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The Enteric Nervous System in Spinal Cord Injury: Study of the Enteric Nervous System and the Intestinal Epithelial Barrier Via Colonic Biopsies in Spinal Cord Injury Patients (TENS-SCI)

Primary Purpose

Spinal Cord Injuries

Status
Not yet recruiting
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
biopsies
Sponsored by
Nantes University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Spinal Cord Injuries focused on measuring Spinal cord injury, Neurogastroenterology, Pathophysiology, Enteric nervous system, Intestinal epithelial barrier

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patient with signed consent Patient over 18 and under 80 years of age Patient with acquired traumatic or non-traumatic spinal cord injury Patient with an indication for colonoscopy or rectosigmoidoscopy at the Nantes University Hospital Gastroenterology Department Eligible for French social security Patient enrolled in the COSCINUS cohort Exclusion Criteria: Patients in emergency situations, deprived of liberty, or not covered by the social security system Patient under legal protection Patient suffering from an inflammatory digestive disease Patient on anticoagulant therapy with no possibility of discontinuation or relay Patient with contraindications to colonoscopy/rectosigmoidoscopy Pregnant or breast-feeding patient

Sites / Locations

  • CHU de Nantes

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

colonic biopsies

Arm Description

participants will have colonic biopsies taken following a colonoscopy/rectosigmoidoscopy previously indicated for spinal cord injured patients.

Outcomes

Primary Outcome Measures

Measurement of sulfonic acid and HRP flux in biopsies placed in Ussing chamber
Quantifying the expression of junction molecules of the ZO-1 type
Number of serotonin-producing cells labelled with anti-5-HT antibody
The degree of expression of TPH1 and SERT in RT-qPCR
Calculation of the number of neurons and the proportion of different neurochemical phenotypes of neurons in relation to the total number of neurons in the submucosal plexus
VIP, ACh and 5-HT concentration in the colonic mucosa
Expression levels of key inflammation cytokines (TNFα, IL 1β, IFNɣ...)

Secondary Outcome Measures

Correlation between intestinal permeability and type of neurological damage
Correlation between intestinal permeability and degree of digestive function impairment

Full Information

First Posted
July 13, 2023
Last Updated
July 13, 2023
Sponsor
Nantes University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05954845
Brief Title
The Enteric Nervous System in Spinal Cord Injury: Study of the Enteric Nervous System and the Intestinal Epithelial Barrier Via Colonic Biopsies in Spinal Cord Injury Patients
Acronym
TENS-SCI
Official Title
The Enteric Nervous System in Spinal Cord Injury : étude du système Nerveux entérique et de la barrière épithéliale Intestinale Via la réalisation de Biopsies Coliques Chez Les Patients Porteurs de lésion médullaire
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
July 2023 (Anticipated)
Primary Completion Date
October 2025 (Anticipated)
Study Completion Date
October 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Nantes University Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The goal of this clinical trial is to learn more about the enteric nervous system (ENS) and the intestinal epithelial barrier (IEB) in patients with spinal cord injury (SCI). The main questions it aims to answer are : to characterize the functional (permeability, serotonin production, enteric neuronal phenotype, etc.), proteomic (junction molecules) and transcriptomic (inflammation genes, neuromediator expression, etc.) remodeling of the colonic mucosa and ENS in SCI patients, in comparison with control data. to correlate intestinal permeability (and all remodeling parameters) with the type of neurological impairment i.e. the neurological level of the lesion, quantification of neurological impairment (motor and sensory scores) and the completeness and incompleteness of a lesion. to identify a link with disease severity markers to identify therapeutic targets that could subsequently be tested in the animal model before being proposed in clinical trials. Participants will have colonic biopsies taken following a colonoscopy/rectosigmoidoscopy previously indicated for spinal cord injured patients. Biopsies will be obtained from the right and left colon.
Detailed Description
Injury to the spinal cord, whether traumatic or not, leads to numerous organ deficiencies, particularly vegetative deficiencies. Digestive and anorectal dysfunctions are among these, and are the main deficiencies that spinal cord injury patients would like to see disappear, even before motor recovery or walking, for example. However, the treatments available are essentially empirical (dietary hygiene rules, use of laxatives, digital exoneration maneuvers) and only partially effective. Pathophysiological knowledge of digestive dysfunction in the medullo-injured is mainly focused on dysfunctions of extrinsic vegetative innervation. In contrast, there are few studies concerning the dysfunction of intrinsic digestive innervation in this pathology, i.e. the enteric nervous system (ENS), and the intestinal epithelial barrier (IEB), which are central players involved in the digestive disorders observed during the course of numerous digestive or extra-digestive pathologies, such as Parkinson's Disease (PD) in particular. To date, the nature of ENS/EIB remodeling has not been correlated with clinical data, in order to potentially link it to a clinical phenotype of these patients, and to determine their capacity to become predictive biomarkers of disease progression, severity and/or response to treatment. By combining functional exploration of the intestinal barrier, protein and transcriptomic analysis of biopsies, the aim is to 1) characterize functional (permeability, serotonin production), proteomic and transcriptomic remodeling of the mucosa in SCI patients compared with control groups, 2) make the link with patients' clinical data, 3) identify markers of disease severity (lesion level, severity of intestinal dysfunction) and 4) identify therapeutic targets that could be tested in the animal model before being proposed in clinical trials.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Spinal Cord Injuries
Keywords
Spinal cord injury, Neurogastroenterology, Pathophysiology, Enteric nervous system, Intestinal epithelial barrier

