In Hepatitis C Patients Treated With Interferon and Ribavirin, Does Hepcidin Contribute to Treatment Induced Anaemia
Study Details
Study Description
Brief Summary
The standard treatment of chronic hepatitis C infection is pegylated interferon alpha combined with ribavirin. Anaemia is a common complication occurring in up to 30% of subjects. Unfortunately, side effects of interferon and ribavirin therapy can require dose reductions, reducing the likelihood of sustained viral response. Recent data shows that interferon alpha may increase hepcidin (a key iron regulator) production, resulting in impaired iron availability for production of red blood cells. In this study, we will evaluate hepcidin levels in 30 patients with Hepatitis C who are treated with interferon containing regimes. If hepcidin plays a role in interferon-induced anaemia, cheap and readily available oral hepcidin inhibitors could be trialled to potentially reduce the impact of interferon alpha induced anaemia.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Interferon and ribavirin Treatment with standard of care pegylated interferon alpha and ribavirin. |
Drug: Pegylated interferon alpha
Subcutaneous weekly pegylated interferon alpha and daily oral ribavirin treatment as per standard treatment. The dosages for interferon and ribavirin are as per therapeutic guidelines and are based on weight, genotype and previous treatments.
Other Names:
Drug: Ribavirin
Subcutaneous weekly pegylated interferon alpha and daily oral ribavirin treatment as per standard treatment. The dosages for interferon and ribavirin are as per therapeutic guidelines and are based on weight, genotype and previous treatments.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Hepcidin levels [Measured at -2 weeks, start of treatment and week 3,4,8, 12 and 24.]
To measure changes in serum hepcidin levels during pegylated interferon alpha and ribavirin therapy in subjects with chronic hepatitis C infection.
Secondary Outcome Measures
- iron metabolism markers [Measured at -2 weeks, start of treatment and week 3,4,8, 12 and 24.]
To measure changes in iron metabolism (reticulocyte haemoglobin, serum iron, transferrin saturation and ferritin levels) during pegylated interferon alpha and ribavirin therapy in subjects with chronic hepatitis C infection.
- heamolysis markers [Measured at -2 weeks, start of treatment and week 3,4,8, 12 and 24.]
To detect ribavirin induced heamolysis by measuring serum haptoglobin and free haemoglobin during pegylated interferon alpha and ribavirin therapy in subjects with chronic hepatitis C infection.
- inosine triphosphatase genetic variants [Baseline]
To measure the effect of inosine triphosphatase genetic variants on anemia during pegylated interferon alpha and ribavirin therapy in subjects with chronic hepatitis C infection.
- erythropoiesis markers [Measured at -2 weeks, start of treatment and week 3,4,8, 12 and 24.]
To measure the level of erythropoiesis (IL1, IL6, erythropoietin and reticulocyte) during pegylated interferon alpha and ribavirin therapy in subjects with chronic hepatitis C infection.
Eligibility Criteria
Criteria
Inclusion Criteria:
- Any patient with hepatitis C eligible for treatment with pegylated interferon alpha containing regimes.
Exclusion Criteria:
- less than 18 years of age
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Fremantle Hospital | Fremantle | Western Australia | Australia | 6160 |
Sponsors and Collaborators
- Fremantle Hospital and Health Service
Investigators
- Principal Investigator: Marius M Van Rijnsoever, MBBS, South Metropolitan Health Service, Perth Western Australia
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- Chua AC, Graham RM, Trinder D, Olynyk JK. The regulation of cellular iron metabolism. Crit Rev Clin Lab Sci. 2007;44(5-6):413-59. Review.
- Ferrari P, Mallon D, Trinder D, Olynyk JK. Pentoxifylline improves haemoglobin and interleukin-6 levels in chronic kidney disease. Nephrology (Carlton). 2010 Apr;15(3):344-9. doi: 10.1111/j.1440-1797.2009.01203.x.
- Kwo PY, Lawitz EJ, McCone J, Schiff ER, Vierling JM, Pound D, Davis MN, Galati JS, Gordon SC, Ravendhran N, Rossaro L, Anderson FH, Jacobson IM, Rubin R, Koury K, Pedicone LD, Brass CA, Chaudhri E, Albrecht JK; SPRINT-1 investigators. Efficacy of boceprevir, an NS3 protease inhibitor, in combination with peginterferon alfa-2b and ribavirin in treatment-naive patients with genotype 1 hepatitis C infection (SPRINT-1): an open-label, randomised, multicentre phase 2 trial. Lancet. 2010 Aug 28;376(9742):705-16. doi: 10.1016/S0140-6736(10)60934-8. Epub 2010 Aug 6. Erratum in: Lancet. 2010 Oct 9;376(9748):1224. SPRINT-1 investigators [added]; multiple investigator names added.
- Olynyk JK, Trinder D, Ramm GA, Britton RS, Bacon BR. Hereditary hemochromatosis in the post-HFE era. Hepatology. 2008 Sep;48(3):991-1001. doi: 10.1002/hep.22507.
- Owen JA, de Gruchy GC, Smith H. SERUM HAPTOGLOBINS IN HAEMOLYTIC STATES. J Clin Pathol. 1960 Nov;13(6):478-82.
- Poordad F. Big changes are coming in hepatitis C. Curr Gastroenterol Rep. 2011 Feb;13(1):72-7. doi: 10.1007/s11894-010-0153-9.
- Russmann S, Grattagliano I, Portincasa P, Palmieri VO, Palasciano G. Ribavirin-induced anemia: mechanisms, risk factors and related targets for future research. Curr Med Chem. 2006;13(27):3351-7. Review.
- Thompson AJ, Clark PJ, Singh A, Ge D, Fellay J, Zhu M, Zhu Q, Urban TJ, Patel K, Tillmann HL, Naggie S, Afdhal NH, Jacobson IM, Esteban R, Poordad F, Lawitz EJ, McCone J, Shiffman ML, Galler GW, King JW, Kwo PY, Shianna KV, Noviello S, Pedicone LD, Brass CA, Albrecht JK, Sulkowski MS, Goldstein DB, McHutchison JG, Muir AJ. Genome-wide association study of interferon-related cytopenia in chronic hepatitis C patients. J Hepatol. 2012 Feb;56(2):313-9. doi: 10.1016/j.jhep.2011.04.021. Epub 2011 May 20.
- Ward DG, Roberts K, Brookes MJ, Joy H, Martin A, Ismail T, Spychal R, Iqbal T, Tselepis C. Increased hepcidin expression in colorectal carcinogenesis. World J Gastroenterol. 2008 Mar 7;14(9):1339-45.
- Zhang X, Rovin BH. Hepcidin expression by human monocytes in response to adhesion and pro-inflammatory cytokines. Biochim Biophys Acta. 2010 Dec;1800(12):1262-7. doi: 10.1016/j.bbagen.2010.08.005. Epub 2010 Aug 27.
- HEPCIDIN-11/225