- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06416085
Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) Therapy for Patients With Advanced Cancer
Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) Therapy for Patients With Advanced Cancer: A Phase II Open-Label Trial
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Sarah Hales, MD
- Phone Number: 8051# 416-340-4800
- Email: UHNPPRG@uhn.ca
Study Locations
-
-
Ontario
-
Toronto, Ontario, Canada, M5G 2M9
- Princess Margaret Cancer Centre
-
Contact:
- Sarah Hales, MD
-
Principal Investigator:
- Sarah Hales, MD
-
Principal Investigator:
- Emma Hapke, MD
-
Principal Investigator:
- Daniel Rosenbaum, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- >18 years of age;
- Ability to speak and read English (patient to provide written informed consent and participate in PEARL intervention, as determined by study personnel);
- No cognitive impairment indicated in medical record or by attending oncologist or palliative care physician;
- Confirmed diagnosis of stage IV solid tumour cancers, sarcoma, endocrine, melanoma cancers, or stage 4 lymphoma with expected survival of greater than 6 months as determined by their oncologist or palliative care physician;
- At least mild depressive symptoms, defined as >8 on the Patient Health Questionnaire-9 (PHQ-9) (Kroenke et la., 2001);
- Interest in and ability to participate in and complete the PEARL intervention and protocol as outlined;
- Normal hepatic functioning as determined by prior medical history or/and screening bloodwork (INR<1.5, Aspartate aminotransferase/Alanine Aminotransferase (AST/ALT) < 2x upper limit of normal, normal range bilirubin, platelets > 150)
- Normal renal functioning as determined by prior medical history or/and screening bloodwork (eGFR>45)
- Participants who are sexually active and could become pregnant must be using effective birth control (per their physician), prior to study entry, during study participation, and for the duration of the study. Participants who are sexually active and could inseminate a partner must agree to use effective birth control after psilocybin administration until the end of study. For participants of child-bearing potential, a negative serum pregnancy test result is required at screening. A urine pregnancy test will be administered on the morning of psilocybin administration for applicable participants. Participants cannot be pregnant or nursing through the duration of the study;
If using prescribed medications or other substances, participants must agree to refrain from taking them if instructed by study investigators. These include:
- not using any non-prescription medication, nutritional supplement, or herbal supplement except when approved by the treatment team (exceptions will be evaluated by the Investigator and will include acetaminophen, non-steroidal anti-inflammatory drugs, and common doses of vitamins and minerals),
- not using nicotine for at least 2 hours before psilocybin administration, and not again until approximately 7 hours after psilocybin administration,
- consuming approximately the same amount of caffeine-containing beverages (e.g., coffee, tea) that they consume on a usual morning before arriving at the treatment centre for the psilocybin session day,
- not taking any as needed medications on the mornings of psilocybin sessions (with the exception of daily and as needed opioid pain medication),
- refraining from using any psychoactive drugs, including alcoholic beverages, within 24 hours of the psilocybin administration.
- Participants must have someone drive them after the session to where they are staying (home, hotel or another location), because psilocybin may affect their alertness and concentration on the evening of the dosing session.
Exclusion Criteria:
- Cancer of the brain or metastasis to the brain;
- Symptoms consistent with delirium, psychosis, or other symptoms judged to be incompatible with establishment of rapport or safe exposure to psilocybin;
- A history of past intolerability of psilocybin or other psychedelics;
- Past/present psychiatric diagnoses including bipolar disorder, psychotic disorders, active substance use disorders or suicidality (as distinguished from desire for hastened death or readiness for death, per the discretion of the study team);
- If participant is under 30 years of age and has first degree relative with a primary psychotic disorder;
- Severe hypertension (defined as systolic blood pressure >140/or diastolic pressure >90) based on two readings on the same day. If the second reading remains over 140/90 patient can be brought in for another reading on a different day. Patients can be re-screened for participation once blood pressure is adequately controlled;
- Known paraneoplastic syndrome or "ectopic" hormone production by the primary tumor if incompatible with psilocybin, determined in consultation with the study palliative care physician. Patients could be enrolled if it is determined that the patient's condition is compatible with psilocybin administration.
