Psilocybin Therapy for Depression and Anxiety in Parkinson's Disease (PDP)

• ClinicalTrials.gov Identifier: NCT04932434
• Recruitment Status: Recruiting
• First Posted: June 21, 2021
• Last Update Posted: February 9, 2023
• Sponsor: Joshua Woolley, MD/PhD
• Information provided by (Responsible Party): Joshua Woolley, MD/PhD, University of California, San Francisco

Tracking Information

• First Submitted Date: May 5, 2021
• First Posted Date: June 21, 2021
• Last Update Posted Date: February 9, 2023
• Actual Study Start Date: August 15, 2021
• Estimated Primary Completion Date: June 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 11, 2021)

• Safety and tolerability of psilocybin therapy for depression and anxiety in people with PD [ Time Frame: Baseline to 3 months following last drug dose ]
  - Incidence, severity, and frequency of Adverse Events (AEs) including Treatment-Emergent AEs (TEAEs) and Serious AEs (SAEs)
• Recruitment rate [ Time Frame: Baseline to 3 months following last drug dose ]
  - Measured by the number of participants entering the trial multiplied by the number of months of active recruitment time
• Retention rate [ Time Frame: Baseline to 3 months following last drug dose ]
  - The number of participants completing all stages of the study will be presented as a percentage of the number of total number of participants recruited
• Treatment Satisfaction of psilocybin therapy for depression and anxiety in people with PD [ Time Frame: Baseline to 3 months following last drug dose ]
  Measured by the treatment satisfaction questionnaire

  • 5-item scale, plus three free response questions
  • items are ranked from 1-to-7, with higher scores representing better treatment satisfaction

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 11, 2021)

• Effects of psilocybin therapy on depression in people with PD (exploratory) [ Time Frame: Baseline to 3 months following last drug dose ]
  • Measured by the Montgomery-Asberg Depression Rating Scale (MADRS)
  • Each item is scored on a on a scale of 0 to 6, with a total score of 0 to 60
  • Higher scores correspond to worse outcomes
• Effects of psilocybin therapy on anxiety in people with PD (exploratory) [ Time Frame: Baseline to 3 months following last drug dose ]
  • Changes in anxiety assessed by the Hamilton Anxiety (HAM-A) Rating Scale
  • Each item is scored on a scale of 0 to 4 with a total score range of 0-56
  • Higher total scores correspond to worse outcomes
• Effects of psilocybin therapy on self-reported apathy (exploratory) [ Time Frame: Baseline to 3 months following last drug dose ]
  Measured using the Patient-Reported Outcomes Measurement Information System (PROMIS) Apathy Scale

  • Each item is scored on a scale of 1 to 4 with a total score range of 7-28
  • Lower total scores correspond to worse outcomes
• Effects of psilocybin therapy on self-reported depression (exploratory) [ Time Frame: Baseline to 3 months following last drug dose ]
  Measured using the Quality of Life in Neurological Disorders (Neuro-QoL) Depression Scale

  • Each item is scored on a scale of 1 to 5 with a total score range of 8-40
  • Higher total scores correspond to worse outcomes
• Effects of psilocybin therapy on self-reported lower extremity function (exploratory) [ Time Frame: Baseline to 3 months following last drug dose ]
  Measured using the Quality of Life in Neurological Disorders (Neuro-QoL) Lower Extremity Function Scale

  • Each item is scored on a scale of 1 to 5 with a total score range of 8-40
  • Lower total scores correspond to worse outcomes
• Effects of psilocybin therapy on self-reported Upper Extremity Function (exploratory) [ Time Frame: Baseline to 3 months following last drug dose ]
  Measured using the Quality of Life in Neurological Disorders (Neuro-QoL) Upper Extremity Function Scale

  • Each item is scored on a scale of 1 to 5 with a total score range of 8-40
  • Lower total scores correspond to worse outcomes
• Effects of psilocybin therapy on self-reported Cognitive Function (exploratory) [ Time Frame: Baseline to 3 months following last drug dose ]
  Measured using the Quality of Life in Neurological Disorders (Neuro-QoL) Cognitive Function Scale

