Study Comparing Three Doses of MDMA Along With Therapy in Veterans With Posttraumatic Stress Disorder

Study Overview
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Brief Summary
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This study is designed to provide information on whether therapy (talk therapy) combined with the drug MDMA is safe and helpful for subjects with posttraumatic stress disorder (PTSD). The study will compare the effects of a low, a medium and a full dose of MDMA on symptoms of PTSD in 24 veterans, firefighters or police officers. MDMA dose will be assigned at random, and the investigators and the subject will not know the dose given. The researchers will also investigate depression symptoms. The researchers believe that the full dose of MDMA will produce a greater reduction in PTSD symptoms than the two lower doses.

Detailed Description
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Posttraumatic stress disorder (PTSD) is a debilitating mental disorder, that can develop after service in the armed forces. Therapy performed along with MDMA is an innovative form of therapy for PTSD. This study will follow on the findings of an initial pilot study in a sample largely made up of people whose PTSD did not develop from serving in the military. This study will investigate whether MDMA-assisted therapy is safe and efficacious in a sample of veterans and whether maintaining an effective double-blind can be better addressed by performing a dose comparison study. This study is a randomized, double-blind, dose comparison study with an open-label cross-over segment that will assess the safety and efficacy of MDMA-assisted therapy in veterans with chronic PTSD. Twelve of 24 participants will receive the full dose of 125 mg, six will receive 75 mg and six will receive 30 mg (active placebo dose). An independent rater blind to condition will assess symptoms of PTSD and depression, general quality of life and posttraumatic growth prior to any therapy sessions one month after the second experimental session. After undergoing three 90-minute non-drug introductory therapy sessions with a male/female co-therapist team, study participants will undergo two eight-hour long experimental sessions scheduled three to five weeks apart, during which they will randomly receive either 30, 75 or 125 mg MDMA on both occasions, followed by a supplemental dose of half the initial dose. Participants will undergo integrative therapy in between each experimental session, including on the day after each session. Vital signs and psychological distress will be measured throughout each experimental session, and suicidality will be assessed throughout the course of the study. Spontaneously reported side effects will be collected on the day of each experimental session, and for six days afterward. PTSD symptoms, symptoms of depression, general psychological function, posttraumatic growth and quality of sleep will be assessed one month after the second experimental session, and the blind will be broken. Participants who received 125 mg MDMA will continue to have a third experimental session, and they will be assessed two months after the third experimental session. Participants who received 30 or 75 mg MDMA may take part in an open-label crossover segment that will follow nearly identical procedures, except that there will only be one introductory session prior to the first experimental session. There will be three experimental sessions. Symptoms of PTSD, depression and posttraumatic growth will be assessed at the start of the study. They will also be assessed one month after the second and two months after the third experimental session. All participants will be assessed 12 months after their final experimental session. PTSD and depression symptoms and posttraumatic growth will be assessed, and participants will complete a questionnaire concerning the costs and benefits of being in the study.

Official Title
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Randomized, Triple-Blind, Phase 2 Pilot Study Comparing 3 Different Doses of MDMA in Conjunction With Manualized Therapy in 24 Veterans, Firefighters and Police Officers With Chronic Posttraumatic Stress Disorder (PTSD)

Conditions
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Posttraumatic Stress Disorder

Intervention / Treatment
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* Drug: Low dose MDMA
* Drug: Medium dose MDMA
* Drug: Full dose MDMA
* Behavioral: Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be diagnosed with chronic PTSD, duration of 6 months or longer resulting from traumatic experience during military service; 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: 5.3.2 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 s

