Clinical trial NCT00237653: MICI-CMV:Valganciclovir in Recurrent Bouts of Cryptogenic Inflammatory Bowel Diseases With an Infection by Cytomegalovirus
Official title: Relevance of Valganciclovir in Recurrent Bouts of Cryptogenic Inflammatory Bowel Diseases With an Infection by Cytomegalovirus
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Cytomegalovirus Infections
Inflammatory Bowel Diseases
Keywords: Valganciclovir
Cytomegalovirus
Cryptogenic inflammatory bowel diseases
Crohn Disease
colitis, ulcerative
Lead sponsor: University Hospital, Grenoble
Sponsor class: OTHER
First posted: 2005-10-12
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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.

Primary outcomes:
measure: Improvement of Crohns disease activity index score
measure: Diminution or disappearance of gravity criteria
measure: Endoscopy: improvement in appearance of lesions, or healing
measure: Anatomopathology: improvement of histological criteria, or total regression
measure: Anatomopathology: disappearance of viral infection criteria
measure: Virology: reversal of CMV IgG serology and PCR results
Secondary outcomes:
Other outcomes:
Locations:
city: Grenoble
country: France
facility: Gastroenterology Department - University Hospital of Grenoble
Study officials:
affiliation: Institut National de la Santé Et de la Recherche Médicale, France
name: Bruno BONAZ, MD
role: PRINCIPAL_INVESTIGATOR
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