Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03595475
Other study ID # RGC14172917
Secondary ID
Status Completed
Phase
First received
Last updated
Start date October 1, 2017
Est. completion date March 31, 2022

Study information

Verified date October 2022
Source Chinese University of Hong Kong
Contact n/a
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial Summary

REM sleep behavior disorder (typical or 'idiopathic' RBD, iRBD) is a novel and distinct parasomnia characterized by recurrent dream enactment behaviours and polysomnographic features of loss of normal REM-sleep related muscle atonia, with a male predominance commonly occurring at the age of 60's. A majority of the patients with iRBD will eventually develop α-synucleinopathy (e.g., Parkinson's disease). On the other hand, growing evidence reveals a specific group of psychiatric patients demonstrating comparable clinical RBD features (pRBD) (e.g., abnormal REM-related electromyographic (EMG) activities) as found in typical iRBD, but with less male predominance occurring at the age of mid 40's to early 50's. Although recent findings from both cross-sectional and prospective studies have suggested that pRBD is likely to be a persistent parasomnia with close association with clinical and neuroimaging biomarkers related to neurodegeneration, the nosology of the development of RBD symptoms among patients with psychiatric disorders, notably major depressive disorder, remains unclear as to whether they are simply antidepressants related, or represent a part of the early phase of α-synucleinopathy neurodegeneration. Family studies on iRBD have confirmed a significant familial aggregation of iRBD with a higher rate of RBD cases and presence of prodromal neurodegenerative biomarkers (e.g. tonic EMG activity during REM sleep, constipation, and motor function impairments) of α-synucleinopathy neurodegeneration among first-degree relatives (FDRs) of patients with iRBD. Thus, the investigators propose this family study to examine the following hypotheses: 1) FDRs of patients with pRBD have a higher rate of RBD symptoms and its core features when compared to FDRs of controls with and without psychiatric disorders; 2) FDRs of pRBD are more likely to exhibit the features associated with prodromal markers of α-synucleinopathy neurodegeneration when compared with FDRs of controls with and without psychiatric disorders; 3) FDRs of patients with pRBD have a higher rate of α-synucleinopathy neurodegeneration when compared with FDRs of controls with and without psychiatric disorders. A total of 176 FDRs from each group (e.g., pRBD cases, psychiatric controls, and healthy controls) will be recruited to undergo a face-to-face clinical interview and a series of assessments on prodromal markers of Parkinson's diseases (as according to the International Parkinson and Movement Disorder Society research criteria) respectively. All FDRs with possible RBD and a subset of FDRs without possible RBD will be invited to undergo one-night video-polysomnographic assessment to confirm the clinical diagnosis of RBD and to assess the abnormal REM-related EMG muscle activities.


Description:

REM sleep behavior disorder (RBD) is a novel REM sleep parasomnia characterized by dream enacting behaviors and sleep-related injuries. Ample evidences have suggested that idiopathic RBD (iRBD) is a precursor of α-synucleinopathy neurodegeneration (e.g. Parkinson's disease, PD) in which dopamine dysfunction is one of the core pathophysiologies. In recent decade, our group has identified a cohort of patients with psychiatric disorders (mainly major depressive disorder, MDD) comorbid with RBD (pRBD). While there was a postulation that RBD symptoms in this psychiatric population may simply be side effects of antidepressant medication (by enhancing REM-sleep related muscle activity), accumulating evidence from case-control and prospective cohort studies suggested that pRBD is only partially explained by antidepressant usage and is better considered as a variant of typical iRBD in terms of comparable clinical presentation with typical iRBD and its close association with neurodegenerative markers. Nonetheless, more evidence is needed to substantiate that pRBD is a distinct diagnostic entity rather than a symptom secondary to antidepressant use. In this study, the investigators will employ genetic epidemiology approach to: 1) determine the familial genetic contribution; 2) search for biomarkers and endophenotypes; and 3) validate the diagnostic entity of a disease. This proposed study will enrich the limited scientific literature of the potential pathogenesis of pRBD and its relationship with α-synucleinopathy. In addition, the understanding of psychiatric disorders, notably MDD, is often limited by its heterogeneity. Our proposed study will, by determining the familial aggregation of pRBD, help us to identify certain subtype of the psychiatric populations who may likely harbour an underlying neurodegenerative basis. By using a family study design, a number of important aspects with regard to the pathogenesis of pRBD will be answered. First, if first-degree relatives (FDRs) of patients with pRBD have a higher rate of possible RBD or clinical diagnosis of RBD (as confirmed by video-polysomnography) as well as the presence of neurodegenerative diseases when compared with FDRs of controls, it will substantiate the argument that pRBD is not merely a side effect of antidepressants but rather harbouring a familial and genetic predisposition to RBD and, ultimately α-synucleinopathy neurodegeneration. Second, the determination of biomarkers of neurodegeneration among unaffected FDRs of patients with pRBD will also help to identify high-risk individuals for clinical intervention and prevention. Third, the calculation of heritability will help to delineate to which extent the additive genetic contribution is responsible for the variance of pRBD phenotypes. Finally, the findings from this proposed study will be compared with our on-going family study of typical iRBD to determine the extent to which iRBD and pRBD are similar or different to each other in terms of genetic and familial associations. In this proposed study, the investigators hypothesize that: 1. FDRs of patients with pRBD have a higher rate of RBD symptoms and its core features compared with FDRs of controls; 2. The unaffected FDRs of patients with pRBD are more likely to exhibit the features associated with prodromal markers of Parkinson's disease compared with FDRs of controls; 3. FDRs of patients with pRBD have a higher rate of Parkinson's disease (and other α-synucleinopathy neurodegeneration) compared with FDRs of controls.


