Randomized, Double-blind, Controlled of MDMA-assisted Psychotherapy in 12 Subjects With PTSD

Phase 2

Terminated

Conditions: Posttraumatic Stress Disorder

Interventions: Drug: Placebo
Drug: Midomafetamine HCl
Behavioral: Psychotherapy

Registration Number: NCT01958593

Lead Sponsor: Lykos Therapeutics

Brief Summary: The goal of this clinical trial is to compare full dose MDMA-assisted therapy to placebo with therapy in participants with chronic, treatment-resistant PTSD. The main question it aims to answer is: Does MDMA-assisted therapy versus placebo with therapy reduce PTSD symptoms?

Participants will receive either MDMA-assisted therapy or placebo with therapy during two blinded experimental sessions spaced three to five weeks apart. During experimental sessions, participants receive an initial dose of 125 mg of MDMA HCl, or placebo, followed by a dose of 62.5 mg of MDMA HCl, or placebo. During this treatment period, participants will also undergo non-drug preparatory therapy sessions and non-drug integration sessions.

Researchers will compare PTSD symptoms in the MDMA-assisted therapy group to the placebo with therapy group to see if there is a reduction in symptoms after the treatment period. Safety measures will also be assessed between groups.

Detailed Description: This randomized, double-blind, placebo-controlled clinical study will assess the safety and efficacy of MDMA-assisted therapy in treating chronic, treatment-resistant PTSD. In Stage 1, participants will be randomized to either MDMA-assisted therapy or placebo with therapy during two blinded experimental sessions, spaced three to five weeks apart. During experimental sessions, participants receive an initial dose of 125 mg of MDMA HCl, or placebo, followed by a dose of 62.5 mg of MDMA HCl, or placebo. During this treatment period, participants will also undergo non-drug preparatory therapy sessions and non-drug integration sessions. After this treatment period, participants will complete the primary endpoint assessment and the study will become unblinded.

Participants who were assigned to receive MDMA-assisted therapy will receive a third session of MDMA-assisted therapy that is open-label and participants assigned to receive placebo with therapy will have the option to enter Stage 2. Stage 2 will explore the optimal therapeutic dose of MDMA in a clinical titration dosing strategy. Participants will receive MDMA-assisted with an initial dose of 100 mg followed by a dose of 50 mg of MDMA HCl for the first experimental session. In the second and third experimental sessions, participants will have the option to increase the dose to an initial dose of 125 mg followed by a dose of 62.5 mg.

A blinded independent rater will assess PTSD symptoms via the CAPS-IV as well as other secondary outcome measures and safety measures.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 6

Inclusion Criteria

Diagnosed with moderate to severe PTSD;
Have chronic PTSD, defined as persisting for longer than 6 months;
Have treatment-resistant PTSD, meaning unable to achieve remission despite previous therapy or medication or discontinued treatment due to inability to tolerate previous therapy or medication;
Are willing to refrain from taking any psychiatric medications during the study period;
Willing to remain overnight at the study site;
Agree to have transportation home after experimental sessions;
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;
Are proficient in speaking and reading English;
Agree not to participate in any other interventional clinical trials during the duration of this study.

Exclusion Criteria

Are pregnant or nursing, or if of child bearing potential, are not practicing an effective means of birth control;
Weigh less than 48 kg;
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;
Have used "Ecstasy" (illicit drug preparations purported to contain MDMA) more than five times in the last 10 years or at least once within six months of enrollment;
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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo with therapy	Placebo	Participants will receive placebo with therapy during each of two experimental sessions.
Placebo with therapy	Psychotherapy	Participants will receive placebo with therapy during each of two experimental sessions.
MDMA-assisted therapy	Midomafetamine HCl	Participants will receive MDMA (initial dose of 125 mg midomafetamine HCl followed by a supplemental dose of 62.5 mg midomafetamine HCl) with therapy during each of two experimental sessions.
MDMA-assisted therapy	Psychotherapy	Participants will receive MDMA (initial dose of 125 mg midomafetamine HCl followed by a supplemental dose of 62.5 mg midomafetamine HCl) with therapy during each of two experimental sessions.

