Trauma
Conditions
Interventions
The treatment consists of a flexible dose of MDMA, followed by a supplemental
half-dose unless contraindicated, administered with manualized psychotherapy in
two open-label Experimental Sessions spa
Sponsors
MAPS Europe B.V.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Are at least 18 years old 2. Are fluent in speaking and reading the predominantly used or recognized language of the study site 3. Are able to swallow pills 4. Agree to have study visits video-recorded, including Experimental Sessions, Independent Rater assessments, and non-drug psychotherapy sessions 5. Must provide a contact (relative, spouse, close friend or other support person) who is willing and able to be reached by the investigators in the event of a participant becoming suicidal or unreachable 6. Must agree to inform the investigators within 48 hours of any medical treatments and procedures 7. If of childbearing potential, must have a negative pregnancy test at study entry and prior to each Experimental Session, and must agree to use adequate birth control through 10 days after the last Experimental Session. Adequate birth control methods include intrauterine device (IUD), injected or implanted hormonal methods, abstinence, oral hormones plus a barrier contraception, vasectomized sole partner or double barrier contraception. Two forms of contraception are required with any barrier method or oral hormones (i.e. condom plus diaphragm, condom or diaphragm plus spermicide, oral hormonal contraceptives plus spermicide or condom). Not of childbearing potential is defined as permanent sterilization, postmenopausal, or assigned male at birth. 8. Agree to the following lifestyle modifications (described in more detail in Section 4.3 Lifestyle Modifications): comply with requirements for fasting and refraining from certain medications prior to Experimental Sessions, not participate in any other interventional clinical trials during the duration of the study, remain overnight at the study site after each Experimental Session and be driven home after, and commit to medication dosing, therapy, and study procedures 9. At Screening, meet DSM-5 criteria for current PTSD with a symptom duration of 6 months or longer 10. At Screening, have at least severe PTSD symptoms in the last month based on PCL-5 total score of 50 or greater 11. At Screening, may have well-controlled hypertension that has been successfully treated with anti-hypertensive medicines, if they pass additional screening to rule out underlying cardiovascular disease 12. At Screening, may have asymptomatic Hepatitis C virus (HCV) that has previously undergone evaluation and treatment as needed 13. At Baseline, have a confirmed diagnosis of PTSD per CAPS-5 and at least severe symptoms in the last month constituting a CAPS-5 Total Severity Score of 35 or greater. 14. Absence of Traumatic Brain Injury 15. Absence of metal implants or metal fragments in the body 16. PTSD must be of non-dissociative sub-type 17. Absence of claustrophobia 18. Absence of tattoos in the head/neck or permanent eye makeup
Exclusion criteria
Exclusion criteria: 1. Are not able to give adequate informed consent 2. Are currently engaged in compensation litigation whereby financial gain would be achieved from prolonged symptoms of PTSD or any other psychiatric disorders 3. Are likely, in the investigator*s opinion and via observation during the Preparatory Period, to be re-exposed to their index trauma or other significant trauma, lack social support, or lack a stable living situation 4. Have used Ecstasy (material represented as containing MDMA) more than 10 times within the last 10 years or at least once within 6 months of the first Experimental Session; or have previously participated in a MAPS-sponsored MDMA clinical trial 5. Have any current problem which, in the opinion of the investigator or Medical Monitor, might interfere with participation, Psychiatric History, 1. Have received Electroconvulsive Therapy (ECT) within 12 weeks of enrollment 2. Have a history of, or a current primary psychotic disorder, bipolar affective disorder type 1 assessed via MINI or dissociative identity disorder assessed via DDIS 3. Have Dissociative Subtype of PTSD assessed via CAPS-5 4. Have a current eating disorder with active purging assessed via MINI 5. Have current major depressive disorder with psychotic features assessed via MINI 6. Meet DSM-5 criteria for current substance use disorder for alcohol or substance use disorder other than caffeine or nicotine assessed via MINI, AUDIT, DUDIT, drug test, and blood %carbohydrate-deficient transferrin (%CDT) 7.Have current Personality Disorders (paranoid, schizoid, antisocial, borderline, histrionic, narcissistic, avoidant, dependent, obsessive-compulsive) assessed via