- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04652843
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)
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.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Laurene LECLAIR-VISONNEAU, MD
- Phone Number: +33 2 40 16 54 95
- Email: laurene.leclair@chu-nantes.fr
Study Locations
-
-
Loire Atlantique
-
Nantes, Loire Atlantique, France, 44093
- Nantes Universitary Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: 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)
|
Rectosignoidoscopy for colonic biospsies collection
Coloscopy for colonic biospsies collection
|
Other: 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
|
Rectosignoidoscopy for colonic biospsies collection
Coloscopy for colonic biospsies collection
|
Other: Parkinson's disease state Phase
Group of 20 patients with Parkinson's Disease for more than 5 years
|
Rectosignoidoscopy for colonic biospsies collection
Coloscopy for colonic biospsies collection
|
Other: Control
Group of 20 patients undergoing coloscopy for family screening for digestive polyps
|
Coloscopy for colonic biospsies collection
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
TNF-α
Time Frame: In the three months following the inclusion
|
TNF-α in colonic biopsies measured by ELISA
|
In the three months following the inclusion
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
IFN-γ
Time Frame: In the three months following the inclusion
|
IFN-γ in colonic biopsies measured by ELISA
|
In the three months following the inclusion
|
IL-6
Time Frame: In the three months following the inclusion
|
IL-6 in colonic biopsies measured by ELISA
|
In the three months following the inclusion
|
IL-1β
Time Frame: In the three months following the inclusion
|
IL-1β in colonic biopsies measured by ELISA
|
In the three months following the inclusion
|
IFN-α2
Time Frame: In the three months following the inclusion
|
IFN-α2 in colonic biopsies measured by ELISA
|
In the three months following the inclusion
|
MCP-1 (CCL2)
Time Frame: In the three months following the inclusion
|
MCP-1 (CCL2) in colonic biopsies measured by ELISA
|
In the three months following the inclusion
|
IL-8 (CXCL8)
Time Frame: In the three months following the inclusion
|
IL-8 (CXCL8) in colonic biopsies measured by ELISA
|
In the three months following the inclusion
|
IL-10
Time Frame: In the three months following the inclusion
|
IL-10 in colonic biopsies measured by ELISA
|
In the three months following the inclusion
|
IL-12p70
Time Frame: In the three months following the inclusion
|
IL-12p70 in colonic biopsies measured by ELISA
|
In the three months following the inclusion
|
IL-17A
Time Frame: In the three months following the inclusion
|
IL-17A in colonic biopsies measured by ELISA
|
In the three months following the inclusion
|
IL-18
Time Frame: In the three months following the inclusion
|
IL-18 in colonic biopsies measured by ELISA
|
In the three months following the inclusion
|
IL-23
Time Frame: In the three months following the inclusion
|
IL-23 in colonic biopsies measured by ELISA
|
In the three months following the inclusion
|
IL-33
Time Frame: In the three months following the inclusion
|
IL-33 in colonic biopsies measured by ELISA
|
In the three months following the inclusion
|
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
|
In the three months following the inclusion
|
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
|
In the three months following the inclusion
|
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
|
In the three months following the inclusion
|
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)
|
In the three months following the inclusion
|
Duration of progression
Time Frame: At inclusion
|
Disease duration of progression as Parkinson's disease clinical severity parameter
|
At inclusion
|
Age
Time Frame: At inclusion
|
Age as Parkinson's disease clinical severity parameter
|
At inclusion
|
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
|
At inclusion
|
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
|
At inclusion
|
Montreal Cognitive Assessment score
Time Frame: At inclusion
|
Montreal Cognitive Assessment score as Parkinson's disease clinical severity parameter
|
At inclusion
|
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
|
At inclusion
|
Olfactory tests
Time Frame: At inclusion
|
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
Time Frame: At inclusion
|
Scales for Outcomes in Parkinson's Disease - Autonomic Dysfunction score as Parkinson's disease clinical severity parameter
|
At inclusion
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Laurène LECLAIR-VISONNEAU, MD, Nantes University Hospital
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- RC19_0401
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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