Clinical trial NCT05790239: MDMA-Assisted Therapy for Veterans With Moderate to Severe Post Traumatic Stress Disorder
Official title: A Randomized, Double-Blind, Single-Site Phase II 2-Arm Study to Compare the Safety and Preliminary Efficacy of Manualized MDMA-Assisted Therapy to Low Dose D-Amphetamine Assisted Therapy in Veterans For The Treatment of Moderate to Severe PTSD
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Post Traumatic Stress Disorder
Keywords: MDMA
Post Traumatic Stress Disorder
PTSD
Functional Impairment
Veteran
Substance Use Disorder
Chronic Pain
Lead sponsor: VA Greater Los Angeles Healthcare System
Sponsor class: FED
First posted: 2023-03-30
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: TREATMENT

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.

Detailed description: 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.

Eligibility criteria: 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:
measure: Compare changes in PTSD symptom severity in the MDMA vs active control group.
timeFrame: Visit 17 (approximately 14 weeks after enrollment)
Secondary outcomes:
measure: Compare changes in clinician-rated functional impairment in the MDMA vs active control group.
timeFrame: Visit 17 (approximately 14 weeks after enrollment)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: VA Greater Los Angeles Healthcare System, Westwood campus
state: California
city: Los Angeles
country: United States
facility: West Los Angeles Veteran Affairs
state: California
Study officials:
affiliation: VA Greater Los Angeles Healthcare System
name: Stephen Marder, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: VA Greater Los Angeles Healthcare System
name: Stephanie L Taylor, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.