Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT03353207 |
Other study ID # |
HMRF04153036 |
Secondary ID |
|
Status |
Completed |
Phase |
|
First received |
|
Last updated |
|
Start date |
October 30, 2017 |
Est. completion date |
February 8, 2021 |
Study information
Verified date |
February 2021 |
Source |
Chinese University of Hong Kong |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Observational [Patient Registry]
|
Clinical Trial Summary
Background:
Previous studies have confirmed that most patients with idiopathic REM sleep behaviour
disorder (iRBD) eventually develop neurodegenerative diseases. In addition, REM sleep without
atonia (RSWA), a hallmark of RBD feature, is a significant predictor of development of
neurodegenerative diseases in patients with iRBD. Some preliminary studies have implied that
isolated RSWA in the absence of RBD symptoms may also indicate neurodegeneration. However,
this speculation needs to be confirmed by more refined study with sophisticated measures in
both RSWA and markers of neurodegeneration
Objectives: 1) to determine the differences in striatal dopamine transmission and other
markers of neurodegeneration among individuals with isolated RSWA and healthy controls; 2) to
examine the correlation of severity of RSWA with striatal dopamine transmission.
Design: Case-control study
Setting: Community-based sample
Participants: 1) iRBD first degree relatives with isolated RSWA (n=18) 2) iRBD first degree
relatives without isolated RSWA (n=18) 3) Community-based health controls without isolated
RSWA (n=18)
Main outcome measures:
1. The dopamine transmission as measured by triple-tracer PET/ CT imaging protocol
including 18F-DOPA, 11C-Raclopride and 18F-FDG images;
2. Brain glucose metabolism and neurocognitive measures;
3. Severity of EMG activity during REM sleep
Description:
In the past two decades, a number of studies have confirmed that most patients with
idiopathic RBD will eventually develop neurodegenerative diseases, especially
α-synucleinopathies. Previous studies, including our preliminary data, suggested that RSWA is
a marker of predicting the conversion of neurodegenerative diseases in idiopathic RBD. In
other words, RSWA is an early marker of neurodegeneration in patients with idiopathic RBD.
However, a number of individuals who are absent of any RBD symptoms (including patients with
α-synucleinopathies, also have RSWA, which is described to have isolated RSWA. Only a few
studies have attempted to understand the clinical importance and predictive prognosis of
isolated RSWA. These preliminary studies suggest that isolated RSWA in healthy subjects may
be a silent biomarker of neurodegeneration. However, these preliminary findings need to be
replicated and confirmed by more refined study with dopamine neurotransmission neuroimaging.
This proposed study will enrich the limited scientific literature of the potential
pathogenesis and progression of isolated RSWA. By using an ongoing family study, we have
screened a number of individuals with isolated RSWA, who are the first degree relatives of
patients with RBD and are presumed to have a higher risk of neurodegeneration. Based on the
existing sample, the current study will provide the first neuroimaging data on isolated RSWA
to test the hypothesis that isolated RSWA, even in the absence of RBD symptoms, is an early
marker of neurodegeneration. Individuals with isolated RSWA are expected to show dopamine
dysfunction when compared with individuals without RSWA. If we confirm this hypothesis, the
findings in the current study will extend our understanding of the spectrum of RBD and RSWA.
The potential implication of our findings is that asymptomatic RSWA, especially in the
presence of family history, will harbour the neurodegenerative progression. The results will
pave the way for future prospective follow up to determine the course of neurodegeneration.
From an etiological understanding, it will help to expand the understanding of the evolution
course of synucleinopathy neurodegeneration. From an interventional angle, this study will
have significant implication for developing a longer prevention window for neuroprotective
trial.
The inclusion criteria for the subjects:
iRBD first degree relatives with isolated RSWA
1. First degree relatives of patients with iRBD;
2. Age 45 years or above;
3. Absence of dream enactment behaviors;
4. A total score on REM Sleep Behavior Questionnaire (RBDQ-HK) less than 19, which is the
cut-off suggestive of a diagnosis of RBD;
5. Presence of RSWA as measured by v-PSG; RSWA is defined as the percentage of increased
EMG activity (phasic or tonic) at least 10% during REM sleep for any channel.
6. for those individuals with moderate to severe obstructive sleep apnea (apnea-hypopnea
index, AHI > 15/hour), effective CPAP treatment should be documented and a second night
of V-PSG is required to determine RSWA.
Community-based health controls without isolated RSWA:
1. No family history of RBD;
2. Age- and sex- matched with isolated RSWA subjects
3. Absence of dream enactment behaviors;
4. A score of RBDQ-HK less than 19;
5. Absence of RSWA as measured by v-PSG;
6. for those individuals with moderate obstructive sleep apnea (AHI > 15/hour), effective
CPAP treatment should be documented and a second night of V-PSG is required to determine
RSWA.