Clinical TrialPTSDMDMAPlaceboUnknown status
Epigenetics and MDMA-Assisted Psychotherapy for PTSD
Add-on substudy (n=45) to a Phase III MDMA-assisted psychotherapy trial collecting salivary DNA at baseline and after treatment to assess epigenetic changes related to PTSD symptom change.
Target Enrollment
45 participants
Study Type
Phase III interventional
Design
Randomized, triple Blind
Registry
Detailed Description
This substudy collects saliva from participants enrolled in the parent Phase III randomized trial of MDMA-assisted psychotherapy to evaluate whether treatment-related changes occur in the epigenetic regulation of stress-associated genes.
Saliva is collected at baseline (prior to the first experimental session) and following the final experimental session (approximately 18 weeks after the first treatment) using Oragene DNA OG-500 kits for downstream analysis of salivary epithelial and white blood cell DNA.
Study Protocol
Preparation
sessions
Dosing
2 sessions
Integration
sessions
Therapeutic Protocol
Manualized psychotherapy included
Study Arms & Interventions
MDMA Assisted Psychotherapy
experimentalLongitudinal course of psychotherapy with administration of MDMA on treatment sessions (per parent protocol).
Interventions
- MDMAvia Oral• two sessions• 2 doses total
Adjunctive MDMA administered during treatment sessions per parent protocol.
- Compound• per protocol
Psychotherapy per parent Phase III protocol (preparatory, experimental and integration sessions).
Placebo Assisted Psychotherapy
inactiveLongitudinal course of psychotherapy with administration of placebo on treatment sessions (per parent protocol).
Interventions
- Placebovia Oral• two sessions• 2 doses total
Placebo administered during treatment sessions.
- Compound• per protocol
Psychotherapy per parent Phase III protocol (preparatory, experimental and integration sessions).
Participants
Ages
18 – 99
Sexes
Male & Female
BMI
-
Psychosis History
-
Inclusion Criteria
- (As per the parent Phase III Trial - "A Multi-Site Phase 3 Study of MDMA-Assisted Psychotherapy for PTSD" (ClinicalTrials.gov Identifier: NCT03537014)).
- 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 support person) who is willing and able to be reached
- 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, 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 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.
Exclusion Criteria
- (As per the parent Phase III Trial - "A Multi-Site Phase 3 Study of MDMA-Assisted Psychotherapy for PTSD" (ClinicalTrials.gov Identifier: NCT03537014)).
- 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 and confirmed via clinical interview or dissociative identity disorder assessed via DDIS and confirmed via clinical interview
- 8. *Have a current eating disorder with active purging assessed via MINI and confirmed via clinical interview
- 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 assessed via combination of clinical judgment, 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.
- 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 millimetres 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