Psilocybin in Alcohol Use Disorder with Comorbid Depression
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Feasibility of the intervention between groups
研究概览
简要总结
Up to 40% of people with alcohol use disorder (AUD) experience depression. Depression is a risk factor for early relapse of AUD after withdrawal in a controlled environment. Promising data suggest the effectiveness of psilocybin, a psychedelic-type treatment, in depression and AUD. Following the acute effects of the psychedelic experience, which lasts approximately 6 hours, psilocybin action appears to be beneficial for preventing alcohol relapse in recently weaned people suffering from comorbid depression. Whilst the public perception of psilocybin therapy is poorly documented in France, the rapid changes in the legal status of psilocybin elsewhere, the positive media coverage of recent trials in depression, and the recent designation as an "innovative therapy" by the FDA could lead to the refusal of randomization of eligible participants. It is therefore essential to evaluate the feasibility and acceptability of psilocybin treatment and blinded randomized design in our clinical population of hospitalized patients with AUD and depressive symptoms. Recent data suggest that the effect size of psilocybin is much higher than other currently available treatments. However, this paradigm shift must be confirmed in our cohort of people with AUD and depressive symptoms, and in the context of treatment in addition to usual care, by an estimation of the expected effect size based on real data. This will allow the sample size to be accurately calculated for a large-scale randomized clinical trial. Finally, the potential mechanisms of action of psilocybin to prevent relapse in AUD with comorbid depression after withdrawal need to be documented. The objective of this pilot study is to evaluate the feasibility, acceptability, neural mechanisms and preliminary results of the effectiveness of psilocybin in the treatment of AUD and depressive symptoms after withdrawal, in addition to usual treatment. The study authors hypothesize that two oral administrations of 25 mg psilocybin at three-week intervals versus a control condition (1 mg psilocybin), in addition to the usual treatment, will be acceptable and feasible in recently withdrawn individuals suffering from AUD and depressive symptoms, between 14 and 60 days after their last alcohol consumption
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)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient with a confirmed DSM-5 diagnosis of severe alcohol use disorder.
- •BDI II (Beck Depression Inventory) score ≥
- •Last alcohol consumption must have occurred between 60 and 14 days prior to study inclusion. The patient must have had at least one heavy drinking day during the last period of alcohol consumption.
- •NB: The last period of alcohol consumption prior to inclusion is defined as the last 4 weeks counted from the last drink.
- •Patient with free and informed consent.
- •The patient must be a member or beneficiary of a health insurance plan
排除标准
- •The subject is participating in an interventional study involving a drug or in a clinical trial according to the REC.
- •The subject is in a period of exclusion determined by a previous study
- •The subject unable to express consent
- •It is impossible to give the subject informed information
- •The patient is under safeguard of justice or state guardianship
- •Schizophrenic disorder, or any history of psychotic disorder according to the clinician's judgment.
- •Past or current manic or hypomanic episode.
- •Need for antipsychotic treatment that may interfere with psilocybin.
- •Need for treatment with monoamine oxidase inhibitors (MAOIs) which may interfere with psilocybin.
- •Current scripted suicidal ideation (according to clinician judgment) corresponding to a "high risk" score on the Columbia-Suicide Severity Rating Scale (C-SSRS).
- •First-degree family member diagnosed with psychotic disorder or bipolar disorder type
- •High risk of negative emotional or behavioral response based on the investigator's clinical judgment (e.g., signs of serious personality disorders, antisocial behavior, severe current stressors, lack of meaningful social support)
- •Patient with dementia or severe cognitive impairment (as judged by the clinician).
- •CIWA-R score ≥
- •Medical conditions that would prevent safe participation in the trial; for example: seizure disorders, significant impairment of liver function, coronary heart disease, history of arrhythmia, heart failure, uncontrolled hypertension (greater than 165/95 mmHg at screening), history of stroke, severe asthma, hyperthyroidism, narrow-angle glaucoma, stenotic peptic ulcer, pyloroduodenal obstruction, symptomatic enlarged prostate or bladder neck obstruction), Uncontrolled type I or type II diabetes or history of ketoacidosis, hyperglycemic coma or severe hypoglycemia with loss of conscience
- •History of hallucinogen use disorder, any use in the past year or >25 lifetime uses.
- •Dependence on cocaine, psychostimulants, opioids or cannabis (last 12 months).
- •Current non-medical use of cocaine, psychostimulants or opioids (past 30 days).
