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Impact of IL-28B rs12979860 and rs4803217 Gene Polymorphisms Associated With miRNAs Deregulation on HCV-related Hepatocellular Carcinoma

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ClinicalTrials.gov Identifier: NCT02507882
Recruitment Status : Unknown
Verified July 2015 by Dr.Waleed Samir, Egyptian Liver Hospital.
Recruitment status was:  Not yet recruiting
First Posted : July 24, 2015
Last Update Posted : July 24, 2015
Sponsor:
Information provided by (Responsible Party):
Dr.Waleed Samir, Egyptian Liver Hospital

Brief Summary:

Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide as well as in Egypt. Despite improvements in HCC therapy, the prognosis for HCC patients remains poor. Today molecular, genomic and epigenomic aberrations in tumors are being deeply investigated. Many biomarkers were associated to HCC onset, and they could be useful for clinicians, but all show some limitations and no one is so early to predict the HCC onset.

It is estimated that 51.5% of HCC cases can be attributed to HCV infection. Moreover, there is a large occult reservoir of HCV caused chronic liver disease in approximately 9 % in the Egyptian with estimated 6 million HCV chronic infections and estimated 150 000 new infections per year. Among them, we have to mention the polymorphism of IL28B gene rs12979860 C/T. and rs 4803217. The IL-28B gene encodes interferon-lambda 3 (IFN-λ3), which belongs to the type III IFN family. IFN-λ interacts with a transmembrane receptor inducing a potent antiviral response. In experimental model of HCV type III IFN was able to inhibit viral replication. IL-28B polymorphisms are linked to the efficiency of the inflammatory process during HCV infection, and to the mechanisms that HCV adopts to escape by innate and adaptive immunity.

During the last years, a number of studies have assessed the association between the IL-28B polymorphisms and risk of HCC and liver cirrhosis (LC) occurrence in various populations; however, results obtained are still inconclusive.

Interestingly, some polymorphisms located at the 3' untranslated region (UTR) of IL28B, e.g. rs 4803217, seem to interfere with the binding of miRNA, to date recognized as important post-transcriptional regulators. In the last years miRNAs acquired a growing relevance as potential biomarkers for several diseases including cancer, and many researches are focusing on understanding their role in cancer.

Thus the objectives of the current proposal are to determine through investigating a cohort of 405 patients, whether IL28B rs12979860 and rs4803217 polymorphisms are associated to the risk of HCC in chronic hepatitis C (CHC) patients and, above all, to identify their role as predictor marker of HCC in CHC, when associated to miRNAs modulation. Data obtained by our work could be helpful in HCC diagnosis, thus leading to the improvement of the patients prognosis. The proposed activities are going to be implemented through a partnership us as Egyptian Liver Research Institute and Hospital (ELRIAH)- Dakhlya- Egypt and Non- Egyptian Partners.


Condition or disease Intervention/treatment Phase
HCV Infection ( Genotype 4) Biological: IL28B Polymorphism Biological: miRNA quantification Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 405 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Impact of IL-28B rs12979860 and rs4803217 Gene Polymorphisms Associated With miRNAs Deregulation on HCV-related Hepatocellular Carcinoma
Study Start Date : January 2016
Estimated Primary Completion Date : December 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: HCC
This group will include patients with chronic hepatitis C (no. =135)
Biological: IL28B Polymorphism
SNP rs12979860 and 4803217 will be determined in whole blood by allelic discrimination using specific probes by real time PCR.

Biological: miRNA quantification

RNAs will be extracted from serum using miRNeasy Mini Kit (Quiagen) according to the manufacturer's instruction.

The RNA purity will be assessed by the RNA concentration and quantified by NanoDrop ND-1000 (Nanodrop, United States).

cDNA will be obtained by miScript II Reverse Transcription Kits (Quiagen) A Preamplification will be performed using miScript PreAMP PCR Kits (Quiagen) Real Time PCRarray will be done using miScript miRNA PCR Arrays, with SYBR Green PCR Master Mix (Quiagen).


Experimental: HCC with Cirrhosis
This group will include patients with chronic hepatitis C (no. =135) with cirrhosis (F4).
Biological: IL28B Polymorphism
SNP rs12979860 and 4803217 will be determined in whole blood by allelic discrimination using specific probes by real time PCR.

Biological: miRNA quantification

RNAs will be extracted from serum using miRNeasy Mini Kit (Quiagen) according to the manufacturer's instruction.

The RNA purity will be assessed by the RNA concentration and quantified by NanoDrop ND-1000 (Nanodrop, United States).

cDNA will be obtained by miScript II Reverse Transcription Kits (Quiagen) A Preamplification will be performed using miScript PreAMP PCR Kits (Quiagen) Real Time PCRarray will be done using miScript miRNA PCR Arrays, with SYBR Green PCR Master Mix (Quiagen).


Experimental: HCV related HCC patients
This group will include patients with HCV related HCC (no. =135) This is confirmed by presence of focal lesion detected by Imaging (computed tomography (CT) and ultrasound), and elevated serum AFP.
Biological: IL28B Polymorphism
SNP rs12979860 and 4803217 will be determined in whole blood by allelic discrimination using specific probes by real time PCR.

Biological: miRNA quantification

RNAs will be extracted from serum using miRNeasy Mini Kit (Quiagen) according to the manufacturer's instruction.

The RNA purity will be assessed by the RNA concentration and quantified by NanoDrop ND-1000 (Nanodrop, United States).

cDNA will be obtained by miScript II Reverse Transcription Kits (Quiagen) A Preamplification will be performed using miScript PreAMP PCR Kits (Quiagen) Real Time PCRarray will be done using miScript miRNA PCR Arrays, with SYBR Green PCR Master Mix (Quiagen).





Primary Outcome Measures :
  1. IL-28B rs12979860 and rs4803217 Genotype evaluation [ Time Frame: 6 months to 1 year from the start of the study ]
    Different types of IL28B and their relation to the progressiveness of HCC

  2. Specific miRNA levels and their association with degree of fibrosis, cirrhosis and HCC [ Time Frame: 1 to 2 years from the start of the study ]


Information from the National Library of Medicine

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Ages Eligible for Study:   10 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HCV-infected patients confirmed by RT-PCR with and without fibrosis, cirrhosis and HCC

Exclusion Criteria:

  • HCV/HIV co-infection

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02507882


Contacts
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Contact: Waleed Samir Abdelrazek, PhD +20507942901 ext 901 waleed_samir1@yahoo.com

Locations
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Egypt
Egyptian Liver Hospital
Sherbein, Dakhlya, Egypt, 35516
Sponsors and Collaborators
Dr.Waleed Samir
Publications of Results:
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Responsible Party: Dr.Waleed Samir, Director of Clinical and Research Laboratory& Head of Molecular Biology Unit, Egyptian Liver Hospital, Egyptian Liver Hospital
ClinicalTrials.gov Identifier: NCT02507882    
Other Study ID Numbers: ELH - 2015 - IL28
First Posted: July 24, 2015    Key Record Dates
Last Update Posted: July 24, 2015
Last Verified: July 2015
Additional relevant MeSH terms:
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Hepatitis C
Carcinoma, Hepatocellular
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Hepatitis, Viral, Human
Virus Diseases
Flaviviridae Infections
RNA Virus Infections
Hepatitis