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Assessment of Intrahepatic Hepatitis C Virus (HCV) RNA Levels at the Time of Liver Transplantation

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Merck Sharpe & Dohme Corporation
Mount Sinai School of Medicine
Information provided by (Responsible Party):
Schiano, Thomas D., MD
ClinicalTrials.gov Identifier:
NCT01836718
First received: April 17, 2013
Last updated: November 17, 2014
Last verified: November 2014
  Purpose

The purpose of this study is to measure intrahepatic HCV RNA levels at the time of liver transplantation in patients receiving antiviral therapy while on the liver transplant waiting list. This will eventually be correlated with the degree of hepatic fibrosis present within different geographic sites in the cirrhotic liver. Tissue samples will be obtained from the patient's liver explant as well as hilar lymph nodes. Upon the removal of the cirrhotic liver at the time of transplantation, the explant will be biopsied multiple times in different segments of the liver and preserved for viral detection studies as well as analysis of the degree of fibrosis. Peripheral blood mononuclear cells (PBMCs) will be obtained for viral detection at the time of transplantation. Serum HCV RNA levels will also be obtained at 1 month, 3 months and 6 months post liver transplantation.

Study Hypotheses:

  • Virological relapse or non-response is higher is patients with cirrhosis due to failure of antiviral medication to concentrate adequately in a fibrotic liver having an altered sinusoidal micro-architecture
  • HCV may persist in different geographic regions of the fibrotic liver in part predicated on blood supply to that area and this may have an effect on overall virological response. These differences in viral persistence and detection may exist in different lobes of the liver or even within a few centimeters within the same portion of the liver parenchyma.
  • PBMC and hilar lymph nodes may be extrahepatic reservoirs of HCV viral persistence in patients receiving antiviral therapy and may account for virological relapse post-therapy
  • There may be varying degrees of fibrosis within the same cirrhotic liver which may impact on hepatic synthetic function and antiviral response to treatment.

Condition
Hepatitis C Virus
Liver Transplantation

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: An Assessment of Intrahepatic HCV RNA Levels at the Time of Liver Transplantation in Patients With HCV Receiving Antiviral Therapy While on the Liver Transplant Waiting List Compared to Those Not Currently Receiving Therapy

Resource links provided by NLM:


Further study details as provided by Schiano, Thomas D., MD:

Primary Outcome Measures:
  • HCV RNA PCR levels [ Time Frame: Time of Transplantation ] [ Designated as safety issue: No ]
    The primary objective is to detect and quantitate HCV RNA PCR levels in different anatomic regions of the liver at the time of liver transplantation to ascertain whether there is similar geographic presence and/or clearance of HCV during antiviral therapy


Secondary Outcome Measures:
  • HCV persistence [ Time Frame: Time of Transplantation ] [ Designated as safety issue: No ]
    To ascertain whether HCV persistence within the liver is predictive of virological relapse post liver transplantation.

  • Hepatic Fibrosis [ Time Frame: Time of Transplantation ] [ Designated as safety issue: No ]
    To assess the degree of hepatic fibrosis at the site of intrahepatic HCV viral detection in order to ascertain whether HCV viral detection correlates with the degree of fibrosis. This study will also examine whether there can be different degrees of hepatic fibrosis in different geographic portions of the same liver and whether there would be a correlation with the patients' natural MELD score, degree of hepatic synthetic function and ultimate virological response to antiviral therapy.

  • Extrahepatic reservoirs [ Time Frame: Time of Transplantation ] [ Designated as safety issue: No ]
    To examine whether hilar lymph nodes and PBMC are extrahepatic reservoirs of HCV in patients receiving antiviral therapy and then to correlate this with intrahepatic detection of HCV and overall virological response.


Biospecimen Retention:   Samples With DNA

Whole blood, serum, liver explant tissue and hilar lymph nodes will be obtained for testing. With subject consent, any unused specimens will be retained indefinitely for use in future research either related or unrelated to this study, which may include genetic testing.


Estimated Enrollment: 20
Study Start Date: June 2013
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts
HCV RNA (-) on anti-viral therapy
Patients undergoing liver transplantation who are documented HCV viral load undetectable while on antiviral therapy
HCV RNA (+) on anti-viral therapy
Patients undergoing liver transplantation who are receiving anti-viral therapy and who have a documented detectable HCV viral load
HCV RNA (+) not on anti-viral therapy
Patients undergoing liver transplantation who are not currently receiving anti-viral therapy and are documented viral load positive will be included and serve as a comparison group

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Patients with Chronic Hepatitis C on the Mount Sinai Recanati/Miller Transplantation Institute's Liver Transplant Waiting list may be eligible for participation

Criteria

Inclusion Criteria:

  • Patients age 18-80 with chronic HCV on the liver transplant waiting list may be eligible for participation
  • The following subjects will be enrolled:

    • Patients undergoing liver transplantation who are documented HCV viral load undetectable while on antiviral therapy
    • Patients receiving anti-viral therapy and who have a detectable HCV viral load
    • Patients not currently receiving antiviral therapy and are HCV PCR (+) will be included and serve as a comparison group

Exclusion Criteria:

  • Patients who are co-infected with HIV and/or HBV will not be included
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01836718

Locations
United States, New York
Mount Sinai School of Medicine Recanati/Miller Transplantation Institute
New York, New York, United States, 10029
Sponsors and Collaborators
Schiano, Thomas D., MD
Merck Sharpe & Dohme Corporation
Mount Sinai School of Medicine
Investigators
Principal Investigator: Thomas D Schiano, MD Mount Sinai School of Medicine Recanati/Miller Transplantation Institute
  More Information

No publications provided

Responsible Party: Schiano, Thomas D., MD
ClinicalTrials.gov Identifier: NCT01836718     History of Changes
Other Study ID Numbers: MISP-50064, 13-00099
Study First Received: April 17, 2013
Last Updated: November 17, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Schiano, Thomas D., MD:
Hepatitis C Virus
Liver Transplantation
Antiviral Therapy
HCV

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Digestive System Diseases
Enterovirus Infections
Flaviviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases
Antiviral Agents
Anti-Infective Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014