High vs. Low-Dose Group-Based Psilocybin-Assisted Therapy (PAT) With or Without Mindfulness-Based (MB) Preparation and Integration for Demoralization in Adults With Advanced Cancer (PAT-MIND): A Pilot Feasibility 2x2 Factorial Multisite Trial
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Overall Trial Feasibility Based on Prespecified RED/YELLOW/GREEN Progression Criteria
研究概览
简要总结
This pilot clinical trial will study psilocybin-assisted therapy for adults with advanced cancer who are experiencing demoralization, existential distress, or related psychological concerns. Demoralization can include feelings of hopelessness, helplessness, loss of meaning, and distress related to illness or end of life.
The purpose of this study is to assess whether a hybrid group-based psilocybin-assisted therapy program is feasible, acceptable, and safe in adults with advanced cancer. The study will also explore which combination of psilocybin dose and psychotherapy approach may be most promising for a future larger trial.
Participants will be randomly assigned by wave to one of four intervention combinations: 25 mg psilocybin with mindfulness-based psilocybin-assisted therapy, 25 mg psilocybin with standard psilocybin-assisted therapy, 5 mg psilocybin with mindfulness-based psilocybin-assisted therapy, or 5 mg psilocybin with standard psilocybin-assisted therapy. The psilocybin dose will be blinded, meaning participants and some members of the study team will not know which dose was assigned. Psychotherapy approach will not be blinded. The study will enroll at least 60 participants across Calgary and Kingston.
详细描述
PAT-MIND is a multi-site, phase IIb pilot feasibility and therapy-optimization trial of psilocybin-assisted therapy in adults with advanced cancer. The study uses a wave-randomized 2×2 factorial design to examine two intervention components: psilocybin dose and psychotherapy intensity. Participants will be enrolled in small waves, and each wave will be randomized to one of four combinations: high-dose psilocybin plus mindfulness-based psilocybin-assisted therapy, high-dose psilocybin plus standard psilocybin-assisted therapy, low-dose psilocybin plus mindfulness-based psilocybin-assisted therapy, or low-dose psilocybin plus standard psilocybin-assisted therapy.
The psilocybin dose comparison is blinded. Participants will receive either 25 mg or 5 mg psilocybin during a monitored in-person group dosing session. The psychotherapy intensity comparison is not blinded. Participants will receive either mindfulness-based psilocybin-assisted therapy or standard psilocybin-assisted therapy, depending on their randomized intervention combination. Preparation and integration sessions will be delivered using a hybrid format, with some sessions conducted in person and some virtually, depending on the session type and site logistics.
The primary aims of this pilot trial are to assess the feasibility, acceptability, and safety of hybrid group-based psilocybin-assisted therapy in adults with advanced cancer, and to explore therapy-optimization signals for psilocybin dose and psychotherapy intensity to inform a future definitive trial. Exploratory objectives include participant experience, demoralization, secondary psychological outcomes, health-related quality of life, health-economic measures, and exploratory biomarker outcomes.
Study procedures include screening, informed consent, trial-specific questionnaires, group and individual preparation and integration sessions, a monitored psilocybin dosing day, dried blood spot collection, stool sample collection, optional wearable device data collection, and medical chart review. Participants will complete online questionnaires at protocol-defined timepoints, including measures of demoralization, psychological distress, quality of life, treatment experience, and resource use.
Safety will be monitored throughout the study, including adverse event monitoring during and after the dosing session.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 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
- •Written informed consent provided before any study-specific procedures.
- •Age 18 years or older.
- •Diagnosis of advanced cancer: Stage III-IV or metastatic solid tumor. Stage II cancer may be eligible if the treating oncologist confirms advanced/refractory disease with clinically significant existential burden, defined as a Demoralization Scale-II (DS-II) score ≥
- •Clinical life expectancy of at least 6 months. Borderline cases of approximately 5-6 months may be considered based on Principal Investigator judgment and documentation.
- •Demoralization Scale-II (DS-II) total score ≥4 at screening, or DS-II total score ≥3 with documented clinical impression of significant existential distress.
- •Willing and cognitively able to complete at least 2 preparation sessions, 1 in-person dosing session, and at least 2 integration sessions over approximately 6-8 weeks.
- •Sufficient spoken and written English proficiency to provide informed consent, participate in group therapy, and complete participant-reported outcome measures.
- •Not pregnant or lactating. Participants of childbearing potential must have a negative pregnancy test at screening and comply with protocol-specified contraception requirements.
- •A responsible adult, such as a family member, friend, or caregiver, must be available to accompany the participant or be on-call for at least 12 hours following the dosing session.
排除标准
- •Psychiatric/Psychological:
- •Active or high-risk suicidality, defined as Columbia-Suicide Severity Rating Scale (C-SSRS) item 4 or 5 within the past 4 weeks, or a suicide attempt within the past 12 months. Passive death wishes and suicidal ideation without intent are not exclusionary.
- •Current psychotic disorder or active psychotic symptoms, including schizophrenia, schizoaffective disorder, hallucinations, delusions, or thought disorganization. Historical psychosis in sustained remission may be considered on a case-by-case basis by the Principal Investigator.
- •Current manic or mixed-state episode. Stable, euthymic bipolar disorder on maintenance pharmacotherapy may be permitted with Principal Investigator judgment and documentation.
- •Moderate-to-severe active alcohol, stimulant, or opioid use disorder within the past 12 months. Severe uncontrolled cannabis use disorder is exclusionary; stable prescribed cannabis use is permitted.
