Exploration of the Activity of DNA Located Outside of Cellular Nucleus to Amplify Inflammation in Inflammatory Bowel Disease in Children Through Biological Pathway Cyclic GMP-AMP Synthase (cGAS) - Stimulator of Interferon Genes (STING)

NCT05916274 | Completed

• 1 other identifier: CHRO-2023-01
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Frequency of Inflammatory Bowel Diseases in children (IBD)-Crohn's disease (CD), Ulcerative colitis (UC) is constantly increasing. Pediatric-onset IBD represent a different nosological entity (from adult IBD) because of their major inflammatory activity, their significant anatomical extent and their stenotic and/or fistulizing character sometimes from diagnosis. Intestinal lesions are due to dysregulation of the intestinal immune system but the cause is unknown. The investigators hypothesize that extranuclear DNA participates in the amplification of the inflammatory response at the intestinal and blood levels during pediatric IBD through the cGAS-STING pathway. The investigators will analyse blood and fecal samples, and colonic biopsies issued from ill children and control participants on age of 6 to 17 years. The investigators think that this study will provide a better understanding of the mechanisms involved in pediatric IBD, assess the place of the cGAS-STING pathway, identify potential biomarkers of pediatric IBD and new potential therapeutic targets based in particular on the inhibition of the cGAS-STING pathway.

Conditions

Inflammatory Bowel Diseases; Crohn Disease; Ulcerative Colitis

Keywords

Inflammatory Bowel disease; Crohn disease; Ulcerative colitis; cell-free DNA; cGAS; STING; Child; intestinal inflammation

Outcome Measures

Primary Outcomes (1)

• Amount of mRNA specific for colonic cGAS

  the comparison, between the 3 groups of patients, of the quantity of specific mRNA of colonic cGAS expressed as the number of "reads" during RNA sequencing (RNAseq), by a Mann-Whitney U test. It is planned from the outset to compare the groups 2 by 2, regardless of the result of an overall test such as a Kruskal-Wallis test.

  Baseline

Secondary Outcomes (14)

• quantitative difference of amount of circulating mtDNA

  Baseline

• Cytokine response

  Baseline

• inflammatory / dysimmune response of cytokines

  Baseline

• Difference of DNA methylation by Methyl-Seq between the 3 groups

  Baseline

• Activation (phosphorylation) of the components of the cGAS-STING pathway

  Baseline

Study Arms (1)

Patients with samples

OTHER

Blood and fecal samples, and colonic biopsies will be analysed and compared between 3 groups of participants :1/ Active IBD; 2/Inactive IBD; 3/Controls "non-IBD".

Biological: Blood and fecal samples; Procedure: Coolonic biopsies

Interventions

Blood and fecal samples BIOLOGICAL

Blood and fecal samples will be performed

Patients with samples

Coolonic biopsies PROCEDURE

colonic biopsies will be analysed

Patients with samples

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Participants aged from 6 years inclusive to 17 years inclusive
• Boys and girls
• Presenting an IBD or suspicion of IBD
• Requiring a colonoscopy for diagnosis or follow-up or other reason (abdominal pain, diarrhoea, rectal bleeding, weight loss) not confirming the diagnosis of Crohn's disease or Ulcerative Colitis
• Active IBD if:
• CD: PCDAI score \>5 and CRP\>20mg/L and faecal calprotectin\> 400 µg/g
• UC: PUCAI score\>10 and faecal calprotectin\>250 µg/g
• IBD in remission if:
• CD: PCDAI score\<5 and CRP\<20mg/L and faecal calprotectin\<400 µg/g
• UC: PUCAI score \<10 and faecal calprotectin \< 250 µg/g
• Patients and their parents who gave their consent to participate in the study

You may not qualify if:

• Refusal of the participant and/or one of his two parents
• Body weight less than or equal to 20 kg
• Blood hemoglobin level less than or equal to 9 g/dl
• Refusal or contraindication to general anesthesia
• Co-existing severe chronic pathology and/or treatment that could interfere with the results of the study; example: trisomy 21, treatment with growth hormone etc.
• Protected person (under guardianship or curatorship)
• Person under legal protection
• Person not affiliated to a social security scheme
• Pregnant or breastfeeding woman

Sponsors & Collaborators

• Centre Hospitalier Régional d'Orléans: lead

Study Sites (1)

CHU Orléans

Orléans, France

Location

Related Publications (8)

• Ahn J, Son S, Oliveira SC, Barber GN. STING-Dependent Signaling Underlies IL-10 Controlled Inflammatory Colitis. Cell Rep. 2017 Dec 26;21(13):3873-3884. doi: 10.1016/j.celrep.2017.11.101.

