Alcohol Use Disorder, Post Traumatic Stress Disorder
Conditions
Keywords
AUD, PTSD
Brief summary
The study investigators are conducting the first open label pilot trial of MDMA-assisted therapy (MDMA-AT) with a comorbid sample of military veterans with a comorbid diagnosis of Alcohol Use Disorder (AUD) and Post-Traumatic Stress Disorder (PTSD). This novel experimental treatment package consists of two once-monthly Experimental Sessions of therapy combined with a divided-dose of MDMA HCl, along with non-drug preparatory and integrative therapy. The Primary Outcome measure, the Timeline Follow-back (TLFB), will evaluate changes in alcohol use over time. Changes in PTSD symptoms will also be evaluated.
Detailed description
The study will use a longitudinal design to conduct an open label pilot trial of MDMA-AT. The study will also collect neuroimaging and biomarker data to examine brain changes pre-post treatment. Eligible participants will complete an in-person baseline assessment, undergo optional imaging protocols (if participant agrees and is medically safe to do so), engage in MDMA-AT with clinicians trained by MAPS PBC, and complete assessments at the post-treatment follow-up For complete description of the investigational plan, please the attached Clinical Protocol.
Interventions
DRUGMDMA
medication and therapy combined
Sponsors
Carolina L Haass-Koffler
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Are able to provide proof of veteran status. 2. Are fluent in speaking and reading English. 3. At Baseline, meet criteria for Alcohol Use Disorder as measured by the SCID-5. 4. Able to safely abstain from alcohol for at least 48 hours without requiring medical detox. 5. At Baseline meet DSM-5 criteria for current PTSD with a symptom duration of at least 6 months. 6. At Baseline, have a PCL-5 score of 33 or greater. 7. At Baseline, have a confirmed PTSD diagnosis per the CAPS-5 and a Total Severity Score of 28 or greater. 8. Are able to swallow pills. 9. Agree to have study visits recorded, including Experimental Sessions, assessments, and non-drug therapy sessions. 10. Able to 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 unwell or unreachable. 11. Able to identify appropriate support person(s) to stay with the participant on the evenings of the Experimental Sessions, see Section Support Person. Weight 12. Body weight of at least 45 kilograms (kg). Participants with a body weight of 45 to 48 kg must also have a body mass index (BMI) within the range of 18 to 30 kg/m2. Sex and Contraceptive/ Barrier Requirements 13. For participants assigned female sex at birth: * A participant is eligible to participate if not pregnant, not planning to become pregnant, or is not breastfeeding and one of the following conditions applies * Is not able to become pregnant * Is a person able to be pregnant (PABP) and using a contraceptive method that is highly effective, with a failure rate of \<1%. The investigator will evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated) in relationship to the first does of study intervention. A PABP must have a highly sensitive negative urine pregnancy test at study entry and prior to each Experimental Session, see Schedule of Activities. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a participant with an early undetected pregnancy. Informed Consent 14. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. Other Inclusions 15. Agree to inform the investigators within 48 hours of any medical conditions and procedures. 16. May have asymptomatic Hepatitis C virus (HCV) that has previously undergone evaluation and treatment as needed. 17. Participants must have a plan, agreed upon by investigator, therapy team, and study clinician, to reduce use of substances and to manage symptoms without self-medicating. Enrollment will require that, in the judgment of the investigator, therapy team, and study physician, the plan for decreasing substance use is realistic and has a good chance of succeeding to prevent substance use from impacting the safety or efficacy of the investigational treatment. 18. May have a history of or current Diabetes Mellitus (Type 2) if additional screening measures rule out underlying cardiovascular disease, if the condition is judged to be stable on effective management, and with approval by the study clinician. 19. May have hypothyroidism if taking adequate and stable thyroid replacement medication. 20. May have a history of, or current, glaucoma if approval for study participation is received from an ophthalmologist.
