Type 2 DIAbeTes With NAFLD: innOvative Biomarkers of Disease progressioN and clInical outComes

Not Applicable

Not yet recruiting

• Conditions: Metabolic Dysfunction-Associated Liver Disease
• Interventions: Diagnostic Test: Non-invasive test for the screening of MASLD-related advanced fibrosis in patients with T2D.

• Registration Number: NCT06567990
• Lead Sponsor: Hospices Civils de Lyon

Brief Summary

Type 2 diabetes (T2DM) patients are at high-risk for advanced fibrosis (AF) due to non-alcoholic fatty liver disease (NAFLD), recently renamed Metabolic dysfunction-Associated Liver Disease (MASLD). Thus, patients with T2DM are recognized as a priority target for the screening of MASLD-related advanced fibrosis and a systematic screening for AF is currently recommended in T2DM patients using FIB-4 and liver stiffness measurement (LSM).The main objective of the project is to investigate the ability of baseline non-invasive biomarkers to discriminate patients with a progression of MASLD from patients without progression of MASLD among patients with T2DM and to investigate the association between clinical outcomes related to the natural evolution of MASLD and T2DM and baseline biomarkers.

Detailed Description

Type 2 diabetes (T2DM) patients are at high-risk for advanced fibrosis (AF) due to non-alcoholic fatty liver disease (NAFLD), recently renamed Metabolic dysfunction-Associated Liver Disease (MASLD). Thus, patients with T2DM are recognized as a priority target for the screening of MASLD-related advanced fibrosis and a systematic screening for AF is currently recommended in T2DM patients using FIB-4 and liver stiffness measurement (LSM). Hence, these Non-Invasive Tests (NITs) are expected to be integrated in the management of T2DM in a near future. Indeed diabetologists are becoming more aware of the need for liver assessment in patients with T2DM recently reinforced by recent clear recommendations supporting the use of non-invasive test (NITs) such as LSM for the detection of liver fibrosis. Several studies indicate that MASLD increases the risk of T2DM complications. However, there are very limited data and no prospective longitudinal data assessing the progression of MASLD and relevant clinical outcomes in T2DM patients included in liver screening using these NITs. This provides a unique opportunity to better stratify T2DM and to understand the heterogeneity among patients with T2DM by defining patient's profiles linked the progression of MASLD and relevant clinical outcomes.

Therefore, the main objective of the project is to investigate the ability of baseline non-invasive biomarkers to discriminate patients with a progression of MASLD from patients without progression of MASLD among patients with T2DM and to investigate the association between clinical outcomes related to the natural evolution of MASLD and T2DM and baseline biomarkers.

Study Timeline

• Status Verified: 2024-08
• Study First Submitted: 2024-08-20
• Study First Submitted QC: 2024-08-20
• Last Update Submitted: 2024-08-20
• Study First Posted: 2024-08-23
• Last Update Posted: 2024-08-23
• Study Start: 2024-09-15
• Primary Completion: 2026-11-15
• Study Completion: 2026-11-15

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 500

Inclusion Criteria

• Patients with T2D and meeting the other inclusion criteria of the NAFLD-Care study:
• Patient aged between 40 and 80 years old,
• Patient with hepatic steatosis determined by conventional abdominal ultrasound as defined by the EASL/EASO/EASD European guidelines.
• Patient who agrees to be included in the study and who signs the informed consent form,
• Patient affiliated to a healthcare insurance plan.

Exclusion Criteria

• Participants with a diagnosis of cirrhosis defined by a liver biopsy with histological stage of fibrosis F4 or a proven diagnosis of cirrhosis by magnetic resonance imaging.

