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Trial record 4 of 38 for:    Saved Studies

A Multi-Site Phase 3 Study of MDMA-Assisted Psychotherapy for PTSD (MAPP1)

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: NCT03537014
Recruitment Status : Active, not recruiting
First Posted : May 25, 2018
Last Update Posted : April 13, 2020
Sponsor:
Information provided by (Responsible Party):
Multidisciplinary Association for Psychedelic Studies

Tracking Information
First Submitted Date  ICMJE May 14, 2018
First Posted Date  ICMJE May 25, 2018
Last Update Posted Date April 13, 2020
Actual Study Start Date  ICMJE November 29, 2018
Estimated Primary Completion Date June 10, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 24, 2018)
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: July 19, 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 24, 2018)
  • Change from Baseline in Beck Depression Inventory II (BDI-II) [ Time Frame: 18 weeks post enrollment confirmation ]
    Assesses self-reported depression symptoms
  • Systolic Blood pressure (SBP) [ Time Frame: 4 weeks after enrollment ]
    Systolic blood pressure assessed 1.5 to 2 hours after initial MDMA/placebo dose during first of three experimental sessions
  • Systolic Blood pressure (SBP) [ Time Frame: 8 weeks after enrollment ]
    Systolic blood pressure assessed 1.5 to 2 hours after initial MDMA/placebo dose during second of three experimental sessions
  • Systolic Blood pressure (SBP) [ Time Frame: 12 weeks after enrollment ]
    Systolic blood pressure assessed 1.5 to 2 hours after initial MDMA/placebo dose during third of three experimental sessions
  • Diastolic blood pressure (DBP) [ Time Frame: 4 weeks after enrollment ]
    Diastolic blood pressure assessed 1.5 to 2 hours after initial MDMA dose during first of three experimental sessions
  • Diastolic blood pressure (DBP) [ Time Frame: 8 weeks after enrollment ]
    Diastolic blood pressure assessed 1.5 to 2 hours after initial MDMA/placebo dose during second of three experimental sessions
  • Diastolic blood pressure (DBP) [ Time Frame: 12 weeks after enrollment ]
    Diastolic blood pressure assessed 1.5 to 2 hours after initial MDMA/placebo dose during third of three experimental sessions
  • Pulse [ Time Frame: 4 weeks after enrollment ]
    Pulse assessed 1.5 to 2 hours after initial dose of MDMA or placebo during first of three experimental sessions
  • Pulse [ Time Frame: 8 weeks after enrollment ]
    Pulse assessed 1.5 to 2 hours after initial dose of MDMA or placebo during second of three experimental sessions
  • Pulse [ Time Frame: 12 weeks after enrollment ]
    Pulse assessed 1.5 to 2 hours after initial dose of MDMA or placebo during third of three experimental sessions
  • Body temperature (BT) [ Time Frame: 4 weeks after enrollment ]
    BT assessed 1.5 to 2 hours after initial dose of MDMA or placebo during first of three experimental sessions.
  • Body temperature (BT) [ Time Frame: 8 weeks after enrollment ]
    BT assessed 1.5 to 2 hours after initial dose of MDMA or placebo during second of three experimental sessions.
  • Body temperature (BT) [ Time Frame: 12 weeks after enrollment ]
    BT assessed 1.5 to 2 hours after initial dose of MDMA or placebo during third of three experimental sessions.
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 (MAPP1)
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 Severe Posttraumatic Stress Disorder
Brief Summary This multi-site double-blind, placebo-controlled randomized Phase 3 study assesses the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy versus psychotherapy with placebo in participants diagnosed with at least severe posttraumatic stress disorder (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 psychotherapy 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. The Primary Outcome measure is change in Clinician Administered PTSD Scale for DSM 5 (CAPS-5) from Baseline. 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 three manualized Experimental Sessions of psychotherapy assisted by flexible doses of MDMA versus placebo. Initial doses per Experimental Session include 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). 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 (MDMA) 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 multi-site, double-blind, randomized Phase 3 study assesses the efficacy and safety of MDMA-assisted psychotherapy versus psychotherapy with placebo control in participants diagnosed with at least severe posttraumatic stress disorder (PTSD). The study will be conducted in N ≈ 100 participants. Participants will be enrolled in one of two groups at a 1:1 ratio. A flexible dose of MDMA or placebo, followed by a supplemental half-dose unless contraindicated, is administered during the Treatment Period with manualized psychotherapy 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. The Primary Outcome measure is change in Clinician Administered PTSD Scale for DSM 5 (CAPS-5) from Baseline. 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 three manualized Experimental Sessions of psychotherapy supported by assisted by flexible doses of MDMA versus placebo. Initial doses per Experimental Session include 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). Total amounts of MDMA to be administered per Experimental Session range from 80 mg to 180

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 third-party vendor to maintain blinding.
Primary Purpose: Treatment
Condition  ICMJE Posttraumatic Stress Disorder
Intervention  ICMJE
  • 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 dose of 40 or 60 mg MDMA offered 1.5/2 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: MDMA
    Administration of 80 or 120 mg MDMA in combination with psychotherapy and a supplemental dose offered 1.5/2 hrs later of 40 or 60 mg MDMA respectively.
    Interventions:
    • Behavioral: Psychotherapy
    • Drug: MDMA
  • Placebo Comparator: Placebo
    Administration of inactive placebo in combination with psychotherapy
    Interventions:
    • Behavioral: Psychotherapy
    • Drug: Placebo
Publications * Not Provided

*   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 Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: May 24, 2018)
100
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 18, 2020
Estimated Primary Completion Date June 10, 2020   (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, 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
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 Canada,   Israel,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03537014
Other Study ID Numbers  ICMJE MAPP1
Has Data Monitoring Committee Not Provided
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.
Responsible Party Multidisciplinary Association for Psychedelic Studies
Study Sponsor  ICMJE Multidisciplinary Association for Psychedelic Studies
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 2020

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