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
participants will have colonic biopsies taken following a colonoscopy/rectosigmoidoscopy previously indicated for spinal cord injured patients. Biopsies will be obtained from the right and left colon.
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
colonic biopsies
Arm Type
Experimental
Arm Description
participants will have colonic biopsies taken following a colonoscopy/rectosigmoidoscopy previously indicated for spinal cord injured patients.
Intervention Type
Other
Intervention Name(s)
biopsies
Intervention Description
Biopsies will be obtained from the right and left colon (5 biopsies per colic region)
Primary Outcome Measure Information:
Title
Measurement of sulfonic acid and HRP flux in biopsies placed in Ussing chamber
Time Frame
1 month
Title
Quantifying the expression of junction molecules of the ZO-1 type
Time Frame
1 month
Title
Number of serotonin-producing cells labelled with anti-5-HT antibody
Time Frame
1 month
Title
The degree of expression of TPH1 and SERT in RT-qPCR
Time Frame
1 month
Title
Calculation of the number of neurons and the proportion of different neurochemical phenotypes of neurons in relation to the total number of neurons in the submucosal plexus
Time Frame
1 month
Title
VIP, ACh and 5-HT concentration in the colonic mucosa
Time Frame
1 month
Title
Expression levels of key inflammation cytokines (TNFα, IL 1β, IFNɣ...)
Time Frame
1 month
Secondary Outcome Measure Information:
Title
Correlation between intestinal permeability and type of neurological damage
Time Frame
1 month
Title
Correlation between intestinal permeability and degree of digestive function impairment
Time Frame
1 month

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patient with signed consent Patient over 18 and under 80 years of age Patient with acquired traumatic or non-traumatic spinal cord injury Patient with an indication for colonoscopy or rectosigmoidoscopy at the Nantes University Hospital Gastroenterology Department Eligible for French social security Patient enrolled in the COSCINUS cohort Exclusion Criteria: Patients in emergency situations, deprived of liberty, or not covered by the social security system Patient under legal protection Patient suffering from an inflammatory digestive disease Patient on anticoagulant therapy with no possibility of discontinuation or relay Patient with contraindications to colonoscopy/rectosigmoidoscopy Pregnant or breast-feeding patient
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Chloé LEFEVRE
Phone
02 40 84 60 66
Ext
+33
Email
chloe.lefevre@chu-nantes.fr
Facility Information:
Facility Name
CHU de Nantes
City
Nantes
ZIP/Postal Code
44000
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chloé LEFEVRE, Dr
Email
chloe.lefevre@chu-nantes.fr
First Name & Middle Initial & Last Name & Degree
Chloé LEFEVRE, Dr

12. IPD Sharing Statement

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The Enteric Nervous System in Spinal Cord Injury: Study of the Enteric Nervous System and the Intestinal Epithelial Barrier Via Colonic Biopsies in Spinal Cord Injury Patients

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