Frontline Clinician Psilocybin Study

• ClinicalTrials.gov Identifier: NCT05163496
• Recruitment Status: Active, not recruiting
• First Posted: December 20, 2021
• Last Update Posted: May 19, 2023
• Sponsor: University of Washington
• Information provided by (Responsible Party): Anthony Back MD, University of Washington

Study Description

Brief Summary:

This study aims to investigate the effects of a single dose of psilocybin, delivered in the contextof pre- and post-dose psychotherapy, on symptoms of depression and burnout suffered by healthcare clinicians as a result of frontline work in the COVID pandemic.

Condition or disease	Intervention/treatment	Phase
Burnout, Caregiver; Burnout, Professional; COVID-19; Depression; Post Traumatic Stress Disorder; Moral Injury	Drug: Psilocybin (Usona Institute); Drug: Active placebo	Phase 3

Detailed Description:

Aim 1:

To assess short- and longer-term effects of psilocybin-assisted psychotherapy (PAP) on symptoms of depression experienced by physicians and nurses with frontline work exposure in the COVID pandemic.

Hypothesis 1.1: Compared to active placebo, PAP will result in short term improvement in symptoms of depression 1 day and 1 week after the psilocybin dose session. Hypothesis 1.2: Compared to active placebo, PAP will result in longer term improvement of symptoms of depression 4 weeks after the medication dosing session. The primary outcome will be a comparison between the psilocybin 25 mg vs control groups of a combination of depression symptoms measured at 4 weeks post medication dose session. 1.1.2. Aim 2: To explore short- and longer-term effects of psilocybin-assisted psychotherapy (PAP) on symptoms of burnout experienced by physicians and nurses with frontline work exposure in the COVID pandemic. Hypothesis 2.1: Compared to active placebo, PAP will result in short term improvement in symptoms of burnout 1 day and 1 week after the psilocybin dose session.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: This study tests a hypothesis that a single session of psilocybin (the 'medication dosing' session) in the context of pre- and post-dose psychotherapy will result in improvement of symptoms of depression and burnout measured 4 weeks post-dose. This study hypothesis will be tested in a single site, double-blind, randomized controlled design involving 30 clinician participants that will compare effects of a single 25mg oral dose of psilocybin to a 250 mg of niacin (active placebo). The primary outcome measurements will be collected 4 weeks after the psilocybin dose, after which the participant group assignment will be unblinded, and participants who received niacin will be offered the opportunity to have a second dose session with a 25 mg dose (with pre- and post-dose psychotherapy).
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Masking Description: The investigators, study therapists, and outcomes assessors will all be blinded in the randomized phase of the study. Participants will be unblinded after the primary outcome, and those receiving placebo will be eligible to receive open label psilocybin.
• Primary Purpose: Treatment
• Official Title: A Randomized, Placebo-controlled Trial of Psychedelic-assisted Psychotherapy With Single Dose Psilocybin for Frontline Clinicians Experiencing COVID-related Symptoms of Depression and Burnout
• Actual Study Start Date: March 3, 2022
• Estimated Primary Completion Date: March 30, 2024
• Estimated Study Completion Date: March 30, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Psilocybin arm; psychedelic assisted psychotherapy + 25mg psilocybin	Drug: Psilocybin (Usona Institute); PAP + psilocybin 25 mg; Other Name: Psychedelic-assisted psychotherapy (PAP)
Active Comparator: Placebo; Psychedelic assisted psychotherapy + 250mg niacin	Drug: Active placebo; PAP + niacin 250mg; Other Name: PAP with placebo

Outcome Measures

Primary Outcome Measures :

1. Montgomery-Asberg Depression Rating Scale [ Time Frame: 4-weeks post psilocybin-assisted psychotherapy ]
   Assesses symptoms of depression (clinician-assessed): minimum score 0, max 60; higher score indicates more severe symptoms

Secondary Outcome Measures :

1. Montgomery-Asberg Depression Rating Scale [ Time Frame: 1, 8, 12, 24 weeks post-psilocybin-assisted psychotherapy ]
   Assesses symptoms of depression (clinician-assessed): minimum score 0, max 60; higher score indicates more severe symptoms
2. Stanford Fulfillment Index [ Time Frame: 1,4,8,12,24 -weeks post psilocybin-assisted psychotherapy ]
   Assesses professional burnout in 3 components that are scored separately (professional fulfillment, interpersonal disengagement, work exhaustion)
3. PTSD Checklist for DSM-5 (PCL5) [ Time Frame: 1, 4, 8, 12, 24-weeks post-psilocybin-assisted psychotherapy ]
   Assesses symptoms of post-traumatic stress disorder; minimum score 0, max 80; higher scores indicate more severe symptoms of PTSD
4. Moral injury symptom scale [ Time Frame: 4, 24 weeks post-psilocybin-assisted psychotherapy ]
   Assesses symptoms of moral injury: minimum score 10, max 100; higher score indicates more severe symptoms
5. Beck Depression Index [ Time Frame: 1, 4, 8, 12, 24-weeks post-psilocybin-assisted psychotherapy ]
   Assess self-reported symptoms of depression: minimum score 0, max 63; higher score indicates more severe symptoms of depression

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Participants must be physicians or nurses with at least 1 month of frontline clinical experience during the COVID pandemic who rate at least 2 of 4 items from the COVID Exposure index as 'more than half the days' during their peak 2 week period of exposure: i. Caring for someone critically ill with COVID-19, or who became critically ill while you were involved; ii. Working longer hours than usual in order to provide assistance or care to individuals with COVID-19; iii. Witnessing or responding to a death related to COVID-19, or losing a patient you had been caring for to COVID-19; iv. Caring for patients who have died without family physically present due to COVID-19 precautions
2. Have a Montgomery-Asberg Depression Rating Scale (MADRS) clinician-administered depression score >21, indicating moderately severe symptoms.
3. Have had persistent symptoms despite at least one medication and/or therapy trial of standard care treatment for depression.
4. English speaking - able to understand the process of consent and the risk and benefits associated with the study, and able to give written informed consent.
5. Must be willing to sign a medical release for the investigators to communicate directly with their therapist and doctors to confirm a medication and/or medical history. This is decided on a case-by-case basis upon the discretion of the PI.
6. Must be driven home after the medication dosing session by a driver (which could be a friend, family, rideshare or taxi).
7. Must provide at least one adult to have continuous contact with the participant, provide participant transportation, monitor changes in the participant's behavior, and notify research staff of behavior changes.
8. Has been off selective serotonin inhibitors (SSRIs) for at least five half-lives of the drug plus 2 weeks.
9. Must avoid taking any psychiatric medications or starting a new psychiatric medication during the study. Should participant's doctor recommend starting a new psychiatric medication, participant will be required to notify the study team and the subject would withdraw from the study
10. Must provide a contact (relative, spouse, close friend or other caregiver) who is willing and able to be reached by the Clinical Investigators in the event of a participant becoming suicidal.
11. If able to bear children, must have a negative pregnancy test at study entry.
12. Are willing to commit to preparation sessions, medication dosing sessions, integration sessions, to complete evaluation instruments and commit to be contacted for all necessary telephone contacts.

Exclusion Criteria:

1. Personal or immediate family history of schizophrenia, bipolar affective disorder, delusion disorder, paranoid disorder, or schizoaffective disorder.
2. Suicidal ideation with a Columbia Suicide Severity Rating Scale (C-SSRS) > 3
3. Current substance abuse disorder (except in the case of mild alcohol use )
4. Neuroleptic and SSRI medications that cannot be tapered and discontinued in conjunction with the participant's prescribing physician.
5. Unstable neurological or medical condition; history of seizure, chronic/severe headaches.
6. Positive urine pregnancy test at the time of screening
7. Any unstable medical condition that my render study procedures unsafe.
8. Any use of psychedelic drugs within the prior 12 months.
9. Use of tramadol, due to the potential for serotonin syndrome with concomitant use of psilocybin.

Contacts and Locations

Locations

United States, Washington

University of Washington

Seattle, Washington, United States, 98195

Sponsors and Collaborators

University of Washington

Investigators

• Principal Investigator: Anthony Back, MD; University of Washington

More Information

• Responsible Party: Anthony Back MD, Professor, School of Medicine, University of Washington
• ClinicalTrials.gov Identifier: NCT05163496
• Other Study ID Numbers: STUDY00013891
• First Posted: December 20, 2021
• Last Update Posted: May 19, 2023
• Last Verified: May 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: IPD that underlie results in a publication
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)
• Time Frame: We anticipate sharing these data starting with publication of study results and for at least 3 years.
• Access Criteria: To be determined.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Anthony Back MD, University of Washington:

psilocybin; psychedelic assisted psychotherapy

Additional relevant MeSH terms:

Burnout, Professional; Depression; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Burnout, Psychological; Caregiver Burden; Behavioral Symptoms; Mental Disorders; Trauma and Stressor Related Disorders; Stress, Psychological; Occupational Stress; Occupational Diseases; Psilocybin; Hallucinogens; Physiological Effects of Drugs; Psychotropic Drugs