Cannabidiol as an add-on Treatment During Inpatient Alcohol Cessation in Patients With Severe Alcohol Use Disorder: A Phase II Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 210
- 试验地点
- 12
- 主要终点
- Percentage of patients in each group with documented continuous abstinence at month 1 after discharge, week 6 of the study. Continuous abstinence will be defined by patients self-report of alcohol abstinence using standardized TLFB (time line follow back) scales TLFB at screening visit and daily from Day 0 to Day 10 and 4 (1 per week) after discharge up to week 6 of the study)
研究概览
简要总结
Randomized clinical trial of 11 days Cannabidiol versus placebo as an adjunctive treatment during inpatient alcohol detoxification to improve abstinence in patients with severe alcohol use disorder.
详细描述
Primary objective: To increase abstinence maintenance rate at week 6 of the study (1 month after discharge of the scheduled alcohol withdrawal inpatient stay).
Primary Endpoint:
Percentage of patients in each group with documented continuous abstinence at month 1 after discharge, week 6 of the study.
Continuous abstinence will be defined by patient's self-report of alcohol abstinence using standardized TLFB (time line follow back) scales TLFB at screening visit and daily from Day 0 to Day 10 and 4 (1 per week) after discharge up to week 6 of the study) Furthermore, this self-declaration will be confirmed by clinical examination at each study visits assessing acute alcohol intoxication signs and 6 ethyl glucuronide (Et-OH) urinary assessments performed at each study visit (2 during the inpatient stay and 4 (1 per week) after discharge up to week 6 of the study).
Secondary objectives :
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
- Single (Outcomes Assessor)
盲法说明
Placebo and CBD pills are looking alike and made on purpose for the study by the same manufacturer(Echo Pharmaceutical, BV)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients hospitalized for a scheduled alcohol inpatient cessation
- •Aged 18-75 years old
- •Meeting DSM 5 criteria for severe AUD
- •Willing to participate
- •Signing a written informed consent
- •Patients with current social insurance
- •For childbearing age, sexually active females: efficacious contraceptive method during treatment and up to seven days after treatment administration
排除标准
- •• Patients already scheduled for long term residential care after acute alcohol inpatient detoxification, not able to maintain the outpatient follow up
- •Patients not willing to attend post-discharge visits whatever the reason
- •Any unstable medical condition at entry, such as delirium, acute hepatic failure, hypokalaemia, liver cirrhosis whatever the stage, acute or chronic severe renal failure or any acute psychiatric condition
- •Liver enzymes (ALT and/or AST) above 3 times the upper limit of normal and/or bilirubin above 2 times the upper limit of normal
- •Current medication or need for medication with treatments metabolized by CYP 2C19 or CYP3A4 or UGT enzymes and having strong inhibitor/inducer properties (see list above), and/or current medication or need for medications containing valproate and derivates
- •Any medical history of epileptic seizure
- •Patients with current or past history of cardiac arrhythmias, myocardial infarction and stroke
- •Any history of suicidal attempt in the past 5 years or a score ≥1 to the Suicidal Ideation Attributes Scale (SIDAS)
- •To facilitate efficacy data interpretation, patients currently receiving or wanting to receive another approved pharmacological treatment aimed at alcohol abstinence maintenance (acamprosate, baclofene, disulfiram, nalmefene, naltrexone).
- •Other major current DSM 5 severe substance use disorder (like opiates, cocaine, amphetamines, ...) except for tobacco, cannabis smoking and benzodiazepines use disorders
- •Pregnancy and breast feeding
- •Known hypersensitivity to the active substance or to any of the excipients (including PEG)
- •Patients under guardianship
- •Patients in exclusion periods of other trials
- •Reversely, cannabis use or cannabis use disorders will not be an exclusion criteria
研究组 & 干预措施
Placebo
add-on placebo (Echo Pharmaceutical, BV) for 11 days during their inpatient stay
干预措施: Placebo (Drug)
Half-dose CBD
add-on cannabidiol (Echo Pharmaceutical, BV) 450 mg per day for 11 days during their inpatient stay
干预措施: Half dose CBD (Drug)
Full dose CBD
add-on cannabidiol (Echo Pharmaceutical, BV) 900 mg per day for 11 days during their inpatient stay
干预措施: Full dose CBD (Drug)
结局指标
主要结局
Percentage of patients in each group with documented continuous abstinence at month 1 after discharge, week 6 of the study. Continuous abstinence will be defined by patients self-report of alcohol abstinence using standardized TLFB (time line follow back) scales TLFB at screening visit and daily from Day 0 to Day 10 and 4 (1 per week) after discharge up to week 6 of the study)
Percentage of patients in each group with documented continuous abstinence at month 1 after discharge, week 6 of the study. Continuous abstinence will be defined by patients self-report of alcohol abstinence using standardized TLFB (time line follow back) scales TLFB at screening visit and daily from Day 0 to Day 10 and 4 (1 per week) after discharge up to week 6 of the study)
Furthermore, this self-declaration will be confirmed by clinical examination at each study visits assessing acute alcohol intoxication signs and 6 ethyl glucuronide (Et-OH) urinary assessments performed at each study visit (2 during the inpatient stay and 4 (1 per week) after discharge up to week 6 of the study).
Furthermore, this self-declaration will be confirmed by clinical examination at each study visits assessing acute alcohol intoxication signs and 6 ethyl glucuronide (Et-OH) urinary assessments performed at each study visit (2 during the inpatient stay and 4 (1 per week) after discharge up to week 6 of the study).
次要结局
- symptoms check list (PRISE-M) of possible side effects every day from day 1 to 10, and then at each outpatient study visit (4 (1 per week) after discharge up to week 6 of the study). Thus any side effect related to treatment exposure as well as treatment cessation (such as anxiety rebound or withdrawal symptoms related to CBD or increase in cannabis use) could be documented
- - in case of relapse: drinking days and drinks per day (self-declared using standardized TLFB time line follow back scale over the past week) at the screening visit and daily from Day 0 to Day 10 and 4 (1 per week) after discharge up to week 6 of the study)
- - alcohol withdrawal scales and craving scales (CIWA-R, , LIKERT craving scale and an adapt version of the OCDS) at the screening visit and every day from day 0 to 10 then at each study visit: 4 (1 per week) after discharge up to week 6 of the study
- - state anxiety scale (STAI-6 the short form of the Spielberger inventory, composed of 6 Likert scales) at the screening visit and every day from day 0 to 10 then at each study visit: 4 (1 per week) after discharge up to week 6 of the study
- - Pittsburgh Sleep Quality Index (PSQI) at the screening visit and the last visit. A modified daily version every day from day 0 to 10 then at each study visit a modified weekly version: 4 (1 per week) after discharge up to week 6 of the study
- - in the subgroup of patients recruited in AP-HP hospitals, plasmatic level of CBD will be determined twice: at D5 and D10. Analysis of cannabinoids in human biological specimens of plasma will rely on an extraction process and a chromatographic separation in LCMSHR (Liquid chromatography coupled to high resolution mass spectrometry) for quantification of Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), 11-OH THC and THC-COOH according to guidelines set forth by COFRAC.
- - self-declared current use of all other substances including tobacco products and nicotine replacement therapies, cannabis, and other substances using standardized TLFB (time line follow back) scales ) at the screening visit and every day from day 0 to 10 then at each study visit: 4 (1 per week) after discharge up to week 6 of the study
- - in the subgroup of patients who declare themselves as current cannabis users at entry, urinary quantitative determination of cannabinoids by an extraction process and a chromatographic separation in LCMSHR
研究者
Pr Florence VORPSAN
Scientific
Assistance Publique Hopitaux De Paris