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RECRUITINGPhase 2INTERVENTIONAL

Mechanisms of SGLT2 Inhibition in Pediatric Steatotic Liver Disease

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

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.

Who May Be Eligible (Plain English)

Who May Qualify: 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 Who Should NOT Join This Trial: - 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 -waiting period after previous treatment 30 days - Previous bariatric surgery - Prior use of empagliflozin - Lower limb infection/ulceration within 3 months of screening ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language
Inclusion Criteria: 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 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 -washout period 30 days * 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) -can re-screen 30 days after getting on birth control * 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).

Treatments Being Tested

DRUG

Empagliflozin 10 MG

Participants will take a 10 mg oral tablet of empagliflozin, an orally-active inhibitor of sodium-glucose co-transporter 2 (SGLT2)

DRUG

Placebo Oral Tablet

Participants will take an identical appearing oral tablet with zero active ingredient.

Locations (1)

Ann & Robert H Lurie Children's Hospital of Chicago
Chicago, Illinois, United States