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

Primary Purpose

Post Traumatic Stress Disorder

Status

Not yet recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

3,4-methylenedioxymethamphetamine

d-amphetamine

Therapy

About this trial

This is an interventional treatment trial for Post Traumatic Stress Disorder focused on measuring MDMA, Post Traumatic Stress Disorder, PTSD, Functional Impairment, Veteran, Substance Use Disorder, Chronic Pain

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

VA Greater Los Angeles Healthcare System, Westwood campus

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

MDMA-Assisted Therapy

Low Dose D-Amphetamine Assisted Therapy

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

NCT ID

NCT05790239

First Posted

March 13, 2023

Last Updated

March 27, 2023

Sponsor

Stephen Robert Marder

1. Study Identification

Unique Protocol Identification Number

NCT05790239

Brief Title

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

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Not yet recruiting

Study Start Date

October 2023 (Anticipated)

Primary Completion Date

May 2025 (Anticipated)

Study Completion Date

March 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Stephen Robert Marder

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Post Traumatic Stress Disorder

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

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.

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

MDMA-Assisted Therapy

Arm Type

Experimental

Arm Description

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

Arm Title

Low Dose D-Amphetamine Assisted Therapy

Arm Type

Active Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

3,4-methylenedioxymethamphetamine

Other Intervention Name(s)

MDMA

Intervention Description

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).

Intervention Type

Drug

Intervention Name(s)

d-amphetamine

Intervention Description

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.

Intervention Type

Behavioral

Intervention Name(s)

Therapy

Intervention Description

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.

Primary Outcome Measure Information:

Title

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

Description

Time Frame

Visit 17 (approximately 14 weeks after enrollment)

Secondary Outcome Measure Information:

Title

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

Description

Time Frame

Visit 17 (approximately 14 weeks after enrollment)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Stephanie L Taylor, PhD

Phone

213-505-1140

Stephanie.Taylor8@va.gov

First Name & Middle Initial & Last Name or Official Title & Degree

Stephen Marder, MD

Stephen.Marder@va.gov

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Stephen Marder, MD

Organizational Affiliation

VA Greater Los Angeles Healthcare System

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Stephanie L Taylor, PhD

Organizational Affiliation

VA Greater Los Angeles Healthcare System

Official's Role

Principal Investigator

Facility Information:

Facility Name

VA Greater Los Angeles Healthcare System, Westwood campus

City

Los Angeles

State/Province

California

ZIP/Postal Code

90073

Country

United States

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Stephanie L Taylor, PhD

First Name & Middle Initial & Last Name & Degree

Stephen Marder, MD

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Some of the outcome data will be shared. The specific data to be shared has not yet been determined.

IPD Sharing Time Frame

6 months after all publications have been published.

IPD Sharing 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.

Citations:

PubMed Identifier

33972795

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.

Results Reference

background

PubMed Identifier

20643699

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. Erratum In: J Psychopharmacol. 2011 Jun;25(6):852.

Results Reference

background

PubMed Identifier

8788485

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.

Results Reference

background

Citation

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.

Results Reference

background

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

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