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 |
| --- | --- |
| Active Comparator: Low dose MDMA<br>Participants will receive 30 mg MDMA during each of two blinded experimental sessions. | Drug: Low dose MDMA<br>* 30 mg MDMA administered p.o. once at start of an experimental session. Upon mutual agreement, this may be followed by a supplemental dose of 15 mg MDMA 1.5 to 2 hours later<br>* Other names: methylenedioxymethamphetamine;Behavioral: Therapy<br>* Non-directive therapy during each session<br>|
| Active Comparator: Medium dose MDMA<br>Participants will receive 75 mg MDMA on each of two blinded experimental sessions | Drug: Medium dose MDMA<br>* 75 mg MDMA administered p.o. once at start of an experimental session. Upon mutual agreement, this may be followed by a supplemental dose of 37.5 mg MDMA 1.5 to 2 hours later<br>* Other names: methylenedioxymethamphetamine;Behavioral: Therapy<br>* Non-directive therapy during each session<br>|
| Experimental: Full dose MDMA<br>Participants will receive 125 mg MDMA during each of two blinded experimental sessions, followed by a third open label session. | Drug: Full dose MDMA<br>* 125 mg MDMA administered p.o. once at start of an experimental session. Upon mutual agreement, this may be followed by a supplemental dose of 62.5 mg MDMA 1.5 to 2 hours later<br>* Other names: methylenedioxymethamphetamine;Behavioral: Therapy<br>* Non-directive therapy during each session<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline Clinician-Administered PTSD Scale (CAPS-IV) Total Score | 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. 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 | 
| Stage 1 Primary Endpoint Clinician-Administered PTSD Scale (CAPS-IV) Total Score | 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. 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. | One month after second experimental session | 
| Change in Clinician-Administered PTSD Scale (CAPS-IV) From Baseline to Primary Endpoint | 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. 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 one month after second experimental session | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Global Assessment of Function (GAF) From Baseline to Primary Endpoint | The Global Assessment of Functioning (GAF) Scale is a numeric scale ranging from 0 through 100 that is used by mental health clinicians and physicians to subjectively rate the social, occupational, and psychological functioning of adults. Higher scores indicate better functioning. | Baseline to one month after second experimental session | 
| Change in Posttraumatic Growth Inventory (PTGI) From Baseline to Primary Endpoint | The Posttraumatic Growth Inventory (PTGI) is a 21-item self-report measure of perceived growth or benefits occurring after a traumatic event. It contains five subscales; relationship to others, new possibilities, personal strength, spiritual change, and appreciation of life. Questions are answered on a scale from 0 (I did not experience this change) to 5 (I experienced this change to a great degree). Items are added to calculate the total PTGI score which ranges from 0 to 105, with higher scores indicative of greater growth. | Baseline to one month after second experimental session | 
| Change in Beck Depression Inventory (BDI-II) From Baseline to Primary Endpoint | Validated self-report measure of symptoms of depression. The BDI-II total score of 0-13 is considered minimal range, 14-19 is mild, 20-28 is moderate, and 29-63 is severe depressive symptoms. The BDI-II is scored by summing the ratings for the 21 items. Each item is rated on a 4-point scale ranging from 0 to 3. The maximum total score is 63. | Baseline to one month after second experimental session | 
| Change in Dissociative Experience Scale (DES-II) From Baseline to Primary Endpoint | The DES-II is a 28-item self-report measure of dissociation, defined as a lack of normal integration of an individual's thoughts, feelings, or experiences into the stream of consciousness or memory. Respondents indicate how often the specific experience happens to them, from never (0% of the time) to always (100%). The scale is scored by treating percentages as single digits and summing to produce a total score, ranging from 0 to 100. The higher the score, the more dissociative symptoms. | Baseline to one month after second experimental session | 
| Change in Pittsburgh Sleep Quality Index (PSQI) From Baseline to Primary Endpoint | The Pittsburgh Sleep Quality Index (PSQI) is a self-rated questionnaire which assesses sleep quality and disturbances. It is comprised of 18 items that yield seven component scores. Component scores are summed to create a total score. Total scores range from 0 (better) to 21 (worse), with higher scores indicating poor sleep quality. | Baseline to one month after second experimental session | 
| Change in Neuroticism-Extroversion-Openness Personality Inventory-Revised (NEO-PI-R) From Baseline to Primary Endpoint | The NEO-PI-R is a 240-item self-report assessment that defines personality structure according to a five-factor model. Items related to neuroticism, extraversion, openness, agreeableness, and conscientiousness are rated on a five-point scale from strongly disagree to strongly agree. T-scores range from 20 to 80 with a mean score of 50. Higher scores in each domain indicating stronger facets of those personality factors. The NEO-PI-R is a measure of personality traits, not psychopathology symptoms. | Baseline to one month after second experimental session | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MDMA, Therapy, Veterans, Posttraumatic Stress Disorder