<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01726400</url>
  </required_header>
  <id_info>
    <org_study_id>HEPCIDIN-11/225</org_study_id>
    <nct_id>NCT01726400</nct_id>
  </id_info>
  <brief_title>In Hepatitis C Patients Treated With Interferon and Ribavirin, Does Hepcidin Contribute to Treatment Induced Anaemia</brief_title>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fremantle Hospital and Health Service</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Fremantle Hospital and Health Service</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The standard treatment of chronic hepatitis C infection is pegylated interferon alpha&#xD;
      combined with ribavirin. Anaemia is a common complication occurring in up to 30% of subjects.&#xD;
      Unfortunately, side effects of interferon and ribavirin therapy can require dose reductions,&#xD;
      reducing the likelihood of sustained viral response. Recent data shows that interferon alpha&#xD;
      may increase hepcidin (a key iron regulator) production, resulting in impaired iron&#xD;
      availability for production of red blood cells. In this study, we will evaluate hepcidin&#xD;
      levels in 30 patients with Hepatitis C who are treated with interferon containing regimes. If&#xD;
      hepcidin plays a role in interferon-induced anaemia, cheap and readily available oral&#xD;
      hepcidin inhibitors could be trialled to potentially reduce the impact of interferon alpha&#xD;
      induced anaemia.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>December 2012</start_date>
  <completion_date type="Actual">July 2014</completion_date>
  <primary_completion_date type="Actual">January 2014</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Hepcidin levels</measure>
    <time_frame>Measured at -2 weeks, start of treatment and week 3,4,8, 12 and 24.</time_frame>
    <description>To measure changes in serum hepcidin levels during pegylated interferon alpha and ribavirin therapy in subjects with chronic hepatitis C infection.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>iron metabolism markers</measure>
    <time_frame>Measured at -2 weeks, start of treatment and week 3,4,8, 12 and 24.</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>heamolysis markers</measure>
    <time_frame>Measured at -2 weeks, start of treatment and week 3,4,8, 12 and 24.</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>inosine triphosphatase genetic variants</measure>
    <time_frame>Baseline</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>erythropoiesis markers</measure>
    <time_frame>Measured at -2 weeks, start of treatment and week 3,4,8, 12 and 24.</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">15</enrollment>
  <condition>Hepatitis C</condition>
  <arm_group>
    <arm_group_label>Interferon and ribavirin</arm_group_label>
    <description>Treatment with standard of care pegylated interferon alpha and ribavirin.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pegylated interferon alpha</intervention_name>
    <description>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.</description>
    <arm_group_label>Interferon and ribavirin</arm_group_label>
    <other_name>pegasys</other_name>
    <other_name>pegatron</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ribavirin</intervention_name>
    <description>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.</description>
    <arm_group_label>Interferon and ribavirin</arm_group_label>
    <other_name>Copegus</other_name>
    <other_name>Rebetol</other_name>
    <other_name>Ribasphere</other_name>
    <other_name>Vilona</other_name>
    <other_name>Virazole</other_name>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Whole blood is collect for genomic DNA extraction. Serum samples will be stored for hepcidin&#xD;
      analysis.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Hepatitis C patients undergoing standard of care treatment with interferon alpha.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Any patient with hepatitis C eligible for treatment with pegylated interferon alpha&#xD;
             containing regimes.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  less than 18 years of age&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Marius M Van Rijnsoever, MBBS</last_name>
    <role>Principal Investigator</role>
    <affiliation>South Metropolitan Health Service, Perth Western Australia</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Fremantle Hospital</name>
      <address>
        <city>Fremantle</city>
        <state>Western Australia</state>
        <zip>6160</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <link>
    <url>http://www.anzctr.org.au/trial_view.aspx?id=347699</url>
    <description>australian new zealand clinical trials register</description>
  </link>
  <reference>
    <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.</citation>
    <PMID>21063814</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>20692693</PMID>
  </reference>
  <reference>
    <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. doi: 10.2174/092986706778773059.</citation>
