Study of Safety and Effects of MDMA-assisted Therapy for Treatment of PTSD (NUMCAP1)

A Phase 2, Open Label Study of the Safety and Effectiveness of MDMA-assisted Therapy for Participants With Posttraumatic Stress Disorder

This Phase 2, Open Label study will provide supportive data on the safety and effectiveness of MDMA-assisted therapy in participants with posttraumatic stress disorder (PTSD). This study will be conducted at a single study site in Vancouver, BC. There will be at least 2 co-therapy pairs. The study will enroll up to 20 participants

The Preparatory Period will consist of three 90-minute non-drug Preparatory Sessions. A flexible divided dose of MDMA, will be administered during the Treatment Period with manualized therapy in up to two open-label Study Drug Sessions. During the Treatment Period, each Study Drug Session is followed by three 90-minute Integrative Sessions of non-drug therapy. The Study Drug Sessions are scheduled roughly 3 to 5 weeks apart.

Study Overview

• Status: Withdrawn
• Conditions: Posttraumatic Stress Disorder
• Intervention / Treatment: Drug: 3,4-methylenedioxymethamphetamine

Detailed Description

Posttraumatic stress disorder (PTSD) is a serious debilitating disorder that negatively impacts a person's daily life. PTSD is a stress-related psychiatric condition that may occur following a traumatic event such as war, disaster, sexual abuse, violence, terrorism, and accidents. PTSD negatively impacts a person's daily life, resulting in relationship difficulties, difficulty in finding and maintaining a job, reduced cognitive and psychosocial functioning, substance abuse, high-cost healthcare use, and increased depression and suicide risk. Available PTSD treatments, including medications and therapy, effectively treat only a fraction of people who try them for adequate dose and duration. People with PTSD can be treated with psychotherapies and pharmacotherapies. In the past decade, there has been a growing amount of research into medications and other methods that may augment the effectiveness of psychotherapy for PTSD

3,4-methylenedioxymethamphetamine is a drug that releases serotonin, norepinephrine and dopamine in the brain and indirectly increases levels of the neurohormones oxytocin, arginine vasopressin and cortisol. The combined neurobiological effects of MDMA increase compassion, reduce defenses and fear of emotional injury, and enhance communication and introspection. MDMA produces anxiolytic and prosocial effects, which counteract avoidance and hyperarousal in the context of therapy. A combined treatment of MDMA and therapy may be especially useful for treating PTSD.

This Phase 2, Open Label study will provide supportive data on the safety and effectiveness of MDMA-assisted therapy in participants with PTSD. This study will be conducted at a single study site in Vancouver, BC. There will be at least 2 co-therapy pairs. The study will enroll up to 20 participants.

The Preparatory Period will consist of three 90-minute non-drug Preparatory Sessions. A flexible divided dose of MDMA, will be administered during the Treatment Period with manualized therapy in up to two open-label Study Drug Sessions. During the Treatment Period, each Study Drug Session is followed by three 90-minute Integrative Sessions of non-drug therapy. The Study Drug Sessions are scheduled roughly 3 to 5 weeks apart.

• Study Type: Interventional
• Phase: Phase 2

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 a recognized language of the study site.
• Are able to swallow pills.
• Agree to have study visits recorded, including Study Drug Sessions and non-drug therapy sessions.
• Must 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.
• 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, 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: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MDMA-assisted therapy; Two sessions of MDMA-assisted therapy with flexible dose of MDMA from 80 mg initial dose and optional supplemental dose half that of initial dose 1.5 to 2 hours later	Drug: 3,4-methylenedioxymethamphetamine; Behavioral: Therapy; Other Names: MDMA; midomafetamine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in PTSD Checklist (adapted PCL-5) total score	20-item self-report questionnaire in which respondents indicate the presence and severity of PTSD symptoms, derived from the symptoms of PTSD per DSM-5. The gold standard for diagnosing PTSD is a structured clinical interview such as the Clinician-Administered PTSD Scale (CAPS-5). When necessary, the PCL-5 can be scored to provide a provisional PTSD diagnosis.The self-report rating scale is 0-4 for each symptom, reflecting a change from 1-5 in the DSM-IV version. Rating scale descriptors are the same: "Not at all," "A little bit," Moderately," "Quite a bit," and "Extremely."	18 weeks post baseline post enrollment confirmation

Collaborators and Investigators

• Sponsor: Lykos Therapeutics

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2022
• Primary Completion (Estimated): August 1, 2023
• Study Completion (Estimated): August 1, 2023

Study Registration Dates

• First Submitted: July 9, 2021
• First Submitted That Met QC Criteria: July 9, 2021
• First Posted (Actual): July 20, 2021

Study Record Updates

• Last Update Posted (Actual): 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: Mental Disorders; Trauma and Stressor Related Disorders; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; 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: NUMCAP1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We will share outcome data appearing in any published reports upon request.
• IPD Sharing Time Frame: Data and study-related documents will be available when the database has been locked and data has been unblinded.
• IPD Sharing Access Criteria: Interested persons should correspond with the central contact for the multisite study.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

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