Diabetes Mellitus, Type 2, Fibrosis, Liver, Liver Diseases, Non-alcoholic Steatohepatitis
Conditions
Brief summary
The goal of this clinical trial is to learn if empagliflozin works to treat non-alcoholic steatohepatitis in adults. The objectives are: Primary Objective To evaluate the change in histological grading and staging of NASH in patients with confirmed non-alcoholic steatohepatitis (NASH) treated with empagliflozin for a duration of 48 weeks. Secondary Objective To evaluate the change in findings from non-invasive liver elasticity measurements, laboratory tests, and anthropometric assessments after 48 weeks of empagliflozin administration. Participants will: Take empagliflozin every day for 12 months. Visit the clinic according to a protocol at weeks: 1, 2, 4, 12, 24, 36, 48 Visits includes checkups and tests (blood count, basic biochemistry, glycosylated hemoglobin, anthropometry, non-invasive liver stiffness measurement).
Interventions
DRUGEmpagliflozin 10 miligrams (mg)
Use of empagliflozin 10 mg daily for 12 months.
Sponsors
Military University Hospital, Prague
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Ability and eligibility to provide informed consent. * Age between 18 and 75 years at the time of study initiation. * Confirmed or excluded diagnosis of type 2 diabetes mellitus (DM2) according to the target group (OGTT test, HbA1c). * Diagnosis of NASH confirmed by a central pathologist based on histological evaluation of a liver biopsy performed within 3 months prior to the initiation of the investigational drug. - The evaluation must include determination of the process activity according to the NAFLD Activity Score (NAS). * HbA1c value ≤ 80 mmol/mol. * For women of childbearing potential, willingness to use at least two adequate methods of contraception.
Exclusion criteria
* Contraindication to liver biopsy. * Documented episode of ketoacidosis. * Contraindication or hypersensitivity to empagliflozin. * Presence of acute or chronic illness that, in the investigator's opinion, could jeopardize the health or safety of the patient. * HbA1c value \> 80 mmol/mol. * Inability to safely discontinue thiazolidinedione (pioglitazone) therapy. * Liver disease of other etiologies, including viral hepatitis B and C, autoimmune hepatitis, alpha-1 antitrypsin deficiency, hemochromatosis, Wilson's disease, primary sclerosing cholangitis, primary biliary cholangitis, or liver cirrhosis (Child-Pugh A, B, C) of any etiology. * Use of medications or medical procedures that induce liver steatosis or fibrosis. * Proven alcohol use exceeding: Men \> 30 g/day, Women \> 20 g/day. * History of acute or chronic pancreatitis. * Known dependence on or use of illegal addictive substances. * Significant weight gain or loss: +/- 10% in the last three months. * Diagnosis of malignant disease (except treated benign or skin tumors) in the last 5 years. * Stroke or myocardial infarction in the last 6 months. * Clinically significant dyspnea New York hear association (NYHA) grade III or higher. * Proven heart failure with a left ventricular ejection fraction below 40%. * estimated glomerular filtration rate(eGFR) values lower than 30 ml/min/1.73 m² or creatinine clearance lower than 30 ml/min. * Proven diabetic foot syndrome requiring amputation or with an existing defect. * Planned pregnancy, ongoing lactation or pregnancy, positive pregnancy test, lack of at least two adequate contraceptive methods in women of childbearing potential. * Participation in another interventional study within the last 3 months before study entry. * Legal incapacity or reduced ability to perform legal acts. * Serving a prison sentence.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in histological activity after 12-month treatment with empagliflozin | 12 months | Non-alcoholic Fatty Liver Disease Activity Score (NAS) change after intervention. The NAS can range from 0 to 8 and is calculated by the sum of scores of steatosis (0-3), lobular inflammation (0-3) and hepatocyte ballooning (0-2). In patients with NAFLD, NAS score of ≥ 5 strongly correlated with a diagnosis of definite NASH whereas NAS ≤ 3 correlated with a diagnosis of not NASH. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Anthropometry (height) | 12 months | Measurement of body height measured in metres (m) to calculate Body Mass Index (BMI). |
| Change of liver stiffness | 12 months | Liver stiffness measured in kilopascals (kPa) by transient elastography at baseline and after intervention. |
| Change of liver steatosis | 12 months | Continuous attenuation parameter measured in decibels per meter (dB/m) at baseline and after intervention. |
| Anthropometry (BMI) | 12 months | Change in BMI from baseline (measured in kg/m\^2). |
| Liver functional tests | 12 months | Change in activity liver functional tests (LFT) all measured in microkatals per liter (ucat/L) from baseline. These tests comprise: Alanine transaminase (ALT) Aspartate transaminase (AST) Gamma-glutamyl transferase (GGT) Alkaline phosphatase (ALP) |
| Bilirubin level | 12 months | Change in activity concentration of bilirubin measured in micromoles per liter (umol/L) from baseline. |
| Lipidogram | 12 months | Change in cholesterol, LDL cholesterol, HDL cholesterol, triglycerides (measured in mmol/L) from baseline. |
| Anthropometry (body weight) | 12 months | Measurement of body weight measured in kilograms (kg) and change from baseline. |
Countries
Czechia
Outcome results
None listed