Clinical trial NCT03537014: A Multi-Site Phase 3 Study of MDMA-Assisted Psychotherapy for PTSD (MAPP1)
Official title: A Randomized, Double-Blind, Placebo-Controlled, Multi-Site Phase 3 Study of the Efficacy and Safety of Manualized MDMA-Assisted Psychotherapy for the Treatment of Severe Posttraumatic Stress Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Posttraumatic Stress Disorder
Lead sponsor: Lykos Therapeutics
Sponsor class: INDUSTRY
First posted: 2018-05-25
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double-blind, between-group comparison of change in PTSD symptoms
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to learn if MDMA-assisted therapy is safe and effective in people with at least severe PTSD.

The main question it aims to answer is: Do three sessions of MDMA-assisted therapy reduce PTSD symptoms?

Researchers will compare three sessions of MDMA-assisted therapy with an initial dose of 80 to 120 mg to three sessions of placebo with therapy.

Participants will undergo three preparatory sessions without any study drug, followed by three MDMA-assisted therapy or placebo with therapy sessions. Each medication session will be followed by three integrative therapy sessions without study drug.

Detailed description: This multi-site, double-blind, placebo-controlled, randomized Phase 3 study will assess the efficacy and safety of MDMA-assisted therapy versus placebo with therapy in participants diagnosed with at least severe PTSD. The study will be conducted in N ≈ 100 participants. Participants will be randomized to one of two groups at a 1:1 ratio. An initial dose of midomafetamine HCl or placebo, followed by a supplemental half-dose unless contraindicated, is administered during the Treatment Period with manualized therapy in three monthly Experimental Sessions. This \~12-week Treatment Period is preceded by three Preparatory Sessions. During the Treatment Period, each Experimental Session is followed by three Integrative Sessions of non-drug psychotherapy. Initial doses per Experimental Session include 80 mg or 120 mg of midomafetamine HCl or placebo followed 1.5 to 2 hours later by a supplemental half-dose (40 or 60 mg). Total amounts of midomafetamine HCl to be administered per Experimental Session range from 80 mg to 180 mg.

The primary endpoint is change from baseline in Clinician Administered PTSD Scale for DSM-V (CAPS-5) to 18 weeks post-Baseline. Drug safety will be assessed by measuring blood pressure, heart rate and body temperature during Experimental Sessions, collecting adverse events and measuring suicidal thoughts or behaviors with the Columbia Suicide Severity Rating Scale (adapted C-SSRS).

Eligibility criteria: Inclusion Criteria:

* Are at least 18 years old
* Are fluent in speaking and reading the predominantly used or recognized language of the study site
* Are able to swallow pills
* Agree to have study visits recorded, including Experimental Sessions, Independent Rater assessments, and non-drug psychotherapy sessions
* Must provide a contact (relative, spouse, close friend or other caregiver) who is willing and able to be reached by the investigators in the event of a participant becoming suicidal or unreachable.
* Must agree to inform the investigators within 48 hours of any medical conditions and procedures
* If of childbearing potential, must have a negative pregnancy test at study entry and prior to each Experimental Session, and must agree to use adequate birth control through 10 days after the last Experimental Session.
* Must not participate in any other interventional clinical trials during the duration of the study
* Must be willing to remain overnight at the study site after each Experimental Session and be driven home after, and commit to medication dosing, therapy, and study procedures
* At baseline, meet DSM-5 criteria for current severe PTSD

Exclusion Criteria:

* Are not able to give adequate informed consent
* Have uncontrolled hypertension
* Have a marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval \>450 milliseconds \[ms\] in males and \>460 ms in females corrected by Bazett's formula)
* Have a history of additional risk factors for Torsade de pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)
* Have evidence or history of significant medical disorders, such as myocardial infarction, cerebrovascular accident, or aneurysm
* Have symptomatic liver disease
* Have history of hyponatremia or hyperthermia
* Weigh less than 48 kilograms (kg)
* Are pregnant or nursing, or are of childbearing potential and are not practicing an effective means of birth control
* Have an active illicit or prescription drug use disorder
* Have used Ecstasy (material represented as containing MDMA) more than 10 times within the last 10 years or at least once within 6 months of the first Experimental Session; or have previously participated in a MAPS-sponsored MDMA clinical trial.

Primary outcomes:
measure: Change From Baseline to Primary Endpoint in Clinician Administered PTSD Scale for DSM-V (CAPS-5)
timeFrame: Baseline to 18 weeks post enrollment confirmation
Secondary outcomes:
measure: Change From Baseline to Primary Endpoint in Sheehan Disability Scale (SDS) Total Score
timeFrame: Baseline to 18 weeks post enrollment confirmation
Other outcomes:
Locations:
city: North Hollywood
country: United States
facility: New School Research LLT
state: California
city: San Francisco
country: United States
facility: San Francisco Insight and Integration Center
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Boulder
country: United States
facility: Aguazul-Blue Water Inc.
state: Colorado
city: Fort Collins
country: United States
facility: Wholeness Center
state: Colorado
city: New Orleans
country: United States
facility: Ray Worthy Psychiatry LLC
state: Louisiana
city: Boston
country: United States
facility: Trauma Research Foundation
state: Massachusetts
city: New York
country: United States
facility: New York University
state: New York
city: New York
country: United States
facility: New York Private Practice
state: New York
city: Mount Pleasant
country: United States
facility: Zen Therapeutic Solutions, LLC
state: South Carolina
city: Madison
country: United States
facility: University of Wisconsin at Madison
state: Wisconsin
city: Vancouver
country: Canada
facility: Providence Health Center
state: British Columbia
city: Montreal
country: Canada
facility: Dr. Simon Amar, Inc.
state: Quebec
city: Be'er Ya'akov
country: Israel
facility: Assaf Harofeh Research Fund
city: Tel HaShomer
country: Israel
facility: Sheba Fund for Health Services and Research
Study officials:
affiliation: Affective Care
name: Casey Paleos, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Trauma Research Foundation
name: Bessel van der Kolk, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dr. Simon Amar, Inc.
name: Emma Hapke, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Chaim Sheba Medical Center, Tel Hashomer Hospital
name: Revital Amiaz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: New York University/Langone Medical Center/Bellevue Hospital
name: Michael Bogenschutz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Wisconsin, Madison
name: Randall Brown, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: San Francisco Insight and Integration Center
name: Sylvestre Quevedo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Francisco
name: Josh Woolley, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ray Worthy Psychiatry, LLC
name: Ray Worthy, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: New School Research, LLC
name: Cole Marta, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Wholeness Center
name: Scott Shannon, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Aguazul-Bluewater, Inc.
name: Wael Garas, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Zen Therapeutics Solutions, LLC
name: Yevgeniy Gelfand, MD
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.