NCT04264026

MDMA-Assisted Psychotherapy in Veterans With Combat-Related, Refractory PTSD

Open-label Phase 2 Study of MDMA-Assisted Psychotherapy in Veterans With Combat-Related, Refractory PTSD

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 5 (actual)
• Sponsor: VA Loma Linda Health Care System · Federal
• Sex: All
• Age: 18 Years – 55 Years
• Healthy volunteers: Not accepted

Summary

This will be a single-site, open-label phase 2 study designed to test the feasibility of administering MDMA in conjunction with psychotherapy for combat-related treatment-resistant PTSD in US military veterans currently enrolled in VA. MDMA will be given in conjunction with structured psychotherapy in three single-dose psychotherapy sessions in a hospital setting over the course of 12 weeks, along with preparatory and integration psychotherapy sessions in-between each active-dose session. The overall objective of this study is to evaluate the risks, benefits, and feasibility of MDMA used in conjunction with manualized psychotherapy, on reduction of symptoms, or remission of PTSD, as evaluated by standard clinical measures, in a VA Healthcare System. The primary outcome measure for the study is the Clinician-Administered PTSD Scale (CAPS-5), a semi-structured interview used in the majority of clinical trials for PTSD, which will be assessed at baseline, primary endpoint, and at the long-term 12-month follow-up visit. Secondary safety and efficacy measures will also be collected. The planned duration of this study is 1-3 years, with each active treatment period lasting approximately 12 weeks, along with a long-term follow-up 12 months after the last active-drug session.

Detailed description

This will be a single-site, open-label study, investigating the use of MDMA-assisted psychotherapy for treatment-resistant combat-related PTSD. This study will consent up to 50 current-era combat veterans for study and the first 10 participants who meet criteria will be eligible to receive study medication. Any patient who drops out before the third Experimental Session will be replaced. Dropout rates will be recorded. In this protocol, enrollment is defined as the time the participant signs informed consent. Time from initial screening/enrollment to collection of the primary endpoint will last approximately 12-18 weeks. To assess durability of treatment, participants will be assessed approximately 12 months after the last MDMA session for the long-term follow-up. The study will consist of a prescreening/screening/enrollment period, three pre-experimental (preparatory) dose psychotherapy sessions (spaced approximately one week apart), three experimental dose therapy sessions, nine integrative follow-up sessions, one assessment of primary endpoint, and a long-term 12-month follow-up assessment. Psychiatric medication tapering will occur after eligibility confirmation (after completion of baseline CAPS-5, prior to Experiential Sessions) to allow for appropriate medication washout. The primary objective of this study is to evaluate the safety and effectiveness of MDMA in Veterans with combat-related, refractory PTSD when used in conjunction with manualized psychotherapy on reduction of symptoms, or remission of PTSD, as evaluated by standard clinical measures. Effectiveness will be measured by evaluating the change in CAPS-5 scores from baseline to the primary endpoint. Primary endpoint will be collected 2 months after the third Experimental Session with MDMA. To access long-term effectiveness, CAPS-5 will also be collected at the long-term follow-up. Secondary Objectives: 1. Assess changes in self-reported PTSD symptoms as measured with the PTSD-symptom checklist at screening and baseline, during most face-to-face visits, at the primary endpoint, and during the long-term follow-up. a. Life Event Checklist (LEC) for PCL-5 will be administered at baseline (screening), primary endpoint, and long-term follow-up. 2. Assess depression symptoms with the Beck Depression Inventory-II (BDI-II) at baseline (screening), primary endpoint, and long-term 12-month follow-up. 3. Assess changes in alcohol consumption. 1. The AUDIT-C (Alcohol Use Disorders Identification Test) will be used to measure baseline alcohol use over the past year prior to study entry (at screening) and at long-term follow up. 2. Alcohol use starting after study screening will be monitored based on participants self-report. Participants will be directed to keep a Drinking Diary throughout the study measuring the number of standard alcoholic beverages consumed per day. Drinking Diary for each participant will be collected weekly until their last psychotherapy visit. Participants will continue to record weekly alcohol use on their own until collection at the primary endpoint. 4. Assess changes in drug consumption. a. Drug Use Disorders Identification Test (DUDIT) will be assessed at baseline (screening) and at long-term follow-up). 5. Assess changes in self-reported sleep quality via the Pittsburgh Sleep Quality Index (PSQI) from baseline (screening) to primary endpoint and long-term 12-month follow-up. 6. Assess changes in posttraumatic growth via Post Traumatic Growth Inventory (PTGI) scores from baseline (at screening) to primary endpoint and long-term 12-month follow-up. 7. Healthcare utilization will also be assessed by retrospective chart review. Twelve months after the final Experimental Session, the long-term effects of MDMA-assisted psychotherapy on symptoms of PTSD will be assessed via CAPS-5 and PCL-5 with LEC, alcohol use via AUDIT, drug use behaviors via DUDIT, depression via BDI-II, self-reported sleep quality via PSQI, post-traumatic growth via PTGI, suicidality via C-SSRS, and response to research participation via RRPQ (Reactions to Research Participation Questionnaire). Participants will also be assessed for suicidality at every face-to-face visit.

Conditions

• Post Traumatic Stress Disorder
• Combat Stress Disorders

Interventions

Type	Name	Description
DRUG	3,4-methylenedioxymethamphetamine	Bottles are labeled with a unique container number, protocol number, IMP name, lot number, sponsor name and a statement that the IMP is restricted to clinical trial use only.

Timeline

• Start date: 2021-07-29
• Primary completion: 2025-05-01
• Completion: 2025-05-01
• First posted: 2020-02-11
• Last updated: 2025-07-20

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study