Recruitment information / eligibility

Status Completed
Enrollment 408
Est. completion date March 31, 2022
Est. primary completion date November 30, 2021
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 40 Years and older
Eligibility Inclusion Criteria: - Age- and sex- matched with pRBD proband; - Without lifetime psychiatric disorder according to Structural Clinical Interview for DSM-IV Disorders (SCID); - Free of narcolepsy and other neurological diseases; - Absence of any RBD features as based on RBDQ-HK and v-PSG; - free of neurodegenerative diseases. Exclusion Criteria: - Not Chinese or aged under 40 years old; - Refuse to participate in this study; - without a biological relationship with proband.

Study Design


Locations

Country Name City State
Hong Kong The Chinese University of Hong Kong Hong Kong
Hong Kong Shatin Hospital Shatin

Sponsors (1)

Lead Sponsor Collaborator
Chinese University of Hong Kong

Country where clinical trial is conducted

Hong Kong, 

Outcome

Type Measure Description Time frame Safety issue
Primary Prevalence of possible REM Sleep Behavior Disorder The prevalence of possible REM Sleep Behavior Disorder based on the self-reported/proxy-reported REM Sleep Behavior Disorder symptoms in REM Sleep Behavior Disorder Questionnaire-HK among First Degree Relatives, 17 months
Secondary Percentage of REM-related EMG activity The mean differences in the percentage of REM-related EMG activity among First Degree Relatives in different groups 17 months
Secondary Weighted prevalence of Polysomnography confirmed REM Sleep Behavior Disorder Prevalence of Polysomnography confirmed REM Sleep Behavior Disorder according to ICSD-3 criteria among First Degree Relatives in different groups 17 months
Secondary Recurrence risk of Parkinson's disease Risk of Parkinson's disease and other a-synucleinopathy neurodegeneration based on family history report and face-to-face interview among First Degree Relatives in different groups 17 months
See also
  Status Clinical Trial Phase
Completed NCT03671772 - Progression of Prodromal Markers of α-synucleinopathy Neurodegeneration in the FDRs of Patients With RBD
Recruiting NCT05109364 - Terazosin and Parkinson's Disease Extension Study Phase 2
Recruiting NCT03288909 - Ultra High Field Magnetic Resonance Imaging as a Biomarker for Premotor Parkinson's Disease
Completed NCT04006925 - Treatment of REM Sleep Behavior Disorder (RBD) With Sodium Oxybate Phase 4
Completed NCT03353207 - Striatal Dopamine Transmission in Individuals With Isolated Rapid Eye Movement Sleep With Atonia: a Search for Precursor Biomarker for Neurodegeneration
Completed NCT02824341 - Exploration of the Reward System by Functional MRI in Parkinson's Disease Patients With and Without REM Sleep Behavior Disorder N/A
Recruiting NCT03671798 - Establish a National Registry of REM Sleep Behavior Disorder
Enrolling by invitation NCT01453127 - DaTSCAN Imaging in Aging and Neurodegenerative Disease Phase 4
Terminated NCT02871427 - Open-label Study of Nelotanserin in Lewy Body Dementia With Visual Hallucinations or REM Sleep Behavior Disorder Phase 2
Recruiting NCT03660982 - Familial Aggregation and Biomarkers in REM Sleep Behaviour Disorder.
Completed NCT03255642 - Efficacy and Safety of Melatonin and Clonazepam for IRBD N/A
Recruiting NCT05904717 - Effect of PXS-4728A on Microglia Activation in Participants With Isolated Rapid Eye Movement Sleep Behaviour Disorder Phase 2
Not yet recruiting NCT06140511 - DREAMER - IsolateD REM Sleep Without Atonia as a Risk Factor for REM Sleep Behavior disordER
Recruiting NCT04386317 - Terazosin Effect on Cardiac Changes in Early Parkinson's Disease Phase 2
Enrolling by invitation NCT05514106 - MIBG in Aging and Neurologic Disorders Phase 4
Completed NCT03645226 - Gut Microbiota Across Early Stages of Synucleinopathy: From High-risk Relatives, REM Sleep Behavior Disorder to Early Parkinson's Disease
Recruiting NCT05262543 - PREdictive Risk Factors of Conversion Into Idiopathic RBD. Italian Study
Recruiting NCT04071899 - French Validation of a Severity Scale in REM Sleep Behavior Disorder (SEV-TCSP)
Recruiting NCT04048603 - Search for Biomarkers of Neurodegenerative Diseases in Idiopathic REM Sleep Behavior Disorder
Completed NCT02708186 - Study Evaluating Nelotanserin for Treatment of REM Sleep Behavior Disorder in Subjects With Dementia (DLB or PDD) Phase 2