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

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ClinicalTrials.gov Identifier: NCT04077437
Recruitment Status : Recruiting
First Posted : September 4, 2019
Last Update Posted : November 17, 2020
Sponsor:
Information provided by (Responsible Party):
Multidisciplinary Association for Psychedelic Studies

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.

Condition or disease Intervention/treatment Phase
Posttraumatic Stress Disorder Behavioral: Behavioral: Psychotherapy Drug: MDMA Drug: Placebo Phase 3

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 (SDS) item scores from Visit 3 (Baseline) to Visit 19 (18 weeks post Baseline) (Leon et al., 1997).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
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
Official Title: 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
Actual Study Start Date : August 27, 2020
Estimated Primary Completion Date : November 10, 2021
Estimated Study Completion Date : November 18, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
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

Placebo Comparator: Placebo Comparator: Placebo
Administration of inactive placebo in combination with psychotherapy.
Behavioral: Behavioral: Psychotherapy
Standardized non-directive psychotherapy performed by therapist team.
Other Name: Manualized MDMA-assisted psychotherapy

Drug: Placebo
Administration of placebo during three sessions of MDMA-assisted psychotherapy.
Other Name: Inactive placebo




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04077437


Contacts
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Contact: Recruitment Officer (215) 645-2466 recruitment@mapsbcorp.com

Locations
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United States, California
New School Research LLC Recruiting
Los Angeles, California, United States, 90004
Contact: Study Coordinator    818-643-5234    info@newschoolresearch.com   
San Francisco Insight and Integration Center Recruiting
San Francisco, California, United States, 94114
Contact: Study Coordinator    415-400-5722    info@sfinsightcenter.com   
University of California San Francisco Not yet recruiting
San Francisco, California, United States, 94122
Contact: Study Coordinator    510-985-3522    mdma.research@ucsf.edu   
United States, Colorado
Aguazul-Blue Water Inc. Recruiting
Boulder, Colorado, United States, 80302
Contact: Study Coordinator    720-892-8395    info.boulderstudy@comcast.net   
Wholeness Center Recruiting
Fort Collins, Colorado, United States, 80525
Contact: Study Coordinator    970-825-6610    wcresearch@wholeness.com   
United States, Louisiana
Ray Worthy Psychiatry LLC Recruiting
New Orleans, Louisiana, United States, 70123
Contact: Study Coordinator    504-323-5584    info@nolamdmaresearch.com   
United States, Massachusetts
Trauma Research Foundation Recruiting
Boston, Massachusetts, United States, 02446
Contact: Study Coordinator    617-651-2646    mdma.study.boston@gmail.com   
United States, New York
New York University Not yet recruiting
New York, New York, United States, 10016
Contact: Study Coordinator    646-501-4206    MDMA.Research@nyumc.org   
New York Private Practice Not yet recruiting
New York, New York, United States, 10024
Contact: Study Coordinator    917-830-4948    info@mdma.nyc   
United States, South Carolina
Zen Therapeutic Solutions, LLC Recruiting
Mount Pleasant, South Carolina, United States, 29464
Contact: Study Coordinator    843-882-5203    information.zts@gmail.com   
United States, Wisconsin
University of Wisconsin at Madison Not yet recruiting
Madison, Wisconsin, United States, 53705
Contact: Study Coordinator    608-225-0718    Maps.madison@mailplus.wisc.edu   
Canada, British Columbia
Providence Health Center Not yet recruiting
Vancouver, British Columbia, Canada, V5R 5H3
Contact: Study Coordinator    604-360-1850    maps.trial.bc@gmail.com   
Israel
Assaf Harofeh Research Fund Not yet recruiting
Be'er Ya'aqov, Israel
Contact: Study Coordinator    +972-8-9258396    bymehkar@moh.gov.il   
Contact    +972-8-9258474      
Sheba Fund for Health Services and Research Not yet recruiting
Tel HaShomer, Israel
Contact: Study Coordinator    +972-3-5303773    mdmastudysheba@gmail.com   
Sponsors and Collaborators
Multidisciplinary Association for Psychedelic Studies
Investigators
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Study Director: Michael Mithoefer, MD MAPS Public Benefit Corp.
Additional Information:
Publications:
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Responsible Party: Multidisciplinary Association for Psychedelic Studies
ClinicalTrials.gov Identifier: NCT04077437    
Other Study ID Numbers: MAPP2
First Posted: September 4, 2019    Key Record Dates
Last Update Posted: November 17, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: We will share outcome data appearing in any published reports upon request.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
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.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Stress Disorders, Traumatic
Stress Disorders, Post-Traumatic
Trauma and Stressor Related Disorders
Mental Disorders
N-Methyl-3,4-methylenedioxyamphetamine
Hallucinogens
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Adrenergic Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Adrenergic Agents