Open Label Multi-Site Study of Safety and Effects of MDMA-assisted Psychotherapy for Treatment of PTSD

• ClinicalTrials.gov Identifier: NCT03282123
• Recruitment Status: Completed
• First Posted: September 13, 2017
• Last Update Posted: February 19, 2020
• Sponsor: Multidisciplinary Association for Psychedelic Studies
• Information provided by (Responsible Party): Multidisciplinary Association for Psychedelic Studies

Study Description

Brief Summary:

This multi-site, open-label, Phase 2, lead-in study assesses the safety and effect of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy in participants diagnosed with at least severe posttraumatic stress disorder (PTSD). Therapy teams that have been identified and trained to work on the sponsor's planned Phase 3 studies will treat at least one open-label participant in this study. The study will be conducted in up to N=60 participants. A flexible dose of MDMA, followed by a supplemental half-dose unless contraindicated, is administered during the Treatment Period with manualized psychotherapy in three open-label 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, the 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 open-label manualized Experimental Sessions of psychotherapy assisted by flexible doses of MDMA. Initial doses per Experimental Session include 80 mg or 120 mg of MDMA compounded with lactose, followed 1.5 to 2 hours later by a supplemental half-dose (40 mg or 60 mg). Total amounts of MDMA to be administered per Experimental Session range from 80 mg to 180 mg.

Condition or disease	Intervention/treatment	Phase
PTSD	Drug: MDMA; Behavioral: Psychotherapy	Phase 2

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 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, open-label, Phase 2, lead-in study assesses the safety and effect of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy in participants diagnosed with at least severe posttraumatic stress disorder (PTSD). Therapy teams that have been identified and trained to work on the sponsor's planned Phase 3 studies will treat at least one open-label participant in this study. The study will be conducted in up to N=60 participants. A flexible dose of MDMA, followed by a supplemental half-dose unless contraindicated, is administered during the Treatment Period with manualized psychotherapy in three open-label 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, the 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 open-label manualized Experimental Sessions of psychotherapy assisted by flexible doses of MDMA. Initial doses per Experimental Session include 80 mg or 120 mg of MDMA compounded with lactose, followed 1.5 to 2 hours later by a supplemental half-dose (40 mg or 60 mg). Total amounts of MDMA to be administered per Experimental Session range from 80 mg to 180 mg.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 38 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Examining safety and effects of three sessions of MDMA-assisted psychotherapy, with Clinician-Administered PTSD Scale for DSM 5 (CAPS-5) severity after treatment compared with baseline
• Masking: None (Open Label)
• Masking Description: This study will be open label
• Primary Purpose: Treatment
• Official Title: An Open-Label, Multi-Site Phase 2 Study of the Safety and Effect of Manualized MDMA-Assisted Psychotherapy for the Treatment of Severe Posttraumatic Stress Disorder
• Actual Study Start Date: October 24, 2017
• Actual Primary Completion Date: October 10, 2019
• Actual Study Completion Date: October 18, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: MDMA-assisted psychotherapy; Three sessions of MDMA-assisted psychotherapy with flexible dose of MDMA from 80 to 120 mg and optional supplemental dose half that of initial dose 1.5 to 2 hours later	Drug: MDMA; 80 to 120 mg MDMA; Other Name: 3,4-methylenedioxymethamphetamine; Behavioral: Psychotherapy; Non-directive psychotherapy conducted during MDMA-assisted psychotherapy session

Outcome Measures

Primary Outcome Measures :

1. Change from Baseline in Clinician Administered PTSD Scale for DSM-5 [ Time Frame: 18 weeks post-enrollment ]
   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 ]
   Sheehan Disability Scale (SDS) total score, a measure of clinician-rated functional impairment.

Eligibility Criteria

• 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
• 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
• Meet DSM-5 Criteria for 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

Contacts and Locations

Locations

United States, California

New School Research LLC

North Hollywood, California, United States, 91601

San Francisco Insight and Integration Center

San Francisco, California, United States, 94114

University of California San Francisco

San Francisco, California, United States, 94122

United States, Colorado

Aguazul-Blue Water Inc.

Boulder, Colorado, United States, 80302

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

Brookline, Massachusetts, United States, 02446

United States, New York

New York University

New York, New York, United States, 10016

Affective Care

New York, New York, United States, 10024

United States, South Carolina

Zen Therapeutic Solutions, LLC

Mount Pleasant, South Carolina, United States, 29464

United States, Wisconsin

University of Wisconsin at Madison

Madison, Wisconsin, United States, 53705

Sponsors and Collaborators

Multidisciplinary Association for Psychedelic Studies

Investigators

• Study Director: Michael C Mithoefer, MD; MAPS Public Benefit Corp.

More Information

• Responsible Party: Multidisciplinary Association for Psychedelic Studies
• ClinicalTrials.gov Identifier: NCT03282123
• Other Study ID Numbers: MP-16
• First Posted: September 13, 2017
• Last Update Posted: February 19, 2020
• Last Verified: August 2019

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 wehn all participants have completed the study
• Access Criteria: Interested persons should correspond with the central contact for the multi-site study.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Multidisciplinary Association for Psychedelic Studies:

MDMA; methylenedioxymethamphetamine; psychotherapy

Additional relevant MeSH terms:

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