A Multi-Site Phase 3 Study of MDMA-Assisted Psychotherapy for PTSD (MAPP2)
Condition: Posttraumatic Stress Disorder
MeSH terms: Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
Intervention: Therapy; Midomafetamine; Placebo
Intervention description: Standardized non-directive therapy performed by therapist team.; Administration of 80 to 120 mg MDMA during three sessions of MDMA-assisted psychotherapy, followed by a supplemental half-dose of 40 or 60 mg MDMA offered 1.5 to 2 hrs after the initial dose, respectively.; Administration of placebo with therapy during three experimental sessions
Intervention MeSH terms: N-Methyl-3,4-methylenedioxyamphetamine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Randomized, double-blind between group comparison of change in PTSD symptoms
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking description: Use of separate databases for outcome measures and safety data. Assessment made by pool of independent raters. Randomization will be managed via an Interactive Web Randomization System (IWRS) based on a centralized randomization schedule developed by an independent thirdparty vendor to maintain blinding.
Enrollment: 121.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Posttraumatic stress disorder (PTSD) is a debilitating psychiatric disorder that can develop
      after a traumatic life experience that severely reduces quality of life. This multi-site,
      double-blind, placebo-controlled, randomized Phase 3 study will assess the efficacy and
      safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy compared to
      psychotherapy with placebo in participants diagnosed with at least moderate PTSD. The study
      will be conducted in up to N ≈ 100 participants. Participants will be randomized to receive a
      flexible dose of 80 or 120 mg MDMA or placebo, followed by a supplemental half-dose of 40 or
      60 mg MDMA or placebo, unless contraindicated, with manualized psychotherapy in three monthly
      Experimental Sessions. This ~12-week Treatment Period will be preceded by three Preparatory
      Sessions with the participant and therapists. During the Treatment Period, each Experimental
      Session will be followed by three Integrative Sessions of non-drug psychotherapy.
    

Eligibility criteria:

        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 recorded, including Experimental Sessions, Independent
             Rater assessments, and non-drug psychotherapy sessions.

          -  Must provide a contact (relative, spouse, close friend or other caregiver) 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 of childbearing potential, must have a 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.

          -  Must not participate in any other interventional clinical trials during the duration
             of the study.

          -  Must be willing to remain overnight at the study site after each Experimental Session
             and be driven home after, and commit to medication dosing, therapy, and study
             procedures.

          -  At baseline, have moderate PTSD diagnosis.

        Exclusion Criteria:

          -  Are not able to give adequate informed consent.

          -  Have uncontrolled hypertension.

          -  Have a marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration
             of a QTc interval >450 milliseconds [ms] corrected by Bazett's formula).

          -  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 disease.

          -  Have history of hyponatremia or hyperthermia.

          -  Weigh less than 48 kilograms (kg).

          -  Are pregnant or nursing, or are of childbearing potential and are not practicing an
             effective means of birth control.

          -  Are abusing illegal drugs.