Enhancing Prolonged Exposure With Cannabidiol to Treat Posttraumatic Stress Disorder

Study Overview
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Brief Summary
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The primary goal of this pilot project is to demonstrate the safety and feasibility of using Cannabidiol (CBD) in combination with standard of care prolonged exposure (PE) psychotherapy to reduce PTSD symptoms.

Detailed Description
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This study is an early Phase II double-blind, pilot randomized controlled clinical trial. The study team will use a permuted block randomization design stratified by a Posttraumatic Stress Disorder (PTSD) severity median score on the PTSD Checklist (PCL-5) derived from a recently completed STRONG STAR repository. Participants will be 24 individuals with PTSD to investigate the safety, feasibility, and PTSD symptom change associated with CBD 250mg taken twice a day for 18 days (n=12) vs. placebo (n=12) in combination with a standard of care, 10-sessions massed PE psychotherapy administered over 2 weeks. Aims 2 and 3 will evaluate biochemical and physiological outcomes associated with the brain endocannabinoid (eCB) and PTSD that may be affected by CBD. Permuted block randomization is advantageous in small clinical trials to ensure equal allocation of participants in each condition. Participant randomization will be subdivided into randomized blocks of four, two patients in each block will be assigned to CBD and two will be assigned to placebo.

Official Title
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Enhancing Prolonged Exposure With Cannabidiol to Treat Posttraumatic Stress Disorder: A Pilot Study

Conditions
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Posttraumatic Stress Disorder, Stress Disorders, Post-Traumatic

Intervention / Treatment
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* Drug: Cannabidiol (CBD) oral solution
* Drug: Placebo
* Behavioral: Massed Prolonged Exposure (mPE)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals between the age of 18 to 65 years old at time of screening. Able to write, read, and speak English PTSD diagnosis as assessed by Clinician-Administered Posttraumatic Stress Scale (CAPS-5) Stable medication regimen for at least four weeks prior to the onset of study participation. Exclusion Criteria: History of opiate, cocaine, methamphetamine, benzodiazepine, or cannabis abuse as determined by the National Institute of Drug Abuse Quick Screen (NIDA-Q). Currently using opiates, cocaine, methamphetamines, benzodiazepines, or cannabis as evidenced by a positive urine drug screen prior to enrollment. Currently pregnant as determined by a positive urine pregnancy test prior to enrollment. Current clinically significant alcohol abuse in the past two weeks on the Quick Drinking Screen (QDS). Currently breastfeeding. Ongoing illness or physical health problem(s) that may be exacerbated by CBD (e.g., history of liver problems) History of significant allergic condition, significant drug-related hypersensitivity, or allergic reaction to cannabinoids. Concomitant medications with possible CBD-drug interactions Alanine transaminase (ALT) or Aspartate transaminase (AST) enzyme levels 3x normal limits. Concurrent engagement in trauma-related psychotherapy for PTSD. Current or past DSM-5 diagnosis of psychotic disorder or bipolar disorder as determined on the Mini International Neuropsychiatric Interview (MINI 7.0). Suicide attempt in the last year and/or suicide risk requiring immediate intervention or requiring a higher level of care than can be provided by the study treatment as determined by the Self-Injurious Thoughts and Behaviors Interview (SIT-BI). Allergy to sesame seed oil.

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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Accepts Healthy Volunteers