- Cardiovascular conditions including uncontrolled hypertension, angina, a clinically significant ECG abnormality (e.g., atrial fibrillation without rate control), transient ischemic attack in the last six months, stroke, peripheral or pulmonary vascular disease (no active claudication);
- Uncontrolled epilepsy or history of seizures in past 6 months;
- Participants with diabetes who are unable to skip a meal (lunch), or whose diabetes requires administration of medication more than twice daily, or who have had symptomatic hypoglycemia within the prior 30 days
- GI bleed in last 6 months;
- Use of other agents that would be inappropriate to take with psilocybin in the judgement of the investigator. These agents may include psychoactive prescription medications (e.g., benzodiazepines, lithium, Selective serotonin reuptake inhibitors), medications having a primary pharmacological effect on serotonin-2a (5-HT2A) receptors (e.g., olanzapine), or medications that are monoamine oxidase (MAO) inhibitors, any potent metabolic inducers (e.g. rifamycin, rifampin, rifabutin, rifapentine, carbamazepine, phenytoin, phenobarbital, nevirapine, efavirenz, taxol, dexamethasone, St John's wort) or inhibitors (e.g. HIV protease inhibitors, itraconazole, ketoconazole, erythromycin, clarithromycin, troleandomycin).
Of note, in suitable patients, these medications may be paused or tapered between study enrolment and prior to the start of the intervention when it is deemed safe to do so. A safe and appropriate tapering regimen will then be developed based on the particular medication, on a case-by-case basis. If taking an MAO inhibitor, the psilocybin session will not be conducted until at least 5 half-lives of the agent have elapsed after the last dose. Patients prescribed opioids will be allowed to take their usual dose regimen for analgesia, including the use of as needed analgesic medications on psilocybin session days.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Supportive Care
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Psilocybin
|
Single high-dose (25mg) capsule of psilocybin taken orally in the context of Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) therapy
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Recruitment feasibility as assessed by the number of patients who consent/number of patients who meet eligibility criteria.
Time Frame: 24 months
|
Used to assess feasibility of PEARL therapy.
|
24 months
|
Retention feasibility as assessed by the number of patients completing primary endpoint measures/number of patients consented.
Time Frame: 24 months
|
Used to assess feasibility of PEARL therapy.
|
24 months
|
Adherence feasibility as assessed by the number of patients completing all PEARL sessions/number of patients consented.
Time Frame: 24 months
|
Used to assess feasibility of PEARL therapy.
|
24 months
|
Acceptability of PEARL therapy from the perspective of advanced cancer patients obtained through qualitative interviews.
Time Frame: 24 months
|
Participants will be interviewed regarding their experiences with PEARL, including acceptability and perceived positive and negative effects of the intervention, with a semi-structured interview guide.
|
24 months
|
Safety of PEARL therapy
Time Frame: 24 months
|
Safety will be assessed throughout the trial. Adverse events (AEs) attributed to psilocybin will be monitored for and recorded after the psilocybin session. This study will use CTCAE v5.0 to assess AEs. Serious adverse events (SAEs) will be tracked until study completion and will be defined as any adverse drug experience that: results in death; that is life-threatening (i.e. any AE that places the participant, in the view of the investigators, at immediate risk of death from the reaction as it occurs); requires hospital admission; results in persistent or significant disability (i.e. a substantial disruption of a person's ability to conduct normal life functions); or may jeopardize the participant or necessitate medical intervention to prevent one of the aforementioned criteria. |
24 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Patient perspectives on the clinical relevance of potential PEARL therapy outcomes: Death anxiety in advanced cancer patients as assessed with the DADDS
Time Frame: 24 months
|
The Death and Dying Distress Scale (DADDS) is a 15-item self-report measure designed for populations facing imminent death and addresses fears about the dying process, and about lost opportunities and self-perceived burden placed on others as a result of impending mortality.
