Psilocybin-assisted Therapy for Comorbid Major Depressive Disorder and Alcohol Use Disorder: A Pilot Randomized Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Adherence
研究概览
简要总结
The goal of this clinical trial is to determine the safety and efficacy of psilocybin assisted Therapy (PAT) in individuals with comorbid Major Depressive Disorder (MDD) and Alcohol Use Disorder (AUD). The main question it aims to answer is:
- What is the feasibility and safety of administering PAT in adults with MDD-AUD by evaluating recruitment, retention, tolerability, and safety?
Researchers will compare the psilocybin (25 mg) and placebo groups to see if there are any significant differences in frequency of dropouts or serious adverse events.
Participants will:
- be randomized to receive either psilocybin (25 mg) or placebo
- visit the site (in-person and remotely) for a total of 14 times to complete study tasks
- receive psilocybin-assisted therapy (PAT) at five various timepoints
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Be between the ages of 18-65
- •Must be deemed to have capacity to provide informed consent;
- •Ability to read and communicate in English, such that their literacy and comprehension is sufficient for understanding the consent form and study questionnaires, as evaluated by study staff obtaining consent;
- •Stated willingness to comply with all study procedures;
- •Be deemed in health compatible with the study procedures according to study physician;
- •Ability to take oral medication and be willing to adhere to the PAT regimen;
- •Individuals who are capable of becoming pregnant: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation;
- •Fulfil Diagnostic and Statistical Manual of Mental Disorders (5th Edition) (DSM-5) criteria for a primary diagnosis of current single or recurrent episodes of MDD of at least moderate severity but without psychotic features and a comorbid AUD diagnosis (moderate or severe) using the SCID-5;
- •A score of at least 14 on the Hamilton Depression Rating Scale for Depression (HAMD);
- •Participants should not be interested in initiating standard pharmacotherapies for MDD or AUD. The need to start/resume standard pharmacotherapies will be reassessed at Week
- •Individuals who are willing to and tapered off current antidepressant or IMAOs, antipsychotic and anti-alcohol/anti-craving medications for a minimum of 2-weeks (or more depending on the medication) prior to Baseline (V2) and for the duration of the study and whose physician confirms that it is safe for them to do so;
- •Individuals who are willing to and have tapered off current inhibitors of 5'-diphospho-glucuronosyltransferase (UGT)1A9 and 1A10, aldehyde dehydrogenase inhibitors (ALDHs) and alcohol dehydrogenase inhibitors (ADHs) for a minimum of 2-weeks (or more depending on the medication) prior to Baseline (V2) and for the duration of the study and whose physician confirms that it is safe for them to do so;
- •Agreement to adhere to Lifestyle Considerations (section 4.5) throughout study duration.
排除标准
- •Pregnant as assessed by a urine pregnancy test at Screening (V1) and Baseline (V2) or individual's that intend to become pregnant during the study or are breastfeeding;
- •Presence of a relative or absolute contraindication to psilocybin, including a drug allergy, recent stroke history, uncontrolled hypertension (over 160/100 mmHG), low or labile blood pressure, recent myocardial infarction, cardiac arrhythmic, severe coronary artery disease, or moderate to severe renal or hepatic impairment.
- •Diagnosis of cirrhosis, AST or ALT elevations > 3x upper limit of normal; significant abnormal liver function that would preclude administration of psilocybin based on the judgement of the QI (assessed notably by bilirubin, albumin, alkaline phosphatase, GGT, and INR functions)
- •Any DSM-5 lifetime diagnosis of a schizophrenia-spectrum disorder; obsessive-compulsive disorder, psychotic disorder (unless substance induced or due to a medical condition), bipolar I or II disorder, paranoid personality disorder, borderline personality disorder, or neurocognitive disorder as determined by medical history and the SCID-5 clinical interview;
- •Any first-degree relative with a diagnosis of schizophrenia-spectrum disorder; psychotic disorder (unless substance-induced or due to a medical condition); or bipolar I or II disorder as determined by the family medical history form and discussions with the participant;
- •Clinical Institute Withdrawal Assessment for Alcohol, revised (CIWA-Ar) score > 9, or any other indication that the participant may experience medically complicated withdrawal from alcohol, such as a score of ≥4 in the Prediction of Alcohol Withdrawal Severity Scale.
- •Use benzodiazepines (with the exception of use of up to 2mg of lorazepam equivalent per day for insomnia and anxiety if it is not taken within 12 hours before the psilocybin dose (Week 2).
- •Have a DSM-5 diagnosis of substance use disorder (excluding alcohol, cannabis, tobacco and caffeine) within the preceding 6 months;
- •Presence of baseline prolonged QTc (more than 0.45 seconds for males and 0.47 seconds for females) or Torsade de Pointes as measured by the ECG or a history of long QTc syndrome or related risk factors;
- •Use of aldehyde dehydrogenase (ALDH) inhibitors and UDG modulators;
- •Use of hallucinogens in the past 5 years; or total hallucinogen use ≥10 times)
- •Current suicidality risk as indicated during the conduct of the Columbia Suicide Severity Rating Scale (C-SSRS) with concurrence after a study physician's evaluation if the response to C-SSRS questions 1 or 2 is "yes")
- •Any other clinically significant physical illness including chronic infectious diseases or any other major concurrent illness that, in the opinion of the investigator, may interfere with the interpretation of the study results or constitute a health risk for the participant if they take part in the study.
