Clinical trial NCT04048603: Search for Biomarkers of Neurodegenerative Diseases in Idiopathic REM Sleep Behavior Disorder
Official title: A 7-year Prospective Study of Idiopathic REM Sleep Behavior Disorder Cohort in Chinese Population: Determining the Optimal Characteristics of Biomarkers to Predict Neurodegenerative Diseases
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: REM Sleep Behavior Disorder
Neurodegeneration
Keywords: REM sleep behavior disorder
Neurodegeneration
α-synucleinopathy
Prodromal markers
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
First posted: 2019-08-07
Enrollment: 182
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The participants in this proposed study will be recruited from our on-going cohort of RBD and control

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.

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.

Primary outcomes:
measure: The overall conversion rate of iRBD to neurodegenerative diseases
timeFrame: Changes from baseline to 7 year follow up
Secondary outcomes:
measure: Changes of the likelihood ratio of probability of prodromal Parkinson's disease in each individual
timeFrame: Baseline and 7 year
measure: Conversion rate of iRBD to neurodegenerative diseases in patients with high and low likelihood ratio of probability of prodromal Parkinson's disease in each individual
timeFrame: Changes from baseline to 7 year follow up
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Department of psychiatry, Faculty of Medicine, The Chinese University of Hong Kong
Study officials:
affiliation: Chinese University of Hong Kong
name: Jihui Zhang, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Chinese University of Hong Kong
name: Yun Kwok Wing, MBChB
role: STUDY_DIRECTOR
affiliation: Chinese University of Hong Kong
name: Yaping Liu, PhD
role: STUDY_DIRECTOR
affiliation: Chinese University of Hong Kong
name: Siu Ping Lam, MBChB
role: STUDY_DIRECTOR
affiliation: The University of Hong Kong
name: Shirley Xin Li, PhD
role: STUDY_DIRECTOR
affiliation: Chinese University of Hong Kong
name: Vincent Chung Tong Mok, MBChB
role: STUDY_DIRECTOR
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