Effect of Immunosuppression Drug Weaning on Hepatitis C Virus (HCV)-Induced Liver Damage After Liver Transplantation

NCT00668369 | Completed Phase 2

• 1 other identifier: Weaning_HCV
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

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.

Conditions

Hepatitis C Virus Infection; Liver Transplantation

Keywords

Liver Transplantation; Tolerance; Hepatitis C virus infection; Immune responses; Allograft tolerance; Immunosuppression weaning; Immunosuppression minimization

Outcome Measures

Primary Outcomes (1)

• Proportion of hepatitis C virus positive liver recipients successfully withdrawing immunosuppressive drugs.

  18 months

Secondary Outcomes (2)

• Effects of immunosuppression withdrawal on hepatitis C virus induced liver damage.

  18 months

• Influence of HCV-induced immune responses on the feasibility of successfully withdrawing immunosuppressive drugs in liver transplant recipients.

  18 months

Study Arms (1)

1

EXPERIMENTAL

Liver transplant recipients with HCV infection fulfilling inclusion criteria.

Procedure: Gradual immunosuppression drug withdrawal.

Interventions

Gradual immunosuppression drug withdrawal. PROCEDURE

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.

1

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Liver transplantation for HCV-related liver disease performed at least 3 years before weaning;
• Peripheral blood Vgd1+/Vgd2+ T cell ratio \>2.33 and/or increased expression of KLRF1 and SLAMF7 genes in peripheral blood (measured by qPCR).
• No indication for treatment with pegylated a-interferon plus ribavirin during the weaning procedure;
• Stability of liver function tests for at least 6 months;
• No evidences of autoimmune liver disease;
• Absence of acute and/or chronic rejection episodes during the 12 months before weaning;
• Basal liver biopsy without signs of acute and/or chronic rejection.
• Absence of decompensated chronic liver disease.

You may not qualify if:

• HIV infection
• Double liver-kidney transplantation
• HCV cholestatic fibrosing hepatitis

Sponsors & Collaborators

• Hospital Clinic of Barcelona: lead

Study Sites (1)

Hospital Clinic Barcelona, University of Barcelona

Barcelona, 08036, Spain

Location

MeSH Terms

Conditions

Hepatitis C

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Study Officials

• Alberto Sanchez-Fueyo, MD

  Hospital Clinic Barcelona / IDIBAPS, Barcelona, Spain

  PRINCIPAL INVESTIGATOR

• Giuseppe Tisone, MD

  University Tor Vergata, Rome, Italy

  STUDY CHAIR

• Marina Berenguer, MD

  Hospital La Fe de Valencia

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director IDIBAPS Transplant Immunology Laboratory

Study Record Dates

• First Submitted: April 24, 2008
• First Posted: April 29, 2008
• Study Start: April 1, 2008
• Primary Completion: September 1, 2011
• Study Completion: September 1, 2011
• Last Updated: December 20, 2013

Record last verified: 2013-12

Locations

ES (1)