Een studie naar de veiligheid en effecten van psychotherapie in combinatie met MDMA als behandeling voor zware post-traumatische stress stoornis

At the completion of Screening, participants must meet all eligibility criteria (except Inclusion Criterion #13) and agree to all lifestyle modifications to be enrolled. Each participant will then enter the Preparatory Period which includes medication tapering, if needed, and non-drug Preparatory Sessions. The Preparatory Period ends with Enrollment Confirmation. A participant’s enrollment will be confirmed if they have completed medication tapering, have a confirmed PTSD diagnosis per the CAPS-5 assessment and a Total Severity Score of 35 or greater, continue to agree to all lifestyle modifications, and continue to meet all eligibility criteria (those criteria marked with an * below will only be assessed at Screening, since they will not change).



Potential participants are eligible to enroll in the protocol if they:



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 recorded, including Experimental Sessions, Independent Rater assessments, and non-drug psychotherapy sessions

5. Must provide a contact (relative, spouse, close friend or other caregiver) 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 conditions 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, 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

Medical History

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 at least severe PTSD per CAPS-5 and symptoms in the last month constituting a CAPS-5 Total Severity Score of 35 or greater.

Potential participants are ineligible to enroll in the protocol if they:

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

6. *Have received Electroconvulsive Therapy (ECT) within 12 weeks of enrollment

7. *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

8. *Have a current eating disorder with active purging assessed via MINI

9. *Have current major depressive disorder with psychotic features assessed via MINI

10. *Meet DSM-5 criteria for active substance use disorder for any substance other than caffeine or nicotine in the past 60 days assessed via MINI, AUDIT, DUDIT, drug test, and blood %carbohydrate-deficient transferrin (%CDT)

11. Have current Personality Disorders Cluster A (paranoid, schizoid, schizotypal), Cluster B (antisocial, borderline, histrionic, narcissistic), or Cluster C (avoidant, dependent, obsessive-compulsive) assessed via SCID-5-PD. Diagnoses will be confirmed via clinical interview

12. 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

13. Would present a serious risk to others as established through clinical interview and contact with treating psychiatrist

14. Require ongoing concomitant therapy with a psychiatric medication with exceptions described in Section 12.0: Concomitant Medications.

Medical History

15. *Have evidence or history of significant (controlled or uncontrolled) hematological, endocrine, cerebrovascular, cardiovascular, coronary, pulmonary, renal, 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 ophthalmologist

16. *Have uncontrolled hypertension using the standard criteria of the American Heart Association (values of 140/90 milligrams of Mercury [mmHg] or higher assessed on three separate occasions)

17. *Have a marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 milliseconds [ms] corrected by Bazett’s formula)

18. *Have a history of additional risk factors for Torsade de pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)

19. *Require use of concomitant medications that prolong the QT/QTc interval during Experimental Sessions. Refer to Section 12.0 Concomitant Medications.

20. *Have symptomatic liver disease

21. *Have history of hyponatremia or hyperthermia

22. *Weigh less than 48 kilograms (kg)

23. Are pregnant or nursing, or are of childbearing potential and are not practicing an effective means of birth control.