French Parkinson's Disease Cohort - NS-PARK

Study Overview
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Brief Summary
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The aim of NS-PARK cohort are to describe the natural history of Parkinson's disease (PD), and to propose patients stratification models based on PD pathophysiological mechanisms. Patients are included at all PD expert centers in France. Standardized demographic, diagnosis, motor and non-motor symptoms evaluation, and treatment information are collected, and clinical data are updated at each visit of the patient at the center. A blood sampling is perform at baseline for genetic testing and implement an associated biocollection.

Detailed Description
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The national clinical research network for Parkinson's disease (NS-PARK/FCRIN) reassembles all expert centers in Parkinson's disease (PD) in France. Its aim is to promote clinical research in Parkinson's disease and movement disorder, to better understand the pathophysiology of PD, foster the development of new therapeutic strategies, and move towards personalized medicine. To help centers for prescreening, a national registry of PD patients followed in each centers has been implemented in 2016 to collect minimal relevant clinical information of patients followed in each center including demographic data, age at diagnosis, standardized motor and non-motor symptoms evaluation, and treatment. Data are updated at each visit of the patient in the center. De facto, this registry became a longitudinal cohort of PD patients followed in NS-PARK centers. In 2020, NS-PARK received funding to associate a biocollection to this clinical cohort. The aim of NS-PARK cohort are to describe the natural history of PD progression in clinical routine in France, to develop new models of PD describing the different progression profiles, and to propose patients stratification based on PD pathophysiological mechanisms. The cohort will also serve as a platform to discover new PD genes and genetic modifiers of disease progression or response to treatment.

Official Title
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Cohort of the French Clinical Research Network for Parkinson's Disease (NS-PARK Cohort)

Conditions
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Parkinson Disease

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Parkinson's disease according to UK PD brain bak criteria OR diagnosis of parkinsonian syndrome: multiple system atrophy, progressive supranuclear palsy, dementia with Lewy body, or corticobasal syndrom OR Subjects at risk of PD defined as : No symptom or diagnosis of Parkinson's disease nor parkinsonian syndrome, and relative to a patient with a diagosis of PD or parkinsonian syndrome, or carrier of a known mutation responsible for a genetic form of PD or patient with a diagnosis of idiopathic REEM sleep disorder or prodromal form of PD as defined by MDS criteria (Berg et al., 2015) AND for all participants Affiliated to social security Age > 10 years Exclusion Criteria: Subject under legal protection Subject who do not consent to the research for the optional skin biopsy only: clinically significant coagulation abnormalities or anticoagulant treatment

Ages Eligible for Study
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Minimum Age: 10 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease progression | Hoehn and Yahr score change | through the end of follow-up in the cohort, at least 2 years, and average of 5 years | 
| Motor and non-motor complications | Occurence of motor (dyskinesia or motor fluctuations) or non-motor (dementia, dysautonomia, behavioral or psychiatric disorders, sleep disorders, falls, ...) complication | through the end of follow-up in the cohort, at least 2 years, and average of 5 years | 
| Modification of antiparkinsonian treatment doses | Modification of antiparkinsonian treatment during follow-up will be measured as levodopa equivalent daily doses | through the end of follow-up in the cohort, at least 2 years, and average of 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Predictive factorsof PD progression: motor or non motor symptoms | Motor or non motor symptoms as measured by MDS-UPDRS scores will be used as predictive factors for primary outcomes | through the end of follow-up in the cohort, at least 2 years, and average of 5 years | 
| Predictive factors of PD progression: genetic variants | Genetic variants in PD genes or the Genetic PD risk score will be used as predictive factors for primary outcomes. | through the end of follow-up in the cohort, at least 2 years, and average of 5 years | 
| Predictive factors of PD progression: brain imaging markers | Brain imaging makers (iron or neuromelanine content of the substantia nigra) will be used as predictive factors for primary outcomes | through the end of follow-up in the cohort, at least 2 years, and average of 5 years | 
| Clusters of patients with similar disease progression profiles | Clustering analyses will be performed on disease progression markers (Hoehn and Yahr score, MDS-UPDRS scores, and doses of treatment (levodopa equivalent daily doses)) to identify homogeneous groups of patients (clusters) sharing similar disease progression profiles. | through the end of follow-up in the cohort, at least 2 years, and average of 5 years | 
| Clusters of patients with similar genetic and disease progression profiles | Co-clustering analysis of disease progression markers (Hoehn and Yahr score, MDS-UPDRS scores, and doses of treatment (levodopa equivalent daily doses)) and genetic markers (variants in PD genes or the Genetic PD risk score). | through the end of follow-up in the cohort, at least 2 years, and average of 5 years | 
| Genetic mutations associated with familal forms of PD | Genetic mutations will be screened by different methods (gene panels, whole exome or whole genome) in familial forms of PD. Mutations co-segregated with PD will be considered as potentially associated with the disease. | through study completion, 15 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson's disease, Genetics