Clinical trial NCT04518059: Misfolded Proteins in the Skin of People With Parkinson's Disease and Other Parkinsonism
Official title: Assessing Skin Biomarkers for Preclinical Diagnosis of PD and Non-PD Parkinsonism
Study type: OBSERVATIONAL
Overall status: RECRUITING
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
Lead sponsor: University Hospitals Cleveland Medical Center
Sponsor class: OTHER
Collaborators: name: Case Western Reserve University
name: National Institute of Neurological Disorders and Stroke (NINDS)
name: National Institute of Allergy and Infectious Diseases (NIAID)
name: Banner Health
name: University of Bologna
name: Universidad Autonoma de San Luis Potosí
First posted: 2020-08-19
Enrollment: 250
Sex: ALL
Minimum age (years): 21
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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 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.

Eligibility 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
* 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.

Primary outcomes:
measure: Amount of alpha-synuclein in the skin
timeFrame: Cross-sectional at baseline
measure: Change in PSPRS measures of progressive supranuclear palsy (PSP) severity in people with PSP
timeFrame: Baseline, 1 year, and optional 2 year assessment
measure: Change in UMSARS measures of multiple system atrophy (MSA) severity in people with MSA
timeFrame: Baseline, 1 year, and optional 2 year assessment
measure: Change in Hoehn and Yahr (H&Y) and modified H&Y Scores
timeFrame: Baseline, 1 year, and optional 2 year assessment
measure: Change in Schwab and England (S&E) Score
timeFrame: Baseline, 1 year, and optional 2 year assessment
Secondary outcomes:
measure: Change in Montreal Cognitive Assessment (MoCA)
timeFrame: Baseline, 1 year, and optional 2 year assessment
measure: Change in Epworth Sleepiness Scale (ESS)
timeFrame: Baseline, 1 year, and optional 2 year assessment
measure: Change in Hamilton depression scale
timeFrame: Baseline, 1 year, and optional 2 year assessment
measure: Change in Hamilton anxiety scale
timeFrame: Baseline, 1 year, and optional 2 year assessment
measure: Change in REM Behavior Disorder Questionnaire
timeFrame: Baseline, 1 year, and optional 2 year assessment
measure: Change in blood pressure with orthostatic posture
timeFrame: Baseline, 1 year, and optional 2 year assessment
measure: Amount of alpha-synuclein in the blood
timeFrame: Baseline, optional 1 year assessment, and optional 2 year assessment
measure: Change in PDQ-39
timeFrame: Baseline, optional 1 year assessment, and optional 2 year assessment
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: South Euclid
country: United States
facility: University Hospitals Suburban Health Center
state: Ohio
Study officials:
affiliation: University Hospitals Cleveland Medical Center and Case Western Reserve University
name: Steven Gunzler, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Alabama at Birmingham
name: Chen Shu, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Case Western Reserve University
name: Zerui Wang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Case Western Reserve University
name: Qingzhong Kong, PhD
role: PRINCIPAL_INVESTIGATOR
References: