Digital Therapeutic for Depression After Head Injury in Current and Former US Military Personnel

Study Overview
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Brief Summary
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The Center for Neuroscience and Regenerative Medicine (CNRM) Clinical Trials Unit has developed the first cognitive-behavioral therapy (CBT) digital therapeutic (DTx) mobile application to counteract depressive symptoms in military service members and veterans with a history of mild traumatic brain injury (mTBI). This trial will assess the efficacy of the novel CBT-DTx for depression following mTBI compared to an educational comparison DTx.

Detailed Description
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This trial is a single-blind, randomized, controlled interventional trial of current and former military personnel with symptoms of depression and a history of mTBI. The study will be conducted remotely.

Official Title
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A Single-Blind, Randomized, Controlled Trial of a Cognitive-Behavioral Therapy Digital Therapeutic to Combat Symptoms of Depression in Service Members and Adults With a History of MildTraumatic Brain Injury

Conditions
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Depressive Symptoms, Mild Traumatic Brain Injury

Intervention / Treatment
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* Device: CNRM DTx
* Other: Psychoeducation Comparison


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be aged ≥ 18 to ≤ 65 years Be able to provide informed consent Diagnosed with mild TBI as defined by the Department of Veteran's Affairs and Department of Defense Clinical Practice Have a PHQ-9 score of ≥ 5 to 27, indicative of mild or greater depressive symptoms Have ownership of or reliable access to a smartphone with a data plan or internet connecting capabilities While participating in this study, be able to ensure that you have access to regular care for mental health and to speak with your provider as necessary Exclusion Criteria: Report of starting pharmacological or non-pharmacological treatment for depression within the 3 months prior to trial enrollment Report a recent change in type or dose of antidepressant medications within 12 weeks prior to trial enrollment Report active psychotic or bipolar symptoms Active plan and/or intent of suicide or homicide 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

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: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CBT DTx<br>Participants randomized to active intervention will access a structured, cognitive behavioral therapy (CBT) intervention. | Device: CNRM DTx<br>* A mobile application intervention adapted from the CBT for Depression and CBT for TBI manuals.<br>|
| Active Comparator: Psychoeducations DTx<br>Participants randomized to the comparison group will access an unstructured educational DTx. | Other: Psychoeducation Comparison<br>* A mobile application that consists of psychoeducational material regarding depression and brain injury.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of the mean difference in Patient Health Questionnaire (PHQ-9) total score | Self-report measure of depression symptom severity; range 0-27; higher score indicates greater severity | Week 12 and Week 16 compared to Baseline | 
| Change of the mean difference in Patient Health Questionnaire (PHQ-9) total scores of participants who complete all treatment modules compared to those who do not | Self-report measure of depression symptom severity; range 0-27; higher score indicates greater severity | Week 12 compared to Baseline | 
| Change of the mean difference in Patient Health Questionnaire (PHQ-9) total scores of participants who report history of depression prior to mTBI compared to those who do not | Self-report measure of depression symptom severity; range 0-27; higher score indicates greater severity | Week 12 compared to Baseline | 
| Change of the mean difference in Patient Health Questionnaire (PHQ-9) total scores of participants who report family history of depression compared to those who do no | Self-report measure of depression symptom severity; range 0-27; higher score indicates greater severity | Week 12 compared to Baseline | 
| Change of the mean difference in Patient Health Questionnaire (PHQ-9) total scores, comparison between depression severity group | Self-report measure of depression symptom severity; range 0-27; higher score indicates greater severity | Week 12 compared to Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of the mean difference in Traumatic Brain Injury-Quality of Life (TBI-QOL) total score | Computerized adaptive test that measures post-concussive symptoms and quality of life across multiple domains | Week 12 and Week 16, compared to Baseline | 
| Change of the mean difference in Posttraumatic Stress Disorder Checklist (PCL-5) total score | Self-report measure of PTSD severity; range 0-80; higher score indicates greater severity | Week 12 and Week 16, compared to Baseline | 
| Change of the mean difference in Insomnia Severity Index (ISI) total score | Self-report measure of insomnia severity; range 0-28; higher score indicates greater severity | Week 12 and Week 16, compared to Baseline | 
| Change in Credibility and Expectancy Questionnaire (CEQ) | Self-report measure of participation expectation of benefit | Week 12 and Week 16, compared to Baseline | 
| Blinding Efficacy | Participant blinding questionnaire | Week 12 and Week 16, compared to Baseline |