Clinical trial NCT06567990: Type 2 DIAbeTes With NAFLD: innOvative Biomarkers of Disease progressioN and clInical outComes
Official title: Type 2 DIAbeTes With NAFLD: innOvative Biomarkers of Disease progressioN and clInical outComes
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Metabolic Dysfunction-Associated Liver Disease
Keywords: MASLD
Type 2 diabetes
Obesity
Advanced fibrosis
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2024-08-23
Enrollment: 500
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Prospective, multi-site, not randomized, national study
Primary purpose: SCREENING

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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).
timeFrame: One time visit planned according to standard care at 4 years+/- 6 months after inclusion in the NAFLD-CARE study
Secondary outcomes:
measure: Assessment of clinical events associated with the natural history of MASLD and T2D for both cohorts
timeFrame: One time visit planned according to standard care at 4 years+/- 6 months after inclusion in the NAFLD-CARE study
Other outcomes:
Locations:
city: Pierre-Bénite
country: France
facility: Service d'Endocrinologie, Diabète et nutrition
Study officials:
References: