Identification and Validation of Noninvasive Biomarkers of the Diagnosis and Severity of NASH in Type 2 Diabetics

NCT03634098 | Completed

• 2 other identifiers: P171105j2018-A00311-54
• Study Type: interventional
• Target: 970
• Locations: 1 country
• Sites: 1

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).

Conditions

Type2 Diabetes

Keywords

Patients

Outcome Measures

Primary Outcomes (1)

• To study in type 2 diabetic participants with liver biopsy, the performance of a composite biomarker (3rd generation test) for the diagnosis of NASH

  Histological diagnosis of NASH (as established by centralized re-reading of liver biopsy slides), blinded to omic results and imaging.

  1 month

Secondary Outcomes (11)

• 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

• 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

• 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

• 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

• To study in type 2 diabetic participants the performance of second-generation tests for the diagnosis of metabolic liver diseases

  1 day

Study Arms (3)

Volunteers

EXPERIMENTAL

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

Device: new quantitative imaging techniques with contast products

T2D liver test abnormalities's participants

EXPERIMENTAL

Exams performed on type 2 diabetic patients with liver test abnormalities : * sample for analysis and biocollection * MRI +/-Primovist * Ultrasound AixPlorer +Sonovue

Device: new quantitative imaging techniques with contast products; Diagnostic Test: blood sample; Diagnostic Test: second generation tests

T2D participants without liver test abnormality

NO INTERVENTION

type 2 diabetic participants without liver test abnormality and not undergoing liver biopsy

Interventions

new quantitative imaging techniques with contast products DEVICE

magnetic resonance +/- Primovist and ultrafast ultrasound UFUS +Sonovue

T2D liver test abnormalities's participants; Volunteers

blood sample DIAGNOSTIC_TEST

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

T2D liver test abnormalities's participants

second generation tests DIAGNOSTIC_TEST

second generation tests NIT-NASHr et NIT-A2F2

T2D liver test abnormalities's participants

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntary
• Person aged 18 or over
• Refusal or inability to sign consent
• Vulnerable person according to article L1121-6 of the CSP
• Protected person of age
• Participant aged 18 or over
• Diabetic type 2 (ADA / WHO criteria mentioned in section 20.5)
• Liver biopsy planned in day hospital (HDJ) as part of routine care (indication of biopsy: or ALT\> 30 IU for men or\> 20 IU for women less than 1 month old) and/or steatosis on ultrasound )
• Hemoglobin\> 7g / dL (or\> 10 g / dL in case of cardiovascular or respiratory pathology)
• Refusal or inability to sign consent
• Vulnerable person: person deprived of liberty by a judicial or administrative decision, or subject to psychiatric care, and person admitted to a health or social institution for purposes other than that of research
• Protected person of age
• No affiliation or non-beneficiary of a social security scheme
• Pregnant or lactating woman
• Contraindication to MRI according to the French Society of Radiology (mentioned in section 20.4)

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Hôpital Beaujon

Clichy, France

Location

Related Publications (3)

• Castera L, Garteiser P, Laouenan C, Vidal-Trecan T, Vallet-Pichard A, Manchon P, Paradis V, Czernichow S, Roulot D, Larger E, Pol S, Bedossa P, Correas JM, Valla D, Gautier JF, Van Beers BE; QUID NASH investigators. Prospective head-to-head comparison of non-invasive scores for diagnosis of fibrotic MASH in patients with type 2 diabetes. J Hepatol. 2024 Aug;81(2):195-206. doi: 10.1016/j.jhep.2024.03.023. Epub 2024 Mar 27.

  PMID: 38548067 DERIVED

• Poynard T, Deckmyn O, Peta V, Paradis V, Gautier JF, Brzustowski A, Bedossa P, Castera L, Pol S, Valla D; Quid-Nash Consortium. Prospective direct comparison of non-invasive liver tests in outpatients with type 2 diabetes using intention-to-diagnose analysis. Aliment Pharmacol Ther. 2023 Nov;58(9):888-902. doi: 10.1111/apt.17688. Epub 2023 Aug 29.

  PMID: 37642160 DERIVED

• Poynard T, Paradis V, Mullaert J, Deckmyn O, Gault N, Marcault E, Manchon P, Si Mohammed N, Parfait B, Ibberson M, Gautier JF, Boitard C, Czernichow S, Larger E, Drane F, Castille JM, Peta V, Brzustowski A, Terris B, Vallet-Pichard A, Roulot D, Laouenan C, Bedossa P, Castera L, Pol S, Valla D; Quid-Nash consortium. Prospective external validation of a new non-invasive test for the diagnosis of non-alcoholic steatohepatitis in patients with type 2 diabetes. Aliment Pharmacol Ther. 2021 Oct;54(7):952-966. doi: 10.1111/apt.16543. Epub 2021 Aug 16.

  PMID: 34398492 DERIVED

MeSH Terms

Interventions

Blood Specimen Collection

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Laurent Castera

  APHP

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2018
• First Posted: August 16, 2018
• Study Start: October 25, 2018
• Primary Completion: July 31, 2022
• Study Completion: September 30, 2022
• Last Updated: December 8, 2022

Record last verified: 2022-03

Locations

FR (1)