Evaluation of Molecular Mechanisms of Non-response to Therapy in Patients With Inflammatory Bowel Disease

NCT05733845 | Recruiting

• 1 other identifier: 2022-A02277-36
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Inflammatory bowel diseases (IBD) represent a group of immune-mediated disorders, in which currently unidentified trigger factors drive the manifestation of chronic relapsing- remitting destructive inflammatory episodes in the gut. IBD comprise two main disease entities, ulcerati\\ie colitis (UC) and Crohn s disease (CD). The diseases differ in anatomical distribution, with continuous, uniform inflammation restricted to the colon in UC, and multifocal inflammation extended throughout the entire gastrointestinal tract from mouth to anus in CD. Clinical symptoms of IBD may include bloody stools, abdominal pain, fatigue, diarrhoea, fever and weight loss. Extra-intestinal symptoms occurring in up to 40% of patients, e.g. anaemia, skin lesions (e.g. erythema nodosum, pyoderma), arthritis and uveitis, and other complications directly related to the disease organ, such as fistula in CD are considered to reflect an overwhelming systemic inflammatory state. Disease onset typically manifests at age 15-35 years, men and women are almost equally affected. In addition, paediatric forms of IBD that often represent complex, se\\/ere monogenic forms of the disease, are seen. The incidence rates of IBD in Europe are about 6.3 (CD) and 11.8 (UC) per 100.000 persons. With growing incidence rates and overall reduced mortality the lifetime prevalence of IBD is expected to rise. The estimated lifetime prevalence of 0.3%-0.5% of the European population corresponds to estimates of 1.5-2 million patients with IBD. Appropriate selection of therapies and their timing of introduction (decision support) in the course of IBD will be essential to reach a higher degree of disease control (across patients and within individual patients) than it is achie\\led today. In many instances, comparati\\ie data is missing and combinations or sequential therapies are not developed. In summary, despite some treatment successes, major challenges remain. The investigators have decided to include patients with inflammatory bowel disease (IBD) in which targeted therapies are administered as part of standard helathcare and which aims at identifiyng solid biomarker signatures as well as molecular pathways and mechanisms linked to response and non-response to therapy. Choice od medications (which are all approved for first line use) is by treating physicians. All follow-up procedures are according to standards of care.

Conditions

Crohn's Disease; Ulcerative Colitis

Keywords

biomarkers; Crohn's disease; ulcerative colitis; disease activity; therapy reponse

Outcome Measures

Primary Outcomes (2)

• To identify solid biomarkers signatures as well as molecular pathways and mechanisms linked to response and non-response to therapy in ulcerative colitis patient.

  -For Ulcerative Colitis (UC) patient: overall Mayo score correlated with Mayo endoscopy and bleeding subscore will be measured. Mayo score composed by 4 items: stool frequency; rectal bleeding, mucosal appearance at endoscopy and physician rating of disease activity. Mayo score: Score \<2 : no activity Score between 3 and 5: mild activity Score between 6 and 10 :moderate activity Score \>11 : severe activity

  week 14

• To identify solid biomarkers signatures as well as molecular pathways and mechanisms linked to response and non-response to therapy in Crohn's disease patient.

  -For Crohn's Disease (CD) patient : Crohn's disease activity index (CDAI) and simple endoscopic response (SES-CD) wil be measured. CDAI is the sum of 8 components: number of liquid or soft stools, daily abdominal pain, patient well-being, complications, use of diphenoxylate or opiates as anti-diarreheal, abdominal mass, hematocrit and body weight. Level of disease activity: Non-active disease: CDAI \< 150 Mild disease activity: CDAI \>= 150 and \<220 Moderate disease activity: CDAI \>= 220 and \<450 Severe disease activity: CDAI \> 450 SES-CD assesses the size of mucosal ulcers, the ulcerated surface, the endoscopic extension and the presence of stenosis. SES-CD score: 0 - 2 remission 3 - 6 mild endoscopic activity 7 - 15 moderate endoscopic activity \> 15 severe endoscopic activity

  week 14

Secondary Outcomes (5)

• To correlate identifed potential biomarkers with disease activity, progression and response to therapy by clinical remission in Crohn's disease patient

  week 52

• To correlate identifed potential biomarkers with disease activity, progression and response to therapy by clinical remission in Ulcerative colitis patient

  week 52

• To correlate identifed potential biomarkers with disease activity, progression and response to therapy by patient-reported outcomes

  week 52

• To correlate identifed potential biomarkers with disease activity, progression and response to therapy by complications-reported.

  week 52

• To correlate identifed potential biomarkers with disease activity, progression and response to therapy by disease progression.

  week 52

Other Outcomes (5)