  PMID: 29281834 BACKGROUND

• Canesso MCC, Lemos L, Neves TC, Marim FM, Castro TBR, Veloso ES, Queiroz CP, Ahn J, Santiago HC, Martins FS, Alves-Silva J, Ferreira E, Cara DC, Vieira AT, Barber GN, Oliveira SC, Faria AMC. The cytosolic sensor STING is required for intestinal homeostasis and control of inflammation. Mucosal Immunol. 2018 May;11(3):820-834. doi: 10.1038/mi.2017.88. Epub 2017 Dec 20.

  PMID: 29346345 BACKGROUND

• Martin GR, Blomquist CM, Henare KL, Jirik FR. Stimulator of interferon genes (STING) activation exacerbates experimental colitis in mice. Sci Rep. 2019 Oct 3;9(1):14281. doi: 10.1038/s41598-019-50656-5.

  PMID: 31582793 BACKGROUND

• Boyapati RK, Dorward DA, Tamborska A, Kalla R, Ventham NT, Doherty MK, Whitfield PD, Gray M, Loane J, Rossi AG, Satsangi J, Ho GT. Mitochondrial DNA Is a Pro-Inflammatory Damage-Associated Molecular Pattern Released During Active IBD. Inflamm Bowel Dis. 2018 Sep 15;24(10):2113-2122. doi: 10.1093/ibd/izy095.

  PMID: 29718255 BACKGROUND

• Vrablicova Z, Tomova K, Tothova L, Babickova J, Gromova B, Konecna B, Liptak R, Hlavaty T, Gardlik R. Nuclear and Mitochondrial Circulating Cell-Free DNA Is Increased in Patients With Inflammatory Bowel Disease in Clinical Remission. Front Med (Lausanne). 2020 Dec 14;7:593316. doi: 10.3389/fmed.2020.593316. eCollection 2020.

  PMID: 33381513 BACKGROUND

• Khan S, Mentrup HL, Novak EA, Siow VS, Wang Q, Crawford EC, Schneider C, Comerford TE 4th, Firek B, Rogers MB, Loughran P, Morowitz MJ, Mollen KP. Cyclic GMP-AMP synthase contributes to epithelial homeostasis in intestinal inflammation via Beclin-1-mediated autophagy. FASEB J. 2022 May;36(5):e22282. doi: 10.1096/fj.202200138R.

  PMID: 35344224 BACKGROUND

• Zhao F, Zheng T, Gong W, Wu J, Xie H, Li W, Zhang R, Liu P, Liu J, Wu X, Zhao Y, Ren J. Extracellular vesicles package dsDNA to aggravate Crohn's disease by activating the STING pathway. Cell Death Dis. 2021 Aug 27;12(9):815. doi: 10.1038/s41419-021-04101-z.

  PMID: 34453041 BACKGROUND

• Chen C, Zhang Y, Tao M, Zhao X, Feng Q, Fei X, Fu Y. Atrial Natriuretic Peptide Attenuates Colitis via Inhibition of the cGAS-STING Pathway in Colonic Epithelial Cells. Int J Biol Sci. 2022 Feb 7;18(4):1737-1754. doi: 10.7150/ijbs.67356. eCollection 2022.

  PMID: 35280696 BACKGROUND

MeSH Terms

Conditions

Inflammatory Bowel Diseases; Crohn Disease; Colitis, Ulcerative; Bites and Stings

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Colitis; Colonic Diseases; Poisoning; Chemically-Induced Disorders; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Georges DIMITROV, MD

  CHU Orleans

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 5, 2023
• First Posted: June 23, 2023
• Study Start: May 31, 2023
• Primary Completion: February 29, 2024
• Study Completion: February 29, 2024
• Last Updated: December 23, 2025

Record last verified: 2025-12

Locations

FR (1)