REM Sleep Behavior DisorderNCT03645226
Gut Microbiota Across Early Stages of Synucleinopathy: From High-risk Relatives, REM Sleep Behavior Disorder to Early Parkinson's Disease
An observational study of REM Sleep Behavior Disorder, run by Chinese University of Hong Kong at 2 sites in Hong Kong.
Trial summary
With the global ageing population, neurodegenerative disorders including synucleinopathy are major burdens to patients, carers and society. Synucleinopathy refers to a group of neurodegenerative diseases characterized by abnormal aggregation of alpha-synuclein protein in the central nervous system (CNS). Read more about this study
- Who is it for?
- Ages 40 years and olderHealthy volunteers can take part
- Conditions the study is for
- REM Sleep Behavior Disorder
- What is being tested?
- Colonoscopy
- Type of treatment
- Injection or infusion
- How many people
- 441 participants
- Where
- 2 sitesHong Kong
- Study dates
- 6 May 2018to 29 Mar 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: In the case-control study, we will recruit 7 groups of subjects, which represent different stages of Parkinson's disease, namely patients with PD (Braak's stages 3 or 4) without dementia, patients with iRBD (Braak's stage 2), first degree relatives of iRBD patients (Braak's stage 0 or 1), healthy controls (Braak's stage 0). In the familial study, another 3 groups of subjects will be recruited to understand the genetic and environmental influences on differential microbiotas, including spouses of iRBD, spouses of healthy controls and first degree relatives of healthy controls. We will document the cohabiting status and contact frequency among family members within the same family and excluded FDRs who are cohabiting with the proband or spouses who are not cohabiting with the proband. In addition, we will also recruit FDRs and spouses with and without biomarkers of neurodegeneration (such as constipation).
Who may be able to join
- fulfill the groups criteria
Who cannot join
- Presence of narcolepsy and other neurodegenerative diseases (except for PD group) that may give rise to RBD and RWSA;
- A total score of the MOCA ≤ 22 and the CDR ≥ 1, indicating dementia;
- The use of probiotics or antibiotics within three months prior to sample collection;
- Pre-existing gastrointestinal diseases, such as inflammatory bowel disease.
Trial locations and contacts
2 sites in 1 country.
Hong Kong2 sites
The Chinese University of Hong Kong
Hong Kong
Shatin Hospital
Shatin
About this study
With the global ageing population, neurodegenerative disorders including synucleinopathy are major burdens to patients, carers and society. Synucleinopathy refers to a group of neurodegenerative diseases characterized by abnormal aggregation of alpha-synuclein protein in the central nervous system (CNS). Common examples of synucleinopathy are Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Among all the premotor clinical markers that have been identified, a sleep disorder known as REM sleep behavior disorder (RBD) is associated with the highest likelihood ratio of developing PD. In addition, it has been shown that almost all RBD patients (over 80%) eventually developed neurodegenerative diseases after 14 years follow-up.
Gut microbiota and synucleinopathy In recent years, several key studies have advanced our understanding regarding the roles that brain-gut-microbiota axis plays in the pathogenesis of brain diseases, including PD. It has been shown that gut microbiota is implicated in a series of pathophysiological changes in PD, including motor deficits, microglia activation, and αSyn pathology in mice model with overexpression of αSyn. Furthermore, some microbiotas, such as enterobacteriaceae, have been shown to be positively associated with the severity of PD symptoms, including postural instability and gait difficulty.
Limitations in previous studies and knowledge gaps Nonetheless, the answers for several key questions regarding the roles of gut microbiota in the progression of synucleinopathy are still unclear. First, whether these microbiotas found in previous studies are the causes or the effects of PD. For example, medications treating PD may also affect the gut microbiome. Moreover, the microbiota may be affected by a number of factors commonly found in PD, such as constipation per se and diet. In this regard, an influential hypothesis of synucleinopahy was proposed by Braak et al at which the early premotor features including gastro-enterology symptoms, such as constipation and RBD would predate the onset of PD by some years. Thus, it is crucial to compare the microbiota among individuals at different stages of synucleinopathy. In view of slow progression of synucleinopathy and a relatively low prevalence of synucleinopathy in the general population, it is impractical to run a prospective study to examine this research question. Finally, gut microbiota is determined by both genetic and environmental factors. A family cohort design will help to understand the genetic and environmental influences on the association between microbiota and synucleinopathy.
