Multinational, Multicentre, Double-blind, Placebo-controlled Evaluation of the Efficacy of GHB in the Long-term Maintenance of Abstinence in Alcoholic Patients After the Initial Weaning Phase, Stratified by Lesch's Taxonomy (GATE 2)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 314
- 主要终点
- Cumulative Abstinence Duration (CAD)
研究概览
简要总结
Additional pharmacotherapies in the treatment of alcohol dependence are needed. Sodium oxybate showed efficacy in the maintenance of abstinence in alcohol-dependent patients in several small randomized trials of short duration. The aim of the present phase III/IV study is to confirm in a randomized-controlled study the efficacy and safety of oral sodium oxybate in the maintenance of abstinence.
详细描述
Alcohol dependence (AD) is the most severe form of alcohol use disorder. It occurs in 2.6% of people aged 15+ years worldwide and can result in a reduction of life-expectancy by several years as compared with the general population.
Currently, disulfiram, acamprosate and naltrexone are the main medicinal products registered for the maintenance of abstinence in AD patients. Although effective on the group level, effects sizes are limited, and many AD patients fail to respond to these medications. Therefore, additional pharmacological treatments are needed.
Sodium oxybate 50mg/kg/day showed evidence of efficacy compared to placebo and naltrexone in the maintenance of abstinence in AD patients in a series of open label and blinded randomized controlled trials (RCTs). However, studies were generally small and did not investigate the sustainability of the Sodium oxybate effect post-treatment.
The present phase III/IV RCT (GATE 2) aimed to confirm the efficacy and safety of oral Sodium oxybate in the maintenance of abstinence. Secondary aims included the assessment of sustained SMO effects during the 6-month medication free period immediately following the 6-month treatment period and monitoring the risk of Sodium oxybate dependence.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The control medication (placebo) was identically-looking and identically tasting as active.
入排标准
- 年龄范围
- 21 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The following subjects were recruited:
- •males and females;
- •of any ethnic group;
- •age between 21 and 75 years at recruitment;
- •documented alcohol dependency before weaning detected according to the CAGE instrument, classified according to the DSM-IV and ICD-10 and severity rated according to the MALT instrument;
- •classified according to Lesch typology;
- •having successfully undergone a detoxification program, encompassing a 10-day treatment period and a subsequent 10-day untreated follow-up;
- •with a responsible relative or caregiver;
- •having issued the informed consent.
排除标准
- •subjects who did not quit alcohol drinking after the detoxification period;
- •subjects with history of epilepsy or epileptics seizures not properly controlled by established anti-epileptic treatment;
- •subjects with dependence from narcotics or other drugs of abuse;
- •subjects without a stable address;
- •subjects without a reference relative or caregiver;
- •subjects with renai failure (blood creatinine >2.5 mg/dL and/or documented proteinuria >500 mg/day);
- •subjects with heart failure or severe respiratory failure;
- •subjects with hepatic encephalopathy stage lI-IV;
- •subjects with severe psychiatric disorders requiring treatment with psychoactive medications (excluding short-term benzodiazepine treatments);
- •subjects under treatment with clonidine, disulfiram (after the end of the detoxification period), haloperidol, bromocryptine, serotonine re-uptake inhibitors or other serotoninergic agents;
- •female subjects who cannot assure not to become pregnant during the 7-month period covering treatment and the first treatment-free month of follow-up;
- •documented pre-existent hypersensitivity to GHB;
- •subjects unable or unwilling to issue the informed consent;
- •participating to another clinica! investigation in the previous month prior to recruitment;
- •any other medicai condition which, according to the investigator, justifies the patient's exclusion from the study.
研究组 & 干预措施
sodium oxybate
Sodium oxybate solution for oral administration (175 mg/mL). Dose (body weight ≤ 65 kg): 19.0 mL daily, in 3 administrations, for 6 months Dose (body weight > 65 kg): 22.5 mL daily, in 3 administrations, for 6 months
干预措施: Sodium Oxybate (Drug)
placebo
Placebo solution for oral administration. Dose (body weight ≤ 65 kg): 19.0 mL daily, in 3 administrations, for 6 months Dose (body weight > 65 kg): 22.5 mL daily, in 3 administrations, for 6 months
干预措施: Placebo (Drug)
结局指标
主要结局
Cumulative Abstinence Duration (CAD)
时间窗: 6-month treatment period
to demonstrate that sodium oxybate is superior to placebo in the CAD during the treatment period.
次要结局
- CAD during the whole study(12 months: 6-month treatment period + 6-month follow-up)
- Assessment of the exposure-corrected CAD(6-month treatment period)
- CAD stratified(6-month treatment period)
- Number of participants with Adverse Events (AEs)(6-month treatment period)
- Risk of Secondary Dependence - treatment period(6-month treatment period)
- Time to the first relapse(6-month treatment period)
- Assessment of the time course of γ-GT as biological marker of alcohol abuse, during treatment and at the end of follow-up.(Month 6)
- Proportion of abstinent patients(12 months: 6-month treatment period + 6-month follow-up)
- Change from baseline in the craving for alcohol intensity and frequency by the Lubecker Craving Risiko Ruckfall (LCRR) questionnaire.(12 months: 6-month treatment period + 6-month follow-up)
- Adverse events(6-month treatment period)
- Assessment of the time course of MCV as biological marker of alcohol abuse, during treatment and at the end of follow-up.(Month 6)