Hepatitis C in Clinically Discordant Hemophilic Siblings

September 22, 2016 updated by: University of North Carolina, Chapel Hill
To define the natural history, immunologic, and genetic factors that influence the clinical outcome of hepatitis C in a cohort of hemophilic siblings.

Study Overview

Status

Completed

Conditions

Detailed Description

BACKGROUND:

The clinical spectrum of hepatitis C is variable and the factors responsible for these divergent outcomes with chronic hepatitis C infection remain unknown. Dr. Fried and his colleagues are studying a cohort of hemophilic siblings infected with hepatitis C to define the natural history, immunologic, and genetic factors that influence its clinical outcome. Patients with hemophilia have a prevalence rate of hepatitis C as high as 90 percent. The sex-linked pattern of inheritance of hemophilia allows them to identify a cohort of siblings both of who have been infected with hepatitis C. Hemophilic siblings are an attractive population to study because: 1) They are all males; 2) Siblings are relatively close in age; 3) The mode of HCV acquisition is identical; 4) The age at acquisition of hepatitis C is similar 5) The date of acquisition can be confidently estimated upon their factor replacement history; 6) Hemophilic sibs share significant amounts of genetic material.

The study is in response to a Request for Applications entitled "Hepatitis C: Natural History, Pathogenesis, Therapy and Prevention" issued by the National Institute of Diabetes and Digestive and Kidney Diseases

DESIGN NARRATIVE:

Hemophilic siblings with hepatitis C undergo a detailed clinical evaluation to stage their liver disease and to identify sibling pairs with clinically and/or histologically discordant levels of disease activity. These siblings pairs are further studied to define antigen recognition patterns of lymphocyte cells including peripheral CD8 plus cytotoxic T lymphocytes (CTL) and CD4 plus cells and determine their functional significance. Using peripheral blood mononuclear cells, CD8 plus cells are assayed for CTL activity against three overlapping vaccinia/hepatitis C virus (HCV) constructs covering the entire HCV genome followed by fine cloning to identify HCV-specific CTL epitopes. Peripheral CD4 plus cells are tested for their ability to proliferate to HCV antigens. Using stimulation index, Drs. Fried and colleagues are quantitating the presence and magnitude of this response. They are also trying to identify immunodominant regions targeted by cytotoxic T cells using HLA class I matched hemophilic siblings. Finally, they are identifying specific host genes that are preferentially expressed or repressed in patients with delayed progression of their HCV disease. They are quantitating the expression of mRNAs encoding host antiviral defense and immunoregulatory elements in peripheral blood mononuclear cells (PBMCs) and liver tissue from sibling pairs that have discordant chronic hepatitis C using mRNA libraries that are screened by high density oligonucleotide arrays. The expression levels of these genes (including, but not limited to, interferon alpha, beta, and gamma; IRF-1 and IRF-2; interferon induced protein kinase; the cellular protein activator of PKR (PACT) RNase L; interferon-inducible RNA-specific adenosine deaminase; a ribonuclease specific for inosine- containing RNA; chemokine receptors CCR1, CCR3, CCR5, and their signal transduction elements; 2'-5'-oligoadenylate synthetase; tumor necrosis factor; FAS receptor; signal transduction components of these antiviral pathways, and both type 1 and 2 cytokines) are correlated with delayed progression and diminished pathogenesis in paired hemophilic siblings.

Study Type

Observational

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 100 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

No eligibility criteria

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of North Carolina, Chapel Hill

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

  • Principal Investigator: Michael Fried, University of North Carolina

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 1999

Primary Completion (Actual)

August 1, 2004

Study Completion (Actual)

August 1, 2004

Study Registration Dates

First Submitted

December 19, 2000

First Submitted That Met QC Criteria

November 27, 2000

First Posted (Estimate)

November 28, 2000

Study Record Updates

Last Update Posted (Estimate)

September 26, 2016

Last Update Submitted That Met QC Criteria

September 22, 2016

Last Verified

January 1, 2005

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 954
  • R01HL064817 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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