Read the detailed description
With the global ageing population, neurodegenerative disorders including synucleinopathy are major burdens to patients, carers and society. Synucleinopathy refers to a group of neurodegenerative diseases characterized by abnormal aggregation of alpha-synuclein protein in the central nervous system (CNS). Common examples of synucleinopathy are Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). These diseases often run debilitating and progressive courses that affect millions of people worldwide. Up till now, there is no curable treatment and hence the development of disease-modifying agents is of utmost importance. However, it is often too late for intervention once the patients start to have the clinical presentations of these diseases. For example, it was reported that there would be at least 80% of dopaminergic neuronal loss when one starts to develop clinical motor features of PD. Thus, researchers are now focusing on identifying at-risk subjects for early intervention. There are on-going studies to look for biomarkers to identify subjects at risk for PD through population based cohort and family studies, such as the Honolulu-Asia Aging Study (HAAS) and the Prospective Validation of Risk factors for the development of Parkinson Syndromes (PRIPS). However, these studies require a very large sample size and long duration of follow-up for the outcome evaluation.1 Another approach is to follow-up subjects at preclinical or premotor phase of PD. Among all the premotor clinical markers that have been identified, REM sleep behavior disorder (RBD) is associated with the highest likelihood ratio of developing PD.2 In addition, it has been shown that almost all RBD patients (over 80%) eventually developed neurodegenerative diseases (mean follow-up years = 14.2).3 Hence, RBD helps to understand the progression of underlying neurodegenerative diseases and will serve as a potential window for neuroprotective interventions.
Gastrointestinal dysfunction and synucleinopathy In addition to RBD, gastrointestinal dysfunction often precedes the onset of motor symptoms in patients with PD. Studies reported that constipation could precede the onset of motor symptoms in PD by 20 years. Comparing to those with daily bowel open, men with bowel movement frequency of less than 1 per day had an odds ratio of 2.7 in developing PD.4 In addition, PD with co-morbid RBD seem to have more severe constipation than PD only subjects. Constipation and other gastrointestinal dysfunction are also more common in patients with iRBD than healthy controls.5 According to Braak staging, the involvement of pontine areas (Stage 2) could result in both RBD and constipation. Hence, RBD and constipation may have an interactive effect in predicting synucleinopathy.6
What is gut microbiota and its associations with PD In recent years, several key studies have advanced our understanding regarding the roles that brain-gut-microbiota axis plays in the pathogenesis of brain diseases, including PD.7 It has been shown that gut microbiota is implicated in a series of pathophysiological changes in PD, including motor deficits, microglia activation, and αSyn pathology in mice model with overexpression of αSyn.8 Furthermore, some microbiotas, such as enterobacteriaceae, have been shown to be positively associated with the severity of PD symptoms, including postural instability and gait difficulty.9 The crucial roles of gut microbiota in the pathogenesis of PD are also evidenced by other observations.10 For example, catecholamine levels are altered in germ-free mice when compared with control mice. Antibiotics are able to reduce Firmicutes/Bacteroidetes ratio and prevent nigrostriatal dopaminergic neurodegeneration in MPTP model of PD. Probiotics increase production of L-DOPA by Bacillus and alleviate constipation in PD patients. Fecal transplantation decreased GI pathology in neurodegenerative diseases. Finally, H. pylori infection seems to increase symptom severity of PD. Taken together, growing evidence suggests that gut microbiota may play a critical role in pathogenesis, disease progression, and symptom fluctuation of synucleinopathy.