  • Each item is scored on a scale of 1 to 5 with a total score range of 8-40
  • Lower total scores correspond to worse outcomes
• Effects of psilocybin therapy on self-reported Fatigue (exploratory) [ Time Frame: Baseline to 3 months following last drug dose ]
  Measured using the Quality of Life in Neurological Disorders (Neuro-QoL) Fatigue Scale

  • Each item is scored on a scale of 1 to 5 with a total score range of 8-40
  • Higher total scores correspond to worse outcomes
• Effects of psilocybin therapy on self-reported Concern with Death and Dying (exploratory) [ Time Frame: Baseline to 3 months following last drug dose ]
  Measured using the Quality of Life in Neurological Disorders (Neuro-QoL) Concern with Death and Dying Scale

  • Each item is scored on a scale of 1 to 5 with a total score range of 6-35
  • Higher total scores correspond to worse outcomes
• Effects of psilocybin therapy on self-reported Social Roles and Activities (exploratory) [ Time Frame: Baseline to 3 months following last drug dose ]
  Measured using the Quality of Life in Neurological Disorders (Neuro-QoL) Social Roles and Activities Scale

  • Each item is scored on a scale of 1 to 5 with a total score range of 8-40
  • Lower total scores correspond to worse outcomes
• Effects of psilocybin therapy on self-reported Positive Affect and Well-Being (exploratory) [ Time Frame: Baseline to 3 months following last drug dose ]
  Measured using the Patient-Reported Outcomes Measurement Information System (PROMIS) Positive Affect and Well-Being Scale

  • Each item is scored on a scale of 1 to 5 with a total score range of 7-45
  • Lower total scores correspond to worse outcomes

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Psilocybin Therapy for Depression and Anxiety in Parkinson's Disease
• Official Title: Psilocybin Therapy for Depression and Anxiety in Parkinson's Disease: a Pilot Study
• Brief Summary: The purpose of this study is to determine the safety, tolerability, and feasibility of psilocybin therapy for depression and anxiety in people with Parkinson's disease.
• Detailed Description: This is an open-label single-arm pilot study of oral psilocybin therapy for depression and anxiety in people with Parkinson's Disease (PD). The primary goal is to examine safety, tolerability, and feasibility of the intervention in this patient population. We will enroll ten people ages 40 to 75 with clinically diagnosed early stage Parkinson's Disease who meet DSM-5 criteria for a depressive or anxious disorder and meet all other inclusion and exclusion criteria at screening. After baseline assessments, participants will complete preparation sessions with trained facilitators followed by an initial drug administration session during which they will receive a low-moderate dose (10 mg) oral psilocybin in a supervised setting with safety monitoring by facilitators and a physician. Participants who do not experience significant adverse events during or following the session will complete a second drug administration session approximately two weeks later during which they will receive a moderate-high dose (25 mg) oral psilocybin. The second session will involve the same procedures and level of monitoring as the first. Participants will subsequently complete multiple follow-up sessions to assess PD motor symptoms, non-motor symptoms, and function. They will also complete integration sessions with facilitators to provide psychological support. Follow-up will continue to 3 months after the second psilocybin administration session. Primary endpoints will assess safety, tolerability and feasibility of study procedures. Exploratory efficacy endpoints will assess changes in depressive symptoms, anxious symptoms, and related measures of function/quality of life.
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

Single Group Assignment

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

• Parkinson Disease
• Depression
• Anxiety

Intervention

Drug: Psilocybin therapy

• Psilocybin administration session 1: 10mg delivered orally with psychological support and monitoring
• Psilocybin administration session 2: 25mg delivered orally with psychological support and monitoring

Other Name: 4-phosphoryloxy-N,N-dimethyltryptamine

Study Arms

Experimental: Psilocybin therapy

Participants will receive one or two doses of psilocybin in a monitored setting approximately two weeks apart, with preparation sessions before and integration sessions after.

