Clinical trial NCT06519448: Reducing Non-Alcoholic Steatohepatitis
Official title: Reducing Non-Alcoholic Steatohepatitis Study
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: NA
Conditions: Non-alcoholic Steatohepatitis
Liver Diseases
Diabetes Mellitus, Type 2
Fibrosis, Liver
Lead sponsor: Military University Hospital, Prague
Sponsor class: OTHER
First posted: 2024-07-25
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: Change in histological activity after 12-month treatment with empagliflozin
timeFrame: 12 months
Secondary outcomes:
measure: Change of liver stiffness
timeFrame: 12 months
measure: Change of liver steatosis
timeFrame: 12 months
measure: Anthropometry (body weight)
timeFrame: 12 months
measure: Anthropometry (height)
timeFrame: 12 months
measure: Anthropometry (BMI)
timeFrame: 12 months
measure: Liver functional tests
timeFrame: 12 months
measure: Bilirubin level
timeFrame: 12 months
measure: Lipidogram
timeFrame: 12 months
Other outcomes:
Locations:
city: Prague
country: Czechia
facility: Central Military Hospital
Study officials:
References: