Ketamine for Reduction of Alcoholic Relapse

Study Overview
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Brief Summary
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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.

Official Title
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A Phase II, Randomised, Double-blind, Placebo- Controlled, Multi-site, Parallel Group Clinical Trial to Examine Ketamine as a Pharmacological Treatment for Alcohol Dependence in an Alcohol Dependent Population

Conditions
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Primary Alcohol Use Disorder

Intervention / Treatment
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* Drug: Ketamine
* Drug: Placebo
* Behavioral: Psychological Therapy
* Behavioral: Alcohol Education


Participation Criteria
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Eligibility Criteria
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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: Barbiturates and/or narcotics 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 methylxanthines. Halogenated anaesthetics 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: 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 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketamine+Psychological Therapy<br>Ketamine with psychological therapy | Drug: Ketamine<br>* 0.8 mg/kg ketamine<br>Behavioral: Psychological Therapy<br>* Manualised relapse prevention based CBT<br>|
| Active Comparator: Ketamine+Education<br>ketamine with alcohol education | Drug: Ketamine<br>* 0.8 mg/kg ketamine<br>Behavioral: Alcohol Education<br>* Simple education about alcohol effects<br>|
| Active Comparator: Placebo+Psychological Therapy<br>placebo with psychological therapy | Drug: Placebo<br>* 0.9% saline<br>Behavioral: Psychological Therapy<br>* Manualised relapse prevention based CBT<br>|
| Placebo Comparator: Placebo+Education<br>placebo with simple alcohol education | Drug: Placebo<br>* 0.9% saline<br>Behavioral: Alcohol Education<br>* Simple education about alcohol effects<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relapse Rates | Time line follow back | 6 months | 
| Percentage Days Abstinent | Time line follow back | 6 months |