Identification and Validation of Noninvasive Biomarkers of the Diagnosis and Severity of NASH in Type 2 Diabetics
- Conditions
- Type2 Diabetes
- Interventions
- Device: new quantitative imaging techniques with contast productsDiagnostic Test: blood sampleDiagnostic Test: second generation tests
- Registration Number
- NCT03634098
- Lead Sponsor
- Assistance Publique - Hôpitaux de Paris
- Brief Summary
Metabolic diseases of the liver are silent affections whose morbidity is important. About 70% of patients with type 2 diabetes (T2D) are concerned. Of these, 50% develop clinically significant lesions (including non-alcoholic steatohepatitis or NASH) as they are associated with an increased risk of complications; and 15% progress to severe fibrosis or cirrhosis. These diseases are slowly progressive and asymptomatic. Their pathophysiology is poorly known. Management is hampered by the absence of a specific diagnostic marker, the need for invasive diagnostic procedures (liver biopsy), and the lack of established treatment.
QUID-NASH aims to develop a virtual liver biopsy in T2D participants, based on the identification of single or combined, multimodal, non-invasive biomarkers obtained by new quantitative imaging techniques (magnetic resonance and ultrafast ultrasound UFUS); and /or extensive clinical-biological phenotyping data; and/or data obtained by different omic approaches (metabolomics, targeted genetics, transcriptomics). Extracellular vesicle and immune cell profiling will complement these phenotyping data. This approach will also enable us to improve our understanding of pathophysiology (new signaling pathways, new therapeutic targets).
- Detailed Description
Metabolic diseases of the liver are silent affections whose morbidity is important. About 70% of patients with type 2 diabetes (T2D) are concerned. Of these, 50% develop clinically significant lesions (including non-alcoholic steatohepatitis or NASH) as they are associated with an increased risk of complications; and 15% progress to severe fibrosis or cirrhosis. These diseases are slowly progressive and asymptomatic. Their pathophysiology is poorly known. Management is hampered by the absence of a specific diagnostic marker, the need for invasive diagnostic procedures (liver biopsy), and the lack of established treatment. Non-invasive methods ("first-generation" tests) have recently seen significant growth: commercialization of FibroTest as a marker of fibrosis; FibroTest, Fibrometer and FibroScan, for the initial assessment of adult chronic hepatitis C; FibroTest, Fibrometer, and Enhanced Liver Fibrosis test (ELF-test) for diagnosis of metabolic liver disease and diagnosis of fibrosis; SteatoTest (APHP patent) for the diagnosis of steatosis. The ActiTest (APHP patent) is widely used in evaluating the necrotic-inflammatory activity of chronic viral hepatitis C and B. For the diagnosis of NASH alone the ActiTest is validated. The NashTest (APHP patent) is little used. Several biomarkers of imaging (liver ultrasound, FibroScan Controller Attenuated Parameter (CAP), elastography and nuclear magnetic resonance) are widely used for the diagnosis of steatosis. Two new "second generation" blood tests (APHP patents) are under development, Non Invasive Test-NASHr (NIT-NASHr), and NIT-A2F2. NIT-NASHr is a new combination of the components of SteatoTest and NASH-Test to assess the severity of NASH. NIT-A2F2 is a combination of NIT-NASHr and FibroTest for the diagnosis of clinically significant liver metabolic disease. These tests will be the subject in the project of a validation of their performances in the context of use (T2D without other liver disease). At the same time, significant progress has been made in integrating omic data to characterize various pathologies and to identify their mechanisms. The transcriptomics and metabolomics of body fluids are particularly promising for the construction of "third generation" tests.
QUID-NASH aims to develop a virtual liver biopsy in T2D participants, based on the identification of single or combined, multimodal, non-invasive biomarkers obtained by new quantitative imaging techniques (magnetic resonance and ultrafast ultrasound UFUS); and / or extensive clinical-biological phenotyping data; and / or data obtained by different omic approaches (metabolomics, targeted genetics, transcriptomics). Extracellular vesicle and immune cell profiling will complement this data. This approach will also enable us to improve knowledge of the pathology (new signaling pathways, new therapeutic targets).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 970
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description T2D liver test abnormalities's participants new quantitative imaging techniques with contast products Exams performed on type 2 diabetic patients with liver test abnormalities : * sample for analysis and biocollection * MRI +/-Primovist * Ultrasound AixPlorer +Sonovue T2D liver test abnormalities's participants second generation tests Exams performed on type 2 diabetic patients with liver test abnormalities : * sample for analysis and biocollection * MRI +/-Primovist * Ultrasound AixPlorer +Sonovue Volunteers new quantitative imaging techniques with contast products Exams performed on volunteers with other purpose than liver disease or diabetes in two centers: * MRI * Ultrasound AixPlorer These examinations are carried out in 2 differents centers at 1month intervals T2D liver test abnormalities's participants blood sample Exams performed on type 2 diabetic patients with liver test abnormalities : * sample for analysis and biocollection * MRI +/-Primovist * Ultrasound AixPlorer +Sonovue
- Primary Outcome Measures
Name Time Method To study in type 2 diabetic participants with liver biopsy, the performance of a composite biomarker (3rd generation test) for the diagnosis of NASH 1 month Histological diagnosis of NASH (as established by centralized re-reading of liver biopsy slides), blinded to omic results and imaging.
- Secondary Outcome Measures
Name Time Method To study in type 2 diabetic participants with liver biopsy, the performance of a single or composite biomarker for the diagnosis of NASH elemental lesions 1 month histological diagnosis of elementary lesions of NASH (lobular inflammation, ballooning, steatosis)
To study inter-center and intra-participants reproducibility of imaging measurements. a graphical evaluation will be conducted using a representation of Bland-Altman. 1 month By MRI: steatosis, biomechanical properties, T1, diffusivity
Constitution of a bio-collection 1 month Liver tissue
To study in type 2 diabetic participants with or without liver biopsy, performance of a composite biomarker for the diagnosis of clinically significant metabolic liver diseases 1 month diagnosis of clinically significant liver metabolic disease (SAF-Score ≥A2 or ≥F2) adjudicated by an independent committee
To study inter-center and intra-participants reproducibility of imaging measurements.a graphical evaluation will be conducted using a representation of Bland-Altman. 1 month By AixPlorer ultrasound: steatosis, biomechanical properties, vascular properties
To study in type 2 diabetic participants the performance of second-generation tests for the diagnosis of metabolic liver diseases 1 day metabolic liver disease (adjudicated by an independent committee)
Trial Locations
- Locations (1)
Hôpital Beaujon
🇫🇷Clichy, France