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

Overview

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.

Interventions

• Drug Psilocybin
  Psilocybin, \[3-\[2-(dimethylamino)ethyl\]-1H-indol-4-yl\] dihydrogen phosphate.
• 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.

Primary outcome measures

• 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.]

Secondary outcome measures (7)

• i) Change in clinician-rated Clinical Global Impression (CGI) for Severity of demoralization. [Time frame: From Enrollment (V1) to ~14-days (V8) and ~35-days (V9) post-drug for patients treated with psilocybin therapy vs active control.]
• ii) Odds ratio of meeting criteria for demoralization on the clinician-rated Demoralization Interview Interview (DI). [Time frame: From Enrollment (V1) to ~14-days (V8) and ~35-days (V9) post-drug for patients treated with psilocybin therapy vs active control.]
• Change in depression symptoms [Time frame: 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 [Time frame: From Enrollment (V1) to ~14-days post drug (V8), and Enrollment (V1) to ~35-days post drug (V9)]
• Change in patient-reported pain [Time frame: From Enrollment (V1) to ~14-days post drug (V8), and from 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 [Time frame: From Pre-dose (V4) to 7-days post-drug.]
• DS-II and PHQ-9 comparison measures assessment [Time frame: Throughout the study]

Eligibility criteria

Inclusion criteria

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)

Exclusion criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 5 centers

• Marin Cancer Care — Greenbrae
• University of California, Los Angeles — Los Angeles
• University of San Francisco — San Francisco
• Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center — Torrance
• Sunstone Therapies — Rockville

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. PMID 34879712
• 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. PMID 31915100
• 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. PMID 28947181
• 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. PMID 30102082
• 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. PMID 27171617
• 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. PMID 27171544
• 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. PMID 33150319
• 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. PMID 20819978

Identifiers

NCT: NCT05403086 · 21-008459

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