HCC Screening Using DNA Methylation Changes in ctDNA

NCT03483922 | Completed Results DMC

• 1 other identifier: HKG-Bng-HCC-100
• Study Type: observational
• Target: 403
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Calculation of M Scores and HCC Probability Scores

  We normalized median methylation values (range 0-100) for 'HCC-detect' (Hepatocellular Carcinoma Detection) and 'HCC-spec' (Hepatocellular Carcinoma Specificity). 'HCC-detect' is derived from CHFR, VASH2, CCNJ, and GRID2IP regions, aiming to broadly identify HCC. Theoretical range is -6.6438 to 8.6438, with observed -3.541 to 7.65; higher scores indicate increased HCC likelihood. 'HCC-spec', focusing on the F12 region, differentiates HCC from 31 other cancers and normal cells, with theoretical range -3.3219 to 6.64385 (observed -3.3219 to 6.6297). Higher scores signify greater HCC specificity. Both scores, modeled via logistic regression in Prism, predict HCC probability, linking higher scores with higher HCC likelihood or specificity

  6 months to 1 year

Study Arms (3)

chronic hepatitis B

This group will include 50 with hepatitis B subjects and the diagnoses will be based on AASLD practice guideline.

Diagnostic Test: ctDNA methylation in and it's Correlation wth Development and prediction of HCC

HCC Cases

This group will include 350 in stage 0, stage A, stage B, Stage C+D of hepatocellular carcinoma. HCC staging will be diagnosed according to EASL-EORTC Clinical Practice Guidelines: Management of hepatocellular carcinoma

Diagnostic Test: ctDNA methylation in and it's Correlation wth Development and prediction of HCC

Healthy

This group will include 50 healthy sex and age matched controls.

Diagnostic Test: ctDNA methylation in and it's Correlation wth Development and prediction of HCC

Interventions

ctDNA methylation in and it's Correlation wth Development and prediction of HCC DIAGNOSTIC_TEST

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.

HCC Cases; Healthy; chronic hepatitis B

Eligibility Criteria

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

Study Population

HCC staging will be diagnosed according to EASL-EORTC Clinical Practice Guidelines: Management of hepatocellular carcinoma. The patients will be divided into four groups, including Stage 0 (1) (n=100), stage A (2) (n=100), stage B (3) (n=100) and stage C+D (4) (n=100). As controls we will recruit chronic hepatitis B (n=100), which diagnose will be confirmed using AASLD practice guideline for chronic Hepatitis B, and healthy sex and age matched controls (n=100).

You may qualify if:

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

You may not qualify if:

• 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.
• Diagnosis of HCC or any other cancer.
• Any known inflammatory or infectious disease including HepB and HepC
• Chronic diseases,
• Cancer
• Medications or drug use

Sponsors & Collaborators

• HKGepitherapeutics: lead
• International Centre for Diarrhoeal Disease Research, Bangladesh: collaborator

Study Sites (1)

Infectious Diseases Division

Dhaka, Bangladesh

Location

Biospecimen

Retention: SAMPLES WITH DNA

Peripheral blood monocyte (PBMC) DNA and plasma free circulating DNA

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Limitations and Caveats

Inherent challenges of our study included a regional focus and a reliance on observational data, which may limit broader applicability and prevent establishing causal relationships. Technical aspects, like the exclusion of participants due to insufficient sequencing depth (less than 100 reads per gene for five out of 402 participants), reflect constraints in data robustness. These elements represent areas for potential enhancement in future research

Results Point of Contact

• Title: David Cheishvili
• Organization: HKG Epitherapeutics

david.cheishvili@hkgepitherapeutics.com

5142601972

Study Officials

• Wasif Ali Khan, PhD

  nternational Centre for Diarrhoeal Disease Research

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2018
• First Posted: March 30, 2018
• Study Start: August 20, 2018
• Primary Completion: June 1, 2020
• Study Completion: November 1, 2020
• Last Updated: July 5, 2024
• Results First Posted: July 5, 2024

Record last verified: 2024-07

Locations

BA (1)