Overview

This trial is active, not recruiting.

Condition posttraumatic stress disorder
Treatments comparator, full-dose mdma, psychotherapy
Phase phase 2
Sponsor Multidisciplinary Association for Psychedelic Studies
Start date September 2013
End date October 2016
Trial size 12 participants
Trial identifier NCT01958593, MP-4

Summary

This small ("pilot") study is designed to provide information on whether the combination of psychotherapy with the drug MDMA is safe and helpful for people with post traumatic stress disorder (PTSD). The researchers will use the results of this study to design more studies of this treatment. The study compares a comparator and a full dose. For each session, there will be an initial dose possibly followed 1.5 to 2.5 hours later by a dose half the size of the initial dose. The study will measure symptoms of PTSD, depression, general psychological well-being, sleep quality, feelings that the self or world is unreal (dissociation), potentially positive effects of surviving traumatic events and cognitive function (thinking, memory and attention). People experiencing pain or tinnitus (ringing in the ears) will record their symptoms throughout the study. Seven people will be randomly (by chance) assigned to receive full-dose MDMA and five will be randomly assigned to receive a comparator. There will be three preparatory psychotherapy sessions before the first experimental session, and subjects will have supportive or "integrative" sessions after each MDMA-assisted psychotherapy session. Subjects will meet with a male and female psychotherapist for all experimental sessions and for sessions before and after each experimental session. Subjects who received comparator can enroll in Stage 2, where they will have three open-label MDMA-assisted psychotherapy sessions, meaning everyone will know they are receiving an active dose of MDMA. Subjects receiving full dose in Stage 1 will have a third experimental session.. Symptoms of PTSD and other symptoms will be measured again at least 12 months after each subject has started the study.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator, outcomes assessor)
Primary purpose prevention
Arm
(Active Comparator)
Participants will receive comparator during each of two experimental sessions.
comparator
Comparator administered in two experimental sessions; may take part in Stage 2 upon learning condition assignment
psychotherapy
Psychotherapy before and after experimental sessions
(Experimental)
Participants will receive full-dose MDMA during each of two experimental sessions.
full-dose mdma 3,4-methyelenedioxymethamphetamine
Participants receive full-dose MDMA during two experimental sessions; after learning their condition assignment, participants will receive a third full-dose session.
psychotherapy
Psychotherapy before and after experimental sessions

Primary Outcomes

Measure
Change in Clinician-Administered PTSD Scale Score
time frame: 0 to 3 months post enrollment

