Ketamine for Reduction of Alcoholic Relapse
Condition: Primary Alcohol Use Disorder
MeSH terms: Alcoholism
Intervention: Ketamine; Placebo; Psychological Therapy; Alcohol Education
Intervention description: 0.8 mg/kg ketamine; 0.9% saline; Manualised relapse prevention based CBT; Simple education about alcohol effects
Intervention MeSH terms: Ketamine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 96.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No

Summary:

      96 recently detoxified alcoholics will be randomized to receive either 3 sessions ketamine
      (0.8 mg/kg IV over 45 minutes) or placebo plus manualised psychological therapy, or 3
      sessions of ketamine or placebo plus simple psychoeducation. Patients will be assessed at 3
      and 6 months on a range of psychological and biological variables. Primary endpoints will be
      % days abstinent at 6 months and relapse rates at 6 months. Secondary endpoints include
      depressive symptoms, craving, quality of life.
    

Eligibility 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:

          -  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.