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Evaluation of Molecular Mechanisms of Non-response to Therapy in Patients With Inflammatory Bowel Disease (3TR)

Primary Purpose

Crohn's Disease, Ulcerative Colitis

Status
Recruiting
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Samples
Sponsored by
Central Hospital, Nancy, France
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Crohn's Disease focused on measuring biomarkers, Crohn's disease, ulcerative colitis, disease activity, therapy reponse

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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 Exclusion Criteria: 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.

Sites / Locations

  • CHRU of NancyRecruiting

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Samples

Arm Description

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

Outcomes

Primary Outcome Measures

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
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

Secondary Outcome Measures

To correlate identifed potential biomarkers with disease activity, progression and response to therapy by clinical remission in Crohn's disease patient
Remission will be evaluated by mucosal healing (simple endoscopic response (SES-CD)). 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
To correlate identifed potential biomarkers with disease activity, progression and response to therapy by clinical remission in Ulcerative colitis patient
Remission will be evaluated by mucosal healing (Mayo score). 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
To correlate identifed potential biomarkers with disease activity, progression and response to therapy by patient-reported outcomes
Symptomatic remission assessed by patient-reported outcomes
To correlate identifed potential biomarkers with disease activity, progression and response to therapy by complications-reported.
Complications-reported: hospitalizations due to inflammatory-bowel disease; treatment intensification including introduction of toxic long-term therapies (i.e. systemic glucocorticoids); presence of new stenosis; presence of new fistula ;new infections or intestinal surgery known
To correlate identifed potential biomarkers with disease activity, progression and response to therapy by disease progression.
Presence of flares e.g.

Full Information

First Posted
January 16, 2023
Last Updated
June 21, 2023
Sponsor
Central Hospital, Nancy, France
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1. Study Identification

Unique Protocol Identification Number
NCT05733845
Brief Title
Evaluation of Molecular Mechanisms of Non-response to Therapy in Patients With Inflammatory Bowel Disease
Acronym
3TR
Official Title
Evaluation of Molecular Mechanisms of Non-response to Treatments, Relapses and Remission in Ulcerative Colitis and Crohn's Disease Patients Receiving First Time Standard of Care Biological Treatment
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 14, 2023 (Actual)
Primary Completion Date
August 1, 2030 (Anticipated)
Study Completion Date
August 1, 2030 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Central Hospital, Nancy, France

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Crohn's Disease, Ulcerative Colitis
Keywords
biomarkers, Crohn's disease, ulcerative colitis, disease activity, therapy reponse

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Samples
Arm Type
Other
Arm Description
The intervention is to collect blood; urine; saliva and stool samples but also mucosal biopsies at each protocol visits (baseline and follow up visits).
Intervention Type
Other
Intervention Name(s)
Samples
Intervention Description
The intervention is to collect blood; urine; saliva and stool samples but also mucosal biopsies at each protocol visits (baseline and follow up visits).
Primary Outcome Measure Information:
Title
To identify solid biomarkers signatures as well as molecular pathways and mechanisms linked to response and non-response to therapy in ulcerative colitis patient.
Description
-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
Time Frame
week 14
Title
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.
Description
-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
Time Frame
week 14
Secondary Outcome Measure Information:
Title
To correlate identifed potential biomarkers with disease activity, progression and response to therapy by clinical remission in Crohn's disease patient
Description
Remission will be evaluated by mucosal healing (simple endoscopic response (SES-CD)). 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
Time Frame
week 52
Title
To correlate identifed potential biomarkers with disease activity, progression and response to therapy by clinical remission in Ulcerative colitis patient
Description
Remission will be evaluated by mucosal healing (Mayo score). 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
Time Frame
week 52
Title
To correlate identifed potential biomarkers with disease activity, progression and response to therapy by patient-reported outcomes
Description
Symptomatic remission assessed by patient-reported outcomes
Time Frame
week 52
Title
To correlate identifed potential biomarkers with disease activity, progression and response to therapy by complications-reported.
Description
Complications-reported: hospitalizations due to inflammatory-bowel disease; treatment intensification including introduction of toxic long-term therapies (i.e. systemic glucocorticoids); presence of new stenosis; presence of new fistula ;new infections or intestinal surgery known
Time Frame
week 52
Title
To correlate identifed potential biomarkers with disease activity, progression and response to therapy by disease progression.
Description
Presence of flares e.g.
Time Frame
week 52
Other Pre-specified Outcome Measures:
Title
Fatigue assessment
Description
Evaluated by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). FACIT-F is a 40-items measure that assesses self-reported fatigue and its impact upon daily activites and function. 5 point Likert-type scale. Subscale domains: Physical Well-Being, Social/Family Well-Being, Emotional Well-Being, Functional Well-Being, Fatigue Minimum value: 0 = better outcome Maximum value: 160= worst outcome
Time Frame
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)
Title
Emotional distress-depression assessment
Description
Evaluated by Patient-Reported Outcomes Measurement Information System® (PROMIS®) Depression scale. PROMIS-Depression is a 8-items scale. Score between 8 and 40. 8= best health statein the past 7 days. 40= worst health state in the past 7 days.
Time Frame
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)
Title
General Health Survey assessment
Description
Evaluated by the The Short Form (36) Health Survey (SF36). SF36 is a patient-reported survey of patient health that covers physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions. Score range from 0 to 100. 100= more favorable health state. 0= worst health state.
Time Frame
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)
Title
Health status assessment
Description
Evaluated by the 5-level EQ-5D version (EQ-5D-5L). The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. Score between 5 and 25. 5=best health state 25= worst health state The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. 100= best health state 0= worst health state.
Time Frame
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)
Title
Medical complications
Description
Long-term outcome (complications until week 104). Complication like stenosis, fistula, development of PSC, infections, flares, hospitalizations, treatment intensification including introduction of toxic long-term therapies (i.e. systemic glucocorticoids) or intestinal surgery will be documented during the entire observational period.
Time Frame
Until week 104

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Laurent PEYRIN-BIROULET, PU-PH
Phone
03.83.15.36.61
Email
peyrinbiroulet@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Ludivine ODOUL, CPM
Phone
0383155580
Email
l.odoul@chru-nancy.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Laurent PEYRIN-BIROULET
Organizational Affiliation
CHRU of Nancy, Hepatogastroenterology Department
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHRU of Nancy
City
Vandoeuvre Les Nancy
State/Province
CHRU De Nancy
ZIP/Postal Code
54511
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Laurent PEYRIN-BIROULET, MD
Phone
0383153661
Email
peyrinbiroulet@gmail.com
First Name & Middle Initial & Last Name & Degree
LUDIVINE ODOUL
Phone
0383155580
Email
l.odoul@chru-nancy.fr

12. IPD Sharing Statement

Citations:
PubMed Identifier
23395397
Citation
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.
Results Reference
result
PubMed Identifier
29050646
Citation
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. Erratum In: Lancet. 2020 Oct 3;396(10256):e56.
Results Reference
result

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

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