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Single-center Pathophysiological Study of the Role of Inflammation, Changes in the Intestinal Epithelial Barrier and the Intestinal Microbiota in Parkinson's Disease (IBIM-Park)

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ClinicalTrials.gov Identifier: NCT04652843
Recruitment Status : Not yet recruiting
First Posted : December 3, 2020
Last Update Posted : December 3, 2020
Sponsor:
Collaborators:
France Parkinson Association
Luxia Scientific
INSERM - TENS - UMR 1235
Information provided by (Responsible Party):
Nantes University Hospital

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Parkinson's Disease Procedure: Rectosignoidoscopy Procedure: Coloscopy Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Single-center Pathophysiological Study of the Role of Inflammation, Changes in the Intestinal Epithelial Barrier and the Intestinal Microbiota in Parkinson's Disease
Estimated Study Start Date : December 2020
Estimated Primary Completion Date : March 2023
Estimated Study Completion Date : June 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Idiopathic REM sleep behavior disorders
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)
Procedure: Rectosignoidoscopy
Rectosignoidoscopy for colonic biospsies collection

Procedure: Coloscopy
Coloscopy for colonic biospsies collection

Beginning Parkinson's disease
Group of 20 patients with Parkinson's Disease which has been progressing for less than 5 years and who have not received dopatherapy
Procedure: Rectosignoidoscopy
Rectosignoidoscopy for colonic biospsies collection

Procedure: Coloscopy
Coloscopy for colonic biospsies collection

Parkinson's disease state Phase
Group of 20 patients with Parkinson's Disease for more than 5 years
Procedure: Rectosignoidoscopy
Rectosignoidoscopy for colonic biospsies collection

Procedure: Coloscopy
Coloscopy for colonic biospsies collection

Control
Group of 20 patients undergoing coloscopy for family screening for digestive polyps
Procedure: Coloscopy
Coloscopy for colonic biospsies collection




Primary Outcome Measures :
  1. TNF-α [ Time Frame: In the three months following the inclusion ]
    TNF-α in colonic biopsies measured by ELISA


Secondary Outcome Measures :
  1. IFN-γ [ Time Frame: In the three months following the inclusion ]
    IFN-γ in colonic biopsies measured by ELISA

  2. IL-6 [ Time Frame: In the three months following the inclusion ]
    IL-6 in colonic biopsies measured by ELISA

  3. IL-1β [ Time Frame: In the three months following the inclusion ]
    IL-1β in colonic biopsies measured by ELISA

  4. IFN-α2 [ Time Frame: In the three months following the inclusion ]
    IFN-α2 in colonic biopsies measured by ELISA

  5. MCP-1 (CCL2) [ Time Frame: In the three months following the inclusion ]
    MCP-1 (CCL2) in colonic biopsies measured by ELISA

  6. IL-8 (CXCL8) [ Time Frame: In the three months following the inclusion ]
    IL-8 (CXCL8) in colonic biopsies measured by ELISA

  7. IL-10 [ Time Frame: In the three months following the inclusion ]
    IL-10 in colonic biopsies measured by ELISA

  8. IL-12p70 [ Time Frame: In the three months following the inclusion ]
    IL-12p70 in colonic biopsies measured by ELISA

  9. IL-17A [ Time Frame: In the three months following the inclusion ]
    IL-17A in colonic biopsies measured by ELISA

  10. IL-18 [ Time Frame: In the three months following the inclusion ]
    IL-18 in colonic biopsies measured by ELISA

  11. IL-23 [ Time Frame: In the three months following the inclusion ]
    IL-23 in colonic biopsies measured by ELISA

  12. IL-33 [ Time Frame: In the three months following the inclusion ]
    IL-33 in colonic biopsies measured by ELISA

  13. Permeability slopes for sulfonic acid [ Time Frame: In the three months following the inclusion ]
    Permeability slopes for sulfonic acid (low molecular weight) and dextran (high molecular weight) measured in a Ussing chamber

  14. Diversity of the intestinal microbiota [ Time Frame: In the three months following the inclusion ]
    Bacterial diversity in each group by genetic sequencing of 16s RNA

  15. Relative abundance of the intestinal microbiota [ Time Frame: In the three months following the inclusion ]
    Relative abundance of different families or genera or bacterial species in each group by genetic sequencing of 16s RNA

