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

NCT05790239 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: IVAPT3
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

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.

Conditions

Post Traumatic Stress Disorder

Keywords

MDMA; Post Traumatic Stress Disorder; PTSD; Functional Impairment; Veteran; Substance Use Disorder; Chronic Pain

Outcome Measures

Primary Outcomes (1)

• Compare changes in PTSD symptom severity in the MDMA vs active control group.

  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.

  Visit 17 (approximately 14 weeks after enrollment)

Secondary Outcomes (1)

• Compare changes in clinician-rated functional impairment in the MDMA vs active control group.

  Visit 17 (approximately 14 weeks after enrollment)

Study Arms (2)

MDMA-Assisted Therapy

EXPERIMENTAL

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

Drug: 3,4-methylenedioxymethamphetamine; Behavioral: Therapy

Low Dose D-Amphetamine Assisted Therapy

ACTIVE COMPARATOR

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

Drug: d-amphetamine; Behavioral: Therapy

Interventions

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).

Also known as: MDMA

MDMA-Assisted Therapy

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.

Low Dose D-Amphetamine Assisted Therapy

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.

Low Dose D-Amphetamine Assisted Therapy; MDMA-Assisted Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Stephen Robert Marder: lead

Study Sites (2)

VA Greater Los Angeles Healthcare System, Westwood campus

Los Angeles, California, 90073, United States

NOT YET RECRUITING

West Los Angeles Veteran Affairs

Los Angeles, California, 90095, United States

RECRUITING

Related Publications (4)

• Mitchell JM, Bogenschutz M, Lilienstein A, Harrison C, Kleiman S, Parker-Guilbert K, Ot'alora G M, Garas W, Paleos C, Gorman I, Nicholas C, Mithoefer M, Carlin S, Poulter B, Mithoefer A, Quevedo S, Wells G, Klaire SS, van der Kolk B, Tzarfaty K, Amiaz R, Worthy R, Shannon S, Woolley JD, Marta C, Gelfand Y, Hapke E, Amar S, Wallach Y, Brown R, Hamilton S, Wang JB, Coker A, Matthews R, de Boer A, Yazar-Klosinski B, Emerson A, Doblin R. MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nat Med. 2021 Jun;27(6):1025-1033. doi: 10.1038/s41591-021-01336-3. Epub 2021 May 10.

  PMID: 33972795 BACKGROUND

• Mithoefer MC, Wagner MT, Mithoefer AT, Jerome L, Doblin R. The safety and efficacy of +/-3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study. J Psychopharmacol. 2011 Apr;25(4):439-52. doi: 10.1177/0269881110378371. Epub 2010 Jul 19.

  PMID: 20643699 BACKGROUND

• Grob CS, Poland RE, Chang L, Ernst T. Psychobiologic effects of 3,4-methylenedioxymethamphetamine in humans: methodological considerations and preliminary observations. Behav Brain Res. 1996;73(1-2):103-7. doi: 10.1016/0166-4328(96)00078-2.

  PMID: 8788485 BACKGROUND

• Ponte L, Jerome L, Hamilton S, Mithoefer MC, Yazar-Klosinski BB, Vermetten E, Feduccia AA. Sleep Quality Improvements After MDMA-Assisted Psychotherapy for the Treatment of Posttraumatic Stress Disorder. J Trauma Stress. 2021 Aug;34(4):851-863. doi: 10.1002/jts.22696. Epub 2021 Jun 10.

  PMID: 34114250 BACKGROUND

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic; Substance-Related Disorders; Chronic Pain

Interventions

N-Methyl-3,4-methylenedioxyamphetamine; Dextroamphetamine; Therapeutics

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders; Chemically-Induced Disorders; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Amphetamines; Phenethylamines; Ethylamines; Amines; Organic Chemicals; Amphetamine

Study Officials

• Stephen Marder, MD

  VA Greater Los Angeles Healthcare System

  PRINCIPAL INVESTIGATOR

• Stephanie L Taylor, PhD

  VA Greater Los Angeles Healthcare System

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stephanie L Taylor, PhD

CONTACT

213-505-1140; Stephanie.Taylor8@va.gov

Stephen Marder, MD

CONTACT

Stephen.Marder@va.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Co-Principal Investigator

Model Details: 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.

Study Record Dates

• First Submitted: March 13, 2023
• First Posted: March 30, 2023
• Study Start: March 1, 2025
• Primary Completion: March 1, 2026
• Study Completion: March 1, 2026
• Last Updated: March 28, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Time Frame: 6 months after all publications have been published.
• Access Criteria: Data will be available only to other researchers at the VA who have completed trials of MDMA for veterans' PTSD for consideration of a pooled analysis.

Locations

US (2)