- •Serious ECG abnormalities (e.g., signs of ischemia, myocardial infarction, QTc prolongation (QTc > 0.45 seconds for men, QTc > 0.47 seconds for women).
- •Hypersensitivity to the active ingredient or excipients
- •No access to email.
- •Insufficient understanding of French to complete the questionnaires.
- •Patient for whom it is impossible to provide informed information.
- •Pregnant or breastfeeding patient.
- •Patient planning a pregnancy
研究组 & 干预措施
Experimental group
干预措施: stool samples (Other)
Experimental group
干预措施: Psilocybin therapy (Drug)
Experimental group
干预措施: Electroencephalogram (Other)
Experimental group
干预措施: Blood samples for the analysis of immune and inflammatory profiles (Other)
Experimental group
干预措施: MRI functional and cerebral (Other)
Control group
干预措施: Inactive Psilocybin therapy (Drug)
Control group
干预措施: Electroencephalogram (Other)
Control group
干预措施: Blood samples for the analysis of immune and inflammatory profiles (Other)
Control group
干预措施: stool samples (Other)
Control group
干预措施: MRI functional and cerebral (Other)
结局指标
主要结局
Feasibility of the intervention between groups
时间窗: After 2nd experimental session (Week 4)
Number of patients who completed both sessions
次要结局
- Feasibility of recruitment between groups(18 Months)
- Feasibility of retainment between groups(18 Months)
- Feasibility of the trial between groups(18 Months)
- Feasibility of randomization between groups(18 Months)
- Feasibility of inclusion between groups(18 Months)
- Feasibility of therapeutic intervention between groups(18 Months)
- Study acceptability between groups(18 Months)
- Patient-reported reasons for abandoning the study between groups(18 Months)
- Decrease in alcohol consumption between groups(Week 12)
- Total alcohol consumption between groups(Week 12)
- Time before first drink(Week 12)
- Time to first day of heavy drinking(Week 12)
- Craving between groups(Week 12)
- Quality of life between groups(Week 12)
- Depression between groups(Week 12)
- Anxiety between groups(Week 12)
- Emotion regulation difficulties between groups(Week 12)
- Rejection sensitivity between groups(Week 12)
- Meaning in life between groups(Week 12)
- Cognitive functioning between groups(Second psilocybin session (Week 4))
- Role of cognitive function at baseline on change in the percentage of heavy drinking days in preceding 4 weeks(Day 0)
- Role of Posttraumatic Stress Disorder at baseline on change in the percentage of heavy drinking days in preceding 4 weeks(Day 0)
- Role of attachment at baseline on change in the percentage of heavy drinking days in preceding 4 weeks(Day 0)
- Change in the percentage of heavy drinking days in preceding 4 weeks according to concomitant Selective serotonin reuptake inhibitors(Week 6)
- Change in the percentage of heavy drinking days in preceding 4 weeks according to concomitant Selective serotonin reuptake inhibitorsof other treatments on change in the percentage of heavy drinking days in preceding 4 weeks(Week 12)
- Role of the patient-reported quality of the hallucinogenic experience on change in the percentage of heavy drinking days in preceding 4 weeks(End of 2nd psilocybin session (Week 4))
- Role of the quality of the hallucinogenic experience according to brain activity on change in the percentage of heavy drinking days in preceding 4 weeks(Day after 2nd experimental session (Week 4))
- Change in the percentage of heavy drinking days in preceding 4 weeks according to the quality of the hallucinogenic experience(Day after 2nd experimental session (Week 4))
- immune profiles through the microbiota(week 3)
- Evolution immune profiles through the microbiota(week 3)
- Immune and inflammatory profiles using cerebral structural and functional MRI(week 3)
- Evolution of Immune and inflammatory profiles using cerebral structural and functional MRI(week 3)
- Inflammatory profiles by measuring the cytokine TNF alpha in plasma(week 3)
- analysis of intestinal microbiota : Number of species detected in the intestinal microbiota(week 3)
- analysis of intestinal microbiota : Distribution of species detected in the intestinal microbiota.(week 3)
- analysis of intestinal microbiota : Diversity of species detected in the intestinal microbiota.(week 3)
- Inflammatory profiles by measuring the cytokine IL-1b in plasma(week 3)
- Inflammatory profiles by measuring the cytokine IL-6 in plasma(week 3)
- Inflammatory profiles by measuring the cytokine IL-8 in plasma(week 3)
- Inflammatory profiles by measuring the cytokine IL-10 in plasma(week 3)