Serum miR-122 as a Real-time Detection Biomarker of Drug-induced Liver Injury by Chemotherapy

Study Overview
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Brief Summary
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This is an open , multicenter, interventional clinical trial to conform the role of of miR-122 a real-time detection biomarker of drug-induced liver injury by chemotherapy.

Detailed Description
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The endorsed standard serum biomarkers, like ALT, AST, total bilirubin, are not tissue-specific, and cannot detect drug-induced liver injury (DILI) at a very early stage, thus unable to properly guide risk assessment and patient management. miR-122 is a liver-enriched miRNA. Many studies have demonstrated that miR-122 is a sensitive and specific biomarker when DILI occurred. However, there is a lack of a standard quantification method for miR-122 and confirmatory studies using a comprehensive list of drugs and patients. The investigators have developed the miRNA-derived Fragment Length Polymorphism (miRFLP) assay for the simultaneous quantification of multiple miRNAs.The methodology improves detection reliability by eliminating intra-assay variables. In this study, the investigators will investigate the role of miR-122 as a real-time detection biomarker of drug-induced liver injury utilizing the miRFLP assay. In addition, the investigators will try to identify the normal physiological range of miR-122 in healthy population and the relationship of miR-122 and hepatic failure in patients of intensive care unit.

Official Title
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Serum miR-122 as a Real-time Detection Biomarker of Drug-induced Liver Injury by Chemotherapy. - an Open , Multicenter, Non-interventional Clinical Trial

Conditions
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Malignant Tumor, Chemotherapeutic Toxicity, Liver Injury

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For all the participants: Normal liver function biomarkers including ALT,AST,ALP,TBIL before recruitment. Patients with liver disease:hepatitis B，hepatitis C，cirrhosis, hepatic failure and so on. For patients in chemotherapy group: Life expectancy at least 12 weeks 40 patients received epirubicin-containing chemotherapY 40 patients received paclitaxel-containing chemotherapy Patients received carboplatin-containing chemotherapy. Patients with congestive heart failure Unstable angina pectoris Previous history of myocardial infarction within 6 month prior to study entry Uncontrolled hypertension as determined by the Investigator or high risk uncontrolled, arrhythmia. Exclusion Criteria: Patients previously received chemotherapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Chemotherapy group<br>A total of 120 malignant tumor patients who need to receive chemotherapy are involved for miR-122 detection. They are from 3 centers, 40 for each center. For the first cycle of chemotherapy, the investigators will collect 0.5-1ml blood from the remained blood sample after routine blood test during chemotherapy for each patient.Each patient will have a routine blood test before(±3 days) each cycle of chemotherapy and 7(±3)days after chemotherapy. A routine blood test will include the test of ALT,AST,ALP and TBIL. Sample collection will stop after 4 cycles of chemotherapy. All blood samples collected by investigators are the remained sample after routine tests. Patients in routine care will also have blood tests before each cycle and on day 7(+/- 3) of each cycle of chemotherapy. These patients will also have blood test at these time points even if they are not in this trial. | |
| Healthy population<br>Twenty healthy women or men who come to hospitals for annual physical examinations are enrolled in this study for miR-122 detection. Investigators will collect 0.5-1 ml blood from the remained blood samples after routine blood tests during their annual physical examinations. | |
| Patients of intensive care unit<br>Fourty patients are enrolled in this group for miR-122 detection. The investigators will collect 0.5-1ml blood from the remained blood samples of their routine blood tests or when they need blood tests. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relationship of serum miR-122 level and DILI or hepatic failure | Serum miR-122 level (copies/uL) and liver function (such as ALT, AST, ALP, and bilirubin levels) will be tested before and after each cycle of chemotherapy, and the relationship of serum miR-122 level fluctuation and liver injury will be investigated. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Normal physiological range of miR-122 in healthy population | To determine a primary normal physiological range of serum miR-122 level (copies/uL) in a group of 20 healthy women and/or men. | 1 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Serum miR-122, drug-induced liver injury by chemotherapy, malignant tumor patients