Ketamine for Reduction of Alcoholic Relapse (KARE)
Randomised, parallel-group, Phase II trial (n=96) comparing three sessions of ketamine (0.8 mg/kg IV over 45 minutes) versus placebo, each combined with either manualised psychological therapy or simple alcohol education in recently detoxified participants with alcohol use disorder.
Detailed Description
This is a randomised, quadruple-blind, parallel-group Phase II trial enrolling recently detoxified participants with alcohol use disorder to compare three 0.8 mg/kg IV ketamine infusions (45 minutes) versus saline placebo, each paired with either manualised CBT relapse-prevention or simple alcohol education.
Primary outcomes are percent days abstinent and relapse rates at 6 months; secondary outcomes include depressive symptoms, craving and quality of life. Assessments occur acutely and at 3 and 6 months with biological and psychological measures.
Study Protocol
Preparation
Dosing
Integration
Therapeutic Protocol
Study Arms & Interventions
Ketamine+Psychotherapy
experimentalKetamine plus manualised relapse-prevention CBT
Interventions
- Ketamine0.8 mg/kgvia IV• three sessions• 3 doses total
0.8 mg/kg IV infusion over 45 minutes per session
- Compoundvia Other
Manualised relapse-prevention CBT delivered alongside dosing
Ketamine+Education
active comparatorKetamine plus simple alcohol education
Interventions
- Ketamine0.8 mg/kgvia IV• three sessions• 3 doses total
0.8 mg/kg IV infusion over 45 minutes per session
- Compoundvia Other
Simple alcohol education
Placebo+Psychotherapy
active comparatorPlacebo infusion plus manualised relapse-prevention CBT
Interventions
- Placebovia IV• three sessions• 3 doses total
0.9% saline infusion over 45 minutes per session
- Compoundvia Other
Manualised relapse-prevention CBT delivered alongside dosing
Placebo+Education
inactivePlacebo infusion plus simple alcohol education
Interventions
- Placebovia IV• three sessions• 3 doses total
0.9% saline infusion over 45 minutes per session
- Compoundvia Other
Simple alcohol education
Participants
Inclusion Criteria
- Inclusion Criteria:
- Meet either a) DSM-5 criteria for severe alcohol use disorder and b) DSM-IV criteria for alcohol dependence within the last 12 months;
- Currently abstinent from alcohol (breathalyser BAC level 0.00) and negative urine drug screening (participants testing positive for THC who do not have a history or current cannabis dependency may be included);
- Minimum of mild depression (>14 on Beck Depression Inventory-II);
- Capacity to give informed consent as defined by GCP guidelines;
- Willing and able to wear SCRAM-X bracelet for 6 months;
- Females of childbearing potential and males must be willing to use an effective method of contraception (hormonal or barrier method of birth control; True abstinence) from the time consent is signed until 6 weeks after treatment discontinuation and inform the trial if pregnancy occurs. For the purpose of clarity, True abstinence is when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence, withdrawal, spermicides only or lactational amenorrhoea method for the duration of a trial, are not acceptable methods of contraception;
- Females of childbearing potential must have a negative pregnancy test within 7 days prior to being registered for trial treatment and on day of first treatment.
Exclusion Criteria
- Exclusion Criteria:
- Currently taking any other relapse prevention medication or anti-depressants;
- Uncontrolled hypertension, systolic 140mm Hg or greater and diastolic 90mm Hg or greater;
- <16 or >35 BMI
- History of psychosis, or in a first-degree relative as identified by DSM-5 or DSM-IV SCID; co-morbid current psychiatric diagnosis excluding depression, identified via self-reported or identified by a medical professional;
- Previous or current diagnosis of substance dependence / severe substance misuse disorder;
- History of neuropsychological difficulties
- One or more previous confirmed seizures;
- Currently taking daily prescribed medication contraindicated in the SPC with ketamine:
- 1. Barbiturates and/or narcotics
- 2. Atracurium and tubocurarine
- 3. Central nervous system (CNS) depressants (e.g. phenothiazines, sedating H1 - blockers or skeletal muscle relaxants)
- 4. Anxiolytics, sedatives and hypnotics
- 5. Thiopental, thyroid hormones
- 6. Antihypertensive agents
- 7. Theophylline and methylxanthines.
- 8. Halogenated anaesthetics
- 9. OR psychotropic drug use at screening assessments or during treatment weeks
- Liver function tests > 3 times normal levels
- Where there are "special warnings or precautions for use" according to the SPC and 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:
- 1. Acute intermittent porphyria
- 2. Dehydration or hypovolemia
- 3. Hyperthyroidism, or patients receiving thyroid replacement
- 4. Pulmonary or upper respiratory tract infection
- 5. Severe Coronary artery disease, Cerebrovascular accident or cerebral trauma
- 6. Diabetes
- 7. Known glaucoma or globe injuries
- 8. Cirrhosis
- 9. Epilepsy
- 10. Neurological condition/brain damage
- 11. Intracranial mass lesions, presence of head injury or hydrocephalus
- Suicidal ideation.
- Not willing to use effective contraception or (females) take pregnancy test;
- Allergic reaction to ketamine;
- >10 previous detoxifications from alcohol;
- Pregnant or breastfeeding;
- Allergies to excipients of IMP or placebo;
- Use of another experimental investigational medicinal product that is likely to interfere with the study medication within 3 months of study enrolment.
Study Details
- StatusCompleted
- PhasePhase II
- Typeinterventional
- DesignRandomizedquadruple Blind
- Target Enrollment96 participants
- TimelineStart: 2016-10-10End: 2020-02-10
- Compounds
- Topic