Exclusion criteria
Medical Conditions 1. Have symptomatic liver disease or have significant liver enzyme elevations. * Alanine transaminase (ALT) or aspartate transaminase (AST) \> 3 x upper limit of normal (ULN). * Total bilirubin \> 1.5 x ULN or direct bilirubin \< 35%. 2. Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. • Note: Stable chronic liver disease (including Gilbert's syndrome, asymptomatic gallstones, and chronic stable hepatitis B (e.g., the presence of hepatitis B surface antigen or positive hepatitis C antibody test result without evidence of active infection at screening or within 3 months prior to starting study intervention) is acceptable if the participant otherwise meets entry criteria. 3. Have a history of seizures or delirium tremens (DTs). 4. Significant alcohol withdrawal symptoms, defined as a Clinical Institute Withdrawal Assessment of alcohol scale, revised (CIWA-Ar) \>10. 5. Have a recent history of clinically significant hyponatremia or hyperthermia. 6. Have a marked Baseline QTcF interval \>450 ms demonstrated on repeated ECG assessments. Participants whose QTcF exceeds this value during screening may be initially enrolled if a pre-study concomitant medication is suspected to be prolonging the QT-interval. ECGs should be repeated after initial enrollment and tapering off the pre-study concomitant medication to ensure the participant meets eligibility criteria prior to enrollment confirmation and to IMP dosing. • Note: The QTcF is the QT interval corrected for heart rate according to Fridericia's formula. It is either machine-read or manually over-read. 7. Have a history of any medical condition that could make receiving a sympathomimetic drug harmful because of increases in blood pressure and heart rate. This includes, but is not limited to, a history of myocardial infarction, cerebrovascular accident, heart failure, severe coronary artery disease, or aneurysm. * Participants with other mild, stable chronic medical problems may be enrolled if the study clinician and principal investigators agree the condition would not significantly increase the risk of MDMA administration or be likely to produce significant symptoms during the study that could interfere with study participation or be confused with side effects of the IMP. * Examples of stable medical conditions that could be allowed include, but are not limited to, Diabetes Mellitus (Type 2), Human Immunodeficiency Virus (HIV) infection, Gastroesophageal Reflux Disease (GERD), hypothyroidism (if taking adequate and stable thyroid replacement medication), glaucoma (if approval for study participation is received from an ophthalmologist). Any medical disorder judged by the investigator to significantly increase the risk of MDMA administration by any mechanism would require exclusion. 8. Have a diagnosis of controlled or uncontrolled hypertension, defined as repeated blood pressure readings of ≥ 140 millimeters of Mercury \[mmHg\] systolic or ≥ 90 mmHg diastolic. The diagnosis may be confirmed by repeated clinic measurements or home blood pressure monitoring if clinically indicated. 9. Have a history of ventricular arrhythmia at any time, other than occasional premature ventricular contractions (PVCs) in the absence of ischemic heart disease. 10. Have Wolff-Parkinson-White syndrome or any other accessory pathway that has not been successfully eliminated by ablation. 11. Have a history of arrhythmia, other than premature atrial contractions (PACs) or occasional PVCs in the absence of ischemic heart disease, within 12 months of screening. • Participants with a history of atrial fibrillation, atrial tachycardia, atrial flutter or paroxysmal supraventricular tachycardia or any other arrhythmia associated with a bypass tract may be enrolled only if they have been successfully treated with ablation and have not had recurrent arrhythmia for at least one year off all antiarrhythmic drugs or are under adequate and stable pharmacologic treatment for atrial fibrillation for at least a year, as confirmed by a cardiologist. 12. Have a history of additional risk factors for Torsade de pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome). 13.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of standard unit drinks form the TLFB | From baseline to post-treatment follow up (18 weeks) | Amount of alcohol consumed |
| CAPS score reduction | From baseline to post-treatment follow up (18 weeks) | Severity score past 30 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability | From baseline to post-treatment follow up (18 weeks) | Number of Adverse Events |
Countries
United States
Outcome results
None listed