Total score range is 0 to 75.
Higher scores indicate greater death-related distress.
|
24 months
|
Patient perspectives on the clinical relevance of potential PEARL therapy outcomes: Depressive symptoms as assessed with the PHQ-9
Time Frame: 24 months
|
The Patient Health Questionnaire-9 (PHQ-9) is a 9-item self-report scale measuring depressive symptoms.
Total score range is 0 to 27.
Higher scores indicate greater severity of depression.
|
24 months
|
Patient perspectives on the clinical relevance of potential PEARL therapy outcomes: Loss of meaning and purpose, disheartenment and helplessness as assessed with the DS
Time Frame: 24 months
|
The Demoralization Symptoms (DS) is a 24-item self-report measure that assesses loss of meaning and purpose, disheartenment, and helplessness.
Total score range is 0 to 96.
Higher scores indicate higher levels of demoralization.
|
24 months
|
Patient perspectives on the clinical relevance of potential PEARL therapy outcomes: Overall measure of spiritual well-being, meaning/peace and faith as assessed with the FACIT-Sp
Time Frame: 24 months
|
The Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being (FACIT-Sp) is a 12-item scale designed to measure important aspects of spirituality including sense of meaning in one's life, harmony, peacefulness and a sense of comfort and strength from one's faith.
Total score range is 0 to 48.
Higher scores indicate higher spiritual well-being.
|
24 months
|
Patient perspectives on the clinical relevance of potential PEARL therapy outcomes: Broad quality of life construct in patients facing end of life as assessed with the QUAL-EC
Time Frame: 24 months
|
The Quality of Life at the End of Life-Cancer (QUAL-EC) is a 17-item measure that includes subscales which assess symptom impact, preparation for end of life (i.e., the extent to which the family is prepared and financial plans have been made), relationship with healthcare providers (i.e., the extent to which patients feel informed and are able to participate in decisions about their care) and sense of life completion (i.e., being able to share important things and feel connected to others).
For Symptom Control, score range is 3 to 15, with higher scores reflecting greater symptom control; for the Relationship with Healthcare Provider, score range is 5 to 25, with higher scores reflecting a better relationship with healthcare providers; for the Preparation for End-of-Life, score range is 4 to 20, with higher scores reflecting greater preparation for end-of-life; and the for Life Completion, score range is 5 to 25, with higher scores reflecting a greater sense of life completion.
|
24 months
|
Patient perspectives on the clinical relevance of potential PEARL therapy outcomes: Desire for death in the medically ill as assessed with the SAHD
Time Frame: 24 months
|
The Schedule of Attitudes Toward Hastened Death (SAHD) is a 20-item self-report measure of desire for death in the medically ill.
Total score range is 0 to 20.
Higher scores indicate greater desire for death.
|
24 months
|
Patient perspectives on the clinical relevance of potential PEARL therapy outcomes: Anxiety symptoms as assessed with the GAD-7
Time Frame: 24 months
|
The Generalized Anxiety Disorder-7 (GAD-7) is a 7-item self-report scale used to screen for and measure anxiety symptoms.
Total score range is 0 to 21.
Higher scores indicate higher levels of anxiety.
|
24 months
|
Collaborators and Investigators
Investigators
- Principal Investigator: Sarah Hales, MD, University Health Network, Toronto
Publications and helpful links
General Publications
- Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001 Sep;16(9):606-13. doi: 10.1046/j.1525-1497.2001.016009606.x.
- Spitzer RL, Kroenke K, Williams JB, Lowe B. A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med. 2006 May 22;166(10):1092-7. doi: 10.1001/archinte.166.10.1092.
- Kissane DW, Wein S, Love A, Lee XQ, Kee PL, Clarke DM. The Demoralization Scale: a report of its development and preliminary validation. J Palliat Care. 2004 Winter;20(4):269-76.
- 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.
