A Multi-Site Phase 3 Study of MDMA-Assisted Psychotherapy for PTSD (MAPP1)
Condition: Posttraumatic Stress Disorder
MeSH terms: Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
Intervention: Therapy; Midomafetamine; Placebo
Intervention description: Non-directive therapy performed by therapist team; Administration of 80 to 120 mg MDMA during three sessions of MDMA-assisted therapy followed by a supplemental dose of 40 or 60 mg MDMA offered 1.5/2 hrs after the initial dose, respectively.; Administration of placebo 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 third-party vendor to maintain blinding.
Enrollment: 100.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This multi-site double-blind, placebo-controlled randomized Phase 3 study assesses the
      efficacy and safety of MDMA-assisted therapy versus placebo with therapy in participants
      diagnosed with at least severe PTSD. The study will be conducted in up to N ≈ 100
      participants. Participants will be randomized to receive a flexible dose of MDMA or placebo,
      followed by a supplemental half-dose, unless contraindicated, during the Treatment Period
      with manualized therapy in three monthly Experimental Sessions. This ~12-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.
    

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, meet DSM-5 criteria for current severe PTSD

        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