Clinical trial NCT06235411: Psilocybin in Alcohol Use Disorder With Comorbid Depression
Official title: Psilocybin in Alcohol Use Disorder With Comorbid Depression
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Alcohol-Related Disorders
Depressive Disorder
Addiction
Keywords: Psilocybin
Psychedelic assisted therapy
Lead sponsor: Centre Hospitalier Universitaire de Nīmes
Sponsor class: OTHER
First posted: 2024-01-31
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: Inclusion Criteria:

* Patient with a confirmed DSM-5 diagnosis of severe alcohol use disorder.
* BDI II (Beck Depression Inventory) score ≥ 14.
* 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

Exclusion Criteria:

* 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 1.
* 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 ≥ 8.
* 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

Primary outcomes:
measure: Feasibility of the intervention between groups
timeFrame: After 2nd experimental session (Week 4)
Secondary outcomes:
measure: Feasibility of recruitment between groups
timeFrame: 18 Months
measure: Feasibility of retainment between groups
timeFrame: 18 Months
measure: Feasibility of the trial between groups
timeFrame: 18 Months
measure: Feasibility of randomization between groups
timeFrame: 18 Months
measure: Feasibility of inclusion between groups
timeFrame: 18 Months
measure: Feasibility of therapeutic intervention between groups
timeFrame: 18 Months
measure: Study acceptability between groups
timeFrame: 18 Months
measure: Patient-reported reasons for abandoning the study between groups
timeFrame: 18 Months
measure: Decrease in alcohol consumption between groups
timeFrame: Day 0
measure: Decrease in alcohol consumption between groups
timeFrame: Week 6 (or discharge if it takes place later)
measure: Decrease in alcohol consumption between groups
timeFrame: Week 12
measure: Total alcohol consumption between groups
timeFrame: Day 0
measure: Total alcohol consumption between groups
timeFrame: Week 6 (or discharge if it takes place later)
measure: Total alcohol consumption between groups
timeFrame: Week 12
measure: Time before first drink
timeFrame: Day 0
measure: Time before first drink
timeFrame: Week 6 (or discharge if it takes place later)
measure: Time before first drink
timeFrame: Week 12
measure: Time to first day of heavy drinking
timeFrame: Day 0
measure: Time to first day of heavy drinking
timeFrame: Week 6 (or discharge if it takes place later)
measure: Time to first day of heavy drinking
timeFrame: Week 12
measure: Craving between groups
timeFrame: Day 0
measure: Craving between groups
timeFrame: Week 12
measure: Quality of life between groups
timeFrame: Day 0
measure: Quality of life between groups
timeFrame: Week 12
measure: Depression between groups
timeFrame: Day 0
measure: Depression between groups
timeFrame: Week 12
measure: Anxiety between groups
timeFrame: Day 0
measure: Anxiety between groups
timeFrame: Week 12
measure: Emotion regulation difficulties between groups
timeFrame: Day 0
measure: Emotion regulation difficulties between groups
timeFrame: Week 12
measure: Rejection sensitivity between groups
timeFrame: Day 0
measure: Rejection sensitivity between groups
timeFrame: Week 12
measure: Meaning in life between groups
timeFrame: Day 0
measure: Meaning in life between groups
timeFrame: Week 3
measure: Meaning in life between groups
timeFrame: Week 6
measure: Meaning in life between groups
timeFrame: Week 12
measure: Cognitive functioning between groups
timeFrame: Day 0
measure: Cognitive functioning between groups
timeFrame: Second psilocybin session (Week 4)
measure: Role of cognitive function at baseline on change in the percentage of heavy drinking days in preceding 4 weeks
timeFrame: Day 0
measure: Role of Posttraumatic Stress Disorder at baseline on change in the percentage of heavy drinking days in preceding 4 weeks
timeFrame: Day 0
measure: Role of attachment at baseline on change in the percentage of heavy drinking days in preceding 4 weeks
timeFrame: Day 0
measure: Change in the percentage of heavy drinking days in preceding 4 weeks according to concomitant Selective serotonin reuptake inhibitors
