North American Prodromal Synucleinopathy Consortium Stage 2 (NAPS2)

This study will enroll participants with idiopathic REM sleep behavior disorder (RBD) and healthy controls for the purpose of preparing for a clinical trial of neuroprotective treatments against synucleinopathies.

Study Overview

• Status: Recruiting
• Conditions: Parkinson Disease; Multiple System Atrophy; REM Sleep Behavior Disorder; Dementia With Lewy Bodies; REM Sleep Parasomnias; Lewy Body Dementia

Detailed Description

REM sleep behavior disorder (RBD) is a disorder where people act out their dreams. People with RBD often, but not always, develop Parkinson's Disease, dementia with Lewy bodies, multiple system atrophy, or other neurodegenerative diseases of the synucleinopathy type.

The North American Prodromal Synucleinopathy Consortium Stage 2 (NAPS2) was formed with the purpose of enrolling participants with RBD, in anticipation of a future clinical trial of a neuroprotective trreatment against synucleinopathies. The NAPS Consortium will collect standardized clinical assessments, biofluids, and neuroimaging data. The RBD group will also undergo two overnight sleep studies. Some of this data will be used to develop biomarkers for synucleinopathies in the prodromal (presymptomatic) stage as well as a trial-ready registry of participants.

RBD group procedures include a clinical assessment, questionnaires, blood draw, neuroimaging (MRI and DaTscan), polysomnogram (sleep study), and optional lumbar puncture.

Control group procedures include a clinical assessment, questionnaires, blood draw, neuroimaging (MRI), and lumbar puncture.

• Study Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

• Study Contact: Name: Jennifer McLeland, PhD; Phone Number: 314-747-3819; Email: mclelandj@wustl.edu
• Study Contact Backup: Name: Leah Taylor; Phone Number: 314-747-7297; Email: ltaylor24@wustl.edu

Study Locations

• Canada
  • Quebec
    • Montréal, Quebec, Canada, H4A 3J1
      • Recruiting
      • McGill University Health Centre Research Institute
      • Contact: Amelie Pelletier, PhD; Phone Number: 2528 514-338-2222; Email: amelie.pellletier@mail.mcgill.ca
      • Principal Investigator: Ron Postuma, MD
• United States
  • California
    • Los Angeles, California, United States, 90095
      • Not yet recruiting
      • University of California Los Angeles
      • Contact: Adreanne Rivera; Phone Number: 310-794-0213; Email: UCLAnaps@mednet.ucla.edu
      • Principal Investigator: Alon Avidan, MD, MPH
    • Redwood City, California, United States, 94063
      • Not yet recruiting
      • Stanford University
      • Principal Investigator: Mitch Miglis, MD
      • Contact: Jordan Seliger; Phone Number: 650-460-9260; Email: jseliger@stanford.edu
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University
      • Contact: Amanda Goodwin; Email: amanda.christine.goodwin@emory.edu
      • Principal Investigator: Dan Huddleston, MD
      • Principal Investigator: Don Bliwise, PhD
  • Massachusetts
    • Boston, Massachusetts, United States, 02145
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Amy Wang; Email: jwang133@mgh.harvard.edu
      • Principal Investigator: Aleks Videnovic, MD, MSc
  • Minnesota
    • Minneapolis, Minnesota, United States, 55414
      • Recruiting
      • University of Minnesota
      • Contact: Carly Schroeder, BS; Phone Number: 612-626-6499; Email: schroedc@umn.edu
      • Principal Investigator: Michael Howell, MD
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic Rochester
      • Contact: Ruth Kraft; Phone Number: 507-422-9780; Email: rbd@mayo.edu
      • Principal Investigator: Brad Boeve, MD
      • Principal Investigator: Erik St. Louis, MD
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine
      • Contact: Maggie Zangrilli; Phone Number: 314-362-0828; Email: zangrillim@wustl.edu
      • Contact: Jennifer McLeland, PhD; Phone Number: 314-747-3819; Email: mclelandj@wustl.edu
      • Principal Investigator: Yo-El Ju, MD, MCSI
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health Sciences University
      • Principal Investigator: Miranda Lim, MD, PhD
      • Contact: Laura Dennis; Email: NAPS@ohsu.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Idiopathic REM sleep behavior disorder, adults.

Description

Inclusion Criteria for RBD Group

1. Polysomnogram-confirmed RBD by ICSD-3 criteria
2. Capable of providing informed consent at time of study enrollment
3. Age > 18 years

Exclusion Criteria for RBD Group

1. Diagnosis of PD, dementia of any type, or MSA unless previous participant in NAPS1.
2. Narcolepsy-associated RBD
3. RBD secondary to any known cause except prodromal synucleinopathy.
4. Participation in a clinical trial, except by specific permission by the Executive Committee
5. In the opinion of the investigator, the individual has a clinically significant uncontrolled medical condition that would impede safe completion of the study protocol

Inclusion Criteria for Control Group

1. Ability to provide written consent
2. Age > 18 years
3. Must meet age, sex, and race matching criteria per the Data Management and Statistical core recommendations for the site
4. Must be willing to undergo all testing procedures, including neuroimaging and lumbar puncture.
5. Normal capacity to perform complex activities of daily living independently based on informant or physician report

Exclusion Criteria for Control Group

1. History of dream enactment behavior to suggest RBD
2. Parkinsonism, MSA, dementia, or mild cognitive impairment
3. Active central nervous system, systemic, psychiatric condition or use of psychoactive medication that would adversely affect cognitive, neuropsychiatric, motor, or autonomic functioning.
4. Contraindications to complete MRI.
5. Contraindications to lumbar puncture.
6. Participation in a clinical trial, except by specific permission by the Executive Committee
7. In the opinion of the investigator, the individual has a clinically significant uncontrolled medical condition that would impede safe completion of the study protocol

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
RBD Group; Clinical observation involving annual visits to a study site for up to 5 years.
Control Group; Clinical observation involving annual visits to a study site for up to 5 years.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prodromal Synucleinopathy Rating Scale	Rating scale combining neurocognitive battery, motor, autonomic, olfaction, color vision functions. Global score range 0-3, with higher score indicating greater symptoms of synucleinopathy.	up to 5 years

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: Massachusetts General Hospital; Mayo Clinic; McGill University; University of California, Los Angeles; National Institute of Neurological Disorders and Stroke (NINDS); Emory University; National Institutes of Health (NIH); National Institute on Aging (NIA); Oregon Health and Science University; Stanford University; University of Minnesota
• Investigators: Principal Investigator: Yo-El Ju, MD, MCSI, Washington University School of Medicine; Principal Investigator: Brad Boeve, MD, Mayo Clinic; Principal Investigator: Ron Postuma, MD, McGill University

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2022
• Primary Completion (Estimated): May 1, 2025
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: February 8, 2023
• First Submitted That Met QC Criteria: April 20, 2023
• First Posted (Actual): April 24, 2023

Study Record Updates

• Last Update Posted (Actual): December 12, 2023
• Last Update Submitted That Met QC Criteria: December 11, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Sleep Wake Disorders; Neurocognitive Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Proteostasis Deficiencies; Autonomic Nervous System Diseases; Primary Dysautonomias; Hypotension; Parkinson Disease; Mental Disorders; Parasomnias; Dementia; Lewy Body Disease; Multiple System Atrophy; Shy-Drager Syndrome; Synucleinopathies; REM Sleep Behavior Disorder; REM Sleep Parasomnias
• Other Study ID Numbers: 1234567; U19AG071754 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified subject level data will be shared upon approved data request. This project will develop a large database of potential neurocognitive, neuroimaging, genetic, and polysomnographic biomarkers in rapid eye movement sleep behavior disorder (RBD), as well as a biobank of blood, DNA, RNA, and cerebrospinal fluid. A large part of the clinical battery is the Uniform Dataset version 3, will be uploaded to the National Alzheimer's Coordinating Center (NACC). Biofluid samples will be banked at the National Cell Repository for Alzheimer's Disease (NCRAD). Genetic data will be submitted to the National Institute on Aging Genetics of Alzheimer's Disease Data Storage (NIAGADS). Brain MRI and DaTscan imaging data will be uploaded to the Laboratory of NeuroImaging (LONI). Polysomnogram data will be uploaded to the National Sleep Research Resource (NSRR).
• IPD Sharing Time Frame: Updated datasets will be made available after completion of each semiannual data cleaning and data freeze. De-identified data will be available for at least the duration of the NAPS2 study.
• IPD Sharing Access Criteria: The NAPS2 Administrative Core will receive, process, and track all requests for data/biospecimens. All requests will be reviewed and tracked per the current NAPS Data Access Policy (https://www.naps-rbd.org/resources at the bottom of the webpage) at the time of request. Approved requests will be filled using data that has been de-identified.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No