Autophagy in Paediatric Crohn's Disease (P-IBDphagy)

Autophagic Activity Characterization in Pediatric Crohn's Disease

Crohn's disease is a multifactorial complex disease resulting in a between microbiota and immune system. Indeed, GWAS (Genome-Wide Association Studies) association study pinpointed polymorphisms as genes susceptibility on more than 200 loci. Among them genes coding for proteins involved in autophagy machinery (i.e: ATG16L1, IRGM et NDP52). Autophagy is a ubiquitous intracellular mechanism mandatory for protein and microorganism recycling.

So far, the role of autophagy in gut inflammation and intestinal homeostasis in Crohn's disease patients is partially understand. Then, investigators plan to evaluate, on native cells, the autophagic flux in pediatric patients suffering of a Crohn's disease compare to controls.

Study Overview

• Status: Not yet recruiting
• Conditions: Crohn Disease; Pediatric Crohns Disease
• Intervention / Treatment: Other: Blood samples; Other: Biopsies

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Rémi DUCLAUX-LORAS, MD, PhD; Phone Number: +33 0472357050; Email: Remi.duclaux-loras@chu-lyon.fr

Study Locations

• France
  • Bron, France, 69500
    • Service Hépatologie, Gastroentérologie et Nutrition pédiatrique, Hôpital Femme Mère Enfant, HCL
    • Contact: Rémi DUCLAUX-LORAS, MD, PhD; Phone Number: +33 0472357050; Email: Remi.duclaux-loras@chu-lyon.fr
    • Principal Investigator: Rémi DUCLAUX-LORAS, MD, PhD
    • Sub-Investigator: Nicolas CARON, MD
    • Sub-Investigator: Sophie HEISSAT, MD
    • Sub-Investigator: Barbara ROHMER, MD
    • Sub-Investigator: Noémie LAVERDURE, MD
    • Sub-Investigator: Mathias RUIZ, MD
    • Sub-Investigator: Pierre POINSOT, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

For Crohn's Disease group :

• Age between 6 and 17 inclusive
• Patients with a weight > 25 kg at the time of inclusion
• Patients with Crohn's disease requiring ileocolonoscopy (diagnosis or follow-up)
• Mild to severe Crohn's disease consistent with PCDAI disease activity score
• Patients on nutritional therapy (Modulen/Modulife), corticosteroids, salicylic derivatives, immunosuppressants, biotherapies (anti-TNF, vedolizumab and ustekinumab) or without treatment
• Consent form signed by the patient or the holder(s) of parental authority.
• Affiliation to a social security scheme or beneficiaries of a similar scheme.

For Control group:

• Between 6 and 17 years old included
• Presenting a weight > 25 kg at the time of inclusion
• Without a diagnosis of Crohn's disease
• Requiring evaluation by ileoendoscopy
• Consent form signed by the patient or the holder(s) of parental authority.
• Affiliation to a social security scheme or beneficiaries of a similar scheme.

Exclusion Criteria:

• Refusal to participate in the protocol
• Intercurrent infection
• Ongoing antibiotic treatment
• Patient involved in another interventional study protocol including an exclusion period still in progress at pre-inclusion
• Pregnant, parturient or breastfeeding women (on questioning)
• Persons deprived of their liberty by a judicial or administrative decision
• Persons subject to psychiatric care
• Persons admitted to a health or social establishment for purposes other than research

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Crohn's Disease Group; Patients followed for a Crohn's Disease in consultation or in day hospital aged between 6 and 18 years old.	Other: Blood samples; Blood sample of maximum 20ml (5 tubes of EDTA of 4ml or 5 tubes of EDTA of 2ml and a tube for the conservation of genomic DNA); Other: Biopsies; 5 biopsies (one for each segment of the intestine explored: ileum, right colon, transverse colon left colon and sigmoid) will be taken during the ileocolonoscopy
Other: Control Group; Patients followed for functional abdominal disorders	Other: Blood samples; Blood sample of maximum 20ml (5 tubes of EDTA of 4ml or 5 tubes of EDTA of 2ml and a tube for the conservation of genomic DNA); Other: Biopsies; 5 biopsies (one for each segment of the intestine explored: ileum, right colon, transverse colon left colon and sigmoid) will be taken during the ileocolonoscopy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantification of autophagic flux by western blot.	LC3II/LC3I will be measured by western blot after booking the autophagic flux at different time point.	1 day (during hospitalization for ileocolonoscopy)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of autophagic polymorphisms in pediatric Crohn's disease population	DNA sequencing of polymorphisms reported in the literature as gene mutations susceptibility for Crohn's disease.	1 day (during hospitalization for ileocolonoscopy)

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2025
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: April 24, 2023
• First Submitted That Met QC Criteria: April 24, 2023
• First Posted (Actual): May 6, 2023

Study Record Updates

• Last Update Posted (Estimated): December 12, 2024
• Last Update Submitted That Met QC Criteria: December 11, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Polymorphism; Crohn's Disease; Autophagy
• Additional Relevant MeSH Terms: Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: 69HCL21_1020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No