Open Label Multi-Site Study of Safety and Effects of MDMA-assisted Psychotherapy for Treatment of PTSD With Optional fMRI Sub-Study

• ClinicalTrials.gov Identifier: NCT04030169
• Recruitment Status: Recruiting
• First Posted: July 23, 2019
• Last Update Posted: May 20, 2022
• Sponsor: MAPS Europe B.V.
• Collaborator: Multidisciplinary Association for Psychedelic Studies
• Information provided by (Responsible Party): MAPS Europe B.V.

Tracking Information

• First Submitted Date: July 19, 2019
• First Posted Date: July 23, 2019
• Last Update Posted Date: May 20, 2022
• Actual Study Start Date: June 24, 2020
• Estimated Primary Completion Date: November 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 29, 2019)

Change in CAPS-5 Total Severity Score [ Time Frame: 13 weeks post-enrollment ]

The primary objective of this study is to evaluate the effectiveness of MDMA-assisted psychotherapy for treatment of PTSD, as measured by the estimand of change in CAPS-5 Total Severity Score

Original Primary Outcome Measures (submitted: July 22, 2019)

Change in CAPS-5 Total Severity Score [ Time Frame: 18 weeks post-enrollment ]

The primary objective of this study is to evaluate the effectiveness of MDMA-assisted psychotherapy for treatment of PTSD, as measured by the estimate of change in CAPS-5 Total Severity Score

Current Secondary Outcome Measures (submitted: July 29, 2019)

Change in Sheehan Disability Scale (SDS) item scores [ Time Frame: 13 weeks post-enrollment ]

The secondary objective is to evaluate the effectiveness of MDMA-assisted psychotherapy for PTSD in clinician-rated functional impairment, as measured by the mean change in Sheehan Disability Scale (SDS) item scores.

Original Secondary Outcome Measures (submitted: July 22, 2019)

Change in Sheehan Disability Scale (SDS) item scores [ Time Frame: 18 weeks post-enrollment ]

The secondary objective is to evaluate the effectiveness of MDMA-assisted psychotherapy for PTSD in clinician-rated functional impairment, as measured by the mean change in Sheehan Disability Scale (SDS) item scores.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Open Label Multi-Site Study of Safety and Effects of MDMA-assisted Psychotherapy for Treatment of PTSD With Optional fMRI Sub-Study
• Official Title: An Open-Label, Phase 2, Multicenter Feasibility Study of Manualized MDMA-Assisted Psychotherapy With an Optional fMRI Sub-Study Assessing Changes in Brain Activity in Subjects With Posttraumatic Stress Disorder
• Brief Summary: This open-label, lead-in Phase 2 study is intended to gather supportive data on the safety and effectiveness of manualized MDMA-assisted psychotherapy as a treatment for PTSD. This will be the first study of MDMA-assisted psychotherapy in Europe using the CAPS-5 as a primary outcome measure to confirm assumptions made for statistical power calculations using the Clinician-Administered PTSD Scale for DSM-4 (CAPS-4) which support planned Phase 3 clinical trials. This study will gather supportive data on the safety and effectiveness of manualized MDMA-assisted psychotherapy as a treatment for PTSD and provide clinical supervision to planned Phase 3 therapy teams. This study will also be the first multi-site study of MDMA-assisted psychotherapy for PTSD in Europe and will explore reproducibility of findings from FDA-regulated trials in a multi-site format to further confirm the Phase 3 study design. This study will compare the effects of two open-label manualized Experimental Sessions of psychotherapy assisted by flexible doses of MDMA. Initial doses per Experimental Session include 80 mg or 120 mg of MDMA compounded with lactose, 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.

Detailed Description

PTSD is a serious debilitating disorder that negatively impacts a person's daily life. PTSD is a stress-related psychiatric condition that may occur following a traumatic event such as war, disaster, sexual abuse, violence, terrorism, and accidents. PTSD negatively impacts a person's daily life, resulting in relationship difficulties, difficulty in finding and maintaining a job, reduced cognitive and psychosocial functioning, substance abuse, high-cost healthcare use, and increased depression and suicide risk. Available PTSD treatments, including medications and therapy, effectively treat only a fraction of people who try them for adequate dose and duration. People with PTSD can be treated with psychotherapies and pharmacotherapies. In the past decade, there has been a growing amount of research into medications and other methods that may augment the effectiveness of psychotherapy for PTSD.

