PSilocybin for psYCHological and Existential Distress in PALliative Care (PSYCHED-PAL)

NCT04754061 | Recruiting Phase 1 DMC

• 1 other identifier: 7745629246
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this multi-centre phase I/II open-label, single-arm study is to determine the safety, feasibility, therapeutic dose, and preliminary efficacy of psilocybin microdosing to treat psychological distress among patients with advanced illness. Forty patients will receive psilocybin drug product (1-3mg per day, Mon-Fri) for 4 weeks to be administered via oral capsules by the participant. Feasibility (recruitment rate, rate of intervention and follow-up completion), safety (rate of adverse events), dosing, and preliminary efficacy (depression, anxiety, overall well-being, and global impression of change) will be measured.

Conditions

Depression, Anxiety; Distress, Emotional

Keywords

existential distress; psychological distress; psilocybin; microdosing

Outcome Measures

Primary Outcomes (18)

• Recruitment Rate

  Number of patients enrolled divided by number of patients approached

  Through study completion, up to 1 year

• Intervention Completion Rate

  Number of participants who complete the intervention divided by number of participants enrolled

  Through study completion, up to 13 months

• Follow-up Completion Rate

  Number of participants who complete follow-up divided by number of participants enrolled

  Through study completion, up to 18 months

• Number of Participants With Adverse Events - Change in Blood Pressure

  Proportion of participants with systolic blood pressure of \>180mmHg or an increase in 40% from baseline measurements

  Measured at baseline and daily (Mon-Fri) from enrolment to intervention completion (up to 4 weeks)

• Number of Participants With Adverse Events - Change in Heart Rate

  Proportion of participants with resting heart rate \>100bpm or an increase in 40% from baseline

  Measured at baseline and daily (Mon-Fri) from enrolment to intervention completion (up to 4 weeks)

• Number of Participants With Adverse Events - Delirium

  Proportion of participants who develop delirium, measured by the Confusion Assessment Method or the Family Confusion Assessment Method

  Through intervention completion, up to 4 weeks

• Number of Participants With Adverse Events - Serotonin Syndrome

  Proportion of participants who develop serotonin syndrome, diagnosed by Study Doctor

  Through intervention completion, up to 4 weeks

• Number of Participants With Adverse Events - Adverse Mood or Behaviour Change

  Proportion of participants who report adverse mood or behaviour changes (recorded daily in a participant diary)

  Measured at baseline and from enrolment to intervention completion (up to 4 weeks); 2-week and 4-week follow-up

• Psychological Distress - Anxiety and Depression

  Measured using the Hospital Anxiety and Depression Scale (higher score indicate worse anxiety/depression)

  Baseline

• Change in Psychological Distress - Anxiety and Depression

  Measured using the Hospital Anxiety and Depression Scale (higher score indicate worse anxiety/depression)

  Weekly (every Friday) during intervention (4 weeks)

• Change in Psychological Distress - Anxiety and Depression

  Measured using the Hospital Anxiety and Depression Scale (higher score indicate worse anxiety/depression)

  Follow-up (1 day, 2 weeks, 4 weeks, 12 weeks, 24 weeks)

• Psychological Distress - Anxiety, Depression, and Well-being

  Measured using the Edmonton Symptom Assessment System anxiety, depression, and well-being item scores (score 0-10 for each item - higher scores indicate worse symptoms)

  Baseline

• Change in Psychological Distress - Anxiety, Depression, and Well-being

  Measured using the Edmonton Symptom Assessment System anxiety, depression, and well-being item scores (score 0-10 for each item - higher scores indicate worse symptoms)

  Weekly (every Friday) during intervention (4 weeks)

• Change in Psychological Distress - Anxiety, Depression, and Well-being

  Measured using the Edmonton Symptom Assessment System anxiety, depression, and well-being item scores (score 0-10 for each item - higher scores indicate worse symptoms)

  Follow-up (1 day, 2 weeks, 4 weeks, 12 weeks, 24 weeks)

• Psychological Distress - Global Impression of Change

  Measured using the Patient Global Impression of Change scale (higher scores indicate greater positive change)

  Weekly (every Friday) during intervention (4 weeks); 1 day, 2 week, 4 week, 12 week, 24 week follow-up

• Dosing

  Dose at which therapeutic benefit, if any, is achieved assessed by change in Hospital Anxiety and Depression Scale score (score reduction of 50% indicates therapeutic benefit)

  Weekly (each Friday) for intervention period (4 weeks)

• Dosing

  Dose at which therapeutic benefit, if any, is achieved assessed by Edmonton Symptom Assessment Scale score (two-point score reduction or absolute score less than 3 indicate therapeutic benefit)

  Weekly (each Friday) for intervention period (4 weeks)

• Dosing

  Dose at which therapeutic benefit, if any, is achieved assessed by Global Impression fo Change score (score of 5 or above indicate therapeutic benefit)

  Weekly (each Friday) for intervention period (4 weeks)

Secondary Outcomes (5)

• Existential Distress

  Baseline (Friday prior to first dose administered on a Monday); 1 day, 2 week, 4 week, 12 week, 24 week follow-up

• Psychological distress

  Baseline (Friday prior to first dose administered on a Monday); 1 day, 2 week, 4 week, 12 week, 24 week follow-up

• Participant Quality of Life

  Baseline (Friday prior to first dose administered on a Monday); 1 day, 2 week, 4 week, 12 week, 24 week follow-up

• Wish to Die

  Baseline (Friday prior to first dose administered on a Monday); 1 day, 2 week, 4 week, 12 week, 24 week follow-up

• Global Distress

  Baseline (Friday prior to first dose administered on a Monday); 1 day, 2 week, 4 week, 12 week, 24 week follow-up

Study Arms (1)

Psilocybin Microdosing

EXPERIMENTAL

Participants will receive a 4-week psilocybin microdosing intervention (1-3mg/day, Monday-Friday for up to 4 weeks; start at 1mg with opportunity to increase dose each week)

Drug: Psilocybin

Interventions

Psilocybin DRUG

Phase 1 (week 1): all enrolled participants will take a single 1mg oral dose of psilocybin once per day on Monday and Thursday. If no adverse events are reported at any point during the week (Mon-Fri), the participant will continue to Phase 2 for week 2. Phase 2: The participant will take a single 1mg oral dose of psilocybin once per day for 5 consecutive days (Monday to Friday). If no adverse events are reported at any point during the week (Mon-Fri), the participant will continue to Phase 3 for week 3. Phase 3: The participant will take two 1mg oral doses (2mg total) of psilocybin once per day for 5 consecutive days (Monday to Friday). If no adverse events are reported at any point during the week (Mon-Fri), the participant will continue to Phase 4 for week 4. Phase 4 (maximum allowable dose): The participant will take three 1mg oral doses (3mg total) of psilocybin once per day for 5 consecutive days (Monday to Friday).

Psilocybin Microdosing

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients \>/=18 years of age
• Advanced illness under palliative care management, defined as having 1 to \<12 months life expectancy (in the judgment of the palliative care provider)
• Experiencing psychological distress, defined as a score of 7 or greater on the Depression, Anxiety or Well-being item of the Edmonton Symptom Assessment System
• Ability to understand and communicate in English or French

You may not qualify if:

