Pragmatic Trial of Psilocybin Therapy in Palliative Care
- Registration Number
- NCT05403086
- Lead Sponsor
- Charles S. Grob, M.D.
- Brief Summary
This multicenter, triple-blind, phase 2, randomized controlled trial will evaluate the efficacy and safety of psilocybin therapy compared to an active control in treating demoralization in adults near the end of life (≤2 years life expectancy).
- Detailed Description
After providing written informed consent, participants deemed eligible for this trial will be randomized to a brief course of talk therapy plus 1 dose of oral psilocybin vs the same brief course of talk therapy plus 1 dose of oral ketamine (the active control). Participants' degree of demoralization and other clinical outcomes (e.g., depression, anxiety) will be assessed at 1, 2, and 5 weeks after the study drug administration. After completing the study, participants will have the option of being told which study drug they took (aka, "unblinded"); those who were randomized to the active control will be offered another brief course of talk therapy plus 1 dose of oral psilocybin, and the same sequence of outcome assessments.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 100
General
- Provision of signed and dated informed consent form and the capacity to consent to research.
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Is currently a patient in a study-engaged clinical site
- Has a life-threatening illness and a life expectancy of ≤2 years
- Has moderate-to-severe demoralization
- Ability to take oral medication (capsules and liquid)
General
- Known allergic or severe reactions to the non-psychoactive components of psilocybin capsules or liquid ketamine
- Treatment with another investigational drug or intervention within 1 month of signing Informed Consent Form (ICF)
- If deemed by clinical judgment of the study investigators to be unsafe for undergoing the intervention
Neurological
- Cognitive impairment sufficient to impede the ability to complete study tasks
- History of intracranial hemorrhage
- Recent embolic stroke
- Recent seizure
- Current intracranial mass
- Advanced stage of a neurologic disease that elevates risk for psychosis
Cardiovascular
- Uncontrolled hypertension
- Clinically significant cardiac disease
Respiratory
- Severe pulmonary disease
- Supplemental oxygen requirement
Gastrointestinal
- Current intractable nausea/vomiting/diarrhea
- Recent, clinically significant GI bleed
- Markedly abnormal liver function tests
Endocrine, Renal, and Reproductive
- Pregnancy or lactation
- Severe renal insufficiency
- Unstable insulin-dependent diabetes mellitus
Prohibited Medications
- Antipsychotics (with exceptions)
- Antidepressants (with exceptions)
- Dopamine agonists
- Drugs known to have adverse interactions with psilocybin or ketamine
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Psilocybin Psilocybin A single moderate-to-high dose of oral psilocybin, plus 4-5 sessions of a brief, existential psychotherapy. Ketamine Ketamine A single low-to-moderate dose of oral liquid ketamine, plus 4-5 sessions of a brief, existential psychotherapy.
- Primary Outcome Measures
Name Time Method Change in patient-reported Demoralization Scale-II.. From Pre-dose V4 to ~14-days post drug (V8), and from Pre-dose (V4) to ~35-days post drug (V9), compared to active control. The DS-II is a validated, patient-reported outcome assessing demoralization with a 2-week recall period.
- Secondary Outcome Measures
Name Time Method i) Change in clinician-rated Clinical Global Impression (CGI) for Severity of demoralization. From Enrollment (V1) to ~14-days (V8) and ~35-days (V9) post-drug for patients treated with psilocybin therapy vs active control. The CGI-I is a widely used and validated assessment of global clinical improvement. Possible scores range "0=Not assessed", "1=Very much improved", to "7=Very much worse." The CGI-I has been adapted here for assessing improvement in demoralization.
DS-II and PHQ-9 comparison measures assessment Throughout the study Change in DS-II and PHQ-9 will be compared to assess if there is a differential response to psilocybin therapy in this population.
ii) Odds ratio of meeting criteria for demoralization on the clinician-rated Demoralization Interview Interview (DI). From Enrollment (V1) to ~14-days (V8) and ~35-days (V9) post-drug for patients treated with psilocybin therapy vs active control. The CGI-I is a widely used and validated clinician-rated assessment of global clinical improvement. Possible scores range "0=Not assessed", "1=Very much improved", to "7=Very much worse." The CGI-I has been adapted here for assessing improvement in demoralization.
Change in patient-reported pain From Enrollment (V1) to ~14-days post drug (V8), and from Enrollment (V1) to ~35-days post drug (V9), A comparison to active control, using the Brief Pain Inventory-Short Form (BPI-SF).
Change in depression symptoms From Pre-dose V4 to ~14-days post drug (V8), and from Pre-dose V4 to ~35-days post drug (V9), A comparison to active control using the following measures: PHQ-9, GRID-HAM-D6.compared to active control
Change in anxiety symptoms, quality of life, and spiritual well-being From Enrollment (V1) to ~14-days post drug (V8), and Enrollment (V1) to ~35-days post drug (V9) A comparison to active control, using the following measures: GAD-7, FACIT-Pal-14 FACIT-Sp-12.
Associations will be explored between change in Demoralization Scale-II and other measures pre-dose and 7 days post drug From Pre-dose (V4) to 7-days post-drug. Associations will be explored between change in Demoralization Scale-II and 1) Credibility Expectancy Questionnaire (CrEQ), 2) Treatment Allocation Questionnaire, 3) Mystical Experience Questionnaire-30 (MEQ-30) and PEQ-4, 4) Challenging Experience Questionnaire (ChEQ), and 5) Change in Death Transcendence Scale-15 item (DTS-15)
Trial Locations
- Locations (3)
University of San Francisco
🇺🇸San Francisco, California, United States
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
🇺🇸Torrance, California, United States
Sunstone Therapies
🇺🇸Rockville, Maryland, United States