CIPD. Diagnoses will be confirmed via clinical interview 8. Any participant presenting current serious suicide risk, as determined through psychiatric interview, responses to C-SSRS, and clinical judgment of the investigator will be excluded; however, history of suicide attempts is not an exclusion. Any participant who is likely to require hospitalization related to suicidal ideation and behavior, in the judgment of the investigator, will not be enrolled 9. Would present a serious risk to others as established through clinical interview and contact with treating psychiatrist 10. Require ongoing concomitant therapy with a psychiatric medication with exceptions described in Section 12.0: Concomitant Medications., Medical History, 1. Have evidence on clinical examination or history of significant (controlled or uncontrolled) hematological, endocrine, cerebrovascular, traumatic brain injury (TBI) with residual neurological signs or symptoms on the physical exam, cardiovascular, coronary artery disease (using the New York Heart Association criteria) cerebral or peripheral vascular disease, pulmonary, renal, hepatic disease with abnormal liver enzymes (outside of the normal clinical range), gastrointestinal, immunocompromising, or neurological disease, including seizure disorder, or any other medical disorder judged by the investigator to significantly increase the risk of MDMA administration (participants with hypothyroidism who are on adequate and stable thyroid replacement will not be excluded). Note: if participants present with a history of glaucoma, enrollment would be allowed only with the approval of their oph
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary objective of this study is to evaluate the effect of MDMA-assisted psychotherapy on PTSD, as measured by the estimand of change in CAPS-5 Total Severity Score from Baseline (Visit 3) to 13 weeks post Baseline (Visit 14). The primary and key secondary endpoint analyses will be based on the mITT analysis set. Change from Visit 3 (Baseline) in CAPS-5 Total Severity Scores to Visit 14 (Primary Endpoint) will be analyzed with least squares means from a Mixed-Effect Repeated Measures model (MMRM). The mITT analysis set will include all participants who receive IP in at least one Experimental Session and have at least one follow-up CAPS-5 assessment. The Primary Outcome measure, the change in CAPS-5 from Baseline (V3), is assessed by a centralized Independent Rater (IR) pool at 13 weeks post Baseline (V14). The CAPS-5 is also administered as an exploratory measure after Treatment 1 (V8). The IR pool will be blinded to visit number and number of treatments received and will not have access to data collected by the sites during the active treatment period. | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary objective is to evaluate the effectiveness of MDMA-assisted psychotherapy for PTSD in clinician-rated functional impairment, as measured by the mean change in Sheehan Disability Scale (SDS) item scores from Visit 3 (Baseline) to Visit 14 (13 weeks post Baseline). Safety Objective The overall safety objective is to assess severity, incidence and frequency of AEs, AEs of Special Interest (AESIs), and Serious Adverse Events (SAEs), concomitant medication use, suicidal ideation and behavior, and vital signs to support the package insert for MDMA-assisted psychotherapy. The following safety objectives will evaluate the safety of MDMA-assisted psychotherapy: 1. Assess incidence of AEs during Experimental Sessions that may be indicative of a medical complication of the Investigational Product (IP), such as clinical signs and symptoms of chest pain, shortness of breath, or neurological symptoms or any other signs or symptoms that prompt additional vital sign measurements. 2. Assess incidence of AEs by severity. 3. Assess incidence of Treatment Emergent AEs (TEAEs) by severity. 4. Assess incidence of TEAEs by severity taken during an Experimental Session and through 2 days after IP administration. 5. Assess incidence of AESIs, defined as AEs specified in the protocol related to cardiac function and abuse liability. 6. Assess incidence of AEs by severity categorized as leading to discontinuation of IP, resulting in death or hospitalization, and continuing at Study Termination. 7. Assess incidence of SAEs. 8. Assess incidence of psychiatric concomitant medications taken during an Experimental Session and through 2 days after IP administration. 9. Assess incidence of any psychiatric concomitant medications taken during the Treatment Period. 10. Assess incidence of serious suicidal ideation and positive suicidal behavior assessed with the Columbia Suicide Severity Rating Scale (C-SSRS). 11. Assess mean changes in blood pressure, heart | — |
Countries
Netherlands
Outcome results
None listed