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
• Results First Posted: September 16, 2021
• Last Update Posted: March 14, 2022
• 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
• Results First Submitted Date: August 20, 2021
• Results First Posted Date: September 16, 2021
• Last Update Posted Date: March 14, 2022
• Study Start Date: October 2006
• Actual Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 20, 2021)

Change From Baseline to Primary Endpoint in Clinician Administered PTSD Scale for DSM-IV (CAPS-IV) [ Time Frame: Less than 4 weeks before first experimental session (Baseline) to 3 weeks post 3rd experimental session (Primary Endpoint) ]

The CAPS-IV is a structured clinical interview designed to assess the symptoms and severity of PTSD. The CAPS-IV provides a means to evaluate the frequency and intensity dimensions of each symptom, the impact of symptoms on the patient's social and occupational functioning, the overall severity of the symptom complex, global improvement since baseline, and the validity of the ratings obtained. Total severity scores range from 0 to 136, with higher scores indicating greater severity of PTSD symptoms.

• 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: August 20, 2021)

Change From Baseline to Primary Endpoint in Posttraumatic Stress Diagnostic Scale (PDS) [ Time Frame: Less than 4 weeks before first experimental session (Baseline) to 3 weeks post 3rd experimental session (Primary Endpoint) ]

The Posstraumatic Stress Diagnostic Scale (PSD) is a 49-item self-report instrument to aid in the diagnosis of PTSD. Questions are asked about symptoms experienced and participants respond on a scale from 0 ("not at all or only one time") to 3 ("5 or more times a week/almost always"). Items are summed to create a total score that ranges from 0 to 51, with higher scores indicating more PTSD symptoms.

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 examine MDMA-assisted psychotherapy in individuals aged 18 years or older diagnosed with PTSD, with PTSD symptoms not improving after trying at least one treatment. This objective of this study is to determine whether three eight-hour long sessions of 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. Participants will be randomly assigned to receive the full dose of MDMA (125 mg) or assigned to receive a low or "active placebo" dose of MDMA (25 mg) during each of three experimental sessions.

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 MDMA-assisted psychotherapy in individuals aged 18 years or older diagnosed with PTSD, with PTSD symptoms not improving after trying at least one treatment. This objective of this study is to determine whether three eight-hour long sessions of 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. Participants will be randomly assigned to receive the full dose of MDMA (125 mg) or assigned to receive a low or "active placebo" dose of MDMA (25 mg) during each of three experimental sessions.

People who receive the low dose of MDMA have the opportunity to take part in a second "open label" study continuation, wherein the participants 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 assessed six and 12 months after the third Phase II MDMA-assisted session.

• 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, 2.5 hours later they will receive 62.5 mg MDMA orally.
  Other Name: MDMA
• Drug: 3,4-methyelendioxymethamphetamine (25 mg)
  Participants will receive a 25 mg MDMA orally, and if investigator and participant agree, 2.5 hours later they will receive 12.5 mg MDMA orally.
  Other Name: MDMA
• Behavioral: Therapy
  Non-directive therapy performed by a team of two co-therapists

Study Arms

• Experimental: Full Dose MDMA-assisted therapy (125 mg)
  Three 8-hour sessions of MDMA-assisted therapy with 125 mg of MDMA, followed by a supplemental dose of 62.5 mg MDMA
  Interventions:

  • Drug: 3,4-methylenedioxymethamphetamine (125 mg)
  • Behavioral: Therapy
• Active Comparator: Active Placebo MDMA-assisted therapy (25 mg)
  Three 8-hour sessions of MDMA-assisted therapy with 25 mg of MDMA, followed by a supplemental dose of 12.5 mg MDMA
  Interventions:

  • Drug: 3,4-methyelendioxymethamphetamine (25 mg)
  • Behavioral: Therapy

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
• Current Responsible Party: Multidisciplinary Association for Psychedelic Studies
• Original Responsible Party: Not Provided
• Current Study Sponsor: Multidisciplinary Association for Psychedelic Studies
• Original Study Sponsor: Same as current
• 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: March 2022