Effect of Immunosuppression Drug Weaning on Hepatitis C Virus (HCV)-Induced Liver Damage After Liver Transplantation
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First Received Date ICMJE | April 24, 2008 | ||||||||||||
Last Updated Date | September 29, 2011 | ||||||||||||
Start Date ICMJE | April 2008 | ||||||||||||
Estimated Primary Completion Date | September 2011 (final data collection date for primary outcome measure) | ||||||||||||
Current Primary Outcome Measures ICMJE |
Proportion of hepatitis C virus positive liver recipients successfully withdrawing immunosuppressive drugs. [ Time Frame: 18 months ] [ Designated as safety issue: Yes ] | ||||||||||||
Original Primary Outcome Measures ICMJE | Same as current | ||||||||||||
Change History | Complete list of historical versions of study NCT00668369 on ClinicalTrials.gov Archive Site | ||||||||||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current | ||||||||||||
Current Other Outcome Measures ICMJE | |||||||||||||
Original Other Outcome Measures ICMJE | |||||||||||||
Descriptive Information | |||||||||||||
Brief Title ICMJE | Effect of Immunosuppression Drug Weaning on Hepatitis C Virus (HCV)-Induced Liver Damage After Liver Transplantation | ||||||||||||
Official Title ICMJE | Effect of Immunosuppression Drug Weaning on Hepatitis C Virus Induced Liver Damage After Liver Transplantation. | ||||||||||||
Brief Summary | 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. |
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Detailed Description | 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. |
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Study Type ICMJE | Interventional | ||||||||||||
Study Phase | Phase 4 | ||||||||||||
Study Design ICMJE | Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
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Condition ICMJE |
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Intervention ICMJE | 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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Study Arm (s) | Experimental: 1
Liver transplant recipients with HCV infection fulfilling inclusion criteria.
Intervention: Procedure: Gradual immunosuppression drug withdrawal. |
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Publications * | |||||||||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||||||||
Recruitment Status ICMJE | Active, not recruiting | ||||||||||||
Estimated Enrollment ICMJE | 53 | ||||||||||||
Estimated Completion Date | September 2011 | ||||||||||||
Estimated Primary Completion Date | September 2011 (final data collection date for primary outcome measure) | ||||||||||||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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Gender | Both | ||||||||||||
Ages | 18 Years to 75 Years | ||||||||||||
Accepts Healthy Volunteers | No | ||||||||||||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||||||||||
Location Countries ICMJE | Spain | ||||||||||||
Administrative Information | |||||||||||||
NCT Number ICMJE | NCT00668369 | ||||||||||||
Other Study ID Numbers ICMJE | Weaning_HCV | ||||||||||||
Has Data Monitoring Committee | No | ||||||||||||
Responsible Party | Alberto Sanchez-Fueyo, Hospital Clinic of Barcelona | ||||||||||||
Study Sponsor ICMJE | Hospital Clinic of Barcelona | ||||||||||||
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Investigators ICMJE |
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Information Provided By | Hospital Clinic of Barcelona | ||||||||||||
Verification Date | September 2011 | ||||||||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |