Blood DiseaseNCT00007371
Hepatitis C in Clinically Discordant Hemophilic Siblings
An observational study of Blood Disease and Hemophilia A, run by University of North Carolina, Chapel Hill.
Trial summary
To define the natural history, immunologic, and genetic factors that influence the clinical outcome of hepatitis C in a cohort of hemophilic siblings. Read more about this study
- Who is it for?
- Ages Up to 100 years, men only
- Conditions the study is for
- Blood Disease, Hemophilia A, Hepatitis, Viral, Human
- How many people
- Not given
- Where
- No sites listed yet
- Study dates
- Sep 1999to Aug 2004
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 100 years
- Men only
- No healthy volunteers
- Child, Adult, Older adult
No eligibility criteria
About this study
To define the natural history, immunologic, and genetic factors that influence the clinical outcome of hepatitis C in a cohort of hemophilic siblings.
Read the 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.
- Conditions
- Blood Disease, Hemophilia A, Hepatitis, Viral, Human
- Medical subject headings
- Hematologic Diseases, Hemophilia A, Hepatitis, Viral, Human
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Nov 2000 (estimated)
- Study startSep 1999
- Primary completionAug 2004
- Study completionAug 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Blood DiseaseStudies of the same condition, open and under way.
- More trials run by University of North Carolina, Chapel HillThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor
- Investigators
- Michael Fried, Principal investigator, University of North Carolina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00007371
- Sponsor's protocol ID
- 954
- Other IDs
- R01HL064817
- Status last verified
- Jan 2005
- First submitted
- 19 Dec 2000
- Last updated
- 26 Sep 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Kweon YO, Goodman ZD, Dienstag JL, Schiff ER, Brown NA, Burchardt E, Schoonhoven R, Brenner DA, Fried MW. Decreasing fibrogenesis: an immunohistochemical study of paired liver biopsies following lamivudine therapy for chronic hepatitis B. J Hepatol. 2001 Dec;35(6):749-55. doi: 10.1016/s0168-8278(01)00218-5.
PubMed 11738102Nelson DR, Soldevila-Pico C, Reed A, Abdelmalek MF, Hemming AW, Van der Werf WJ, Howard R, Davis GL. Anti-interleukin-2 receptor therapy in combination with mycophenolate mofetil is associated with more severe hepatitis C recurrence after liver transplantation. Liver Transpl. 2001 Dec;7(12):1064-70. doi: 10.1053/jlts.2001.29414.
PubMed 11753908Fried MW. Side effects of therapy of hepatitis C and their management. Hepatology. 2002 Nov;36(5 Suppl 1):S237-44. doi: 10.1053/jhep.2002.36810.
PubMed 12407599Fried MW, Peter J, Hoots K, Gaglio PJ, Talbut D, Davis PC, Key NS, White GC, Lindblad L, Rickles FR, Abshire TC. Hepatitis C in adults and adolescents with hemophilia: a randomized, controlled trial of interferon alfa-2b and ribavirin. Hepatology. 2002 Oct;36(4 Pt 1):967-72. doi: 10.1053/jhep.2002.35529.
PubMed 12297845Nelson DR, Tu Z, Soldevila-Pico C, Abdelmalek M, Zhu H, Xu YL, Cabrera R, Liu C, Davis GL. Long-term interleukin 10 therapy in chronic hepatitis C patients has a proviral and anti-inflammatory effect. Hepatology. 2003 Oct;38(4):859-68. doi: 10.1053/jhep.2003.50427.
PubMed 14512873Liu C, Zhu H, Tu Z, Xu YL, Nelson DR. CD8+ T-cell interaction with HCV replicon cells: evidence for both cytokine- and cell-mediated antiviral activity. Hepatology. 2003 Jun;37(6):1335-42. doi: 10.1053/jhep.2003.50207.
PubMed 12774012Zhu H, Zhao H, Collins CD, Eckenrode SE, Run Q, McIndoe RA, Crawford JM, Nelson DR, She JX, Liu C. Gene expression associated with interferon alfa antiviral activity in an HCV replicon cell line. Hepatology. 2003 May;37(5):1180-8. doi: 10.1053/jhep.2003.50184.
PubMed 12717400Cabrera R, Tu Z, Xu Y, Firpi RJ, Rosen HR, Liu C, Nelson DR. An immunomodulatory role for CD4(+)CD25(+) regulatory T lymphocytes in hepatitis C virus infection. Hepatology. 2004 Nov;40(5):1062-71. doi: 10.1002/hep.20454.
