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

NCT04784143 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: MPVA6
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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.

Conditions

PTSD

Outcome Measures

Primary Outcomes (2)

• Change in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) Total Severity Score From Baseline to Primary Outcome

  The Clinician-Administered PTSD Scale for DSM-5 (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.

  2 Session Group: ~12 weeks from baseline to primary outcome; 3 Session Group: ~16 weeks from baseline to primary outcome

• Change in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) Total Severity Score From Baseline to Secondary Outcome Timepoint in the 2 Session Group

  The Clinician-Administered PTSD Scale for DSM-5 (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.

  ~16 weeks from baseline to secondary outcome (note: secondary outcome timepoint assessed in 2 session group to evaluate the primary outcome measure in a follow up period equivalent to that of the 3 session group in the primary analysis.)

Secondary Outcomes (2)

• Change in Sheehan Disability Scale (SDS) Total Score From Baseline to Primary Outcome

  2 Session Group: ~12 weeks from baseline to primary outcome; 3 Session Group: ~16 weeks from baseline to primary outcome

• Change in Sheehan Disability Scale (SDS) Total Score From Baseline to Secondary Outcome Timepoint in the 2 Session Group

  ~16 weeks from baseline to secondary outcome (note: secondary outcome timepoint assessed in 2 session group to evaluate the primary outcome measure in a follow up period equivalent to that of the 3 session group in the primary analysis.)

Study Arms (2)

Two sessions of MDMA-assisted therapy

ACTIVE COMPARATOR

Two experimental sessions of MDMA-assisted therapy

Drug: Midomafetamine; Behavioral: Psychotherapy

Three sessions of MDMA-assisted therapy

ACTIVE COMPARATOR

Three experimental sessions of MDMA-assisted therapy

Drug: Midomafetamine; Behavioral: Psychotherapy

Interventions

Midomafetamine DRUG

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

Also known as: 3,4-methylenedioxymethamphetamine, MDMA, midomafetamine HCl

Three sessions of MDMA-assisted therapy; Two sessions of MDMA-assisted therapy

Psychotherapy BEHAVIORAL

Manualized psychotherapy performed by therapist team

Three sessions of MDMA-assisted therapy; Two sessions of MDMA-assisted therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Lykos Therapeutics: lead

Study Sites (1)

James J. Peters VA Medical Center

The Bronx, New York, 10468, United States

Location

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

N-Methyl-3,4-methylenedioxyamphetamine; Psychotherapy

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Amphetamines; Phenethylamines; Ethylamines; Amines; Organic Chemicals; Behavioral Disciplines and Activities

Results Point of Contact

• Title: Study Director
• Organization: Lykos Therapeutics

trialdata@lykospbc.com

877-627-7722

Study Officials

• Rachel Yehuda

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2021
• First Posted: March 5, 2021
• Study Start: November 8, 2021
• Primary Completion: June 25, 2024
• Study Completion: June 27, 2024
• Last Updated: July 15, 2025
• Results First Posted: July 15, 2025

Record last verified: 2025-06

Locations

US (1)