The main non-inclusion criteria for the NAFLD-CARE study are:

• Evidence of other causes of chronic liver disease :

  1. Hepatitis B as defined as presence of hepatitis B surface antigen (HBsAg).
  2. Previous or current infection with Hepatitis C as defined by presence of hepatitis C virus Ab in serum (anti-HCV Ab).
  3. Autoimmune hepatitis as defined by anti-nuclear antibody (ANA) of 1:160 or greater and liver histology consistent with autoimmune hepatitis or previous response to immunosuppressive therapy.
  4. Autoimmune cholestatic liver disorders as defined by elevation of alkaline phosphatase and anti-mitochondrial antibody of greater than 1:80 or liver histology consistent with primary biliary cirrhosis or elevation of alkaline phosphatase and liver histology consistent with sclerosing cholangitis.
  5. Wilson disease as defined by ceruloplasmin below the limits of normal and liver histology consistent with Wilson disease.
  6. Alpha-1-antitrypsin deficiency as defined by alpha-1-antitrypsin level less than normal and liver histology consistent with alpha-1-antitrypsin deficiency.
  7. Hemochromatosis as defined by presence of 3+ or 4+ stainable iron on liver biopsy and homozygosity for C282Y or compound heterozygosity for C282Y/H63D.
  8. Drug-induced liver disease as defined on the basis of typical exposure and history.
  9. Bile duct obstruction as shown by imaging studies.

• History of ingestion of medications known to produce steatosis in the previous 6 months.

• Evidence of cirrhosis or previously known cirrhosis based on the results from previous liver biopsy or history of portal hypertension presented by ascites, hepatic encephalopathy or varices

• Presence of regular and/or excessive use of alcohol (defined as >30g/day for males and >15g/day for females) for a period longer than 2 years at any times in the last 10 years

• The subject is a pregnant or nursing female

• Life expectancy less than 5 years

• History of known HIV infection

• History of type 1 diabetes

• BMI ≥ 45 kg/m2

• Mentally unbalanced patients, under supervision or guardianship,

• Patient deprived of liberty,

• Patient who does not understand French/ is unable to give consent,

• Patient already included in a trial who may interfere with the study or in a period of exclusion following participation in a previous study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Patients with T2D and MASLD without advanced fibrosis (AF) (COHORT A)	Non-invasive test for the screening of MASLD-related advanced fibrosis in patients with T2D.	Patients with T2D and MASLD without advanced fibrosis (AF) at baseline in the NAFLD-Care study
Patients with T2D and MASLD, without diagnosis of cirrhosis (COHORT B)	Non-invasive test for the screening of MASLD-related advanced fibrosis in patients with T2D.	Patients with T2D and MASLD with presence of advanced fibrosis (AF) and without cirrhosis at baseline in the NAFLD-Care study

Primary Outcome Measures

Name	Time	Method
Progression of MASLD for T2D and MASLD patients without AF at baseline (cohort A) or progression to confirmed diagnosis of cirrhosis for T2D and MASLD patients with presence of AF at baseline and without cirrhosis (cohort B).	One time visit planned according to standard care at 4 years+/- 6 months after inclusion in the NAFLD-CARE study	COHORT A = Composite outcome defined by either histological stage of fibrosis ≥ F3 if a liver biopsy is performed in clinical care or concordant patented Fibrotest≥ F3 and LSM≥ 8 kPa according to EASL guidelines or overt imaging evidence of cirrhosis via ultrasound, computed tomography (CT), or MRI COHORT B = Histological stage of fibrosis 4 or imaging evidence of cirrhosis via ultrasound, computed tomography (CT), or MRI

Secondary Outcome Measures

Name	Time	Method
Assessment of clinical events associated with the natural history of MASLD and T2D for both cohorts	One time visit planned according to standard care at 4 years+/- 6 months after inclusion in the NAFLD-CARE study	Occurrence of T2D COMPLICATIONS (retinopathy, neuropathy, nephropathy, diabetes foot ulcer ), CARDIOVASCULAR EVENTS (coronary artery disease, myocardial infarction, coronary revascularization, stroke, arteriopathy of the lower limbs), LIVER RELATED EVENTS (ascites, esophageal variceal bleeding or needed prophylactic treatment, liver transplantation, hepatocellular carcinoma), KIDNEY RELATED EVENTS (occurence or progression of diabetic nephropathy), DEATHS (all causes).

Trial Locations

Locations (1)

Service d'Endocrinologie, Diabète et nutrition; 🇫🇷 Pierre-Bénite, France