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

NCT04652843 | Terminated

• 1 other identifier: RC19_0401
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 1

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.

Conditions

Parkinson's Disease

Outcome Measures

Primary Outcomes (1)

• TNF-α

  TNF-α in colonic biopsies measured by ELISA

  In the three months following the inclusion

Secondary Outcomes (24)

• IFN-γ

  In the three months following the inclusion

• IL-6

  In the three months following the inclusion

• IL-1β

  In the three months following the inclusion

• IFN-α2

  In the three months following the inclusion

• MCP-1 (CCL2)

  In the three months following the inclusion

Study Arms (4)

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)

Procedure: Rectosignoidoscopy; Procedure: Coloscopy

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

Procedure: Rectosignoidoscopy; Procedure: Coloscopy

Parkinson's disease state Phase

OTHER

Group of 20 patients with Parkinson's Disease for more than 5 years

Procedure: Rectosignoidoscopy; Procedure: Coloscopy

Control

OTHER

Group of 20 patients undergoing coloscopy for family screening for digestive polyps

Procedure: Coloscopy

Interventions

Rectosignoidoscopy PROCEDURE

Rectosignoidoscopy for colonic biospsies collection

Beginning Parkinson's disease; Idiopathic REM sleep behavior disorders; Parkinson's disease state Phase

Coloscopy PROCEDURE

Coloscopy for colonic biospsies collection

Beginning Parkinson's disease; Control; Idiopathic REM sleep behavior disorders; Parkinson's disease state Phase

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Nantes University Hospital: lead
• France Parkinson Association: collaborator
• Luxia Scientific: collaborator
• Institut National de la Santé Et de la Recherche Médicale, France: collaborator

Study Sites (1)

Nantes Universitary Hospital

Nantes, Loire Atlantique, 44093, France

Location

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Laurène LECLAIR-VISONNEAU, MD

  Nantes University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 25, 2020
• First Posted: December 3, 2020
• Study Start: December 17, 2020
• Primary Completion: January 12, 2024
• Study Completion: January 12, 2024
• Last Updated: February 1, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)