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Despite an extension of the planned duration of inclusion and an enrolled patient number inferior than planned, coordinating investigator considered that it was more reasonable to stop inclusions in order to analyze the data already available
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| Name | Class |
|---|---|
| France Parkinson Association | OTHER |
| Luxia Scientific | INDUSTRY |
| Institut National de la Santé Et de la Recherche Médicale, France | OTHER_GOV |
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Converging evidence from the literature suggests that digestive inflammation may play a role in the development of Parkinson's disease (PD). The investigators showed in the laboratory in a pilot study that PD patients have digestive inflammation and that the level of inflammation was inversely related to the length of the disease course. This digestive inflammation could be at the origin of an increased intestinal permeability in a subpopulation of parkinsonian patients, cause or consequence of modifications of the intestinal microbiota, thus offering a potential portal of entry for a pathogen according to Braak's theory. To opponents of this theory, it could also reflect the spread of inflammation from the Central nervous System to the Enteral Nervous System (ENS), via the brain-gut axis.
Investigators' hypothesis is that digestive inflammation occurs very early in Parkinson's disease and that it is associated with hyperpermeability of the intestinal epithelial barrier and a change in the intestinal microbiota composition. The investigators propose to study the inflammation markers in the ENS of patients with a pre-motor form of PD (idiopathic Rapid Eye Movement (REM) sleep behavior disorder, n = 20), early-stage PD (<5 years, without dopatherapy, n = 20), more advanced PD (> 5 years, n = 20) and control subjects (n = 20), on colonic biopsies taken during a rectosigmoidoscopy or a coloscopy. Intestinal permeability will be measured by ex-vivo techniques (in a Ussing chamber), the composition of the microbiota will be established by sequencing 16s RNA and the lesional load of phosphorylated alpha-synuclein will be evaluated by immunohistochemistry. All of these parameters will be correlated with clinical data on the severity of PD: duration of development, age, total Unified Parkinson's Disease Rating Scale (UPDRS) motor score and axial sub-score, cognitive tests (Montreal Cognitive Assessment, MoCA), existence of a probable idiopathic REM sleep behavior disorder (REM Sleep Behavior Disorder Screening Questionnaire RBDSQ), olfactory tests, complaint of dysautonomia (SCales for Outcomes in Parkinson's disease - autonomic dysfunction, SCOPA-Aut).
The analysis of inflammation markers, the intestinal barrier and the microbiota could be a first step making it possible to formulate physiopathological hypotheses on the development of PD, to propose predictive biomarkers of the disease and its severity and to design early interventions in the hope of modifying the evolutionary course of the pathological process.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Idiopathic REM sleep behavior disorders | Other | Group of 20 Patients with an Idiopathic REM sleep behavior disorder confirmed by video-polysomnography (International Classification of Sleep Disorders-3 criteria), not explained by a pathology (narcolepsy, brainstem injury, neurodegenerative disease) |
|
| Beginning Parkinson's disease | Other | Group of 20 patients with Parkinson's Disease which has been progressing for less than 5 years and who have not received dopatherapy |
|
| Parkinson's disease state Phase | Other | Group of 20 patients with Parkinson's Disease for more than 5 years |
|
| Control | Other | Group of 20 patients undergoing coloscopy for family screening for digestive polyps |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Rectosignoidoscopy | Procedure | Rectosignoidoscopy for colonic biospsies collection |
|
| Measure | Description | Time Frame |
|---|---|---|
| TNF-α | TNF-α in colonic biopsies measured by ELISA | In the three months following the inclusion |
| Measure | Description | Time Frame |
|---|---|---|
| IFN-γ | IFN-γ in colonic biopsies measured by ELISA | In the three months following the inclusion |
| IL-6 | IL-6 in colonic biopsies measured by ELISA |