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
Interventional Model Description: A double-blind randomized controlled clinical trial. Permuted block randomization will ensure equal allocation of participants to either study drug or placebo. Randomization will be performed by a designated study team member.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cannabidiol (CBD)<br>Epidiolex oral solution 500mg (5ml) per day | Drug: Cannabidiol (CBD) oral solution<br>* An oral strawberry flavored liquid, taken as a 2.5ml (250mg) dose twice a day<br>* Other names: Epidiolex;Behavioral: Massed Prolonged Exposure (mPE)<br>* mPE, delivered daily Monday through Friday over two weeks, utilizes exposure-based interventions to target psychological mechanisms (i.e., experiential and behavioral avoidance; maladaptive cognitive changes) that are thought to maintain trauma-related symptoms.<br>* Other names: Behavioral Therapy;|
| Placebo Comparator: Placebo<br>Placebo oral solution 5ml per day | Drug: Placebo<br>* An inert strawberry flavored oral solution, taken as a 2.5ml dose twice a day<br>* Other names: Placebo oral solution;Behavioral: Massed Prolonged Exposure (mPE)<br>* mPE, delivered daily Monday through Friday over two weeks, utilizes exposure-based interventions to target psychological mechanisms (i.e., experiential and behavioral avoidance; maladaptive cognitive changes) that are thought to maintain trauma-related symptoms.<br>* Other names: Behavioral Therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinician Administered PTSD Scale (CAPS-5) | The CAPS-5 is structured interview that assesses the Diagnostic and Statistical Manual of Mental Disorders v5 (DSM-5) criteria for PTSD. Each item is rated on a severity scale ranging from 0 (Absent) to 4 (Extreme/incapacitating) and combines information about frequency and intensity for each of the 20 symptoms.Subscale scores are calculated by summing severity scores for items in the following PTSD symptom clusters: re-experiencing, avoidance, negative alterations in cognitions and mood, and hyperarousal. Scores ≥ 25 indicate a probable diagnosis of PTSD. Change in score will be reported. | Baseline and at about 45 days (1 month follow-up visit) | 
| Posttraumatic Stress Disorder Checklist (PCL-5) | The PCL-5 is a 20-item self-report measure update of the PCL designed to assess PTSD symptoms as defined by the DSM-5. The PCL-5 evaluates how much participants have been bothered by PTSD symptoms in the past week (for all assessments during treatment) or the past two weeks (all other assessment time points) as a result of a specific life event. Each item of the PCL-5 is scored on a five-point scale ranging from 0 not at all) to 4 (extremely). Scores range from 0 to 80 with a higher score indicating that subjects have been bothered more by PTSD symptoms. Change in score will be reported. | Baseline, Day 4, Day 8, Day 15 and at about 45 days (1 month follow-up visit) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Depressive Symptoms Index-Suicidality Subscale (DSI-SS) | The DSI-SS is a 4-item self-report measure of suicidal ideation that focuses on ideation, plans, perceived control over ideation, and impulses for suicide. Scores on each item range from 0 to 3, with higher scores reflecting greater severity of suicidal ideation. Total scores range from 0-12. Change in score will be reported. | Baseline, Day 4, Day 8, Day 15 and at about 45 Days (1 month follow-up visit) | 
| Patient Health Questionnaire-9 (PHQ-9) | It consists of 9 items that assess both affective and somatic symptoms related to depression and depressive disorders; these 9 items correspond to the diagnostic criteria for Diagnostic Statistical Manual of Mental Disorders - Major Depressive Disorder (DSM MDD). Respondents rate the frequency with which they have been bothered by depressive symptoms within the past two weeks on a scale ranging from 0 (not at all) to 3 (nearly every day). Scores on all items are summed to obtain a total severity score between 0 and 27. Scores reflect no significant depressive symptoms (0-4), mild depressive symptoms (5-9), moderate depressive symptoms (10-14), moderately severe depressive symptoms (15-19), and severe depressive symptoms (>19). Change in score is reported. | Baseline, Day 4, Day 8, Day 15 and at about 45 Days (1 month follow-up visit) | 
| Generalized Anxiety Disorder Screener (GAD-7) | This is a 7-item measure that asks participants to rate the frequency with which they have been bothered by anxiety symptoms within the past two weeks on a scale ranging from 0 (not at all) to 3 (nearly every day). Scores on all items are summed to obtain a total severity score ranging from 0-21. Scores reflect no significant anxiety symptoms (0-4), mild anxiety symptoms (5-9), moderate anxiety symptoms (10-14), and severe anxiety symptoms (>15). Change in score is reported. | Baseline, Day 4, Day 8, Day 15 and at about 45 Days (1 month follow-up visit) | 
| Brief Inventory of Psychosocial Functioning (BIPF) | The BIPF is a 7-item self-report instrument measuring respondents' level of functioning in seven life domains: romantic relationship, relationship with children, family relationships, friendships and socializing, work, training and education, and activities of daily living. Respondents indicate the degree to which they had trouble in the last 30 days in each area on a 7-point scale ranging from 0 = Not at all to 6 = Very much. Total scores range from 0 - 42 with a lower score indicating that the participants is less functional in these domains. Change in total score is reported. | Baseline and at about 45 days (1 month follow-up visit) | 
| Veterans Rand 12-Item Heath Survey (VR-12) | The questions in this survey correspond to seven different health domains: general health perceptions, physical functioning, role limitations due to physical and emotional problems, bodily pain, energy/fatigue levels, social functioning and mental health in the past 30 days. Items are summarized into two component scores, a Physical Component Score (PCS) and a Mental Component Score (MCS). VR-12 scores are standardized using a T-score metric with a mean of 50 and a standard deviation of 10 with higher scores indicative of better health. Change in component scores is reported. | Baseline and at about 45 days (1 month follow-up visit) | 
| Insomnia Severity Index (ISI) | A 7-item self-report measure that assesses perceived severity of insomnia. Each item uses a 4-point Likert type scale from 0 (not at all satisfied) to 4 (very much satisfied). The items sum to produce a total score (range 0 - 28) with a higher score indicating less insomnia. Change in total score will be reported. | Baseline and at about 45 days (1 month follow-up visit) | 
| Posttraumatic Cognitions Inventory (PTCI). | The PTCI is a 36-item questionnaire that was developed to determine how an individual views the trauma and its sequelae in an attempt to understand both how PTSD develops and is maintained. The scale uses 3 subscales, Negative cognition about self (21 items), Negative cognition about the World (7 items) and Self blame (5 items). A total score is obtained by adding the 3 scores to give a possible score of 0 - 33. Items 13, 32 and 34 are experimental and not included in the subscales. A higher score implies greater negativity. A change in score will be reported. | Baseline, Day 4, Day 8, Day 15 and at about 45 Days (1 month follow-up visit) |