Clinical TrialPTSDMDMAMDMARecruiting
MDMA-assisted Massed Prolonged Exposure for PTSD
Randomized, quadruple-blind Phase III parallel pilot (n=20) evaluating MDMA-assisted Massed Prolonged Exposure (one MDMA medicine session plus 12 90-minute PE sessions) in US veterans with PTSD; doses randomized (exact doses not disclosed).
Target Enrollment
20 participants
Study Type
Phase III interventional
Design
Randomized, quadruple Blind
Registry
Detailed Description
This randomized pilot evaluates the VASDHS-adapted Emory MDMA-PE protocol in veterans with PTSD using a parallel design with two active dose arms; one MDMA medicine session is paired with a massed PE course of twelve 90-minute sessions spanning roughly three weeks.
Primary outcome is change in clinician-rated PTSD symptoms (CAPS-5); secondary assessments include safety, tolerability, acceptability, SUDS during imaginal exposure, and remote CAPS-5 follow-ups at 1 week, 2 months, and 4 months. An optional fMRI substudy will be offered pre- and post-treatment.
Preparatory and integration sessions are included (one preparatory session prior to MDMA and at least one integration session after); optional additional MDMA/integration sessions may be offered after unblinding at 2-month follow-up.
Study Protocol
Preparation
1 sessions
Dosing
1 sessions
Integration
1 sessions
Therapeutic Protocol
other
Study Arms & Interventions
Dose A
experimentalProlonged Exposure with one MDMA medicine session (Dose A); 12 non-medicine PE sessions plus one MDMA session.
Interventions
- MDMAvia Oral• single dose• 1 doses total
Exact MDMA dose not disclosed; one medicine session.
- Compoundvia Other• 12 sessions
Prolonged Exposure: 12 90-minute PE sessions (initial two sessions at first treatment visit; third and fourth during MDMA session; remaining daily or every other day).
Dose B
experimentalProlonged Exposure with one MDMA medicine session (Dose B); 12 non-medicine PE sessions plus one MDMA session.
Interventions
- MDMAvia Oral• single dose• 1 doses total
Exact MDMA dose not disclosed; one medicine session.
- Compoundvia Other• 12 sessions
Prolonged Exposure: 12 90-minute PE sessions (initial two sessions at first treatment visit; third and fourth during MDMA session; remaining daily or every other day).
Participants
Ages
18 – 64
Sexes
Male & Female
BMI
-
Psychosis History
-
Inclusion Criteria
- Inclusion Criteria:
- 1. Be a veteran (age 18-64 years old) who meets criteria for PTSD on the CAPS-5 (severity ≥ 25).
- 2. Be fluent in speaking and reading English.
- 3. Are willing to commit to medication dosing, therapy sessions, follow-up sessions, completing evaluation instruments, and all necessary telephone contact.
- 4. Be able to swallow pills.
- 5. Agree to have study visits audio and/or video recorded, including MDMA session, assessments, and PE sessions, and aware that Independent Rater assessments for PE sessions will occur.
- 6. Have a contact able to drive the participant home after the MDMA session.
- 7. 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.
- 8. Agree to inform the investigators within 48 hours of any new medical conditions or procedures.
- 9. If able to become pregnant, must have a highly sensitive negative pregnancy test at study entry and prior to the MDMA session, and must agree to use adequate birth control for 1 month before through 10 days after the MDMA session (two forms required with any barrier method or oral hormones).
- 10. Agree to the following lifestyle modifications: comply with requirements for fasting and refraining from certain medications prior to and following the MDMA session, including a possible medication taper if on SSRIs, medications for ADHD, and/or other medications described in the concomitant medications section.
- 11. Agree not to participate in other PTSD psychotherapy during study treatment.
- 12. Not enroll in any other interventional clinical trials during the duration of the study, and commit to medication dosing, therapy, and study procedures.
- 13. At Pre-Screening, have at least moderate PTSD symptoms in the last month based on PCL-5 total score of 40 or greater (index).
- 14. 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.
