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

Spinal Cord Injuries Clinical Trial

— 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05954845
• Other study ID #: RC23_0075
• Status: Recruiting
• Phase: N/A
• Start date: July 24, 2023
• Est. completion date: October 2025

Study information

• Verified date: November 2023
• Source: Nantes University Hospital
• Contact: Chloé LEFEVRE
• Phone: 02 40 84 60 66
• Email: chloe.lefevre[@]chu-nantes.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: October 2025
• Est. primary completion date: October 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Spinal Cord Injuries
• Wounds and Injuries

Intervention

Other:
• biopsies
Biopsies will be obtained from the right and left colon (5 biopsies per colic region)

Locations

Country	Name	City	State
France	CHU de Nantes	Nantes

Sponsors (1)

Lead Sponsor	Collaborator
Nantes University Hospital

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Measurement of sulfonic acid and HRP flux in biopsies placed in Ussing chamber		1 month
Primary	Quantifying the expression of junction molecules of the ZO-1 type		1 month
Primary	Number of serotonin-producing cells labelled with anti-5-HT antibody		1 month
Primary	The degree of expression of TPH1 and SERT in RT-qPCR		1 month
Primary	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		1 month
Primary	VIP, ACh and 5-HT concentration in the colonic mucosa		1 month
Primary	Expression levels of key inflammation cytokines (TNFa, IL 1ß, IFN?...)		1 month
Secondary	Correlation between intestinal permeability and type of neurological damage		1 month
Secondary	Correlation between intestinal permeability and degree of digestive function impairment		1 month