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

Primary Purpose

Crohn Disease, Adherent-invasive E. Coli

Status
Terminated
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Ciprofloxacin
Rifaximin
Ciprofloxacin Placebo
Rifaximin Placebo
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Crohn Disease focused on measuring Adult, AIEC

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

  • Gastroenterology department
  • Kremlin-Bicetre hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Experimental arm

Control arm

Arm Description

oral Ciprofloxacin 500 mg bid and oral Rifaximin 800 mg bid for 12 weeks

a placebo of Ciprofloxacin bid and a placebo of Rifaximin bid for 12 weeks

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

Full Information

First Posted
November 30, 2015
Last Updated
August 21, 2023
Sponsor
Assistance Publique - Hôpitaux de Paris
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1. Study Identification

Unique Protocol Identification Number
NCT02620007
Brief Title
Evaluation of Adherent Invasive E. Coli Eradication in Adult Crohn Disease
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2019
Overall Recruitment Status
Terminated
Why Stopped
insufficient recruitment
Study Start Date
December 2015 (undefined)
Primary Completion Date
August 2021 (Actual)
Study Completion Date
June 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Crohn Disease, Adherent-invasive E. Coli
Keywords
Adult, AIEC

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
24 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Experimental arm
Arm Type
Experimental
Arm Description
oral Ciprofloxacin 500 mg bid and oral Rifaximin 800 mg bid for 12 weeks
Arm Title
Control arm
Arm Type
Placebo Comparator
Arm Description
a placebo of Ciprofloxacin bid and a placebo of Rifaximin bid for 12 weeks
Intervention Type
Drug
Intervention Name(s)
Ciprofloxacin
Intervention Description
oral Ciprofloxacin 500 mg bis in die (bid) for 12 weeks
Intervention Type
Drug
Intervention Name(s)
Rifaximin
Intervention Description
oral Rifaximin 800 mg bid for 12 weeks
Intervention Type
Drug
Intervention Name(s)
Ciprofloxacin Placebo
Intervention Description
a placebo of Ciprofloxacin bid for 12 weeks
Intervention Type
Drug
Intervention Name(s)
Rifaximin Placebo
Intervention Description
a placebo of Rifaximin bid for 12 weeks
Primary Outcome Measure Information:
Title
Percentage of patients with Endoscopic Endoscopic Index of Severity (CDEISm)< 6 and a decrease in CDEISm ≥ 3
Description
(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.
Time Frame
week 12
Secondary Outcome Measure Information:
Title
Mean variation of CDEISm
Description
assessed by centralized, anonymous and blinded reading of ileocolonoscopies
Time Frame
week 12
Title
Complete endoscopic remission
Description
assessed by centralized, anonymous and blinded reading of ileocolonoscopies, and defined by a CDEISm <3
Time Frame
week 12
Title
No ulceration
Time Frame
week 12
Title
Clinical remission
Description
defined by Crohn's disease activity index (CDAI)<150 without steroids, anti-Tumor Necrosis Factor (TNF), and surgery
Time Frame
12 and 48 weeks
Title
Microbiota composition
Time Frame
weeks 12 and 48
Title
lpf positive AIEC bacteria in the stools
Description
Detection (by PCR)
Time Frame
weeks 12 and 48
Title
Biological remission
Description
defined by haemoglobin level ≥13g/dL and C-Reactive Protein (CRP) serum level ≤5 mg/L and fecal calprotectin <300 mg/L
Time Frame
weeks 4, 8, 12, 24, 36 and 48
Title
Side effects
Description
adverse events
Time Frame
week 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nicolas Barnich, MD PhD
Organizational Affiliation
Intestinal bacterial pathogenesis laboratory
Official's Role
Study Chair
Facility Information:
Facility Name
Gastroenterology department
City
Le Kremlin Bicetre
ZIP/Postal Code
94
Country
France
Facility Name
Kremlin-Bicetre hospital
City
Le Kremlin-Bicêtre
ZIP/Postal Code
94043
Country
France

12. IPD Sharing Statement

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

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