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Pharmacogenomics Study on IL28B Genetic Variants in Italian Patients With HCV Infection naïve to Treatment.

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ClinicalTrials.gov Identifier: NCT01437969
Recruitment Status : Unknown
Verified April 2012 by Alessandra Mangia, Casa Sollievo della Sofferenza IRCCS.
Recruitment status was:  Recruiting
First Posted : September 21, 2011
Last Update Posted : April 17, 2012
Information provided by (Responsible Party):

September 20, 2011
September 21, 2011
April 17, 2012
September 2011
September 2012   (Final data collection date for primary outcome measure)
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Complete list of historical versions of study NCT01437969 on ClinicalTrials.gov Archive Site
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Pharmacogenomics Study on IL28B Genetic Variants in Italian Patients With HCV Infection naïve to Treatment.
Pharmacogenomics Study on IL28B Genetic Variants in Italian Patients With HCV Chronic Infection naïve to Antiviral Treatment.

More than 1.5 millions individuals are infected with HCV in Italy. They are at risk to develop related morbidity and mortality from cirrhosis and hepatocellular carcinoma, unless the evolution of their disease is halted by treatment-induced HCV RNA clearance. Indeed, it is well recognized that a curative antiviral treatment, leading to HCV RNA undetectability 24 weeks after the end of therapy, may prevent the occurrence of complications of HCV chronic liver disease.

Several pre-treatment host and viral factors have been associated with the outcome of pegylated Interferon and Ribavirin treatment. These predictors are relevant as the ability to identify patients with the highest likelihood of achieving HCV RNA clearance may increase the number of patients who agree to be treated and who maintain their adherence to treatment.

Several pre-treatment predictors as HCV genotype, HCV viral load, age, gender, body mass index, stage of fibrosis and race are very well recognized and have been used for many years during the treatment decision-making process. Based on studies of viral kinetics, HCV RNA undetectable at week 4 on treatment has been shown to represent the best on treatment predictor of response. In addition to these well known factors, very recently, a single nucleotide polymorphism (SNP) upstream of the gene IL28B on chromosome 19, coding for IFN-lambda 3 has been identified as associated with both spontaneous and treatment induced HCV RNA clearance.

We have developed the molecular technique needed to evaluate this polymorphism in our laboratory. This technical process was a consequence of the genetics expertise of our research Institute. We have also performed a valuable comparison of the different methods to evaluate this polymorphism. Comparison of different technologies allow us to know the rate of variability between the different assays used.

With this methodology we have evaluated "a posteriori" patients previously enrolled in Randomized Controlled Trial. The results of these studies confirmed the association between IL28B CC allele and a favorable outcome of HCV infection in our geographic area (Mangia et al Gastroenterology 2010; Mangia et al Hepatology 2010, AASLD presentation). We are now interested in prospective evaluation of patients referring to our center at the aim of understanding whether there are differences in the rates of IL28B frequencies in patients with different HCV genotypes.

In fact, we hypothesize that the frequency of IL28B might be different according with different HCV genotypes and that this difference may explain the different rates of response to antiviral treatment reported in patients with HCV infection.

Since we lead a collaborative group of hepatologists named AL-LIVER operating in Puglia, Lazio, Basilicata, Sicilia and Campania regions in Italy we would like to extend this evaluation to our collaborative group to explore in a large number of patients whether the prevalence of CC, CT and TT genotypes is inversely associated with HCV G1, 4, 3 and 2.

This study is a prevalence study involving naïve patients and without links with treatment. Five hundred patients with HCV infection consecutively observed during 2011 will be requested to sign an informed consent at the aim to be tested for genetics. The study will be evaluated and approved by the Central Ethic Committee. It will have a planned duration of 12 months and will involve 15 centers.

All the HCV infected patients previously untreated can be enrolled once they have signed the Informed consent for genetic testing.

Each patient enrolled at the single center will be evaluated for demographical, virological, biochemical, histological and genetic (IL28B) characteristics. In case of unavailable liver biopsy at least APRI score and Fibroscan evaluation should be used to assess the severity of the underlying liver disease. All the blood specimens will be stored and evaluated by a pre-developed TaqMan allelic discrimination assay (Applied Biosystem) or by direct sequencing for IL28B genetic variation. A serum sample will be also stored to evaluate HCV genotype and HCV RNA levels.

Data will be collected in a database that can be used in the future to select patients needing antiviral treatment.

The association between IL28B variants and the other predictors will be explored by means of descriptive statistical analyses. Number of patients, mean, standard deviation, median will be calculated for continuous variables. Absolute frequencies and per cent will be used to describe frequencies parameters

Observational Model: Cohort
Time Perspective: Prospective
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Retention:   Samples With DNA
DNA from blood sample
Probability Sample
HCV infected patients previously untreated
Liver Disease
Genetic: genotyping and/or sequencing
genotyping and/or sequencing DNA for IL28
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Unknown status
September 2012
September 2012   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients with chronic HCV infection irrespective of HCV genotype

Exclusion Criteria:

  • HCV infected patients previously treated with antiviral drugs; co-infected Patients with HIV or Hepatitis B virus (HBsAg positive)
Sexes Eligible for Study: All
18 Years to 70 Years   (Adult, Senior)
Contact information is only displayed when the study is recruiting subjects
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Alessandra Mangia, Casa Sollievo della Sofferenza IRCCS
Casa Sollievo della Sofferenza IRCCS
  • INMI L Spallanzani IRCCS Roma
  • Azienda Ospedaliera Universitaria di Bologna Policlinico S. Orsola Malpighi
  • Azienda Ospedaliera San Camillo Forlanini
  • IRCCS Policlinico S. Matteo
  • Azienda ospedaliera Garibaldi Nesinma Catania
  • Azienda Ospedaliero-Universitaria Careggi
  • University of Milan
  • Catholic University, Italy
  • Ospedale Francesco Ferrari
  • Ospedale di Canosa di Puglia
  • Ospedale di Venosa
  • Clinica Santa Rita Bari
  • Ospedale SS. Annunziata, Taranto
  • Ospedali Riuniti di Foggia
Principal Investigator: Alessandra Mangia, MD Liver Unit, Casa Sollievo della Sofferenza
Casa Sollievo della Sofferenza IRCCS
April 2012