Posttraumatic Stress Disorder, Stress Disorders, Post-Traumatic
Conditions
Brief summary
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
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 up to 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=up to 12) vs. placebo (n=up to12) 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.
Interventions
An oral strawberry flavored liquid, taken as a 2.5ml (250mg) dose twice a day
DRUGPlacebo
An inert strawberry flavored oral solution, taken as a 2.5ml dose twice a day
BEHAVIORALMassed Prolonged Exposure (mPE)
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.
Sponsors
National Center for Advancing Translational Sciences (NCATS)
The University of Texas Health Science Center at San Antonio
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
A compounding pharmacy will supply both the study drug and a matching strawberry flavored liquid.
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Individuals between the age of 18 to 65 years old at time of screening. 2. Able to write, read, and speak English 3. PTSD diagnosis as assessed by Clinician-Administered Posttraumatic Stress Scale (CAPS-5) 4. Stable medication regimen for at least four weeks prior to the onset of study participation.
Exclusion criteria
1. History of opiate, cocaine, methamphetamine, benzodiazepine, or cannabis abuse as determined by the National Institute of Drug Abuse Quick Screen (NIDA-Q). 2. Currently using opiates, cocaine, methamphetamines, benzodiazepines, or cannabis as evidenced by a positive urine drug screen prior to enrollment. 3. Currently pregnant as determined by a positive urine pregnancy test prior to enrollment. 4. Current clinically significant alcohol abuse in the past two weeks on the Quick Drinking Screen (QDS). 5. Currently breastfeeding. 6. Ongoing illness or physical health problem(s) that may be exacerbated by CBD (e.g., history of liver problems) 7. History of significant allergic condition, significant drug-related hypersensitivity, or allergic reaction to cannabinoids. 8. Concomitant medications with possible CBD-drug interactions 9. Alanine transaminase (ALT) or Aspartate transaminase (AST) enzyme levels 3x normal limits. 10. Concurrent engagement in trauma-related psychotherapy for PTSD. 11. Current or past DSM-5 diagnosis of psychotic disorder or bipolar disorder as determined on the Mini International Neuropsychiatric Interview (MINI 7.0). 12. 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). 13. Allergy to sesame seed oil.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinician Administered PTSD Scale (CAPS-5) | Baseline and at about 45 days (1 month follow-up visit) | 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. Scores range from 0 to 80. Change in score will be reported. |
| Posttraumatic Stress Disorder Checklist (PCL-5) | Baseline and at about 45 days (1 month follow-up visit) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient Health Questionnaire-9 (PHQ-9) | Baseline and at about 45 Days (1 month follow-up visit) | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cannabidiol (CBD) Epidiolex oral solution 500mg (5ml) per day
Cannabidiol (CBD) oral solution: An oral strawberry flavored liquid, taken as a 2.5ml (250mg) dose twice a day
Massed Prolonged Exposure (mPE): 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. | 11 |
| Placebo Placebo oral solution 5ml per day
Placebo: An inert strawberry flavored oral solution, taken as a 2.5ml dose twice a day
Massed Prolonged Exposure (mPE): 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. | 10 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 3 | 0 |
Baseline characteristics
| Characteristic | Cannabidiol (CBD) | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 45.9 years STANDARD_DEVIATION 12.2 | 38.9 years STANDARD_DEVIATION 8.5 | 42.5 years STANDARD_DEVIATION 11 |
| Race/Ethnicity, Customized Race/Ethnicity Black, Non-Hispanic | 2 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized Race/Ethnicity White, Hispanic | 8 Participants | 6 Participants | 14 Participants |
| Race/Ethnicity, Customized Race/Ethnicity White, Non-Hispanic | 1 Participants | 2 Participants | 3 Participants |
| Region of Enrollment United States | 11 participants | 10 participants | 21 participants |
| Sex: Female, Male Female | 3 Participants | 5 Participants | 8 Participants |
| Sex: Female, Male Male | 8 Participants | 5 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 10 |
| other Total, other adverse events | 10 / 11 | 7 / 10 |
| serious Total, serious adverse events | 0 / 11 | 0 / 10 |
Outcome results
Primary
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. Scores range from 0 to 80. Change in score will be reported.
Time frame: Baseline and at about 45 days (1 month follow-up visit)
Population: Intent to treat analysis were completed in the total sample (n=21; CBD = 11, Placebo = 10).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cannabidiol (CBD) | Clinician Administered PTSD Scale (CAPS-5) | Baseline | 42.8 score on a scale | Standard Error 2.3 |
| Cannabidiol (CBD) | Clinician Administered PTSD Scale (CAPS-5) | 1-Month Follow-Up | 15.2 score on a scale | Standard Error 2.6 |
| Placebo | Clinician Administered PTSD Scale (CAPS-5) | Baseline | 42.9 score on a scale | Standard Error 2.2 |
| Placebo | Clinician Administered PTSD Scale (CAPS-5) | 1-Month Follow-Up | 10.1 score on a scale | Standard Error 2.6 |
Primary
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.
Time frame: Baseline and at about 45 days (1 month follow-up visit)
Population: Intent to treat analysis were completed in the total sample (n=21; CBD = 11, Placebo = 10).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cannabidiol (CBD) | Posttraumatic Stress Disorder Checklist (PCL-5) | Baseline | 50.8 score on a scale | Standard Error 0.9 |
| Cannabidiol (CBD) | Posttraumatic Stress Disorder Checklist (PCL-5) | 1-Month Follow-Up | 19.97 score on a scale | Standard Error 7.6 |
| Placebo | Posttraumatic Stress Disorder Checklist (PCL-5) | Baseline | 52.1 score on a scale | Standard Error 0.9 |
| Placebo | Posttraumatic Stress Disorder Checklist (PCL-5) | 1-Month Follow-Up | 27.3 score on a scale | Standard Error 8.1 |
Secondary
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.
Time frame: Baseline and at about 45 Days (1 month follow-up visit)
Population: Intent to treat analysis were completed in the total sample (n=21; CBD = 11, Placebo = 10).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cannabidiol (CBD) | Patient Health Questionnaire-9 (PHQ-9) | Baseline | 14.6 score on a scale | Standard Error 0.5 |
| Cannabidiol (CBD) | Patient Health Questionnaire-9 (PHQ-9) | 1-Month Follow-Up | 5.4 score on a scale | Standard Error 2.4 |
| Placebo | Patient Health Questionnaire-9 (PHQ-9) | Baseline | 15.5 score on a scale | Standard Error 0.5 |
| Placebo | Patient Health Questionnaire-9 (PHQ-9) | 1-Month Follow-Up | 7.3 score on a scale | Standard Error 2.4 |