In Hepatitis C Patients Treated With Interferon and Ribavirin, Does Hepcidin Contribute to Treatment Induced Anaemia

Hepatitis C Clinical Trial

Official title:

Is Hepcidin a Possible Contributor to Impaired Iron Mobilization and Anaemia in Hepatitis C Patients Treated With Pegylated Interferon Alpha and Ribavirin Therapy? A Pilot Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01726400
• Other study ID #: HEPCIDIN-11/225
• Status: Completed
• Phase: N/A
• First received: November 9, 2012
• Last updated: November 9, 2015
• Start date: December 2012
• Est. completion date: July 2014

Study information

• Verified date: November 2015
• Source: Fremantle Hospital and Health Service
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: July 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Any patient with hepatitis C eligible for treatment with pegylated interferon alpha containing regimes.

Exclusion Criteria:

• less than 18 years of age

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C

Intervention

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.
• 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.

Locations

Country	Name	City	State
Australia	Fremantle Hospital	Fremantle	Western Australia

Sponsors (1)

Lead Sponsor	Collaborator
Fremantle Hospital and Health Service

Country where clinical trial is conducted

Australia, 

References & Publications (10)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Owen JA, de Gruchy GC, Smith H. SERUM HAPTOGLOBINS IN HAEMOLYTIC STATES. J Clin Pathol. 1960 Nov;13(6):478-82. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hepcidin levels	To measure changes in serum hepcidin levels during pegylated interferon alpha and ribavirin therapy in subjects with chronic hepatitis C infection.	Measured at -2 weeks, start of treatment and week 3,4,8, 12 and 24.
Secondary	iron metabolism markers	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.	Measured at -2 weeks, start of treatment and week 3,4,8, 12 and 24.
Secondary	heamolysis markers	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.	Measured at -2 weeks, start of treatment and week 3,4,8, 12 and 24.
Secondary	inosine triphosphatase genetic variants	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.	Baseline
Secondary	erythropoiesis markers	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.	Measured at -2 weeks, start of treatment and week 3,4,8, 12 and 24.

External Links

•   australian new zealand clinical trials register