GAMBIT Task With PTSD and Healthy Control Participants

Study Overview
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Brief Summary
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This is a pilot study of a digital training task called GAMBIT. This study will be the first to examine potential relationships between GAMBIT task completion and brain circuit flexibility, behavior, and symptoms in participants with PTSD.

Detailed Description
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This is a single-site pilot study for the GAMBIT intervention, which is a computerized task that addresses behavioral inhibition. The primary objective of this study is to determine whether the GAMBIT task improves mental health symptoms associated with PTSD over time. The secondary objective of this study is to determine whether the GAMBIT task promotes flexibility in inhibitory control network as determined by functional neuroimaging. Additional laboratory measures associated with cognitive flexibility, and clinician and patient-rated symptom data, will be collected.

Official Title
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Gamified Approach to Maximizing Biobehavioral Inhibition in Trauma-related Conditions (GAMBIT)

Conditions
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Posttraumatic Stress Disorder

Intervention / Treatment
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* Behavioral: GAMBIT Task


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female aged 18-55 years Participants must be able to provide informed consent Participants must have a level of understanding of the English language sufficient to agree to all tests and examinations required by the study and must be able to participate fully in the informed consent process Must meet criteria for one of the following study groups: PTSD Group: i. Meets diagnostic criteria for current PTSD according to the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) Has been exposed to a Criterion A trauma of the civilian type (e.g., non-combat, threatened or actual interpersonal violence) or non-civilian Must have a total score ≥30 on the CAPS-5 (past-month version) at the time of screening, indicating moderate PTSD symptom severity, of at least 3 months symptom duration. Healthy Control Group: i. Has no lifetime history of any psychiatric disorder Exclusion Criteria: Current or lifetime history of schizophrenia or other psychotic disorder, bipolar disorder, obsessive-compulsive disorder (OCD), eating or feeding disorder, neurodevelopmental disorder, or neurocognitive disorder; Any neuropsychiatric disorder that is judged to be the primary presenting problem, other than that which is specified as study group eligibility criteria; Substance use disorder within the past 1 year; Urine toxicology positive for illicit drugs or dis-allowed concomitant medications as per study protocol; intermittent cannabis use that does not meet criteria for a substance use disorder may be permitted under the protocol. Suicidal ideation or risk of self-harm that is judged by the PI to be clinically significant and to warrant intervention Concurrent treatment with opioid medication, or with long-acting or daytime short-acting benzodiazepines within two weeks of study start Current cognitive impairment, as defined by a score <23 on the Montreal Cognitive Assessment (MoCA) Estimated IQ <80 Currently receiving evidence-based psychotherapy for PTSD (e.g., prolonged exposure, cognitive processing therapy).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PTSD Group<br>The PTSD Group will receive the GAMBIT intervention and complete all study tasks and assessments at every study visit (Visits 0-4). N=20 participants will be recruited for this arm. | Behavioral: GAMBIT Task<br>* The GAMBIT task is a novel inhibitory control task. Participants in the PTSD group will receive the GAMBIT intervention repeatedly over the study period.<br>|
| No Intervention: Healthy Control Group<br>The Healthy Control Group will only complete study tasks and assessments at the screening visit (Visit 0) and the Pre-Assessment visit (Visit 1). This arm will not receive any intervention. N=20 participants will be recruited for this arm. Additionally, N=10 Healthy Control participants will be recruited for the Pilot Phase of the study. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinician Administered PTSD Scale for DSM-5 (CAPS-5) at Baseline | The CAPS is a structured clinical interview designed to assess the essential features of PTSD. A total symptom severity score is calculated on a scale of 0-80, with a higher score representing greater symptom severity. | Baseline | 
| Clinician Administered PTSD Scale for DSM-5 (CAPS-5) at Day 23 | The CAPS is a structured clinical interview designed to assess the essential features of PTSD. A total symptom severity score is calculated on a scale of 0-80, with a higher score representing greater symptom severity. | Day 23 | 
| Clinician Administered PTSD Scale for DSM-5 (CAPS-5) at Day 52 | The CAPS is a structured clinical interview designed to assess the essential features of PTSD. A total symptom severity score is calculated on a scale of 0-80, with a higher score representing greater symptom severity. | Day 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inhibitory Control Network Flexibility at Baseline | Network flexibility will be determined from resting state FMRI-derived metrics using relatively novel statistical techniques. | Baseline | 
| Inhibitory Control Network Flexibility at Day 52 | Network flexibility will be determined from resting state FMRI-derived metrics using relatively novel statistical techniques. | Day 52 | 
| PTSD Checklist for DSM-5 (PCL-5) at Baseline | The PTSD Checklist for DSM-5 (PCL-5) is a widely used clinical self-report scale to evaluate current symptoms of PTSD. Each question on the 20-item checklist corresponds to a symptom of PTSD in the DSM-5. A total severity score is calculated on a scale of 0-80, with a higher score indicating greater severity. | Baseline | 
| PTSD Checklist for DSM-5 (PCL-5) Weekly for Weeks 1-6 | The PTSD Checklist for DSM-5 (PCL-5) is a widely used clinical self-report scale to evaluate current symptoms of PTSD. Each question on the 20-item checklist corresponds to a symptom of PTSD in the DSM-5. A total severity score is calculated on a scale of 0-80, with a higher score indicating greater severity. | Weekly [Weeks 1-6] | 
| PTSD Checklist for DSM-5 (PCL-5) at Day 23 | The PTSD Checklist for DSM-5 (PCL-5) is a widely used clinical self-report scale to evaluate current symptoms of PTSD. Each question on the 20-item checklist corresponds to a symptom of PTSD in the DSM-5. A total severity score is calculated on a scale of 0-80, with a higher score indicating greater severity. | Day 23 | 
| PTSD Checklist for DSM-5 (PCL-5) at Day 52 | The PTSD Checklist for DSM-5 (PCL-5) is a widely used clinical self-report scale to evaluate current symptoms of PTSD. Each question on the 20-item checklist corresponds to a symptom of PTSD in the DSM-5. A total severity score is calculated on a scale of 0-80, with a higher score indicating greater severity. | Day 52 | 
| Combined Think/No-Think and Go/No-Go Paradigm | The combined Think/No-Think and Go/No-Go paradigm requires participants to learn 35 cue-target word pairs (for approximately 15 minutes) and then asked to alternatively suppress, recall, or think about the cue-target word pairs, when prompted. The percentage of correctly processed trials (go/think trials and no-go/no-think trials) are calculated per block, on a scale from 0% (0/35 trials) to 100% (35/35 trails), with higher recall scores on no-go/no-think trials indicating worse inhibitory control. | up to 52 days | 
| Face-Stroop Task | The Face-Stroop task is a modified version of the widely used Stroop task which assesses reaction time between congruent and incongruent stimuli. During the Face-Stroop task, participants are simultaneously presented with images of emotional faces and emotional words (e.g., Happy, Sad), with some trials presenting congruent stimuli (happy face + Happy) and other trials presenting incongruent stimuli (happy face + Sad), and asked to identify the faces and words separately. Variables of interest include reaction time (range 250-1000 milliseconds, with lower RT indicating better performance) and accuracy (0-100%, with greater accuracy denoting better performance). | up to 52 days |