The exact mechanisms underlying the association between microbiota and Parkinson's disease remain unclear. It is believed that local and systemic inflammation and oxidative stress play a critical role in the pathogenesis of Parkinson's disease.11 In human subjects, it has been shown that proinflammatory dysbiosis is present in PD patients, which may trigger inflammation-induced misfolding of α-Syn and development of PD pathology.12 Gut microbiota is considered as an important but neglected organ for immune and inflammation. It has been shown that anti-inflammatory butyrate-producing bacteria and proinflammatory proteobacteria were significantly more abundant in feces and mucosa samples in patients with PD than healthy controls.12 Taken together, these findings suggest that gut microbiota, which is likely to increase inflammatory pathway, plays a critical role in the pathogenesis of Parkinson's disease.
Limitations and knowledge gaps Nonetheless, the answers for several key questions regarding the roles of gut microbiota in the progression of synucleinopathy are still unclear. First, whether these microbiotas found in previous studies are the causes or the effects of PD should be further clarified. It has been shown that medications treating PD also affect the gut microbiome.13 Moreover, the microbiota may be affected by a number of factors commonly found in PD, such as constipation per se and diet.14. In this regard, it is crucial to compare the microbiota among individuals at different stages of synucleinopathy. In view of slow progression of synucleinopathy and a relatively low prevalence of synucleinopathy in the general population, it is impractical to run a prospective study to examine this research question. In this regard, a case-control study with high-risk subjects is able to recruit sufficient cases at different stages of synucleinopathy.
Aims:
- To identify the differences in colonic bacterial composition in mucosa and feces among early PD converted from iRBD, iRBD, first degree relatives (FDRs) of patients with iRBD, and healthy controls;
- To correlate the abundance of those microbiota with clinical biomarkers of synucleinopathy.
We hypothesize that
- Colonic bacterial composition, especially those related to inflammation (such as Blautia, Coprococcus, and Roseburia), in mucosa and feces is more abundant in different stages of synucleinopathy, namely early PD without dementia (converted from iRBD), iRBD, FDRs of patients with iRBD, and healthy controls with a dose-response pattern.
- The abundance of microbiota is associated with other biomarkers, for example, subtle motor signs and constipation, in relation to PD and RBD.
- Conditions
- REM Sleep Behavior Disorder
- Being tested
- Colonoscopy
- Keywords
- Idiopathic REM sleep, Parkinson's disease, Gut microbiota, Syncleinpathy
- Medical subject headings
- REM Sleep Behavior Disorder, Parkinson Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ColonoscopyDiagnostic test
All subjects will undergo standard mechanical bowel preparation with 4 liters of polyethylene glycol (Klean-Prep, Norgine Ltd., Middlesex, UK). Total colonoscopy will be performed by experienced endoscopists under conscious sedation with intravenous benzodiazepines and narcotics. A conventional intermediate-length colonoscope (Olympus Corporation, Tokyo, Japan) will be used. One mucosal biopsy will be taken in the descending colon. Biopsies will be performed using standard biopsy forces without needle (Olympus Corporation, Tokyo, Japan). Half of the samples will be immersed in 4 oC normal saline solution. All samples will be immediately sent to pathology department and will be stored in a -80 oC freeze for processing of microbiota analyses.
| Study group | Role | What they receive |
|---|---|---|
| Early PD subjects converted from iRBD | 1. Chinese aged 50 or above
2. Being capable of giving informed consent for participation of the study
3. PD diagnosis confirmed by neurologists according to the United Kingdom Parkinson's Disease Survey Brain Bank. Assessment tools including Unified Parkinson's Disease Rating Scale (UPDRS) and Hoehn \& Yahr Staging will be used for severity grading.
