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Reducing Non-Alcoholic Steatohepatitis

Not Applicable
Conditions
Non-alcoholic Steatohepatitis
Liver Diseases
Diabetes Mellitus, Type 2
Fibrosis, Liver
Interventions
Registration Number
NCT06519448
Lead Sponsor
Military University Hospital, Prague
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).

Detailed Description

Not available

Recruitment & Eligibility

Status
ENROLLING_BY_INVITATION
Sex
All
Target Recruitment
30
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
NASHEmpagliflozin 10 miligrams (mg)Patients with histological proven NASH (either diabetics and non-diabetics).
Primary Outcome Measures
NameTimeMethod
Change in histological activity after 12-month treatment with empagliflozin12 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 Outcome Measures
NameTimeMethod
Change of liver stiffness12 months

Liver stiffness measured in kilopascals (kPa) by transient elastography at baseline and after intervention.

Anthropometry (height)12 months

Measurement of body height measured in metres (m) to calculate Body Mass Index (BMI).

Change of liver steatosis12 months

Continuous attenuation parameter measured in decibels per meter (dB/m) at baseline and after intervention.

Liver functional tests12 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)

Anthropometry (BMI)12 months

Change in BMI from baseline (measured in kg/m\^2).

Lipidogram12 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.

Bilirubin level12 months

Change in activity concentration of bilirubin measured in micromoles per liter (umol/L) from baseline.

Trial Locations

Locations (1)

Central Military Hospital

🇨🇿

Prague, Czechia

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