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

NCT01726400 | Completed DMC

• 1 other identifier: HEPCIDIN-11/225
• Study Type: observational
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Hepatitis C

Keywords

Hepatitis C; Interferon; Ribavirin; Hepcidin; Iron metabolism

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• iron metabolism markers

  Measured at -2 weeks, start of treatment and week 3,4,8, 12 and 24.

• heamolysis markers

  Measured at -2 weeks, start of treatment and week 3,4,8, 12 and 24.

• inosine triphosphatase genetic variants

  Baseline

• erythropoiesis markers

  Measured at -2 weeks, start of treatment and week 3,4,8, 12 and 24.

Study Arms (1)

Interferon and ribavirin

Treatment with standard of care pegylated interferon alpha and ribavirin.

Drug: Pegylated interferon alpha; Drug: Ribavirin

Interventions

Pegylated interferon alpha DRUG

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.

Also known as: pegasys, pegatron

Interferon and ribavirin

Ribavirin DRUG

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.

Also known as: Copegus, Rebetol, Ribasphere, Vilona, Virazole

Interferon and ribavirin

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Hepatitis C patients undergoing standard of care treatment with interferon alpha.

You may qualify if:

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

You may not qualify if:

• less than 18 years of age

Sponsors & Collaborators

• Fremantle Hospital and Health Service: lead

Study Sites (1)

Fremantle Hospital

Fremantle, Western Australia, 6160, Australia

Location

Related Publications (11)

• 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.

  PMID: 21063814 BACKGROUND

• 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.

  PMID: 20692693 BACKGROUND

• 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. doi: 10.2174/092986706778773059.

  PMID: 17168855 BACKGROUND

• 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. doi: 10.1080/10408360701428257.

  PMID: 17943492 BACKGROUND

• 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.

  PMID: 18752323 BACKGROUND

• 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.

  PMID: 20801192 BACKGROUND

• 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. doi: 10.3748/wjg.14.1339.

  PMID: 18322945 BACKGROUND

• 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.

  PMID: 20470305 BACKGROUND

• Owen JA, de Gruchy GC, Smith H. SERUM HAPTOGLOBINS IN HAEMOLYTIC STATES. J Clin Pathol. 1960 Nov;13(6):478-82. doi: 10.1136/jcp.13.6.478.

  PMID: 16810960 BACKGROUND

• 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.

  PMID: 21703177 BACKGROUND

• van Rijnsoever M, Galhenage S, Mollison L, Gummer J, Trengove R, Olynyk JK. Dysregulated Erythropoietin, Hepcidin, and Bone Marrow Iron Metabolism Contribute to Interferon-Induced Anemia in Hepatitis C. J Interferon Cytokine Res. 2016 Nov;36(11):630-634. doi: 10.1089/jir.2016.0043. Epub 2016 Sep 12.

  PMID: 27617496 DERIVED

Related Links

• australian new zealand clinical trials register

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood is collect for genomic DNA extraction. Serum samples will be stored for hepcidin analysis.

MeSH Terms

Conditions

Hepatitis C

Interventions

peginterferon alfa-2a; Ribavirin

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Marius M Van Rijnsoever, MBBS

  South Metropolitan Health Service, Perth Western Australia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Registrar

Study Record Dates

• First Submitted: November 9, 2012
• First Posted: November 14, 2012
• Study Start: December 1, 2012
• Primary Completion: January 1, 2014
• Study Completion: July 1, 2014
• Last Updated: November 10, 2015

Record last verified: 2015-11

Locations

AU (1)