Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) Therapy for Caregivers of Patients With Advanced Cancer

NCT07048743 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: PEARL-C1
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The PEARL-C1 trial is a phase II open-label trial. Participants will receive a single high-dose (25 mg) of psilocybin in the context of Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) therapy.

Conditions

Caregiver Distress

Outcome Measures

Primary Outcomes (5)

• Recruitment feasibility as assessed by the number of caregivers who consent/number of caregivers who meet eligibility criteria.

  Used to assess feasibility of PEARL therapy.

  30 months

• Retention feasibility as assessed by the number of caregivers completing primary endpoint measures/number of caregivers consented.

  Used to assess feasibility of PEARL therapy.

  30 months

• Adherence feasibility as assessed by the number of caregivers completing all PEARL sessions/number of caregivers consented.

  Used to assess feasibility of PEARL therapy.

  30 months

• Acceptability of PEARL therapy from the perspective of the caregivers of patients with advanced cancer obtained through qualitative interviews.

  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.

  30 months

• Safety of PEARL therapy.

  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.

  30 months

Secondary Outcomes (6)

• Caregiver perspectives on the clinical relevance of potential PEARL therapy outcomes: Anxiety symptoms as assessed with the GAD-7.

  30 months

• Caregiver perspectives on the clinical relevance of potential PEARL therapy outcomes: Depressive symptoms as assessed with the PHQ-9.

  30 months

• Caregiver perspectives on the clinical relevance of potential PEARL therapy outcomes: Broad quality of life construct for family members of patients with serious illness as assessed with the QUAL-E (Fam).

  30 months

• Patient perspectives on the clinical relevance of potential PEARL therapy outcomes: Anticipatory grief as assessed with the AGS.

  30 months

• Caregiver perspectives on the clinical relevance of potential PEARL therapy outcomes: Subjective burden as assessed with the short version of the BSFC-s.

  30 months

Study Arms (1)

PEARL Therapy

EXPERIMENTAL

Drug: Psilocybin

Interventions

Psilocybin DRUG

Single high-dose (25mg) capsule of psilocybin taken orally in the context of Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) therapy

PEARL Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age or older.
• Participant must reside in Ontario, Canada.
• Ability to speak and read English (participant to provide written informed consent and participate in PEARL intervention, as determined by study personnel).
• No cognitive impairment indicated in medical record or by the primary care physician.
• At least mild anxiety or depression symptoms, defined as a score of \>5 on the General Anxiety Disorder-7 (GAD-7) or \>8 on the Patient Health Questionnaire-9 (PHQ-9).
• 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 (international normalized ratio \[INR\]\<1.5, aspartate aminotransferase \[AST\]/alanine transaminase \[ALT\] \< 2x upper limit of normal, normal range bilirubin, platelets ≥150).
• Normal renal functioning as determined by prior medical history or/and screening bloodwork (estimated glomerular filtration rate \[eGFR\]\>45).
• Participants who are sexually active and could become pregnant or inseminate a partner must be using one method of highly effective contraception (hormonal contraceptives (e.g. combined oral contraceptives, patch, vaginal ring, injectables, and implants); intrauterine device (IUD) or intrauterine system (IUS); vasectomy or tubal ligation). Alternatively, they may use a combination of two or more effective methods of contraception which include male condom, female condom, cervical cap, diaphragm, or contraceptive sponge. These acceptable methods of contraception must be used prior to study entry, during study participation, and for the duration of the 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 Sponsor-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 consumes 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).

You may not qualify if:

• A history of past intolerability to psilocybin or other psychedelics.
• Past/present psychiatric diagnoses of bipolar disorder, any psychotic disorder, active substance use disorders, or dementia.
• a. Participants may have current mild alcohol or cannabis use disorder (meets 3 of 11 diagnostic criteria per The Diagnostic and Statistical Manual of Mental Illnesses \[DSM-5\]) or moderate alcohol or cannabis use disorder in early remission for the 3 months prior to enrollment (meets 5 of 11 diagnostic criteria per DSM-5).
• Clinically significant suicidal ideation either currently or within the past 6 months, as judged by study clinicians.
• Participant under the age of 30 years who has a first degree relative with a primary psychotic disorder.
• Other personal circumstances or behaviour judged to be incompatible with establishment of rapport or safe exposure to psilocybin.
• 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 the participant can be brought in for another reading on a different day. Participants can be re-screened for participation once blood pressure is adequately controlled.
• Hepatic dysfunction (history of cirrhosis and/or abnormal parameters \[INR\>1.5, elevated AST/ALT 2x upper limit, elevated bilirubin, platelets \< 150\]) or liver failure, defined as clinical diagnosis of liver fibrosis, cirrhosis of the liver, or advanced liver disease.
• Cardiovascular conditions including uncontrolled hypertension, heart failure (defined as class IV of the New York Heart Association classification), angina, a clinically significant electrocardiogram \[ECG\] abnormality (e.g., atrial fibrillation without rate control, prolonged Corrected QT Interval (QTc) defined as \> 450ms for males or \> 470ms for females), transient ischemic attack in the last six months, stroke, peripheral or pulmonary vascular disease (no active claudication).
• Uncontrolled epilepsy or history of seizures.
• Diabetes with inability to skip a meal (lunch), requiring administration of medication more than twice daily, or symptomatic hypoglycemia within the prior 30 days.
• GI bleed in last 6 months.
• Use of other investigational agents that would be inappropriate to take with psilocybin in the judgement of the investigator, psychoactive prescription medications (e.g., benzodiazepines, lithium, SSRIs), medications having a pharmacological effect on serotonin-2a (5-HT2A) receptors (e.g., olanzapine, mirtazapine, or trazodone), 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). Note: Inhibitors of UGT1A9 and 1A10 may increase systemic psilocin exposure (i.e., the Cmax and AUC) of psilocin and should be discontinued at least five half-lives prior to the administration of psilocybin. Similarly, aldehyde or alcohol dehydrogenase inhibitors should be discontinued at least 5 half-lives prior to the dose of psilocybin.
• In suitable participants, contraindicated medications may be tapered by a study physician between study enrolment and the psilocybin session when it is deemed safe to do so and in coordination with the prescribing physician. 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. Participants 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.

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (1)

Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

Location

Related Publications (19)

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• 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.

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• Nissim RS, Hales S. Caring for the Family Caregiver: Development of a Caregiver Clinic at a Cancer Hospital as Standard of Care. J Clin Psychol Med Settings. 2023 Mar;30(1):111-118. doi: 10.1007/s10880-022-09891-8. Epub 2022 Jun 14.

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• Nissim, R., Hales, S., Zimmermann, C., Deckert, A., Edwards, B., & Rodin, G. (2017). Supporting Family Caregivers of Advanced Cancer Patients: A Focus Group Study. Family Relations, 66(5), 867-879

  BACKGROUND

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  PMID: 29609600 BACKGROUND

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MeSH Terms

Interventions

Psilocybin

Intervention Hierarchy (Ancestors)

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

Study Officials

• Sarah Hales, MD, PhD

  Princess Margaret Cancer Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sarah Hales, MD, PhD

CONTACT

416-340-4800; uhnpprg@uhn.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2025
• First Posted: July 2, 2025
• Study Start: July 2, 2025
• Primary Completion (Estimated): December 2, 2027
• Study Completion (Estimated): December 2, 2027
• Last Updated: July 11, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)