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Clinical Trials/NCT05403086
NCT05403086RecruitingPhase 2

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

Charles S. Grob, M.D.5 sites in 1 country100 target enrollmentStarted: January 19, 2025Last updated:
Conditions
Interventions
Drugs

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

Experimental

A single moderate-to-high dose of oral psilocybin, plus 4-5 sessions of a brief, existential psychotherapy.

Intervention: Psilocybin (Drug)

Ketamine

Active Comparator

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

Sponsor
Charles S. Grob, M.D.
Sponsor Class
Other
Responsible Party
Sponsor Investigator
Principal Investigator

Charles S. Grob, M.D.

Professor of Psychiatry and Behavioral Sciences

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Study Sites (5)

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