Open Label Study of MDMA-assisted Psychotherapy for Treatment of PTSD With Optional fMRI Sub-Study

Phase 2

Completed

Conditions: PTSD

Interventions: Drug: Midomafetamine HCl

Registration Number: NCT04030169

Lead Sponsor: MAPS Europe B.V.

Brief Summary: The goal of this clinical trial is to learn if MDMA-assisted therapy is safe and effective in people diagnosed with at least severe PTSD.

The main question it aims to answer is: Do two open-label sessions of MDMA-assisted therapy reduce PTSD symptoms?

Participants will receive three non-drug preparatory sessions followed by two sessions of MDMA-assisted therapy. Each MDMA-assisted therapy session is followed by three non-drug integrative therapy sessions.

Detailed Description: This multi-site, open-label, Phase 2, lead-in study conducted in Europe assesses the safety and efficacy of MDMA-assisted therapy in participants diagnosed with at least severe posttraumatic stress disorder (PTSD). This study additionally provides an opportunity for clinical supervision to planned Phase 3 therapy teams. Select sites will also participate in an optional fMRI (brain imaging) sub-study.

This study compares the effects of two open-label manualized Experimental Sessions of psychotherapy assisted by flexible doses of MDMA HCl. Initial doses per Experimental Session include 80 mg or 120 mg of MDMA HCl, followed 1.5 to 2 hours later by a supplemental half-dose (40 mg or 60 mg). Total amounts of MDMA to be administered per Experimental Session range from 80 mg to 180 mg. This \~8-week Treatment Period is preceded by three non-drug Preparatory Sessions. During the Treatment Period, each Experimental Session is followed by three Integrative Sessions of non-drug psychotherapy.

The primary endpoint is the change in Clinician Administered PTSD Scale for DSM 5 (CAPS-5) from Baseline to 13 weeks post-baseline (Visit 14). The secondary endpoint is the change in Sheehan Disability Scale (adapted SDS) item scores from Baseline to 13 weeks post-baseline (Visit 14).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 21

Inclusion Criteria

Are at least 18 years old
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 video-recorded, including Experimental Sessions, Independent Rater assessments, and non-drug psychotherapy sessions
Must provide a contact (relative, spouse, close friend or other support person) 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 treatments and procedures
People able to become pregnant (PABP) (i.e., assigned female at birth, fertile, following menarche and until becoming post-menopausal unless permanently sterile), must have a highly sensitive negative pregnancy test at study entry and prior to each Experimental Session, and must agree to use adequate birth control through 10 days after the last Experimental Session. Adequate birth control methods include intrauterine device (IUD), injected or implanted hormonal methods, abstinence, oral hormones plus a barrier contraception, vasectomized sole partner.
Agree to the following lifestyle modifications: comply with requirements for fasting and refraining from certain medications prior to Experimental Sessions, not enroll in any other interventional clinical trials during the duration of the study, remain overnight at the study site after each Experimental Session and be driven home after, and commit to medication dosing, therapy, and study procedures

Exclusion Criteria

Are not able to give adequate informed consent
Have any current problem which, in the opinion of the investigator or Medical Monitor, might interfere with participation
Would present a serious risk to others as established through clinical interview and contact with treating psychiatrist
Require ongoing concomitant therapy with a psychiatric medication (exceptions apply)
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.
Have a history of any medical condition that could make receiving a sympathomimetic drug harmful because of increases in blood pressure (BP) and heart rate.
Have current alcohol or substance use disorder.
Have used Ecstasy (material represented as containing MDMA) more than 10 times within the last 10 years or at least once within 6 months of the first Experimental Session; or have previously participated in a clinical trial conducted by the sponsor.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Experimental: MDMA-assisted psychotherapy	Midomafetamine HCl	Administration of 80 to 120 mg midomafetamine (MDMA) HCl followed by a supplemental half-dose 1.5 to 2 hrs after the initial dose of 40 or 60 mg, respectively, in combination with manualized psychotherapy.

Primary Outcome Measures

Name	Time	Method
Change in CAPS-5 Total Severity Score	13 weeks post-baseline	The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) is a 30-item semi-structured interview assessing PTSD in the past month through diagnostic and symptom severity scores anchored to a DSM-5 defined traumatic event. The CAPS-5 produces a Total Severity Score based on severity of PTSD domains described in the DSM-5, as well as a categorical rating indicating whether a participant meets PTSD diagnostic criteria. CAPS-5 Total Symptom Severity scores range from 0 to 80 with higher values designating greater symptom severity. CAPS-5 assigns PTSD diagnosis as being present or absent.

Secondary Outcome Measures

Name	Time	Method
Change in Sheehan Disability Scale (SDS) Item Scores	13 weeks post-baseline	The Sheehan Disability Scale (SDS) is a clinician-rated assessment of functional impairment for PTSD. The SDS is a 3-item scale measuring the severity of disability (i.e., the degree of impairment) in the domains of work, family life/home responsibilities and social/leisure activities. Responses are recorded using an 11-point scale (0 = not at all to 10 = extremely) and 5 verbal tags (not at all, mildly, moderately, markedly, extremely). For participants who are not able to work for reasons unrelated to PTSD, the measure includes an option to skip the work-related impairment item, and the reason was collected. The impact of missing item-level data was mitigated by averaging across the items to obtain a Total Score, rather than a straight sum.

Trial Locations

Locations (6): Charité - Universitätsmedizin, Berlin Campus Benjamin Franklin
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Berlin, Germany
The Institute of Psychiatry, Psychology and Neuroscience
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London, United Kingdom
Stichting Centrum '45/Arq
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Oegstgeest, Noord Holand, Netherlands
Sykehuset Østfold Hf, DPS Norder
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Moss, Norway
University Hospital of Wales - Research Facility
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Cardiff, United Kingdom
NUDZ - National Institute of Mental Health
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Klecany, Středočeský Kraj, Czechia