MDMA Assisted Therapy for BN

MDMA Assisted Therapy for Bulimia Nervosa: A Treatment Development Protocol

This project will evaluate MDMA Assisted Therapy (MDMA-AT) assisted psychotherapy for the treatment of Bulimia Nervosa (BN) over a 10-week period. Preliminary data suggests that MDMA can facilitate heightened openness and reduce anxiety. This study will determine whether MDMA-assisted therapy can serve as a new treatment for BN. Participants are assigned to one of three groups: MDMA-AT, MDMA-AT-BN, and Standard Treatment (ST). MDMA groups include three experimental session that include dosing, which are each followed by three integrative sessions and also include 12 psychotherapy sessions. A follow-up will take place at 6-months post baseline.

Three groups (MDMA-AT, MDMA-AT-BN, and ST) will be compared on changes in Binge Eating frequency, severity of symptoms, body image, weight, retention, acceptability of treatment, motivation, and safety. Assessments include a screening phase, baseline, MDMA-preparation phase, intervention, and a follow-up. MDMA-AT includes 3 sessions of MDMA-assisted psychotherapy, 9 integrative sessions that involve discussing the experiences during MDMA sessions and processing thoughts, emotions, and distress. Additionally, 12 weekly non-specific therapy sessions take place after the dosing and integrative sessions. MDMA-AT-BN includes the same visits, but the psychotherapy is specific to BN. ST includes 22 weekly sessions focusing on thoughts and behaviors related to BN. A final follow-up visit will take place 6-months after baseline.

Inclusion Criteria:

Participants will be included in the protocol if they meet the following criteria:

• At least 18 years of age
• Meet criteria for Bulimia Nervosa as measured by the EDA-5
• Able to provide written, informed consent
• Able to swallow pills
• Agree to have study visits recorded, including Experimental Sessions and non-medication therapy sessions
• Provides 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
• Agrees to inform the investigators within 48 hours of any medical conditions and procedures
• If able to become pregnant, must have a negative pregnancy test at study entry and prior to each Experimental Session, and must agree to use adequate contraceptive methods through 10 days after the last Experimental Session. Adequate contraceptive methods include intrauterine device (IUD), injected, implanted, intravaginal, or transdermal 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 able to become pregnant' is defined as permanent sterilization, postmenopausal, or assigned male at birth
• Agrees to the lifestyle modifications
• Live within reasonable driving distance of the study site (equal to or less than an estimated 2-hour drive from the study site).
• Have an identified Primary Care Physician (PCP) and provide consent for the investigator to communicate with PCP, as needed.
• Current or past treatment were not successful to retain remission (i.e., continued to meet criteria for BN) despite participating in at least one ED-specific episode of treatment (inpatient, residential, partial hospitalization, intensive outpatient), as confirmed by medical records, by a general practitioner, or by a specialist in ED.
• Are medically stable according to screening 12-lead Electrocardiogram (ECG), blood pressure monitoring, blood and urine laboratory screening results, and medical history.

Exclusion Criteria:

Participants will be excluded from participation for the following reasons:

• Alanine transaminase (ALT) [or aspartate transaminase (AST)] > 2 x upper limit of normal (ULN). Total bilirubin > 1.5 x ULN (isolated bilirubin > 1.5 x ULN is acceptable if total bilirubin is fractionated and direct bilirubin < 35%).
• Estimated glomerular filtration rate (eGFR) less than 60.
• Current unstable liver or biliary disease per investigator assessment defined by 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.
• Self-induced vomiting of over 14 times per week
• Symptomatic Hepatitis C virus (HCV)
• Moderate alcohol or cannabis use disorder (meets > 3 of 11 diagnostic criteria per DSM-5) or moderate alcohol or cannabis use disorder in early remission for the 3 months prior to enrollment (meets 4 or 5 of 11 diagnostic criteria per DSM-5)
• Diabetes Type 1 or Unstable Type 2 Diabetes
• Untreated hypothyroidism
• Are likely, in the investigator's opinion and via observation during the Preparatory Period, to lack social support or a stable living situation
• 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;
• Have previously participated in a MAPS-sponsored MDMA clinical trial
• Have any current problem which, in the opinion of the investigator or study clinician, might interfere with participation
• Have hypersensitivity to any ingredient of the IMP (Investigational Medicinal Product)
• Have received Electroconvulsive Therapy (ECT) within 12 weeks of enrollment
• Have a history of or a current primary psychotic disorder, bipolar disorder 1 assessed via CAT-MH and confirmed via clinical interview or dissociative identity disorder assessed via DDIS and confirmed via clinical interview
• Have current major depressive disorder with psychotic features assessed via CAT-MH
• Have a current moderate (not in early remission in the 3 months prior to enrollment; meets 4 or 5 of 11 diagnostic criteria per DSM-5) or severe alcohol or cannabis use disorder within the 12 months prior to enrollment (meets at least 6 of 11 diagnostic criteria per DSM-5)
• Have an active illicit drug or prescription drug substance use disorder at any severity (other than cannabis) within 12 months prior to enrollment
• 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. Any participant presenting with the following on the Baseline C-SSRS will be excluded: a. Suicidal ideation score of 4 or greater within the last month of the assessment at a frequency of once a week or more; b. Suicidal ideation score of 5 within the last 6 months of the assessment; c. Any suicidal behavior, including suicide attempts or preparatory acts, within the last 6 months of the assessment. Participants with non-suicidal self-injurious behavior may be included if approved by the study clinician
• Would present a serious risk to others as established through clinical interview and contact with treating psychiatrist
• Require ongoing concomitant therapy with a psychiatric medication with exceptions described the Concomitant Medications Section
• 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, or aneurysm. Participants with other mild, stable chronic medical problems may be enrolled if the study physician and Sponsor-investigator 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), etc. Any medical disorder judged by the investigator to significantly increase the risk of MDMA administration by any mechanism would require exclusión
• ASCVD Risk Estimator 10-year cardiovascular risk of 7.5% or higher
• Duke Activity Status Index (DASI) METs score less than 4
• Have a diagnosis of uncontrolled essential hypertension which is assessed using the recommended criteria of the American Heart Association for Stage 2 hypertension (values of 140/90 milligrams of Mercury [mmHg] or higher assessed on three separate occasions)
• Have a history of ventricular arrhythmia at any time, other than occasional premature ventricular contractions (PVCs) in the absence of ischemic heart disease
• Have Wolff-Parkinson-White syndrome or any other accessory pathway that has not been successfully eliminated by ablation
• Have a history of supraventricular arrhythmia within the last 12 months. Participants with a history of an allowable supraventricular arrhythmia (see list below) more than 12 months prior to screening and in the absence of any accessory pathway may be enrolled if successfully treated at least 12 months prior and cleared by a cardiologist, and the study clinician. These arrhythmias may include, and must be limited to, paroxysmal supraventricular tachycardia, paroxysmal atrial tachycardia, or atrial fibrillation that has been successfully treated (e.g., with ablation or cardioversion) at least 12 months previously. Atrial flutter or other arrhythmias will be excluded
• Have a marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTcF interval >450 milliseconds [ms]
• Have a history of additional risk factors for Torsade de pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)
• Require use of concomitant medications that prolong the QT/QTc interval during Experimental Sessions. Refer to Concomitant Medications Section
• Have history of hyponatremia or hyperthermia
• Weigh less than 48 kilograms (kg)
• Are pregnant or nursing or are able to become pregnant and are not practicing an effective means of contraception
• Have a blood or needle phobia that interferes with obtaining necessary blood work.
• Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the sponsor-investigator or study clinician, contraindicates participation in the study.
• Expressed that they are not comfortable in participating in therapy and conducting assessments in English.
• Blood disorder or infection indicated by CBC assay that would be contraindicated for MDMA.
• Thyroid condition (hyperthyroidism) indicated by TSH that would prevent body temperature regulation and be contraindicated for MDMA
• Urinalysis results indicating electrolytes/kidney disfunction