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HCC Screening Using DNA Methylation Changes in ctDNA

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ClinicalTrials.gov Identifier: NCT03483922
Recruitment Status : Recruiting
First Posted : March 30, 2018
Last Update Posted : May 4, 2020
Sponsor:
Collaborator:
International Centre for Diarrhoeal Disease Research, Bangladesh
Information provided by (Responsible Party):
HKGepitherapeutics

Tracking Information
First Submitted Date March 20, 2018
First Posted Date March 30, 2018
Last Update Posted Date May 4, 2020
Actual Study Start Date August 20, 2018
Estimated Primary Completion Date June 1, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: March 28, 2018)
DNA methylation of circulated tumor and PBMC DNA and its Correlation to Development and prediction of HCC [ Time Frame: 6 months to 1 year ]
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.
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures Not Provided
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title HCC Screening Using DNA Methylation Changes in ctDNA
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
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, T-cells and circulated tumor DNA in hepatocellular carcinomas patients.

Detailed Description Not Provided
Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
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).
Condition 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.
Study Groups/Cohorts
  • chronic hepatitis B
    This group will include 50 with hepatitis B subjects and the diagnoses will be based on AASLD practice guideline.
    Intervention: 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

    Intervention: 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.
    Intervention: Diagnostic Test: ctDNA methylation in and it's Correlation wth Development and prediction of HCC
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: March 28, 2018)
400
Original Estimated Enrollment Same as current
Estimated Study Completion Date September 1, 2020
Estimated Primary Completion Date June 1, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria

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
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts
Listed Location Countries Bangladesh
Removed Location Countries  
 
Administrative Information
NCT Number NCT03483922
Other Study ID Numbers HKG-Bng-HCC-100
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: Undecided
Responsible Party HKGepitherapeutics
Study Sponsor HKGepitherapeutics
Collaborators International Centre for Diarrhoeal Disease Research, Bangladesh
Investigators Not Provided
PRS Account HKGepitherapeutics
Verification Date May 2020