4. Onset of PD symptoms of <5 years
5. In view of the heterogeneity of PD, we will only include those patients with RBD preceding the onset of motor symptom of PD. Receives: Diagnostic Test: Colonoscopy | |
| iRBD subjects | 1. Age-and sex-matched with PD subjects
2. Chinese aged 50 or above
3. Being capable of giving informed consent for participation of the study
4. RBD diagnosis according to the International classification of sleep disorder 3rd edition (ICSD 3rd), fulfilling both the clinical and video-polysomnography (vPSG) criteria. Receives: Diagnostic Test: Colonoscopy | |
| First degree relatives of patients with iRBD | 1. First degree relatives of patients with iRBD;
2. Age-and sex-matched with PD subjects
3. Chinese aged 40 or above;
4. Absence of dream enactment behaviors;
5. Not cohabiting with proband Receives: Diagnostic Test: Colonoscopy | |
| Healthy Controls | 1. Age-and sex-matched with PD subjects;
2. Chinese aged 50 or above;
3. Being capable of giving informed consent for participation of the study;
4. Without a personal history or a family history of PD or RBD;
5. Absence of dream enactment behaviors;
6. A total score on REM Sleep Behavior Questionnaire (RBDQ-HK) less than 19, which is the suggestive cut-off of a diagnosis of RBD;
7. Absence of RSWA as measured by v-PSG. Receives: Diagnostic Test: Colonoscopy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Differential abundances of colonic mucosal and fecal microbial taxa by 16S ribosomal RNA sequencing across early stages of synucleinopathy
To investigate differential abundances of colonic mucosal and fecal microbial taxa by 16S ribosomal RNA sequencing across early stages of synucleinopathy compared with healthy controls
Measured: 12 months
Abundances of fecal microbial taxa by 16S ribosomal RNA sequencing in control and iRBD families
To investigate the abundances of fecal microbial taxa by 16S ribosomal RNA sequencing among probands, first-degree relatives and spouses in both healthy control and iRBD families
Measured: 12 months
Biomarkers of Parkinson's disease during early stages of synucleinopathy according to questionnaire and clinical interview
To investigate the background risk and prodromal markers according to the MDS research criteria for prodromal Parkinson's disease in each group by questionnaire and clinical interview, for example , subtle motor signs , constipation and olfactory function
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2018
- Study start6 May 2018
- Primary completion27 Mar 2023
- Study completion29 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for REM Sleep Behavior DisorderStudies of the same condition, open and under way.
- More trials run by Chinese University of Hong KongThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 441 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chinese University of Hong Kong
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Professor Wing Yun Kwok, Chinese University of Hong Kong
- Investigators
- Yun Kwok Wing, Professor, Principal investigator, Chinese University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03645226
- Sponsor's protocol ID
- HMRF05162876
- Status last verified
- Aug 2023
- First submitted
- 19 Jul 2018
- Last updated
- 30 Aug 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: In this stage, we didn't decide whcih information of IPD will share with other researchers.
Study at a glance
From the registry record, last updated by the sponsor on 30 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Gut Microbiota Across Early Stages of Synucleinopathy: From High-risk Relatives, REM Sleep Behavior Disorder to Early Parkinson's Disease
- ClinicalTrials.gov ID
- NCT03645226
- Acronym / sponsor ID
- HMRF05162876
- Conditions
- REM Sleep Behavior Disorder
- Keywords
- Idiopathic REM sleep, Parkinson's disease, Gut microbiota, Syncleinpathy
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 441 participants (actual)
- Lead sponsor
- Chinese University of Hong KongUniversity, hospital or other
- Study start
- 6 May 2018 (actual)
- Primary completion
- 27 Mar 2023 (actual)
- Study completion
- 29 Mar 2023 (actual)
- First posted
- 24 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
With the global ageing population, neurodegenerative disorders including synucleinopathy are major burdens to patients, carers and society. Synucleinopathy refers to a group of neurodegenerative diseases characterized by abnormal aggregation of alpha-synuclein protein in the central nervous system (CNS). Common examples of synucleinopathy are Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Among all the premotor clinical markers that have been identified, a sleep disorder known as REM sleep behavior disorder (RBD) is associated with the highest likelihood ratio of developing PD. In addition, it has been shown that almost all RBD patients (over 80%) eventually developed neurodegenerative diseases after 14 years follow-up.
Gut microbiota and synucleinopathy In recent years, several key studies have advanced our understanding regarding the roles that brain-gut-microbiota axis plays in the pathogenesis of brain diseases, including PD. It has been shown that gut microbiota is implicated in a series of pathophysiological changes in PD, including motor deficits, microglia activation, and αSyn pathology in mice model with overexpression of αSyn. Furthermore, some microbiotas, such as enterobacteriaceae, have been shown to be positively associated with the severity of PD symptoms, including postural instability and gait difficulty.
Limitations in previous studies and knowledge gaps Nonetheless, the answers for several key questions regarding the roles of gut microbiota in the progression of synucleinopathy are still unclear. First, whether these microbiotas found in previous studies are the causes or the effects of PD. For example, medications treating PD may also affect the gut microbiome. Moreover, the microbiota may be affected by a number of factors commonly found in PD, such as constipation per se and diet. In this regard, an influential hypothesis of synucleinopahy was proposed by Braak et al at which the early premotor features including gastro-enterology symptoms, such as constipation and RBD would predate the onset of PD by some years. Thus, it is crucial to compare the microbiota among individuals at different stages of synucleinopathy. In view of slow progression of synucleinopathy and a relatively low prevalence of synucleinopathy in the general population, it is impractical to run a prospective study to examine this research question. Finally, gut microbiota is determined by both genetic and environmental factors. A family cohort design will help to understand the genetic and environmental influences on the association between microbiota and synucleinopathy.
Detailed description
With the global ageing population, neurodegenerative disorders including synucleinopathy are major burdens to patients, carers and society. Synucleinopathy refers to a group of neurodegenerative diseases characterized by abnormal aggregation of alpha-synuclein protein in the central nervous system (CNS). Common examples of synucleinopathy are Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). These diseases often run debilitating and progressive courses that affect millions of people worldwide. Up till now, there is no curable treatment and hence the development of disease-modifying agents is of utmost importance. However, it is often too late for intervention once the patients start to have the clinical presentations of these diseases. For example, it was reported that there would be at least 80% of dopaminergic neuronal loss when one starts to develop clinical motor features of PD. Thus, researchers are now focusing on identifying at-risk subjects for early intervention. There are on-going studies to look for biomarkers to identify subjects at risk for PD through population based cohort and family studies, such as the Honolulu-Asia Aging Study (HAAS) and the Prospective Validation of Risk factors for the development of Parkinson Syndromes (PRIPS). However, these studies require a very large sample size and long duration of follow-up for the outcome evaluation.1 Another approach is to follow-up subjects at preclinical or premotor phase of PD. Among all the premotor clinical markers that have been identified, REM sleep behavior disorder (RBD) is associated with the highest likelihood ratio of developing PD.2 In addition, it has been shown that almost all RBD patients (over 80%) eventually developed neurodegenerative diseases (mean follow-up years = 14.2).3 Hence, RBD helps to understand the progression of underlying neurodegenerative diseases and will serve as a potential window for neuroprotective interventions.
Gastrointestinal dysfunction and synucleinopathy In addition to RBD, gastrointestinal dysfunction often precedes the onset of motor symptoms in patients with PD. Studies reported that constipation could precede the onset of motor symptoms in PD by 20 years. Comparing to those with daily bowel open, men with bowel movement frequency of less than 1 per day had an odds ratio of 2.7 in developing PD.4 In addition, PD with co-morbid RBD seem to have more severe constipation than PD only subjects. Constipation and other gastrointestinal dysfunction are also more common in patients with iRBD than healthy controls.5 According to Braak staging, the involvement of pontine areas (Stage 2) could result in both RBD and constipation. Hence, RBD and constipation may have an interactive effect in predicting synucleinopathy.6
What is gut microbiota and its associations with PD In recent years, several key studies have advanced our understanding regarding the roles that brain-gut-microbiota axis plays in the pathogenesis of brain diseases, including PD.7 It has been shown that gut microbiota is implicated in a series of pathophysiological changes in PD, including motor deficits, microglia activation, and αSyn pathology in mice model with overexpression of αSyn.8 Furthermore, some microbiotas, such as enterobacteriaceae, have been shown to be positively associated with the severity of PD symptoms, including postural instability and gait difficulty.9 The crucial roles of gut microbiota in the pathogenesis of PD are also evidenced by other observations.10 For example, catecholamine levels are altered in germ-free mice when compared with control mice. Antibiotics are able to reduce Firmicutes/Bacteroidetes ratio and prevent nigrostriatal dopaminergic neurodegeneration in MPTP model of PD. Probiotics increase production of L-DOPA by Bacillus and alleviate constipation in PD patients. Fecal transplantation decreased GI pathology in neurodegenerative diseases. Finally, H. pylori infection seems to increase symptom severity of PD. Taken together, growing evidence suggests that gut microbiota may play a critical role in pathogenesis, disease progression, and symptom fluctuation of synucleinopathy.
The exact mechanisms underlying the association between microbiota and Parkinson's disease remain unclear. It is believed that local and systemic inflammation and oxidative stress play a critical role in the pathogenesis of Parkinson's disease.11 In human subjects, it has been shown that proinflammatory dysbiosis is present in PD patients, which may trigger inflammation-induced misfolding of α-Syn and development of PD pathology.12 Gut microbiota is considered as an important but neglected organ for immune and inflammation. It has been shown that anti-inflammatory butyrate-producing bacteria and proinflammatory proteobacteria were significantly more abundant in feces and mucosa samples in patients with PD than healthy controls.12 Taken together, these findings suggest that gut microbiota, which is likely to increase inflammatory pathway, plays a critical role in the pathogenesis of Parkinson's disease.
Limitations and knowledge gaps Nonetheless, the answers for several key questions regarding the roles of gut microbiota in the progression of synucleinopathy are still unclear. First, whether these microbiotas found in previous studies are the causes or the effects of PD should be further clarified. It has been shown that medications treating PD also affect the gut microbiome.13 Moreover, the microbiota may be affected by a number of factors commonly found in PD, such as constipation per se and diet.14. In this regard, it is crucial to compare the microbiota among individuals at different stages of synucleinopathy. In view of slow progression of synucleinopathy and a relatively low prevalence of synucleinopathy in the general population, it is impractical to run a prospective study to examine this research question. In this regard, a case-control study with high-risk subjects is able to recruit sufficient cases at different stages of synucleinopathy.
Aims:
- To identify the differences in colonic bacterial composition in mucosa and feces among early PD converted from iRBD, iRBD, first degree relatives (FDRs) of patients with iRBD, and healthy controls;
- To correlate the abundance of those microbiota with clinical biomarkers of synucleinopathy.
We hypothesize that
- Colonic bacterial composition, especially those related to inflammation (such as Blautia, Coprococcus, and Roseburia), in mucosa and feces is more abundant in different stages of synucleinopathy, namely early PD without dementia (converted from iRBD), iRBD, FDRs of patients with iRBD, and healthy controls with a dose-response pattern.
- The abundance of microbiota is associated with other biomarkers, for example, subtle motor signs and constipation, in relation to PD and RBD.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Early PD subjects converted from iRBD | – | Diagnostic Test: Colonoscopy1. Chinese aged 50 or above 2. Being capable of giving informed consent for participation of the study 3. PD diagnosis confirmed by neurologists according to the United Kingdom Parkinson's Disease Survey Brain Bank. Assessment tools including Unified Parkinson's Disease Rating Scale (UPDRS) and Hoehn \& Yahr Staging will be used for severity grading. 4. Onset of PD symptoms of <5 years 5. In view of the heterogeneity of PD, we will only include those patients with RBD preceding the onset of motor symptom of PD. |
| iRBD subjects | – | Diagnostic Test: Colonoscopy1. Age-and sex-matched with PD subjects 2. Chinese aged 50 or above 3. Being capable of giving informed consent for participation of the study 4. RBD diagnosis according to the International classification of sleep disorder 3rd edition (ICSD 3rd), fulfilling both the clinical and video-polysomnography (vPSG) criteria. |
| First degree relatives of patients with iRBD | – | Diagnostic Test: Colonoscopy1. First degree relatives of patients with iRBD; 2. Age-and sex-matched with PD subjects 3. Chinese aged 40 or above; 4. Absence of dream enactment behaviors; 5. Not cohabiting with proband |
