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

Crohn Disease Clinical Trial

— TEOREM  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02620007
• Other study ID #: P140503
• Status: Terminated
• Phase: Phase 2
• Start date: December 2015
• Est. completion date: June 2022

Study information

• Verified date: February 2019
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 24
• Est. completion date: June 2022
• Est. primary completion date: August 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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).

Related Conditions & MeSH terms

• Adherent-invasive E. Coli
• Crohn Disease

Intervention

Drug:
• Ciprofloxacin
oral Ciprofloxacin 500 mg bis in die (bid) for 12 weeks
• Rifaximin
oral Rifaximin 800 mg bid for 12 weeks
• Ciprofloxacin Placebo
a placebo of Ciprofloxacin bid for 12 weeks
• Rifaximin Placebo
a placebo of Rifaximin bid for 12 weeks

Locations

Country	Name	City	State
France	Gastroenterology department	Le Kremlin Bicetre
France	Kremlin-Bicetre hospital	Le Kremlin-Bicêtre

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Mean variation of CDEISm	assessed by centralized, anonymous and blinded reading of ileocolonoscopies	week 12
Secondary	Complete endoscopic remission	assessed by centralized, anonymous and blinded reading of ileocolonoscopies, and defined by a CDEISm <3	week 12
Secondary	No ulceration		week 12
Secondary	Clinical remission	defined by Crohn's disease activity index (CDAI)<150 without steroids, anti-Tumor Necrosis Factor (TNF), and surgery	12 and 48 weeks
Secondary	Microbiota composition		weeks 12 and 48
Secondary	lpf positive AIEC bacteria in the stools	Detection (by PCR)	weeks 12 and 48
Secondary	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
Secondary	Side effects	adverse events	week 12