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The North American Prodromal Synucleinopathy study: protocol for a multi-site, longitudinal, observational study of idiopathic/isolated rapid eye movement sleep behavior disorder
Journal article   Open access   Peer reviewed

The North American Prodromal Synucleinopathy study: protocol for a multi-site, longitudinal, observational study of idiopathic/isolated rapid eye movement sleep behavior disorder

Miranda M Lim, Lee E Neilson, Jonathan E Elliott, Bianca Hoang-Dang, Jessica R Locke, Hannah Cunningham, Jessica Brewer, Laura Dennis, Laura Dovek, Amélie Pelletier, …
Sleep advances, Vol.7(1), zpag007
2026
DOI: 10.1093/sleepadvances/zpag007
PMCID: PMC12920605
PMID: 41725984
url
https://doi.org/10.1093/sleepadvances/zpag007View
Published (Version of record) Open Access

Abstract

Isolated/idiopathic rapid eye movement sleep behavior disorder (iRBD) is a usually prodromal manifestation of neurodegenerative disorders with α-synuclein pathology: Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Clinical trials in the iRBD population face substantial barriers: limited access to well-characterized cohorts, inconsistent assessment protocols across centers, and the absence of validated biomarkers of disease burden. The North American Prodromal Synucleinopathy (NAPS) Consortium was established to address these challenges and facilitate clinical trials for neuroprotective therapies targeting synucleinopathy at the earliest known stages. In this multi-site, longitudinal, observational study, nine academic centers across North America will enroll and follow over 500 individuals with iRBD from existing sleep centers. Sixty control participants, matched for age, sex, and race will also be recruited. A harmonized protocol—including a standardized clinical battery assessing motor, cognitive, autonomic, psychiatric, sensory, and sleep function; structured diagnostic adjudication; biospecimen collection; and centralized analysis of both polysomnography and neuroimaging data—is outlined herein and reflects NAPS Stage 2. Each participants completes these assessments annually, and are replaced in the event of phenoconversion. By unifying assessments and expanding geographic reach, NAPS lays the groundwork for efficient, well-powered clinical trials designed to delay or prevent progression of iRBD to overt PD, DLB, or MSA—ultimately enabling earlier, more effective therapeutic intervention for neurodegenerative disease. Registered at clinicaltrials.gov (NCT05826457).
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