• Current or previously diagnosed, or first-degree relative, with psychotic or bipolar disorder
• Previously deemed eligible for MAiD with intention to proceed with MAiD regardless of study intervention effectiveness (this criteria is meant to exclude patients who would be unlikely to complete follow-up - those considering or being assessed for MAiD will still be eligible)
• Documented or suspected delirium in the past 3 months without a clearly defined reversible cause (e.g. opioid toxicity, infection) and resolution
• Documented moderate or severe dementia diagnosis
• Inability to provide first-person informed consent
• Severe or unstable physical symptoms based on the judgment of the palliative care provider
• Palliative Performance Scale \<30%
• Cancer with known central nervous system (CNS) involvement or other CNS disease
• Use of high-dose psychedelic substances in the past year
• Taking lithium at any dose
• Taking tramadol at any dose
• Taking any monoamine oxidase inhibitor at any dose \[American Hospital Formulary Service (AFHS) group 28:16.04.12 or 28:36.32, including, but not limited to, moclobemide, tranylcypromine, phenelzine, selegiline, rasagiline\]
• Taking any atypical antipsychotic (aripiprazole, asenapine, brexpiprazole, clozapine, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, ziprasidone) (patients can be included if their atypical antipsychotic is either stopped, or if appropriate, substituted with haloperidol 48 hours prior to the start and for the duration of the intervention period and follow-up)
• Inability to ingest oral capsule
• Pregnancy or lactation

Sponsors & Collaborators

• Ottawa Hospital Research Institute: lead
• Bruyère Health Research Institute.: collaborator
• The Ottawa Hospital: collaborator
• St. Joseph's Healthcare Hamilton: collaborator
• CHU de Quebec-Universite Laval: collaborator
• Centre de recherche du Centre hospitalier universitaire de Sherbrooke: collaborator
• Jewish General Hospital: collaborator
• William Osler Health System: collaborator
• Queen's University: collaborator

Study Sites (2)

The Ottawa Hospital

Ottawa, Ontario, K1H 8L6, Canada

RECRUITING

Bruyere Continuing Care

Ottawa, Ontario, K1R 6K9, Canada

RECRUITING

Related Publications (16)

• Steis MR, Evans L, Hirschman KB, Hanlon A, Fick DM, Flanagan N, Inouye SK. Screening for delirium using family caregivers: convergent validity of the Family Confusion Assessment Method and interviewer-rated Confusion Assessment Method. J Am Geriatr Soc. 2012 Nov;60(11):2121-6. doi: 10.1111/j.1532-5415.2012.04200.x. Epub 2012 Oct 5.

  PMID: 23039310 BACKGROUND

• Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983 Jun;67(6):361-70. doi: 10.1111/j.1600-0447.1983.tb09716.x.

  PMID: 6880820 BACKGROUND

• Mitchell AJ, Meader N, Symonds P. Diagnostic validity of the Hospital Anxiety and Depression Scale (HADS) in cancer and palliative settings: a meta-analysis. J Affect Disord. 2010 Nov;126(3):335-48. doi: 10.1016/j.jad.2010.01.067. Epub 2010 Mar 5.

  PMID: 20207007 BACKGROUND

• Kamper SJ, Maher CG, Mackay G. Global rating of change scales: a review of strengths and weaknesses and considerations for design. J Man Manip Ther. 2009;17(3):163-70. doi: 10.1179/jmt.2009.17.3.163.

  PMID: 20046623 BACKGROUND

• Watanabe SM, Nekolaichuk C, Beaumont C, Johnson L, Myers J, Strasser F. A multicenter study comparing two numerical versions of the Edmonton Symptom Assessment System in palliative care patients. J Pain Symptom Manage. 2011 Feb;41(2):456-68. doi: 10.1016/j.jpainsymman.2010.04.020. Epub 2010 Sep 15.

  PMID: 20832987 BACKGROUND

• Galiana L, Rudilla D, Oliver A, Barreto P. The Short Demoralization Scale (SDS): A new tool to appraise demoralization in palliative care patients. Palliat Support Care. 2017 Oct;15(5):516-523. doi: 10.1017/S1478951516000973. Epub 2017 Jan 9.

  PMID: 28065203 BACKGROUND

• Templer DI. The construction and validation of a Death Anxiety Scale. J Gen Psychol. 1970 Apr;82(2d Half):165-77. doi: 10.1080/00221309.1970.9920634. No abstract available.

