Cytomegalovirus InfectionsPhase 3NCT00237653
MICI-CMV:Valganciclovir in Recurrent Bouts of Cryptogenic Inflammatory Bowel Diseases With an Infection by Cytomegalovirus
A Phase 3 study testing Valganciclovir in people with Cytomegalovirus Infections and Inflammatory Bowel Diseases, run by University Hospital, Grenoble at 1 site in France.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Cytomegalovirus Infections, Inflammatory Bowel Diseases
- What is being tested?
- Valganciclovir
- How many people
- 40 participants
- Where
- 1 siteFrance
- Study dates
- Feb 2004to Dec 2007
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
France1 site
Gastroenterology Department - University Hospital of Grenoble
Grenoble, 38043
About this study
Official title: Relevance of Valganciclovir in Recurrent Bouts of Cryptogenic Inflammatory Bowel Diseases With an Infection by Cytomegalovirus
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.
Read the 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
- Being tested
- Valganciclovir
- Keywords
- Valganciclovir, Cytomegalovirus, Cryptogenic inflammatory bowel diseases, Crohn Disease, colitis, ulcerative
- Medical subject headings
- Cytomegalovirus Infections, Inflammatory Bowel Diseases, Crohn Disease, Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ValganciclovirDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Oct 2005 (estimated)
- Study startFeb 2004
- Study completionDec 2007
Why it stopped: difficulty to include patients
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for Cytomegalovirus InfectionsStudies of the same condition, open and under way.
- More trials run by University Hospital, GrenobleThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Grenoble
- Sponsor type
- University, hospital or other
- Investigators
- Bruno BONAZ, MD, Principal investigator, Institut National de la Santé Et de la Recherche Médicale, France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00237653
- Sponsor's protocol ID
- DCIC 03 21
- Status last verified
- Apr 2009
- First submitted
- 11 Oct 2005
- Last updated
- 3 Apr 2009
- Results posted
- No
Publications
Orvar K, Murray J, Carmen G, Conklin J. Cytomegalovirus infection associated with onset of inflammatory bowel disease. Dig Dis Sci. 1993 Dec;38(12):2307-10. doi: 10.1007/BF01299914. No abstract available.
PubMed 8261839Hofkin GA, Ting CD. Case report: recurrence of chronic ulcerative colitis induced by intercurrent cytomegalic virus infection. Md Med J. 1995 Dec;44(12):1047-8.
PubMed 8544671Rachima C, Maoz E, Apter S, Thaler M, Grossman E, Rosenthal T. Cytomegalovirus infection associated with ulcerative colitis in immunocompetent individuals. Postgrad Med J. 1998 Aug;74(874):486-9. doi: 10.1136/pgmj.74.874.486.
PubMed 9926125Begos DG, Rappaport R, Jain D. Cytomegalovirus infection masquerading as an ulcerative colitis flare-up: case report and review of the literature. Yale J Biol Med. 1996 Jul-Aug;69(4):323-8.
PubMed 9273986Vega R, Bertran X, Menacho M, Domenech E, Moreno de Vega V, Hombrados M, Cabre E, Ojanguren I, Gassull MA. Cytomegalovirus infection in patients with inflammatory bowel disease. Am J Gastroenterol. 1999 Apr;94(4):1053-6. doi: 10.1111/j.1572-0241.1999.01013.x.
PubMed 10201482Kaufman HS, Kahn AC, Iacobuzio-Donahue C, Talamini MA, Lillemoe KD, Hamilton SR. Cytomegaloviral enterocolitis: clinical associations and outcome. Dis Colon Rectum. 1999 Jan;42(1):24-30. doi: 10.1007/BF02235178.
PubMed 10211516Berk T, Gordon SJ, Choi HY, Cooper HS. Cytomegalovirus infection of the colon: a possible role in exacerbations of inflammatory bowel disease. Am J Gastroenterol. 1985 May;80(5):355-60.
PubMed 2859801Pfau PR, Lichtenstein GR. Cytomegalovirus infection as a cause of ileoanal pouchitis. Dis Colon Rectum. 2000 Jan;43(1):113-4. doi: 10.1007/BF02237255. No abstract available.
PubMed 10813135Pfau P, Kochman ML, Furth EE, Lichtenstein GR. Cytomegalovirus colitis complicating ulcerative colitis in the steroid-naive patient. Am J Gastroenterol. 2001 Mar;96(3):895-9. doi: 10.1111/j.1572-0241.2001.03672.x.
PubMed 11280572Munoz-Juarez M, Pemberton JH, Sandborn WJ, Tremaine WJ, Dozois RR. Misdiagnosis of specific cytomegalovirus infection of the ileoanal pouch as refractory idiopathic chronic pouchitis: report of two cases. Dis Colon Rectum. 1999 Jan;42(1):117-20. doi: 10.1007/BF02235196.
PubMed 10211531Moonka D, Furth EE, MacDermott RP, Lichtenstein GR. Pouchitis associated with primary cytomegalovirus infection. Am J Gastroenterol. 1998 Feb;93(2):264-6. doi: 10.1111/j.1572-0241.1998.00264.x.
PubMed 9468256Papadakis KA, Tung JK, Binder SW, Kam LY, Abreu MT, Targan SR, Vasiliauskas EA. Outcome of cytomegalovirus infections in patients with inflammatory bowel disease. Am J Gastroenterol. 2001 Jul;96(7):2137-42. doi: 10.1111/j.1572-0241.2001.03949.x.
