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

Phase 2

Completed

Conditions: Posttraumatic Stress Disorder

Interventions: Drug: Low dose MDMA-assisted therapy
Drug: Medium dose MDMA-assisted therapy
Drug: Full dose MDMA-assisted therapy
Drug: Medium dose MDMA
Drug: Full dose MDMA
Drug: Low dose MDMA
Behavioral: Therapy

Registration Number: NCT01211405

Lead Sponsor: Lykos Therapeutics

Brief Summary: The goal of this clinical trial is to learn if MDMA-assisted therapy is safe and effective and reducing PTSD symptoms in veterans with chronic PTSD. The main question it aims to answer is: Do three doses of MDMA reduce PTSD symptoms?

Researchers will compare 30, 75, and 125 mg of MDMA HCl with therapy to see which dose best reduces PTSD symptoms.

Participants will undergo three preparatory non-drug therapy sessions with a male and female co-therapist team, then undergo three day-long MDMA-assisted therapy sessions after receiving an initial dose of 30, 75, or 125 mg MDMA HCl. After each MDMA-assisted therapy session, participants will undergo three integrative therapy sessions.

Detailed Description: 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) of MDMA HCl. 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, prior to which they will be randomized to receive an initial dose of 30, 75 or 125 mg MDMA HCl , followed by a supplemental dose of half the initial dose 1.5 to 2.5 hours later. 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 HCl 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 HCl 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 26

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

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;
Have used ecstasy (material representing itself as MDMA) more than 5 times or at least once in the last 6 months;
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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Low dose MDMA-assisted therapy	Low dose MDMA-assisted therapy	Participants will receive 30 mg midomafetamine HCl (MDMA) with therapy during each of two blinded experimental sessions.
Low dose MDMA-assisted therapy	Therapy	Participants will receive 30 mg midomafetamine HCl (MDMA) with therapy during each of two blinded experimental sessions.
Medium dose MDMA-assisted therapy	Medium dose MDMA-assisted therapy	Participants will receive 75 mg midomafetamine HCl (MDMA) with therapy on each of two blinded experimental sessions.
Medium dose MDMA-assisted therapy	Therapy	Participants will receive 75 mg midomafetamine HCl (MDMA) with therapy on each of two blinded experimental sessions.
Full dose MDMA-assisted therapy	Full dose MDMA-assisted therapy	Participants will receive 125 mg midomafetamine HCl (MDMA) with therapy during each of two blinded experimental sessions, followed by a third open label session.
Full dose MDMA-assisted therapy	Therapy	Participants will receive 125 mg midomafetamine HCl (MDMA) with therapy during each of two blinded experimental sessions, followed by a third open label session.
Low dose MDMA	Therapy	Participants will receive 30 mg MDMA during each of two blinded experimental sessions.
Medium dose MDMA	Medium dose MDMA	Participants will receive 75 mg MDMA on each of two blinded experimental sessions
Medium dose MDMA	Therapy	Participants will receive 75 mg MDMA on each of two blinded experimental sessions
Full dose MDMA	Full dose MDMA	Participants will receive 125 mg MDMA during each of two blinded experimental sessions, followed by a third open label session.
Low dose MDMA	Low dose MDMA	Participants will receive 30 mg MDMA during each of two blinded experimental sessions.
Full dose MDMA	Therapy	Participants will receive 125 mg MDMA during each of two blinded experimental sessions, followed by a third open label session.

Primary Outcome Measures

Name	Time	Method
Change in Clinician-Administered PTSD Scale (CAPS-IV) From Baseline to Primary Endpoint	Baseline to one month after second experimental session	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.

Secondary Outcome Measures

Name	Time	Method
Change in Posttraumatic Growth Inventory (PTGI) From Baseline to Primary Endpoint	Baseline to one month after second experimental session	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.
Change in Beck Depression Inventory (BDI-II) From Baseline to Primary Endpoint	Baseline to one month after second experimental session	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.
Change in Dissociative Experience Scale (DES-II) From Baseline to Primary Endpoint	Baseline to one month after second experimental session	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.
Change in Pittsburgh Sleep Quality Index (PSQI) From Baseline to Primary Endpoint	Baseline to one month after second experimental session	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.
Change in Global Assessment of Function (GAF) From Baseline to Primary Endpoint	Baseline to one month after second experimental session	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.