Evaluation of Adherent Invasive E. Coli Eradication in Adult Crohn Disease (TEOREM)

Multicenter Double Blind Randomized Clinical Trial Assessing the Benefit of Adherent Invasive E. Coli Eradication in Adult Ileal and Ileo-colonic Crohn Disease

The primary objective of this trial is to assess whether a 12-week treatment with Ciprofloxacin and Rifaximin is superior to placebo to obtain endoscopic remission in adherent-invasive E. coli (AIEC)-colonized patients with ileal Crohn disease (CD), with or without involvement of the caecum or the right colon.

Study Overview

• Status: Terminated
• Conditions: Crohn Disease; Adherent-invasive E. Coli
• Intervention / Treatment: Drug: Ciprofloxacin; Drug: Rifaximin; Drug: Ciprofloxacin Placebo; Drug: Rifaximin Placebo

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Franck Carbonnel, MDPhD; Phone Number: 33 1 45 32 37 22; Email: fcarbonnel7@gmail.com

Study Locations

• France
  • Le Kremlin Bicetre, France, 94
    • Gastroenterology department
  • Le Kremlin-Bicêtre, France, 94043
    • Kremlin-Bicêtre Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• CD of the ileum, with or without involvement of the caecum or the right colon
• Colonoscopy showing active lesions defined by a CDEISm score >6
• Informed consent to participate in this study
• Prescription of steroid treatments : Budesonide, Prednisone (or Prednisolone) independently from entry in study
• Patients who respond to budesonide (initial dose 9 mg/d) or prednisone or prednisolone (initial dose 40 mg/d), defined as a 70 points decrease in CDAI between the pre-inclusion and the inclusion visit,
• Patients colonized with AIEC on initial ileal biopsies.

Exclusion Criteria:

• Ileal stenosis that cannot be crossed by the endoscope,
• Infliximab treatment received less than 8 weeks before inclusion in this study,
• Adalimumab treatment received less than 4 weeks before inclusion in this study,
• Vedolizumab treatment received less than 8 weeks before inclusion in the study,
• Hypersensitivity to Ciprofloxacin, to other quinolones, or to any of the excipients (cellulose microcrystalline, crospovidone, maize starch, magnesium stearate, silica colloidal anhydrous,, hypromellose titanium dioxide E171, macrogol 4000,),
• Tizanidine, Probenecid, Theophylline, Xanthine derivatives, Phenytoin, oral anticoagulants, and Ropinirole treatment,
• Hypersensitivity to Rifaximin, or to any excipients (sodium starch glycolate type A, glycerol distearate, colloidal anhydrous silica, talc, microcrystalline cellulose, hypromellose, titanium dioxide, disodium edentate, propylene glycol, red iron oxide E172),
• Previous extensive ileal surgery (≥ 1 meter as measured on the pathology and/or surgical report),
• Short bowel syndrome,
• Need for an intestinal resection for fistula, abscess or intestinal obstruction,
• Renal failure (creatinine clearance<30 mL/min/1.73m2),
• Liver failure (V factor<50%),
• Past history of epilepsy,
• No health insurance,
• Pregnant or lactating women,
• Refusal to have a double effective contraception,
• Patients already included in a biomedical research other than an observational study (e.g: registry, cohort).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental arm; oral Ciprofloxacin 500 mg bid and oral Rifaximin 800 mg bid for 12 weeks	Drug: Ciprofloxacin; oral Ciprofloxacin 500 mg bis in die (bid) for 12 weeks; Drug: Rifaximin; oral Rifaximin 800 mg bid for 12 weeks
Placebo Comparator: Control arm; a placebo of Ciprofloxacin bid and a placebo of Rifaximin bid for 12 weeks	Drug: Ciprofloxacin Placebo; a placebo of Ciprofloxacin bid for 12 weeks; Drug: Rifaximin Placebo; a placebo of Rifaximin bid for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients with Endoscopic Endoscopic Index of Severity (CDEISm)< 6 and a decrease in CDEISm ≥ 3	(assessed within each site quotation), defined by the modified Crohn's Disease Endoscopic Index of Severity (CDEISm)< 6 and a decrease in CDEISm ≥ 3, as compared to baseline values.	week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean variation of CDEISm	assessed by centralized, anonymous and blinded reading of ileocolonoscopies	week 12
Complete endoscopic remission	assessed by centralized, anonymous and blinded reading of ileocolonoscopies, and defined by a CDEISm <3	week 12
No ulceration		week 12
Clinical remission	defined by Crohn's disease activity index (CDAI)<150 without steroids, anti-Tumor Necrosis Factor (TNF), and surgery	12 and 48 weeks
Microbiota composition		weeks 12 and 48
lpf positive AIEC bacteria in the stools	Detection (by PCR)	weeks 12 and 48
Biological remission	defined by haemoglobin level ≥13g/dL and C-Reactive Protein (CRP) serum level ≤5 mg/L and fecal calprotectin <300 mg/L	weeks 4, 8, 12, 24, 36 and 48
Side effects	adverse events	week 12

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Study Chair: Nicolas Barnich, MD PhD, Intestinal bacterial pathogenesis laboratory

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (Actual): August 1, 2021
• Study Completion (Actual): June 1, 2022

Study Registration Dates

• First Submitted: November 30, 2015
• First Submitted That Met QC Criteria: December 1, 2015
• First Posted (Estimated): December 2, 2015

Study Record Updates

• Last Update Posted (Actual): August 23, 2023
• Last Update Submitted That Met QC Criteria: August 21, 2023
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: Adult; AIEC
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Gastrointestinal Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 CYP1A2 Inhibitors; Rifaximin; Ciprofloxacin
• Other Study ID Numbers: P140503