Clinical trial NCT04158778: Bristol Imperial MDMA in Alcoholism Study
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Alcohol Use Disorder
Keywords: Alcohol Use Disorder
Lead sponsor: Imperial College London
Sponsor class: OTHER
First posted: 2019-11-12
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open label
Primary purpose: TREATMENT

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

Detailed description: 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.

Eligibility criteria: 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).

Primary outcomes:
measure: Safety and tolerability as measured by adverse event
timeFrame: 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 outcomes:
measure: Intensity of MDMA drug effect during MDMA-assisted psychotherapy sessions
timeFrame: MDMA-assisted psychotherapy sessions, at dosing and hourly for up to 8 hours after dosing.
measure: Degree of psychological (subjective) distress (SUDS), participant and observer scores
timeFrame: MDMA-assisted psychotherapy sessions, -1 hour before dosing, at dosing and hourly following dosing for 8 hours. P
measure: Change in Vital signs during MDMA-assisted psychotherapy sessions: Heart Rate
timeFrame: 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).
measure: Change in Vital signs during MDMA-assisted psychotherapy sessions: Temperature
timeFrame: 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).
measure: Change in Vital signs during MDMA-assisted psychotherapy sessions: Systolic Blood pressure
timeFrame: 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).
measure: Change in Vital signs during MDMA-assisted psychotherapy sessions: Diastolic Blood pressure
timeFrame: 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).
measure: Subjective sleep following MDMA assisted psychotherapy
timeFrame: Daily for 7 days following both MDMA-assisted psychotherapy sessions (session 3 and 7).
measure: Mood rating during 7 days following MDMA assisted psychotherapy
timeFrame: Daily for 7 days following both MDMA-assisted psychotherapy sessions (session 3 and 7).
measure: Acceptability of MDMA-Assisted therapy program: questionnaire
timeFrame: 2 months , completed at psychotherapy therapy sessions (1,2,3,4,5,6,7,8,9 & 10)
measure: Change in Drinking behaviour
timeFrame: 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
measure: Change in Quality of Life: SF-36
timeFrame: Screening (day 0), 3, 6 and 9 months
measure: Change in Subjective Sleep Quality: PSQI
timeFrame: Screening (day 0), 3, 6 and 9 months
measure: Change in psychosocial functioning: Short Inventory of Problems for Alcohol (SIP)
timeFrame: Screening (day 0), 3, 6 and 9 months
measure: Change in psychosocial functioning: Generalized Anxiety Disorder 7 (GAD-7)
timeFrame: Screening (day 0), 3, 6 and 9 months
measure: Change in psychosocial functioning: The Patient Health Questionnaire (PHQ-9)
timeFrame: Screening (day 0), 3, 6 and 9 months
measure: Change in psychosocial functioning: Interpersonal reactivity Index (IRI)
timeFrame: Baseline, 3, 6 and 9 months
measure: Change in psychosocial functioning: The self compassion scale (SCS)
timeFrame: Baseline, psychotherapy session 10 (final psychotherapy session), follow-up visits at 3, 6 and 9 months
measure: The Penn Alcohol Craving Scale
timeFrame: Screening (day 0), 3, 6 and 9 months
measure: Obsessive Compulsive Drinking Scale
timeFrame: Screening (day 0), 3, 6 and 9 months
measure: Prescribed medication use
timeFrame: Screening (day 0), 3, 6 and 9 months
measure: Assessment of MDMA/Ecstasy use following MDMA-assisted therapy
timeFrame: Screening (day 0), session 10, 3, 6 and 9 months
measure: Assessment of ability to collect follow-up data
timeFrame: Follow up 3,6 and 9 months
measure: Trauma History Questionnaire (THQ)
timeFrame: 2 month (Session 10)
Other outcomes:
Locations:
city: Bristol
country: United Kingdom
facility: Study Center: University of Bristol
Study officials:
affiliation: Imperial College London
name: Prof Nutt
role: PRINCIPAL_INVESTIGATOR
References: