Evaluating the Feasibility, Clinical Effects, and Safety of Psilocybin-assisted Psychotherapy for Treatment-resistant Obsessive-compulsive Disorder: An Open-label Clinical Trial
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Feasibility of administering psilocybin (25 mg) in adults with treatment-resistant OCD
研究概览
简要总结
Psilocybin, the chemical component of "magic mushrooms", has been administered with psychotherapy in several randomized clinical trials (RCTs) showing large and sustained antidepressant effects. There is interest to see if similar effects may be provided in those with obsessive compulsive disorder (OCD).
The purpose of this study is to evaluate the safety, feasibility, and clinical effects of psilocybin administration in those with OCD. Ten participants with treatment-resistant OCD will receive two doses of 25mg of psilocybin under supportive conditions, two weeks apart. The investigators hypothesize that two sessions of psilocybin 25mg administered under supportive conditions to participants with treatment-resistant OCD will lead to significant reductions in OCD symptoms.
详细描述
Literature suggests that up to 40 percent of individuals with OCD do not respond to conventional treatment and experience treatment resistant OCD (TROCD) (1, 2). Psilocybin, the chemical component of "magic mushrooms", has been administered with psychotherapy in several randomized clinical trials (RCTs) showing large and sustained antidepressant effects (3). Results of these trials have led to growing calls for transition to clinical use, as well as increased research for other mental health disorders. It is presumed that psilocybin's therapeutic effects are induced by the psychedelic "trip", which is dependent on serotonin 2A receptor (5-HT2AR) activation (4, 5). All studies have used psilocybin in conjunction with psychotherapy involving two therapists present during full-day dosing sessions. There is a need for more data in the TROCD population as there is only one clinical trial published for this specific population, followed by various case reports.
Using a proof-of-concept, open-label, clinical trial approach, 10 participants with TROCD will receive 2 doses of 25mg of psilocybin, with two weeks between each dosing day. The objectives of this study are as follows:
- To assess the safety, and feasibility, of psilocybin, administered with psychological support to adult participants with TROCD. Hypothesis 1: The investigators will be able to recruit and retain ten participants with TROCD for the duration of the trial and that psychedelic-assisted psychotherapy for obsessive compulsive disorder (PAP-OCD) will be safe in those with TROCD, as measured by monitoring adverse events and using the Columbia Suicide Severity Rating Scale (C-SSRS).
- To assess the clinical effects of PAP in those with TROCD. Hypothesis 2: Two sessions of psilocybin (25mg) administered under supportive conditions to participants with TROCD will lead to significant reductions in OCD symptoms as measured by the Yale-Brown Obsessive Compulsive Scale (YBOCS) when comparing baseline to Week 3.
- Provide pilot data on the effect of psilocybin and supportive therapy on TROCD in preparation of a future larger RCT.
Overview of Study Design:
All 10 participants will follow the same study design. Each participant will undergo a screening assessment where they will complete lab tests, and clinical and psychiatric assessments to determine eligibility. Following the screening visit, participants will undergo a washout period where they will be tapered off concomitant medications over a medication the participant is being tapered off (based on the half-life of the medication) and the participant's preference for the length of the tapering period. All medications will require a minimum of a 2-week tapering period with the exception of fluoxetine which will require a minimum of 4-weeks. Additional time may be added at the discretion of the study investigator. During this period, there will be weekly check-ins with the study physician.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •Adults 18 to 65 years old;
- •Are outpatients
- •Must be deemed to have capacity to provide informed consent;
- •Must sign and date the informed consent form;
- •Stated willingness to comply with all study procedures;
- •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;
- •Primary The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnosis of obsessive compulsive disorder (OCD) based on medical records and assessment using the Structured Clinical Interview for DSM-5 (SCID-5) administered at the first screening visit;
- •Participants diagnosed with treatment-resistant OCD defined as individuals with a score of ≥ 16 on the YBOCS (i.e. moderate symptom severity) and that have not responded to two or more separate pharmacological interventions and one or more trials of cognitive behavioural therapy (CBT); there is no upper limit on the number of treatment failures;
- •Individuals with an estimated glomerular filtration rate (eGFR) above 40mL/min/1.73m2 and all blood work within normal limits as assessed by clinical laboratory tests at Screening (V1)
- •Ability to take oral medication;
- •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;
- •Individuals who are willing to and have tapered off current OCD medications for a minimum of 2-weeks prior to Baseline (V2) 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; and
- •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 individuals that intend to become pregnant during the study or are breastfeeding;
- •Treatment with another investigational drug or other intervention within 30 days of Screening (V1);
- •Have initiated psychotherapy in the preceding 12 weeks prior to Screening (V1);
- •Have a DSM-5 diagnosis of substance use disorder (use of tobacco and prescribed opioids are permitted) within the preceding 6 months;
- •Have active suicidal ideation as determined by the C-SSRS and/or clinical interview. Significant suicide risk is defined by suicidal ideation as endorsed by items 4 or 5 of the C-SSRS;
- •Any DSM-5 lifetime diagnosis of a schizophrenia-spectrum 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;
- •Have contraindications to transcranial magnetic stimulation (TMS) as determined by the transcranial magnetic stimulation adult safety screen (TASS) questionnaire;
- •Have a history of seizures;
- •Are taking anticonvulsants or benzodiazepines (Lorazepam up to 2mg/day is acceptable);
- •Presence of a relative or absolute contraindication to psilocybin, including a drug allergy, recent stroke history, uncontrolled hypertension, low or labile blood pressure, recent myocardial infarction, cardiac arrhythmic, severe coronary artery disease, or moderate to severe renal or hepatic impairment;
- •Use of classic psychedelic drugs within the previous 12 months; OR
- •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.
研究组 & 干预措施
Experimental: Psilocybin 25 mg
Participants will receive a 25 mg dose of psilocybin, twice throughout the trial, with two weeks in between doses.
干预措施: Psilocybin (Drug)
结局指标
主要结局
Feasibility of administering psilocybin (25 mg) in adults with treatment-resistant OCD
时间窗: Screening Period, Intervention (2 weeks), Follow-up after 2nd dosing session (up to 10 weeks after 2nd dose)
Percentage of participants recruited and retained
Change in the Yale-Brown Obsessive-Compulsive Scale (YBOCS) total score from baseline
时间窗: Baseline (Day -1) to Week 3 (Day 21)
The Yale-Brown Obsessive-Compulsive Scale is a test to rate the severity of obsessive-compulsive disorder symptoms. It is a 10-item scale, with questions 1-5 regarding obsessions, and questions 6-10 regarding compulsions. Each item is scored from 1-4, for a total possible score of 40. Higher scores represent a more severe condition.
Incidence of adverse events (Safety and Tolerability)
时间窗: Screening Period, Intervention (2 weeks), Follow-up after 2nd dosing session (up to 10 weeks after 2nd dose)
Frequency of dropouts attributed to adverse effects or serious adverse events
次要结局
- Proportion of participants who respond to treatment(Baseline (Day -1) to Week 3 (Day 21))
- Change in the Clinical Global Impression (CGI) scale from Baseline to Week 3(Baseline (Day -1) to Week 3 (Day 21))
- Changes in behavioural assessments for well-being (Warwick-Edinburgh Mental Wellbeing Scale; WEMWBS) from Baseline to Week 3(Baseline (Day -1) to Week 3 (Day 21))
- Change in the World Health Organization Quality of Life Short Version (WHOQOL-BREF) score from Baseline to Week 3(Baseline (Day -1) to Week 3 (Day 21))
- Changes in Patient Health Questionnaire (PHQ-9) from Baseline to Week 3(Baseline (Day -1) to Week 3 (Day 21))
- Change in World Health Organization Disability Assessment Schedule (WHODAS 2.0) from Baseline to Week 3(Baseline (Day -1) to Week 3 (Day 21))
- Change in Generalized Anxiety Disorder (GAD-7) scores from Baseline to Week 3(Baseline (Day -1) to Week 3 (Day 21))