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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.
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:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MDMA-Assisted Therapy | Experimental | Participants will receive a flexible divided-dose of MDMA plus therapy at Experimental Sessions. |
|
| Low Dose D-Amphetamine Assisted Therapy | Active Comparator | Participants will receive a flexible divided dose plus therapy at Experimental Sessions. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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). |
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| Compare changes in clinician-rated functional impairment in the MDMA vs active control group. | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Stephanie L Taylor, PhD | Contact | 213-505-1140 | Stephanie.Taylor8@va.gov | |
| Stephen Marder, MD | Contact | Stephen.Marder@va.gov |
| Name | Affiliation | Role |
|---|---|---|
| Stephen Marder, MD | VA Greater Los Angeles Healthcare System | Principal Investigator |
| Stephanie L Taylor, PhD | VA Greater Los Angeles Healthcare System | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| VA Greater Los Angeles Healthcare System, Westwood campus | Not yet recruiting | Los Angeles | California | 90073 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33972795 | Background | 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. | |
| 20643699 |
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Some of the outcome data will be shared. The specific data to be shared has not yet been determined.
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6 months after all publications have been published.
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.
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| ID | Term |
|---|---|
| D013313 | Stress Disorders, Post-Traumatic |
| D019966 | Substance-Related Disorders |
| D059350 | Chronic Pain |
| ID | Term |
|---|---|
| D040921 | Stress Disorders, Traumatic |
| D000068099 | Trauma and Stressor Related Disorders |
| D001523 | Mental Disorders |
| D064419 | Chemically-Induced Disorders |
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| ID | Term |
|---|---|
| D018817 | N-Methyl-3,4-methylenedioxyamphetamine |
| D003913 | Dextroamphetamine |
| D013812 | Therapeutics |
| ID | Term |
|---|---|
| D000662 | Amphetamines |
| D010627 | Phenethylamines |
| D005021 | Ethylamines |
| D000588 | Amines |
| D009930 |
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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.
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|
| 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. |
|
| Visit 17 (approximately 14 weeks after enrollment) |
| West Los Angeles Veteran Affairs | Recruiting | Los Angeles | California | 90095 | United States |
|
| 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. |
| 8788485 | 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. |
| Background | Mithoefer, M., A Manual for MDMA-Assisted Psychotherapy in the Treatment of Posttraumatic Stress Disorder; Version 8.1. 2017: http://www.maps.org/research/mdma/mdma-research-timeline/4887-a-manual-for-mdma-assisted-psychotherapy-in-the-treatment-of-ptsd. |
| D010146 | Pain |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Organic Chemicals |
| D000661 | Amphetamine |