Study of Feasibility and Safety of MDMA-Assisted Group Therapy for the Treatment of PTSD in Veterans (MPG1)

An Open-Label Feasibility and Safety Study of MDMA-Assisted Group Therapy for the Treatment of Posttraumatic Stress Disorder in Veterans

The goal of this clinical trial is to learn if MDMA-assisted group therapy is safe and effective in in people with at least moderate PTSD.

The main question it aims to answer is: Do two sessions of open-label MDMA-assisted group therapy reduce PTSD symptoms?

Participants will undergo non-drug preparatory therapy sessions before their MDMA-assisted therapy sessions. After, they will undergo non-drug integrative therapy sessions.

Study Overview

• Status: Withdrawn
• Conditions: PTSD
• Intervention / Treatment: Drug: Midomafetamine; Behavioral: Therapy

Detailed Description

To further assess the feasibility and safety of MDMA-assisted group therapy for participants with at least moderate PTSD, the sponsor is conducting a Phase 2, open-label, non-randomized, 3-cohort study. This novel treatment package consists of two once-monthly Experimental Sessions of therapy combined with a divided-dose of MDMA (120 mg midomafetamine HCl and optional supplemental dose of 60 mg 1.5 to 2 hours later), along with non-drug preparatory and integrative therapy administered in both individual and group sessions.

The Primary Outcome measure, the Clinician Administered PTSD Scale (CAPS-5), evaluates changes in PTSD symptom severity and is assessed by a blinded centralized Independent Rater (IR) pool. The therapeutic approach will combine manualized MDMA-assisted therapy for PTSD with group therapy components.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

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 a U.S. Military Veteran
• 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, outcome assessments, and non-drug psychotherapy sessions.
• Must provide a contact 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 able to become pregnant, must have a negative pregnancy test at study entry and prior to each Experimental Session, and must agree to use adequate contraception through 10 days after the last Experimental Session.
• Must not participate in any other interventional clinical trials during the duration of the study.
• Have a current PTSD diagnosis at the time of screening.

Exclusion Criteria:

• Are not able to give adequate informed consent.
• Have uncontrolled hypertension.
• Have a marked baseline QTcF interval >450 milliseconds [ms] demonstrated on repeated ECG assessments.
• 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 or biliary disease.
• Have history of hyponatremia or hyperthermia.
• Weigh less than 48 kilograms (kg).
• Are pregnant or nursing, or are able to become pregnant and are not practicing an effective means of birth control.
• Have an active illicit drug or prescription drug substance use disorder

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Two Sessions of MDMA-assisted therapy; Two MDMA-assisted Therapy Sessions with 120 mg midomafetamine HCl and optional supplemental dose of 60 mg 1.5 to 2 hours later	Drug: Midomafetamine; Initial dose of 120 mg midomafetamine HCl and optional supplemental dose of 60 mg 1.5 to 2 hours later; Other Names: MDMA; 3,4-methylenedioxymethamphetamine; Behavioral: Therapy; Manualized therapy performed by therapist team

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in CAPS-5 Total Severity Score	The CAPS-5 is a semi-structured interview that assesses index history of DSM-5-defined traumatic event exposure [114], including the most distressing event, time since exposure, to produce a diagnostic score (presence vs. absence) and a PTSD Total Severity score [114]. The CAPS-5 rates intrusion symptoms (intrusive thoughts or memories), avoidance, cognitive and mood symptoms, arousal and reactivity symptoms, duration and degree of distress and dissociation. 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.	Baseline - 3 months from first Experimental Session

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Sheehan Disability Scale (SDS)	Sheehan Disability Scale (SDS) total score, a measure of clinician-rated functional impairment. The first three 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). The remaining two items assess Days Lost and Days Unproductive during the reporting period.	Baseline - 3 months from First Experimental Session

Collaborators and Investigators

• Sponsor: Lykos Therapeutics
• Investigators: Principal Investigator: Chris Stauffer, MD, Associate Professor of Psychiatry at Oregon Health & Science University

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2023
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: December 13, 2021
• First Submitted That Met QC Criteria: December 13, 2021
• First Posted (Actual): December 30, 2021

Study Record Updates

• Last Update Posted (Actual): October 30, 2024
• Last Update Submitted That Met QC Criteria: October 28, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Membrane Transport Modulators; Psychotropic Drugs; Adrenergic Agents; Neurotransmitter Uptake Inhibitors; Adrenergic Uptake Inhibitors; Serotonin Agents; Hallucinogens; N-Methyl-3,4-methylenedioxyamphetamine
• Other Study ID Numbers: MPG1

Drug and device information, study documents

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