Ignite Creation Date:
2025-12-24 @ 5:46 PM
Ignite Modification Date:
2026-01-01 @ 2:59 PM
Study NCT ID:
NCT05353868
Status:
RECRUITING
Last Update Posted:
2024-04-19
First Post:
2022-01-13
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Gut Microbiota in the Progression of Alpha-synucleinopathies
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D020187', 'term': 'REM Sleep Behavior Disorder'}, {'id': 'D010300', 'term': 'Parkinson Disease'}], 'ancestors': [{'id': 'D020923', 'term': 'REM Sleep Parasomnias'}, {'id': 'D020447', 'term': 'Parasomnias'}, {'id': 'D012893', 'term': 'Sleep Wake Disorders'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D001523', 'term': 'Mental Disorders'}, {'id': 'D020734', 'term': 'Parkinsonian Disorders'}, {'id': 'D001480', 'term': 'Basal Ganglia Diseases'}, {'id': 'D001927', 'term': 'Brain Diseases'}, {'id': 'D002493', 'term': 'Central Nervous System Diseases'}, {'id': 'D009069', 'term': 'Movement Disorders'}, {'id': 'D000080874', 'term': 'Synucleinopathies'}, {'id': 'D019636', 'term': 'Neurodegenerative Diseases'}]}}, 'protocolSection': {'designModule': {'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 490}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2022-02-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-04', 'completionDateStruct': {'date': '2024-06-30', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2024-04-17', 'studyFirstSubmitDate': '2022-01-13', 'studyFirstSubmitQcDate': '2022-04-25', 'lastUpdatePostDateStruct': {'date': '2024-04-19', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2022-04-29', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2024-06-30', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Composition of gut microbiota', 'timeFrame': '2 years', 'description': 'Correlation of baseline gut microbiota features and the progression of α-synucleinopathy neurodegeneration.'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Gut microbiota', "Parkinson's disease", 'REM sleep behavior disorder'], 'conditions': ['REM Sleep Behavior Disorder']}, 'descriptionModule': {'briefSummary': "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.", 'detailedDescription': "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.\n\nIn 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.\n\nIn 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."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT', 'OLDER_ADULT'], 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': "We will recruit from the subjects who completed the baseline study, which represent different stages of α-synucleinopathies, 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 (iRBD-FDRs, Braak's stage 0 or 1), and healthy controls (Braak's stage 0).", 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* recruit from the subjects who completed the baseline study\n\nExclusion Criteria:\n\n* The use of probiotics or antibiotics within three months prior to sample collection;\n* Pre-existing gastrointestinal diseases, such as inflammatory bowel disease.\n* Not capable of giving informed consent for participation of the study.'}, 'identificationModule': {'nctId': 'NCT05353868', 'briefTitle': 'Gut Microbiota in the Progression of Alpha-synucleinopathies', 'organization': {'class': 'OTHER', 'fullName': 'Chinese University of Hong Kong'}, 'officialTitle': 'Gut Microbiota in the Progression of Alpha-synucleinopathies: a Prospective Follow-up Study', 'orgStudyIdInfo': {'id': 'NTEC-2021-0614'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'Early PD', 'description': '1. Recruited in the baseline study as a subject of the Early PD group\n2. Completed baseline assessment and stool sample collection\n3. Being capable of giving informed consent for participation of the study', 'interventionNames': ['Other: No intervention']}, {'label': 'iRBD', 'description': '1. Recruited in the baseline study as a subject of the iRBD group\n2. Completed baseline assessment and stool sample collection\n3. Being capable of giving informed consent for participation of the study', 'interventionNames': ['Other: No intervention']}, {'label': 'First degree relatives of patient with iRBD', 'description': "1. Recruited in the baseline study as a subject of the 'First degree relatives of patients with iRBD' group\n2. Completed baseline assessment and stool sample collection\n3. Not cohabiting with iRBD proband", 'interventionNames': ['Other: No intervention']}, {'label': 'Health control', 'description': "1. Recruited in the baseline study as a subject of the 'healthy controls' group\n2. Completed baseline assessment and stool sample collection\n3. Being capable of giving informed consent for participation of the study", 'interventionNames': ['Other: No intervention']}], 'interventions': [{'name': 'No intervention', 'type': 'OTHER', 'description': 'No intervention', 'armGroupLabels': ['Early PD', 'First degree relatives of patient with iRBD', 'Health control', 'iRBD']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Hong Kong', 'status': 'RECRUITING', 'country': 'Hong Kong', 'contacts': [{'name': 'Mandy Yu, MPH', 'role': 'CONTACT', 'email': 'mandyyu@cuhk.edu.hk', 'phone': '852-39197593'}, {'name': 'Rachel Chan, MPhil', 'role': 'CONTACT', 'email': 'Rachel.chan@cuhk.edu.hk', 'phone': '852-39197449'}], 'facility': 'The Chinese University of Hong Kong', 'geoPoint': {'lat': 22.27832, 'lon': 114.17469}}]}, 'ipdSharingStatementModule': {'ipdSharing': 'UNDECIDED', 'description': 'Data will be handled and stored under Department of Psychiatry and PI will be responsible for the safekeeping.'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Chinese University of Hong Kong', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Professor', 'investigatorFullName': 'Professor Wing Yun Kwok', 'investigatorAffiliation': 'Chinese University of Hong Kong'}}}}