Clinical trial NCT01211405: Study Comparing Three Doses of MDMA Along With Therapy in Veterans With Posttraumatic Stress Disorder
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Posttraumatic Stress Disorder
Keywords: MDMA
Therapy
Veterans
Posttraumatic Stress Disorder
Lead sponsor: Lykos Therapeutics
Sponsor class: INDUSTRY
First posted: 2010-09-29
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in Clinician-Administered PTSD Scale (CAPS-IV) From Baseline to Primary Endpoint
timeFrame: Baseline to one month after second experimental session
Secondary outcomes:
measure: Change in Global Assessment of Function (GAF) From Baseline to Primary Endpoint
timeFrame: Baseline to one month after second experimental session
measure: Change in Posttraumatic Growth Inventory (PTGI) From Baseline to Primary Endpoint
timeFrame: Baseline to one month after second experimental session
measure: Change in Beck Depression Inventory (BDI-II) From Baseline to Primary Endpoint
timeFrame: Baseline to one month after second experimental session
measure: Change in Dissociative Experience Scale (DES-II) From Baseline to Primary Endpoint
timeFrame: Baseline to one month after second experimental session
measure: Change in Pittsburgh Sleep Quality Index (PSQI) From Baseline to Primary Endpoint
timeFrame: Baseline to one month after second experimental session
Other outcomes:
Locations:
city: Mount Pleasant
country: United States
facility: Offices of Michael Mithoefer
state: South Carolina
Study officials:
affiliation: Private Practice
name: Michael Mithoefer, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mithoefer MC, Mithoefer AT, Feduccia AA, Jerome L, Wagner M, Wymer J, Holland J, Hamilton S, Yazar-Klosinski B, Emerson A, Doblin R. 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder in military veterans, firefighters, and police officers: a randomised, double-blind, dose-response, phase 2 clinical trial. Lancet Psychiatry. 2018 Jun;5(6):486-497. doi: 10.1016/S2215-0366(18)30135-4. Epub 2018 May 1.
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.