Prodromal Markers in Recurrent Dream Enactment Behaviors Without REM Sleep Without Atonia

Striatal Dopamine Transmission and Prodromal Markers of α-synucleinopathy Neurodegeneration in Recurrent Dream Enactment Behaviors Without REM Sleep Without Atonia: a Case-control Study

REM sleep behavior disorder is a novel and distinct parasomnia characterized by recurrent dream enactment behaviors (DEBs) and REM sleep without atonia (RSWA) during polysomnographic assessment, with a male predominance and typical onset age at early 60's. The majority of patients with idiopathic RBD (iRBD) will eventually develop α-synucleinopathy, for instance Parkinson's disease (PD). Thus, iRBD has been considered as a highly specific precursor of α-synucleinopathy-related neurodegeneration. Recently, increasing studies have found that some participants present with only RSWA or DEBs (but without sufficient RSWA), which does not meet the diagnostic criteria for RBD. It has been suggested that these participants with subclinical features (either DEBs or RSWA) might represent a condition known as prodromal RBD. Several emerging evidence, including our own study, have implied a link between isolated RSWA (RSWA without DEBs) and markers of α-synucleinopathy-related neurodegeneration. However, it is still unclear whether the other condition related to RBD, i.e. recurrent DEBs but without sufficient RSWA, is related to a certain degree of α-synucleinopathy. In this regard, the novel concept of recurrent DEBs but without sufficient RSWA, also termed as prodromal/isolated RBD by some researchers, requires validation by further evidence in terms of clinical feature and neurodegenerative prodromal markers perspectives.

Study Overview

• Status: Recruiting
• Conditions: REM Sleep Behavior Disorder
• Intervention / Treatment: Other: No intervention

Detailed Description

This proposed study is a case-control study, which aims to determine whether recurrent DEBs but without sufficient RSWA represents an early stage of α-synucleinopathy. The investigators will recruit 62 participants with recurrent DEBs but without sufficient RSWA and their age-, sex- matched controls from the community and on-going projects. All participants will undergo clinical interview, comprehensive measures of prodromal markers of neurodegeneration (including excessive daytime sleepiness, olfactory functioning, constipation, erectile dysfunction, urinary dysfunction, symptomatic hypotension, depression, and clinical motor markers) as suggested by the International Parkinson and Movement Disorder Society (MDS) research criteria. In addition, a subset of the sample (n = 26 in each group) will undergo the triple-tracer positron emission tomography/computed tomography (PET/CT) imaging protocol of 18F-DOPA, to determine dopamine functions in putamen. This proposed study will help to disentangle the core features of RBD and validate the concept of prodromal RBD with reference to prodromal markers related to α-synucleinopathy neurodegeneration.

• Study Type: Observational
• Enrollment (Estimated): 102

Contacts and Locations

• Study Contact: Name: Steven Chau, Doctor; Phone Number: 852-39197792; Email: stevenwaihochau@cuhk.edu.hk
• Study Contact Backup: Name: Mandy Yu, MPH; Phone Number: 852-39197593; Email: mandyyu@cuhk.edu.hk

Study Locations

• Hong Kong
  • Shatin, Hong Kong
    • Recruiting
    • Shatin Hospital
    • Contact: Mandy Yu, MPH; Phone Number: 852-26367593; Email: mandyyu@cuhk.edu.hk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

The recruiting ability for the current study is further evidenced by a series of studies and publications in the past few years. For example, in our ongoing case-control family study, the investigator have recruited 89 control proband and 64 their FDRs who have all underwent v-PSG (Liu et al, Annals of Neurology 2019). By now, the investigator have expanded the number to 103 control probands and 91 FDRs. The investigator believe that this cohort will help us to recruit sufficient number of control subjects in this proposed study.

Description

Inclusion Criteria:

• Age between 45 and 65 years old
• RBDQ-HK behavior factor greater > 8
• Recurrent DEBs by interview and/or video analysis
• Absence of sufficient RSWA

Exclusion Criteria:

• Age- and sex- matched with cases
• RBDQ-HK behavior factor < 8
• No DEBs by either interview or video analysis
• Absence of sufficient RSWA

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of Parkinson's Disease	overall probability of prodromal PD based on the MDS research criteria for prodromal PD	1 year

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong
• Investigators: Principal Investigator: Yun Kwok Wing, Professor, Chinese University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2022
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: December 21, 2021
• First Submitted That Met QC Criteria: April 25, 2022
• First Posted (Actual): April 29, 2022

Study Record Updates

• Last Update Posted (Actual): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Prodromal markers; Striatal dopamine; REM sleep without atonia
• Additional Relevant MeSH Terms: Nervous System Diseases; Sleep Wake Disorders; Parasomnias; REM Sleep Parasomnias; Mental Disorders; REM Sleep Behavior Disorder
• Other Study ID Numbers: RGC14107520

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: In this stage, we didn't decide which information of IPD will be share with other researchers

Drug and device information, study documents

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