    <PMID>17168855</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>17943492</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>18752323</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>20801192</PMID>
  </reference>
  <reference>
    <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. doi: 10.3748/wjg.14.1339.</citation>
    <PMID>18322945</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>20470305</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>16810960</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>21703177</PMID>
  </reference>
  <verification_date>November 2015</verification_date>
  <study_first_submitted>November 9, 2012</study_first_submitted>
  <study_first_submitted_qc>November 13, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 14, 2012</study_first_posted>
  <last_update_submitted>November 9, 2015</last_update_submitted>
  <last_update_submitted_qc>November 9, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 10, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Fremantle Hospital and Health Service</investigator_affiliation>
    <investigator_full_name>Dr Marius van Rijnsoever</investigator_full_name>
    <investigator_title>Medical Registrar</investigator_title>
  </responsible_party>
  <keyword>Hepatitis C</keyword>
  <keyword>Interferon</keyword>
  <keyword>Ribavirin</keyword>
  <keyword>Hepcidin</keyword>
  <keyword>Iron metabolism</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hepatitis A</mesh_term>
    <mesh_term>Hepatitis C</mesh_term>
    <mesh_term>Hepatitis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Interferons</mesh_term>
    <mesh_term>Ribavirin</mesh_term>
    <mesh_term>Interferon-alpha</mesh_term>
  </intervention_browse>
  <pending_results>
    <submitted>November 22, 2015</submitted>
    <returned>December 24, 2015</returned>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01726400
org study id: HEPCIDIN-11/225
nct id: NCT01726400
lead sponsor: 
has dmc: Yes
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.
observational model: Case-Only
time perspective: Prospective
measure: Hepcidin levels
time frame: Measured at -2 weeks, start of treatment and week 3,4,8, 12 and 24.
description: To measure changes in serum hepcidin levels during pegylated interferon alpha and ribavirin therapy in subjects with chronic hepatitis C infection.
measure: iron metabolism markers
time frame: Measured at -2 weeks, start of treatment and week 3,4,8, 12 and 24.
description: 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.
measure: heamolysis markers
time frame: Measured at -2 weeks, start of treatment and week 3,4,8, 12 and 24.
description: 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.
measure: inosine triphosphatase genetic variants
time frame: Baseline
description: 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.
measure: erythropoiesis markers
time frame: Measured at -2 weeks, start of treatment and week 3,4,8, 12 and 24.
description: 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.
arm group label: Interferon and ribavirin
description: Treatment with standard of care pegylated interferon alpha and ribavirin.
intervention type: Drug
intervention name: Pegylated interferon alpha
description: 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.
arm group label: Interferon and ribavirin
other name: pegasys
other name: pegatron
intervention type: Drug
intervention name: Ribavirin
description: 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.
arm group label: Interferon and ribavirin
other name: Copegus
other name: Rebetol
other name: Ribasphere
other name: Vilona
other name: Virazole
Whole blood is collect for genomic DNA extraction. Serum samples will be stored for hepcidin
      analysis.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Marius M Van Rijnsoever, MBBS
role: Principal Investigator
affiliation: South Metropolitan Health Service, Perth Western Australia
facility: 
country: Australia
url: http://www.anzctr.org.au/trial_view.aspx?id=347699
description: australian new zealand clinical trials register
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.
PMID: 21063814
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.
PMID: 20692693
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. doi: 10.2174/092986706778773059.
PMID: 17168855
citation: 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
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.
PMID: 18752323
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.
PMID: 20801192
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. doi: 10.3748/wjg.14.1339.
PMID: 18322945
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.
PMID: 20470305
citation: 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
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.
PMID: 21703177
responsible party type: Principal Investigator
investigator affiliation: Fremantle Hospital and Health Service
investigator full name: Dr Marius van Rijnsoever
investigator title: Medical Registrar
mesh term: Hepatitis A
mesh term: Hepatitis C
mesh term: Hepatitis
mesh term: Interferons
mesh term: Ribavirin
mesh term: Interferon-alpha
submitted: November 22, 2015
returned: December 24, 2015