Multisite Advancement of Research on Chronic Posttraumatic Headache

Official title

Project MARCH: Multisite Advancement of Research on Chronic Posttraumatic Headache

Overview

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. \*VA Palo Alto Health Care System is temporarily randomizing into TAU and TCBT only.

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.

Interventions

• Behavioral Cognitive Behavioral Therapy for Posttraumatic Headache
  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.
• Other Treatment as Usual
  Participants will continue to engage in medical care as usual for 8 weeks.
• Other Telemedicine-based Cognitive Behavioral Therapy (TCBT)
  Participants assigned to TCBT will receive 8 sessions of cognitive behavioral therapy using telemedicine rather than face-to face office visits.

Primary outcome measures

• Change in Headache Impact Test (HIT-6) [Time frame: Baseline to 3-month follow-up]

Secondary outcome measures (4)

• Change in Standardized Headache Diary [Time frame: Baseline to 3-month follow-up]
• Change in Patient Health Questionnaire-9 [Time frame: Baseline to 3-month follow-up]
• Change in Generalized Anxiety Disorder Screener-7 [Time frame: Baseline to 3-month follow-up]
• Change in PTSD Checklist-5 [Time frame: Baseline to 3-month follow-up]

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 or study physician clinical judgement confirms stability; 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

United States · 8 centers

• VA Greater Los Angeles Healthcare System — Los Angeles
• VA Palo Alto Health Care System — Palo Alto
• Tripler Army Medical Center (Desmond Doss Health Clinic, Schofield Barracks) — Honolulu
• Walter Reed National Military Medical Center — Bethesda
• Minneapolis VA Health Care System — Minneapolis
• Carl R. Darnall Army Medical Center (Fort Cavazos) — Killeen
• South Texas Veterans Health Care System — San Antonio
• Brooke Army Medical Center — San Antonio

Publications

• Arcaya MC, Lowe SR, Asad AL, Subramanian SV, Waters MC, Rhodes J. Association of posttraumatic stress disorder symptoms with migraine and headache after a natural disaster. Health Psychol. 2017 May;36(5):411-418. doi: 10.1037/hea0000433. Epub 2016 Dec 8. PMID 27929328
• Cameron IM, Crawford JR, Lawton K, Reid IC. Psychometric comparison of PHQ-9 and HADS for measuring depression severity in primary care. Br J Gen Pract. 2008 Jan;58(546):32-6. doi: 10.3399/bjgp08X263794. PMID 18186994
• Dave A, Ganesh A, Adil MM, Tsao JW. Practice Current: How do you diagnose and treat post-concussive headache? Neurol Clin Pract. 2019 Jun;9(3):263-270. doi: 10.1212/CPJ.0000000000000656. PMID 31341715
• Eckner JT, Seifert T, Pescovitz A, Zeiger M, Kutcher JS. Is Migraine Headache Associated With Concussion in Athletes? A Case-Control Study. Clin J Sport Med. 2017 May;27(3):266-270. doi: 10.1097/JSM.0000000000000346. PMID 27428679
• Holtkamp MD, Grimes J, Ling G. Concussion in the Military: an Evidence-Base Review of mTBI in US Military Personnel Focused on Posttraumatic Headache. Curr Pain Headache Rep. 2016 Jun;20(6):37. doi: 10.1007/s11916-016-0572-x. PMID 27084376
• Jaramillo CA, Eapen BC, McGeary CA, McGeary DD, Robinson J, Amuan M, Pugh MJ. A cohort study examining headaches among veterans of Iraq and Afghanistan wars: Associations with traumatic brain injury, PTSD, and depression. Headache. 2016 Mar;56(3):528-39. doi: 10.1111/head.12726. Epub 2015 Dec 21. PMID 26688427
• Kosinski M, Bayliss MS, Bjorner JB, Ware JE Jr, Garber WH, Batenhorst A, Cady R, Dahlof CG, Dowson A, Tepper S. A six-item short-form survey for measuring headache impact: the HIT-6. Qual Life Res. 2003 Dec;12(8):963-74. doi: 10.1023/a:1026119331193. PMID 14651415
• Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001 Sep;16(9):606-13. doi: 10.1046/j.1525-1497.2001.016009606.x. PMID 11556941

Identifiers

NCT: NCT05620719 · HSC20220592H

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