Clinical trial NCT05403086: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Demoralization
Keywords: Palliative Care
Serious Medical Illness
Life-threatening Condition
Advanced and Progressive Illness
Lead sponsor: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Sponsor class: OTHER
Collaborators: name: University of California, San Francisco
First posted: 2022-06-03
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel with optional Crossover for the control arm
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change in patient-reported Demoralization Scale-II..
timeFrame: 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 outcomes:
measure: i) Change in clinician-rated Clinical Global Impression (CGI) for Severity of demoralization.
timeFrame: From Enrollment (V1) to ~14-days (V8) and ~35-days (V9) post-drug for patients treated with psilocybin therapy vs active control.
measure: ii) Odds ratio of meeting criteria for demoralization on the clinician-rated Demoralization Interview Interview (DI).
timeFrame: From Enrollment (V1) to ~14-days (V8) and ~35-days (V9) post-drug for patients treated with psilocybin therapy vs active control.
measure: Change in depression symptoms
timeFrame: From Pre-dose V4 to ~14-days post drug (V8), and from Pre-dose V4 to ~35-days post drug (V9),
measure: Change in anxiety symptoms, quality of life, and spiritual well-being
timeFrame: From Enrollment (V1) to ~14-days post drug (V8), and Enrollment (V1) to ~35-days post drug (V9)
measure: Change in patient-reported pain
timeFrame: From Enrollment (V1) to ~14-days post drug (V8), and from Enrollment (V1) to ~35-days post drug (V9),
measure: Associations will be explored between change in Demoralization Scale-II and other measures pre-dose and 7 days post drug
timeFrame: From Pre-dose (V4) to 7-days post-drug.
measure: DS-II and PHQ-9 comparison measures assessment
timeFrame: Throughout the study
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of San Francisco
state: California
city: Torrance
country: United States
facility: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
state: California
city: Rockville
country: United States
facility: Sunstone Therapies
state: Maryland
Study officials:
affiliation: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
name: Charles S. Grob, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.