| Healthy Controls | – | Diagnostic Test: Colonoscopy1. Age-and sex-matched with PD subjects; 2. Chinese aged 50 or above; 3. Being capable of giving informed consent for participation of the study; 4. Without a personal history or a family history of PD or RBD; 5. Absence of dream enactment behaviors; 6. A total score on REM Sleep Behavior Questionnaire (RBDQ-HK) less than 19, which is the suggestive cut-off of a diagnosis of RBD; 7. Absence of RSWA as measured by v-PSG. |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- In the case-control study, we will recruit 7 groups of subjects, which represent different stages of Parkinson's disease, namely patients with PD (Braak's stages 3 or 4) without dementia, patients with iRBD (Braak's stage 2), first degree relatives of iRBD patients (Braak's stage 0 or 1), healthy controls (Braak's stage 0). In the familial study, another 3 groups of subjects will be recruited to understand the genetic and environmental influences on differential microbiotas, including spouses of iRBD, spouses of healthy controls and first degree relatives of healthy controls. We will document the cohabiting status and contact frequency among family members within the same family and excluded FDRs who are cohabiting with the proband or spouses who are not cohabiting with the proband. In addition, we will also recruit FDRs and spouses with and without biomarkers of neurodegeneration (such as constipation).
Key inclusion criteria (1 listed)
- fulfill the groups criteria
Key exclusion criteria (4 listed)
- Presence of narcolepsy and other neurodegenerative diseases (except for PD group) that may give rise to RBD and RWSA;
- A total score of the MOCA ≤ 22 and the CDR ≥ 1, indicating dementia;
- The use of probiotics or antibiotics within three months prior to sample collection;
- Pre-existing gastrointestinal diseases, such as inflammatory bowel disease.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ColonoscopyAll subjects will undergo standard mechanical bowel preparation with 4 liters of polyethylene glycol (Klean-Prep, Norgine Ltd., Middlesex, UK). Total colonoscopy will be performed by experienced endoscopists under conscious sedation with intravenous benzodiazepines and narcotics. A conventional intermediate-length colonoscope (Olympus Corporation, Tokyo, Japan) will be used. One mucosal biopsy will be taken in the descending colon. Biopsies will be performed using standard biopsy forces without needle (Olympus Corporation, Tokyo, Japan). Half of the samples will be immersed in 4 oC normal saline solution. All samples will be immediately sent to pathology department and will be stored in a -80 oC freeze for processing of microbiota analyses. | Diagnostic test | Early PD subjects converted from iRBD, First degree relatives of patients with iRBD, Healthy Controls, iRBD subjects |
Primary outcome
Differential abundances of colonic mucosal and fecal microbial taxa by 16S ribosomal RNA sequencing across early stages of synucleinopathy
Time frame: 12 months
To investigate differential abundances of colonic mucosal and fecal microbial taxa by 16S ribosomal RNA sequencing across early stages of synucleinopathy compared with healthy controls
Abundances of fecal microbial taxa by 16S ribosomal RNA sequencing in control and iRBD families
Time frame: 12 months
To investigate the abundances of fecal microbial taxa by 16S ribosomal RNA sequencing among probands, first-degree relatives and spouses in both healthy control and iRBD families
Biomarkers of Parkinson's disease during early stages of synucleinopathy according to questionnaire and clinical interview
Time frame: 12 months
To investigate the background risk and prodromal markers according to the MDS research criteria for prodromal Parkinson's disease in each group by questionnaire and clinical interview, for example , subtle motor signs , constipation and olfactory function
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Aug 2023.
- Individual participant dataSharing planned: Undecided. In this stage, we didn't decide whcih information of IPD will share with other researchers.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yun Kwok Wing, Professor principal investigator
Chinese University of Hong Kong
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of REM Sleep Behavior Disorder, run by Chinese University of Hong Kong at 2 sites in Hong Kong.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Hong Kong. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Differential abundances of colonic mucosal and fecal microbial taxa by 16S ribosomal RNA sequencing across early stages of synucleinopathy (time frame: 12 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Aug 2023.