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

Parkinson's Disease Clinical Trial

— IBIM-Park  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04652843
• Other study ID #: RC19_0401
• Status: Terminated
• Phase: N/A
• Start date: December 17, 2020
• Est. completion date: January 12, 2024

Study information

• Verified date: January 2024
• Source: Nantes University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 77
• Est. completion date: January 12, 2024
• Est. primary completion date: January 12, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Inflammation
• Parkinson Disease
• Parkinson's Disease

Intervention

Procedure:
• Rectosignoidoscopy
Rectosignoidoscopy for colonic biospsies collection
• Coloscopy
Coloscopy for colonic biospsies collection

Locations

Country	Name	City	State
France	Nantes Universitary Hospital	Nantes	Loire Atlantique

Sponsors (4)

Lead Sponsor	Collaborator
Nantes University Hospital	France Parkinson Association, INSERM - TENS - UMR 1235, Luxia Scientific

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	TNF-a	TNF-a in colonic biopsies measured by ELISA	In the three months following the inclusion
Secondary	IFN-?	IFN-? in colonic biopsies measured by ELISA	In the three months following the inclusion
Secondary	IL-6	IL-6 in colonic biopsies measured by ELISA	In the three months following the inclusion
Secondary	IL-1ß	IL-1ß in colonic biopsies measured by ELISA	In the three months following the inclusion
Secondary	IFN-a2	IFN-a2 in colonic biopsies measured by ELISA	In the three months following the inclusion
Secondary	MCP-1 (CCL2)	MCP-1 (CCL2) in colonic biopsies measured by ELISA	In the three months following the inclusion
Secondary	IL-8 (CXCL8)	IL-8 (CXCL8) in colonic biopsies measured by ELISA	In the three months following the inclusion
Secondary	IL-10	IL-10 in colonic biopsies measured by ELISA	In the three months following the inclusion
Secondary	IL-12p70	IL-12p70 in colonic biopsies measured by ELISA	In the three months following the inclusion
Secondary	IL-17A	IL-17A in colonic biopsies measured by ELISA	In the three months following the inclusion
Secondary	IL-18	IL-18 in colonic biopsies measured by ELISA	In the three months following the inclusion
Secondary	IL-23	IL-23 in colonic biopsies measured by ELISA	In the three months following the inclusion
Secondary	IL-33	IL-33 in colonic biopsies measured by ELISA	In the three months following the inclusion
Secondary	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
Secondary	Diversity of the intestinal microbiota	Bacterial diversity in each group by genetic sequencing of 16s RNA	In the three months following the inclusion
Secondary	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
Secondary	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
Secondary	Duration of progression	Disease duration of progression as Parkinson's disease clinical severity parameter	At inclusion
Secondary	Age	Age as Parkinson's disease clinical severity parameter	At inclusion
Secondary	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
Secondary	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
Secondary	Montreal Cognitive Assessment score	Montreal Cognitive Assessment score as Parkinson's disease clinical severity parameter	At inclusion
Secondary	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
Secondary	Olfactory tests	Olfactory tests (Sniffin 'sticks test score) as Parkinson's disease clinical severity parameter	At inclusion
Secondary	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