  16. Quantification of phosphorylated alpha-synuclein [ Time Frame: In the three months following the inclusion ]
    Presence or absence of inclusion of phosphorylated alpha-synuclein, if presence: quantification (in thioflavin fluorescence intensity and amplification time in minutes)

  17. Duration of progression [ Time Frame: At inclusion ]
    Disease duration of progression as Parkinson's disease clinical severity parameter

  18. Age [ Time Frame: At inclusion ]
    Age as Parkinson's disease clinical severity parameter

  19. Total Unified Parkinson Disease Rating Scale motor score [ Time Frame: At inclusion ]
    Total Unified Parkinson Disease Rating Scale motor score as Parkinson's disease clinical severity parameter

  20. Unified Parkinson Disease Rating Scale axial sub-score [ Time Frame: At inclusion ]
    Unified Parkinson Disease Rating Scale axial sub-score as Parkinson's disease clinical severity parameter

  21. Montreal Cognitive Assessment score [ Time Frame: At inclusion ]
    Montreal Cognitive Assessment score as Parkinson's disease clinical severity parameter

  22. Presence or absence of a probable Idiopathic REM sleep behavior disorders [ Time Frame: At inclusion ]
    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

  23. Olfactory tests [ Time Frame: At inclusion ]
    Olfactory tests (Sniffin 'sticks test score) as Parkinson's disease clinical severity parameter

  24. Scales for Outcomes in Parkinson's Disease - Autonomic Dysfunction score [ Time Frame: At inclusion ]
    Scales for Outcomes in Parkinson's Disease - Autonomic Dysfunction score as Parkinson's disease clinical severity parameter



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Parkinson's Disease patients :

  • patients with Parkinson's disease according to the criteria of the United Kingdom Parkinson's disease survey brain bank (UKPDSBB)
  • aged over 18 years
  • who have given their consent to participate in this study

Idiopathic REM sleep behavior disorders patients:

  • 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)
  • aged over 18 years
  • having given their consent to participate in this study

Control:

  • patients undergoing coloscopy for family screening for digestive polyps
  • aged over 18
  • who have given their consent to participate in this study

Exclusion Criteria:

  • dementia (MINI MENTAL STATE EXAMINATION score <24)
  • history of authenticated colonic disease (inflammatory disease, adenocarcinoma) or functional colopathy in control subjects or having preceded the first signs of Parkinson's Disease or Idiopathic REM sleep behavior disorder for more than 5 years, respectively in Parkinson's Disease and Idiopathic REM sleep behavior disorder patients
  • history of prescription of antibiotic treatment, acute gastrointestinal illness or hospitalization for an acute medical pathology or for a surgical procedure in the last month
  • anticoagulant treatment or coagulopathy
  • pregnant or breastfeeding women, woman not benefiting from effective contraception if of childbearing age
  • adults under tutorship, curatorship or under legal protection

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:

  • presence of a Parkinson's Disease according to United Kindom Parkinson's Disease Brain Bank criteria
  • complaint of nighttime unrest in favor of a probable Idiopathic REM sleep behavior disorder

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04652843


Contacts
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Contact: Laurène LECLAIR-VISONNEAU, MD +33 2 40 16 54 95 Laurene.LECLAIR@chu-nantes.fr

Locations
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France
Nantes Universitary Hospital
Nantes, Loire Atlantique, France, 44093
Contact: Laurene LECLAIR-VISONNEAU, MD    +33 2 40 16 54 95    laurene.leclair@chu-nantes.fr   
Principal Investigator: Laurene LECLAIR-VISONNEAU, MD         
Principal Investigator: Emmanuel CORON, MD         
Sponsors and Collaborators
Nantes University Hospital
France Parkinson Association
Luxia Scientific
INSERM - TENS - UMR 1235
Investigators
Layout table for investigator information
Principal Investigator: Laurène LECLAIR-VISONNEAU, MD CHU Nantes
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Responsible Party: Nantes University Hospital
ClinicalTrials.gov Identifier: NCT04652843    
Other Study ID Numbers: RC19_0401
First Posted: December 3, 2020    Key Record Dates
Last Update Posted: December 3, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Parkinson Disease
Inflammation
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Pathologic Processes