Treating Nightmares in Posttraumatic Stress Disorder With Dronabinol

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

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.

Study Overview

• Status: Recruiting
• Conditions: Posttraumatic Stress Disorder
• Intervention / Treatment: Drug: BX-1; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 176
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Stefan Roepke, MD; Phone Number: 004930450517545; Email: stefan.roepke@charite.de

Study Locations

• Germany
  • Berlin, Germany, 10115
    • Recruiting
    • Berlin St. Hedwig
    • Contact: Nikola Schoofs; Email: nikola.schoofs@charite.de
    • Principal Investigator: Nikola Schoofs
  • Berlin, Germany, 12203
    • Recruiting
    • Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Klinik für Psychiatrie und Psychotherapie
    • Contact: Stefan Roepke; Phone Number: 004930450517545; Email: stefan.roepke@charite.de
    • Principal Investigator: Stefan Roepke
  • Mannheim, Germany, 86159
    • Terminated
    • Zentralinstitut für Seelische Gesundheit Mannheim

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Diagnosis of posttraumatic stress disorder (PTSD) according to DSM 5 with a 20 item CAPS-5 total score ≥ 26
2. At least two nightmares a week, an intensity score ≥ 2, with a CAPS-IV B2 (frequency and intensity for the last week) score ≥ 5
3. Men and women between 18 and 65 years of age
4. Written informed consent
5. 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)
6. The patient is not breastfeeding
7. Women of child-bearing potential must have a negative urine or serum pregnancy test
8. All participants must use highly effective contraception
9. 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:

1. Lifetime cannabis use disorder
2. Current substance/alcohol use disorder (≤ 3 months);
3. Acute suicidality;
4. Psychotic disorder;
5. Bipolar disorder;
6. Current anorexia nervosa;
7. Current major depressive episodes and a MADRS score > 29;
8. Dementia;
9. Trauma-focused psychotherapy four weeks before the trial
10. Initiation of sleep medication 4 weeks prior screening or initiation of alpha adrenergic agents 4 weeks prior to screening
11. Acute or unstable medical illness.
12. Epilepsy
13. Relevant heart diseases
14. Known HIV- and/or active Hepatitis-B- or Hepatitis-C-infection
15. Current or past malignant illness
16. The patient is unwilling to consent to saving, processing and propagation of pseudonymized medical data for study reasons
17. Patients, who may be dependent on the sponsor, the investigator or the trial sites, have to be excluded from the trial
18. The patient is legally detained in an official institution
19. The patient does have a known allergy or contraindication against Dronabinol
20. The patient does have clinically significant abnormalities in 12-lead ECG
21. The patient does have clinically significant laboratory abnormalities
22. The patient did participate in other interventional trials during the 3 months before and at the time of this trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany
• Collaborators: Bionorica SE
• Investigators: Principal Investigator: Stefan Roepke, MD, Charite University, Berlin, Germany

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2020
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: June 16, 2020
• First Submitted That Met QC Criteria: June 24, 2020
• First Posted (Actual): June 26, 2020

Study Record Updates

• Last Update Posted (Actual): February 16, 2024
• Last Update Submitted That Met QC Criteria: February 15, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Posttraumatic Stress Disorder; Nightmares; Dronabinol
• Additional Relevant MeSH Terms: Mental Disorders; Trauma and Stressor Related Disorders; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
• Other Study ID Numbers: THC-PTBS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No