Demoralization
Conditions
Keywords
Palliative Care, Serious Medical Illness, Life-threatening Condition, Advanced and Progressive Illness
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.
Interventions
DRUGPsilocybin
Psilocybin, \[3-\[2-(dimethylamino)ethyl\]-1H-indol-4-yl\] dihydrogen phosphate.
DRUGKetamine
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.
Sponsors
University of California, San Francisco
Charles S. Grob, M.D.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
A Multicenter Triple-blind Phase 2 Randomized Controlled Trial.
Intervention model description
Parallel with optional Crossover for the control arm
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in patient-reported Demoralization Scale-II.. | 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
| Measure | Time frame | Description |
|---|---|---|
| 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. | 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. |
| 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), | A comparison to active control using the following measures: PHQ-9, GRID-HAM-D6.compared to active control |
| 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) | A comparison to active control, using the following measures: GAD-7, FACIT-Pal-14 FACIT-Sp-12. |
| 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. | 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. |
| 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. | Associations will be explored between change in Demoralization Scale-II and 1) Credibility Expectancy Questionnaire (CrEQ), 2) Treatment Allocation Questionnaire, 3) Mystical Experience Questionnaire-30 (MEQ-30) and PEQ-4, 4) Challenging Experience Questionnaire (ChEQ), and 5) Change in Death Transcendence Scale-15 item (DTS-15) |
| DS-II and PHQ-9 comparison measures assessment | Throughout the study | Change in DS-II and PHQ-9 will be compared to assess if there is a differential response to psilocybin therapy in this population. |
| Change in patient-reported pain | From Enrollment (V1) to ~14-days post drug (V8), and from Enrollment (V1) to ~35-days post drug (V9), | A comparison to active control, using the Brief Pain Inventory-Short Form (BPI-SF). |
Countries
United States
Contacts
Primary ContactCharles S. Grob, M.D.
Backup ContactBrian T Anderson, M.D.
Outcome results
None listed