Rifaximin-treatment of Collagenous Colitis (XiCoCo)

Rifaximin-treatment of Collagenous Colitis:

The hypothesis of this study is that an altered gut microbiota is a contributory factor in initiating an inflammatory process in the colonic mucosa leading to collagenous colitis. The investigators suggest that treatment with budesonide reduces the inflammation without treating the underlying cause. In this trial the investigators will try to modullate gut microbiota by adding rifaximin. The aim of this study is to assess if 4 weeks treatment with rifaximin as a supplement to a standard course of budesonide against active CC can reduce the risk of relapse after treatment cessation.

Study Overview

• Status: Unknown
• Conditions: Collagenous Colitis
• Intervention / Treatment: Drug: Rifaximin 550 MG

Detailed Description

Patients with biopsy-verified CC and active disease defined by >3 bowel movements/day or >1 watery stool measured as a mean for a week. Patients will be invited to participate in the study independently of age and disease duration.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 3

Contacts and Locations

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:

• • Signed informed consent

  • Histological findings fulfill criteria for CC:

    • A subepithelial collagenous band >10 μm in colonic biopsies
    • Increased count of inflammatory cells in lamina propria
  • Diagnostic biopsies are a maximum of two years old
  • A history of nonbloody, watery diarrhea for more than two weeks prior to screening in patients with recently diagnosed CC or a history of clinical relapse for more than a week in patients with known CC
  • Active disease: > 3 stools/day or >1 watery stool/day measured as a mean during a week prior to baseline

Exclusion Criteria:

• - Significant findings at colonoscopy that could cause diarrhea (colonic diverticulosis and polyps < 2 cm are not considered significant findings)
• Biopsies more than two years old in a patient, who does not accept a new sigmoidoscopy
• Untreated celiac disease
• Positive stool cultures for pathogenic intestinal bacteria including Clostridium difficile
• Suspected colitis induced by medication (diarrhea shortly after commencement of NSAID's, statins, SSRI or PPI)
• Severe comorbidity (cardiovascular, renal, endocrine, neurologic, pulmonal or psychiatric) or history of cancer during the last 5 years
• Abnormal liver biochemistry (ALAT or ALP > 2,5 x upper limit), cirrhosis or portal hypertension
• Pregnancy or lactation (assured by negative P-hCG at inclusion)
• History of significant intestinal resection
• Treatment with 5-ASA, Salazopyrin, immunemudulators (Azathioprine, 6-mercaptopurine or Methotrexate), biologic drugs (TNF-alfa-inhibitors), local or systemic glucocorticoids (except for Budesonide) within the last three month
• Allergy or intolerance to Rifaximin (or similar antibiotics such as Rifampicin or Rifabutin)
• Expectation of lack of cooperation or insufficient comprehension
• Concomitant participation in an other clinical trial or participation within the last 30 days
• Patients receiving Warfarin or Marcoumar (interaction with risk of uncontrolled INR-levels)

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
Active Comparator: Rifaxamine 550 mg; Study drug Oral Rifaximin 550 mg TID for 4 weeks .	Drug: Rifaximin 550 MG; Oral Rifaximin 550 mg TID for 4 weeks.; Other Names: Xifaxan
Placebo Comparator: Placebo; Placebo TID for 4 weeks	Drug: Rifaximin 550 MG; Oral Rifaximin 550 mg TID for 4 weeks.; Other Names: Xifaxan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical remission	The number of patients in clinical remission in the Rifaximin group compared to the placebo group.	The number of patients in clinical remission 12 weeks after randomisation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to relapse.	Time to relapse after cessation of treatment with Rifaxamin compared to placebo	Last visit is one year after treatment cessation.
Difference in Quality of life: short health scale (SHS)	Difference in Quality of life assessed by a visual analog scale (SHS) after cessation of treatment with Rifaxamin compared to placebo. The scale extends from 0 to 10 with 0 as worst outcome and 10 as best outcome.	12 weeks after treatment
Microbioma	Changes is gut microbiome after treatment	12 weeks after treatment

Collaborators and Investigators

• Sponsor: Bonderup, Ole K., M.D.
• Investigators: Principal Investigator: Sabine K Becker, MD, Clinic of Gastrointestinal- and Infectious Diseases, Diagnostic Center Silkeborg Regional Hospital, Falkevej 1-3, 8600 Silkeborg, Denmark

Study record dates

Study Major Dates

• Study Start (Anticipated): November 1, 2018
• Primary Completion (Anticipated): November 1, 2020
• Study Completion (Anticipated): November 1, 2021

Study Registration Dates

• First Submitted: September 3, 2018
• First Submitted That Met QC Criteria: September 5, 2018
• First Posted (Actual): September 6, 2018

Study Record Updates

• Last Update Posted (Actual): September 6, 2018
• Last Update Submitted That Met QC Criteria: September 5, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: Microbiome; Microscopic colitis; Diarrhoea; Rifaxamine
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Colitis, Microscopic; Colitis; Colitis, Collagenous; Anti-Infective Agents; Gastrointestinal Agents; Anti-Bacterial Agents; Rifaximin
• Other Study ID Numbers: BonderupO

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: De-identified individual participant data for all primary and secondary outcome measures will be made available
• IPD Sharing Time Frame: Within 6 months of study completion
• IPD Sharing Access Criteria: Requestors will be required to sign a Data Access Agreement
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

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