MDMA-Assisted Psychotherapy in People With Posttraumatic Stress Disorder

Phase 2

Completed

Conditions: Posttraumatic Stress Disorder

Interventions: Drug: Midomafetamine HCl
Drug: Lactose placebo pill
Behavioral: Therapy

Registration Number: NCT00090064

Lead Sponsor: Lykos Therapeutics

Brief Summary: The goal of this clinical trial is to compare MDMA-assisted therapy to placebo with therapy in people with chronic, treatment-resistant posttraumatic stress disorder (PTSD). The main question it aims to answer is: Is there a reduction in PTSD symptoms among people given MDMA-assisted therapy compared to placebo with therapy?

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 psychotherapy sessions and non-drug integrative sessions.

The study will test whether MDMA-assisted therapy can be safely given to participants. 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.

Detailed Description: This randomized, double-blind placebo-controlled pilot study assessed the safety and effectiveness of MDMA-assisted therapy among people with chronic, treatment-resistant PTSD, including veterans. Participants were assigned to receive either MDMA-assisted therapy or placebo with therapy during two blinded experimental sessions spaced three to five weeks apart during Stage 1 of the study. During these experimental sessions, participants received an initial dose of 125 mg of MDMA HCl followed by a supplemental dose of 62.5 mg of MDMA HCl, or they received initial and supplemental doses of inactive placebo. Psychotherapists and independent raters were blinded to participants' treatment conditions. This treatment period also consisted of non-drug preparatory therapy sessions and non-drug integration therapy sessions.

During Stage 2 of the study, the blind was broken and participants assigned to receive MDMA-assisted therapy in Stage 1 underwent a third open-label experimental session of MDMA-assisted therapy. Participants assigned placebo with therapy during Stage 1 who chose to enroll in Stage 2 underwent three open-label sessions of MDMA-assisted therapy. Outcome measures were administered two months after the second experimental session in Stage 1 and four to six weeks after the second MDMA-assisted therapy session in Stage 2. A final data-collection session took place at two months after the third experimental session.

The primary objective of the study was to measure change in PTSD symptoms via CAPS-IV across the study in participants receiving MDMA-assisted therapy versus placebo with therapy.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 23

Inclusion Criteria

Have current PTSD (within the past 6 months) in response to crime victimization, including childhood sexual or physical abuse, or meet criteria for PTSD in response to combat;
Have a CAPS score showing moderate to severe PTSD symptoms;
They must either:
1. Have had at least one unsuccessful attempt at treatment for PTSD with a SSRI and psychotherapy;
2. Be a veteran with PTSD symptoms that have endured for no less than one year but no more than five years
Be at least 18 years old;
Must be generally healthy;
Willing to remain overnight at the study site;
Agree to have transportation home the morning 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 reading English;

Exclusion Criteria

Are pregnant or nursing, or are able to bear children and are not practicing an effective means of birth control;
Weigh less than 50 kg or more than 105 kg;
Are unable to give adequate informed consent;
Prior use of "Ecstasy" (illicit drug preparations purported to contain MDMA) more than 5 times or at any time within the previous 6 months;
Have a history of certain excluded medical disorders.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MDMA-assisted therapy (125 mg)	Midomafetamine HCl	Participants will receive an initial dose of 125 mg midomafetamine HCl orally followed 2 to 2.5 hours later by a second dose of 62.5 mg midomafetamine HCl during two 8-hour long blinded therapy sessions.
MDMA-assisted therapy (125 mg)	Therapy	Participants will receive an initial dose of 125 mg midomafetamine HCl orally followed 2 to 2.5 hours later by a second dose of 62.5 mg midomafetamine HCl during two 8-hour long blinded therapy sessions.
Placebo with therapy	Lactose placebo pill	Participants will receive an initial dose of 125 mg placebo orally followed 2 to 2.5 hours later by a second dose of 62.5 mg placebo during two 8-hour long blinded therapy sessions.
Placebo with therapy	Therapy	Participants will receive an initial dose of 125 mg placebo orally followed 2 to 2.5 hours later by a second dose of 62.5 mg placebo during two 8-hour long blinded therapy sessions.

Primary Outcome Measures

Name	Time	Method
Change in Clinician-Administered PTSD Scale (CAPS-IV) From Baseline to 2-month Follow-up	Baseline to 2 months post 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 Impact of Events Scale Revised (IES-R) From Baseline to 2-month Follow-up	Baseline to 2 months post second experimental session	The Impact of Events Scale Revised (IES-R) is a 22-item self-report measure (for DSM-IV) designed to measure the extent to which a given stressful life event produces subjective distress. Each item corresponds directly to 14 of the 17 DSM-IV symptoms of PTSD and is rated on a 5-point scale ranging from 0 ("not at all") to 4 ("extremely") for the extent to which the item was true for the participant during the past seven days. The IES-R yields a total score ranging from 0 to 88 with higher scores indicated greater distress.