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.
