The Syn-Sleep Study

Study Overview
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Brief Summary
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In collaboration with approximately 8 centers that specialize in iRBD we will recruit a total of 80 individuals for the study. All subjects will be enrolled into a 2-year longitudinal study where skin biopsies will be performed at 3 sites on each patient at 12-month intervals (baseline, year 1, year 2). Plasma blood collection will be performed at 12-month intervals (baseline, year 1, year 2). Detailed quantified examination, cognitive evaluation, medical history, and questionnaires will be performed at each visit. Additional biomarker, imaging and clinical information (if available) will be obtained for the purpose of determining phenoconversion to clinically apparent synucleinopathy. Subjects enrolled in the study will have baseline evaluations and follow up visits at 12 and 24 months to define any changes to clinical diagnosis (clinical phenoconversion). Skin biopsies will be repeated at the 12- and 24-month follow up visits to determine the rate of P-SYN accumulation over time and the rates of nerve fiber degeneration within punch skin biopsies.

Official Title
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Cutaneous Phosphorylated Alpha-Synuclein for Detection of Prodromal Synucleinopathies

Conditions
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REM Sleep Behavior Disorder (iRBD)

Intervention / Treatment
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* Diagnostic Test: Syn-One Test


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females age 18-85 Subjects will have repeated episodes of sleep related vocalizations and/or complex motor behaviors Sleep-related behaviors/disturbances must be documented by polysomnography to occur during REM sleep Polysomnographic recording is consistent with REM sleep without atonia Exclusion Criteria: Subjects with MoCA < 19, Hoehn and Yahr score >/=1, contraindications to skin biopsy Diagnosis of Parkinson's disease Diagnosis of dementia of any type Diagnosis of multiple system atrophy REM sleep behaviors/disturbances secondary to another cause (e.g., narcolepsy, dementia, and Parkinson's disease) Contra-indications to skin biopsy: Clinical evidence of severe vascular disease (history of ulceration, poor wound healing, and vascular claudication) History of allergic reaction to local anesthesia for skin biopsies Use of blood thinners (aspirin of Plavix alone is allowed) Significantly impaired wound healing or history of scarring or keloid formation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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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Arms and Interventions

| Intervention/Treatment |
| --- |
|Diagnostic Test: Syn-One Test|Participating subjects will have three small skin punch biopsies.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Advance the diagnostic utility of the Syn-One Test | Pathologically distinguish DLB from AD early in the course of disease using the Syn-One Test, confirming disease diagnosis through prospective clinical assessments (Neuro exam, NACC data set, and DLB Module) and follow-up analyses over 12 months. | 3 years | 
| Enhance pathological reading through digital quantitative analysis of the Syn-One Test | Define the rates of neuronal degeneration in DLB through systematic pathological quantitation, measuring P-SYN deposition and cutaneous nerve fiber degeneration, compared to AD, and correlating pathological findings with clinical assessments (Neuro exam, NACC data set, and DLB Module) over the course of 12 months. | 3 years |