Mechanisms of SGLT2 Inhibition in Pediatric Steatotic Liver Disease

Recruitment & Eligibility

Status: Not yet recruiting

Sex: All

Target Recruitment: Not specified

Inclusion Criteria

Inclusion Criteria: - For clinical referral to screening visit: - BMI >30 kg/m2 or >95th BMI-Percentile - Age 16 to <21 at baseline - Elevated alanine aminotransferase (ALT) more than twice the upper limit of normal by gender (= 44 U/L for girls, = 50 U/L for boys)63 within 3 months prior to screening (used for historic ALT value) OR diagnosis of NAFLD from ultrasound, MRI, or participants with biopsy-proven NASH within 12 months of screening. - History of lifestyle modification to treat obesity or NAFLD. - Tanner stage >2 - Normal fasting glucose (fasting blood glucose <100 mg/dL) To be obtained at screening visit: - Confirmation of obesity; - Tanner stage 2,3,4 or 5; - Normal fasting glucose tolerance (fasting blood glucose <100 mg/dL); - If Screening ALT is used as inclusion criteria (if > 2x historic ALT value (historical value obtained clinically within 12 months of screening visit), repeated after 4 weeks [unable to randomize until completed]. If the repeat ALT is more than 50% increased or decreased over the screening ALT, a third ALT should be obtained. If a third ALT is not within 50% of the previous value, then the subject is ineligible but may be rescreened at a later date. If - ALT is not used: - An ultrasound will be done to diagnose NAFLD if the diagnosis has not previously been made by ultrasound, MRI or biopsy. - A MRI-derived HFF = 5.5% - Willingness to adhere to lifestyle considerations throughout the study Exclusion Criteria: - •ALT > 250U/L at screening - History of significant alcohol intake or current use - Impaired fasting glucose (>100 mg/dL) - Diabetes (type 1 or 2) - Current or recent (<6 months prior to enrollment) use of weight loss medication(s) - Vitamin E supplementation or use of metformin - Previous bariatric surgery - Prior use of empagliflozin - Lower limb infection/ulceration within 3 months of screening - Metal or magnetic implants, devices or objects inside of or on the body, which are not MRI compatible - Structural and functional urogenital abnormalities, that predispose for urogenital infections - Recent initiation (<3 months prior to enrollment) of anti-hypertensive or lipid medication(s) - Major psychiatric disorder - Known hypothalamic or pituitary dysfunction - Current pregnancy or plans to become pregnant - Females unwilling to be tested for pregnancy - Females who are sexually active and not protects by an effective method of birth control (e.g. UID or medication or patch) - Tobacco use - Significant liver dysfunction (levels >5 times the upper limit of normal (ULN)): - ALT (ULN = 50 U/L) - AST (ULN = 48 U/L) - GGT (ULN = 48 U/L) - ALP (ULN = 115 U/L) - Platelets < 150,000 cells/mm3 - Total bilirubin 1.3 mg/dL - INR 1.3 - Albumin <3.2 g/dL - Gilbert's Syndrome - Any known causes of liver disease (except NAFLD and NASH) - Significant renal dysfunction (estimated glomerular filtration rate [eGFR] < 80 mL/min/1.73 m2), - Diagnosed monogenic obesity - History of cancer - Untreated thyroid disorder - History of decompensation events (ascites, variceal bleeding, hepatic encephalopathy, or hepatocellular carcinoma) - Current or recent (<6 months prior to enrollment) use of medication(s) associated with weight gain (e.g. atypical anti-psychotics).

Exclusion Criteria

Not provided

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Hepatic Fat

Secondary Outcome Measures

Name	Time	Method
Body mass index

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