Treating Nightmares in Posttraumatic Stress Disorder With Dronabinol

Study Overview
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Brief Summary
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This randomized controlled exploratory phase II trial will test the hypothesis that oral dronabinol improves nightmares (primary outcome) and other PTSD symptoms (secondary outcomes) to a greater extent than placebo over a ten week intervention phase in a parallel group design.

Official Title
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Treating Nightmares in Posttraumatic Stress Disorder With Dronabinol: A Randomized Controlled Study (THC PTSD-trial)

Conditions
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Posttraumatic Stress Disorder

Intervention / Treatment
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* Drug: BX-1
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of posttraumatic stress disorder (PTSD) according to DSM 5 with a 20 item CAPS-5 total score ≥ 26 At least two nightmares a week, an intensity score ≥ 2, with a CAPS-IV B2 (frequency and intensity for the last week) score ≥ 5 Men and women between 18 and 65 years of age Written informed consent The patient has the capacity to give consent (He/she is able to understand the nature and anticipated effects/side effects of the proposed medical intervention) The patient is not breastfeeding Women of child-bearing potential must have a negative urine or serum pregnancy test All participants must use highly effective contraception The patient received stable pharmacological medication for at least 4 weeks prior to study entry (any changes in medication dose or frequency of therapy must be answered with no) Exclusion Criteria: Lifetime cannabis use disorder Current substance/alcohol use disorder (≤ 3 months); Acute suicidality; Psychotic disorder; Bipolar disorder; Current anorexia nervosa; Current major depressive episodes and a MADRS score > 29; Dementia; Trauma-focused psychotherapy four weeks before the trial Initiation of sleep medication 4 weeks prior screening or initiation of alpha adrenergic agents 4 weeks prior to screening Acute or unstable medical illness. Epilepsy Relevant heart diseases Known HIV- and/or active Hepatitis-B- or Hepatitis-C-infection Current or past malignant illness The patient is unwilling to consent to saving, processing and propagation of pseudonymized medical data for study reasons Patients, who may be dependent on the sponsor, the investigator or the trial sites, have to be excluded from the trial The patient is legally detained in an official institution The patient does have a known allergy or contraindication against Dronabinol The patient does have clinically significant abnormalities in 12-lead ECG The patient does have clinically significant laboratory abnormalities The patient did participate in other interventional trials during the 3 months before and at the time of this trial

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
Interventional Model Description: Randomized controlled study (double-blind)
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BX-1 (dronabinol)<br>BX-1 | Drug: BX-1<br>* BX-1 (dronabinol), oral solution. All patients enrolled establish their individually tolerable dose by dose Titration.<br>|
| Placebo Comparator: Placebo<br>Placebo of BX-1 | Drug: Placebo<br>* Placebo of BX-1, oral solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency and intensity of nightmares | Frequency and intensity of nightmares, measured with the Clinician-Administered PTSD Scale-IV (CAPS-IV) B2 score for the last week, range 0-8. A lower score indicates less frequent and/or intense nightmares. | 10 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline of the frequency and intensity of nightmares | Change from baseline of the frequency and intensity of nightmares, measured with the Clinician-Administered PTSD Scale-IV (CAPS-IV) B2 score for the last week, range 0-8. | 1, 2, 3, 4,6 and 8 weeks | 
| Change from baseline of the CAPS-5 total score | Change from baseline of the CAPS-5 total score (overall PTSD symptoms, last week) | 6 and 10 weeks | 
| Change from baseline of the Pittsburgh Sleep Quality Index-Addendum for PTSD | Change from baseline of the Pittsburgh Sleep Quality Index-Addendum for PTSD (PSQI A) (PTSD related sleep symptoms) | 6 and 10 weeks | 
| Change from baseline of the Montgomery-Åsberg Depression Rating Scale | Change from baseline of the Montgomery-Åsberg Depression Rating Scale (MADRS, depressive symptoms) | 4 and 10 weeks | 
| Weekly mean of change from baseline of daily total sleep time | Weekly mean of change from baseline of the patients daily total sleep time (in minutes), assessed with sleep diaries | during 10 weeks | 
| Weekly mean of change from baseline of the patients sleep onset latency at night | Weekly mean of change from baseline of the patients sleep onset latency at night (in minutes), assessed with sleep diaries | during 10 weeks | 
| Weekly mean of change from baseline of the patients recuperation of night sleep | Weekly mean of change from baseline of the patients recuperation of night sleep (5-point Likert scale, 1 = very much; 5 = not at all), assessed with sleep diaries | during 10 weeks | 
| Weekly mean of change from baseline of the patients time awake at night | Weekly mean of change from baseline of the patients time awake at night (in minutes), assessed with sleep diaries | during 10 weeks | 
| Weekly mean of change from baseline of the patients number of nightmares last night | Weekly mean of change from baseline of the patients number of nightmares last night (0, 1, 3, 4 or more) assessed with sleep diaries | during 10 weeks | 
| Weekly mean of change from baseline of the patients intensity of nightmares | Weekly mean of change from baseline of the patients intensity of nightmares (5-point Likert scale, 0 = not at all; 5 = extreme) assessed with sleep diaries | during 10 weeks | 
| Change from baseline of PTSD symptoms assessed with the PTSD Checklist for DSM-5 | Change from baseline of PTSD symptoms assessed with the PTSD Checklist for DSM-5 (PCL-5) | 6 and 10 weeks | 
| Change from baseline of the Borderline Symptom List 23 | Change from baseline of the Borderline Symptom List 23 (BSL-23) score | 6 and 10 weeks | 
| Change from baseline of the Health-Related Quality of Life | Change from baseline of the Health-Related Quality of Life (EQ-5D) score | 6 and 10 weeks | 
| Overall patients status measured by the Patient Global Impression of Change | Overall patients status measured by the Patient Global Impression of Change (PGIC) | 6 and 10 weeks | 
| Change from baseline of the Social and Occupational Functioning Assessment Scale | Change from baseline of the Social and Occupational Functioning Assessment Scale (SOFAS) | 6 and 10 weeks | 
| Change from baseline of the Pittsburgh Sleep Quality Index | Change from baseline of the Pittsburgh Sleep Quality Index (PSQI) | 6 and 10 weeks | 
| Change from baseline of symptoms of PTSD and complex PTSD according to ICD-11 assessed with the International Trauma Questionnaire | Change from baseline of symptoms of PTSD and complex PTSD according to ICD-11 assessed with the International Trauma Questionnaire (ITQ) | 6 and 10 weeks | 
| Change from baseline of THC withdraw symptoms assessed with the Marijuana Withdrawal Checklist | Change from baseline of THC withdraw symptoms assessed with the Marijuana Withdrawal Checklist (MWC) | 6 and 10 weeks and Follow- Up Visit 9 | 
| Responder analysis: proportion of patients showing improvement in nightmares | Responder analysis: proportion of patients showing improvement in nightmares (change from baseline) defined as decrease of CAPS-IV B2 ≥50% assessed at the end of treatment | 10 weeks | 
| Remitter analysis: proportion of patients showing full remission of nightmares | Remitter analysis: proportion of patients showing full remission of nightmares defined as CAPS-IV B2 = 0, assessed at the end of treatment | 10 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nightmares, Posttraumatic Stress Disorder, Dronabinol