  PMID: 4394812 BACKGROUND

• Skevington SM, Lotfy M, O'Connell KA; WHOQOL Group. The World Health Organization's WHOQOL-BREF quality of life assessment: psychometric properties and results of the international field trial. A report from the WHOQOL group. Qual Life Res. 2004 Mar;13(2):299-310. doi: 10.1023/B:QURE.0000018486.91360.00.

  PMID: 15085902 BACKGROUND

• World Health Organization Division of Mental Health. WHOQOL-BREF : introduction, administration, scoring and generic version of the assessment : field trial version, December 1996. Geneva: World Health Organization; 1996

  BACKGROUND

• Durst AV, Spencer B, Bula C, Fustinoni S, Mazzocato C, Rochat E, Rubli Truchard E, Monod S, Jox RJ. Wish to Die in Older Patients: Development and Validation of Two Assessment Instruments. J Am Geriatr Soc. 2020 Jun;68(6):1202-1209. doi: 10.1111/jgs.16392. Epub 2020 Feb 29.

  PMID: 32112569 BACKGROUND

• National Comprehensive Cancer Network. NCCN Distress Thermometer and Problem List for Patients. Version 2, dated March 11th, 2020. https://www.nccn.org/about/permissions/thermometer.aspx

  BACKGROUND

• Anderson F, Downing GM, Hill J, Casorso L, Lerch N. Palliative performance scale (PPS): a new tool. J Palliat Care. 1996 Spring;12(1):5-11.

  PMID: 8857241 BACKGROUND

• Inouye SK, van Dyck CH, Alessi CA, Balkin S, Siegal AP, Horwitz RI. Clarifying confusion: the confusion assessment method. A new method for detection of delirium. Ann Intern Med. 1990 Dec 15;113(12):941-8. doi: 10.7326/0003-4819-113-12-941.

  PMID: 2240918 BACKGROUND

• Griffiths RR, Johnson MW, Carducci MA, Umbricht A, Richards WA, Richards BD, Cosimano MP, Klinedinst MA. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. J Psychopharmacol. 2016 Dec;30(12):1181-1197. doi: 10.1177/0269881116675513.

  PMID: 27909165 BACKGROUND

• Ross S, Bossis A, Guss J, Agin-Liebes G, Malone T, Cohen B, Mennenga SE, Belser A, Kalliontzi K, Babb J, Su Z, Corby P, Schmidt BL. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. J Psychopharmacol. 2016 Dec;30(12):1165-1180. doi: 10.1177/0269881116675512.

  PMID: 27909164 BACKGROUND

• Downar J, Lapenskie J, Anderson K, Parsons G, Polskaia N, Lalumiere G, Lawlor P. PSilocybin for psYCHological and existential distress in PALliative care (PSYCHED-PAL): A single arm unblinded clinical trial. Palliat Med. 2026 Jan 30:2692163261416269. doi: 10.1177/02692163261416269. Online ahead of print.

  PMID: 41617652 DERIVED

MeSH Terms

Conditions

Depression; Anxiety Disorders

Interventions

Psilocybin

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Mental Disorders

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines

Study Officials

• James Downar, MDCM, MSc

  The Ottawa Hospital Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

James Downar, MDCM, MSc

CONTACT

6135626262; jdownar@toh.ca

Julie Lapenskie, MSc

CONTACT

6135626262; jlapenskie@bruyere.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head, Division of Palliative Care

Model Details: The study is a multi-site, open-label, single-arm phase 1/2 proof-of-concept dose-finding, feasibility and preliminary efficacy clinical trial.

Study Record Dates

• First Submitted: November 11, 2020
• First Posted: February 15, 2021
• Study Start: January 8, 2024
• Primary Completion: January 1, 2025
• Study Completion: June 1, 2025
• Last Updated: August 9, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2)