Secondary Outcomes

Measure
Change in CAPS score
time frame: 5 or 7 months post enrollment to 15 - 18 months post-enrollment
Change in CAPS score
time frame: 3 to 5 months or 5-7 months post-enrollment
Change in Beck Depression Inventory Score
time frame: 0 to 3 months post enrollment
Change in Beck Depression Inventory Score
time frame: 5 or 7 months post-enrollment to 15 - 18 months post enrollment
Change in Beck Depression Inventory Score
time frame: 3 to 5 months or 5-7 months post enrollment
Change in Global Assessment of Functioning
time frame: 0 to 3 months post enrollment
Change in Global Assessment of Functioning
time frame: 5 or 7 months post-enrollment to 15-18 months post enrollment
Change in Global Assessment of Functioning
time frame: 3 to 5 months post enrollment or 5-7 months post enrollment
Change in Post traumatic Diagnostic Scale score
time frame: 0 to 3 months post enrollment
Change in Post traumatic Diagnostic Scale score
time frame: 5 or 7 months post-enrollment to 15-18 months post enrollment
Change in Post traumatic Diagnostic Scale score
time frame: 3 to 5 months post-enrollment or 5-7 months post-enrollment
Post traumatic Diagnostic Scale score
time frame: 1.75 months post enrollment
Post traumatic Diagnostic Scale score
time frame: 2.75 months post enrollment
Post traumatic Diagnostic Scale score
time frame: 3.75 months post enrollment
Change in Pittsburgh Sleep Quality Index (PSQI)
time frame: 0 to 3 months post-enrollment
Change in Pittsburgh Sleep Quality Index (PSQI)
time frame: 5 or 7 months post-enrollment to to 15-18 months post enrollment
Change in Pittsburgh Sleep Quality Index (PSQI)
time frame: 3 to 5 months post-enrollment or 5-7 months poist-enrollment
Change in Post traumatic Growth Inventory scores
time frame: 0 to 3 months post-enrollment
Change in Post traumatic Growth Inventory scores
time frame: 5 or 7 months post-enrollment to 15-18 months post-enrollment
Change in Post traumatic Growth Inventory scores
time frame: 3 to 5 months post-enrollment or 5-7 months post-enrollment
Changes in Dissociation Experiences Scale II Scores
time frame: 0 to 3 months post-enrollment
Changes in Dissociation Experiences Scale II Scores
time frame: 5 or 7 mo post-enrollment to 15-18 mo post-enrollment
Changes in Dissociation Experiences Scale II Scores
time frame: 3 to 5 mo post-enrollment or 5-7 mo post enrollment
Change in VAS scale somatic symptoms of pain/tinnitus
time frame: 0 to 3 mo post-enrollment
Change in VAS scale somatic symptoms of pain/tinnitus
time frame: 5 or 7 mo post enrollment to 15-18 mo post-enrollment
Change in VAS scale somatic symptoms of pain/tinnitus
time frame: 3 or 5 mo post-enrollment
Average VAS scale somatic symptoms of pain/tinnitus - baseline to primary endpoint
time frame: 0 to 3 mo post-enrollment
Change in Neuroticism Extroversion Openness Personality Inventory Revised (NEO-PI-R)
time frame: 0 to 3 mo post-enrollment
Change in Neuroticism Extroversion Openness Personality Inventory Revised (NEO-PI-R)
time frame: 3 or 7 mo post-enrollment to 15-18 mo post enrollment
Change in Neuroticism Extroversion Openness Personality Inventory Revised (NEO-PI-R)
time frame: 3 to 7 mo post-enrollment
Repeatable Battery for the Assessment of Neuropsychological Status Total score
time frame: 0 months post-enrollment
Repeatable Battery for the Assessment of Neuropsychological Status Total score
time frame: 3 months post-enrollment
Repeatable Battery for the Assessment of Neuropsychological Status Total score
time frame: 5 or 7 months post-enrollment
Paced Auditory Serial Addition Test 3 seconds Correct
time frame: 0 months post-enrollment
Paced Auditory Serial Addition Test 3 seconds Correct Centile
time frame: 0 months post-enrollment
Paced Auditory Serial Addition Test 2 seconds Correct
time frame: 0 months post-enrollment
Paced Auditory Serial Addition Test 2 seconds Correct Centile score
time frame: 0 months post-enrollment
Paced Auditory Serial Addition Test 3 seconds Correct
time frame: 3 months post-enrollment
Paced Auditory Serial Addition Test 3 seconds Correct Centile
time frame: 3 months post-enrollment
Paced Auditory Serial Addition Test 2 seconds Correct
time frame: 3 months post-enrollment
Paced Auditory Serial Addition Test 2 seconds Correct Centile score
time frame: 3 months post-enrollment
Paced Auditory Serial Addition Test 3 seconds Correct
time frame: 5 or 7 months post-enrollment
Paced Auditory Serial Addition Test 3 seconds Correct Centile
time frame: 5 or 7 months post-enrollment
Paced Auditory Serial Addition Test 2 seconds Correct
time frame: 5 or 7 months post-enrollment
Paced Auditory Serial Addition Test 2 seconds Correct Centile score
time frame: 5 or 7 months post-enrollment
Columbia Suicide Severity Rating Scale (CSSRS)
time frame: 0 month post-enrollment
Columbia Suicide Severity Rating Scale (CSSRS)
time frame: up to 0.8 month post-enrollment
Average Columbia Suicide Severity Rating Scale (CSSRS)
time frame: 1 to 3 month post-enrollment
Peak Columbia Suicide Severity Rating Scale (CSSRS)
time frame: 1 to 3 months post-enrollment
Average Columbia Suicide Severity Rating Scale (CSSRS)
time frame: 3 to 6 months post-enrollment
Peak Columbia Suicide Severity Rating Scale (CSSRS)
time frame: 3 to 6 mo post-enrollment
Columbia Suicide Severity Rating Scale (CSSRS)
time frame: 15 to 18 months post-enrollment
Stage 1 average pre-drug systolic blood pressure
time frame: 1, 2 and 3 months post-enrollment
Stage 2 average pre-drug systolic blood pressure
time frame: 4, 5 and 6 months post-enrollment
Stage 1 average peak systolic blood pressure
time frame: 1, 2 and 3 months post-enrollment
Stage 2 average peak systolic blood pressure
time frame: 4, 5 and 6 months post-enrollment
Stage 1 average session end systolic blood pressure
time frame: 1, 2 and 3 months post-enrollment
Stage 2 average session-end systolic blood pressure
time frame: 4, 5 and 6 months post-enrollment
Stage 1 average pre-drug diastolic blood pressure
time frame: 1, 2 and 3 months post-enrollment
Stage 2 average pre-drug diastolic blood pressure
time frame: 4, 5 and 6 months post-enrollment
Stage 1 average peak diastolic blood pressure
time frame: 1, 2 and 3 months post-enrollment
Stage 2 average peak diastolic blood pressure
time frame: 4, 5 and 6 months post-enrollment
Stage 1 average session end diastolic blood pressure
time frame: 1, 2 and 3 months post-enrollment
Stage 2 average session-end diastolic blood pressure
time frame: 4, 5 and 6 months post-enrollment
Stage 1 average pre-drug heart rate
time frame: 1, 2 and 3 months post-enrollment
Stage 2 average pre-drug heart rate
time frame: 4, 5 and 6 months post-enrollment
Stage 1 average peak heart rate
time frame: 1, 2 and 3 months post-enrollment
Stage 1 average session end heart rate
time frame: 1, 2 and 3 months post-enrollment
Stage 2 average session-end heart rate
time frame: 4, 5 and 6 months post-enrollment
Stage 2 average peak heart rate
time frame: 4, 5 and 6 months post-enrollment
Stage 1 average pre-drug body temperature
time frame: 1, 2 and 3 months post-enrollment
Stage 2 average pre-drug body temperature
time frame: 4, 5 and 6 months post-enrollment
Stage 1 average peak body temperature
time frame: 1, 2 and 3 months post-enrollment
Stage 2 average body temperature
time frame: 4, 5 and 6 months post-enrollment
Stage 1 average session end body temperature
time frame: 1, 2 and 3 months post-enrollment
Stage 2 average session-end body temperature
time frame: 4, 5 and 6 months post-enrollment
Stage 1 average pre-drug Subjective Unit of Distress
time frame: 1, 2 and 3 months post-enrollment
Stage 2 average pre-drug Subjective Unit of Distress
time frame: 4, 5 and 6 months post-enrollment
Stage 1 average peak Subjective Unit of Distress
time frame: 1, 2 and 3 months post-enrollment
Stage 2 average peak Subjective Unit of Distress
time frame: 4, 5 and 6 months post-enrollment
Stage 1 average session end Subjective Unit of Distress
time frame: 1, 2 and 3 months post-enrollment
Stage 2 average session-end Subjective Unit of Distress
time frame: 4, 5 and 6 months post-enrollment

