TCBT compared to TAU.

Aim 2: Establish the non-inferiority of TCBT to CCBT in the treatment of PTH-related disability. This second aim will be pursued if either CCBT or TCBT is superior to TAU in Aim 1.

Hypothesis 2: TCBT will be non-inferior to CCBT on headache-related disability (measured by the HIT-6) at 3-month follow-up.

Aim 3: Assess contribution of heterogeneity treatment effects on PTH treatment outcome. A patient-level model to assess heterogeneity treatment effect (HTE) based on site, system, and patient-level factors including all participants across sites will be run and the degree of benefit conditional on the model predictors using procedures from the Predictive Approaches to Treatment Effect Heterogeneity statement (PATH) will be assessed.

Hypothesis 3: A prognostic model consisting of baseline predictors will adequately predict disability risk with good precision and calibration. Individuals predicted to be at high risk of disability will exhibit differential treatment response, with less expected benefit than individuals with less risk.

Aim 4: Solicit participant perspectives on their treatment experience and identify patient-centered treatment targets that might better reflect their response to treatment.

Hypothesis 4A: Patients will identify measurable treatment targets across multiple domains.

Hypothesis 4B: Patients will provide treatment insights that might better reflect their response to treatment.

Eligibility criteria: Inclusion Criteria:

* Any veteran or active duty service member (DEERS-eligible; age 18 to 70 years) with mild or moderate TBI whose headache began or exacerbated within 3 months of a head or neck injury.
* Headache meets ICHD-3 A5.2 criterion for delayed-onset persistent headache attributable to mild or moderate 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 where they can receive reminders and complete the on-line Headache Diaries.
* Participant speaks and reads/understands English well enough to fully participate in the intervention and to reliably complete assessment measures.

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 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.

Primary outcomes:
measure: Change in Headache Impact Test (HIT-6)
timeFrame: Baseline to 3-month follow-up
Secondary outcomes:
measure: Change in Standardized Headache Diary
timeFrame: Baseline to 3-month follow-up
measure: Change in Patient Health Questionnaire-9
timeFrame: Baseline to 3-month follow-up
measure: Change in Generalized Anxiety Disorder Screener-7
timeFrame: Baseline to 3-month follow-up
measure: Change in PTSD Checklist-5
timeFrame: Baseline to 3-month follow-up
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: VA Greater Los Angeles Healthcare System
state: California
city: Palo Alto
country: United States
facility: VA Palo Alto Health Care System
state: California
city: Honolulu
country: United States
facility: Tripler Army Medical Center (Desmond Doss Health Clinic, Schofield Barracks)
state: Hawaii
city: Bethesda
country: United States
facility: Walter Reed National Military Medical Center
state: Maryland
city: Minneapolis
country: United States
facility: Minneapolis VA Health Care System
state: Minnesota
city: Killeen
country: United States
facility: Carl R. Darnall Army Medical Center (Fort Cavazos)
state: Texas
city: San Antonio
country: United States
facility: South Texas Veterans Health Care System
state: Texas
city: San Antonio
country: United States
facility: Brooke Army Medical Center
state: Texas
Study officials:
affiliation: The University of Texas Health Science Center at San Antonio
name: Donald D McGeary, PhD
role: PRINCIPAL_INVESTIGATOR
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