Severe alcohol use disorder Mental and Behavioural Disorders
Conditions
Interventions
In this double-blind trial, 280 participants will either receive three 40-minute intravenous infusions, one per week, of either 0.8 mg/kg or 0.05 mg/kg ketamine at a research facility. Participants wi
Sponsors
University of Exeter
Eligibility
Sex/Gender
All
Age
18 Years to 100 Years
Inclusion criteria
Inclusion criteria: Current participant inclusion criteria as of 28/06/2024: 1. 18 years old and over 2. Meet DSM-5 criteria for severe Alcohol Use Disorder 3. Abstinent from alcohol at randomisation (verified with withdrawal symptom checklist and breathalyser BAC level 0.00) 4. Seeking to reduce or quit alcohol long-term 5. Willing and able to consent and comply with trial procedure 6. People of childbearing potential and their sexual partners must be willing to use an effective method of contraception* (and must agree to continue for 6 weeks after the last dose of the IMP). Participants must be willing to inform the trial team if pregnancy occurs. 7. People of childbearing potential must have a negative pregnancy test within 28 days prior to being registered for trial treatment and on the day of first treatment. * Highly effective contraception is defined as one of the following: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal); progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable); intrauterine device; intrauterine hormone-releasing system; bilateral tubal occlusion; vasectomised partner; practising true abstinence (when this is in line with the preferred and usual lifestyle of the subject). People of child-bearing potential could also be post-menopausal (no menses for 12 months without an alternative medical cause) or be surgically sterile (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy). Previous participant inclusion criteria: 1. 18 years old and over 2. Meet DSM-5 criteria for severe Alcohol Use Disorder 3. Abstinent from alcohol at randomisation (verified with withdrawal symptom checklist and breathalyser BAC level 0.00) 4. Seeking to reduce or quit alcohol long-term 5. Willing and able to consent and comply with trial procedure 6. People of childbearing potential and their sexual partners must be willing to use an effective method of contraception* (and must agree to continue for 6 weeks after the last dose of the IMP). Participants must be willing to inform the trial team if pregnancy occurs. 7. People of childbearing potential must have a negative pregnancy test within 7 days prior to being registered for trial treatment and on the day of first treatment. * Highly effective contraception is defined as one of the following: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal); progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable); intrauterine device; intrauterine hormone-releasing system; bilateral tubal occlusion; vasectomised partner; practising true abstinence (when this is in line with the preferred and usual lifestyle of the subject). People of child-bearing potential could also be post-menopausal (no menses for 12 months without an alternative medical cause) or be surgically sterile (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy).
Exclusion criteria
Exclusion criteria: Current participant inclusion criteria as of 28/06/2024: 1. Currently taking any other alcohol relapse prevention medication 2. Current uncontrolled hypertension (systolic =150 mmHg or diastolic =100 mmHg) 3. Being actively treated for a current co-morbid substance use disorder (SUD) or having been treated in the past 12 months. If the participant is currently in treatment for a comorbid SUD but is abstinent from any substance use and has a negative urine drug screen (except cannabis and benzodiazepine) participant could be included at the discretion of the investigator. 4. History of ketamine use disorder as assessed by the SCID. 5. Pregnant or breast-feeding 6. Not willing to use effective contraception or (people of child-bearing potential) take pregnancy test. 7. Use of another experimental IMP that is likely to interfere with the trial medication within 3 months of trial enrolment. 8. Known allergies to ketamine or excipients of IMP. 9. Meets current criteria for or has a history of any psychotic illness including substance induced psychosis. 10. Current suicide risk as judged clinically and using CSSR or a history of a suicide attempt within the past year. 11. BMI 35 kg/m² 12. Positive urine drug screen for ketamine. 