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A Multi-Site Phase 3 Study of MDMA-Assisted Psychotherapy for PTSD (MAPP2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04077437
Recruitment Status : Completed
First Posted : September 4, 2019
Last Update Posted : January 6, 2023
Sponsor:
Information provided by (Responsible Party):
Multidisciplinary Association for Psychedelic Studies

Tracking Information
First Submitted Date  ICMJE August 30, 2019
First Posted Date  ICMJE September 4, 2019
Last Update Posted Date January 6, 2023
Actual Study Start Date  ICMJE August 27, 2020
Actual Primary Completion Date November 2, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 30, 2019)
Change from Baseline in Clinician-Administered PTSD for DSM 5 [ Time Frame: 18 weeks post baseline post enrollment confirmation ]
Global severity Scores on the CAPS-5, a measure of PTSD symptoms
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 11, 2021)
Change from Baseline in Sheehan Disability Scale (adapted SDS) total score [ Time Frame: 18 weeks post enrollment confirmation ]
Sheehan Disability Scale (adapted SDS) total score, a measure of clinician-rated functional impairment.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 30, 2019)
Change from Baseline in Sheehan Disability Scale (SDS) total score [ Time Frame: 18 weeks post enrollment confirmation ]
Sheehan Disability Scale (SDS) total score, a measure of clinician-rated functional impairment.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Multi-Site Phase 3 Study of MDMA-Assisted Psychotherapy for PTSD (MAPP2)
Official Title  ICMJE A Randomized, Double-Blind, Placebo-Controlled, Multi-Site Phase 3 Study of the Efficacy and Safety of Manualized MDMA-Assisted Psychotherapy for the Treatment of Posttraumatic Stress Disorder of Moderate or Greater Severity
Brief 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.
Detailed Description

Posttraumatic stress disorder (PTSD) is a debilitating psychiatric disorder that can develop after a person experiences a traumatic event, such as sexual assault, war, or any other life-threatening event. PTSD is a worldwide health problem that severely reduces a person's quality of life and is associated with high rates of psychiatric and medical comorbidity, disability, suffering, and suicide. At least a third of PTSD patients fail to respond to established PTSD psychotherapies. A wider array of effective treatments for PTSD are needed.

3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy may be a potential treatment option for PTSD. MDMA is a monoamine releaser that affects serotonin, norepinephrine, and dopamine. MDMA is capable of inducing unique psychopharmacological effects such as decreased feelings of fear, increased feelings of wellbeing, increased sociability and extroversion, increased interpersonal trust, and an alert state of consciousness. In the U.S., MDMA was used as an adjunct to psychotherapy by a considerable number of psychiatrists and therapists before it was placed in Schedule I in 1985 as a result of non-medical use.

This multi-site, double-blind, placebo-controlled, randomized Phase 3 study will assess the efficacy and safety of MDMA-assisted psychotherapy versus psychotherapy with placebo control in participants diagnosed with at least moderate PTSD. The study will be conducted in N ≈ 100 participants. Participants will be randomized into one of two groups (MDMA or placebo) in a 1:1 ratio. A flexible dose of MDMA or placebo, followed by a supplemental half-dose unless contraindicated, will be administered during the Treatment Period 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. Initial doses in each Experimental Session will be 80 mg or 120 mg of MDMA compounded with mannitol and magnesium stearate or placebo alone (mannitol and magnesium stearate), followed 1.5 to 2 hours later by a supplemental half-dose (40 or 60 mg, respectively). Total amounts of MDMA to be administered per Experimental Session range from 80 mg to 180 mg. Each Experimental Session will be followed by three Integrative Sessions of non-drug psychotherapy to help the participants process and understand their experiences during the Experimental Sessions.

The primary objective of this study is to evaluate the efficacy of MDMA-assisted psychotherapy for PTSD compared to identical psychotherapy with inactive placebo, as measured by change in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) Total Severity Score from Visit 3 (Baseline) to Visit 19 (18 weeks post Baseline) (Blake et al., 1995). The key secondary objective of this study is to evaluate the efficacy of MDMA-assisted psychotherapy for PTSD compared to identical psychotherapy with inactive placebo in clinician-rated functional impairment, as measured by the change in Sheehan Disability Scale (adapted SDS) item scores from Visit 3 (Baseline) to Visit 19 (18 weeks post Baseline) (Leon et al., 1997).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE 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.
Primary Purpose: Treatment
Condition  ICMJE Posttraumatic Stress Disorder
Intervention  ICMJE
  • Behavioral: Behavioral: Psychotherapy
    Standardized non-directive psychotherapy performed by therapist team.
    Other Name: Manualized MDMA-assisted psychotherapy
  • Drug: MDMA
    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.
    Other Name: 3,4-methylenedioxymethamphetamine
  • Drug: Placebo
    Administration of placebo during three sessions of MDMA-assisted psychotherapy.
    Other Name: Inactive placebo
Study Arms  ICMJE
  • Experimental: Experimental: MDMA-assisted psychotherapy
    Administration of 80 to 120 mg MDMA in combination with psychotherapy, followed by a supplemental half-dose of 40 or 60 mg MDMA offered 1.5 to 2 hrs after the initial dose, respectively.
    Interventions:
    • Behavioral: Behavioral: Psychotherapy
    • Drug: MDMA
  • Placebo Comparator: Placebo Comparator: Placebo
    Administration of inactive placebo in combination with psychotherapy.
    Interventions:
    • Behavioral: Behavioral: Psychotherapy
    • Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 8, 2022)
121
Original Estimated Enrollment  ICMJE
 (submitted: August 30, 2019)
100
Actual Study Completion Date  ICMJE November 2, 2022
Actual Primary Completion Date November 2, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Israel,   United States
Removed Location Countries Canada
 
Administrative Information
NCT Number  ICMJE NCT04077437
Other Study ID Numbers  ICMJE MAPP2
Has Data Monitoring Committee Yes
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  ICMJE
Plan to Share IPD: Yes
Plan Description: We will share outcome data appearing in any published reports upon 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 the database has been locked and data has been unblinded.
Access Criteria: Interested persons should correspond with the central contact for the multisite study.
Current Responsible Party Multidisciplinary Association for Psychedelic Studies
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Multidisciplinary Association for Psychedelic Studies
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Michael Mithoefer, MD MAPS Public Benefit Corp.
PRS Account Multidisciplinary Association for Psychedelic Studies
Verification Date January 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP