PAPR: PAP + MBSR for Front-line Healthcare Provider COVID-19 Related Burnout

NCT05557643 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: IRB_00152312
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This project is an open-label randomized study looking at an 8-week Mindfulness-Based Stress Reduction (MBSR) curriculum vs. an 8-week MBSR curriculum + a group psilocybin-assisted psychotherapy intervention for frontline healthcare providers struggling with symptoms of depression and burnout associated with the SARS-CoV-2 pandemic. Following consenting and enrollment a total of 24 participants will be randomized to receive either an 8-week MBSR curriculum or the same 8-week MBSR curriculum + a group psilocybin-assisted psychotherapy intervention. The group psilocybin-assisted psychotherapy intervention will involve 3 group preparatory sessions (2 hours each), a single 8 hour group psilocybin administration session with a 1:1 therapist to participant ratio (25mg psilocybin dose), and 3 group integration sessions (2 hours each).

Conditions

Depression; Burnout, Professional

Keywords

burnout; psilocybin; psychedelic-assisted psychotherapy; healthcare; COVID-19

Outcome Measures

Primary Outcomes (1)

• Efficacy of MBSR + PAP vs. MBSR alone in reducing symptoms of depression, as measured by the QIDS-SR-16

  Efficacy will be assessed through mean reduction in QIDS-SR-16 scores at 2-weeks post intervention with between-group comparison. To understand longitudinal effects, the investigators will gather data to 6 months post intervention for both arms. Participants will be screened for eligibility with the PHQ-9 with a cut-off score of ≥ 8 required for enrollment.

  6 months

Secondary Outcomes (7)

• Effect of MBSR + PAP vs. MBSR alone on participant reported symptoms of burnout as measured by the Maslach Burnout Inventory, MBI-HSS(MP).

  Study enrollment to 2 weeks post completion of intervention as well as 6 months post intervention.

• Effect of MBSR+PAP vs. MBSR alone on symptoms of demoralization

  Study enrollment to 2 weeks post completion of intervention

• Effect of MBSR + PAP vs. MBSR alone on symptoms of post-traumatic stress

  Study enrollment to 2 weeks post completion of intervention

• Effect of MBSR + PAP vs. MBSR alone on participant reported quality of life.

  Study enrollment to 2 weeks post intervention

• Effect of MBSR + PAP vs. MBSR alone on measures of connectedness to self, other, and world

  Study enrollment to 2 weeks post intervention

Study Arms (2)

Mindfulness-Based Stress Reduction (MBSR)

ACTIVE COMPARATOR

Participants in the MBSR arm will complete an 8-week Mindfulness-Based Stress Reduction Curriculum involving a weekly 2 hour group meeting (either in person or virtual) as well as a 8 hour group mindfulness retreat in week 6-7 of the curriculum.

Behavioral: Mindfulness-Based Stress Reduction (MBSR)

Mindfulness-Based Stress Reduction (MBSR) + Psilocybin-Assisted Psychotherapy (PAP)

EXPERIMENTAL

Participants in the MBSR + PAP arm will complete an 8-week Mindfulness-Based Stress Reduction Curriculum involving a weekly 2 hour group meeting (either in person or virtual). They will additionally complete a psilocybin-assisted psychotherapy (PAP) intervention that involves three 2-hour group preparatory sessions, a single 8-hour group psilocybin administration session (done in place of the mindfulness retreat), and three 2-hour group integration sessions. All PAP intervention sessions will utilize a 1:1 therapist to participant ratio with an additional lead therapist present.

Drug: Psilocybin; Behavioral: Mindfulness-Based Stress Reduction (MBSR)

Interventions

Psilocybin DRUG

Psilocybin is a classic psychedelic of medium duration that is well-tolerated and has a documented safety and efficacy record that makes it uniquely well-suited to the issues that arise in this participant population. Psilocybin has been described as an 'existential medicine' given patient testimonials as to its acute and lasting effects on interpersonal connection, ability to more deeply engage with meaningful activities and relationships, dramatic reductions in fear of death, and a renewed sense of well-being.

Mindfulness-Based Stress Reduction (MBSR) + Psilocybin-Assisted Psychotherapy (PAP)

Mindfulness-Based Stress Reduction (MBSR) BEHAVIORAL

Mindfulness-Based Stress Reduction (MBSR) is a well-established evidence-based mindfulness training program initially developed by Jon Kabat-Zinn that has been shown to reduce symptoms of depression, anxiety, and burnout. The 8-week MBSR curriculum provides training in formal meditation practices including body scan techniques, mindfulness meditation, and yoga. Mindfulness can be understood as the non-judgmental acceptance and investigation of present experience, including body sensations, internal mental states, thoughts, emotions, impulses and memories, in order to reduce suffering or distress and to increase well-being.

