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Inflammatory Bowel DiseasesROXANENCT05916274

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)

A study testing Blood and fecal samples and Coolonic biopsies in people with Inflammatory Bowel Diseases and Crohn Disease, run by Centre Hospitalier Régional d'Orléans at 1 site in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 6 to 17 years
What is being tested?
Blood and fecal samples and Coolonic biopsies
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
1 siteFrance
Study dates
31 May 2023to 29 Feb 2024
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 6 to 17 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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
Show all 11Show fewer
  • 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

Who cannot join

  • 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)
Show all 9Show fewer
  • Person under legal protection
  • Person not affiliated to a social security scheme
  • Pregnant or breastfeeding woman

Trial locations and contacts

1 site in 1 country.

France1 site
  • CHU Orléans

    Orléans

Other trials in France

About this study

Official title: Pro-inflammatory Role of Extracellular DNA in Inflammatory Bowel Disease in Children: Study of the cGAS-STING Pathway

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.

Read the detailed description

Inflammatory Bowel Diseases in children (IBD)-Crohn's disease (CD), ulcerative colitis (UC) are severe pathology that can affect the entire digestive tract. Their annual incidence is however constantly increasing.

IBD are complex multifactorial pathologies whose cause is still unknown today. IBD occurs on a predisposing genetic background in the presence of exogenous factors and alteration of the intestinal microbiota. Intestinal lesions are due to dysregulation of the intestinal immune system with increased secretion of pro-inflammatory cytokines at the expense of anti-inflammatory cytokines.

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. Their impact is not only individual (growth retardation, puberty delay, psychological disorders) but also family/parental, school and social. These particularities justify that biomedical research focuses on it in a more specific way.

Extracellular and extranuclear DNA (enDNA) play a major role in innate immunity by stimulating pro-inflammatory responses and activating type I interferon production. The pro-inflammatory action of enDNA is mediated by enzyme cGAS, protein STING, toll-like receptor 9 (TLR9), and the inflammasome complex NLRP3.

The investigators hypothesize that enDNA participates in the amplification of the inflammatory response at the intestinal and blood levels during pediatric IBD through the cGAS-STING pathway. They also hypothesize that there are links between the cGAS-STING pathway and other pathways involved in pediatric IBD such as NOD2 and Autophagy. The investigators will analyse blood and fecal samples, and colonic biopsies issued from ill children and controls 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.

Being tested
Blood and fecal samples, Coolonic biopsies
Keywords
Inflammatory Bowel disease, Crohn disease, Ulcerative colitis, cell-free DNA, cGAS, STING, Child, intestinal inflammation
Medical subject headings
Inflammatory Bowel Diseases, Crohn Disease, Colitis, Ulcerative, Bites and Stings

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Blood and fecal samplesBiological

    Blood and fecal samples will be performed

  • Coolonic biopsiesProcedure or surgery

    colonic biopsies will be analysed

Study groups in NCT05916274
Study groupRoleWhat they receive
Patients with samplesOtherBlood 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".
Receives: Biological: Blood and fecal samples; Procedure: Coolonic biopsies

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline

Secondary outcomes (14)
  1. quantitative difference of amount of circulating mtDNA

    to find quantitative differences between the 3 groups concerning the circulating mtDNA, the circulating total DNA, by the qPCR technique: by specific primer sequences to identify the origin of the DNA (mitochondrial or nuclear). Results will be expressed by the -2∆∆Ct method ("fold increase") compared to the control.

    Measured: Baseline

  2. Cytokine response

    to find quantitative differences between the 3 groups concerning the cytokine response by Luminex®: in pg/ml or in ng/ml depending on the cytokines

    Measured: Baseline

  3. inflammatory / dysimmune response of cytokines

    to find quantitative differences between the 3 groups concerning the inflammatory / dysimmune response of cytokines, components of the cGAS-STING pathways autophagy, NOD2, intestinal mucins, integrins, cadherins by RNAseq type transcriptomic analysis in Transcript Per Million (TPM).

    This outcome wil be mesured at the blood level abd the colonic level.

    Measured: Baseline

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

    to find quantitative differences between the 3 groups concerning the study of DNA methylation by Methyl-Seq. Results expessed in pourcentage of methylation. This outcome will be mesured at the bllod level and the colonic level.

    Measured: Baseline

  5. Activation (phosphorylation) of the components of the cGAS-STING pathway

    Activation (phosphorylation) of the components of the cGAS-STING pathway (proteins cGAS, p-CGAS, STING,p-STING,TBK1, p-TBK1,IRF-3, p-IRF-3) by Western-Blot

    Measured: Baseline

  6. plasma DNase activity

    plasma DNase activity in Kunitz unitz

    Measured: baseline

  7. differences in microbial distribution

    search for quantitative differences in microbial distribution between the 3 groups by pyrosequencing RNA 16s of the microbiota at the fecal level

    Measured: Baseline

  8. quantity (number of "reads") of colonic STING-specific mRNA

    quantitative differences between the 3 groups concerning the quantity (number of "reads") of colonic STING-specific mRNA at the colonic level

    Measured: Baseline

  9. extracellular DNA by qPCR

    We will use specific primer sequences to identify the origin of the DNA (mitochondrial or nuclear). Results will be expressed by the -2∆∆Ct method ("fold increase") compared to the control. This outcome will be mesured at the colonic level.

    Measured: Baseline

  10. Amount of STING in the cytoplasm

    cytoplasmic presence of STING by histology, immunohistochemical staining and optical microscopy analysis. Results will be qualitative (present/absent; localization) and quantitative based on optical density (pourcentage of positive cells)

    Measured: Baseline

  11. Amount of cGAS in the cytoplasm

    cytoplasmic presence of cGAS by histology, immunohistochemical staining and optical microscopy analysis. Results will be qualitative (present/absent; localization) and quantitative based on optical density (pourcentage of positive cells)

    Measured: Baseline

  12. Amount of nuclear DNA in teh cytoplasm

    cytoplasmic presence of nuclear DNA by histology, immunohistochemical staining and optical microscopy analysis. Results will be qualitative (present/absent; localization) and quantitative based on optical density (pourcentage of positive cells)

    Measured: Baseline

  13. Amount of mitochondrial DNA in the cytoplasm

    cytoplasmic presence of mitochondrial DNA by histology, immunohistochemical staining and optical microscopy analysis. Results will be qualitative (present/absent; localization) and quantitative based on optical density (pourcentage of positive cells)

    Measured: Baseline

  14. Amount of colonic DNase activity

    Measurement of colonic DNase activity in Kunitz unitz

    Measured: Baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Jun 2023
  2. Study start31 May 2023
  3. Primary completion29 Feb 2024
  4. Study completion29 Feb 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Health services research
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05916274
Sponsor's protocol ID
CHRO-2023-01
Acronym
ROXANE
Status last verified
Dec 2025
First submitted
5 May 2023
Last updated
23 Dec 2025
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 29281834
  • 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.

    PubMed 29346345
  • 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.

    PubMed 31582793
  • 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.

    PubMed 29718255
  • 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.

    PubMed 33381513
  • 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.

    PubMed 35344224
  • 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.

    PubMed 34453041
  • 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.

    PubMed 35280696

Questions about this trial

What is this clinical trial studying?

A study testing Blood and fecal samples and Coolonic biopsies in people with Inflammatory Bowel Diseases and Crohn Disease, run by Centre Hospitalier Régional d'Orléans at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Amount of mRNA specific for colonic cGAS (time frame: Baseline). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05916274, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Dec 2025.

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