NAPS: prodromal synucleinopathy consortium

The research record

This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".

Who

The North American Prodromal Synucleinopathy (NAPS) Consortium. Both registry records (stage 1, NCT03623672; stage 2, NCT05826457) name Washington University School of Medicine as lead sponsor. Stage 2 lists Mayo Clinic, the University of Minnesota, UCLA, McGill, Emory, Massachusetts General Hospital, Stanford and Oregon Health and Science University as sites, with NINDS, NIA and NIH as collaborators. Ronald Postuma is a named author on consortium papers; the 2026 protocol paper is led by Miranda Lim.

What happened

REM sleep behaviour disorder (RBD) is a sleep disorder in which people act out dreams. Most people with the polysomnogram-confirmed form later develop Parkinson's or a related disease (landmark 221). That makes them the best-defined group for testing a drug before motor symptoms, along with the research criteria in landmark 222.

• Stage 1. Registered 9 August 2018 and started 29 August 2018 (NCT03623672); the record lists 500 as the planned enrolment, was last updated in November 2024, and shows an estimated completion of July 2026. A 2024 sub-study reports enrolment from August 2018 to at least April 2021. One validation paper used 261 participants.
• Stage 2 (NAPS2). Started 12 August 2022; observational, case-control; the registry aims for 500 people (RBD group plus controls), annual visits for up to 5 years. The 2026 protocol paper (Lim et al., Sleep Advances) says over 500 people with isolated RBD plus 60 matched controls across nine centres, replaced if they develop disease. Status "enrolling by invitation" (record verified May 2026). Primary completion is estimated at 1 May 2027 and study completion at 1 May 2028.
• Main measure. A Prodromal Synucleinopathy Rating Scale, a 0 to 3 composite of thinking, movement, autonomic, smell and colour-vision measures; higher means more synuclein-disease signs.
• Stated purpose. To prepare for a future trial of neuroprotective treatment.

Why it moved us toward a cure

A prevention trial needs to know how fast the pre-motor group changes, which measures move, and how many people are needed. NAPS is meant to supply that. The first registered prevention-style trial in this project, PRISMS (landmark 225), draws on the same patient group (the link is my reading; the registry record for PRISMS does not name NAPS).

Outcome

Open. No trial results yet; the stage 2 data are not due until 2027–28. Whether the composite scale will serve as a trial endpoint: unknown.

Sources

• ClinicalTrials.gov NCT05826457, NAPS2
• Choudhury et al., Neurology 2024, RBD Symptom Severity Scale in NAPS, DOI 10.1212/WNL.0000000000208008
• Elliott et al., Sleep 2024, NAPS neurotrauma sub-study, DOI 10.1093/sleep/zsae007 (enrolment dates)
• ClinicalTrials.gov NCT03623672, NAPS stage 1
• Lim et al., Sleep Adv 2026;7(1):zpag007, DOI 10.1093/sleepadvances/zpag007, PMID 41725984 (NAPS protocol; abstract via Europe PMC)
• Not yet verified: the number enrolled in stage 1 and 2; funders beyond the registry's NIH list; whether PRISMS uses NAPS sites. The Choudhury 2024 paper has an erratum (Neurology 2024;102:e209355) whose content was not read.