MDMA-Assisted Therapy for Veterans With Moderate to Severe Post Traumatic Stress Disorder

Therapy

Brief Summary

This randomized, double-blind, single-site phase II 2-arm study will investigate the safety and preliminary efficacy of MDMA-assisted therapy compared with low dose d-amphetamine-assisted therapy on the severity of PTSD symptoms in participants aged 18 years and older with PTSD of at least moderate severity.

Intervention / Treatment

This is a randomized study. Participants will be 1:1 randomized to receive either MDMA or d-amphetamine. Stratified randomization will be used, with gender as the stratification variable. Within each of the two strata, the investigators use permuted randomized blocks with a block size of 4.
  • 3,4-methylenedioxymethamphetamine (DRUG)
    Initial doses per Experimental Session include 68 mg or 100 mg MDMA (equivalent to 80 mg or 120 mg MDMA HCl), followed 1.5 to 2 hours later by a supplemental dose of 34 mg or 50 mg MDMA (equivalent to 40 mg or 60 mg MDMA HCl).
  • d-amphetamine (DRUG)
    Initial dose per experimental session will be 5 mg or 10 mg d-amphetamine, followed 1.5 to 2 hours later by supplemental dose of 2.5 mg or 5 mg d-amphetamine.
  • Therapy (BEHAVIORAL)
    Participants assigned to MDMA and d-amphetamine will undergo a therapeutic approach, which is detailed in the MDMA-Assisted Therapy Treatment Manual and administered by MAPS-trained therapists. In brief, this therapy is guided by the subject's own recollections of traumatic events. The subject and two therapists provide a comfortable and supportive environment and allow the subject to guide the discussion. Subjects are encouraged to experience and express fear, anger, and grief with less likelihood of feeling overwhelmed by these emotions. MDMA seems to engender internal awareness that even painful feelings that arise are an important part of the therapeutic process. In addition, feelings of empathy, love, and deep appreciation often emerge, along with a clearer perspective of the trauma as a past event, a more accurate perspective about its significance, and a heightened awareness of the support and safety that exists in the present.

Condition or Disease

  • Post Traumatic Stress Disorder

Phase

  • Phase 2

    • Study Design

    Study type: INTERVENTIONAL
    Status: Not yet recruiting
    Study results: No Results Available
    Enrollment: 40 (ESTIMATED)
    Allocation: Randomized
    Primary Purpose: Treatment

    Masking

    TRIPLE:
    • Participant
    • Care Provider
    • Investigator

    Clinical Trial Dates

    Start date: Oct 01, 2023 ESTIMATED
    Primary Completion: May 01, 2025 ESTIMATED
    Completion Date: Mar 01, 2026 ESTIMATED
    Study First Posted: Mar 30, 2023 ACTUAL
    Last Updated: Mar 27, 2023

    Sponsors / Collaborators

    Lead Sponsor: N/A
    Responsible Party: N/A

    This randomized, double-blind, single-site phase II 2-arm study will compare MDMA-assisted therapy with low dose d-amphetamine-assisted therapy to treat PTSD symptoms in veteran participants aged 18 years and older with PTSD of at least moderate severity, as measured by the change in CAPS-5 total severity score. The study will be conducted in up to N=40 participants from the Greater Los Angeles VA randomized with a 1:1 allocation to Group 1: MDMA-assisted therapy or Group 2: low dose d-amphetamine assisted therapy.

    For each participant, the study will consist of:

    * Screening Period: phone screen, informed consent, eligibility assessment, Screening CAPS-5, and Initial Enrollment of eligible participants.
    * Preparatory Period: medication tapering, three Preparatory Sessions, baseline assessments (including Baseline CAPS-5), leading to Enrollment Confirmation.
    * Treatment Period: three Experimental Sessions, and three Integrative Sessions following each Experimental Session including CAPS-5 assessments.
    * Follow-up Period and Study Termination: Primary Outcome CAPS-5 assessment and Study Termination visit.

    Participant Groups

    • Participants will receive a flexible divided-dose of MDMA plus therapy at Experimental Sessions.

    • Participants will receive a flexible divided dose plus therapy at Experimental Sessions.

    Eligibility Criteria

    Sex: All
    Minimum Age: 18
    Age Groups: Adult / Older Adult
    Healthy Volunteers: Yes

    Inclusion Criteria:

    * At Screening, meet DSM-5 criteria for current PTSD with a symptom duration of at least 6 months.
    * Fluent in speaking and reading the predominantly used or recognized language of the study site (English).
    * Must be a veteran enrolled at a VA Healthcare Center in the Greater Los Angeles area.
    * Able to swallow pills.
    * Agree to have study visits audiovisually recorded, including Experimental Sessions, IR assessments, and non-drug therapy sessions.
    * Able to 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 the participant becoming unwell or unreachable.
    * Able to identify appropriate support person(s) to stay with the participant on the evenings of Experimental Sessions if needed.
    * 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.
    * Body weight of at least 45 kilograms (kg). Participants with a body weight of 45-48 kg must also have a body mass index (BMI) within the range of 18 to 30 kg/m2. BMI must be within 18 to 32 kg/m2 (inclusive).
    * A person able to be pregnant (PABP) must use a highly effective contraceptive method.

    Exclusion Criteria:

    * Are not able to give adequate informed consent.
    * Have evidence or history of significant medical or psychiatric disorders.
    * Are abusing illegal drugs.
    * Unable or unwilling to safely taper off prohibited psychiatric medication.
    * Current enrollment in any other clinical study involving an investigational study treatment or any other type of medical research, unless approved by the study clinician.

    Primary Outcomes

    • The Primary Outcome measure will be the change in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) Total Severity Score from Baseline to Visit 17, assessed by a blinded study staff rater. 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

    • The secondary outcome measure will be the change in the Sheehan Disability Scale (SDS), assessed by a blinded study staff rater. The SDS is a 5-item measure of functional impairment. The items indicate the degree of impairment in the domains of work/school, social life, and home life, with response options based on a 10-point scale (0=not at all to 10=extremely), and five verbal tags (not at all, mildly, moderately, markedly, extremely). The first three items indicate the degree of impairment in the domains of work/school, social life, and home life, with response options based on a 10-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. The three numerical items can be scored, and total scores range from 0 to 30, with higher scores indicating higher impairment.

    More Details

    NCT Number: NCT05790239
    Other IDs: IVAPT3
    Study URL: https://clinicaltrials.gov/study/NCT05790239
    Last updated: Sep 29, 2023