Study of 3,4-Methylenedioxymethamphetamine-assisted Psychotherapy in People With Posttraumatic Stress Disorder

• ClinicalTrials.gov Identifier: NCT00353938
• Recruitment Status: Completed
• First Posted: July 19, 2006
• Last Update Posted: March 28, 2017
• Sponsor: Multidisciplinary Association for Psychedelic Studies
• Collaborator: Swiss Medical Association for Psycholytic Therapy
• Information provided by (Responsible Party): Multidisciplinary Association for Psychedelic Studies

Tracking Information

• First Submitted Date: July 17, 2006
• First Posted Date: July 19, 2006
• Last Update Posted Date: March 28, 2017
• Study Start Date: October 2006
• Actual Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: February 3, 2009): Clinician Administered PTSD Scale (CAPS [ Time Frame: baseline, three weeks post-experimental session 2, three weeks post-experimental session 3, two, six and 12 months post-experimental session 3 ]
• Original Primary Outcome Measures (submitted: July 17, 2006): Clinician Administered PTSD Scale (CAPS)- baseline, three weeks post-experimental session 2, three weeks post-experimental session 3, 2 months post-experimental session 3, six months post-experimental session 3, and 12 months post experimental session 3.

Current Secondary Outcome Measures (submitted: February 3, 2009)

• Posttraumatic Diagnostic Scale (PDS) [ Time Frame: - baseline, three weeks post experimental session 2, three weeks post-experimental session 3, 2, 6 and 12 months post-experimental session 3 ]
• Reactions to Research Participation Questionnaire (RRPQ) - 12 months post-experimental session 3; in Phase II participants, 12 months post-MDMA session 3 [ Time Frame: 2 months post-experimental session 3; in Phase II participants, 12 months post-MDMA session 3 ]
• Subjective Units of Distress (SUD) [ Time Frame: During each of three experimental sessions, and, if applicable, during each of three Phase II MDMA-assisted session ]
• EEG and ERP with acoustic startle - [ Time Frame: baseline, three weeks post experimental session 3 ]

Original Secondary Outcome Measures (submitted: July 17, 2006)

• SCID-II - at baseline, screening measure
• Posttraumatic Diagnostic Scale - baseline, three weeks post experimental session 2, three weeks post-experimental session 3, 2, 6 and 12 months post-experimental session 3
• Reactions to Research Participation Questionnaire (RRPQ) - 12 months post-experimental session 3; in Phase II participants, 12 months post-MDMA session 3
• Subjective Units of Distress (SUD) - During each of three experimental sessions, and, if applicable, during each of three Phase II MDMA-assisted session

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of 3,4-Methylenedioxymethamphetamine-assisted Psychotherapy in People With Posttraumatic Stress Disorder
• Official Title: Phase II Pilot Randomized Double-Blind Placebo-Controlled Study of 3,4-methylenedioxymethamphetamine (MDMA)Assisted Psychotherapy in Posttraumatic Stress Disorder (PTSD)- Switzerland
• Brief Summary: This study will look at the safety and efficacy of MDMA-assisted psychotherapy in people with posttraumatic stress disorder (PTSD).

Detailed Description

Posttraumatic stress disorder (PTSD) occurs after experiencing a traumatic event or events. PTSD is a public health problem that causes a great deal of suffering. This study will examine whether three six to eight-hour long sessions of methylenedioxymethamphetamine (MDMA)-assisted psychotherapy scheduled three to five weeks apart can be safely administered to participants with PTSD, and whether combining a fully therapeutic dose of MDMA with psychotherapy, when compared with a low ("active placebo") dose of MDMA, will reduce PTSD symptoms, with symptoms measured three times during the study. People who receive the low dose of MDMA have the opportunity to take part in a second "open label" study continuation, wherein the participant will undergo three MDMA-assisted sessions, with the participant and the researchers knowing that a full dose of MDMA is being administered. People who receive the full dose of MDMA, and any person who received low-dose MDMA and does not undergo the open-label study continuation will have PTSD symptoms measured six and twelve months after the third session. People who take part in the open label study continuation have their PTSD symptoms checked six and 12 months after the third Phase II MDMA-assisted session.

MDMA is a substance possessing unique effects that make it well suited to intensive psychotherapy. MDMA may belong to a new class of drugs, called entactogens, that produce feelings of closeness to others, empathy, well being, and insightfulness. Currently, MDMA is scheduled (illegal) in the US and Switzerland and cannot be used outside of research studies like this one. Anecdotal reports of therapy conducted before MDMA was made illegal suggest that MDMA-assisted psychotherapy may benefit people with PTSD, and there is an ongoing placebo-controlled study of MDMA-assisted psychotherapy in people with crime or war-related PTSD occurring in the US.

This study will examine MDMA-assisted psychotherapy in 12 individuals aged 18 years or older diagnosed with PTSD, with PTSD symptoms not improving after trying at least one treatment. Eight of 12 participants will be assigned to receive the full dose of MDMA, and four will be assigned to receive a low or "active placebo" dose of MDMA during each of three experimental sessions. People will be assigned to full or low-dose MDMA "by chance," as by flipping a coin.

The study will last approximately four and a half months. In addition, people assigned to receive full-dose MDMA will have their PTSD symptoms measured six and 12 months later. The study involves up to eleven ordinary psychotherapy visits, without any MDMA, and three low or full-dose MDMA-assisted sessions. One psychotherapy session is scheduled 24 hours after each MDMA-assisted session.

PTSD symptoms will be measured at the start of the study, three weeks after the second of three low or full-dose MDMA sessions, three weeks after the third low or full-dose MDMA session (approximately six weeks after the second session), two months after the third experimental session, and six and 12 months after either the third experimental session, or, if enrolled in Phase II, six and 12 months after the third open-label MDMA-assisted therapy session. Participants will undergo EEG (measuring brain waves) in combination with ERP (evoked response potential) technique before and after MDMA-assisted therapy that aim at spotting specific changes in brain function and structure that might be related to problems with early information processing, for which people with PTSD are known to have difficulties.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Posttraumatic Stress Disorder

Intervention

• Drug: 3,4-methylenedioxymethamphetamine 125 mg
  Participants will receive an initial dose of 125 mg MDMA orally and, if investigator and participant deem appropriate, 2-2.5 hours later they receive 62.5 mg MDMA orally.
  Other Name: MDMA
• Drug: 3,4-methyelendioxymethamphetamine 25 mg
  Participants will receive a 25 mg MDMA and if investigator and participant agree, 2 to 2.5 hours later a dose of 12.5 mg MDMA.
  Other Name: MDMA
• Behavioral: Psychotherapy
  Psychotherapy performed by a team of two co-therapists

Study Arms

• Experimental: 3,4-methylenedioxymethamphetamine 125 mg & Psychotherapy
  3,4-methylenedioxymethamphetamine 125 and 62.5 m
  Interventions:

  • Drug: 3,4-methylenedioxymethamphetamine 125 mg
  • Behavioral: Psychotherapy
• Active Comparator: 3,4-methyelendioxymethamphetamine 25 mg & Psychotherapy
  3,4-methylenedioxymethamphetamine 25 and 12.5 mg MDMA
  Interventions:

  • Drug: 3,4-methyelendioxymethamphetamine 25 mg
  • Behavioral: Psychotherapy

Publications *

• Oehen P, Traber R, Widmer V, Schnyder U. A randomized, controlled pilot study of MDMA (± 3,4-Methylenedioxymethamphetamine)-assisted psychotherapy for treatment of resistant, chronic Post-Traumatic Stress Disorder (PTSD). J Psychopharmacol. 2013 Jan;27(1):40-52. doi: 10.1177/0269881112464827. Epub 2012 Oct 31.
• 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.
• 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. Review.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 22, 2014): 14
• Original Enrollment (submitted: July 17, 2006): 12
• Actual Study Completion Date: February 2011
• Actual Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Diagnosed with posttraumatic stress disorder (PTSD).
• PTSD still remains after one or more prior treatment, with treatment including psychotherapy (talk therapy) or drug therapy
• May meet criteria for a mood disorder
• Must be at least 18 years old
• Must be able to stop taking psychiatric medication during the course of the study, from the start of the study to the follow-up two months after experimental session 3.
• Must agree to follow all rules and instructions relating to the experimental session, including restrictions on food and substance (alcohol and drug) consumption.
• Must be willing to stay overnight at the researcher's office after each experimental session until the non-drug session occurring the next morning.
• Must be willing to be contacted by one of the researchers on a daily basis for a week after each experimental session.
• Female participants of childbearing potential must have a negative pregnancy test and must agree to use an effective form of birth control.
• Participants must have sufficient proficiency in speaking the German language to participate in MDMA-assisted psychotherapy. Participants must be able to read documents in German.

Exclusion Criteria:

• Cannot have history of or current primary psychotic disorder or bipolar affective disorder-1.
• Dissociative identity disorder, or an eating disorder with active purging or borderline personality disorder.
• Evidence or history of significant hematological, endocrine, cerebrovascular, cardiovascular, coronary, pulmonary, renal, gastrointestinal, immunocompromising, or neurological disease, including seizure disorder. (People with hypothyroidism who are on adequate and stable thyroid replacement will not be excluded).
• Uncontrolled hypertension, peripheral vascular disease, hepatic disease (with or without abnormal liver enzymes), or history of hyponatremia or hyperthermia.
• Being pregnant or lactating (nursing), or not practicing an effective method of birth control.
• Weight of less than 50 or more than 105 kg.
• Patients reporting prior use of "Ecstasy" more than 5 times or at any time within the previous 6 months.
• People who would present a serious suicide risk or who are likely to require hospitalization during the course of the study.
• People who need ongoing concomitant therapy with a psychotropic drug.
• Meeting DSM-IV criteria for substance abuse or dependence for any substance save caffeine or nicotine in the past 60 days.
• People who cannot give adequate consent.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Switzerland

Administrative Information

• NCT Number: NCT00353938
• Other Study ID Numbers: M-P2
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Multidisciplinary Association for Psychedelic Studies
• Study Sponsor: Multidisciplinary Association for Psychedelic Studies
• Collaborators: Swiss Medical Association for Psycholytic Therapy

Investigators

• Principal Investigator: Peter Oehen, MD; private practice, Biberist, Switzerland

• PRS Account: Multidisciplinary Association for Psychedelic Studies
• Verification Date: May 2014