Clinical trial NCT01958593: Randomized, Double-blind, Controlled of MDMA-assisted Psychotherapy in 12 Subjects With PTSD
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Posttraumatic Stress Disorder
Keywords: PTSD
Posttraumatic stress disorder
MDMA
psychotherapy
therapy
Lead sponsor: Lykos Therapeutics
Sponsor class: INDUSTRY
First posted: 2013-10-09
Enrollment: 6
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in Clinician-Administered PTSD Scale (CAPS-IV) Score From Baseline to Primary Endpoint
timeFrame: Baseline to Primary Endpoint (Primary Endpoint was approximately 18 weeks after Baseline and 1 month after the 2nd experimental session)
Secondary outcomes:
measure: Change in PTSD Diagnostic Scale (PDS) Total Severity Score From Baseline to Primary Endpoint
timeFrame: Baseline to Primary Endpoint (Primary Endpoint was approximately 18 weeks after Baseline and 1 month after the 2nd experimental session)
measure: Change in Beck Depression Inventory (BDI-II) Score From Baseline to Primary Endpoint
timeFrame: Baseline to Primary Endpoint (Primary Endpoint was approximately 18 weeks after Baseline and 1 month after the 2nd experimental session)
measure: Change in Global Assessment of Functioning (GAF) Score From Baseline to Primary Endpoint
timeFrame: Baseline to Primary Endpoint (Primary Endpoint was approximately 18 weeks after Baseline and 1 month after the 2nd experimental session)
measure: Change in Pittsburgh Sleep Quality Index (PSQI) Score From Baseline to Primary Endpoint
timeFrame: Baseline to Primary Endpoint (Primary Endpoint was approximately 18 weeks after Baseline and 1 month after the 2nd experimental session)
measure: Change in Dissociation Experiences Scale II (DES-II) Total Score From Baseline to Primary Endpoint
timeFrame: Baseline to Primary Endpoint (Primary Endpoint was approximately 18 weeks after Baseline and 1 month after the 2nd experimental session)
measure: Change in Posttraumatic Growth Inventory (PTGI) Total Score From Baseline to Primary Endpoint
timeFrame: Baseline to Primary Endpoint (Primary Endpoint was approximately 18 weeks after Baseline and 1 month after the 2nd experimental session)
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: Offices of Dr. Ingrid Pacey MBBS FRCP[C]
state: British Columbia
Study officials:
affiliation: University of Victoria
name: Ingrid Pacey, MBBS FRCP[C]
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jerome L, Feduccia AA, Wang JB, Hamilton S, Yazar-Klosinski B, Emerson A, Mithoefer MC, Doblin R. Long-term follow-up outcomes of MDMA-assisted psychotherapy for treatment of PTSD: a longitudinal pooled analysis of six phase 2 trials. Psychopharmacology (Berl). 2020 Aug;237(8):2485-2497. doi: 10.1007/s00213-020-05548-2. Epub 2020 Jun 4.
citation: Feduccia AA, Jerome L, Yazar-Klosinski B, Emerson A, Mithoefer MC, Doblin R. Breakthrough for Trauma Treatment: Safety and Efficacy of MDMA-Assisted Psychotherapy Compared to Paroxetine and Sertraline. Front Psychiatry. 2019 Sep 12;10:650. doi: 10.3389/fpsyt.2019.00650. eCollection 2019.
citation: Mithoefer MC, Feduccia AA, Jerome L, Mithoefer A, Wagner M, Walsh Z, Hamilton S, Yazar-Klosinski B, Emerson A, Doblin R. MDMA-assisted psychotherapy for treatment of PTSD: study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials. Psychopharmacology (Berl). 2019 Sep;236(9):2735-2745. doi: 10.1007/s00213-019-05249-5. Epub 2019 May 7.