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

NCT04518059 | Completed

• 2 other identifiers: 201811891U01NS112010-01
• Study Type: observational
• Target: 184
• Locations: 1 country
• Sites: 2

Brief 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).

Conditions

Parkinson Disease; Parkinsonism; Dementia With Lewy Bodies; Multiple System Atrophy; Progressive Supranuclear Palsy; Corticobasal Degeneration

Keywords

Parkinson disease; Parkinson's disease; dementia with Lewy bodies; multiple system atrophy; progressive supranuclear palsy; corticobasal degeneration; biomarker; parkinsonism; alpha-synuclein

Outcome Measures

Primary Outcomes (5)

• Amount of alpha-synuclein in the skin

  Alpha-synuclein will be measured by RT-QuIC and sPMCA

  Cross-sectional at baseline

• 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

• 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

• 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

• 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 Outcomes (8)

• Change in Montreal Cognitive Assessment (MoCA)

  Baseline, 1 year, and optional 2 year assessment

• Change in Epworth Sleepiness Scale (ESS)

  Baseline, 1 year, and optional 2 year assessment

• Change in Hamilton depression scale

  Baseline, 1 year, and optional 2 year assessment

• Change in Hamilton anxiety scale

  Baseline, 1 year, and optional 2 year assessment

• Change in REM Behavior Disorder Questionnaire

  Baseline, 1 year, and optional 2 year assessment

Study Arms (2)

Parkinsonism Group

Participants with Parkinson's disease (PD), dementia with Lewy bodies (DLB), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD)

Procedure: punch skin biopsy

Control Group

Participants without parkinsonism

Procedure: punch skin biopsy

Interventions

punch skin biopsy PROCEDURE

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

Control Group; Parkinsonism Group

Eligibility Criteria

• Age: 21 Years - 89 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

People with parkinsonism, Parkinson's disease (PD), dementia with Lewy bodies (DLB), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD), and also controls without parkinsonism.

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Hospitals Cleveland Medical Center: lead
• Case Western Reserve University: collaborator
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• Banner Health: collaborator
• University of Bologna: collaborator
• Universidad Autonoma de San Luis Potosí: collaborator

Study Sites (2)

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

University Hospitals Suburban Health Center

South Euclid, Ohio, 44121, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Skin and blood samples are collected and used for analysis in the Case Western Reserve University Department of Pathology. Blood samples are obtained for NIH affiliated biobanks BioSEND/PDBP and RUCDR.

MeSH Terms

Conditions

Parkinson Disease; Parkinsonian Disorders; Lewy Body Disease; Multiple System Atrophy; Supranuclear Palsy, Progressive; Corticobasal Degeneration; Parkinson Disease 4, Autosomal Dominant Lewy Body

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Dementia; Neurocognitive Disorders; Mental Disorders; Primary Dysautonomias; Autonomic Nervous System Diseases; Ophthalmoplegia; Ocular Motility Disorders; Cranial Nerve Diseases; Tauopathies; Paralysis; Neurologic Manifestations; Eye Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Steven Gunzler, MD

  University Hospitals Cleveland Medical Center and Case Western Reserve University

  PRINCIPAL INVESTIGATOR

• Chen Shu, PhD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

• Zerui Wang, MD, PhD

  Case Western Reserve University

  PRINCIPAL INVESTIGATOR

• Qingzhong Kong, PhD

  Case Western Reserve University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 2 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Neurology

Study Record Dates

• First Submitted: July 31, 2020
• First Posted: August 19, 2020
• Study Start: March 12, 2019
• Primary Completion: May 31, 2025
• Study Completion: May 31, 2025
• Last Updated: July 1, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)