Eligibility Criteria

Male or female participants at least 21 years old.

Inclusion Criteria: - Diagnosed with PTSD, duration of six months or longer - Have a CAPS score showing moderate to severe PTSD symptoms; - Have had at least one unsuccessful attempt at treatment for PTSD either with talk therapy or with drugs, or discontinuing treatment because of inability to tolerate psychotherapy or drug therapy. - Are at least 18 years old; - Must be generally healthy; - Must sign a medical release for the investigators to communicate directly with their therapist and doctors; - Are willing to refrain from taking any psychiatric medications during the study period; - Willing to follow restrictions and guidelines concerning consumption of food, beverages, and nicotine the night before and just prior to each experimental session; - Willing to remain overnight at the study site; - Agree to have transportation other than driving themselves home or to where they are staying after the integrative session on the day after the MDMA session; - 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; - Must provide a contact in the event of a participant becoming suicidal; - Are proficient in speaking and reading English; - Agree to have all clinic visit sessions recorded to audio and video - Agree not to participate in any other interventional clinical trials during the duration of this study. Exclusion Criteria: - Are pregnant or nursing, or if a woman who can have children, those who are not practicing an effective means of birth control - Weigh less than 48 kg - Are abusing illegal drugs - Are unable to give adequate informed consent - Upon review of past and current drugs/medication must not be on or have taken a medication that is exclusionary - Upon review of medical or psychiatric history must not have any current or past diagnosis that would be considered a risk to participation in the study

Additional Information

Official title A Randomized, Double-Blind, Controlled Phase 2 Pilot Study of Manualized 3,4-methylenedioxymethamphetamine (MDMA)-Assisted Psychotherapy in 12 Subjects With Treatment-Resistant Posttraumatic Stress Disorder (PTSD) - Canada
Principal investigator Ingrid Pacey, MBBS FRCP[C]
Description Post traumatic stress disorder (PTSD) is a debilitating disorder that can develop after people experience a traumatic event, such as a rape, car accident or other life threatening event. PTSD is a worldwide health problem. PTSD is treated with psychotherapy or drugs, but these treatments do not help everyone. 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy might be a potential treatment for PTSD. MDMA is the active ingredient in ecstasy. Before it was made illegal, some psychotherapists combined MDMA with psychotherapy to help treat people with psychological problems, including PTSD. This is a Phase 2 randomized, dose comparison, double-blind study to assess safety and efficacy of manualized MDMA-assisted psychotherapy in treating chronic, treatment-resistant PTSD. Seven subjects will be randomized to receive full dose MDMA (full dose condition) and five subjects will receive a comparator (comparator condition), with an optional supplemental half-dose available 1.5 to 2.5 hours after the initial dose. Global Clinician-Administered PTSD Scale (CAPS) score one month after two sessions of MDMA-assisted psychotherapy is the primary outcome measure. MDMA or comparator will be administered in two blinded experimental sessions lasting up to eight hours and scheduled three to five weeks apart. The will last up to one and a half years, including approximately three to five months of psychotherapy, and a long-term follow up visit scheduled a year after the final experimental session. Study subjects will have a medical and psychiatric examination to assess eligibility for enrollment. Once in the study, they will see the same male and female psychotherapist for the entire study. The subject will learn more about MDMA-assisted psychotherapy and the investigators will learn more about the subject during three preparatory sessions occurring before the first experimental session. During experimental sessions, subjects will receive an initial dose of either full dose MDMA or comparator along with psychotherapy, and one and a half to two and a half hours later, the subject may have a supplemental half the size of the initial dose. Vital signs and psychological distress will be measured throughout the experimental session. There will be three integrative psychotherapy sessions after each experimental session, including one occurring the day after an experimental session. Subjects will express, understand and connect any of their thoughts or feelings about PTSD symptoms and their causes, and they will discuss their experience during experimental sessions with the therapists. Subjects will learn the dose of MDMA they received one month after the second MDMA-assisted psychotherapy session. Subjects who received full dose will complete Stage 1, with a third open-label session, and subjects who received comparator dose MDMA will go on to Stage 2, an open label period of the study that is nearly identical to stage 1, but with one instead of three preparatory sessions and one of two active doses of MDMA used in all three experimental sessions. Symptoms of PTSD, depression, dissociation, general psychological well-being, sleep quality and potential positive effects of experiencing traumatic events will be measured in all subjects at baseline, one month after the second experimental session and 12 months after their final experimental session, and any subjects reporting pain or tinnitus at the start of the study will record these symptoms throughout the study.Subjects who received the full dose and go on to the third experimental session will complete questionnaires and measures of PTSD and other symptoms two months after the third experimental session. Subjects who received comparator dose MDMA will be tested one month after their second Stage 2 experimental session and two months after the third experimental session. Measures of cognitive function will be given to subjects in Stage two months after their third experimental session, and to Stage 2 subjects two months after their third Stage 2 session. People will also complete measures of their experience of the experimental session soon after each experimental session. At least 12 months after their final Stage 1 or Stage 2 session, measures of PTSD symptoms, other symptoms, sleep quality, general well-being and and post traumatic growth will be assessed again, and subjects will complete a questionnaire on the benefits and harms of study participation and other life events and views related to study participation. This study will compare the effects of MDMA-assisted psychotherapy with comparator versus full dose MDMA, and it will also assess the duration of any changes in symptoms a year after MDMA-assisted psychotherapy.
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by Multidisciplinary Association for Psychedelic Studies.