Clinical trial NCT00090064: MDMA-Assisted Psychotherapy in People With Posttraumatic Stress Disorder
Official title: Phase II Clinical Trial Testing the Safety and Efficacy of 3,4-Methylenedioxymethamphetamine (MDMA)-Assisted Psychotherapy in Subjects With Chronic Posttraumatic Stress Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Posttraumatic Stress Disorder
Keywords: MDMA
Methylenedioxymethamphetamine
PTSD
psychotherapy
midomafetamine
Lead sponsor: Lykos Therapeutics
Sponsor class: INDUSTRY
First posted: 2004-08-25
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to compare MDMA-assisted therapy to placebo with therapy in people with chronic, treatment-resistant posttraumatic stress disorder (PTSD). The main question it aims to answer is: Is there a reduction in PTSD symptoms among people given MDMA-assisted therapy compared to placebo with therapy?

Participants will receive either MDMA-assisted therapy or placebo with therapy during two blinded experimental sessions spaced three to five weeks apart. During experimental sessions, participants receive an initial dose of 125 mg of MDMA HCl, or placebo, followed by a dose of 62.5 mg of MDMA HCl, or placebo. During this treatment period, participants will also undergo non-drug preparatory psychotherapy sessions and non-drug integrative sessions.

The study will test whether MDMA-assisted therapy can be safely given to participants. Researchers will compare PTSD symptoms in the MDMA-assisted therapy group to the placebo with therapy group to see if there is a reduction in symptoms after the treatment period.

Detailed description: This randomized, double-blind placebo-controlled pilot study assessed the safety and effectiveness of MDMA-assisted therapy among people with chronic, treatment-resistant PTSD, including veterans. Participants were assigned to receive either MDMA-assisted therapy or placebo with therapy during two blinded experimental sessions spaced three to five weeks apart during Stage 1 of the study. During these experimental sessions, participants received an initial dose of 125 mg of MDMA HCl followed by a supplemental dose of 62.5 mg of MDMA HCl, or they received initial and supplemental doses of inactive placebo. Psychotherapists and independent raters were blinded to participants' treatment conditions. This treatment period also consisted of non-drug preparatory therapy sessions and non-drug integration therapy sessions.

During Stage 2 of the study, the blind was broken and participants assigned to receive MDMA-assisted therapy in Stage 1 underwent a third open-label experimental session of MDMA-assisted therapy. Participants assigned placebo with therapy during Stage 1 who chose to enroll in Stage 2 underwent three open-label sessions of MDMA-assisted therapy. Outcome measures were administered two months after the second experimental session in Stage 1 and four to six weeks after the second MDMA-assisted therapy session in Stage 2. A final data-collection session took place at two months after the third experimental session.

The primary objective of the study was to measure change in PTSD symptoms via CAPS-IV across the study in participants receiving MDMA-assisted therapy versus placebo with therapy.

Eligibility criteria: Inclusion Criteria:

* Have current PTSD (within the past 6 months) in response to crime victimization, including childhood sexual or physical abuse, or meet criteria for PTSD in response to combat;
* Have a CAPS score showing moderate to severe PTSD symptoms;
* They must either:

  1. Have had at least one unsuccessful attempt at treatment for PTSD with a SSRI and psychotherapy;
  2. Be a veteran with PTSD symptoms that have endured for no less than one year but no more than five years
* Be at least 18 years old;
* Must be generally healthy;
* Willing to remain overnight at the study site;
* Agree to have transportation home the morning after experimental sessions;
* Are willing to be contacted via telephone for all necessary telephone contacts;
* Must have a negative pregnancy test if able to bear children and agree to use an effective form of birth control;
* Are proficient in reading English;

Exclusion Criteria:

* Are pregnant or nursing, or are able to bear children and are not practicing an effective means of birth control;
* Weigh less than 50 kg or more than 105 kg;
* Are unable to give adequate informed consent;
* Prior use of "Ecstasy" (illicit drug preparations purported to contain MDMA) more than 5 times or at any time within the previous 6 months;
* Have a history of certain excluded medical disorders.

Primary outcomes:
measure: Change in Clinician-Administered PTSD Scale (CAPS-IV) From Baseline to 2-month Follow-up
timeFrame: Baseline to 2 months post second experimental session
Secondary outcomes:
measure: Change in Impact of Events Scale Revised (IES-R) From Baseline to 2-month Follow-up
timeFrame: Baseline to 2 months post second experimental session
Other outcomes:
Locations:
city: Mount Pleasant
country: United States
facility: Offices of Michael Mithoefer MD
state: South Carolina
Study officials:
affiliation: Private Practice
name: Michael Mithoefer, MD
role: PRINCIPAL_INVESTIGATOR
References:
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: Mithoefer MC, Wagner MT, Mithoefer AT, Jerome L, Martin SF, Yazar-Klosinski B, Michel Y, Brewerton TD, Doblin R. Durability of improvement in post-traumatic stress disorder symptoms and absence of harmful effects or drug dependency after 3,4-methylenedioxymethamphetamine-assisted psychotherapy: a prospective long-term follow-up study. J Psychopharmacol. 2013 Jan;27(1):28-39. doi: 10.1177/0269881112456611. Epub 2012 Nov 20.
citation: Jerome L, Feduccia AA, Wang JB, Hamilton S, Yazar-Klosinski B, Emerson A, Mithoefer MC, Doblin R. Long-term follow-up outcomes of MDMA-assisted psychotherapy for treatment of PTSD: a longitudinal pooled analysis of six phase 2 trials. Psychopharmacology (Berl). 2020 Aug;237(8):2485-2497. doi: 10.1007/s00213-020-05548-2. Epub 2020 Jun 4.
citation: Feduccia AA, Jerome L, Yazar-Klosinski B, Emerson A, Mithoefer MC, Doblin R. Breakthrough for Trauma Treatment: Safety and Efficacy of MDMA-Assisted Psychotherapy Compared to Paroxetine and Sertraline. Front Psychiatry. 2019 Sep 12;10:650. doi: 10.3389/fpsyt.2019.00650. eCollection 2019.
citation: Mithoefer MC, Feduccia AA, Jerome L, Mithoefer A, Wagner M, Walsh Z, Hamilton S, Yazar-Klosinski B, Emerson A, Doblin R. MDMA-assisted psychotherapy for treatment of PTSD: study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials. Psychopharmacology (Berl). 2019 Sep;236(9):2735-2745. doi: 10.1007/s00213-019-05249-5. Epub 2019 May 7.