HCC Screening Using DNA Methylation Changes in ctDNA

Hepatocellular Carcinoma Clinical Trial

Official title:

Clinical Trials on Detection of Hepatocellular Carcinoma With Non-invasive Method Based on DNA Methylation of Circulated Tumor DNA, PBMC and T Cells

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03483922
• Other study ID #: HKG-Bng-HCC-100
• Status: Completed
• Start date: August 20, 2018
• Est. completion date: November 1, 2020

Study information

• Verified date: December 2020
• Source: HKGepitherapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Hepatocellular Carcinoma (HCC) is the fifth most common cancer world-wide. It is particularly prevalent in Asia, and its occurrence is highest in areas where hepatitis B is prevalent, indicating a possible causal relationship. Follow up of high-risk populations such as chronic hepatitis patients and early diagnosis of transitions from chronic hepatitis to HCC would improve cure rates. In most cases HCC is detected late resulting in increased mortality and morbidity. The purpose of this study is to develop and test non-invasive biomarkers based on methylation changes in PBMC and circulated tumor DNA in hepatocellular carcinomas patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 403
• Est. completion date: November 1, 2020
• Est. primary completion date: June 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Confirmed diagnosis of HCC by EASL-EORTC guidelines
• Confirmed hepatitis B diagnosis for HepB patients using AASLD practice guidelines.

Exclusion Criteria for HCC:

• Cirrhosis, any other known inflammatory disease (bacterial or viral infection with the exception of hepatitis B or C, diabetes, asthma, autoimmune disease, active thyroid disease) which could alter T cells and monocytes characteristics
• Other cancers.

Exclusion Criteria for HepB:

• Diagnosis of HCC or any other cancer.

Exclusion Criteria for Healthy Controls:

• Any known inflammatory or infectious disease including HepB and HepC
• Chronic diseases,
• Cancer
• Medications or drug use

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Diagnostic Test:
• ctDNA methylation in and it's Correlation wth Development and prediction of HCC
Blood sample from patients with HCC, healthy individuals and individuals with hepatitis B will be collected, and DNA will extracted from PBMC and circulated tumor DNA will be subjected to bisulfite conversion. DNA from PBMC DNA will be analyzed with primers developed for the AHNAK-STAP1 genes. Plasma samples will be subjected to EZ direct DNA extraction and bisulfite conversion kit and will be amplified with primers developed to amplify the target regions. DNA will be used for the subsequent PCR amplification with specific primer to generate PCR amplicon for sequencing using a double PCR procedure. The product of PCR reaction will be subjected to indexed MiSeq Next-Generation sequencing that will allow us quantify DNA methylation level.

Locations

Country	Name	City	State
Bangladesh	Infectious Diseases Division	Dhaka

Sponsors (2)

Lead Sponsor	Collaborator
HKGepitherapeutics	International Centre for Diarrhoeal Disease Research, Bangladesh

Country where clinical trial is conducted

Bangladesh, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	DNA methylation of circulated tumor and PBMC DNA and its Correlation to Development and prediction of HCC	We will develop the linear model and a threshold value differentiating breast cancer from control based on the 100 patient training set. The model will be provided to the researchers: Methylation score=CG1*b1+CG2*b2+ CG3*b3 + e; CG1 is the methylation value of the first CG b1 is the regression coefficient for the first CG and e equals the intercept.; We will develop the regression coefficient and intercept as well as the DNA methylation values for each patient for each CG. We will first compute the polygenic methylation score for each patient. Then based on the computer threshold based on the training cohort will call the samples as liver cancer or not.	6 months to 1 year