Intervention: Drug: Psilocybin therapy

Publications *

• GBD 2016 Parkinson's Disease Collaborators. Global, regional, and national burden of Parkinson's disease, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2018 Nov;17(11):939-953. doi: 10.1016/S1474-4422(18)30295-3. Epub 2018 Oct 1. Erratum In: Lancet Neurol. 2021 Dec;20(12):e7.
• Weintraub D, Burn DJ. Parkinson's disease: the quintessential neuropsychiatric disorder. Mov Disord. 2011 May;26(6):1022-31. doi: 10.1002/mds.23664.
• Maillet A, Krack P, Lhommee E, Metereau E, Klinger H, Favre E, Le Bars D, Schmitt E, Bichon A, Pelissier P, Fraix V, Castrioto A, Sgambato-Faure V, Broussolle E, Tremblay L, Thobois S. The prominent role of serotonergic degeneration in apathy, anxiety and depression in de novo Parkinson's disease. Brain. 2016 Sep;139(Pt 9):2486-502. doi: 10.1093/brain/aww162. Epub 2016 Aug 17.
• Schapira AHV, Chaudhuri KR, Jenner P. Non-motor features of Parkinson disease. Nat Rev Neurosci. 2017 Jul;18(7):435-450. doi: 10.1038/nrn.2017.62. Epub 2017 Jun 8. Erratum In: Nat Rev Neurosci. 2017 Aug;18(8):509.
• Weintraub D, Moberg PJ, Duda JE, Katz IR, Stern MB. Effect of psychiatric and other nonmotor symptoms on disability in Parkinson's disease. J Am Geriatr Soc. 2004 May;52(5):784-8. doi: 10.1111/j.1532-5415.2004.52219.x.
• Barone P, Antonini A, Colosimo C, Marconi R, Morgante L, Avarello TP, Bottacchi E, Cannas A, Ceravolo G, Ceravolo R, Cicarelli G, Gaglio RM, Giglia RM, Iemolo F, Manfredi M, Meco G, Nicoletti A, Pederzoli M, Petrone A, Pisani A, Pontieri FE, Quatrale R, Ramat S, Scala R, Volpe G, Zappulla S, Bentivoglio AR, Stocchi F, Trianni G, Dotto PD; PRIAMO study group. The PRIAMO study: A multicenter assessment of nonmotor symptoms and their impact on quality of life in Parkinson's disease. Mov Disord. 2009 Aug 15;24(11):1641-9. doi: 10.1002/mds.22643.
• Ishihara L, Brayne C. A systematic review of depression and mental illness preceding Parkinson's disease. Acta Neurol Scand. 2006 Apr;113(4):211-20. doi: 10.1111/j.1600-0404.2006.00579.x.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 11, 2021): 10
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 2023
• Estimated Primary Completion Date: June 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Age 40 to 75
• Comfortable speaking and writing in English
• Clinically diagnosed early stage Parkinson's Disease (Hoehn and Yahr Stage 1-3 during an "off" period) who meet DSM-5 criteria for a depressive or anxious disorder and meet all other inclusion and exclusion criteria at screening
• Currently experiencing depression and/or anxiety (a formal diagnosis is not necessary)
• Able to attend all in-person visits at UCSF as well as virtual visits
• Have a care partner/support person available throughout the study
• Have an established primary care provider, neurologist, or psychiatrist

Exclusion Criteria:

• Psychotic symptoms involving loss of insight
• Significant cognitive impairment
• Regular use of medications that may have problematic interactions with psilocybin, including but not limited to dopamine agonists, MAO inhibitors, N-methyl-D-aspartate (NMDAR) antagonists, antipsychotics, and stimulants
• A health condition that makes this study unsafe or unfeasible, determined by study physicians

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 40 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Zach Busby; 415-881-8273; psilocybinstudies@ucsf.edu

Contact: Ellen Bradley, MD; ellen.bradley@ucsf.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04932434
• Other Study ID Numbers: 20-32641
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Joshua Woolley, MD/PhD, University of California, San Francisco
• Original Responsible Party: Same as current
• Current Study Sponsor: Joshua Woolley, MD/PhD
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Joshua Woolley, MD/PhD; University of California, San Francisco
• Study Director: Ellen Bradley, MD; University of California, San Francisco

• PRS Account: University of California, San Francisco
• Verification Date: February 2023