Donoghue Kim, Rose Abigail, Coulton Simon, Milward Joanna, Reed Kylie, Drummond Colin, Little Hilary
Addictions Department, National Addiction Centre, Institute of Psychiatry, King's College London, 4 Windsor Walk, London, SE5 8BB, UK.
Department of Psychological Sciences, University of Liverpool, 2.32, Eleanor Rathbone Building, Bedford Street South, Liverpool, L69 7ZA, UK.
BMC Psychiatry. 2016 Feb 24;16:40. doi: 10.1186/s12888-016-0757-1.
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/DESIGN: 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.
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.
ISRCTN54001953, Registered 29th September 2011.
急性酒精戒断期间皮质醇水平升高与认知缺陷和抑郁有关。临床前研究发现，糖皮质激素II型受体拮抗剂米非司酮可预防戒断的一些神经毒性作用和记忆丧失。临床试验表明米非司酮对抑郁症治疗有效。本研究旨在探讨在酒精戒断急性期给予酒精依赖男性糖皮质激素II型受体拮抗剂米非司酮，在戒酒期间预防随后出现的记忆丧失和抑郁症状的程度。
方法/设计：该研究为4期治疗用途的“概念验证”试验。该试验是米非司酮与无活性安慰剂的双盲随机对照临床试验。试验旨在招募120名由社区酒精治疗团队转介来进行住院酒精解毒治疗且符合纳入标准的参与者；1）男性，2）年龄在18至60岁之间（含18和60岁），3）酒精依赖5年或更长时间。在入住住院酒精治疗单元之前将进行一次筛查预约，以确保个体符合纳入和排除标准，适合纳入试验。入院时，参与者被随机分配接受每天600毫克米非司酮（早上、下午和晚上各200毫克），持续7天，随后7天每天400毫克（早上和晚上各200毫克），或等效数量的安慰剂片，持续14天。参与者将在试验中停留4周（至少2周住院），并在随机分组后3、6和12个月进行随访。主要结局指标分别为戒酒第3周和第4周的认知功能以及戒酒4周内的抑郁症状，分别使用剑桥神经心理测试自动成套测验和贝克抑郁量表进行测量。次要结局指标为酒精戒断急性期的严重程度、酒精渴望、长期戒断症状、戒酒维持情况以及随访时复饮的水平。
当前试验将提供有关糖皮质激素II型受体激活在急性酒精戒断期间认知功能和抑郁中的作用以及米非司酮治疗效果的证据。
ISRCTN54001953，2011年9月29日注册。