13. Where there are “Special warnings and precautions for use for ketamine infusion” according to the SmPC. 14. Where risk vs benefit ratio is not in favour of giving ketamine, with assessment made by physical examination by medically qualified trial personnel, self-report, or inspection of the medical notes. 15. Received any previous ketamine treatment. Previous participant exclusion criteria: 1. Currently taking any other alcohol relapse prevention medication 2. Current uncontrolled hypertension (systolic >140 mmHg or diastolic >90 mmHg) 3. Being actively treated for a current co-morbid substance use disorder (SUD) or having been treated in the past 12 months. If the participant is currently in treatment for a comorbid SUD but is abstinent from any substance use and has a negative urine drug screen (except cannabis and benzodiazepine) participant could be included at the discretion of the investigator. 4. History of ketamine use disorder as assessed by the SCID. 5. Pregnant or breast-feeding 6. Not willing to use effective contraception or (people of child-bearing potential) take pregnancy test. 7. Use of another experimental IMP that is likely to interfere with the trial medication within 3 months of trial enrolment. 8. Known allergies to ketamine or excipients of IMP. 9. Meets current criteria for or has a history of any psychotic illness including substance induced psychosis. 10. Current suicide risk as judged clinically and using CSSR or a history of a suicide attempt within the past year. 11. BMI 35 kg/m² 12. Positive urine drug screen for ketamine. 13. Where there are “Special warnings and precautions for use for ketamine infusion” according to the SmPC. 14. Where risk vs benefit ratio is not in favour of giving ketamine, with assessment made by physical examination by medically qualified trial personnel, self-report, or inspection of the medical notes.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The number of days heavy drinking at six-month follow-up (Time Line Follow Back : TLFB, the most commonly used method in Alcohol Use Disorder clinical trials). TLFB data will be cross-referenced with self-report data using self-breathalyser data, BACtrack Skyn (continuous transdermal alcohol monitoring) and alcohol glucuronide urine dipstick and breathalyser at trial visits. A minimum of 180 days of data will be required with the measurement period capped at 187 days. Heavy drinking will be defined using EMA guidelines (60g/day for males, 40g/day for females). | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Relapse (zero heavy drinking days, above 60g/day for males, 40g/day for females) is measured using the TimeLine Follow Back (TLFB) at baseline and at each trial visit during treatment as well as at 3- and 6-month follow-up. 2. Percentage of days abstinent from alcohol is measured using the TLFB at baseline and each study visit during treatment as well as at 3- and 6-month follow-up. 3. Clinical Global Impression (CGI Severity and CGI Improvement) is measured at baseline, visit 8 (end of treatment), as well as at 3- and 6-month follow-up. 4. Liver biomarkers (bilirubin, Gamma-GT, aspartate aminotransferase (AST) and alanine transaminase (ALT)) are measured at baseline, visit 4, visit 6, visit 8 (end of treatment), as well as at 3- and 6-month follow-up. 5. Percentage of heavy drinking days (above 60g/day for males, 40g/day for females) is measured using the TLFB at baseline and each study visit during treatment as well as at 3- and 6-month follow-up. 6. Reduction in WHO risk level for alcohol by at least two risk levels: from very high to moderate or high to low is measured at baseline, visit 8 (end of treatment), as well as at 3-, 6-, and 12-month follow-up. 7. Social functioning is measured using the SF-36 at baseline, visit 8 (end of treatment), as well as at 3-, 6-, and 12-month follow-up. 8. Depressive symptoms are measured by the Beck Depression Inventory (BDI) and Montgomery-Asberg Depression Rating Scale (MADRS) at baseline, visit 8 (end of treatment), as well as at 3- and 6-month follow-up. The BDI is also collected at 12-month follow-up. 9. Anhedonia is measured by the Snaith-Hamilton Pleasure Scale (SHAPS) at baseline, visit 4, visit 6, visit 8 (end of treatment), as well as at 3- and 6-month follow-up. 10. Craving is measured by the Alcohol Craving Questionnaire (ACQ-NOW) at baseline and each trial visit during treatment as well as at 3- and 6-month follow-up. 11. Alcohol dependence is measured by the Severity of Alcohol Dependence Scale (SADQ) at | — |
Countries
England, United Kingdom
Outcome results
None listed