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)
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 2,002
- 试验地点
- 24
- 主要终点
- Changes in the profile of circulating micro-RNA biomarkers as high-risk patients develop HCC
研究概览
简要总结
Hepatocellular carcinoma (HCC) is the 7th 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.
详细描述
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). There will be an option for patients to continue to receive standard-of-care surveillance for HCC until end of study or up to 6 additional assessments (Visits 8-13), whichever occurs first.
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 40 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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:
- •liver cirrhosis of any etiology, identified by elastography (liver stiffness > 13 kPa), US, CT, MRI or liver biopsy, Child-Pugh class A and B
- •non-cirrhotic chronic viral hepatitis (B or C) or both
- •non-alcoholic fatty liver disease (NAFLD)
- •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
排除标准
- •Patient with confirmed diagnosis of HCC by the American Association for the Study of the Liver Disease (AASLD) 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
结局指标
主要结局
Changes in the profile of circulating micro-RNA biomarkers as high-risk patients develop HCC
时间窗: Baseline and every 6 months thereafter, and at HCC diagnosis every 6 months thereafter up to 70 months.
Changes in the profile of circulating micro-RNA biomarkers as high-risk patients develop HCC
value of cT1, PDFF and T2* levels to predict individual's risk of developing and progression of HCC.
时间窗: Baseline and upon elevated AFP or US which is suggestive of HCC, up to 70 months.
value of cT1, PDFF and T2\* levels to predict individual's risk of developing and progression of HCC.
Changes in the profile of gut microbiota as high-risk patients develop HCC.
时间窗: Baseline and every 6 months thereafter, up to 70 months
Changes in the profile of gut microbiota as high-risk patients develop HCC.
Changes in the profile of metabolome in urine and plasma as high-risk patients develop HCC.
时间窗: Baseline and every 6 months thereafter, up to 70 months.
Changes in the profile of metabolome in urine and plasma as high-risk patients develop HCC.
次要结局
未报告次要终点