Clinical trial NCT04932434: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Parkinson Disease
Depression
Anxiety
Keywords: Parkinson Disease
Depression
Anxiety
Psilocybin
Psilocybin therapy
Movement disorder
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
First posted: 2021-06-21
Enrollment: 12
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single Group Assignment
Primary purpose: TREATMENT

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 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.

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

Primary outcomes:
measure: Parkinson's Disease (PD) symptom severity
timeFrame: Baseline to 30 days following last drug dose
measure: Suicide Risk
timeFrame: Baseline to 30 days following last drug dose
measure: Psychotic symptoms
timeFrame: Baseline to 30 days following last drug dose
measure: Psychotic symptoms
timeFrame: Baseline to 30 days following last drug dose
measure: Cognitive Safety
timeFrame: Baseline to 30 days following last drug dose
measure: Caregiver/support person-reported distress
timeFrame: Baseline to 90 days following last drug dose
measure: Participant-reported subjective experience
timeFrame: Measured on each drug administration session day, following drug dose
measure: Safety and tolerability of psilocybin therapy for depression and anxiety in people with PD
timeFrame: Baseline to 3 months following last drug dose
measure: Recruitment rate
timeFrame: Baseline to 3 months following last drug dose
measure: Retention rate
timeFrame: Baseline to 3 months following last drug dose
measure: Treatment Satisfaction of psilocybin therapy for depression and anxiety in people with PD
timeFrame: Baseline to 3 months following last drug dose
Secondary outcomes:
Other outcomes:
measure: Effects of psilocybin therapy on depression in people with PD (exploratory)
timeFrame: Baseline to 3 months following last drug dose
measure: Effects of psilocybin therapy on anxiety in people with PD (exploratory)
timeFrame: Baseline to 3 months following last drug dose
measure: Cognitive Flexibility
timeFrame: Baseline to 30 days following last drug dose
measure: Cognitive Flexibility
timeFrame: Baseline to 30 days following last drug dose
measure: Transformational Experience
timeFrame: Baseline to 90 days following last drug dose
measure: Self-report changes to wellbeing
timeFrame: Baseline to 90 days following last drug dose
measure: Self-report changes to wellbeing
timeFrame: Baseline to 90 days following last drug dose
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
Study officials:
affiliation: University of California, San Francisco
name: Joshua Woolley, MD/PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Francisco
name: Ellen Bradley, MD
role: STUDY_DIRECTOR
References:
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.
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.
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.
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.
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.
citation: 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.
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.