MICI-CMV:Valganciclovir in Recurrent Bouts of Cryptogenic Inflammatory Bowel Diseases With an Infection by Cytomegalovirus

This study has been terminated.
(difficulty to include patients)
Sponsor:
Information provided by:
University Hospital, Grenoble
ClinicalTrials.gov Identifier:
NCT00237653
First received: October 11, 2005
Last updated: April 2, 2009
Last verified: April 2009
  Purpose

The main objective of this study is to demonstrate the relevance of Valganciclovir on recurrent bouts of cryptogenic inflammatory bowel diseases with infection by cytomegalovirus (CMV). The goal is to obtain 90% (for Valganciclovir treated patients) versus 50% (for placebo treated patients) remission at 3 months (including the discontinuation of corticoids or reducing their dose to under 20 mg of prednisone equivalence), without any relapse over the 6 following months.


Condition Intervention Phase
Cytomegalovirus Infections
Inflammatory Bowel Diseases
Drug: Valganciclovir
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Relevance of Valganciclovir in Recurrent Bouts of Cryptogenic Inflammatory Bowel Diseases With an Infection by Cytomegalovirus

Resource links provided by NLM:


Further study details as provided by University Hospital, Grenoble:

Primary Outcome Measures:
  • Improvement of Crohns disease activity index score
  • Diminution or disappearance of gravity criteria
  • Endoscopy: improvement in appearance of lesions, or healing
  • Anatomopathology: improvement of histological criteria, or total regression
  • Anatomopathology: disappearance of viral infection criteria
  • Virology: reversal of CMV IgG serology and PCR results

Estimated Enrollment: 40
Study Start Date: February 2004
Study Completion Date: December 2007
  Hide Detailed Description

Detailed Description:

The cytomegalovirus (CMV) is a DNA virus from the herpes virus family. It is passed on between humans and even if infection is widespread (50 to 80% of people older than 35 are CMV immunoglobulin G positive) it is often asymptomatic for immunocompetent people. However, for immunocompromised people, such an infection takes on particular frequency, expression and seriousness, with a high frequency of attack to the digestive track (CMV colitis).

For immunocompetent people, colitis causes feverish bloody diarrhea associated with abdominal pain. Colitis diagnosis is often late and cases with complications have been reported (digestive bleeding, toxic giant colon and perforation). The endoscopic aspect of colitis is not specific and diagnosis is based on serology, anatomopathology or immunochemistry. Recently, PCR approaches have allowed more sensitive diagnosis.

CMV INVOLVEMENT IN CIBD PHYSIOPATHOLOGY:

Even though CMV involvement in colitis is rare but sure for immunocompetent people, its involvement in CIBD triggering and morbidity has not been solved yet.

Some authors think infection by CMV may act on CIBD as a trigger factor; since 2 cases of CMV colitis coinciding with the onset of a CIBD have been reported. For other authors, infection by CMV acts by direct pathogenicity causing ulcerative lesions of colonic mucosa and just imitates a CIBD without triggering it.

A third hypothesis is that infection by CMV aggravates inflammatory bowel diseases acting as an exacerbating factor.

In all cases, people suffering from CIBD are highly-exposed to infection by CMV due to immunosuppressive treatment (corticoids, cyclosporine, azathioprin, and methotrexate) and the inflammation itself (which is supposed to be a proning factor).

CMV AND POUCHITIS:

Pouchitis is the most common long-term complication after total proctocolectomy. Usually, it can be cured by antibiotic therapy, but in 15% of cases it becomes chronic and turns onto refractory pouchitis which is difficult to cure.

Infection by CMV can imitate a chronic pouchitis from a clinical and endoscopic view. In such cases, it had been shown that Valganciclovir treatment (10mg/kg/day) led to significant improvement over a 21 day treatment period.

CONCLUSION:

Infection by CMV seems to play an important role and has to be taken into account in CIBD physiopathogeny. Probably underestimated since it is not necessarily searched, it could be a triggering factor or a treatment resistance factor. Immunosuppressive drugs used towards recurrent bouts, in particularly cyclosporine, favors viral reactivation. Then, recurrent bouts of CIBD may be complicated by CMV infection. That is why it could be interesting to establish relevance of antiviral treatment on recurrent bouts of CIBD with infection by CMV.

The main objective of this study is to demonstrate relevance of Valganciclovir on recurrent bouts of Cryptogenic Inflammatory Bowel Diseases with infection by Cytomegalovirus. The goal is to obtain 90% (for Valganciclovir treated patients) versus 50% (for placebo treated patients) of remission at 3 months (including the discontinuation of corticoids or reducing their dose to under 20 mg of prednisone equivalence), without any relapse over the 6 following months.

Secondary objectives are:

  • Reversal of CMV immunoglobulin G serology and PCR results on colonic biopsies.
  • Improvement in appearance of histological lesions
  • Reduction in the number of colectomies
  • Evaluation of Valganciclovir tolerance and its side effects
  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient suffering from Crohn's disease, ulcerative colitis, unclassifiable colitis or pouchitis.
  • Disease needing to be treated by corticoids and/or immunosuppressive drugs.
  • Infection by cytomegalovirus.
  • New attack during the three previous months.

Exclusion Criteria:

  • Serious or complicated attack, needing to be operated.
  • Patient suffering from a psychiatric disease or is uncooperative.
  • Patient suffering from another serious disease.
  • Patient already participating in another clinical trial.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00237653

Locations
France
Gastroenterology Department - University Hospital of Grenoble
Grenoble, France, 38043
Sponsors and Collaborators
University Hospital, Grenoble
Investigators
Principal Investigator: Bruno BONAZ, MD Institut National de la Santé Et de la Recherche Médicale, France
  More Information

Publications:

ClinicalTrials.gov Identifier: NCT00237653     History of Changes
Other Study ID Numbers: DCIC 03 21
Study First Received: October 11, 2005
Last Updated: April 2, 2009
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Grenoble:
Valganciclovir
Cytomegalovirus
Cryptogenic inflammatory bowel diseases
Crohn Disease
Crohn disease
colitis, ulcerative

Additional relevant MeSH terms:
Cytomegalovirus Infections
Inflammatory Bowel Diseases
Intestinal Diseases
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Valganciclovir
Ganciclovir
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 19, 2014