• Fatigue assessment

  Baseline visit (time -4 weeks to 0), visit 1 (time 0), visit 2 (time 0+2 weeks), visit 3 (time 0+14 weeks), visit 4 (time 0+26 weeks) and visit 5 (time 0+52 weeks)

• Emotional distress-depression assessment

  Baseline visit (time -4 weeks to 0), visit 1 (time 0), visit 2 (time 0+2 weeks), visit 3 (time 0+14 weeks), visit 4 (time 0+26 weeks) and visit 5 (time 0+52 weeks)

• General Health Survey assessment

  Baseline visit (time -4 weeks to 0), visit 1 (time 0), visit 2 (time 0+2 weeks), visit 3 (time 0+14 weeks), visit 4 (time 0+26 weeks) and visit 5 (time 0+52 weeks)

Study Arms (1)

Samples

OTHER

The intervention is to collect blood; urine; saliva and stool samples but also mucosal biopsies at each protocol visits (baseline and follow up visits).

Other: Samples

Interventions

Samples OTHER

The intervention is to collect blood; urine; saliva and stool samples but also mucosal biopsies at each protocol visits (baseline and follow up visits).

Samples

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients ≥ 18 years of age (at the time of signing the Informed Consent)
• Person informed about study organization and having signed the informed consent.
• Established diagnosis of Crohn's dsease or ulcerative colitis with a minimum disease duration of 3 months
• Moderate to severe disease activity
• UC : Mayo Score ≥ 6 including endoscopy score of ≥ 2
• CD : CDAI score betwenn 220 and 450 (inclusive)
• Indication to start any biological or small molecule agent (anti-TNF, anti-IL 21/23, anti-integrin and JAK-inhibitors)
• In case of treatment with corticosteroid : stable dose for at least 3 weeks prior to baseline, dosage ≤ 20 mg prednisone
• Indication for colonoscopy for the assessment of disease activity as for standards of care and current guidelines
• Person affiliated to or beneficiary of a social security plan

You may not qualify if:

• Diagnosis of indeterminate colitis, microscopic colitis, ischaemic colitis, infectious colitis, radiation colitis
• Absolute contraindications to colonoscopy procedures, complication during previous endoscopy
• Bleeding disorders
• Indication for surgery for UC
• Rectal topical therapy (enemas or suppositories) ≤ 2 weeks prior to baseline
• Treatment with \> 20 mg prednisone within 3 weeks prior to baseline
• Anaemia (haemoglobbin \< 10g/dl) at baseline
• Subject unable to comply with the study procedures
• Person referred in articles L.1121-5, L. 1121-7 and L.1121-8 of the Public Health Code:
• Pregnant, parturient or breastfeeding woman
• Minor person (non-emancipated)
• Adult person under legal protection (any form of public guardianship)
• Adult person incapable of giving consent and not under legal protection
• Person deprived of liberty for judicial or administrative decision, person under psychiatric care as referred in articles L. 3212-1 and L. 3213-1.

Sponsors & Collaborators

• Central Hospital, Nancy, France: lead

Study Sites (1)

CHRU of Nancy

Vandœuvre-lès-Nancy, CHRU de Nancy, 54511, France

RECRUITING

Related Publications (2)

• Burisch J, Jess T, Martinato M, Lakatos PL; ECCO -EpiCom. The burden of inflammatory bowel disease in Europe. J Crohns Colitis. 2013 May;7(4):322-37. doi: 10.1016/j.crohns.2013.01.010. Epub 2013 Feb 8.

  PMID: 23395397 RESULT

• Ng SC, Shi HY, Hamidi N, Underwood FE, Tang W, Benchimol EI, Panaccione R, Ghosh S, Wu JCY, Chan FKL, Sung JJY, Kaplan GG. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet. 2017 Dec 23;390(10114):2769-2778. doi: 10.1016/S0140-6736(17)32448-0. Epub 2017 Oct 16.

  PMID: 29050646 RESULT

MeSH Terms

Conditions

Crohn Disease; Colitis, Ulcerative

Interventions

Sampling Studies

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Colitis; Colonic Diseases

Intervention Hierarchy (Ancestors)

Epidemiologic Study Characteristics; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Officials

• Laurent PEYRIN-BIROULET

  CHRU of Nancy, Hepatogastroenterology Department

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Laurent PEYRIN-BIROULET, PU-PH

CONTACT

03.83.15.36.61; peyrinbiroulet@gmail.com

Marine BECK, CPM

CONTACT

0383155280; m.beck@chru-nancy.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Doctor

Study Record Dates

• First Submitted: January 16, 2023
• First Posted: February 17, 2023
• Study Start: June 14, 2023
• Primary Completion (Estimated): August 1, 2030
• Study Completion (Estimated): August 1, 2030
• Last Updated: May 6, 2025

Record last verified: 2025-05

Locations

FR (1)