- Lo C, Hales S, Zimmermann C, Gagliese L, Rydall A, Rodin G. Measuring death-related anxiety in advanced cancer: preliminary psychometrics of the Death and Dying Distress Scale. J Pediatr Hematol Oncol. 2011 Oct;33 Suppl 2:S140-5. doi: 10.1097/MPH.0b013e318230e1fd.
- Breitbart W, Rosenfeld B, Gibson C, Pessin H, Poppito S, Nelson C, Tomarken A, Timm AK, Berg A, Jacobson C, Sorger B, Abbey J, Olden M. Meaning-centered group psychotherapy for patients with advanced cancer: a pilot randomized controlled trial. Psychooncology. 2010 Jan;19(1):21-8. doi: 10.1002/pon.1556.
- Rodin G, Lo C, Rydall A, Shnall J, Malfitano C, Chiu A, Panday T, Watt S, An E, Nissim R, Li M, Zimmermann C, Hales S. Managing Cancer and Living Meaningfully (CALM): A Randomized Controlled Trial of a Psychological Intervention for Patients With Advanced Cancer. J Clin Oncol. 2018 Aug 10;36(23):2422-2432. doi: 10.1200/JCO.2017.77.1097. Epub 2018 Jun 29.
- Albers G, Echteld MA, de Vet HC, Onwuteaka-Philipsen BD, van der Linden MH, Deliens L. Evaluation of quality-of-life measures for use in palliative care: a systematic review. Palliat Med. 2010 Jan;24(1):17-37. doi: 10.1177/0269216309346593. Epub 2009 Oct 20.
- Grossman CH, Brooker J, Michael N, Kissane D. Death anxiety interventions in patients with advanced cancer: A systematic review. Palliat Med. 2018 Jan;32(1):172-184. doi: 10.1177/0269216317722123. Epub 2017 Aug 8.
- Krause S, Rydall A, Hales S, Rodin G, Lo C. Initial validation of the Death and Dying Distress Scale for the assessment of death anxiety in patients with advanced cancer. J Pain Symptom Manage. 2015 Jan;49(1):126-34. doi: 10.1016/j.jpainsymman.2014.04.012. Epub 2014 May 28.
- Morita T, Murata H, Kishi E, Miyashita M, Yamaguchi T, Uchitomi Y; Japanese Spiritual Care Task Force. Meaninglessness in terminally ill cancer patients: a randomized controlled study. J Pain Symptom Manage. 2009 Apr;37(4):649-58. doi: 10.1016/j.jpainsymman.2008.04.017. Epub 2008 Oct 1.
- Rodin G, Lo C, Mikulincer M, Donner A, Gagliese L, Zimmermann C. Pathways to distress: the multiple determinants of depression, hopelessness, and the desire for hastened death in metastatic cancer patients. Soc Sci Med. 2009 Feb;68(3):562-9. doi: 10.1016/j.socscimed.2008.10.037. Epub 2008 Dec 7.
- Rosenfeld B, Breitbart W, Galietta M, Kaim M, Funesti-Esch J, Pessin H, Nelson CJ, Brescia R. The schedule of attitudes toward hastened death: Measuring desire for death in terminally ill cancer patients. Cancer. 2000 Jun 15;88(12):2868-75. doi: 10.1002/1097-0142(20000615)88:123.0.co;2-k.
- Smith KA, Harvath TA, Goy ER, Ganzini L. Predictors of pursuit of physician-assisted death. J Pain Symptom Manage. 2015 Mar;49(3):555-61. doi: 10.1016/j.jpainsymman.2014.06.010. Epub 2014 Aug 10.
- Steinhauser KE, Clipp EC, Bosworth HB, McNeilly M, Christakis NA, Voils CI, Tulsky JA. Measuring quality of life at the end of life: validation of the QUAL-E. Palliat Support Care. 2004 Mar;2(1):3-14. doi: 10.1017/s1478951504040027.
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- PEARL
- 21-5781 (Other Identifier: University Health Network)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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