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Early Detection of Hepatocellular Carcinoma in a High-risk Prospective Cohort (ELEGANCE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04965259
Recruitment Status : Recruiting
First Posted : July 16, 2021
Last Update Posted : August 18, 2022
Sponsor:
Collaborators:
Duke-NUS Graduate Medical School
Singapore Phenome Centre
Nanyang Technological University
MiRXES Pte Ltd
Perspectum Asia Pte Ltd
Asian Microbiome Library Pte Ltd
Information provided by (Responsible Party):
National Cancer Centre, Singapore

Brief Summary:

Hepatocellular carcinoma (HCC) is the 4th most common cause of cancer death globally but only 20% are diagnosed in its early stages where cure is possible. Current standard-of-care surveillance of patients at high risk of developing HCC with 6-monthly serum alpha-fetoprotein (AFP) and ultrasound imaging (US) has a sensitivity of approximately 63% for detecting early HCC. There is an urgent need for a more efficacious and convenient modality of surveillance of high-risk patients to diagnose HCC at an early stage.

This prospective study aims to address this unmet clinical need by validating a panel of circulating miRNA biomarkers to develop an in-vitro diagnostic (IVD) kit for the detection of early HCC in a cohort of high-risk patients.

Additionally, this study also aims to develop a multi-parametric MRI-based AI algorithm to quantify individual risks of developing HCC and to predict the progression of chronic liver disease in this cohort to enable targeted surveillance. Lastly, by identifying changes in the microbiome and metabolites as HCC develops in this cohort enables the establishment of actionable biomarkers that can prevent and predict the development of HCC.


Condition or disease
Liver Diseases

Detailed Description:
Eligible patients will receive 6-monthly standard-of-care surveillance (US, serum AFP and liver function test) for HCC until end of study or up to a maximum of 7 assessments (1 baseline and 6 follow-up assessments). Patients with elevated AFP or abnormalities detected on US will be investigated with multi-phasic CT scan or MRI to confirm or refute the diagnosis of HCC. Additionally, patients shall be scheduled for sequential bio-samples collection (blood, urine and stool) and blood tests (Hba1c and Lipid Panel) during the course of the study.

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Study Type : Observational
Estimated Enrollment : 2000 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Early Detection of Hepatocellular Carcinoma (HCC): miRNA, Microbiome and Imaging Biomarkers in the Evolution of Chronic Liver Disease in a High-risk Prospective Cohort (ELEGANCE)
Actual Study Start Date : April 15, 2021
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : February 21, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Liver Diseases




Primary Outcome Measures :
  1. Changes in the profile of circulating micro-RNA biomarkers as high-risk patients develop HCC [ Time Frame: Baseline and every 6 months thereafter, and at HCC diagnosis every 6 months thereafter up to 48 months. ]
    Changes in the profile of circulating micro-RNA biomarkers as high-risk patients develop HCC

  2. value of cT1, PDFF and T2* levels to predict individual's risk of developing and progression of HCC. [ Time Frame: Baseline and upon elevated AFP or US which is suggestive of HCC, up to 48 months. ]
    value of cT1, PDFF and T2* levels to predict individual's risk of developing and progression of HCC.

  3. Changes in the profile of gut microbiota as high-risk patients develop HCC. [ Time Frame: Baseline and every 6 months thereafter, up to 48 months ]
    Changes in the profile of gut microbiota as high-risk patients develop HCC.

  4. Changes in the profile of metabolome in urine and plasma as high-risk patients develop HCC. [ Time Frame: Baseline and every 6 months thereafter, up to 48 months. ]
    Changes in the profile of metabolome in urine and plasma as high-risk patients develop HCC.


Biospecimen Retention:   Samples With DNA
Bloods shall be used for relevant laboratory assessments. Blood, urine and stool samples shall be used for miRNA, microbiome and metabolome profiling.


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   40 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients at high-risk of developing HCC forming a cohort of 800 patients with cirrhosis from any etiology, 970 chronic hepatitis B without significant cirrhosis, 30 chronic hepatitis C without significant cirrhosis and 200 NAFLD/NASH without significant cirrhosis.
Criteria

Inclusion Criteria:

  • Male and female patients, 50 to 90 years of age at the time of signing the informed consent form, except for patients recruited under the cirrhotic group, patients of 40 to 90 years of age can be included.
  • Patient has serum alpha-fetoprotein (AFP) within normal range of the investigating laboratory in the past 3 months. For patients with AFP level out of the normal range of the investigating laboratory and up to 15.0ug/L, patient will be eligible if patient has a CT/MRI scan that exclude HCC in the past 3 months.
  • Patient has ultrasound hepatobiliary system (US HBS) that does not show lesion suspicious for HCC or, CT / MRI scan that exclude HCC, in the past 3 months
  • Patient is estimated to survive more than 3 years
  • Patient with any of the following chronic liver disease:

    1. liver cirrhosis of any etiology, identified by elastography (liver stiffness > 13 kPa), US, CT, MRI or liver biopsy, Child-Pugh class A and B
    2. non-cirrhotic chronic viral hepatitis (B or C) or both
    3. non-alcoholic fatty liver disease (NAFLD)
    4. non-alcoholic steatohepatitis (NASH)
  • Patient is able to comply with scheduled visits, assessments and other study procedures
  • Patient is willing to provide informed consent before enrolment in the study

Exclusion Criteria:

  • Patient with confirmed diagnosis of HCC by the American Association for the Study of the Liver Disease (AASLDC) imaging criteria or histology / cytology within the last 5 years
  • Patient with Child-Pugh C cirrhosis at time of enrolment (based on the judgement of the Investigator)
  • Patient with active hepatic encephalopathy at time of enrolment
  • Patient is known to be positive for the Human Immunodeficiency Virus (HIV)
  • Patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent, or to comply with the study procedures
  • Patient is unable to provide informed consent or refuse blood taking
  • Patient has any other condition which, in the opinion of the Investigators, would make the patient unsuitable for enrolment or could interfere with completion of the study

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): NCT04965259


Contacts
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Contact: Pierce Chow, MD, PhD +65 6436 8000 pierce.chow.k.h@singhealth.com.sg

Locations
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Singapore
National University Hospital Recruiting
Singapore, Singapore, 119228
Contact: Guan Huei LEE, MD, PhD         
SingHealth Polyclinics - Bukit Merah Recruiting
Singapore, Singapore, 150163
Contact: Sabrina WEE, MD         
SingHealth Polyclinics - Outram Recruiting
Singapore, Singapore, 168937
Contact: Kok Kiong ONG, MD         
Singapore General Hospital Recruiting
Singapore, Singapore, 169608
Contact: Jason Pik Eu CHANG, MD         
National Cancer Center Singapore Recruiting
Singapore, Singapore, 169690
Contact: Pierce CHOW, MD, PhD         
Contact: Han Chong TOH, MD         
Tan Tock Seng Hospital Recruiting
Singapore, Singapore, 308433
Contact: Wei Lyn YANG, MD         
SingHealth Polyclinics - Marine Parade Recruiting
Singapore, Singapore, 440080
Contact: Kee Tung TAN, MD         
SingHealth Polyclinics - Bedok Recruiting
Singapore, Singapore, 469662
Contact: Oi Fong CHONG, MD         
SingHealth Polyclinics - Pasir Ris Recruiting
Singapore, Singapore, 519457
Contact: Ngiap Chuan TAN, MD         
SingHealth Polyclinics - Tampines Recruiting
Singapore, Singapore, 529203
Contact: SULAIHA Binte Ithnin, MD         
Changi General Hospital Recruiting
Singapore, Singapore, 529889
Contact: Eugene Yu Jun WONG, MD         
Sengkang General Hospital Recruiting
Singapore, Singapore, 544886
Contact: Marianne Anastasia DE ROZA, MD         
SingHealth Polyclinics - Sengkang Recruiting
Singapore, Singapore, 545025
Contact: Jeremy Wei Song CHOO, MD         
SingHealth Polyclinics - Punggol Recruiting
Singapore, Singapore, 820681
Contact: Xin Yi YEAP, MD         
Sponsors and Collaborators
National Cancer Centre, Singapore
Duke-NUS Graduate Medical School
Singapore Phenome Centre
Nanyang Technological University
MiRXES Pte Ltd
Perspectum Asia Pte Ltd
Asian Microbiome Library Pte Ltd
Investigators
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Principal Investigator: Pierce Chow, MD, PhD National Cancer Centre, Singapore
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Responsible Party: National Cancer Centre, Singapore
ClinicalTrials.gov Identifier: NCT04965259    
Other Study ID Numbers: AHCC10 ELEGANCE
First Posted: July 16, 2021    Key Record Dates
Last Update Posted: August 18, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Cancer Centre, Singapore:
Hepatocellular Carcinoma(HCC)
Surveillance
Patients-at-risk
miRNA
Precision medicine
Gut microbiota
Metabolites
Microbiome biomarkers
Circulating biomarkers
MRI
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Hepatocellular
Liver Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases