Bristol Imperial MDMA in Alcoholism Study (BIMA)

• ClinicalTrials.gov Identifier: NCT04158778
• Recruitment Status: Unknown
• First Posted: November 12, 2019
• Last Update Posted: November 12, 2019
• Sponsor: Imperial College London
• Information provided by (Responsible Party): Imperial College London

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Alcohol Use Disorder	Drug: MDMA; Other: Psychotherapy	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Open label
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: April 18, 2018
• Estimated Primary Completion Date: June 12, 2020
• Estimated Study Completion Date: June 12, 2020

Arms and Interventions

Arm

Intervention/treatment

Experimental: MDMA assisted Psychotherapy; All participants receive 2 sessions of MDMA-assisted psychotherapy

Drug: MDMA; 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.; Other Name: 3,4-methylenedioxymethamphetamine; Other: Psychotherapy; Two sessions of MDMA-assisted psychotherapy will take place (session 3 & 7) within the 10 week course of psychotherapy.

Outcome Measures

Primary Outcome Measures :

1. Safety and tolerability as measured by adverse event [ Time Frame: 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). ]

   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.

Secondary Outcome Measures :

1. Intensity of MDMA drug effect during MDMA-assisted psychotherapy sessions [ Time Frame: MDMA-assisted psychotherapy sessions, at dosing and hourly for up to 8 hours after dosing. ]
   Intensity of drug effect assessed by verbal analogue scale 0 (none) 10 (most intense drug effect), participant and observer scores recorded.
2. Degree of psychological (subjective) distress (SUDS), participant and observer scores [ Time Frame: MDMA-assisted psychotherapy sessions, -1 hour before dosing, at dosing and hourly following dosing for 8 hours. P ]
   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.
3. Change in Vital signs during MDMA-assisted psychotherapy sessions: Heart Rate [ Time Frame: 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). ]

   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.

4. Change in Vital signs during MDMA-assisted psychotherapy sessions: Temperature [ Time Frame: 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). ]

   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.

5. Change in Vital signs during MDMA-assisted psychotherapy sessions: Systolic Blood pressure [ Time Frame: 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). ]

   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.

6. Change in Vital signs during MDMA-assisted psychotherapy sessions: Diastolic Blood pressure [ Time Frame: 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). ]

   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.

7. Subjective sleep following MDMA assisted psychotherapy [ Time Frame: Daily for 7 days following both MDMA-assisted psychotherapy sessions (session 3 and 7). ]
   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.
8. Mood rating during 7 days following MDMA assisted psychotherapy [ Time Frame: Daily for 7 days following both MDMA-assisted psychotherapy sessions (session 3 and 7). ]
   Profile of Mood States questionnaire (POMS), a measure of mood states, 40 self-reported items, on a 5 point scale.
9. Acceptability of MDMA-Assisted therapy program: questionnaire [ Time Frame: 2 months , completed at psychotherapy therapy sessions (1,2,3,4,5,6,7,8,9 & 10) ]
   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.
10. Change in Drinking behaviour [ Time Frame: 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 ]
    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.
11. Change in Quality of Life: SF-36 [ Time Frame: Screening (day 0), 3, 6 and 9 months ]
    The Short Form Health Survey (SF-36). Gold standard, patient reported, quality of life questionnaire. Scores at follow-up visits, compared to screening/baseline.
12. Change in Subjective Sleep Quality: PSQI [ Time Frame: Screening (day 0), 3, 6 and 9 months ]
    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.
13. Change in psychosocial functioning: Short Inventory of Problems for Alcohol (SIP) [ Time Frame: Screening (day 0), 3, 6 and 9 months ]
    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.
14. Change in psychosocial functioning: Generalized Anxiety Disorder 7 (GAD-7) [ Time Frame: Screening (day 0), 3, 6 and 9 months ]
    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.
15. Change in psychosocial functioning: The Patient Health Questionnaire (PHQ-9) [ Time Frame: Screening (day 0), 3, 6 and 9 months ]
    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.
16. Change in psychosocial functioning: Interpersonal reactivity Index (IRI) [ Time Frame: Baseline, 3, 6 and 9 months ]
    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.
17. Change in psychosocial functioning: The self compassion scale (SCS) [ Time Frame: Baseline, psychotherapy session 10 (final psychotherapy session), follow-up visits at 3, 6 and 9 months ]
    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.
18. The Penn Alcohol Craving Scale [ Time Frame: Screening (day 0), 3, 6 and 9 months ]
    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.
19. Obsessive Compulsive Drinking Scale [ Time Frame: Screening (day 0), 3, 6 and 9 months ]
    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
20. Prescribed medication use [ Time Frame: Screening (day 0), 3, 6 and 9 months ]
    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.
21. Assessment of MDMA/Ecstasy use following MDMA-assisted therapy [ Time Frame: Screening (day 0), session 10, 3, 6 and 9 months ]
    Participants will be asked to record any recreational MDMA use or craving to use recreational MDMA outside of the study.
22. Assessment of ability to collect follow-up data [ Time Frame: Follow up 3,6 and 9 months ]
    Attrition at follow-up. Number of drop-outs at each visit.
23. Trauma History Questionnaire (THQ) [ Time Frame: 2 month (Session 10) ]
    A self-report measure examining potentially traumatic experiences using a yes/no format. Administered on one occasion at the final therapy session (session 10)

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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).

Contacts and Locations

Locations

United Kingdom

Study Center: University of Bristol

Bristol, United Kingdom

Sponsors and Collaborators

Imperial College London

Investigators

• Principal Investigator: Prof Nutt; Imperial College London

More Information

• Responsible Party: Imperial College London
• ClinicalTrials.gov Identifier: NCT04158778
• Other Study ID Numbers: BIMA2016; 2016-002547-42 ( EudraCT Number )
• First Posted: November 12, 2019
• Last Update Posted: November 12, 2019
• Last Verified: November 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Imperial College London:

Alcohol Use Disorder

Additional relevant MeSH terms:

Alcoholism; Alcohol Drinking; Drinking Behavior; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; N-Methyl-3,4-methylenedioxyamphetamine; Hallucinogens; Physiological Effects of Drugs; Psychotropic Drugs; Serotonin Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Adrenergic Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Adrenergic Agents