Randomized Placebo-controlled Study of MDMA-assisted Therapy in People With PTSD - Israel

Study Overview
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Brief Summary
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This is a study of the safety and efficacy of MDMA-assisted therapy in people with war or terrorism-related posttraumatic stress disorder (PTSD).

Detailed Description
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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 two six to eight-hour long sessions of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy scheduled three to five weeks apart are safe, and whether combining a fully therapeutic dose of MDMA with psychotherapy, compared with a low (active placebo) dose of MDMA, will reduce PTSD symptoms, with symptoms measured four times, twice during the study, and during two follow-up assessments six and twelve months after the second experimental session. People who received the active placebo dose of MDMA can then take part in an open label study continuation, with the participant receiving a fully active dose of MDMA on two more six to eight hour-long psychotherapy sessions. Open-label means that the participants and the researchers know that the participant will receive the fully active dose of MDMA. People who receive the full dose of MDMA, and anyone 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 second fully active or low dose MDMA session. People who take part in the open label study continuation have their PTSD symptoms checked six and 12 months after the second open label MDMA-assisted session. MDMA is a substance that has unique effects that make it well suited to intensive therapy. 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 in the US and Israel, and doctors and therapists cannot give it to people outside of research studies like this one. Anecdotal reports of therapy conducted before MDMA was made illegal suggest that MDMA-assisted therapy may benefit people with PTSD, and there is an ongoing placebo-controlled study of MDMA-assisted therapy in people with crime or war-related PTSD occurring in the US. This study will look at MDMA-assisted therapy in 12 individuals aged 18 years or older diagnosed with PTSD that arose out of war or terrorism-related trauma, 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 two experimental sessions. People will be assigned to full or low-dose MDMA by chance, as by flipping a coin. The fully active dose consists of an initial dose of 125 mg MDMA and a supplemental dose of 62.5 mg given 2 to 2.5 hours later. The active placebo dose consists of an initial dose of 25 mg MDMA and a supplemental dose of 12.5 mg. The study will last approximately four months, and will include two sixty minute long introductory therapy sessions, two active placebo or fully active dose MDMA-assisted therapy sessions, a sixty to ninety minute long therapy session 24 hours after each experimental session, and one to two hour-long therapy sessions occurring weekly between the first and second experimental session, and between the second experimental session and the end of the study. PTSD symptoms will be measured at the start of the study and eight weeks (two months) after the second experimental session. PTSD symptoms are assessed six and twelve months after the second experimental session in people who do not take part in the open-label study continuation. People who take part in the open-label study continuation will have their PTSD symptoms measured six and twelve months after the second MDMA-assisted therapy session.

Official Title
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MDMA-assisted Therapy in Twelve People With War and Terrorism-related Posttraumatic Stress Disorder (PTSD)

Conditions
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Posttraumatic Stress Disorder

Intervention / Treatment
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* Drug: 3,4-methylenedioxymethemphetmaine (MDMA_
* Drug: 3,4-methylenedioxymethamphetamine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Posttraumatic stress disorder arising from war or terrorism-related events. PTSD still remains after at last one treatment, with treatment including psychotherapy or pharmacotherapy. May meet criteria for a mood disorder. Must be at least 18 years old. Must be able to stop taking psychiatric medication from the start of the study until the two-month follow-up. May continue seeing an outside therapist during the study, but cannot increase the length or frequency of treatments. Must be able to follow all the rules and instructions relating to the experimental session, including restrictions on food and substance (alcohol and drug) consumption Must be willing to stay overnight in the clinic 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. If a woman of childbearing potential, must have a negative pregnancy test and must agree to use an effective form of birth control. Must be able to speak and read Hebrew. Exclusion Criteria: Cannot have a non-war or non-terrorism event as significant contributor to PTSD symptoms. Cannot have history of or be diagnosed with psychotic disorder or bipolar affective disorder - 1. Cannot be diagnosed with dissociative identity disorder, an eating disorder with active purging or borderline personality disorder. Cannot have 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). Cannot have uncontrolled hypertension, peripheral vascular disease, hepatic disease (with or without abnormal liver enzymes), or history of hyponatremia or hyperthermia. Cannot weigh less than 50 or more than 105 kg. Cannot have used Ecstasy more than five times during lifetime or in the past six months. Cannot present a serious suicide risk or be likely to require hospitalization during the course of the study. Cannot require ongoing concomitant therapy with a psychotropic drug. Cannot meet DSM-IV criteria for substance abuse or dependence for any substance save caffeine or nicotine in the past 60 days. Unable to give adequate consent.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Full dose (125 mg) MDMA-assisted therapy<br>Participants will receive an initial dose of 125 mg MDMA followed 2.5 hours later by a supplemental dose of 62.5 mg MDMA during the course of two day-long therapy sessions. | Drug: 3,4-methylenedioxymethemphetmaine (MDMA_<br>* Participants will receive an initial dose of 125 mg MDMA orally followed 2.5 hours later by 62.5 mg MDMA orally during the course of a day-long therapy session.<br>|
| Active Comparator: Active Comparator (25 mg) MDMA-assisted therapy<br>Participants will receive an initial dose of 25 mg MDMA followed 2.5 hours later by a supplemental dose of 12.5 mg MDMA during the course of two day-long therapy sessions. | Drug: 3,4-methylenedioxymethamphetamine<br>* Participants will receive an initial dose of 25 mg MDMA orally followed 2.5 hours alter by a supplemental dose of 12.5 mg MDMA orally during the course of each of two day-long therapy sessions.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Clinician-Administered PTSD Scale for DSM-IV (CAPS-IV) at 2-month Follow-up | The Clinician-Administered PTSD Scale for DSM-IV (CAPS-IV) is a clinician administered and scored assessment of PTSD symptoms via structured interview based upon PTSD diagnosis in DSM-IV. It contains symptom subscales, a CAPS-IV total severity score, and a diagnostic score. The total severity score is a sum of symptom frequency and intensity scores for the subscales B (re-experiencing), C (avoidance) and D (hypervigilance) and ranges from 0 to 136, with higher scores indicating greater severity of PTSD symptoms. | Baseline to two months after second MDMA-assisted experimental session | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Clinician-Administered PTSD Scale for DSM-IV (CAPS-IV) at 6-month Follow-up | The Clinician-Administered PTSD Scale for DSM-IV (CAPS-IV) is a clinician administered and scored assessment of PTSD symptoms via structured interview based upon PTSD diagnosis in DSM-IV. It contains symptom subscales, a CAPS-IV total severity score, and a diagnostic score. The total severity score is a sum of symptom frequency and intensity scores for the subscales B (re-experiencing), C (avoidance) and D (hypervigilance) and ranges from 0 to 136, with higher scores indicating greater severity of PTSD symptoms. | Baseline to 6 months after second MDMA-assisted experimental session | 
| Change in Clinician-Administered PTSD Scale for DSM-IV (CAPS-IV) at 12-month Follow-up | The Clinician-Administered PTSD Scale for DSM-IV (CAPS-IV) is a clinician administered and scored assessment of PTSD symptoms via structured interview based upon PTSD diagnosis in DSM-IV. It contains symptom subscales, a CAPS-IV total severity score, and a diagnostic score. The total severity score is a sum of symptom frequency and intensity scores for the subscales B (re-experiencing), C (avoidance) and D (hypervigilance) and ranges from 0 to 136, with higher scores indicating greater severity of PTSD symptoms. | Baseline to twelve months after second MDMA-assisted experimental session | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Israel, PTSD, MDMA, therapy, Posttraumatic stress disorder