Clinical trial NCT06669780: E-CBT DTx for Post Traumatic Headaches in Adults with History of TBI
Official title: Single-Blind, Randomized, Controlled Pilot Trial of a Cognitive-Behavioral Therapy Digital Therapeutic Delivered Online for Post-Traumatic Headaches in Adults with History of Concussive Traumatic Brain Injury
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Post-Traumatic Headache
Lead sponsor: Henry M. Jackson Foundation for the Advancement of Military Medicine
Sponsor class: OTHER
Collaborators: name: Uniformed Services University of the Health Sciences
name: Military Traumatic Brain Injury Initiative
First posted: 2024-11-01
Enrollment: 100
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: The AMMO digital therapeutic (DTx) study will provide an online based program for participants with migraines after head injury to follow for 12 weeks. This study aims to see if using cognitive behavioral therapy aimed at military service members in an online self administered platform is effective therapy in the relief of migraines compared. The study will use a single blind online comparative program to test the effect.

Detailed description: The AMMO digital therapeutic (DTx) will be a novel intervention for PTH following concussive TBI, therefore this project is a pilot trial designed to test this new treatment. This pilot is a single-blind, randomized, controlled, interventional trial of current and former military personnel along with civilians with a history of concussive TBI and current PTH. The pilot trial will be conducted via online portal accessible by smartphone, tablet, or computer with remote interaction between participants and study staff. The pilot trial will include up to 100 participants randomized to either the active intervention or a comparison condition at a 1:1 ratio, and will provide preliminary data to determine the sample size of a future full clinical trial. Participants will complete a 12 week intervention period followed by a follow-up assessment 4 weeks after intervention is complete. Participants randomized to the comparison group will be provided access to the open label after end of 16 week follow-up.

In addition, updates to the DTx to improve usability and acceptability will be made if necessary based on feedback from the pilot trial, then applied to the final DTx used in a future, larger, clinical trial.

Eligibility criteria: Inclusion Criteria:

* Be aged ≥ 18 to ≤ 70 years
* Have a history of concussive TBI ≥ 3 months prior to enrollment:
* A concussive TBI is defined by having at least one of the following after a head trauma (ACRM, 1993) oAny period of loss of consciousness; oAny loss of memory for events immediately before or after the accident; oAny alteration in mental state at the time of the accident (e.g., feeling dazed, disoriented, or confused); and oFocal neurological deficit(s) that may or may not be transient oThe injury must not exceed any of the following (ACRM, 1993):
* Loss of consciousness of approximately 30 minutes or less;
* After 30 minutes an initial GCS score of 13-15; and
* PTA not greater than 24 hours

  * Head trauma resulting in concussive TBI can be due to blast or non-blast mechanisms
  * Head trauma resulting in concussive TBI can have occurred any time in the participant's life: prior to military service, during deployment, in garrison, or after leaving military service
* Have a history of chronic PTH defined as:

  o Headache is reported to have developed (or worsened) after one of the following\*:
* The injury to the head;
* Regaining of consciousness following the injury to the head; or
* Discontinuation of medication(s) impairing ability to sense or report headache following the injury to the head
* Not better accounted for by another ICHD-3 diagnosis\*\*

  o The headache persists for \>3 months after its onset (ICHD, 2013)
* Have a HIT-6™ score of ≥ 56 to 78 indicative of substantial impact (56-59) or severe impact (60-78) on functioning (Yang, Rendas-Baum, Varon, \& Kosinski, 2011)
* Be able to provide written, informed consent in English and follow study-related instructions
* Have ownership of or reliable access to a smartphone with a data plan or internet connecting capabilities
* Be aged ≥ 18 to ≤ 70 years
* Have a history of concussive TBI ≥ 3 months prior to enrollment:
* A concussive TBI is defined by having at least one of the following after a head trauma (ACRM, 1993):

  * Any period of loss of consciousness;
  * Any loss of memory for events immediately before or after the accident;
  * Any alteration in mental state at the time of the accident (e.g., feeling dazed, disoriented, or confused); and
  * Focal neurological deficit(s) that may or may not be transient
  * The injury must not exceed any of the following (ACRM, 1993):
* Loss of consciousness of approximately 30 minutes or less;
* After 30 minutes an initial GCS score of 13-15; and
* PTA not greater than 24 hours

