Severe Alcohol Use Disorder MedDRA version: 21.0 Level: LLT Classification code 10001585 Term: Alcohol abuse chronic System Organ Class: 100000004873
Conditions
Interventions
Trade Name: Ketalar
Product Name: Ketalar
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: Ketamine
CAS Number: 6740-88-1
Concentration unit: mg/ml milligram(s)/millilitre
Co
Sponsors
University College London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 18 - 60 years old Meet either a) DSM-5 criteria for severe alcohol use disorder and b) DSM-IV criteria for alcohol dependence Currently abstinent (breathlyser BAC level 0.02 and negative urine drug and alcohol screen) 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 a 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; abstinence) from the time consent is signed until 6 weeks after treatment discontinuation and inform the trial if pregnancy occurs 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. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 96 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
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 35 BMI History of psychosis, or in a first-degree relative; co-morbid current psychiatric diagnosis excluding depression as identified by DSM-5 or DSM-IV SCID 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 Summary of Product Characteristics with ketamine: Barbiturates and/or narcotics Halogenated anaesthetics Atracurium and tubocurarine Central nervous system (CNS) depressants (e.g. phenothiazines, sedating H1 – blockers or skeletal muscle relaxants) Anxiolytics, sedatives and hypnotics Thiopental, thyroid hormones Antihypertensive agents Theophylline and methylxanthine OR psychotropic drug use at screening assessment or during treatment weeks Liver function tests > 3 times normal levels Where there are "Special warnings or precautions for use" according to the Summary of Product Characteristics 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: Acute intermittent porphyria Dehydration or hypovolemia Hyperthyroidism, or patients receiving thyroid replacement Pulmonary or upper respiratory tract infection Severe Coronary artery disease, Cerebrovascular accident or cerebral trauma Diabetes Known glaucoma or globe injuries Cirrhosis Epilepsy Neurological condition/brain damage 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 Investigational Medicinal Product and placebo Use of another investigational medicinal product that is likely to interfere with the study medication within 3 months of study enrolment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1) To obtain preliminary data on whether ketamine is effective in promoting and prolonging abstinence in patients with severe alcohol use disorder following detoxification. 2) To assess safety and tolerability of ketamine in severe alcohol use disorder. ;Secondary Objective: 1) To make an early assessment on likely compliance to a combined ketamine and relapse prevention based psychological therapy 2) To obtain preliminary data as to whether ketamine alone is as effective as a combined ketamine and psychological therapy treatment. ;Primary end point(s): Relapse rates at 6 months and percentage days abstinent at 6 months, indexed by the SCRAM-X bracelet and patient reports on the time line follow back scale.;Timepoint(s) of evaluation of this end point: As an interim analysis with regarding to trial continuation, attrition among participants receiving ketamine only will be determined; the trial will be discontinued if more than 21/24 (88%) of participants who were randomised to ketamine are lost to follow-up at 3 months. Only aggregate data will be provided to the statistician at 3-month follow-up to ensure that treatment arm allocation will remain concealed. Due to the short duration of follow-up, no interim analyses for the primary or secondary outcomes are planned. From a safety perspective, adverse events will be monitored by the TSC and any concerns will be addressed. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Number of days of continuous abstinence 3 months (SCRAM-X and Time-line follow back) Percentage days abstinent at 3 months (SCRAM-X and timeline follow-back) State mood (Profile of Mood states) Depression (Beck Depression Inventory; Hamilton Depression Scale) Anxiety (Speilberger Trait Anxiety Inventory) Psychotic symptoms (Brief Psychiatric Rating Scale; Psychotomimetic States Inventory) Cigarette smoking (Fagerstrom Smoking) Craving (Visual Aanalogue Scales) Quality of Life (SF-12) Episodic Memory (Prose Recall) Delay discounting Response Inhibition (Stop Signal Reaction time) Working Memory Hippocampal Functioning (Pattern Recognition Test) Adverse Effects (Adverse Effects VAS);Timepoint(s) of evaluation of this end point: These endpoints will be evaluated following trial end when all patients have 6 month follow up data. | — |
Countries
United Kingdom
Outcome results
None listed