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Psilocybin for Psychological and Existential Distress in Palliative Care

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04754061
Recruitment Status : Not yet recruiting
First Posted : February 15, 2021
Last Update Posted : November 18, 2021
Sponsor:
Collaborators:
Bruyere Research Institute
The Ottawa Hospital
St. Joseph's Healthcare Hamilton
CHU de Quebec-Universite Laval
Centre de recherche du Centre hospitalier universitaire de Sherbrooke
Jewish General Hospital
William Osler Health System
Kingston Health Sciences Centre
Information provided by (Responsible Party):
James Downar, University of Ottawa

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.

Condition or disease Intervention/treatment Phase
Depression, Anxiety Distress, Emotional Drug: Psilocybin Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: The study is a multi-site, open-label, single-arm phase 1/2 proof-of-concept dose-finding, feasibility and preliminary efficacy clinical trial.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Psilocybin for Psychological and Existential Distress in Palliative Care: A Multi-site, Open-label, Single Arm Phase 1/2 Proof-of-concept, Dose-finding, and Feasibility Clinical Trial
Estimated Study Start Date : March 2022
Estimated Primary Completion Date : February 2023
Estimated Study Completion Date : August 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Psilocybin Microdosing
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

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).





Primary Outcome Measures :
  1. Recruitment Rate [ Time Frame: Through study completion, up to 1 year ]
    Number of patients enrolled divided by number of patients approached

  2. Intervention Completion Rate [ Time Frame: Through study completion, up to 13 months ]
    Number of participants who complete the intervention divided by number of participants enrolled

  3. Follow-up Completion Rate [ Time Frame: Through study completion, up to 18 months ]
    Number of participants who complete follow-up divided by number of participants enrolled

  4. Number of Participants With Adverse Events - Change in Blood Pressure [ Time Frame: Measured at baseline and daily (Mon-Fri) from enrolment to intervention completion (up to 4 weeks) ]
    Proportion of participants with systolic blood pressure of >180mmHg or an increase in 40% from baseline measurements

  5. Number of Participants With Adverse Events - Change in Heart Rate [ Time Frame: Measured at baseline and daily (Mon-Fri) from enrolment to intervention completion (up to 4 weeks) ]
    Proportion of participants with resting heart rate >100bpm or an increase in 40% from baseline

  6. Number of Participants With Adverse Events - Delirium [ Time Frame: Through intervention completion, up to 4 weeks ]
    Proportion of participants who develop delirium, measured by the Confusion Assessment Method or the Family Confusion Assessment Method

  7. Number of Participants With Adverse Events - Serotonin Syndrome [ Time Frame: Through intervention completion, up to 4 weeks ]
    Proportion of participants who develop serotonin syndrome, diagnosed by Study Doctor

  8. Number of Participants With Adverse Events - Adverse Mood or Behaviour Change [ Time Frame: Measured at baseline and from enrolment to intervention completion (up to 4 weeks); 2-week and 4-week follow-up ]
    Proportion of participants who report adverse mood or behaviour changes (recorded daily in a participant diary)

  9. Psychological Distress - Anxiety and Depression [ Time Frame: Baseline ]
    Measured using the Hospital Anxiety and Depression Scale (higher score indicate worse anxiety/depression)

  10. Change in Psychological Distress - Anxiety and Depression [ Time Frame: Weekly (every Friday) during intervention (4 weeks) ]
    Measured using the Hospital Anxiety and Depression Scale (higher score indicate worse anxiety/depression)

  11. Change in Psychological Distress - Anxiety and Depression [ Time Frame: Follow-up (1 day, 2 weeks, 4 weeks, 12 weeks, 24 weeks) ]
    Measured using the Hospital Anxiety and Depression Scale (higher score indicate worse anxiety/depression)

  12. Psychological Distress - Anxiety, Depression, and Well-being [ Time Frame: Baseline ]
    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)

  13. Change in Psychological Distress - Anxiety, Depression, and Well-being [ Time Frame: Weekly (every Friday) during intervention (4 weeks) ]
    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)

  14. Change in Psychological Distress - Anxiety, Depression, and Well-being [ Time Frame: Follow-up (1 day, 2 weeks, 4 weeks, 12 weeks, 24 weeks) ]
    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)

  15. Psychological Distress - Global Impression of Change [ Time Frame: Weekly (every Friday) during intervention (4 weeks); 1 day, 2 week, 4 week, 12 week, 24 week follow-up ]
    Measured using the Patient Global Impression of Change scale (higher scores indicate greater positive change)

  16. Dosing [ Time Frame: Weekly (each Friday) for intervention period (4 weeks) ]
    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)

  17. Dosing [ Time Frame: Weekly (each Friday) for intervention period (4 weeks) ]
    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)

