Bristol Imperial MDMA in Alcoholism Study

Study Overview
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Brief Summary
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The Safety, Tolerability and Role of MDMA-Assisted Psychotherapy for the treatment of detoxified patients with Alcohol Use Disorder.

Detailed Description
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This is an open label within-subject feasibility study, in 20 patients with Alcohol Use Disorder who have recently undergone detoxification. All patients will receive MDMA-Assisted drug therapy. This study aims to assess if MDMA-Assisted Psychotherapy can be delivered safely and can be tolerated by patients with alcohol use disorder post-detoxification. Outcomes regarding abstinence from alcohol, quality of life and psychosocial functioning will be evaluated.

Official Title
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Open-Label Proof of Concept Feasibility Study to Explore the Safety, Tolerability and Potential Role of MDMA-Assisted Psychotherapy for the Treatment of Detoxified Patients With Alcohol Use Disorder

Conditions
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Alcohol Use Disorder

Intervention / Treatment
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* Drug: MDMA
* Other: Psychotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Informed consent Primary diagnosis (as defined by DSM-5) of alcohol use disorder. Successful alcohol detoxification (no longer consuming any alcoholic substances). Between 18 and 65 years old. Be able to identify in advance a supportive significant other(s): who could accompany the patient to study visits if required -who can be contacted by the study team in order to remind the patient about follow- up appointments or collect outcome data (such as drinking behaviour) in the event that the patient themselves cannot be contacted. Proficient in speaking and reading English. Agree to comply with requirements of protocol. Exclusion Criteria Lacking capacity History of, or a current, primary psychotic disorder, bipolar affective disorder type 1 or personality disorder; Present a serious suicide risk; this will be determined using the clinical judgement of the qualified mental health professionals within the research team. They will use information from the Columbia-Suicide Severity Risk Scale (C-SSRS) which allows classification of severity of suicidal ideation and behaviour. This scale classifies severe risk as a) current suicidal ideation with intent and/or plan; b) suicidal behaviour in the last 3 months. A clinical judgement regarding the level of risk and subsequent decisions regarding eligibility and care would use a combination of the information provided by the C-SSRS, the participant's history of previous risk behaviours, any presenting mental health difficulties and environmental and clinical factors. A final decision would usually include a discussion with qualified mental health professionals within the research team. Relevant abnormal clinical findings at screening visit judged by the investigator to render subject unsuitable for study. Including but not limited to: History of cardiac disease, hypertension and stroke History of severe liver disease, as evidenced by abnormal liver function test results, particularly reduction in albumin (normal > to 3.5 gm/dl). History of epilepsy; History of Malignant Hyperthermia (Central Core Disease); Regular user of Ecstasy (material represented as containing MDMA). E.g. more than five times in the last five years or at least twice in the 6 months prior to the start of the study; Currently taking or unwilling/unable to stop any medications inhibiting CYP 2D6, and the following medications Monoamine Oxidase Inhibitors, Ritonavir (HIV treatment), paroxetine, fluoxetine, citalopram, regular benzodiazepines or any other medications likely to interact with MDMA the opinion of the investigators, during 8 week MDMA assisted therapy only Regular use of/dependence on other drugs such as benzodiazepines, synthetic cannabinoids, cocaine and heroin. For females of childbearing age/potential Must use an effective form of birth control for at least six days after administration of MDMA Must not be pregnant and/or breast-feeding, until the end of the treatment phase. For males with partners of childbearing age/potential Must themselves confirm use of an effective form of birth control for at least six days after administration of MDMA and confirm their partner will also, defined in detail in protocol. Taken part in a study involving an investigational product in the last three months Patients that might face additional risks from immunosuppression (for example patients with immunological diseases, patients with active infection or history of infections within 4 weeks of MDMA administration, etc).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Open label
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MDMA assisted Psychotherapy<br>All participants receive 2 sessions of MDMA-assisted psychotherapy | Drug: MDMA<br>* Two sessions of MDMA-assisted psychotherapy will take place (session 3 & 7) within the 10 week course of psychotherapy. An initial dose of 125mg MDMA will be followed by an optional dose of 62.5mg 2 hours later.<br>* Other names: 3,4-methylenedioxymethamphetamine;Other: Psychotherapy<br>* Two sessions of MDMA-assisted psychotherapy will take place (session 3 & 7) within the 10 week course of psychotherapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability as measured by adverse event | Number of patients completing 8-week course of MDMA-assisted psychotherapy. Number of patients accepting second booster dose of MDMA during MDMA drug- assisted psychotherapy sessions. All adverse events/reactions during the study will be tabulated, serious adverse events/ reactions will be coded according to CTCAE v4. The number of participants with treatment-related adverse events during the treatment period will be reported. | Treatment period defined as: From first attendance for a psychotherapy session (Session 1) to the last psychotherapy session (session 10, approximately 8 weeks from treatment start). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intensity of MDMA drug effect during MDMA-assisted psychotherapy sessions | Intensity of drug effect assessed by verbal analogue scale 0 (none) 10 (most intense drug effect), participant and observer scores recorded. | MDMA-assisted psychotherapy sessions, at dosing and hourly for up to 8 hours after dosing. | 
| Degree of psychological (subjective) distress (SUDS), participant and observer scores | Subjective Units of Distress scale (SUDS), degree of psychological (subjective) distress, rated from 0 (not at all distressed/completely relaxed) to 10 (most distressed imaginable/ panic attack). Participant and observer scores recorded. | MDMA-assisted psychotherapy sessions, -1 hour before dosing, at dosing and hourly following dosing for 8 hours. P | 
| Change in Vital signs during MDMA-assisted psychotherapy sessions: Heart Rate | The following will be measured 1 hour before dosing, at dosing, every 30 mins for 2 hours and hourly thereafter for 6 hours (extra measures taken if clinically required). -Heart rate (bpm) Pre-dosing measures will be compared to those taken after dosing. | MDMA-assisted psychotherapy sessions: 1 hour before dosing, at dosing, every 30 mins for 2 hours and hourly thereafter for 6 hours (extra measures taken if clinically required). | 
| Change in Vital signs during MDMA-assisted psychotherapy sessions: Temperature | The following will be measured 1 hour before dosing, at dosing, every 30 mins for 2 hours and hourly thereafter for 6 hours (extra measures taken if clinically required). -Temperature (degrees celsius) Pre-dosing measures will be compared to those taken after dosing. | MDMA-assisted psychotherapy sessions: 1 hour before dosing, at dosing, every 30 mins for 2 hours and hourly thereafter for 6 hours (extra measures taken if clinically required). | 
| Change in Vital signs during MDMA-assisted psychotherapy sessions: Systolic Blood pressure | The following will be measured 1 hour before dosing, at dosing, every 30 mins for 2 hours and hourly thereafter for 6 hours (extra measures taken if clinically required). Blood Pressure (mmHg) Pre-dosing measures will be compared to those taken after dosing. | MDMA-assisted psychotherapy sessions: 1 hour before dosing, at dosing, every 30 mins for 2 hours and hourly thereafter for 6 hours (extra measures taken if clinically required). | 
| Change in Vital signs during MDMA-assisted psychotherapy sessions: Diastolic Blood pressure | The following will be measured 1 hour before dosing, at dosing, every 30 mins for 2 hours and hourly thereafter for 6 hours (extra measures taken if clinically required). Blood Pressure (mmHg) Pre-dosing measures will be compared to those taken after dosing. | MDMA-assisted psychotherapy sessions: 1 hour before dosing, at dosing, every 30 mins for 2 hours and hourly thereafter for 6 hours (extra measures taken if clinically required). | 
| Subjective sleep following MDMA assisted psychotherapy | Leeds Evaluation Questionnaire, subjective, self-report measure, assessing changes in sleep quality and early morning behaviour. Visual analogue, positive end means improvement, negative ends mean decline in sleeping. | Daily for 7 days following both MDMA-assisted psychotherapy sessions (session 3 and 7). | 
| Mood rating during 7 days following MDMA assisted psychotherapy | Profile of Mood States questionnaire (POMS), a measure of mood states, 40 self-reported items, on a 5 point scale. | Daily for 7 days following both MDMA-assisted psychotherapy sessions (session 3 and 7). | 
| Acceptability of MDMA-Assisted therapy program: questionnaire | Acceptability questionnaire designed for the study, this self report measure includes visual analogue scales and free text addressing the participants acceptability of taking part in the trial. | 2 months , completed at psychotherapy therapy sessions (1,2,3,4,5,6,7,8,9 & 10) | 
| Change in Drinking behaviour | Drinking behaviour will be assessed using the clinician administered Time Line Follow Back scale- this tool allows collection of information about alcohol and illicit drug use. Pre-detoxification (screening visit) levels will be compared to levels at the final psychotherapy visit (session 10) and follow-up visits 3, 6 and 9 months. Any illicit drug use will also be recorded using this scale and assessed similarly. | Baseline, Screening (day 0), Completed at psychotherapy therapy sessions, 1,2,3,4,5,6,7,8,9 & 10', Follow-up 3, 6, 9 months | 
| Change in Quality of Life: SF-36 | The Short Form Health Survey (SF-36). Gold standard, patient reported, quality of life questionnaire. Scores at follow-up visits, compared to screening/baseline. | Screening (day 0), 3, 6 and 9 months | 
| Change in Subjective Sleep Quality: PSQI | The Pittsburgh Sleep Quality Index. (PSQI). Sleep report questionnaire assessing the level of sleep disturbance. Scores collected at psychotherapy session 10 (final psychotherapy session), and follow-up visits compared to screening/ baseline. | Screening (day 0), 3, 6 and 9 months | 
| Change in psychosocial functioning: Short Inventory of Problems for Alcohol (SIP) | Short Inventory of Problems for Alcohol (SIP) Scale. This is a 15-item instrument assessing the self-attributable consequences of drinking. Scores collected at psychotherapy session 10 (final psychotherapy session), and follow-up visits compared to screening/ baseline. | Screening (day 0), 3, 6 and 9 months | 
| Change in psychosocial functioning: Generalized Anxiety Disorder 7 (GAD-7) | Generalized Anxiety Disorder 7 (GAD-7) scale. Brief self-administered questionnaire assessing anxiety. Scores collected at psychotherapy session 10 (final psychotherapy session), and follow-up visits compared to screening/ baseline. | Screening (day 0), 3, 6 and 9 months | 
| Change in psychosocial functioning: The Patient Health Questionnaire (PHQ-9) | The Patient Health Questionnaire (PHQ-9). Brief self-administered questionnaire assessing depressive symptoms.Scores collected at psychotherapy session 10 (final psychotherapy session), and follow-up visits compared to screening/ baseline. | Screening (day 0), 3, 6 and 9 months | 
| Change in psychosocial functioning: Interpersonal reactivity Index (IRI) | Interpersonal reactivity Index (IRI) self-administered scale assessing aspects of empathy Scores collected at psychotherapy session 10 (final psychotherapy session), and follow-up visits compared to baseline. | Baseline, 3, 6 and 9 months | 
| Change in psychosocial functioning: The self compassion scale (SCS) | The self compassion scale (SCS) self-administered scale assesses core aspects of self compassion including components of mindfulness. Scores collected at psychotherapy session 10 (final psychotherapy session), and follow-up visits compared to baseline. | Baseline, psychotherapy session 10 (final psychotherapy session), follow-up visits at 3, 6 and 9 months | 
| The Penn Alcohol Craving Scale | The Penn Alcohol Craving Scale (PACS) will assess craving, specifically frequency, intensity and duration of thoughts about drinking.Scores collected at psychotherapy session 10 (final psychotherapy session), and follow-up visits compared to baseline. | Screening (day 0), 3, 6 and 9 months | 
| Obsessive Compulsive Drinking Scale | Obsessive Compulsive Drinking Scale self-rated scale, used to measure obsessive and compulsive thoughts in relation to alcohol. Scores at psychotherapy session 10 (final psychotherapy session) and follow up visits will be compared to baseline | Screening (day 0), 3, 6 and 9 months | 
| Prescribed medication use | Prescribed medication use will be collected at every face-to-face visit and number and type of medications at psychotherapy session 10 (final psychotherapy session), and follow-up visits compared to screening/baseline. | Screening (day 0), 3, 6 and 9 months | 
| Assessment of MDMA/Ecstasy use following MDMA-assisted therapy | Participants will be asked to record any recreational MDMA use or craving to use recreational MDMA outside of the study. | Screening (day 0), session 10, 3, 6 and 9 months | 
| Assessment of ability to collect follow-up data | Attrition at follow-up. Number of drop-outs at each visit. | Follow up 3,6 and 9 months | 
| Trauma History Questionnaire (THQ) | A self-report measure examining potentially traumatic experiences using a yes/no format. Administered on one occasion at the final therapy session (session 10) | 2 month (Session 10) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alcohol Use Disorder