Mechanisms of SGLT2 Inhibition in Pediatric Steatotic Liver Disease
This study is a randomized, double-blind, placebo-controlled trial specifically designed to evaluate the preliminary feasibility, initial efficacy and safety of SGLT2 inhibitors for treating NAFLD in adolescents with obesity.
∙ For clinical referral to screening visit:
• BMI \>30 kg/m2 or \>95th BMI-Percentile
• Weight Range of 75kg to 150kg
• 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