Pragmatic Trial of Psilocybin Therapy in Palliative Care (PT2PC)

Charles S. Grob, M.D.

Status and phase: Begins enrollment this month; Phase 2

Conditions: Demoralization

Treatments: Drug: Psilocybin; Drug: Ketamine

Study type: Interventional

Funder types: Other

Identifiers

NCT05403086

21-008459

Details and patient eligibility

About

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).

Full 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.

Enrollment: 100 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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100 participants in 2 patient groups

Psilocybin

Experimental group

Description:

A single moderate-to-high dose of oral psilocybin, plus 4-5 sessions of a brief, existential psychotherapy.

Treatment:

Drug: Psilocybin

Ketamine

Active Comparator group

Description:

A single low-to-moderate dose of oral liquid ketamine, plus 4-5 sessions of a brief, existential psychotherapy.

Treatment:

Drug: Ketamine