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Sponsored by: |
Hospital Clinic of Barcelona |
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Information provided by: | Hospital Clinic of Barcelona |
ClinicalTrials.gov Identifier: | NCT00668369 |
Viral infections can profoundly influence alloimmune responses and hamper allograft tolerance induction. Persistent hepatitis C virus (HCV) infection occurs in 50% of liver and 20% of kidney transplant recipients, but the impact of HCV on the acquisition of allograft tolerance has not been elucidated. Liver transplantation constitutes a unique clinical model to address this question, given that up to 20% of liver recipients can completely discontinue immunosuppressive drugs and attain operational tolerance.
The goal of our study is to determine the influence of HCV-driven immune responses on the acquisition of operational tolerance in liver transplant recipients following drug weaning, and to assess whether immunosuppression withdrawal ameliorates HCV-induced liver damage.
This is a prospective trial in which immunosuppressive drug weaning will be offered to HCV-positive liver recipients (selected on the basis of a high likelihood of tolerance) as a strategy to improve HCV-mediated liver disease.
Condition | Intervention | Phase |
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Hepatitis C Virus Infection Liver Transplantation |
Procedure: Gradual immunosuppression drug withdrawal. |
Phase IV |
Study Type: | Interventional |
Study Design: | Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study |
Official Title: | Effect of Immunosuppression Drug Weaning on Hepatitis C Virus Induced Liver Damage After Liver Transplantation. |
Estimated Enrollment: | 53 |
Study Start Date: | April 2008 |
Estimated Study Completion Date: | April 2011 |
Estimated Primary Completion Date: | April 2010 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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1: Experimental
Liver transplant recipients with HCV infection fulfilling inclusion criteria.
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Procedure: Gradual immunosuppression drug withdrawal.
Ater obtention of biological samples (peripheral blood, liver tissue) enrolled patients undergo gradual decrease in the doses of immunosuppression drugs (tacrolimus, cyclosporine A and/or mofetil mycophenolate) until complete discontinuation or appearance of rejection.
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Objective: To determine the influence of hepatitis C virus (HCV)-driven immune responses on the acquisition of operational tolerance in liver transplant recipients following drug weaning, and to assess whether immunosuppression withdrawal ameliorates HCV-induced liver damage.
Background: Viral infections can profoundly influence alloimmune responses and hamper allograft tolerance induction. Persistent HCV infection occurs in 50% of liver and 20% of kidney transplant recipients, but the impact of HCV on the acquisition of allograft tolerance has not been elucidated. Liver transplantation constitutes a unique clinical model to address this question, given that up to 20% of liver recipients can completely discontinue immunosuppressive drugs and attain operational tolerance.
Hypothesis/Specific Aims: We hypothesize that HCV positive patients failing to attain operational tolerance will exhibit both decreased anti-HCV specific T cell responses and exacerbated non-specific immunoactivation. Furthermore, we anticipate that successful immunosuppression withdrawal will decrease the progression of HCV-induced liver damage. Thus our aims are:
Proposed methods: On the basis of a previously identified immunophenotypic signature of tolerance (high ratio of delta 1 to delta 2 gammadelta T cell in peripheral blood), drug weaning will be offered to HCV-positive liver recipients as a strategy to improve HCV-mediated liver disease. We estimate that patients selected on the basis of this biomarker will have a likelihood of successful weaning greater than 50%. Both peripheral blood and liver tissue samples will be collected for diagnostic purposes before the initiation of drug weaning in order to perform the following assays: measurement of anti-HCV CD4+ and CD8+ T cell immunity, peripheral blood and liver tissue gene expression profiling, peripheral blood cell phenotyping and functional assays and, in a subset of patients, measurement of anti-donor T cell responses. Immunosuppression drugs will be weaned over a period of 6 months, and thereafter patients will be followed for 12 additional months. Patients not undergoing rejection during this 18 month period will be considered tolerant. Liver biopsies will be obtained before the beginning of the study and at the end. Progression of HCV-induced liver diseased will be compared to that of patients with a low delta1/delta2 ratio, in whom no changes in immunosuppressive drugs will be conducted and liver biopsies will be obtained yearly (according to our clinical guidelines).
Expected results: We expect to precisely define how HCV influences the acquisition of operational tolerance after liver transplantation, and confirm the beneficial effect of immunosuppression withdrawal in these patients.
Ages Eligible for Study: | 18 Years to 75 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Contact: Alberto Sanchez-Fueyo, MD | 34-93-227-5400 ext 2344 | afueyo@clinic.ub.es |
Spain | |
Hospital Clinic Barcelona, University of Barcelona | Recruiting |
Barcelona, Spain, 08036 | |
Contact: Alberto Sanchez-Fueyo, MD afueyo@clinic.ub.es |
Principal Investigator: | Alberto Sanchez-Fueyo, MD | Hospital Clinic Barcelona / IDIBAPS, Barcelona, Spain |
Study Chair: | Giuseppe Tisone, MD | University Tor Vergata, Rome, Italy |
Study Chair: | Marina Berenguer, MD | Hospital La Fe Valencia |
Responsible Party: | Hospital Clinic Barcelona / IDIBAPS ( Alberto Sanchez-Fueyo ) |
Study ID Numbers: | Weaning_HCV |
Study First Received: | April 24, 2008 |
Last Updated: | December 19, 2008 |
ClinicalTrials.gov Identifier: | NCT00668369 |
Health Authority: | Spain: Spanish Agency of Medicines |
Liver Transplantation Tolerance Hepatitis C virus infection Immune responses |
Allograft tolerance Immunosuppression weaning Immunosuppression minimization |
Virus Diseases Hepatitis Liver Diseases Cyclosporine Digestive System Diseases |
Mycophenolate mofetil Hepatitis, Viral, Human Tacrolimus Hepatitis C Cyclosporins |
RNA Virus Infections Flaviviridae Infections Infection |