- 15. May have asymptomatic Hepatitis C virus (HCV) that has previously undergone evaluation and treatment as needed.
- 16. May have alcohol or substance use disorder if participant is not in withdrawal or requiring detox; must have a realistic plan to reduce use agreed by investigator, therapy team, and study physician and pass urine toxicology prior to enrollment and before the MDMA session.
- 17. May have a history of or current Diabetes Mellitus (Type 2) if additional screening measures rule out underlying cardiovascular disease and the condition is stable and approved by the study physician.
- 18. May have hypothyroidism if taking adequate and stable thyroid replacement medication.
- 19. May have a history of, or current, glaucoma if approval for study participation is received from an ophthalmologist.
Exclusion Criteria
- Exclusion Criteria:
- 1. Are not able to give adequate, written informed consent.
- 2. Are currently engaged in compensation and pension (C&P) 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 assessment 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) or have participated in an MDMA clinical trial.
- 5. Have a positive screen for amphetamine or cocaine.
- 6. Have any current problem which, in the clinical opinion of the investigator and study physician, might interfere with participation due to it impacting the patient's safety and/or ability to participate in the protocol.
- 7. Have hypersensitivity to any ingredient of the IMP (Investigational Medicinal Product).
- 8. Have received Electroconvulsive Therapy (ECT) within 12 weeks of enrollment.
- 9. Have dementia.
- 10. Have a history of or a current primary psychotic disorder assessed via the DIAMOND and clinical interview.
- 11. Have a history of or current Bipolar 1 disorder, Bipolar 2 disorder, or manic episode assessed via the DIAMOND and clinical interview.
- 12. Have a current eating disorder with active purging assessed via DIAMOND and clinical interview.
- 13. Have current major depressive disorder with psychotic features assessed via DIAMOND.
- 14. Have a current panic disorder assessed via the DIAMOND.
- 15. Have a history of amphetamine or cocaine substance use disorder.
- 16. Have a current alcohol or substance use disorder other than caffeine or nicotine that the investigators, therapy team, and/or study physician judge to be a safety concern for enrollment in the study or that could interfere with the therapeutic process or with other aspects of study participation.
- 17. Present with current serious suicide risk, as determined through psychiatric interview, responses to C-SSRS (scores of four or greater), and clinical judgment of the investigator; however, history of suicide attempts is not an exclusion. Any participant who is likely to require hospitalization related to suicidal ideation and behaviour, in the judgment of the investigator, will not be enrolled.
- 18. Would present a serious risk to others as established through clinical interview and if necessary, discussion with treating psychiatrist.
- 19. Require ongoing concomitant therapy with a psychiatric medication other than the exceptions described in protocol section on Concomitant Medications.
- 20. Have a history of any medical condition that could make receiving a sympathomimetic drug harmful because of increases in blood pressure and heart rate (e.g., myocardial infarction, cerebrovascular accident, or aneurysm); other stable medical conditions may be allowed with approval.
- 21. Have a diagnosis of uncontrolled hypertension (repeated readings ≥ 140/90 mmHg).
- 22. Have a history of ventricular arrhythmia at any time, other than occasional PVCs in the absence of ischemic heart disease.
- 23. Have Wolff-Parkinson-White syndrome or any other accessory pathway not successfully eliminated by ablation.
- 24. Have a history of arrhythmia within 12 months of screening (exceptions apply with cardiologist confirmation).
- 25. Have marked baseline prolongation of QT/QTc (QTcF >450 ms).
- 26. Have additional risk factors for Torsade de pointes.
- 27. Require use of concomitant medications that prolong the QT/QTc interval during sessions.
- 28. Have symptomatic liver disease or repeated significant liver enzyme elevations.
- 29. Have history of hyponatraemia or hyperthermia.
- 30. Have a BMI of 18.5 or less.
- 31. Are pregnant or nursing or are able to become pregnant and are not willing/able to practice effective birth control.
- 32. Have engaged in ketamine-assisted therapy or used ketamine within 12 weeks of enrollment.
- 33. Have any preexisting condition affecting renal functioning.