A Multi-Site Phase 3 Study of MDMA-Assisted Psychotherapy for PTSD (MAPP2)
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| ClinicalTrials.gov Identifier: NCT04077437 |
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Recruitment Status :
Completed
First Posted : September 4, 2019
Last Update Posted : May 9, 2023
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Posttraumatic Stress Disorder | Behavioral: Behavioral: Psychotherapy Drug: MDMA Drug: Placebo | Phase 3 |
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 : | Interventional (Clinical Trial) |
| Actual Enrollment : | 121 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 : | September 2, 2020 |
| Actual Primary Completion Date : | October 30, 2022 |
| Actual Study Completion Date : | November 2, 2022 |
| Arm | Intervention/treatment |
|---|---|
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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.
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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 |
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Placebo Comparator: Placebo Comparator: Placebo
Administration of inactive placebo in combination with psychotherapy.
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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 |
- 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
- 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.
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.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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.
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
| United States, California | |
| New School Research | |
| Los Angeles, California, United States, 90004 | |
| UCSF | |
| San Francisco, California, United States, 94122 | |
| United States, Colorado | |
| Aguazul Bluewater, Inc. | |
| Boulder, Colorado, United States, 80304 | |
| Wholeness Center | |
| Fort Collins, Colorado, United States, 80525 | |
| United States, Connecticut | |
| University of Connecticut | |
| Farmington, Connecticut, United States, 06030 | |
| United States, Louisiana | |
| Ray Worthy Psychiatry LLC | |
| New Orleans, Louisiana, United States, 70123 | |
| United States, Massachusetts | |
| Trauma Research Foundation | |
| Boston, Massachusetts, United States, 02446 | |
| United States, New York | |
| New York University | |
| New York, New York, United States, 10016 | |
| New York Private Practice | |
| New York, New York, United States, 11012 | |
| United States, Wisconsin | |
| University of Wisconsin - Madison | |
| Madison, Wisconsin, United States, 53705-2222 | |
| Canada, British Columbia | |
| Providence Health Center | |
| Vancouver, British Columbia, Canada, V5R 5H3 | |
| Canada, Quebec | |
| Dr. Simon Amar, LLC | |
| Montréal, Quebec, Canada, H2W 1Y9 | |
| Study Director: | Michael Mithoefer, MD | MAPS Public Benefit Corp. |
Documents provided by Multidisciplinary Association for Psychedelic Studies:
Publications:
| 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: | May 9, 2023 |
| Last Verified: | May 2023 |
| 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. |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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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 |