title: Double-blind, 12 month follow-up, placebo-controlled trial of mifepristone on cognition in alcoholics: the MIFCOG trial protocol.
abstract: BACKGROUND
  Increased levels of cortisol during acute alcohol withdrawal have been linked to cognitive deficits and depression. Preclinical research found that the glucocorticoid Type II receptor antagonist, mifepristone, prevented some of the neurotoxic effects of withdrawal and memory loss. Clinical trials have shown mifepristone effective in the treatment of depression. This study aims to examine the extent to which the glucocorticoid Type II receptor antagonist, mifepristone, when given to alcohol dependent males during the acute phase of alcohol withdrawal, will protect against the subsequent memory loss and depressive symptoms during abstinence from alcohol.
  
  
  METHODS
  The study is a Phase 4 therapeutic use, "Proof of Concept" trial. The trial is a double-blind randomised controlled clinical trial of mifepristone versus inactive placebo. The trial aims to recruit 120 participants referred for an inpatient alcohol detoxification from community alcohol teams, who meet the inclusion criteria; 1) Male, 2) Aged 18-60 inclusive, 3) alcohol dependent for 5 or more years. A screening appointment will take place prior to admission to inpatient alcohol treatment units to ensure that the individual is suitable for inclusion in the trial in accordance with the inclusion and exclusion criteria. On admission participants are randomised to receive 600 mg a day of mifepristone (200 mg morning, afternoon and evening) for 7 days and 400 mg for the subsequent 7 days (200 mg morning and evening) or the equivalent number of placebo tablets for 14 days. Participants will remain in the trial for 4 weeks (at least 2 weeks as an inpatient) and will be followed up at 3, 6 and 12 months post randomisation. Primary outcome measures are cognitive function at week 3 and 4 after cessation of drinking and symptoms of depression over the 4 weeks after cession of drinking, measured using the Cambridge Neuropsychological Test Automated battery and Beck Depression Inventory, respectively. Secondary outcome measures are severity of the acute phase of alcohol withdrawal, alcohol craving, symptoms of protracted withdrawal and maintenance of abstinence and levels of relapse drinking at follow-up.
  
  
  CONCLUSIONS
  The current trial will provide evidence concerning the role of glucocorticoid Type II receptor activation in cognitive function and depression during acute alcohol withdrawal and the efficacy of treatment with mifepristone.
  
  
  BACKGROUND
  
  ISRCTN54001953, Registered 29th September 2011.
authors.affiliation: Addictions Department, National Addiction Centre, Institute of Psychiatry, King's College London, 4 Windsor Walk, London, SE5 8BB, UK. kim.donoghue@kcl.ac.uk.
authors.forename: Kim
authors.initials: K
authors.lastname: Donoghue
authors.affiliation: Department of Psychological Sciences, University of Liverpool, 2.32, Eleanor Rathbone Building, Bedford Street South, Liverpool, L69 7ZA, UK. Abi.Rose@liverpool.ac.uk.
authors.forename: Abigail
authors.initials: A
authors.lastname: Rose
authors.affiliation: Centre for Health Service Studies, University of Kent, Canterbury, Kent, CT2 7NF, UK. s.coulton@kent.ac.uk.
authors.forename: Simon
authors.initials: S
authors.lastname: Coulton
authors.affiliation: Addictions Department, National Addiction Centre, Institute of Psychiatry, King's College London, 4 Windsor Walk, London, SE5 8BB, UK. joanna.milward@kcl.ac.uk.
authors.forename: Joanna
authors.initials: J
authors.lastname: Milward
authors.affiliation: Addictions Department, National Addiction Centre, Institute of Psychiatry, King's College London, 4 Windsor Walk, London, SE5 8BB, UK. kylie.reed@kcl.ac.uk.
authors.forename: Kylie
authors.initials: K
authors.lastname: Reed
authors.affiliation: Addictions Department, National Addiction Centre, Institute of Psychiatry, King's College London, 4 Windsor Walk, London, SE5 8BB, UK. colin.drummond@kcl.ac.uk.
authors.forename: Colin
authors.initials: C
authors.lastname: Drummond
authors.affiliation: Addictions Department, National Addiction Centre, Institute of Psychiatry, King's College London, 4 Windsor Walk, London, SE5 8BB, UK. hilary.little@kcl.ac.uk.
authors.forename: Hilary
authors.initials: H
authors.lastname: Little
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000188:drug therapy*; D057229:Alcoholics; D000437:Alcoholism / Q000150:complications / Q000188:drug therapy*; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology; D004311:Double-Blind Method; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D015735:Mifepristone / Q000627:therapeutic use*; D013375:Substance Withdrawal Syndrome / Q000209:etiology* / Q000517:prevention & control
chemical_list: D015735:Mifepristone