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

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

Sponsors

Lead Sponsor: University Hospitals Cleveland Medical Center

Collaborator: Case Western Reserve University
National Institute of Neurological Disorders and Stroke (NINDS)
National Institute of Allergy and Infectious Diseases (NIAID)
Banner Health
University of Bologna
Universidad Autonoma de San Luis Potosí

Source University Hospitals Cleveland Medical Center
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).

Detailed 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 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.

Overall Status Recruiting
Start Date March 12, 2019
Completion Date May 31, 2024
Primary Completion Date May 31, 2024
Study Type Observational [Patient Registry]
Primary Outcome
Measure Time Frame
Amount of alpha-synuclein in the skin Cross-sectional at baseline
Change in PSPRS measures of progressive supranuclear palsy (PSP) severity in people with PSP Baseline, 1 year, and optional 2 year assessment
Change in UMSARS measures of multiple system atrophy (MSA) severity in people with MSA Baseline, 1 year, and optional 2 year assessment
Change in Hoehn and Yahr (H&Y) and modified H&Y Scores Baseline, 1 year, and optional 2 year assessment
Change in Schwab and England (S&E) Score Baseline, 1 year, and optional 2 year assessment
Secondary Outcome
Measure Time Frame
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
Change in orthostatic vital signs Baseline, 1 year, and optional 2 year assessment
Amount of alpha-synuclein in the blood Baseline, optional 1 year assessment, and optional 2 year assessment
Change in PDQ-39 Baseline, optional 1 year assessment, and optional 2 year assessment
Enrollment 250
Condition
Intervention

Intervention Type: Procedure

Intervention Name: punch skin biopsy

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

Eligibility

Sampling Method: Non-Probability Sample

Criteria:

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

- User of anticoagulation or blood clotting disorder

- 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

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

Gender: All

Minimum Age: 21 Years

Maximum Age: 89 Years

Healthy Volunteers: Accepts Healthy Volunteers

Overall Official
Last Name Role Affiliation
Wenquan Zou, MD, PhD Principal Investigator Case Western Reserve University
Overall Contact

Last Name: David Korosec, RN

Phone: 216-844-1800

Email: [email protected]

Location
Facility: Status: Contact: Investigator:
University Hospitals Cleveland Medical Center | Cleveland, Ohio, 44106, United States Recruiting Steven Gunzler, MD Steven Gunzler, MD Principal Investigator
University Hospitals Suburban Health Center | South Euclid, Ohio, 44121, United States Recruiting Steven Gunzler, MD Steven Gunzler, MD Principal Investigator
Location Countries

United States

Verification Date

August 2020

Responsible Party

Type: Principal Investigator

Investigator Affiliation: University Hospitals Cleveland Medical Center

Investigator Full Name: Steven Gunzler, MD

Investigator Title: Assistant Professor, Neurology

Keywords
Has Expanded Access No
Condition Browse
Arm Group

Label: Parkinsonism Group

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

Label: Control Group

Description: Participants without parkinsonism

Patient Data No
Study Design Info

Observational Model: Cohort

Time Perspective: Prospective

Source: ClinicalTrials.gov