3,4-methylenedioxymethamphetamine is a drug that releases serotonin, norepinephrine and dopamine in the brain and indirectly increases levels of the neurohormones oxytocin, arginine vasopressin and cortisol. The combined neurobiological effects of MDMA increase compassion, reduce defenses and fear of emotional injury, and enhance communication and introspection. MDMA produces anxiolytic and prosocial effects, which counteract avoidance and hyperarousal in the context of therapy. A combined treatment of MDMA and psychotherapy may be especially useful for treating PTSD.

This multicenter, open-label, lead-in study assesses the safety and effectiveness of MDMA- assisted psychotherapy in participants diagnosed with at least severe PTSD. All safety data will be included in the global safety database for MDMA maintained by MAPS. Some sites will participate in the imaging sub-study. A flexible dose of MDMA, followed by a supplemental half-dose unless contraindicated, is administered during the Treatment Period with manualized psychotherapy in two open-label Experimental Sessions spaced approximately a month apart. This 8-week Treatment Period is preceded by three Preparatory Sessions. During the Treatment Period, each Experimental Session is followed by three Integrative Sessions of non-drug psychotherapy. Exploratory measures will address specific symptoms or behavior that is sometimes related to PTSD. Drug safety will be assessed by measuring blood pressure, heart rate and body temperature during experimental sessions, collecting adverse events and measuring suicidal thoughts or behaviors with the Columbia Suicide Severity Rating Scale (CSSRS). This study will compare the effects of two open-label manualized Experimental Sessions of psychotherapy assisted by flexible doses of MDMA. Initial doses per Experimental Session include 80 mg or 120 mg of MDMA compounded with lactose, 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 study will be the first multi-site study of MDMA-assisted psychotherapy for PTSD in Europe and will explore reproducibility of findings from FDA-regulated trials in a multi-site format to further confirm the Phase 3 study design.

• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

Examining safety and effects of two sessions of MDMA-assisted psychotherapy, with Clinician-Administered PTSD Scale for DSM 5 (CAPS-5) severity after treatment compared with baseline

Masking: None (Open Label)
Masking Description:

This study will be open label

Primary Purpose: Treatment

• Condition: PTSD

Intervention

Drug: MDMA

Non-directive psychotherapy conducted during MDMA-assisted psychotherapy session

Other Name: 3,4-methylenedioxymethamphetamine

Study Arms

Experimental: Experimental: MDMA-assisted psychotherapy

Two sessions of MDMA-assisted psychotherapy with flexible dose of MDMA from 80 to 120 mg and optional supplemental dose half that of initial dose 1.5 to 2 hours later

Intervention: Drug: MDMA

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 22, 2019): 40
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: November 2022
• Estimated Primary Completion Date: November 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Are at least 18 years old
2. Are fluent in speaking and reading the predominantly used or recognized language of the study site
3. Are able to swallow pills
4. Agree to have study visits video-recorded, including Experimental Sessions, Independent Rater assessments, and non-drug psychotherapy sessions
5. 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
6. Must agree to inform the investigators within 48 hours of any medical treatments and procedures
7. 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.
8. 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:

1. Are not able to give adequate informed consent
2. Have any current problem which, in the opinion of the investigator or Medical Monitor, might interfere with participation
3. Would present a serious risk to others as established through clinical interview and contact with treating psychiatrist
4. Require ongoing concomitant therapy with a psychiatric medication (exceptions apply)
5. Weigh less than 48 kilograms (kg)
6. Are pregnant or nursing or are able to become pregnant and are not practicing an effective means of birth control.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Recruitment Officer; askmapseu@mapseurope.eu

• Listed Location Countries: Norway, Czechia, Germany, Netherlands, Portugal, United Kingdom

Administrative Information

• NCT Number: NCT04030169
• Other Study ID Numbers: MP18
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: We will share outcome data appearing in any published reports upn request.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Time Frame: Data and study-related documents will be available when all participants have completed the study.
• Access Criteria: Interested persons should correspond with the central contact for the multi-site study.

• Current Responsible Party: MAPS Europe B.V.
• Original Responsible Party: Multidisciplinary Association for Psychedelic Studies
• Current Study Sponsor: MAPS Europe B.V.
• Original Study Sponsor: Multidisciplinary Association for Psychedelic Studies
• Collaborators: Multidisciplinary Association for Psychedelic Studies

Investigators

• Principal Investigator: Prof. Dr. Eric Vermetten, MD; Leiden University Medical Center

• PRS Account: MAPS Europe B.V.
• Verification Date: November 2021