A Randomized, Double-Blind, Dose Response Phase 2 Pilot Study of Manualized MDMA-Assisted Psychotherapy in Subjects With Chronic, Treatment-Resistant Posttraumatic Stress Disorder (PTSD)
Overview
- Phase
- Phase 2
- Intervention
- Psychotherapy
- Conditions
- Posttraumatic Stress Disorder
- Sponsor
- Lykos Therapeutics
- Enrollment
- 29
- Locations
- 1
- Primary Endpoint
- Change in Clinician Administered PTSD Scale for DSM-IV (CAPS-IV) Total Severity Score From Baseline to One Month Post 2nd Experimental Session
- Status
- Completed
- Last Updated
- 11 months ago
Overview
Brief Summary
The goal of this clinical trial is to learn if MDMA in combination with therapy is safe and effective in people with chronic, treatment-resistant PTSD.
The main questions it aims to answer are:
- Does MDMA-assisted therapy reduce PTSD symptoms?
- Is there a difference in PTSD symptoms between the 40 mg, 100 mg, and 125 mg groups?
Researchers will compare two active doses (100 mg and 125 mg) of MDMA-assisted therapy versus a comparator dose of 40 mg MDMA-assisted therapy to determine if there is a reduction in PTSD symptoms.
Participants will undergo three non-drug preparatory sessions, three MDMA-assisted therapy sessions and three non-drug integrative therapy sessions after each MDMA-assisted therapy session.
Detailed Description
This Phase 2 pilot study is a randomized, double-blind, dose response study to examine the safety and efficacy of MDMA-assisted psychotherapy in 23 subjects with chronic, treatment-resistant PTSD of at least six months duration. This study assessed two active doses of MDMA, active dose 1 (100 mg) and active dose 2 (125 mg), to a comparator dose of MDMA (40 mg) during psychotherapy sessions. The initial dose of MDMA was followed 1.5 to 2.5 hours later by an optional supplemental dose of MDMA that was half the size of the first dose. MDMA was administered orally in two experimental sessions lasting up to eight hours and scheduled three to five weeks apart. Subjects were prepared for MDMA-assisted psychotherapy in three preparatory sessions prior to the first experimental session, and worked with the same pair of therapists throughout the study. After each experimental session, three integrative sessions were scheduled with the subject, including one integrative session the morning after the experimental session. During integrative sessions, subjects processed and connected their thoughts and feelings about the experience with their therapist team. Subjects who received the comparator dose (40 mg) were given the option to enroll in Stage 2, where they underwent three open-label MDMA-assisted psychotherapy sessions. 100 mg of MDMA was administered in the first session and therapists determined whether to increase to 125 mg of MDMA for the second and third experimental sessions. People who received 125 mg of MDMA during the first two experimental sessions received the same dose during an open-label third experimental session. People who received 100 mg of MDMA during the first two sessions were able to choose, in consultation with their therapist, to either continue to receive 100 mg in a third session or to increase their dose to 125 mg. A blinded independent rater (IR) assessed the severity of PTSD symptoms at baseline, one month after the second experimental session (the primary endpoint), two months after the third open-label experimental session, and at equivalent points in Stage 2.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Diagnosed with chronic PTSD for six months or longer.
- •Have a CAPS score showing moderate to severe PTSD symptoms.
- •At least one unsuccessful attempt at treatment for PTSD either with talk therapy or with drugs, or discontinuing treatment because of inability to tolerate psychotherapy or drug therapy.
- •Are at least 18 years old.
- •Must be generally healthy.
- •Are willing to refrain from taking any psychiatric medications during the study period.
- •Willing to follow restrictions and guidelines concerning consumption of food, beverages or nicotine the night before and just prior to each MDMA session.
- •Willing to remain overnight at the study site.
- •Are willing to be driven home after experimental sessions either by a driver they arrange, a taxi, or study personnel.
- •Are willing to be contacted via telephone by study personnel.
Exclusion Criteria
- •Are pregnant or nursing, or if of child-bearing age and do not use an effective means of birth control.
- •Weigh less than 48 kg.
- •Meet DSM-IV criteria for substance abuse or dependence for any substance in the past 60 days.
- •Have used "Ecstasy" (material represented as containing MDMA) more than five times in the last ten years or at least once within 6 months of the MDMA session.
- •Are unable to give adequate informed consent.
- •Upon review of past and current drugs/medication, must not be on or have taken a medication that is exclusionary.
- •Upon review of medical or psychiatric history, must not have any current or past diagnosis that would be considered a risk to participation in the study.
Arms & Interventions
Active Dose 2 (100 mg) MDMA-assisted therapy
Participants receive an initial dose of Active Dose 2 midomafetamine HCl (100 mg) during each of two therapy sessions.
Intervention: Psychotherapy
Active Dose 1 (125 mg) MDMA-assisted therapy
Participants receive an initial dose of Active Dose 1 midomafetamine HCl (125 mg) during each of two therapy sessions.
Intervention: Active Dose 1 (125 mg) MDMA HCl
Comparator Dose (40 mg) MDMA-assisted therapy
Participants receive an initial dose of comparator dose midomafetamine HCl (40 mg) during each of two therapy sessions.
Intervention: Comparator Dose (40mg) MDMA HCl
Comparator Dose (40 mg) MDMA-assisted therapy
Participants receive an initial dose of comparator dose midomafetamine HCl (40 mg) during each of two therapy sessions.
Intervention: Psychotherapy
Active Dose 2 (100 mg) MDMA-assisted therapy
Participants receive an initial dose of Active Dose 2 midomafetamine HCl (100 mg) during each of two therapy sessions.
Intervention: Active Dose 2 (100 mg) MDMA HCl
Active Dose 1 (125 mg) MDMA-assisted therapy
Participants receive an initial dose of Active Dose 1 midomafetamine HCl (125 mg) during each of two therapy sessions.
Intervention: Psychotherapy
Outcomes
Primary Outcomes
Change in Clinician Administered PTSD Scale for DSM-IV (CAPS-IV) Total Severity Score From Baseline to One Month Post 2nd Experimental Session
Time Frame: Baseline Enrollment to 1-Month Post 2nd Experimental Session (Stage 1 Primary Endpoint)
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.
Secondary Outcomes
- Change in PTSD Diagnostic Scale (PDS) From Baseline to One Month Post 2nd Experimental Session(Baseline Enrollment to 1-Month Post 2nd Experimental Session (Stage 1 Primary Endpoint))
- Change in Beck Depression Inventory II (BDI-II) From Baseline to One Month Post 2nd Experimental Session(Baseline Enrollment to 1-Month Post 2nd Experimental Session (Stage 1 Primary Endpoint))
- Change in Global Assessment of Functioning (GAF) Total Score From Baseline to One Month Post 2nd Experimental Session(Baseline Enrollment to 1-Month Post 2nd Experimental Session (Stage 1 Primary Endpoint))
- Change in Pittsburgh Sleep Quality Index (PSQI) From Baseline to One Month Post 2nd Experimental Session(Baseline Enrollment to 1-Month Post 2nd Experimental Session (Stage 1 Primary Endpoint))
- Change in Dissociative Experiences Scale (DES-II) From Baseline to One Month Post 2nd Experimental Session(Baseline Enrollment to 1-Month Post 2nd Experimental Session (Stage 1 Primary Endpoint))
- Change in Posttraumatic Growth Inventory (PTGI) From Baseline to One Month Post 2nd Experimental Session(Baseline Enrollment to 1-Month Post 2nd Experimental Session (Stage 1 Primary Endpoint))