  * Head trauma resulting in concussive TBI can be due to blast or non-blast mechanisms
  * Head trauma resulting in concussive TBI can have occurred any time in the participant's life: prior to military service, during deployment, in garrison, or after leaving military service
* Have a history of chronic PTH defined as:

  o Headache is reported to have developed (or worsened) after one of the following\*:
* The injury to the head;
* Regaining of consciousness following the injury to the head; or
* Discontinuation of medication(s) impairing ability to sense or report headache following the injury to the head
* Not better accounted for by another ICHD-3 diagnosis\*\*

  o The headache persists for \>3 months after its onset (ICHD, 2013)
* Have a HIT-6™ score of ≥ 56 to 78 indicative of substantial impact (56-59) or severe impact (60-78) on functioning (Yang, Rendas-Baum, Varon, \& Kosinski, 2011)
* Be able to provide written, informed consent in English and follow study-related instructions
* Have ownership of or reliable access to a smartphone with a data plan or internet connecting capabilities

Exclusion Criteria:

* They experienced a moderate or severe TBI
* Their secondary headache is better accounted for by the ICHD-3 diagnosis of 8.2 medication-overuse headache; must meet diagnostic criteria for at least 1 medication-overuse headache diagnosis (8.2.1-8.2.8)
* They are currently engaged in psychotherapeutic treatment or have engaged in psychotherapeutic treatment within 8 weeks prior to trial enrollment (for more information regarding recent treatment in potential participants, see section '3.2 Study Procedures,' sub-section 'Baseline Evaluation')
* They report change or discontinuation of headache prophylaxis in the past 4 weeks
* They report active psychotic or bipolar symptoms
* In the opinion of the investigator, they have other considerations that may adversely affect patient safety, participation, or scientific validity of the data being collected (including, but not limited to, active plan or intent for suicide, visual impairment, hand dysfunction or amputation, substantial cognitive impairment, life expectancy of less than 6 months)

Primary outcomes:
measure: 6-Item Headache Impact Test™ (HIT-6™)
timeFrame: 16 weeks
Secondary outcomes:
measure: Determine the appropriate sample size for a future full clinical trial based on preliminary estimates of effect size for outcome measures
timeFrame: 12 weeks
measure: Post Traumatic Stress Disorder Checklist (DSM-5)
timeFrame: 16 weeks
measure: Traumatic Brain Injury Quality of Life Scale (TBI-QOL)
timeFrame: 16 weeks
measure: Patient Health Questionnaire-9
timeFrame: 16 weeks
measure: Insomnia Severity Index (ISI)
timeFrame: 16 weeks
measure: User Version of the Mobile Application Rating Scale
timeFrame: 12 weeks
measure: Mobile Agnew Relationship Measure
timeFrame: 12 weeks
measure: User Program Feedback Questionnaire
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: 100% Remote Recruitment: Center for Neurscience and Regenerative Medicine
state: Maryland
Study officials:
References:
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citation: Stoyanov SR, Hides L, Kavanagh DJ, Wilson H. Development and Validation of the User Version of the Mobile Application Rating Scale (uMARS). JMIR Mhealth Uhealth. 2016 Jun 10;4(2):e72. doi: 10.2196/mhealth.5849.
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citation: Tulsky DS, Kisala PA, Victorson D, Carlozzi N, Bushnik T, Sherer M, Choi SW, Heinemann AW, Chiaravalloti N, Sander AM, Englander J, Hanks R, Kolakowsky-Hayner S, Roth E, Gershon R, Rosenthal M, Cella D. TBI-QOL: Development and Calibration of Item Banks to Measure Patient Reported Outcomes Following Traumatic Brain Injury. J Head Trauma Rehabil. 2016 Jan-Feb;31(1):40-51. doi: 10.1097/HTR.0000000000000131.
citation: 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.
citation: Blevins CA, Weathers FW, Davis MT, Witte TK, Domino JL. The Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5): Development and Initial Psychometric Evaluation. J Trauma Stress. 2015 Dec;28(6):489-98. doi: 10.1002/jts.22059. Epub 2015 Nov 25.
citation: Kosinski M, Bjorner JB, Ware JE Jr, Batenhorst A, Cady RK. The responsiveness of headache impact scales scored using 'classical' and 'modern' psychometric methods: a re-analysis of three clinical trials. Qual Life Res. 2003 Dec;12(8):903-12. doi: 10.1023/a:1026111029376.
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