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Caregiver DistressPhase 2PEARL-C1NCT07048743

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

A Phase 2 study testing Psilocybin in people with Caregiver Distress, run by University Health Network, Toronto at 1 site in Canada.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for
Caregiver Distress
What is being tested?
Psilocybin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
1 siteCanada
Study dates
16 Jul 2025to 2 Dec 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 18 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.
  • Primary or significant caregiver of a patient with advanced cancer enrolled in a companion trial of PEARL for patients with advanced cancer or caregiver of a patient receiving psilocybin-therapy through the Special Access Program (SAP) at University Health Network (UHN); such patients will have been recruited from psychosocial oncology or palliative care clinics at Princess Margaret (study physicians to assess appropriateness of inclusion and whether treatment will support the family system).
  • 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).
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  • 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).
  • refraining from using any psychoactive drugs, including alcoholic beverages, within 24 hours of the psilocybin administration.
  • Participants must have a responsible individual to drive them after the dosing session to where they are staying (home, hotel or another location) and to accompany/attend to them because psilocybin may affect their alertness and concentration on the evening of the dosing session.
  • Participants must agree not to drive or operate machinery for at least 24 hours after dose administration.
  • The therapist involved in the participant's psilocybin dosing session and/or the principal investigators will provide their phone number, in advance of the session, to the participant, in case the participant needs to reach them for emergency support in the 24 hours following the psilocybin dosing session. Because the therapists will change from participant to participant, the study team cannot provide the same emergency phone number to every study participant.

Who cannot join

  • 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.
  • 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.
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  • 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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Sarah Hales, MD, PhD contact

416-340-4800 ext. 8051

uhnpprg@uhn.ca

Canada1 site, 1 recruiting

  • Toronto General Hospital

    Toronto, Ontario, M5G 2C4

    Sarah Hales, MD, PhD, 416-340-4800 ext. 8051, uhnpprg@uhn.ca

    Recruiting

Other trials in Canada

About this study

Official title: Psilocybin-assisted Existential, Attachment and Relational (PEARL) Therapy for Caregivers of Patients With Advanced Cancer: A Phase II Open-Label Trial

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.

Read the detailed description

Caregivers of patients with advanced cancer often experience high levels of distress but there is currently little evidence-based guidance on how to help caregivers who experience depression, anxiety, anticipatory grief, spiritual suffering, caregiving burden and/or impaired quality of life. Over the past decade, research has shown that psychotherapies incorporating existential, attachment and relational approaches can address the specific needs and challenges of the advanced cancer population and thus help to reduce related distress. Simultaneously, recent research has shown that psilocybin-assisted psychotherapy, in which an individual ingests the psychoactive drug within a carefully monitored therapy, can reduce end-of-life distress and greatly benefit those with advanced disease. The multidisciplinary team has combined these two evidence-based approaches into Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) therapy. PEARL therapy combines elements from psilocybin-assisted psychotherapy, including preparatory therapy sessions, a high-dose drug session, and integration sessions, with important elements from manualized individual psychotherapies designed for patients and their families facing advanced cancer. This study will assess the feasibility, acceptability, and safety of PEARL therapy among caregivers of patients with advanced cancer. This study will contribute to the growing research around the efficacy of psychedelic-assisted therapies for the psychological distress associated with advanced disease and mortality. This type of therapy has the potential to improve quality of life among caregivers of those with advanced disease, to build upon previous findings to help outline the necessary components of therapy, and to inform public policy and clinical guidelines.

Being tested
Psilocybin

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PsilocybinDrug

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

Study groups in NCT07048743
Study groupRoleWhat they receive
PEARL TherapyExperimentalNot described
Receives: Drug: Psilocybin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 30 months

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

    Used to assess feasibility of PEARL therapy.

    Measured: 30 months

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

    Used to assess feasibility of PEARL therapy.

    Measured: 30 months

  4. 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.

    Measured: 30 months

  5. 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.

    Measured: 30 months

Secondary outcomes (6)

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

    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.

    Measured: 30 months

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

    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.

    Measured: 30 months

  3. 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).

    The Quality of Life at the End of Life Measure - Family experience (QUAL-E (Fam)) is a 17-item measure that includes subscales assessing symptom impact, relationship with health care provider, completion, and preparation. For symptom impact, score range is 4 to 20, with higher scores reflecting greater symptom control; for the relationship with healthcare provider, score range is 1 to 5, with lower scores reflecting a better relationship with healthcare providers; for completion, score range is 1 to 5, with lower scores reflecting a greater sense of completion in their relationship with the patient; and for preparation, score range is 4 to 20, with lower scores reflecting greater sense of preparation.

    Measured: 30 months

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

    The Anticipatory Grief Scale (AGS) is a 27-item self-report measure of grief before loss in family caregivers. Total score range is 27 to 135. Higher scores indicate higher levels of anticipatory grief.

    Measured: 30 months

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

    The short version of the Burden Scale for Family Caregivers (BSFC-s) is a 10-item self-report scale designed to measure the subjective burden of family caregivers. Total score range is 0 to 30. Higher scores indicate greater caregiver burden.

    Measured: 30 months

  6. Caregiver 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.

    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.

    Measured: 30 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Jul 2025
  2. Study start16 Jul 2025
  3. Primary completion2 Dec 2027 (estimated)
  4. Study completion2 Dec 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Supportive care
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
15 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07048743
Sponsor's protocol ID
PEARL-C1
Acronym
PEARL-C1
Status last verified
Jun 2026
First submitted
4 Jun 2025
Last updated
23 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Braun M, Mikulincer M, Rydall A, Walsh A, Rodin G. Hidden morbidity in cancer: spouse caregivers. J Clin Oncol. 2007 Oct 20;25(30):4829-34. doi: 10.1200/JCO.2006.10.0909.

    PubMed 17947732

  • Burton LC, Newsom JT, Schulz R, Hirsch CH, German PS. Preventive health behaviors among spousal caregivers. Prev Med. 1997 Mar-Apr;26(2):162-9. doi: 10.1006/pmed.1996.0129.

    PubMed 9085384

  • Glajchen M. The emerging role and needs of family caregivers in cancer care. J Support Oncol. 2004 Mar-Apr;2(2):145-55.

    PubMed 15328817

  • Grunfeld E, Coyle D, Whelan T, Clinch J, Reyno L, Earle CC, Willan A, Viola R, Coristine M, Janz T, Glossop R. Family caregiver burden: results of a longitudinal study of breast cancer patients and their principal caregivers. CMAJ. 2004 Jun 8;170(12):1795-801. doi: 10.1503/cmaj.1031205.

    PubMed 15184333

  • Hales S, Chiu A, Husain A, Braun M, Rydall A, Gagliese L, Zimmermann C, Rodin G. The quality of dying and death in cancer and its relationship to palliative care and place of death. J Pain Symptom Manage. 2014 Nov;48(5):839-51. doi: 10.1016/j.jpainsymman.2013.12.240. Epub 2014 Apr 3.

    PubMed 24703943

  • Holm M, Alvariza A, Furst CJ, Ohlen J, Arestedt K. Psychometric evaluation of the anticipatory grief scale in a sample of family caregivers in the context of palliative care. Health Qual Life Outcomes. 2019 Mar 5;17(1):42. doi: 10.1186/s12955-019-1110-4.

    PubMed 30837000

  • Johansson AK, Grimby A. Anticipatory grief among close relatives of patients in hospice and palliative wards. Am J Hosp Palliat Care. 2012 Mar;29(2):134-8. doi: 10.1177/1049909111409021. Epub 2011 May 19.

    PubMed 21596732

  • Kershaw T, Ellis KR, Yoon H, Schafenacker A, Katapodi M, Northouse L. The Interdependence of Advanced Cancer Patients' and Their Family Caregivers' Mental Health, Physical Health, and Self-Efficacy over Time. Ann Behav Med. 2015 Dec;49(6):901-11. doi: 10.1007/s12160-015-9743-y.

    PubMed 26489843

  • 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.

    PubMed 11556941

  • 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.

    PubMed 35699840

  • 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

  • Pendergrass A, Malnis C, Graf U, Engel S, Graessel E. Screening for caregivers at risk: Extended validation of the short version of the Burden Scale for Family Caregivers (BSFC-s) with a valid classification system for caregivers caring for an older person at home. BMC Health Serv Res. 2018 Apr 2;18(1):229. doi: 10.1186/s12913-018-3047-4.

    PubMed 29609600

  • Peterman AH, Fitchett G, Brady MJ, Hernandez L, Cella D. Measuring spiritual well-being in people with cancer: the functional assessment of chronic illness therapy--Spiritual Well-being Scale (FACIT-Sp). Ann Behav Med. 2002 Winter;24(1):49-58. doi: 10.1207/S15324796ABM2401_06.

    PubMed 12008794

  • Pitceathly C, Maguire P. The psychological impact of cancer on patients' partners and other key relatives: a review. Eur J Cancer. 2003 Jul;39(11):1517-24. doi: 10.1016/s0959-8049(03)00309-5.

    PubMed 12855257

  • Reinhard SC, Given B, Petlick NH, Bemis A. Supporting Family Caregivers in Providing Care. In: Hughes RG, editor. Patient Safety and Quality: An Evidence-Based Handbook for Nurses. Rockville (MD): Agency for Healthcare Research and Quality (US); 2008 Apr. Chapter 14. Available from http://www.ncbi.nlm.nih.gov/books/NBK2665/

    PubMed 21328765

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Psilocybin in people with Caregiver Distress, run by University Health Network, Toronto at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 23 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Sarah Hales, MD, PhD (416-340-4800 ext. 8051, uhnpprg@uhn.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Recruitment feasibility as assessed by the number of caregivers who consent/number of caregivers who meet eligibility criteria. (time frame: 30 months). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07048743, which also lists 19 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jun 2026.

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