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Rifaximin-treatment of Collagenous Colitis

Phase 3
Conditions
Collagenous Colitis
Interventions
Registration Number
NCT03658993
Lead Sponsor
Bonderup, Ole K., M.D.
Brief Summary

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.

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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
50
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Rifaxamine 550 mgRifaximin 550 MGStudy drug Oral Rifaximin 550 mg TID for 4 weeks .
PlaceboRifaximin 550 MGPlacebo TID for 4 weeks
Primary Outcome Measures
NameTimeMethod
Clinical remissionThe number of patients in clinical remission 12 weeks after randomisation

The number of patients in clinical remission in the Rifaximin group compared to the placebo group.

Secondary Outcome Measures
NameTimeMethod
Time to relapse.Last visit is one year after treatment cessation.

Time to relapse after cessation of treatment with Rifaxamin compared to placebo

Difference in Quality of life: short health scale (SHS)12 weeks after treatment

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.

Microbioma12 weeks after treatment

Changes is gut microbiome after treatment

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