STUDY OF THE ADDED VALUE OF A TRANSMURAL EVALUATION IN PATIENTS WITH CROHN'S DISEASE UNDER BIOTHERAPY WITH CLOSE FECAL CALPROTECTIN FOLLOW-UP (Deeper)

Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD) that can dramatically affect the quality of life of patients. Due to its transmural nature (involvement of the entire thickness of the intestinal wall), it naturally progresses to intestinal destruction (stenosis, fistula) which requires intestinal resection in approximately half of patients during their follow-up. The long-term goal for patients is to maintain a normal life, that is, without symptoms and without intestinal destruction. For this, the short and medium term therapeutic objectives have evolved in recent years. Clinical remission is not a sufficient goal since it has failed to alter the natural history of the disease. The current objective to be achieved is the combination of clinical remission and endoscopic mucosal healing since it is associated with a reduced risk of progression (reappearance of symptoms, hospitalization, intestinal resection). Fecal calprotectin, better accepted than colonoscopy, is a non-invasive biomarker of endoscopic inflammatory activity in CD. The CALM study recently showed that close follow-up with clinical and biological evaluation (assays of CRP and fecal calprotectin), called "tight control", associated with therapeutic intensification in the absence of clinical or biological remission, was associated with a better rate of endoscopic mucosal healing at 1 year than follow-up based solely on symptoms. Thus, the "CALM" strategy is considered to be the current benchmark.

Transmural healing evaluated by MRI is also a promising objective associated with a reduced risk of progression (reappearance of symptoms, hospitalization, bowel resection). In addition, it could prevent intestinal destruction. A recent study by our team suggested that calprotectin (mucosal assessment) and MRI (transmural assessment) may be complementary and be a better therapeutic goal. We hypothesize that a "CALM + MRI" strategy concomitantly targeting transmural healing would be superior to the "CALM" strategy alone in maintaining clinical remission without corticosteroids in patients with CD treated with biotherapies.

Study Overview

• Status: Recruiting
• Conditions: MRI; Crohn Disease; Calprotectin
• Intervention / Treatment: Radiation: MRI

Detailed Description

This is a randomized, open-label controlled study comparing two therapeutic strategies in patients with CD (see inclusion criteria) starting biotherapy. Randomization, by minimization (Stata version 15), will be stratified by center, by biotherapy line and on the location of the disease: MC colic isolated (L2 according to the Montreal classification) vs. Ileal or ileocolic MC (L1 + L3), for a maximum of L1 + L3 patients of 70%.

The reference arm will be based on that of the CALM study, i.e. regular follow-up (S0, S12, S24, S52, S76, S100, S124 and S152) with therapeutic intensification in the absence of at least one criterion among CDAI <150, CRP <5 or fecal calprotectin <250. After checking the inclusion criteria, the patients will be included and randomized. The initial choice of biotherapy, therapeutic intensifications (dose increase, interval reduction, treatment change) and treatment sequences will be based on the French consensus of 2020. MRI will be performed in all patients at weeks 0, 76 and 152. In the MRI arm, an additional MRI will be performed at W24 and W52 with therapeutic intensification at W24, W52 and W76 in the presence of residual MRI activity. Patients will be followed for 152 weeks (≈ 3 years). In the event of a missing examination (calprotectin or MRI), the intensification will be carried out or not with the available data. Therefore, the analysis will be performed by intention to treat (ITT). Patients will be given a symptom calendar (abdominal pain score (between 0 = no pain and 3 = severe pain) and number of stools). Each month without data (lost to follow-up) will be considered as in the absence of clinical remission without corticosteroids (ITT). The fecal calprotectin dosage will be standardized and performed with the same test in all patients. Therapeutic intensification based on MRI will be carried out after a centralized review. The secondary endpoints (response and transmural healing, Lémann index) will be centrally blinded in the study arm to avoid any evaluation bias.

• Study Type: Interventional
• Enrollment (Anticipated): 180
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Amiens, France
    • Not yet recruiting
    • Amiens university hospital
    • Principal Investigator: Mathurin Fumery
  • Aurillac, France
    • Not yet recruiting
    • Aurillac Hospital
    • Principal Investigator: Clément PASTAUD
  • Bayonne, France
    • Not yet recruiting
    • Bayonne Hospital
    • Principal Investigator: Félix GOUTORBE
  • Bordeaux, France
    • Not yet recruiting
    • Bordeaux University Hospital
    • Principal Investigator: David Laharie
  • Chambéry, France
    • Not yet recruiting
    • Chambéry Hospital
    • Principal Investigator: Christophe Allimant
  • Clermont-Ferrand, France
    • Recruiting
    • Clermont-Ferrand University Hospital
    • Principal Investigator: Anthony Buisson
  • Grenoble, France
    • Not yet recruiting
    • Grenoble University Hospital
    • Principal Investigator: Nicolas MATHIEU
  • Issoire, France
    • Not yet recruiting
    • Issoire Hospital
    • Principal Investigator: Camille Sautel
  • Lille, France
    • Not yet recruiting
    • Lille University Hospital
    • Principal Investigator: Maria Nachury
  • Lyon, France
    • Not yet recruiting
    • Lyon Hospital, Hospices civils de Lyon
    • Principal Investigator: Stephane Nancey
  • Montluçon, France
    • Not yet recruiting
    • Montluçon Hospital
    • Principal Investigator: Cédric DURON
  • Montpellier, France
    • Not yet recruiting
    • Montpellier University Hospital
    • Principal Investigator: Romain ALTWEGG
  • Nancy, France
    • Not yet recruiting
    • Nancy University Hospital
    • Principal Investigator: Laurent Peyrin-Biroulet
  • Nice, France
    • Not yet recruiting
    • Nice University Hospital
    • Principal Investigator: Xavier Hebuterne
  • Rennes, France
    • Not yet recruiting
    • Rennes University hospital
    • Principal Investigator: Guillaume Bouguen
  • Saint-Étienne, France
    • Not yet recruiting
    • Saint Etienne University Hospital
    • Principal Investigator: Xavier Roblin
  • Thiers, France
    • Not yet recruiting
    • Thiers Hospital
    • Principal Investigator: Julien SCANZI

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult Crohn's disease (age ≥ 18 years)
• Symptomatic with Crohn's disease activity index (CDAI)> 150
• Presence of objective signs of inflammatory activity (fecal calprotectin> 250 AND sign of MRI activity)
• Requiring treatment with biotherapy according to the investigator
• Able to give informed consent to participate in research
• Affiliation to a Social Security scheme.

Exclusion Criteria:

• Severe obstructive symptoms
• Uncontrolled intra-abdominal abscess
• Isolated anoperineal lesions
• Prevention of postoperative endoscopic recurrence
• Temporary or definitive ostomy
• Total colectomy
• Contraindication to MRI
• Pregnant or breastfeeding women
• Protected adults (curatorship, guardianship, saving justice)
• Refusal of participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: CALM; Tight control of inflammatory activity by calprotectin.
Other: CALM + IRM; Tight control of inflammatory activity by calprotectin associated with transmural evaluation.	Radiation: MRI; 2 additional MRI will be done for the CALM + MRI group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of months spent in clinical remission	Proportion of months (4 week period) spent in clinical remission without corticosteroids according to PRO-2 (<3 very soft or watery stools per day and no moderate to severe abdominal pain).	Between week 24 and week 76.

Collaborators and Investigators

• Sponsor: University Hospital, Clermont-Ferrand

Study record dates

Study Major Dates

• Study Start (Actual): March 21, 2022
• Primary Completion (Anticipated): March 21, 2027
• Study Completion (Anticipated): August 21, 2027

Study Registration Dates

• First Submitted: July 13, 2021
• First Submitted That Met QC Criteria: July 13, 2021
• First Posted (Actual): July 22, 2021

Study Record Updates

• Last Update Posted (Actual): April 26, 2022
• Last Update Submitted That Met QC Criteria: April 19, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: PHRC IR 2020 BUISSON

Drug and device information, study documents

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