PubMed 11467645Surawicz CM, Myerson D. Self-limited cytomegalovirus colitis in immunocompetent individuals. Gastroenterology. 1988 Jan;94(1):194-9. doi: 10.1016/0016-5085(88)90630-0.
PubMed 2826283
Study at a glance
From the registry record, last updated by the sponsor on 3 Apr 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Relevance of Valganciclovir in Recurrent Bouts of Cryptogenic Inflammatory Bowel Diseases With an Infection by Cytomegalovirus
- ClinicalTrials.gov ID
- NCT00237653
- Acronym / sponsor ID
- DCIC 03 21
- Keywords
- Valganciclovir, Cytomegalovirus, Cryptogenic inflammatory bowel diseases, Crohn Disease, colitis, ulcerative
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: difficulty to include patients
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- University Hospital, GrenobleUniversity, hospital or other
- Study start
- Feb 2004
- Study completion
- Dec 2007 (actual)
- First posted
- 12 Oct 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Valganciclovir | Drug | – |
Primary outcome
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
Results and safety
The study was stopped early (reason given: difficulty to include patients). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Apr 2009.
- Background: PubMed 8261839Orvar K, Murray J, Carmen G, Conklin J. Cytomegalovirus infection associated with onset of inflammatory bowel disease. Dig Dis Sci. 1993 Dec;38(12):2307-10. doi: 10.1007/BF01299914. No abstract available.
- Background: PubMed 8544671Hofkin GA, Ting CD. Case report: recurrence of chronic ulcerative colitis induced by intercurrent cytomegalic virus infection. Md Med J. 1995 Dec;44(12):1047-8.
- Background: PubMed 9926125Rachima C, Maoz E, Apter S, Thaler M, Grossman E, Rosenthal T. Cytomegalovirus infection associated with ulcerative colitis in immunocompetent individuals. Postgrad Med J. 1998 Aug;74(874):486-9. doi: 10.1136/pgmj.74.874.486.
- Background: PubMed 9273986Begos DG, Rappaport R, Jain D. Cytomegalovirus infection masquerading as an ulcerative colitis flare-up: case report and review of the literature. Yale J Biol Med. 1996 Jul-Aug;69(4):323-8.
- Background: PubMed 10201482Vega R, Bertran X, Menacho M, Domenech E, Moreno de Vega V, Hombrados M, Cabre E, Ojanguren I, Gassull MA. Cytomegalovirus infection in patients with inflammatory bowel disease. Am J Gastroenterol. 1999 Apr;94(4):1053-6. doi: 10.1111/j.1572-0241.1999.01013.x.
- Background: PubMed 10211516Kaufman HS, Kahn AC, Iacobuzio-Donahue C, Talamini MA, Lillemoe KD, Hamilton SR. Cytomegaloviral enterocolitis: clinical associations and outcome. Dis Colon Rectum. 1999 Jan;42(1):24-30. doi: 10.1007/BF02235178.
- Background: PubMed 2859801Berk T, Gordon SJ, Choi HY, Cooper HS. Cytomegalovirus infection of the colon: a possible role in exacerbations of inflammatory bowel disease. Am J Gastroenterol. 1985 May;80(5):355-60.
- Background: PubMed 10813135Pfau PR, Lichtenstein GR. Cytomegalovirus infection as a cause of ileoanal pouchitis. Dis Colon Rectum. 2000 Jan;43(1):113-4. doi: 10.1007/BF02237255. No abstract available.
- Background: PubMed 11280572Pfau P, Kochman ML, Furth EE, Lichtenstein GR. Cytomegalovirus colitis complicating ulcerative colitis in the steroid-naive patient. Am J Gastroenterol. 2001 Mar;96(3):895-9. doi: 10.1111/j.1572-0241.2001.03672.x.
- Background: PubMed 10211531Munoz-Juarez M, Pemberton JH, Sandborn WJ, Tremaine WJ, Dozois RR. Misdiagnosis of specific cytomegalovirus infection of the ileoanal pouch as refractory idiopathic chronic pouchitis: report of two cases. Dis Colon Rectum. 1999 Jan;42(1):117-20. doi: 10.1007/BF02235196.
- Background: PubMed 9468256Moonka D, Furth EE, MacDermott RP, Lichtenstein GR. Pouchitis associated with primary cytomegalovirus infection. Am J Gastroenterol. 1998 Feb;93(2):264-6. doi: 10.1111/j.1572-0241.1998.00264.x.
- Background: PubMed 11467645Papadakis KA, Tung JK, Binder SW, Kam LY, Abreu MT, Targan SR, Vasiliauskas EA. Outcome of cytomegalovirus infections in patients with inflammatory bowel disease. Am J Gastroenterol. 2001 Jul;96(7):2137-42. doi: 10.1111/j.1572-0241.2001.03949.x.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bruno BONAZ, MD principal investigator
Institut National de la Santé Et de la Recherche Médicale, France
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Valganciclovir in people with Cytomegalovirus Infections and Inflammatory Bowel Diseases, run by University Hospital, Grenoble at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 3 Apr 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: difficulty to include patients). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Improvement of Crohns disease activity index score. The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00237653, which also lists 13 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Apr 2009.