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Inclusion Criteria:
Parkinson's Disease patients :
Idiopathic REM sleep behavior disorders patients:
Control:
Exclusion Criteria:
For patients with Idiopathic REM sleep behavior disorder:
- presence of Parkinson's Disease according to United Kindom Parkinson's Disease Brain Bank criteria
For control:
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| Name | Affiliation | Role |
|---|---|---|
| Laurène LECLAIR-VISONNEAU, MD | Nantes University Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Nantes Universitary Hospital | Nantes | Loire Atlantique | 44093 | France |
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| Coloscopy | Procedure | Coloscopy for colonic biospsies collection |
|
| In the three months following the inclusion |
| IL-1β | IL-1β in colonic biopsies measured by ELISA | In the three months following the inclusion |
| IFN-α2 | IFN-α2 in colonic biopsies measured by ELISA | In the three months following the inclusion |
| MCP-1 (CCL2) | MCP-1 (CCL2) in colonic biopsies measured by ELISA | In the three months following the inclusion |
| IL-8 (CXCL8) | IL-8 (CXCL8) in colonic biopsies measured by ELISA | In the three months following the inclusion |
| IL-10 | IL-10 in colonic biopsies measured by ELISA | In the three months following the inclusion |
| IL-12p70 | IL-12p70 in colonic biopsies measured by ELISA | In the three months following the inclusion |
| IL-17A | IL-17A in colonic biopsies measured by ELISA | In the three months following the inclusion |
| IL-18 | IL-18 in colonic biopsies measured by ELISA | In the three months following the inclusion |
| IL-23 | IL-23 in colonic biopsies measured by ELISA | In the three months following the inclusion |
| IL-33 | IL-33 in colonic biopsies measured by ELISA | In the three months following the inclusion |
| Permeability slopes for sulfonic acid | Permeability slopes for sulfonic acid (low molecular weight) and dextran (high molecular weight) measured in a Ussing chamber | In the three months following the inclusion |
| Diversity of the intestinal microbiota | Bacterial diversity in each group by genetic sequencing of 16s RNA | In the three months following the inclusion |
| Relative abundance of the intestinal microbiota | Relative abundance of different families or genera or bacterial species in each group by genetic sequencing of 16s RNA | In the three months following the inclusion |
| Quantification of phosphorylated alpha-synuclein | Presence or absence of inclusion of phosphorylated alpha-synuclein, if presence: quantification (in thioflavin fluorescence intensity and amplification time in minutes) | In the three months following the inclusion |
| Duration of progression | Disease duration of progression as Parkinson's disease clinical severity parameter | At inclusion |
| Age | Age as Parkinson's disease clinical severity parameter | At inclusion |
| Total Unified Parkinson Disease Rating Scale motor score | Total Unified Parkinson Disease Rating Scale motor score as Parkinson's disease clinical severity parameter | At inclusion |
| Unified Parkinson Disease Rating Scale axial sub-score | Unified Parkinson Disease Rating Scale axial sub-score as Parkinson's disease clinical severity parameter | At inclusion |
| Montreal Cognitive Assessment score | Montreal Cognitive Assessment score as Parkinson's disease clinical severity parameter | At inclusion |
| Presence or absence of a probable Idiopathic REM sleep behavior disorders | Presence or absence of a probable Idiopathic REM sleep behavior disorders (REM Sleep Behavior Disorder Screening Questionnaire score ≥ 5) as Parkinson's disease clinical severity parameter | At inclusion |
| Olfactory tests | Olfactory tests (Sniffin 'sticks test score) as Parkinson's disease clinical severity parameter | At inclusion |
| Scales for Outcomes in Parkinson's Disease - Autonomic Dysfunction score | Scales for Outcomes in Parkinson's Disease - Autonomic Dysfunction score as Parkinson's disease clinical severity parameter | At inclusion |
| ID | Term |
|---|---|
| D010300 | Parkinson Disease |
| ID | Term |
|---|---|
| D020734 | Parkinsonian Disorders |
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D009069 | Movement Disorders |
| D000080874 | Synucleinopathies |
| D019636 | Neurodegenerative Diseases |
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