Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05353868 |
| Other study ID # |
NTEC-2021-0614 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
February 1, 2022 |
| Est. completion date |
June 30, 2024 |
Study information
| Verified date |
April 2024 |
| Source |
Chinese University of Hong Kong |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The aim of this study is to correlate baseline gut microbiota features and the progression of
neurodegeneration in the established cohort of patients with early Parkinson's disease.
Description:
Alpha-synucleinopathy is a major group of neurodegenerative diseases that include Parkinson's
disease and Dementia of Lewy bodies. They are known to have a long preclinical development,
and prodromal markers that indicate the onset of early phase of the neurodegenerative process
present along the way. Among the markers, idiopathic REM sleep behavior disorder (iRBD), a
distinct form of parasomnia characterised by the presence of dream-enactment behaviour and
REM sleep without atonia, represent a particularly high conversion likelihood that makes it a
de facto precursor of clinical diseases (14 years conversion rate >95%). Thus, RBD serves as
an exclusive opportunity for us to study the early-stage progression of α-synucleinpathies,
and a window for early neuroprotective intervention.
In the context of α-synucleinopathic neurodegenerative diseases, high prevalence of
gastrointestinal dysfunction and the presence of alpha-synuclein aggregates in the enteric
nervous system at the early stage of disease have been found. These early findings were
embedded in an influential Braak's hypothesis that the process of neurodegeneration can be
started by 'unknown pathogen' from gut and spread to the central nervous system via vagus
nerve in a caudal-rostral manner (medulla->pon->mid/forebrain->cortex). Human data showed
that microbiome composition in patient with Parkinson's disease is different from control.
The relative abundance of certain microbiotas, such as Enterobacteriaceae, have been shown to
be associated with the severity of motor symptoms in patients with Parkinson's disease. It is
hypothesized that microbiota dysbiosis resulting in a pro-inflammatory gut environment, which
in turn create excessive oxidative stress and trigger alpha-synuclein misfolding cascade.
While available evidence suggests that gut-brain hypothesis potentially plays a role in the
disease process of α-synucleinopathies, the exact detail of microbiota involvement will need
further examination. The key question of whether microbiota dysbiosis is driving or being
driven by the process of neurodegeneration, need to be answered by prospective empirical
studies that examine the longitudinal course of neurodegeneration from early to late stage,
and to relate such course with the corresponding dynamic profile of the subjects' gut
microbiota composition. Most of the available studies on this subject were cross-sectional
studies that based on patients with Parkinson's disease, the terminal stage of the
neurodegenerative process. There has been only two studies that include RBD patients,
suggesting some alteration of microbiota happens in RBD stage already, but the number of RBD
subjects included was small (n = 21 and 26), and there was no follow-up data (10, 11). In
other words, there is no study that can answer such question at the moment. This remarkable
gap in literature probably reflects two major obstacles researchers would face in planning
such study: the difficulties in identifying and recruiting subjects with early-stage
α-synucleinopathies, and the need for sufficient follow-up period to unfold the
neurodegeneration process. In this regard, the investigators investigated gut microbiota
composition in our established cohort of RBD and RBD family. Preliminary finding indicated
gut dysbiosis has already occurred at or likely before the onset of RBD, at an even earlier
stage of synucleinopathy (i.e., high-risk relatives of RBD). For example, consistent
overabundance of Ruminococcaceae UCG-002 were found in RBD relatives, patient with RBD and
early PD, as compared with controls.
In this study, the investigators will perform 3-year follow-up of clinical assessments and
gut microbiota measurement. The investigators aim to correlate baseline gut microbiota
features and the progression of neurodegeneration, e.g., emerged autonomic dysfunctions,
phenoconversion, in the established cohort of patients with early Parkinson's disease,
idiopathic RBD, first-degree relatives (FDRs) of patients with iRBD and healthy controls.
Besides, the investigator will examine the associations between long-term gut microbiota
changes and progression of neurodegenerative biomarkers and compare the long-term changes of
gut microbiota between controls and different early stages of α-synucleinopathies.