PubMed 15486925Theodore D, Fried MW, Kleiner DE, Kroner BL, Goedert JJ, Eyster ME, Faust SP, Sherman KE, Kessler CM, Francis C, Aledort LM. Liver biopsy in patients with inherited disorders of coagulation and chronic hepatitis C. Haemophilia. 2004 Sep;10(5):413-21. doi: 10.1111/j.1365-2516.2004.00919.x.
PubMed 15357765
Study at a glance
From the registry record, last updated by the sponsor on 26 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hepatitis C in Clinically Discordant Hemophilic Siblings
- ClinicalTrials.gov ID
- NCT00007371
- Acronym / sponsor ID
- 954
- Conditions
- Blood Disease, Hemophilia A, Hepatitis, Viral, Human
- Study type
- Observational
- Recruitment status
- Completed
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Sep 1999
- Primary completion
- Aug 2004 (actual)
- Study completion
- Aug 2004 (actual)
- First posted
- 28 Nov 2000 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To define the natural history, immunologic, and genetic factors that influence the clinical outcome of hepatitis C in a cohort of hemophilic siblings.
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 design
Who may qualify
- Ages
- Up to 100 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Sep 2016.
- Background: PubMed 11738102Kweon YO, Goodman ZD, Dienstag JL, Schiff ER, Brown NA, Burchardt E, Schoonhoven R, Brenner DA, Fried MW. Decreasing fibrogenesis: an immunohistochemical study of paired liver biopsies following lamivudine therapy for chronic hepatitis B. J Hepatol. 2001 Dec;35(6):749-55. doi: 10.1016/s0168-8278(01)00218-5.
- Background: PubMed 11753908Nelson DR, Soldevila-Pico C, Reed A, Abdelmalek MF, Hemming AW, Van der Werf WJ, Howard R, Davis GL. Anti-interleukin-2 receptor therapy in combination with mycophenolate mofetil is associated with more severe hepatitis C recurrence after liver transplantation. Liver Transpl. 2001 Dec;7(12):1064-70. doi: 10.1053/jlts.2001.29414.
- Background: PubMed 12407599Fried MW. Side effects of therapy of hepatitis C and their management. Hepatology. 2002 Nov;36(5 Suppl 1):S237-44. doi: 10.1053/jhep.2002.36810.
- Background: PubMed 12297845Fried MW, Peter J, Hoots K, Gaglio PJ, Talbut D, Davis PC, Key NS, White GC, Lindblad L, Rickles FR, Abshire TC. Hepatitis C in adults and adolescents with hemophilia: a randomized, controlled trial of interferon alfa-2b and ribavirin. Hepatology. 2002 Oct;36(4 Pt 1):967-72. doi: 10.1053/jhep.2002.35529.
- Background: PubMed 14512873Nelson DR, Tu Z, Soldevila-Pico C, Abdelmalek M, Zhu H, Xu YL, Cabrera R, Liu C, Davis GL. Long-term interleukin 10 therapy in chronic hepatitis C patients has a proviral and anti-inflammatory effect. Hepatology. 2003 Oct;38(4):859-68. doi: 10.1053/jhep.2003.50427.
- Background: PubMed 12774012Liu C, Zhu H, Tu Z, Xu YL, Nelson DR. CD8+ T-cell interaction with HCV replicon cells: evidence for both cytokine- and cell-mediated antiviral activity. Hepatology. 2003 Jun;37(6):1335-42. doi: 10.1053/jhep.2003.50207.
- Background: PubMed 12717400Zhu H, Zhao H, Collins CD, Eckenrode SE, Run Q, McIndoe RA, Crawford JM, Nelson DR, She JX, Liu C. Gene expression associated with interferon alfa antiviral activity in an HCV replicon cell line. Hepatology. 2003 May;37(5):1180-8. doi: 10.1053/jhep.2003.50184.
- Background: PubMed 15486925Cabrera R, Tu Z, Xu Y, Firpi RJ, Rosen HR, Liu C, Nelson DR. An immunomodulatory role for CD4(+)CD25(+) regulatory T lymphocytes in hepatitis C virus infection. Hepatology. 2004 Nov;40(5):1062-71. doi: 10.1002/hep.20454.
- Background: PubMed 15357765Theodore D, Fried MW, Kleiner DE, Kroner BL, Goedert JJ, Eyster ME, Faust SP, Sherman KE, Kessler CM, Francis C, Aledort LM. Liver biopsy in patients with inherited disorders of coagulation and chronic hepatitis C. Haemophilia. 2004 Sep;10(5):413-21. doi: 10.1111/j.1365-2516.2004.00919.x.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Fried principal investigator
University of North Carolina
Questions about this trial
What is this clinical trial studying?
An observational study of Blood Disease and Hemophilia A, run by University of North Carolina, Chapel Hill.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00007371, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Sep 2016.