Reducing Non-Alcoholic Steatohepatitis (RedNASH)

Reducing Non-Alcoholic Steatohepatitis Study

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).

Study Overview

• Status: Enrolling by invitation
• Conditions: Liver Diseases; Diabetes Mellitus, Type 2; Fibrosis, Liver; Non-alcoholic Steatohepatitis
• Intervention / Treatment: Drug: Empagliflozin 10 miligrams (mg)

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Czechia
  • Prague, Czechia, 16902
    • Central Military Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NASH; Patients with histological proven NASH (either diabetics and non-diabetics).	Drug: Empagliflozin 10 miligrams (mg); Use of empagliflozin 10 mg daily for 12 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in histological activity after 12-month treatment with empagliflozin	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".	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of liver stiffness	Liver stiffness measured in kilopascals (kPa) by transient elastography at baseline and after intervention.	12 months
Change of liver steatosis	Continuous attenuation parameter measured in decibels per meter (dB/m) at baseline and after intervention.	12 months
Anthropometry (body weight)	Measurement of body weight measured in kilograms (kg) and change from baseline.	12 months
Anthropometry (height)	Measurement of body height measured in metres (m) to calculate Body Mass Index (BMI).	12 months
Anthropometry (BMI)	Change in BMI from baseline (measured in kg/m^2).	12 months
Liver functional tests	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)	12 months
Bilirubin level	Change in activity concentration of bilirubin measured in micromoles per liter (umol/L) from baseline.	12 months
Lipidogram	Change in cholesterol, LDL cholesterol, HDL cholesterol, triglycerides (measured in mmol/L) from baseline.	12 months

Collaborators and Investigators

• Sponsor: Military University Hospital, Prague

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: July 3, 2024
• First Submitted That Met QC Criteria: July 19, 2024
• First Posted (Actual): July 25, 2024

Study Record Updates

• Last Update Posted (Actual): July 25, 2024
• Last Update Submitted That Met QC Criteria: July 19, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Fibrosis; Liver Diseases; Diabetes Mellitus, Type 2; Fatty Liver; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Empagliflozin
• Other Study ID Numbers: RedNASH

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No