Study Comparing Two Versus Three Active MDMA-assisted Sessions in U.S. Military Veterans With Chronic PTSD

NCT ID: NCT04784143

Last Updated: 2025-07-15

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-08
• Study Completion Date: 2024-06-27

Brief Summary

The goal of this clinical trial is to learn if MDMA-assisted therapy is effective in U.S. military veterans with at least moderate chronic PTSD. The main question it aims to answer is: Are two versus three MDMA-assisted therapy sessions in an outpatient treatment clinic more effective?

Researchers will compare two MDMA-assisted therapy sessions to three MDMA-assisted therapy sessions.

Participants will undergo three non-drug preparatory sessions prior to their first MDMA-assisted therapy session. Each MDMA-assisted therapy session will be followed by three non-drug integrative therapy sessions.

Detailed Description

This open-label, randomized study will assess the comparative effectiveness of two versus three active MDMA-assisted therapy sessions in U.S. military veterans with at least moderate chronic PTSD treated in an outpatient VA treatment clinic. The study will be conducted in up to 60 participants. Prior to the randomized portion of the study, each therapist pair team will treat one participant under the 3-session model, and one participant under the 2-session model. In total, 8 participants will be treated under this proof of principle therapist training lead-in. A 120 mg dose of MDMA, followed by a supplemental dose (60 mg) unless contraindicated, is administered during the treatment period with manualized psychotherapy in 2 or 3 open-label monthly Experimental Sessions. This ~ 8-12-week Treatment Period includes three Preparatory Sessions prior to the first MDMA-assisted session. During the treatment period, each Experimental Session is followed by three Integrative Sessions of non-drug therapy. The Primary Outcome measure, the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), is assessed by a centralized, blinded Independent Rater (IR) pool at post-treatment for each group.

Conditions

PTSD

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Two sessions of MDMA-assisted therapy

Two experimental sessions of MDMA-assisted therapy

Group Type: ACTIVE_COMPARATOR

Midomafetamine

Intervention Type: DRUG

120 mg midomafetamine HCl followed by a supplemental dose of 60 mg

Psychotherapy

Intervention Type: BEHAVIORAL

Manualized psychotherapy performed by therapist team

Three sessions of MDMA-assisted therapy

Three experimental sessions of MDMA-assisted therapy

Group Type: ACTIVE_COMPARATOR

Midomafetamine

Intervention Type: DRUG

120 mg midomafetamine HCl followed by a supplemental dose of 60 mg

Psychotherapy

Intervention Type: BEHAVIORAL

Manualized psychotherapy performed by therapist team

Interventions

Midomafetamine

120 mg midomafetamine HCl followed by a supplemental dose of 60 mg

Intervention Type: DRUG

Psychotherapy

Manualized psychotherapy performed by therapist team

Intervention Type: BEHAVIORAL

Other Intervention Names

3,4-methylenedioxymethamphetamine; MDMA; midomafetamine HCl

Eligibility Criteria

Inclusion Criteria

• U.S. military veteran
• 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.
• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Lykos Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rachel Yehuda

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Locations

James J. Peters VA Medical Center

The Bronx, New York, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

MPVA6

Identifier Type: -

Identifier Source: org_study_id