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

Study Description

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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

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	60 participants
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
Estimated Primary Completion Date :	July 2019
Estimated Study Completion Date :	August 2019

Arms and Interventions

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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

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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 Beck Depression Inventory II (BDI-II) [ Time Frame: 18 weeks post-enrollment ]
   Assesses self-reported depression symptoms
2. Systolic blood pressure (SBP) [ Time Frame: Seven weeks after enrollment ]
   Systolic blood pressure assessed 1.5 to 2 hours after initial MDMA dose
3. Systolic blood pressure (SBP) [ Time Frame: 11 weeks after enrollment ]
   Systolic blood pressure assessed 1.5 to 2 hours after initial MDMA dose
4. Systolic blood pressure (SBP) [ Time Frame: 15 weeks after enrollment ]
   Systolic blood pressure assessed 1.5 to 2 hours after initial MDMA dose
5. Diastolic blood pressure (DBP) [ Time Frame: Seven weeks after enrollment ]
   Diastolic blood pressure assessed 1.5 to 2 hours after initial MDMA dose
6. Diastolic blood pressure (DBP) [ Time Frame: 11 weeks after enrollment ]
   Diastolic blood pressure assessed 1.5 to 2 hours after initial MDMA dose
7. Diastolic blood pressure (DBP) [ Time Frame: 15 weeks after enrollment ]
   Diastolic blood pressure assessed 1.5 to 2 hours after initial MDMA dose
8. Pulse [ Time Frame: Seven weeks after enrollment ]
   Pulse assessed 1.5 to 2 hours after initial MDMA dose
9. Pulse [ Time Frame: 11 weeks after enrollment ]
   Pulse assessed 1.5 to 2 hours after initial MDMA dose
10. Pulse [ Time Frame: 15 weeks after enrollment ]
    Pulse assessed 1.5 to 2 hours after initial MDMA dose
11. Body temperature (BT) [ Time Frame: Seven weeks after enrollment ]
    BT assessed 1.5 to 2 hours after initial MDMA dose
12. Body temperature (BT) [ Time Frame: 11 weeks after enrollment ]
    BT assessed 1.5 to 2 hours after initial MDMA dose
13. Body temperature (BT) [ Time Frame: 15 weeks after enrollment ]
    BT assessed 1.5 to 2 hours after initial MDMA dose

Eligibility Criteria

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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
• 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

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Contacts

Contact: B

Locations

United States, California
New School Research LLC	Active, not recruiting
North Hollywood, California, United States, 91601
San Francisco Insight and Integration Center	Active, not recruiting
San Francisco, California, United States, 94114
University of California San Francisco	Recruiting
San Francisco, California, United States, 94122
Contact: Study coordinator 510-985-3522 mdma.research@ucsf.edu
United States, Colorado
Aguazul-Blue Water Inc.	Active, not recruiting
Boulder, Colorado, United States, 80302
Wholeness Center	Active, not recruiting
Fort Collins, Colorado, United States, 80525
United States, Connecticut
University of Connecticut	Active, not recruiting
Farmington, Connecticut, United States, 06030
United States, Louisiana
Ray Worthy Psychiatry LLC	Active, not recruiting
New Orleans, Louisiana, United States, 70123
United States, Massachusetts
Trauma Research Foundation	Recruiting
Brookline, Massachusetts, United States, 02446
Contact: Study coordinator 617-651-2646 mdma.study.boston@gmail.com
Principal Investigator: Bessel Van der Kolk, MD
United States, New York
New York University	Active, not recruiting
New York, New York, United States, 10016
Affective Care	Active, not recruiting
New York, New York, United States, 10024
United States, South Carolina
Zen Therapeutic Solutions, LLC	Active, not recruiting
Mount Pleasant, South Carolina, United States, 29464
United States, Wisconsin
University of Wisconsin at Madison	Recruiting
Madison, Wisconsin, United States, 53705
Contact: Study coordinator 608-265-8926 Maps.madison@mailplus.wisc.edu

Sponsors and Collaborators

Multidisciplinary Association for Psychedelic Studies

Investigators

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

More Information

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Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Multidisciplinary Association for Psychedelic Studies
ClinicalTrials.gov Identifier:	NCT03282123 History of Changes
Other Study ID Numbers:	MP-16
First Posted:	September 13, 2017
Last Update Posted:	February 21, 2019
Last Verified:	February 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