Psilocybin Therapy for Depression and Anxiety in Parkinson's Disease

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Parkinson Disease, Depression, Anxiety

Intervention / Treatment
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* Drug: Psilocybin therapy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Psilocybin therapy<br>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. | Drug: Psilocybin therapy<br>* Psilocybin administration session 1: 10mg delivered orally with psychological support and monitoring Psilocybin administration session 2: 25mg delivered orally with psychological support and monitoring<br>* Other names: 4-phosphoryloxy-N,N-dimethyltryptamine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| Effects of psilocybin therapy on self-reported apathy (exploratory) | 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 | Baseline to 3 months following last drug dose | 
| Effects of psilocybin therapy on self-reported depression (exploratory) | 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 | Baseline to 3 months following last drug dose | 
| Effects of psilocybin therapy on self-reported lower extremity function (exploratory) | 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 | Baseline to 3 months following last drug dose | 
| Effects of psilocybin therapy on self-reported Upper Extremity Function (exploratory) | 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 | Baseline to 3 months following last drug dose | 
| Effects of psilocybin therapy on self-reported Cognitive Function (exploratory) | 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 | Baseline to 3 months following last drug dose | 
| Effects of psilocybin therapy on self-reported Fatigue (exploratory) | 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 | Baseline to 3 months following last drug dose | 
| Effects of psilocybin therapy on self-reported Concern with Death and Dying (exploratory) | 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 | Baseline to 3 months following last drug dose | 
| Effects of psilocybin therapy on self-reported Social Roles and Activities (exploratory) | 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 | Baseline to 3 months following last drug dose | 
| Effects of psilocybin therapy on self-reported Positive Affect and Well-Being (exploratory) | 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 | Baseline to 3 months following last drug dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Depression, Anxiety, Parkinson Disease, Psilocybin, Psilocybin therapy, Movement disorder