Search for Biomarkers of Neurodegenerative Diseases in Idiopathic REM Sleep Behavior Disorder

NCT ID: NCT04048603

Last Updated: 2021-08-06

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 182 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-05-15
• Study Completion Date: 2022-10-01

Brief Summary

This study is a prospective study with a mean of 7-year follow-up interval, aims to monitor the progression of α-synucleinopathy neurodegeneration by the evolution of prodromal markers and development of clinical disorders in patients with idiopathic REM Sleep Behavior Disorder (iRBD) and healthy controls.

Detailed Description

REM sleep behavior disorder (RBD) is a parasomnia characterized by dream enactment behaviors and REM sleep without muscle atonia (excessive EMG activity) during REM sleep.Increasing studies revealed that iRBD eventually converts to α-synucleinopathy, such as Parkinson's disease (PD), dementia with Lewy Bodies (DLB), and multiple system atrophy (MSA). Recent studies reported that over 80% of patients with iRBD eventually developed neurodegeneration at a mean interval of 14 years after iRBD onset or diagnosed. Thus, iRBD is regarded as a precursor of α-synucleinopathies. In addition to iRBD, a large series of other non-motor symptoms also present before the emergence of typical motor symptoms of PD, including autonomic dysfunction, olfactory loss, color vision impairment, neurocognitive impairment,neuroimaging of dopamine dysfunction, daytime sleepiness, and psychiatric disorders. In recent years, several longitudinal studies have found that patients with iRBD with a higher rate of these markers may have a faster progression of neurodegeneration. On the other hand, a variety of external risk factors of PD including environmental toxic exposure, lifestyle factors, and some medications have long been recognized, which affect numerous fundamental cellular processes by interaction with genetic predisposition.

However, several knowledge gaps still need further studies to uncover. First, few studies have explored the predictive value of dynamic change of biomarkers in prodromal stage of PD. Second, few previous prospective studies also employed a control group to compare the change of these prodromal markers between patients and healthy controls over time. Third, as some of previous studies employed a retrospective study design, potential recall bias may contaminate the results. Moreover, the sample sizes of most previous studies investigating biomarkers were relative small (n < 80) and follow-up durations in most study are relatively short, which may have limited the statistical power to detect the risk factors with mild to moderate effect size. Finally, as previous reported longitudinal studies of iRBD mainly focused on Caucasian or other ethnic groups, there is only limited data about neurodegenerative biomarkers in Chinese iRBD. In conclusion, prospective longitudinal studies with larger sample size, regular follow-up, and relative long follow-up duration are needed to better map the progression of neurodegeneration.

Conditions

REM Sleep Behavior Disorder; Neurodegeneration

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

idiopathic REM sleep behavior disorder

Subjects with the diagnosis of idiopathic REM sleep behavior disorder

No interventions assigned to this group

Controls without iRBD

Healthy controls without the diagnosis of idiopathic REM sleep behavior disorder

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

for iRBD at baseline:

1. Fulfilling the diagnostic criteria for iRBD. As patients with iRBD were recruited during a long period, the diagnosis of RBD was based on ICSD and ICSD-2 (before 2014), and ICSD-3 (2014 and thereafter) criteria. The diagnosis for all patients were confirmed by video-PSG. In summary, patient diagnosed with RBD should present excessive EMG activity during REM sleep on video-PSG assessment and report a history of repeated dream enactment behaviors;

2. Having neurocognitive test and neurological examination since 2008;

3. Free of neurodegenerative diseases at the last visit.

for controls without iRBD at baseline:

1. Age- and sex- matched with patients with iRBD;

2. Free of narcolepsy and other neurological diseases;

3. Without any RBD features as confirmed by both clinical history and video-PSG;

4. Without neurodegenerative diseases;

5. Having neurocognitive test and neurological examination at baseline.

Exclusion Criteria

1. Patients with narcolepsy;

2. Patients with known neurodegenerative diseases;

3. Pseudo-RBD (e.g., RBD symptoms were eliminated after severe obstructive sleep apnea had treated with continuous positive airway pressure therapy.);

4. Early-onset RBD (e.g., before the age of 50 years old) which might have a different pathogenesis from iRBD.

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Chinese University of Hong Kong

OTHER

Sponsor Role: lead

Responsible Party

Dr. Zhang Jihui

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jihui Zhang, PhD

Role: PRINCIPAL_INVESTIGATOR

Chinese University of Hong Kong

Yun Kwok Wing, MBChB

Role: STUDY_DIRECTOR

Chinese University of Hong Kong

Yaping Liu, PhD

Role: STUDY_DIRECTOR

Chinese University of Hong Kong

Siu Ping Lam, MBChB

Role: STUDY_DIRECTOR

Chinese University of Hong Kong

Shirley Xin Li, PhD

Role: STUDY_DIRECTOR

The University of Hong Kong

Vincent Chung Tong Mok, MBChB

Role: STUDY_DIRECTOR

Chinese University of Hong Kong

Locations

Department of psychiatry, Faculty of Medicine, The Chinese University of Hong Kong

Hong Kong, , Hong Kong

Site Status: RECRUITING

Countries

Hong Kong

Central Contacts

Jihui Zhang, PhD

Role: CONTACT

jihui.zhang@cuhk.edu.hk

(852)39197647

Facility Contacts

Jihui Zhang, PhD

Role: primary

Other Identifiers

2018.641

Identifier Type: -

Identifier Source: org_study_id