- •Pharmacological/Drug Interactions:
- •Use of concomitant medications that does not meet the requirements of the protocol-specified Concomitant Medications Policy.
- •Known allergy, anaphylaxis, or serious hypersensitivity to psilocybin, psilocin, related tryptamines, or capsule excipients.
- •Severe hepatic impairment, defined as a current unstable diagnosis of liver disease with AST or ALT >5 times the upper limit of normal and clinical symptoms.
- •Severe renal impairment, including current unstable acute kidney injury or advanced kidney disease (CKD Stage 4) with eGFR <30 mL/min/1.73 m².
- •Unstable cardiovascular disease, including myocardial infarction or stroke within the past 3 months, decompensated heart failure (NYHA III-IV), or uncontrolled arrhythmia. Elevated blood pressure on dosing day may require dosing deferral and reassessment according to protocol-defined thresholds.
- •Seizure within the past 12 months or currently uncontrolled epilepsy. Well-controlled epilepsy with no seizures for more than 12 months on stable therapy may be permitted with monitoring.
- •Uncontrolled diabetes, including unstable Type 1 diabetes with diabetic ketoacidosis within the past 3 months, or Type 2 diabetes with HbA1c >11% and symptomatic hyperglycemia.
- •Any medical, neurological, or psychiatric condition, or concurrent cancer-directed therapy, that in the Principal Investigator's clinical judgment would materially increase risk or prevent meaningful protocol participation.
- •Cancer Treatment-Related:
- •Systemic anti-cancer therapy that does not meet protocol requirements. Chemotherapy, immunotherapy, and targeted therapy are permitted when the regimen is stable, treatment-related toxicities are CTCAE Grade 2 or lower, and protocol-specified timing requirements before psilocybin dosing are met.
- •Opioid analgesic or corticosteroid use that does not meet protocol requirements. Opioids must be on a stable dose for at least 1 week without opioid-induced delirium or clinically significant respiratory compromise. Corticosteroids must generally be stable for at least 2 weeks; high-dose dexamethasone for acute central nervous system edema requires dosing to be deferred until clinically stable.
研究组 & 干预措施
5 mg Psilocybin + Standard PAT
干预措施: PEX010 5 mg psilocybin (Drug)
5 mg Psilocybin + Mindfulness-Based PAT
干预措施: PEX010 5 mg psilocybin (Drug)
5 mg Psilocybin + Standard PAT
干预措施: Standard Psilocybin-Assisted Therapy (Behavioral)
5 mg Psilocybin + Mindfulness-Based PAT
干预措施: Mindfulness-Based Psilocybin-Assisted Therapy (Behavioral)
25 mg Psilocybin + Standard PAT
干预措施: PEX010 25 mg psilocybin (Drug)
25 mg Psilocybin + Standard PAT
干预措施: Standard Psilocybin-Assisted Therapy (Behavioral)
25 mg Psilocybin + Mindfulness-Based PAT
干预措施: PEX010 25 mg psilocybin (Drug)
25 mg Psilocybin + Mindfulness-Based PAT
干预措施: Mindfulness-Based Psilocybin-Assisted Therapy (Behavioral)
结局指标
主要结局
Overall Trial Feasibility Based on Prespecified RED/YELLOW/GREEN Progression Criteria
时间窗: From initial referral/screening through the 3-month follow-up (A5), up to approximately 4 months
Overall trial feasibility will be assessed using prespecified progression criteria covering recruitment, intervention delivery, and retention. Component metrics include screening completion among referred individuals, eligibility among screened individuals, enrollment among eligible individuals, preparation-session attendance, integration-session attendance, completion of the 1-week post-dose assessment (A3), and completion of the 3-month follow-up (A5). Each component will be expressed as a proportion and classified according to prespecified RED (review), YELLOW (amend), or GREEN (go) thresholds. The overall feasibility classification will be determined by the worst-performing component, resulting in a single overall RED/YELLOW/GREEN progression classification. Feasibility will be assessed pooled across all four intervention arms.
Incidence of Adverse Events (AEs)
时间窗: From informed consent through the 3-month follow-up (A5), approximately up to 4 months
Safety will be assessed in all participants who receive psilocybin. Adverse events will be collected from informed consent through the 3-month follow-up (A5) and summarized as the number and proportion of participants experiencing one or more adverse events. Events will be characterized by severity, relationship to psilocybin, dose group, and timing. Serious adverse events (SAEs) and protocol-defined adverse events of special interest (AESIs) will be identified and summarized as prespecified safety categories.
次要结局
- Change in Demoralization Scale-II (DS-II) Total Score(Baseline to 1 week post-dose)
- Change in anxiety symptoms assessed by PROMIS Anxiety Short Form 8a(Baseline through 3 months post-dose)
- Change in depressive symptoms assessed by PROMIS Depression Short Form 8a(Baseline through 3 months post-dose)
- Change in Death and Dying Distress Scale (DADDS) Total Score(Baseline through 3 months post-dose)
- Change in Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being 12-Item Scale (FACIT-Sp-12) Score(Baseline through 3 months post-dose)
- Change in PROMIS Pain Intensity Score(Baseline through 3 months post-dose)
- Change in PROMIS Pain Interference Score(Baseline through 3 months post-dose)
- Change in EuroQol Five-Dimension Five-Level (EQ-5D-5L) Health Utility Score(Baseline through 3 months post-dose)
- Change in Mindfulness Assessed by the Mindful Allowance 8-Item Short Form(Baseline through 3 months post-dose)
研究者
Linda E. Carlson
Professor
University of Calgary