Primary Outcome Measures

Name	Time	Method
Change in Clinician-Administered PTSD Scale (CAPS-IV) Score From Baseline to Primary Endpoint	Baseline to Primary Endpoint (Primary Endpoint was approximately 18 weeks after Baseline and 1 month after the 2nd experimental session)	Clinician-administered and scored assessment of PTSD symptoms via structured interview, including global symptom severity, dichotomous diagnostic score and subscale scores. The Clinician-Administered PTSD Scale for DSM-4 (CAPS-4) is a clinician administered and scored assessment of PTSD symptoms via structured interview based upon PTSD diagnosis in DSM-4. It contains symptom subscales, a CAPS-4 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.

Secondary Outcome Measures

Name	Time	Method
Change in PTSD Diagnostic Scale (PDS) Total Severity Score From Baseline to Primary Endpoint	Baseline to Primary Endpoint (Primary Endpoint was approximately 18 weeks after Baseline and 1 month after the 2nd experimental session)	The PTSD Diagnostic Scale (PDS) is a 49 item self-report measure designed to follow DSM-IV criteria for assessing PTSD. The PDS consists of a checklist to identify potentially traumatizing events experienced by the respondent and respondents then indicate which of the experienced events has troubled them the most in the last month and rate their response to this event at the time of its occurrence. Respondents then rate the severity of 17 items representing the cardinal symptoms of PTSD experienced in the past 30 days on a scale from 0 ("not at all") to 3 ("5 or more times a week") as well as the level of impairment caused by their symptoms across nine areas of life functioning. The 17 symptom severity items are summed to create a total symptom severity score, which ranges from 0 to 51, with higher scores indicating greater symptom severity and/or frequency.
Change in Beck Depression Inventory (BDI-II) Score From Baseline to Primary Endpoint	Baseline to Primary Endpoint (Primary Endpoint was approximately 18 weeks after Baseline and 1 month after the 2nd experimental session)	The BDI-II is a validated 21-item self-report measure of symptoms of depression according to DSM-IV criteria. A 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 scores range from 0 to 63, with higher score indicating greater severity of depressive symptoms.
Change in Global Assessment of Functioning (GAF) Score From Baseline to Primary Endpoint	Baseline to Primary Endpoint (Primary Endpoint was approximately 18 weeks after Baseline and 1 month after the 2nd experimental session)	The GAF Scale is a numeric scale ranging from 0 (serious risk of causing harm to the self or others) through 100 (superior function) that is used by mental health clinicians and physicians to subjectively rate the social, occupational, and psychological functioning of adults. The GAF is a reliable, validated measure of social functioning (Goldman, Skodol, and Lave, 1992). Higher scores indicate better functioning.
Change in Pittsburgh Sleep Quality Index (PSQI) Score From Baseline to Primary Endpoint	Baseline to Primary Endpoint (Primary Endpoint was approximately 18 weeks after Baseline and 1 month after the 2nd experimental session)	The PSQI is a self-rated questionnaire which assesses sleep quality and disturbances. It is comprised of 19 items that yield 7 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 Dissociation Experiences Scale II (DES-II) Total Score From Baseline to Primary Endpoint	Baseline to Primary Endpoint (Primary Endpoint was approximately 18 weeks after Baseline and 1 month after the 2nd 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. It is an established measure of dissociative symptoms. The scale consists of statements describing facets of dissociation. Respondents indicate how often the specific experience happens to them, from from "never" (0% of the time) to "always" (100%). The scale is scored by treating percentages as single digits and averaging to produce a total score, ranging from 0 to 100. The higher the score, the more dissociative symptoms.
Change in Posttraumatic Growth Inventory (PTGI) Total Score From Baseline to Primary Endpoint	Baseline to Primary Endpoint (Primary Endpoint was approximately 18 weeks after Baseline and 1 month after the 2nd experimental session)	The PTGI is a 21-item self-report measure of perceived growth or benefits occurring after a traumatic event. It contains 5 subscales: relationship to others, new possibilities, personal strength, spiritual change, and appreciation of life. Responses to each question are made on a scale of 0 (no change) to 5 (great degree of change), with higher scores indicating greater personal growth. Items are added to calculate the total PTGI score which ranges from 0 to 105, with higher scores indicative of greater growth.