MDMA-assisted Massed Prolonged Exposure for PTSD

NCT06117306 | Recruiting Phase 3 FDA Drug

• 1 other identifier: IVAPT4
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The overall objective of this study is to pilot the VASDHS-adapted Emory MDMA-PE Protocol (aE-MDMA-PE) and assess the effect on clinician-rated PTSD symptoms in veterans who receive different doses of MDMA.

Conditions

Post-Traumatic Stress Disorder

Keywords

Post Traumatic Stress Disorder; MDMA; 3,4-methylenedioxymethamphetamine; Veterans; Prolonged Exposure Therapy

Outcome Measures

Primary Outcomes (1)

• Clinician-rated PTSD symptoms

  The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) is a 20-item diagnostic interview administered by trained evaluators to assess PTSD in a participant. Based on DSM-5 diagnostic criteria, evaluators ask about the severity of four PTSD-related symptom clusters: re-experiencing, avoidance, negative alterations in cognition and mood, and alterations in arousal and reactivity. The evaluator rates responses on a 5-point Likert scale (0 = Absent to 4 = Extreme/Incapacitating). Total scores range from 0 to 80 with higher scores indicating greater severity.

  Baseline - 4-months post-treatment

Secondary Outcomes (12)

• Self-reported PTSD symptoms

  Baseline - 4-months post-treatment

• Depressive Symptoms

  Baseline - 4-months post-treatment

• Functioning

  Baseline - 4-months post-treatment

• Sleep

  Baseline - 4-months post-treatment

• Safety/Suicidality

  Baseline - 4-months post-treatment

Other Outcomes (4)

• Satisfaction with Care

  1 week post-treatment

• Acceptability of Care

  1 week post-treatment

• Treatment Expectations

  Baseline, Visit 3

Study Arms (2)

Dose A (exact dose not disclosed)

EXPERIMENTAL

Non-medicine sessions of PE + One Medicine Session with 3,4-methylenedioxymethamphetamine (MDMA) PE Non-medicine sessions: 12 sessions MDMA Medicine session: Dose: exact dose not disclosed

Drug: 3,4 Methylenedioxymethamphetamine; Behavioral: Prolonged Exposure

Dose B (exact dose not disclosed)

EXPERIMENTAL

Non-medicine sessions of PE + One Medicine Session with 3,4-methylenedioxymethamphetamine (MDMA) PE Non-medicine sessions: 12 sessions MDMA Medicine session: Dose: exact dose not disclosed

Drug: 3,4 Methylenedioxymethamphetamine; Behavioral: Prolonged Exposure

Interventions

3,4 Methylenedioxymethamphetamine DRUG

1 MDMA session

Also known as: MDMA

Dose A (exact dose not disclosed); Dose B (exact dose not disclosed)

Prolonged Exposure BEHAVIORAL

12 90-minute PE sessions; initial two sessions both occurring during the first treatment visit, third and fourth sessions occurring during the MDMA session, and the remaining sessions occurring daily or every other day

Also known as: PE

Dose A (exact dose not disclosed); Dose B (exact dose not disclosed)

Eligibility Criteria

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

You may qualify if:

• Be a veteran (age 18-64 years old) who meets criteria for PTSD on the CAPS-5 (severity ≥ 25).
• Be fluent in speaking and reading English.
• Are willing to commit to medication dosing, therapy sessions, follow-up sessions, completing evaluation instruments, and all necessary telephone contact
• Be able to swallow pills.
• Agree to have study visits audio and/or video recorded, including MDMA session, assessments, and PE sessions, and aware that Independent Rater assessments for PE sessions will occur.
• Have a contact able to drive the participant home after the MDMA session.
• Provide a contact (relative, spouse, close friend, or other support person) who is willing and able to be reached by the investigators in the event of a participant becoming suicidal or unreachable.
• Agree to inform the investigators within 48 hours of any new medical conditions or procedures.
• If able to become pregnant (i.e., assigned female at birth, fertile, following menarche and until becoming post-menopausal unless permanently sterile), must have a highly sensitive negative pregnancy test at study entry and prior to the MDMA session, and must agree to use adequate birth control for 1 month before through 10 days after the MDMA session. Adequate birth control methods include intrauterine device (IUD), injected, implanted, intravaginal, or transdermal hormonal methods, abstinence, oral hormones plus a barrier contraception, vasectomized sole partner, or double barrier contraception. Two forms of contraception are required with any barrier method or oral hormones (i.e., condom plus diaphragm, condom or diaphragm plus spermicide, oral hormonal contraceptives plus spermicide or condom).
• Agree to the following lifestyle modifications (described in more detail in Section 3.3 Lifestyle Modifications): comply with requirements for fasting and refraining from certain medications prior to and following the MDMA session, including a possible medication taper if on SSRIs, medications for ADHD, and/or other medications described in the concomitant medications section.
• Agree not to participate in other PTSD psychotherapy during study treatment.
• Not enroll in any other interventional clinical trials during the duration of the study, and commit to medication dosing, therapy, and study procedures.
• At Pre-Screening, have at least moderate PTSD symptoms in the last month based on PCL-5 total score of 40 or greater (index).
• May have well-controlled hypertension that has been successfully treated with anti- hypertensive medicines if they pass additional screening to rule out underlying cardiovascular disease.
• May have asymptomatic Hepatitis C virus (HCV) that has previously undergone evaluation and treatment as needed.

You may not qualify if:

• Are not able to give adequate, written informed consent.
• Are currently engaged in compensation and pension (C\&P) litigation whereby financial gain would be achieved from prolonged symptoms of PTSD or any other psychiatric disorders.
• Are likely, in the investigator's opinion and via assessment period, to be re- exposed to their index trauma or other significant trauma, lack social support, or lack a stable living situation.
• Have used Ecstasy (material represented as containing MDMA) or have participated in an MDMA clinical trial.
• Have a positive screen for amphetamine or cocaine.
• Have any current problem which, in the clinical opinion of the investigator and study physician, might interfere with participation due to it impacting the patient's safety and/or ability to participate in the protocol.
• Have hypersensitivity to any ingredient of the IMP (Investigational Medicinal Product).
• Have received Electroconvulsive Therapy (ECT) within 12 weeks of enrollment.
• Have dementia.
• Have a history of or a current primary psychotic disorder assessed via the DIAMOND and clinical interview.
• Have a history of or current Bipolar 1 disorder, Bipolar 2 disorder, or manic episode assessed via the DIAMOND and clinical interview.
• Have a current eating disorder with active purging assessed via DIAMOND and clinical interview.
• Have current major depressive disorder with psychotic features assessed via DIAMOND.
• Have a current panic disorder assessed via the DIAMOND
• Have a history of amphetamine or cocaine substance use disorder

Sponsors & Collaborators

• Healing Breakthrough: lead
• San Diego Veterans Healthcare System: collaborator
• White River Junction VA Medical Center: collaborator
• National Center for PTSD: collaborator
• Lykos Therapeutics: collaborator

Study Sites (1)

VA San Diego Healthcare System, San Diego, CA

San Diego, California, 92161, United States

RECRUITING

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

N-Methyl-3,4-methylenedioxyamphetamine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Amphetamines; Phenethylamines; Ethylamines; Amines; Organic Chemicals

Study Officials

• Leslie Morland, Psy.D.

  San Diego Veterans Affairs Health System

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Leslie A Morland, Psy.D.

CONTACT

858-226-5765; Leslie.Morland@va.gov

Bettye Chargin

CONTACT

Bette.Chargin@va.gov

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Access to the randomization code will be strictly controlled and only available to the un-blinded VA San Diego Research Pharmacist.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: UNKNOWN
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. Leslie Morland

Model Details: Eligible participants will be randomized in a stratified 1:1 manner to receive a dose of MDMA (exact doses not disclosed).

Study Record Dates

• First Submitted: October 27, 2023
• First Posted: November 7, 2023
• Study Start: October 25, 2024
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): August 31, 2027
• Last Updated: April 24, 2026

Record last verified: 2026-04

Locations

US (1)