Study Comparing Two Versus Three Active MDMA-assisted Sessions in U.S. Military Veterans With Chronic PTSD (MPVA6)

A Phase 2, Open-Label, Randomized Comparative Effectiveness Study for MDMA-Assisted Psychotherapy in U.S. Veterans With Chronic PTSD

This open-label, randomized study will assess the comparative effectiveness of two versus three active MDMA-assisted sessions in U.S. military veterans with at least moderate chronic PTSD treated in an outpatient VA treatment clinic.

Study Overview

• Status: Active, not recruiting
• Conditions: PTSD
• Intervention / Treatment: Behavioral: Psychotherapy; Drug: Midomafetamine

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 change in CAPS-5 from Baseline, is assessed by a centralized, blinded Independent Rater (IR) pool at post-treatment for each group.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Bronx, New York, United States, 10468
      • James J. Peters VA Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.
• Are abusing illegal drugs.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Two sessions of MDMA-assisted therapy; Two experimental sessions of MDMA-assisted therapy	Behavioral: Psychotherapy; Standardized non-directive psychotherapy performed by therapist team; Drug: Midomafetamine; Administration of MDMA; Other Names: MDMA; 3,4-methylenedioxymethamphetamine
Active Comparator: Three sessions of MDMA-assisted therapy; Three experimental sessions of MDMA-assisted therapy	Behavioral: Psychotherapy; Standardized non-directive psychotherapy performed by therapist team; Drug: Midomafetamine; Administration of MDMA; Other Names: MDMA; 3,4-methylenedioxymethamphetamine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in CAPS-5 Total Severity Score from Baseline to Visit 12 for 2 Session Group	The Clinician-Administered PTSD Scale for DSM-IV (CAPS-IV) is a clinician administered and scored assessment of PTSD symptoms via structured interview based upon PTSD diagnosis in DSM-IV. It contains symptom subscales, a CAPS-IV total severity score, and a diagnostic score. The total severity score is a sum of symptom frequency and intensity scores for the subscales B (re-experiencing), C (avoidance) and D (hypervigilance) and ranges from 0 to 136, with higher scores indicating greater severity of PTSD symptoms. The dichotomous diagnostic score is based upon meeting each of five criteria, including index trauma, presence or absence of Criteria B, C, D described above, duration of symptoms and distress and is scored as meeting versus not meeting criteria for diagnosis.	Baseline - 3 months from enrollment
Change in CAPS-5 Total Severity Score from Baseline to Visit 16 for 3 Session Group	The Clinician-Administered PTSD Scale for DSM-IV (CAPS-IV) is a clinician administered and scored assessment of PTSD symptoms via structured interview based upon PTSD diagnosis in DSM-IV. It contains symptom subscales, a CAPS-IV total severity score, and a diagnostic score. The total severity score is a sum of symptom frequency and intensity scores for the subscales B (re-experiencing), C (avoidance) and D (hypervigilance) and ranges from 0 to 136, with higher scores indicating greater severity of PTSD symptoms. The dichotomous diagnostic score is based upon meeting each of five criteria, including index trauma, presence or absence of Criteria B, C, D described above, duration of symptoms and distress and is scored as meeting versus not meeting criteria for diagnosis.	Baseline - 4 months from enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Sheehan Disability Scale (SDS) from Baseline to Visit 12 for 2 Session Group	Sheehan Disability Scale (SDS) total score, a measure of clinician-rated functional impairment. The items indicate degree of impairment in the domains of work/school, social life, and home life, with response options based on an eleven-point scale (0=not at all to 10=extremely), and five verbal tags (not at all, mildly, moderately, markedly, extremely).	Baseline - 3 months from enrollment
Change in Sheehan Disability Scale (SDS) from Baseline to Visit 16 for 3 Session Group	Sheehan Disability Scale (SDS) total score, a measure of clinician-rated functional impairment. The items indicate degree of impairment in the domains of work/school, social life, and home life, with response options based on an eleven-point scale (0=not at all to 10=extremely), and five verbal tags (not at all, mildly, moderately, markedly, extremely).	Baseline - 4 months from enrollment

Collaborators and Investigators

• Sponsor: Lykos Therapeutics
• Investigators: Principal Investigator: Rachel Yehuda, Icahn School of Medicine at Mount Sinai

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2021
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): July 1, 2025

Study Registration Dates

• First Submitted: March 2, 2021
• First Submitted That Met QC Criteria: March 2, 2021
• First Posted (Actual): March 5, 2021

Study Record Updates

• Last Update Posted (Estimated): January 24, 2024
• Last Update Submitted That Met QC Criteria: January 22, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Hallucinogens; Adrenergic Uptake Inhibitors; N-Methyl-3,4-methylenedioxyamphetamine
• Other Study ID Numbers: MPVA6

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No