Study of Feasibility and Safety of MDMA-Assisted Group Therapy for the Treatment of PTSD in Veterans

Study Overview
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Brief Summary
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This Phase 2, open-label, non-randomized, 3-cohort study assesses the feasibility and safety of MDMA-assisted group therapy for the treatment of PTSD in veterans. The study will be conducted in up to N=18 participants, recruited in three cohorts of six participants and receive therapy sessions throughout their participation in these groups.

Detailed Description
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To further assess the feasibility and safety of MDMA-assisted group therapy for participants with at least moderate PTSD, the sponsor is conducting a phase 2, open-label, non-randomized, 3-cohort study. This novel treatment package consists of two once-monthly Experimental Sessions of therapy combined with a divided-dose of MDMA, along with non-drug preparatory and integrative therapy administered in both individual and group sessions. The Primary Outcome measure, the Clinician Administered PTSD Scale (CAPS-5), evaluates changes in PTSD symptom severity and is assessed by a blinded centralized Independent Rater (IR) pool. The therapeutic approach will combine manualized MDMA-assisted therapy for PTSD with group therapy components.

Official Title
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An Open-Label Feasibility and Safety Study of MDMA-Assisted Group Therapy for the Treatment of Posttraumatic Stress Disorder in Veterans

Conditions
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PTSD

Intervention / Treatment
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* Drug: Midomafetamine
* Behavioral: Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Are at least 18 years old. Are a U.S. Military Veteran Are fluent in speaking and reading the predominantly used or recognized language of the study site. Are able to swallow pills. Agree to have study visits recorded, including Experimental Sessions, outcome assessments, and non-drug psychotherapy sessions. Must provide a contact who is willing and able to be reached by the investigators in the event of a participant becoming suicidal or unreachable. Must agree to inform the investigators within 48 hours of any medical conditions and procedures. If able to become pregnant, must have a negative pregnancy test at study entry and prior to each Experimental Session, and must agree to use adequate contraception through 10 days after the last Experimental Session. Must not participate in any other interventional clinical trials during the duration of the study. Must commit to medication dosing, therapy, and study procedures. Have a current PTSD diagnosis at the time of screening. Exclusion Criteria: Are not able to give adequate informed consent. Have uncontrolled hypertension. Have a marked baseline QTcF interval >450 milliseconds [ms] demonstrated on repeated ECG assessments. Have a history of additional risk factors for Torsade de pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome). Have evidence or history of significant medical disorders. Have symptomatic liver or biliary disease. Have history of hyponatremia or hyperthermia. Weigh less than 48 kilograms (kg). Are pregnant or nursing, or are able to become pregnant and are not practicing an effective means of birth control. Are abusing illegal drugs or alcohol.

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Interventional Model Description: Open-label study examining safety and effects of two sessions of MDMA-assisted therapy each followed by four integrative therapy sessions
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Two MDMA-assisted Therapy Sessions<br>Two Experimental MDMA-assisted Therapy Sessions, and four Integrative Sessions following each Experimental Sessions. | Drug: Midomafetamine<br>* Initial dose of 120 mg MDMA HCL and optional supplemental dose of 60 mg MDMA HCL at 1.5 to 2 hours after first dose<br>* Other names: MDMA;Behavioral: Therapy<br>* Standardized non-directive psychotherapy performed by therapist team<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in CAPS-5 Total Severity Score | The CAPS-5 is a semi-structured interview that assesses index history of DSM-5-defined traumatic event exposure [114], including the most distressing event, time since exposure, to produce a diagnostic score (presence vs. absence) and a PTSD Total Severity score [114]. The CAPS-5 rates intrusion symptoms (intrusive thoughts or memories), avoidance, cognitive and mood symptoms, arousal and reactivity symptoms, duration and degree of distress and dissociation. The total severity score is a sum of symptom frequency and intensity scores for the subscales B (re-experiencing), C (avoidance) and D (hypervigilance) and ranges from 0 to 136, with higher scores indicating greater severity of PTSD symptoms. | Baseline - 3 months from first Experimental Session | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Sheehan Disability Scale (SDS) | Sheehan Disability Scale (SDS) total score, a measure of clinician-rated functional impairment. The first three items indicate degree of impairment in the domains of work/school, social life, and home life, with response options based on an eleven-point scale (0=not at all to 10=extremely), and five verbal tags (not at all, mildly, moderately, markedly, extremely). The remaining two items assess Days Lost and Days Unproductive during the reporting period. | Baseline - 3 months from First Experimental Session |