timeFrame: Day 0
measure: Change in the percentage of heavy drinking days in preceding 4 weeks according to concomitant Selective serotonin reuptake inhibitors
timeFrame: Week 3
measure: Change in the percentage of heavy drinking days in preceding 4 weeks according to concomitant Selective serotonin reuptake inhibitors
timeFrame: Week 6
measure: 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
timeFrame: Week 12
measure: Role of the patient-reported quality of the hallucinogenic experience on change in the percentage of heavy drinking days in preceding 4 weeks
timeFrame: End of 1st psilocybin session (Week 1)
measure: Role of the patient-reported quality of the hallucinogenic experience on change in the percentage of heavy drinking days in preceding 4 weeks
timeFrame: End of 2nd psilocybin session (Week 4)
measure: 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
timeFrame: Before 1st experimental session (Week 1)
measure: 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
timeFrame: During the 1st experimental session (Week 1)
measure: 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
timeFrame: Day after 2nd experimental session (Week 4)
measure: Change in the percentage of heavy drinking days in preceding 4 weeks according to the quality of the hallucinogenic experience
timeFrame: Day after 1st experimental session (Week 1)
measure: Change in the percentage of heavy drinking days in preceding 4 weeks according to the quality of the hallucinogenic experience
timeFrame: Day after 2nd experimental session (Week 4)
measure: immune profiles through the microbiota
timeFrame: day 0
measure: Evolution immune profiles through the microbiota
timeFrame: day 0
measure: Immune and inflammatory profiles using cerebral structural and functional MRI
timeFrame: day 0
measure: Immune and inflammatory profiles using cerebral structural and functional MRI
timeFrame: week 3
measure: Evolution of Immune and inflammatory profiles using cerebral structural and functional MRI
timeFrame: day 0
measure: Evolution of Immune and inflammatory profiles using cerebral structural and functional MRI
timeFrame: week 3
measure: immune profiles through the microbiota
timeFrame: week 3
measure: Evolution immune profiles through the microbiota
timeFrame: week 3
measure: Inflammatory profiles by measuring the cytokine TNF alpha in plasma
timeFrame: day 0
measure: Inflammatory profiles by measuring the cytokine TNF alpha in plasma
timeFrame: week 3
measure: analysis of intestinal microbiota : Number of species detected in the intestinal microbiota
timeFrame: day 0
measure: analysis of intestinal microbiota : Number of species detected in the intestinal microbiota
timeFrame: week 3
measure: analysis of intestinal microbiota : Distribution of species detected in the intestinal microbiota.
timeFrame: day 0
measure: analysis of intestinal microbiota : Distribution of species detected in the intestinal microbiota.
timeFrame: week 3
measure: analysis of intestinal microbiota : Diversity of species detected in the intestinal microbiota.
timeFrame: day 0
measure: analysis of intestinal microbiota : Diversity of species detected in the intestinal microbiota.
timeFrame: week 3
measure: Inflammatory profiles by measuring the cytokine IL-1b in plasma
timeFrame: day 0
measure: Inflammatory profiles by measuring the cytokine IL-1b in plasma
timeFrame: week 3
measure: Inflammatory profiles by measuring the cytokine IL-6 in plasma
timeFrame: day 0
measure: Inflammatory profiles by measuring the cytokine IL-6 in plasma
timeFrame: week 3
measure: Inflammatory profiles by measuring the cytokine IL-8 in plasma
timeFrame: day 0
measure: Inflammatory profiles by measuring the cytokine IL-8 in plasma
timeFrame: week 3
measure: Inflammatory profiles by measuring the cytokine IL-10 in plasma
timeFrame: day 0
measure: Inflammatory profiles by measuring the cytokine IL-10 in plasma
timeFrame: week 3
Other outcomes:
Locations:
city: Nîmes
country: France
facility: CHU
Study officials:
affiliation: CHU de Nimes
name: Amandine Luquiens
role: PRINCIPAL_INVESTIGATOR
References: