Misfolded Proteins in the Skin of People With Parkinson's Disease and Other Parkinsonism

Parkinson Disease Clinical Trial

Official title:

Assessing Skin Biomarkers for Preclinical Diagnosis of PD and Non-PD Parkinsonism

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04518059
• Other study ID #: 20181189
• Secondary ID: 1U01NS112010-01
• Status: Recruiting
• Start date: March 12, 2019
• Est. completion date: May 31, 2025

Study information

• Verified date: June 2024
• Source: University Hospitals Cleveland Medical Center
• Contact: Kailey Sajewski
• Phone: 216-286-6597
• Email: Kailey.Sajewski[@]UHhospitals.org
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

The purpose of this study is to determine whether identification of misfolded proteins in the skin will help to determine what sort of parkinsonism someone has. We seek to demonstrate whether someone has a synucleinopathy such as Parkinson's disease (PD), multiple system atrophy (MSA), or dementia with Lewy bodies(DLB), as opposed to a tauopathy such as progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD) or no parkinsonism at all (control).

Description:

This is a clinical research study for patients with parkinsonism, including Parkinson's disease, progressive supranuclear palsy, corticobasal degeneration, multiple system atrophy, and dementia with Lewy bodies. Parkinsonism can be difficult to diagnose, especially in the early stages of the disease. Skin punch biopsy could be a useful and way to diagnose and measure the severity of these conditions. Given that there currently is no proven way to determine that someone has a synucleinopathy such as PD and not a tauopathy, this is a novel study that may lead to better ways to diagnose people with parkinsonism. The purpose of the study is to identify changes on a skin punch biopsy, in which small samples of skin are removed and sent to the laboratory for examination. We are seeking to measure the amount of misfolded alpha-synuclein in someone's skin. Participation will last between 1 and 2 years and will involve between 2 and 4 visits. Visits will include a physical examination, questionnaires, a memory test, blood draws and saliva collection, and a single visit for skin punch biopsies. We will also be looking to enroll volunteers to serve as "controls," who do not have any neurological illness.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 250
• Est. completion date: May 31, 2025
• Est. primary completion date: May 31, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 89 Years

Eligibility

Inclusion Criteria:

• Age 21 years old and age <90 years of age at the time of the baseline visit 1

• Age of diagnosis at least 40 years old for PD, DLB, and PSP and at least 30 years old for MSA

• A confirmed diagnosis of PD, PSP, CBD, MSA, DLB, or healthy control

• Montreal Cognitive Assessment (MoCA) > 10 at the outset of the study

Exclusion Criteria:

• Age 90 or above

• Allergy to local anesthetic

• History of deep brain stimulation (DBS) or other brain surgery prior to Visit 1

• For PD or DLB diagnoses, any other neurodegenerative or central nervous system process that would interfere with examination

• For PD or DLB, history of negative DATscan

• Use of investigational drugs or devices within 60 days prior to baseline visit (except for dietary supplements)

• In control subjects, family history of a neurodegenerative disease in a first degree or second degree blood relative

• History of schizophrenia

• History of antipsychotic medication use or exposure in controls or history of antipsychotic medication leading to parkinsonism (drug induced parkinsonism) in the parkinsonism group

• Blood clotting disorder

• On multiple (more than one) antiplatelet and/or anticoagulant blood thinner medications in combination (except for aspirin if it can be safely held for 1 week)

• Any other medical, psychiatric, or cognitive illness that in the investigator's opinion would interfere with cooperation or ability to undergo the study procedures.

Related Conditions & MeSH terms

• Atrophy
• Corticobasal Degeneration
• Dementia
• Dementia With Lewy Bodies
• Lewy Body Disease
• Multiple System Atrophy
• Parkinson Disease
• Parkinsonian Disorders
• Parkinsonism
• Progressive Supranuclear Palsy
• Shy-Drager Syndrome
• Supranuclear Palsy, Progressive

Intervention

Procedure:
• punch skin biopsy
An anesthetic medication is injected to numb the areas of skin and two samples of skin are obtained from punch biopsy.

Locations

Country	Name	City	State
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	University Hospitals Suburban Health Center	South Euclid	Ohio

Sponsors (7)

Lead Sponsor	Collaborator
University Hospitals Cleveland Medical Center	Banner Health, Case Western Reserve University, National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Neurological Disorders and Stroke (NINDS), Universidad Autonoma de San Luis Potosí, University of Bologna

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Amount of alpha-synuclein in the skin	Alpha-synuclein will be measured by RT-QuIC and sPMCA	Cross-sectional at baseline
Primary	Change in PSPRS measures of progressive supranuclear palsy (PSP) severity in people with PSP	Questionnaire and examination. Lower scores are better.	Baseline, 1 year, and optional 2 year assessment
Primary	Change in UMSARS measures of multiple system atrophy (MSA) severity in people with MSA	Questionnaire and examination. Lower scores are better.	Baseline, 1 year, and optional 2 year assessment
Primary	Change in Hoehn and Yahr (H&Y) and modified H&Y Scores	Zero to 5 parkinsonism rating scale score. Lower score is better.	Baseline, 1 year, and optional 2 year assessment
Primary	Change in Schwab and England (S&E) Score	0% to 100% rating scale score. Higher score is better.	Baseline, 1 year, and optional 2 year assessment
Secondary	Change in Montreal Cognitive Assessment (MoCA)	Zero to 30 cognitive rating scale score. Higher score is better.	Baseline, 1 year, and optional 2 year assessment
Secondary	Change in Epworth Sleepiness Scale (ESS)	Zero to 24 sleepiness rating scale score. Lower score is better.	Baseline, 1 year, and optional 2 year assessment
Secondary	Change in Hamilton depression scale	17 item depression rating scale score. Lower score is better.	Baseline, 1 year, and optional 2 year assessment
Secondary	Change in Hamilton anxiety scale	14 item depression rating scale score. Lower score is better.	Baseline, 1 year, and optional 2 year assessment
Secondary	Change in REM Behavior Disorder Questionnaire	10 item depression rating scale score. Lower score is better.	Baseline, 1 year, and optional 2 year assessment
Secondary	Change in blood pressure with orthostatic posture	Blood pressure from lying down to sitting to standing. Smaller drop in blood pressure is better.	Baseline, 1 year, and optional 2 year assessment
Secondary	Amount of alpha-synuclein in the blood	Alpha-synuclein will be measured in the blood sample	Baseline, optional 1 year assessment, and optional 2 year assessment
Secondary	Change in PDQ-39	39 item health status questionnaire. Lower is better.	Baseline, optional 1 year assessment, and optional 2 year assessment