A Multi-Site Phase 3 Study of MDMA-Assisted Psychotherapy for PTSD (MAPP1)
- Conditions
- Posttraumatic Stress Disorder
- Interventions
- Registration Number
- NCT03537014
- Lead Sponsor
- Lykos Therapeutics
- Brief Summary
The goal of this clinical trial is to learn if MDMA-assisted therapy is safe and effective in people with at least severe PTSD.
The main question it aims to answer is: Do three sessions of MDMA-assisted therapy reduce PTSD symptoms?
Researchers will compare three sessions of MDMA-assisted therapy with an initial dose of 80 to 120 mg to three sessions of placebo with therapy.
Participants will undergo three preparatory sessions without any study drug, followed by three MDMA-assisted therapy or placebo with therapy sessions. Each medication session will be followed by three integrative therapy sessions without study drug.
- Detailed Description
This multi-site, double-blind, placebo-controlled, randomized Phase 3 study will assess the efficacy and safety of MDMA-assisted therapy versus placebo with therapy in participants diagnosed with at least severe PTSD. The study will be conducted in N ≈ 100 participants. Participants will be randomized to one of two groups at a 1:1 ratio. An initial dose of midomafetamine HCl or placebo, followed by a supplemental half-dose unless contraindicated, is administered during the Treatment Period with manualized therapy 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. Initial doses per Experimental Session include 80 mg or 120 mg of midomafetamine HCl or placebo followed 1.5 to 2 hours later by a supplemental half-dose (40 or 60 mg). Total amounts of midomafetamine HCl to be administered per Experimental Session range from 80 mg to 180 mg.
The primary endpoint is change from baseline in Clinician Administered PTSD Scale for DSM-V (CAPS-5) to 18 weeks post-Baseline. 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 (adapted C-SSRS).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 100
- 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
- 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] in males and >460 ms in females 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, such as myocardial infarction, cerebrovascular accident, or aneurysm
- 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
- Have an active illicit or prescription drug use disorder
- Have used Ecstasy (material represented as containing MDMA) more than 10 times within the last 10 years or at least once within 6 months of the first Experimental Session; or have previously participated in a MAPS-sponsored MDMA clinical trial.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description MDMA-assisted therapy Therapy Administration of 80 or 120 mg midomafetamine HCl with a supplemental dose 1.5 to 2 hours later of 40 or 60 mg midomafetamine HCl, respectively, in combination with therapy during 3 experimental sessions scheduled 3-5 weeks apart. MDMA-assisted therapy midomafetamine HCl Administration of 80 or 120 mg midomafetamine HCl with a supplemental dose 1.5 to 2 hours later of 40 or 60 mg midomafetamine HCl, respectively, in combination with therapy during 3 experimental sessions scheduled 3-5 weeks apart. Placebo with therapy Therapy Administration of inactive placebo in combination with therapy during 3 experimental sessions scheduled 3-5 weeks apart Placebo with therapy Placebo Administration of inactive placebo in combination with therapy during 3 experimental sessions scheduled 3-5 weeks apart
- Primary Outcome Measures
Name Time Method Change From Baseline to Primary Endpoint in Clinician Administered PTSD Scale for DSM-V (CAPS-5) Baseline to 18 weeks post enrollment confirmation The CAPS-5 is a 30-item semi-structured interview assessing PTSD in the past month through diagnostic and symptom severity scores anchored to a DSM-5 defined traumatic event. The CAPS-5 produces a Total Severity Score based on severity of PTSD domains described in the DSM-5, as well as a categorical rating indicating whether a participant meets PTSD diagnostic criteria. CAPS-5 Total Symptom Severity scores range from 0 to 80 with higher values indicating greater symptom severity. CAPS-5 assigns PTSD diagnosis as being present or absent.
- Secondary Outcome Measures
Name Time Method Change From Baseline to Primary Endpoint in Sheehan Disability Scale (SDS) Total Score Baseline to 18 weeks post enrollment confirmation The Sheehan Disability Scale (SDS) is a clinician-rated assessment of functional impairment that was adapted for the purposes of this study to limit missing item-level data as per the FDA requirements and included use of the three-item mean as the total score and imputation of work-related impairment. The SDS is a 3-item scale measuring the severity of disability in the domains of work, family life/home responsibilities and social/leisure activities, with each item scored on a ten-point Likert scale from 0 ('not at all impaired') to 10 ('very severely impaired'). The SDS total score was the mean of the 3 item responses. The SDS total score ranged from 0 to 10, with higher scores indicating greater functional impairment.
Trial Locations
- Locations (15)
Trauma Research Foundation
🇺🇸Boston, Massachusetts, United States
Dr. Simon Amar, Inc.
🇨🇦Montreal, Quebec, Canada
Sheba Fund for Health Services and Research
🇮🇱Tel HaShomer, Israel
Zen Therapeutic Solutions, LLC
🇺🇸Mount Pleasant, South Carolina, United States
Ray Worthy Psychiatry LLC
🇺🇸New Orleans, Louisiana, United States
Aguazul-Blue Water Inc.
🇺🇸Boulder, Colorado, United States
Assaf Harofeh Research Fund
🇮🇱Be'er Ya'akov, Israel
New School Research LLT
🇺🇸North Hollywood, California, United States
University of California San Francisco
🇺🇸San Francisco, California, United States
San Francisco Insight and Integration Center
🇺🇸San Francisco, California, United States
Wholeness Center
🇺🇸Fort Collins, Colorado, United States
New York University
🇺🇸New York, New York, United States
University of Wisconsin at Madison
🇺🇸Madison, Wisconsin, United States
New York Private Practice
🇺🇸New York, New York, United States
Providence Health Center
🇨🇦Vancouver, British Columbia, Canada