Pragmatic Trial of Psilocybin Therapy in Palliative Care (PT2PC): A Multicenter Triple-blind Phase 2 Randomized Controlled Trial of Psilocybin Therapy for Demoralized Adults Near the End of Life
Trial Snapshot
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Enrollment
- 100
- Locations
- 5
- Primary Endpoint
- Change in patient-reported Demoralization Scale-II..
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
A Multicenter Triple-blind Phase 2 Randomized Controlled Trial.
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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)
Exclusion Criteria
- •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
Arms & Interventions
Psilocybin
A single moderate-to-high dose of oral psilocybin, plus 4-5 sessions of a brief, existential psychotherapy.
Intervention: Psilocybin (Drug)
Ketamine
A single low-to-moderate dose of oral liquid ketamine, plus 4-5 sessions of a brief, existential psychotherapy.
Intervention: Ketamine (Drug)
Outcomes
Primary Outcomes
Change in patient-reported Demoralization Scale-II..
Time Frame: 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 Outcomes
- 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.)
- DS-II and PHQ-9 comparison measures assessment(Throughout the study)
- 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.)
- Change in patient-reported pain(From Enrollment (V1) to ~14-days post drug (V8), and from Enrollment (V1) to ~35-days post drug (V9),)
- 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),)
- 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))
- 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.)
Investigators
Charles S. Grob, M.D.
Professor of Psychiatry and Behavioral Sciences
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center