- •Participants that are responding to anti-alcohol or anti-craving medications
研究组 & 干预措施
Psilocybin (25 mg)
Participant is administered one oral capsule (25 mg psilocybin) with water.
干预措施: Psilocybin 25 mg (Drug)
Placebo
Participant is administered one oral capsule (0 mg psilocybin) with water.
干预措施: Placebo (Drug)
结局指标
主要结局
Adherence
时间窗: Week 2 (Visit 4)
Although all administration of psilocybin will be administered by qualified staff, the investigators will measure adherence through visit compliance (i.e., missed visits).
Montgomery-Asberg Depression Rating Scale (MADRS)
时间窗: Baseline; 1-day post dose; 1-week post dose; 2-week post dose; 3-week post dose; 4-week post dose; week 10; week 14; week 18; week 22; week 26.
Used to assess changes in depressive symptoms on a 10-item scale with each item rated on a scale of 0-6. Higher scores indicate greater severity of symptoms.
Hamilton Depression Rating Scale (HAMD-17)
时间窗: 4-week post dose; week 26.
Used to assess changes in depressive symptoms using 3-point (0-2) or 5-point (0-4) Likert scales. Higher scores indicate greater severity of symptoms.
Quick Inventory of Depressive Symptomatology - Self Report (QUIDS-SR)
时间窗: Baseline; 1-day post dose; 1-week post dose; 2-week post dose; 3-week post dose; 4-week post dose; week 10; week 14; week 18; week 22; week 26.
Used to assess changes in depressive symptoms with a minimum score of 0 to a maximum score of 27.
Alcohol Timeline Followback (TLFB)
时间窗: Baseline; week 2 (visit 3); 1-day post dose; 1-week post dose; 2-week post dose; 3-week post dose; 4-week post dose; week 10; week 14; week 18; week 22; week 26.
To monitor alcohol consumption, heavy drinking days, drinks per day, drinks per drinking day, percent very heavy drinking days, percent participants with no heavy drinking days, and abstinent percent will be measured.
Clinical Institute Withdrawal Assessment (CIWA)
时间窗: Baseline; week 2 (visit 3); week 2 (visit 4); 1-day post dose; 1-week post dose; 2-week post dose; 3-week post dose; 4-week post dose; week 10; week 14; week 18; week 22; week 26.
Used to assess alcohol withdrawal symptoms. Scores range from 0 to 67 with higher scores indicating greater severity of withdrawal symptoms.
Prediction of Alcohol Withdrawal Severity Scale (PAWSS)
时间窗: Baseline; 1-day post dose; 1-week post dose; 2-week post dose; 3-week post dose; 4-week post dose; week 10; week 14; week 18; week 22; week 26.
Used to assess risk of alcohol withdrawal symptoms using a 10-item scale with the total score ranging from 0 to 10. Higher scores indicate greater risk of withdrawal symptoms.
Penn Alcohol Craving Scale (PACS)
时间窗: Baseline; 1-day post dose; 1-week post dose; 2-week post dose; 3-week post dose; 4-week post dose; week 10; week 14; week 18; week 22; week 26.
Used to assess history, frequency, and consequences of alcohol use. Scores range from 0 to 30 with higher scores indicating greater craving.
Addiction Severity Index (ASI)
时间窗: Baseline; 1-day post dose; 1-week post dose; 2-week post dose; 3-week post dose; 4-week post dose; week 10; week 14; week 18; week 22; week 26.
Used to assess history, frequency, and consequences of alcohol use
次要结局
- 5 Dimensional Altered States of Consciousness (5-DASC)(Week 2 (visit 4).)
- Psychological Insight Questionnaire (PIQ)(Week 2 (visit 4).)
- Mystical Experience Questionnaire (MEQ)(Week 2 (visit 4).)
- Challenging Experience Questionnaire (CEQ)(Week 2 (visit 4).)
- General Anxiety Disorder-7th edition (GAD-7)(Baseline; week 26.)
- State Trait Anxiety Index (STAI)(Baseline; week 26.)
- World Health Organization Quality of Life Questionnaire Brief Version (WHOQOL-BREF)(Baseline; week 26.)
- Big Five Inventory (BFI)(Baseline; week 26.)
- Pittsburgh Sleep Quality Index (PSQI)(Baseline; week 26.)
- Acceptance & Action Questionnaire II (AAQ-II)(Baseline; 1-day post dose; 1-week post dose; 2-week post dose; 3-week post-dose; 4-week post-dose; week 10; week 14; week 18; week 22; week 26.)
- Stanford Expectations of Treatment Scale (SETS)(Baseline)
- Working Alliance Inventory (WAI)(Week 2 (visit 3); 1-day post dose; 1-week post dose.)
研究者
Bernard Le Foll
Principal Investigator
Centre for Addiction and Mental Health