Clinical trial NCT00353938: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Posttraumatic Stress Disorder
Keywords: PTSD, MDMA, psychotherapy, Switzerland
Lead sponsor: Lykos Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: Swiss Medical Society for Psycholytic Therapy
First posted: 2006-07-19
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change From Baseline to Primary Endpoint in Clinician Administered PTSD Scale for DSM-IV (CAPS-IV)
timeFrame: Less than 4 weeks before first experimental session (Baseline) to 3 weeks post 3rd experimental session (Primary Endpoint)
Secondary outcomes:
measure: Change From Baseline to Primary Endpoint in Posttraumatic Stress Diagnostic Scale (PDS)
timeFrame: Less than 4 weeks before first experimental session (Baseline) to 3 weeks post 3rd experimental session (Primary Endpoint)
Other outcomes:
Locations:
city: Biberist
country: Switzerland
facility: Offices of Peter Oehen MD
state: Solothurn
Study officials:
affiliation: private practice, Biberist, Switzerland
name: Peter Oehen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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.