Pragmatic Trial of Psilocybin Therapy in Palliative Care (PT2PC)

• ClinicalTrials.gov Identifier: NCT05403086
• Recruitment Status: Not yet recruiting
• First Posted: June 3, 2022
• Last Update Posted: May 7, 2024
• Sponsor: Charles S. Grob, M.D.
• Collaborator: University of California, San Francisco
• Information provided by (Responsible Party): Charles S. Grob, M.D., Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Tracking Information

• First Submitted Date: April 24, 2022
• First Posted Date: June 3, 2022
• Last Update Posted Date: May 7, 2024
• Estimated Study Start Date: August 15, 2024
• Estimated Primary Completion Date: December 31, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 1, 2022)

• 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.
• 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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 1, 2022)

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: June 1, 2022)

• 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%.
• 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%.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Pragmatic Trial of Psilocybin Therapy in Palliative Care
• Official Title: 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
• 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 Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Parallel with optional Crossover for the control arm

Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

• Condition: Demoralization

Intervention

• Drug: Psilocybin
  Psilocybin, [3-[2-(dimethylamino)ethyl]-1H-indol-4-yl] dihydrogen phosphate.
  Other Name: Hallucinogen
• 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 Name: Ketalar

Study Arms

• Experimental: Psilocybin
  A single moderate-to-high dose of oral psilocybin, plus 4-5 sessions of a brief, existential psychotherapy.
  Intervention: Drug: Psilocybin
• Active Comparator: Ketamine
  A single low-to-moderate dose of oral liquid ketamine, plus 4-5 sessions of a brief, existential psychotherapy.
  Intervention: Drug: Ketamine

Publications *

• Gan LL, Gong S, Kissane DW. Mental state of demoralisation across diverse clinical settings: A systematic review, meta-analysis and proposal for its use as a 'specifier' in mental illness. Aust N Z J Psychiatry. 2022 Sep;56(9):1104-1129. doi: 10.1177/00048674211060746. Epub 2021 Dec 8.
• Caruso R, Breitbart W. Mental health care in oncology. Contemporary perspective on the psychosocial burden of cancer and evidence-based interventions. Epidemiol Psychiatr Sci. 2020 Jan 9;29:e86. doi: 10.1017/S2045796019000866.
• Reiche S, Hermle L, Gutwinski S, Jungaberle H, Gasser P, Majic T. Serotonergic hallucinogens in the treatment of anxiety and depression in patients suffering from a life-threatening disease: A systematic review. Prog Neuropsychopharmacol Biol Psychiatry. 2018 Feb 2;81:1-10. doi: 10.1016/j.pnpbp.2017.09.012. Epub 2017 Sep 22.
• Ross S. Therapeutic use of classic psychedelics to treat cancer-related psychiatric distress. Int Rev Psychiatry. 2018 Aug;30(4):317-330. doi: 10.1080/09540261.2018.1482261. Epub 2018 Aug 13.
• Robinson S, Kissane DW, Brooker J, Michael N, Fischer J, Franco M, Hempton C, Sulistio M, Pallant JF, Clarke DM, Burney S. Refinement and revalidation of the demoralization scale: The DS-II-internal validity. Cancer. 2016 Jul 15;122(14):2251-9. doi: 10.1002/cncr.30015. Epub 2016 May 12.
• Robinson S, Kissane DW, Brooker J, Hempton C, Michael N, Fischer J, Franco M, Sulistio M, Clarke DM, Ozmen M, Burney S. Refinement and revalidation of the demoralization scale: The DS-II-external validity. Cancer. 2016 Jul 15;122(14):2260-7. doi: 10.1002/cncr.30012. Epub 2016 May 12.
• Anderson BT, Danforth A, Daroff PR, Stauffer C, Ekman E, Agin-Liebes G, Trope A, Boden MT, Dilley PJ, Mitchell J, Woolley J. Psilocybin-assisted group therapy for demoralized older long-term AIDS survivor men: An open-label safety and feasibility pilot study. EClinicalMedicine. 2020 Sep 24;27:100538. doi: 10.1016/j.eclinm.2020.100538. eCollection 2020 Oct.
• Grob CS, Danforth AL, Chopra GS, Hagerty M, McKay CR, Halberstadt AL, Greer GR. Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Arch Gen Psychiatry. 2011 Jan;68(1):71-8. doi: 10.1001/archgenpsychiatry.2010.116. Epub 2010 Sep 6.
• Ross S, Bossis A, Guss J, Agin-Liebes G, Malone T, Cohen B, Mennenga SE, Belser A, Kalliontzi K, Babb J, Su Z, Corby P, Schmidt BL. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. J Psychopharmacol. 2016 Dec;30(12):1165-1180. doi: 10.1177/0269881116675512.
• Griffiths RR, Johnson MW, Carducci MA, Umbricht A, Richards WA, Richards BD, Cosimano MP, Klinedinst MA. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. J Psychopharmacol. 2016 Dec;30(12):1181-1197. doi: 10.1177/0269881116675513.

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: June 1, 2022): 100
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 31, 2026
• Estimated Primary Completion Date: December 31, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Charles S. Grob, M.D.; (310) 961-2662; psilocybin@lundquist.org

Contact: Brian T Anderson, M.D.; (310) 961-2662; psilocybin@lundquist.org

• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT05403086
• Other Study ID Numbers: 21-008459
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Time Frame: Data will become available 2 years after completion of the primary endpoint.
• Access Criteria: Data will be made available to qualified investigators who agree to the data sharing policies of the study.

• Current Responsible Party: Charles S. Grob, M.D., Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
• Original Responsible Party: Same as current
• Current Study Sponsor: Charles S. Grob, M.D.
• Original Study Sponsor: Same as current
• Collaborators: University of California, San Francisco

Investigators

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

• PRS Account: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
• Verification Date: May 2024