  18. Dosing [ Time Frame: Weekly (each Friday) for intervention period (4 weeks) ]
    Dose at which therapeutic benefit, if any, is achieved assessed by Global Impression fo Change score (score of 5 or above indicate therapeutic benefit)


Secondary Outcome Measures :
  1. Existential Distress [ Time Frame: Baseline (Friday prior to first dose administered on a Monday); 1 day, 2 week, 4 week, 12 week, 24 week follow-up ]
    Measured using the Short Demoralization Scale (scored 0-20; higher scores indicate greater demoralization and distress)

  2. Death Anxiety [ Time Frame: Baseline (Friday prior to first dose administered on a Monday); 1 day, 2 week, 4 week, 12 week, 24 week follow-up ]
    Measured using the Death Anxiety Scale (scored 0-15; higher scores indicate greater death anxiety)

  3. Participant Quality of Life [ Time Frame: Baseline (Friday prior to first dose administered on a Monday); 1 day, 2 week, 4 week, 12 week, 24 week follow-up ]
    Measured using the World Health Organization Quality of Life, Brief Version (higher scores indicate higher quality of life)

  4. Wish to Die [ Time Frame: Baseline (Friday prior to first dose administered on a Monday); 1 day, 2 week, 4 week, 12 week, 24 week follow-up ]
    Measured using the Categories of Attitudes Towards Death Occurrence (scored 1-6 with scores 4-6 indicating a wish to die)

  5. Global Distress [ Time Frame: Baseline (Friday prior to first dose administered on a Monday); 1 day, 2 week, 4 week, 12 week, 24 week follow-up ]
    Measured using the Distress Thermometer



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients >/=18 years of age
  2. Advanced illness under palliative care management, defined as having 1 to <12 months life expectancy (in the judgment of the palliative care provider)
  3. 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
  4. Ability to understand and communicate in English or French

Exclusion Criteria:

  1. Current or previously diagnosed, or first-degree relative, with psychotic or bipolar disorder
  2. 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)
  3. Documented or suspected delirium in the past 3 months without a clearly defined reversible cause (e.g. opioid toxicity, infection) and resolution
  4. Documented moderate or severe dementia diagnosis
  5. Inability to provide first-person informed consent
  6. Severe or unstable physical symptoms based on the judgment of the palliative care provider
  7. Palliative Performance Scale <30%
  8. Cancer with known central nervous system (CNS) involvement or other CNS disease
  9. Use of high-dose psychedelic substances in the past year
  10. Taking lithium at any dose
  11. Taking tramadol at any dose
  12. 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]
  13. 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)
  14. Inability to ingest oral capsule
  15. Pregnancy or lactation

For participants taking either an SSRI or an antipsychotic medication, there are several conditions for participation: (1) the PC provider must approve their participation in the study; (2) the SSRI/anti-psychotic medication dose cannot change for the duration of the intervention trial and follow-up, and; (3) the patient must not be taking more than the maximum allowable trial dose for each SSRI.

All trial participants must agree to not take any other psychedelic substance for the duration of the clinical trial and follow-up, and to notify the investigative team of any medication changes during intervention or follow-up. Participants must also agree not to take their benzodiazepine or antipsychotic medication, if applicable, within 12 hours (6 hours pre and 6 hours post) of taking their psilocybin dose (participants will be given detailed instructions about this in their Instruction Leaflet). Participants must also agree not to drive or operate any heavy machinery on any treatment day for the duration of the 4-week intervention.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04754061


Contacts
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Contact: James Downar, MDCM, MSc 6135626262 ext 1502 jdownar@toh.ca
Contact: Julie Lapenskie, MSc 6135626262 ext 1498 jlapenskie@bruyere.org

Sponsors and Collaborators
Ottawa Hospital Research Institute
Bruyere Research Institute
The Ottawa Hospital
St. Joseph's Healthcare Hamilton
CHU de Quebec-Universite Laval
Centre de recherche du Centre hospitalier universitaire de Sherbrooke
Jewish General Hospital
William Osler Health System
Kingston Health Sciences Centre
Investigators
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Principal Investigator: James Downar, MDCM, MSc The Ottawa Hospital Research Institute
Publications:
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
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

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Responsible Party: James Downar, Head, Division of Palliative Care, University of Ottawa
ClinicalTrials.gov Identifier: NCT04754061    
Other Study ID Numbers: 7745629246
First Posted: February 15, 2021    Key Record Dates
Last Update Posted: November 18, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by James Downar, University of Ottawa:
existential distress
psychological distress
psilocybin
microdosing
Additional relevant MeSH terms:
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Depression
Behavioral Symptoms
Psilocybin
Hallucinogens
Physiological Effects of Drugs
Psychotropic Drugs