Mindfulness-Based Stress Reduction (MBSR); Mindfulness-Based Stress Reduction (MBSR) + Psilocybin-Assisted Psychotherapy (PAP)

Eligibility Criteria

• Age: 25 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \_\_\_ Participants must be physicians or nurses with at least 1 month of frontline clinical experience during the COVID pandemic.
• Yes/No Eligibility Questions (Response of "no" = subject ineligible)
• PHQ-9 score ≥ 10 and meet criteria for a DSM-5 depressive disorder (including adjustment disorder with depressed mood).
• Meet the study working definition of burnout which will involve a score on the emotional exhaustion subscale (≥ 27) and a 'high' score on one other subscale (either depersonalization ≥ 13 or personal accomplishment ≤ 21).
• Not taking regularly scheduled medications to treat depression and/or anxiety, including benzodiazepines, for at least 4 weeks prior to initiation of the study.
• Fluent in English.
• Reading literacy and comprehension sufficient for understanding the consent form and study questionnaires, as evaluated by study staff obtaining consent.
• Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.
• ECOG Performance Status \< or = 2.
• Have a support person that would be able to escort the subject home on the evening of the psilocybin dosing session. The use of ride services will not be permitted (e.g., Uber, Lift, taxi, etc.)
• Adequate liver function as defined as:
• Total Bilirubin \< 1.5x institutional upper limit of normal (ULN) unless elevated bilirubin is related to Gilbert's Syndrome.
• AST(SGOT)/ALT(SGPT) \<3 x institutional ULN
• For female subjects: Negative pregnancy test and agreement to use highly effective contraception or evidence of post-menopausal status. The post-menopausal status will be defined as having been amenorrheic for 12 months without an alternative medical cause.
• For male subjects: agree to condom use during intercourse for 24 hours post-psilocybin dose.

You may not qualify if:

• Yes/No Eligibility Questions (Response of "yes" = subject ineligible)
• Prior systemic antidepressants, antipsychotic, or anxiolytic medication within four weeks prior to study initiation.
• Personal history or first- or second-degree relatives with schizophrenia, bipolar affective disorder, delusional disorder, schizoaffective disorder, psychosis, or other psychotic spectrum illness as determined by patient report and chart review.
• Current or history within the last two years of meeting DSM-V criteria of substance use disorder (excluding caffeine and nicotine). Current substance use disorders may be identified through the drug urine screening test as determined by patient report and chart review.
• Currently meeting DSM-V criteria for Dissociative Disorder, or other psychiatric conditions judged to be incompatible with the establishment of rapport or safe exposure to psilocybin as determined by patient report and chart review.
• Currently meeting DSM-V criteria for Cluster B Personality Disorder as determined by patient report and chart review.
• Severe depression requiring immediate standard-of-care treatment (e.g., hospitalization).
• Suicidal ideation over the past month as assessed as a yes to question 3, 4, or 5 on the Columbia-Suicide Severity Rating Scale, Suicidal Ideation section
• Cancer with known CNS involvement, previously treated brain metastasis, or other major CNS disease.
• Employment as house staff/residents
• The subject has uncontrolled significant intercurrent or recent illness including, but not limited to, the following conditions:
• Cardiovascular disorders: Congestive heart failure, including all New York Heart Association Classes.
• Angina pectoris, cardiac hypertrophy, cardiac ischemia, myocardial infarction
• Uncontrolled hypertension at the time of enrollment (BP\>140 systolic or 90 diastolic), coronary artery disease, artificial heart valve
• Prolonged or congenital long QT syndrome (\>450 ms), serious cardiac arrhythmias, tachycardia, a clinically significant screening ECG abnormality

Sponsors & Collaborators

• University of Utah: lead
• Heffter Research Institute: collaborator
• Usona Institute: collaborator

Study Sites (1)

Huntsman Mental Health Institute

Salt Lake City, Utah, 84108, United States

Location

Related Publications (2)

• Lewis BR, Hendrick J, Byrne K, Odette M, Wu C, Garland EL. Psilocybin-assisted group psychotherapy and mindfulness-based stress reduction for frontline healthcare provider COVID-19-related depression and burnout: A randomized controlled trial. PLoS Med. 2025 Sep 19;22(9):e1004519. doi: 10.1371/journal.pmed.1004519. eCollection 2025 Sep.

  PMID: 40972137 DERIVED

• Lewis BR, Garland EL, Byrne K, Durns T, Hendrick J, Beck A, Thielking P. HOPE: A Pilot Study of Psilocybin Enhanced Group Psychotherapy in Patients With Cancer. J Pain Symptom Manage. 2023 Sep;66(3):258-269. doi: 10.1016/j.jpainsymman.2023.06.006. Epub 2023 Jun 10.

  PMID: 37302533 DERIVED

MeSH Terms

Conditions

Depression; Burnout, Professional; Burnout, Psychological; COVID-19

Interventions

Psilocybin; Mindfulness-Based Stress Reduction

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Occupational Stress; Occupational Diseases; Stress, Psychological; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines; Mindfulness; Cognitive Behavioral Therapy; Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Psychiatry

Model Details: 2-arm, randomized, open-label trial for 24 participants.

Study Record Dates

• First Submitted: September 23, 2022
• First Posted: September 28, 2022
• Study Start: January 2, 2023
• Primary Completion: September 20, 2024
• Study Completion: September 20, 2024
• Last Updated: November 12, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)