Pragmatic Trial of Psilocybin Therapy in Palliative Care (PT2PC)

October 21, 2023 updated by: Charles S. Grob, M.D.

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

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).

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

100

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Aged 18 years and older
  • Has the capacity to consent to research
  • 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:

General

  • 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
  • Antidepressants (with exceptions)
  • Dopamine agonists
  • Drugs known to have adverse interactions with psilocybin or ketamine

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Psilocybin
A single moderate-to-high dose of oral psilocybin, plus 4-5 sessions of a brief, existential psychotherapy.
Drug: Psilocybin
Psilocybin, [3-[2-(dimethylamino)ethyl]-1H-indol-4-yl] dihydrogen phosphate.
Other Names:
  • Hallucinogen
Active Comparator: Ketamine
A single low-to-moderate dose of oral liquid ketamine, plus 4-5 sessions of a brief, existential psychotherapy.
Drug: Ketamine
ketamine hydrochloride injection, for intravenous or intramuscular use, contains ketamine, a nonbarbiturate general anesthetic and has a molecular formula of C13H16ClNO•HCl and a molecular weight of 274.19. The chemical name for ketamine hydrochloride is (±)-2-(o-Chlorophenyl)-2-(methylamino)cyclohexanone hydrochloride.
Other Names:
  • Ketalar

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from Baseline on 16-item Demoralization Scale - II (DS-II) at Week 5
Time Frame: Baseline and Week 5
The DS-II is a validated, patient-reported outcome assessing demoralization with a 2-week recall period. Possible scores range 0-32 with higher scores indicating a greater degree of demoralization.
Baseline and Week 5
Change from Baseline on 16-item Demoralization Scale - II (DS-II) at Week 2
Time Frame: Baseline and Week 2
The DS-II is a validated, patient-reported outcome assessing demoralization with a 2-week recall period. Possible scores range 0-32 with higher scores indicating a greater degree of demoralization.
Baseline and Week 2

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Odds of improvement from Baseline on Clinical Global Impression scale (CGI-I) for demoralization at Week 5.
Time Frame: Baseline and Week 5
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.
Baseline and Week 5
Odds of improvement from Baseline on Clinical Global Impression scale (CGI-I) for demoralization at Week 2.
Time Frame: Baseline and Week 2
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.
Baseline and Week 2
Odds of meeting criteria for demoralization on the Diagnostic Criteria for Psychosomatic Research-Revised (DCPR-R) at Week 5.
Time Frame: Week 5
The DCPR-R is a validated clinician-rated assessment of various psychosomatic conditions, including demoralization, which is rated as Present or Absent with a 1-month recall period.
Week 5
Odds of meeting criteria for demoralization on the Diagnostic Criteria for Psychosomatic Research-Revised (DCPR-R) at Week 2.
Time Frame: Week 2
The DCPR-R is a validated clinician-rated assessment of various psychosomatic conditions, including demoralization, which is rated as Present or Absent with a 1-month recall period.
Week 2
Change from Baseline on GRID Hamilton Rating Scale for Depression 6-item (GRID-HAMD-6) at Week 5.
Time Frame: Baseline and Week 5
The GRID-HAMD-6 is a validated, clinician-rated measure of the core symptoms of major depression. Possible scores range 0-4 with higher scores indicating a greater degree of depressed mood.
Baseline and Week 5
Change from Baseline on GRID Hamilton Rating Scale for Depression 6-item (GRID-HAMD-6) at Week 2.
Time Frame: Baseline and Week 2
The GRID-HAMD-6 is a validated, clinician-rated measure of the core symptoms of major depression. Possible scores range 0-4 with higher scores indicating a greater degree of depressed mood.
Baseline and Week 2
Change from Baseline on Patient Health Questionnaire-9 (PHQ-9) at Week 5.
Time Frame: Baseline and Week 5
The PHQ-9 is a validated, patient-reported outcome assessing depression symptom severity with a 2-week recall period. Possible scores range 0-27 with higher scores indicating worse depression.
Baseline and Week 5
Change from Baseline on Patient Health Questionnaire-9 (PHQ-9) at Week 2.
Time Frame: Baseline and Week 2
The PHQ-9 is a validated, patient-reported outcome assessing depression symptom severity with a 2-week recall period. Possible scores range 0-27 with higher scores indicating worse depression.
Baseline and Week 2
Change from Baseline on Generalized Anxiety Disorder-7 (GAD-7) at Week 5.
Time Frame: Baseline and Week 5
The GAD-7 is a validated, patient-reported outcome assessing the severity of generalized anxiety disorder (GAD) symptoms with a 2-week recall period. Possible scores range 0-21 with higher scores indicating greater severity of symptoms of GAD.
Baseline and Week 5
Change from Baseline on Generalized Anxiety Disorder-7 (GAD-7) at Week 2.
Time Frame: Baseline and Week 2
The GAD-7 is a validated, patient-reported outcome assessing the severity of generalized anxiety disorder (GAD) symptoms with a 2-week recall period. Possible scores range 0-21 with higher scores indicating greater severity of symptoms of GAD.
Baseline and Week 2
Change from Baseline on Functional Assessment of Chronic Illness Therapy-Palliative Care 14-item scale (FACIT-Pal-14) at Week 5.
Time Frame: Baseline and Week 5
The FACIT-Pal-14 is a validated, patient-reported outcome assessing quality of life in palliative care patients with a 7-day recall period. Possible scores range 0-56 with higher scores indicating a better quality of life.
Baseline and Week 5
Change from Baseline on Functional Assessment of Chronic Illness Therapy-Palliative Care 14-item scale (FACIT-Pal-14) at Week 2.
Time Frame: Baseline and Week 2
The FACIT-Pal-14 is a validated, patient-reported outcome assessing quality of life in palliative care patients with a 7-day recall period. Possible scores range 0-56 with higher scores indicating a better quality of life.
Baseline and Week 2
Change from Baseline on Functional Assessment of Chronic Illness Therapy-Spiritual Well-being 12-item scale (FACIT-Sp-12) at Week 5.
Time Frame: Baseline and Week 5
The FACIT-Sp-12 is a validated, patient-reported outcome assessing spiritual well-being with a 7-day recall period. Scores range 0-48 with a higher score indicating better spiritual well-being.
Baseline and Week 5
Change from Baseline on Functional Assessment of Chronic Illness Therapy-Spiritual Well-being 12-item scale (FACIT-Sp-12) at Week 2.
Time Frame: Baseline and Week 2
The FACIT-Sp-12 is a validated, patient-reported outcome assessing spiritual well-being with a 7-day recall period. Scores range 0-48 with a higher score indicating better spiritual well-being.
Baseline and Week 2
Change from Baseline on Hopelessness Assessment in Illness Questionnaire (HAI) at Week 5.
Time Frame: Baseline and Week 5
The HAI is a validated patient-reported measure of hopelessness in terminally ill cancer patients. Scores range 0-16 with higher scores indicating higher levels of hopelessness.
Baseline and Week 5
Change from Baseline on Hopelessness Assessment in Illness Questionnaire (HAI) at Week 2.
Time Frame: Baseline and Week 2
The HAI is a validated patient-reported measure of hopelessness in terminally ill cancer patients. Scores range 0-16 with higher scores indicating higher levels of hopelessness.
Baseline and Week 2
Relative risks for treatment-related, clinically significant adverse events
Time Frame: Through study completion (up to 4 months)
Relative risks for treatment-related serious adverse events, unexpected adverse events, common adverse events, and adverse events of special interest
Through study completion (up to 4 months)

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Treatment Allocation Questionnaire (TAQ) at Week 2.
Time Frame: Baseline and Week 2
The TAQ is a questionnaire made for this study. Participants will be asked what study drug they believed they received at their medication visit (psilocybin or ketamine). They will then be asked to rate with which certainty they believe this using a visual analog scale 0-100%.
Baseline and Week 2
Treatment Allocation Questionnaire (TAQ) at Week 5.
Time Frame: Baseline and Week 5
The TAQ is a questionnaire made for this study. Participants will be asked what study drug they believed they received at their medication visit (psilocybin or ketamine). They will then be asked to rate with which certainty they believe this using a visual analog scale 0-100%.
Baseline and Week 5
Mystical Experience Questionnaire-30 (MEQ30) at Medication Visit.
Time Frame: At the end of the Medication Visit (Visit 4 / Day 0)
The MEQ30 is a validated, patient-reported outcome assessing mystical-type experiences, derived from the earlier surveys of subjective responses to psilocybin. Scores range 0-150 with a higher score indicating a more mystical-type experience.
At the end of the Medication Visit (Visit 4 / Day 0)
Challenging Experience Questionnaire (ChEQ) at Medication Visit.
Time Frame: At the end of the Medication Visit (Visit 4 / Day 0)
The ChEQ is a validated, patient-reported outcome assessing challenging experiences with psychedelics. Possible scores range 0-130 with a higher score indicating greater psychologically adverse reactions to psilocybin.
At the end of the Medication Visit (Visit 4 / Day 0)
Change from Baseline in 15-item Death Transcendence Scale (DTS-15) at Week 1.
Time Frame: Baseline and Week 1
The DTS-15 is a validated, patient-reported outcome assessing death transcendence. Possible scores range 0-60 with a higher score indicating a higher level of death transcendence.
Baseline and Week 1
Persisting Effects Questionnaire 4-item (PEQ-4) at Week 5.
Time Frame: Week 5
The PEQ-4 is a patient-reported outcome assessing the enduring effects of psilocybin. Ratings are made with respect to other life experiences. Possible scores range 0-32 with a higher score indicating higher enduring effects of psilocybin.
Week 5
Change in patient-reported pain from Baseline in Brief Pain Inventory-Short Form (BPI-SF) at Week 5.
Time Frame: Baseline and Week 5
The BPI-SF is a validated, patient-reported outcome assessing pain over the last 24-hours, with higher scores on subscales indicating higher severity of pain, and/or higher impact on functioning. This measure will assess change in pain in the subset of patients with moderate-to-severe pain at Baseline.
Baseline and Week 5
Change in patient-reported pain from Baseline in Brief Pain Inventory-Short Form (BPI-SF) at Week 2.
Time Frame: Baseline and Week 2
The BPI-SF is a validated, patient-reported outcome assessing pain over the last 24-hours, with higher scores on subscales indicating higher severity of pain, and/or higher impact on functioning. This measure will assess change in pain in the subset of patients with moderate-to-severe pain at Baseline.
Baseline and Week 2

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Charles S. Grob, M.D.

Collaborators

University of California, San Francisco

Investigators

  • Principal Investigator: Charles S. Grob, M.D., Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

January 14, 2024

Primary Completion (Estimated)

December 31, 2025

Study Completion (Estimated)

March 31, 2026

Study Registration Dates

First Submitted

April 24, 2022

First Submitted That Met QC Criteria

June 1, 2022

First Posted (Actual)

June 3, 2022

Study Record Updates

Last Update Posted (Actual)

October 24, 2023

Last Update Submitted That Met QC Criteria

October 21, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 21-008459

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Data from this study may be requested from other researchers 2 years after the completion of the primary endpoint by contacting the study sponsor.

IPD Sharing Time Frame

Data will become available 2 years after completion of the primary endpoint.

IPD Sharing Access Criteria

Data will be made available to qualified investigators who agree to the data sharing policies of the study.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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