Psilocybin Therapy for Depression and Anxiety in Parkinson's Disease

Depression Clinical Trial

— PDP1  

Official title:

Psilocybin Therapy for Depression and Anxiety in Parkinson's Disease: a Pilot Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04932434
• Other study ID #: 20-32641
• Status: Completed
• Phase: Phase 2
• Start date: August 15, 2021
• Est. completion date: December 31, 2023

Study information

• Verified date: June 2024
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 people ages 40 to 75 with 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. After baseline assessments, participants will complete preparation sessions designed to provide information about the psilocybin experience and to build rapport/trust with the study team. Next, participants will complete a first psilocybin administration session, receiving a low-moderate dose of 10 mg oral psilocybin in a supervised setting with safety monitoring by a physician. Participants who do not experience significant adverse events during or following the session will complete a second psilocybin administration session approximately two weeks later. During the second psilocybin administration session, participants will receive a moderate-high dose of 25 mg oral. The second session will involve the same procedures and level of monitoring as the first. Participants will subsequently complete multiple follow-up sessions designed to assess PD and psychiatric symptoms as well as to provide support as they process their psilocybin experiences. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Anxiety
• Anxiety Disorders
• Depression
• Depressive Disorder
• Parkinson Disease

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

Locations

Country	Name	City	State
United States	University of California, San Francisco	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Joshua Woolley, MD, PhD

Country where clinical trial is conducted

United States, 

References & Publications (7)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Weintraub D, Burn DJ. Parkinson's disease: the quintessential neuropsychiatric disorder. Mov Disord. 2011 May;26(6):1022-31. doi: 10.1002/mds.23664. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Effects of psilocybin therapy on depression in people with PD (exploratory)	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	Baseline to 3 months following last drug dose
Other	Effects of psilocybin therapy on anxiety in people with PD (exploratory)	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	Baseline to 3 months following last drug dose
Other	Cognitive Flexibility	Measured by the Probabilistic Reversal Learning (PRL) task	Baseline to 30 days following last drug dose
Other	Cognitive Flexibility	Measured by the Cognitive Control and Flexibility Questionnaire	Baseline to 30 days following last drug dose
Other	Transformational Experience	Measured by the study-specific Transformational Experiences Questionnaire (TEQ)	Baseline to 90 days following last drug dose
Other	Self-report changes to wellbeing	Measured by the Quality of Life in Neurological Disorders; Each item is scored on a scale of 1 to 5; Higher total scores correspond to worse outcomes	Baseline to 90 days following last drug dose
Other	Self-report changes to wellbeing	Measured using the Patient-Reported Outcomes Measurement Information Systems; Each item is scored on a scale of 1 to 5; Lower total scores correspond to worse outcomes	Baseline to 90 days following last drug dose
Primary	Parkinson's Disease (PD) symptom severity	Measured by Unified Parkinson's Disease Rating Scale (MDS-UPDRS)	Baseline to 30 days following last drug dose
Primary	Suicide Risk	Measured by Columbia Suicide Severity Rating Scale (C-SSRS)	Baseline to 30 days following last drug dose
Primary	Psychotic symptoms	Measured by Enhanced Scale for the Assessment of Positive Symptoms for Parkinson's Disease (eSAPS-PD)	Baseline to 30 days following last drug dose
Primary	Psychotic symptoms	Measured by Psychosis and Hallucinations Questionnaire in Parkinson's Disease (PsycH-Q)	Baseline to 30 days following last drug dose
Primary	Cognitive Safety	Measured by Cambridge Neuropsychological Test Automated Battery (CANTAB)	Baseline to 30 days following last drug dose
Primary	Caregiver/support person-reported distress	Measured by Neuropsychiatric Inventory Caregiver Distress Questionnaire (NPI-Q)	Baseline to 90 days following last drug dose
Primary	Participant-reported subjective experience	Measured by 5-Dimensional Altered States of Consciousness Rating Scale (5D-ASC)	Measured on each drug administration session day, following drug dose
Primary	Safety and tolerability of psilocybin therapy for depression and anxiety in people with PD	Incidence, severity, and frequency of Adverse Events (AEs) including Treatment-Emergent AEs (TEAEs) and Serious AEs (SAEs)	Baseline to 3 months following last drug dose
Primary	Recruitment rate	Measured by the number of participants entering the trial multiplied by the number of months of active recruitment time	Baseline to 3 months following last drug dose
Primary	Retention rate	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	Baseline to 3 months following last drug dose
Primary	Treatment Satisfaction of psilocybin therapy for depression and anxiety in people with PD	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	Baseline to 3 months following last drug dose