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SGLT2 Inhibitors as a Novel Treatment for Pediatric Non-Alcoholic Fatty Liver Disease

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This is a pilot drug study to evaluate the feasibility and obtain a preliminary estimate of efficacy and safety of the SGLT2 inhibitor, empagliflozin, in adolescents with obesity (BMI-percentile ≥95th) who have MRI-confirmed NAFLD (hepatic fat fraction ≥ 5.5%) and have normal fasting glucose. We will examine changes in body composition, arterial stiffness, biomarkers of fatty liver disease, and insulin sensitivity over 26-weeks.

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All
12 Years to 17 Years old
This study is NOT accepting healthy volunteers
Inclusion Criteria:
For clinical referral to screening visit:
• Age: 12 to <20 years old
• Diagnosis of Obesity: BMI-percentile ≥95th (using age- and sex- based Center for Disease Control definitions) or BMI ≥30 kg/m2
• Elevated alanine aminotransferase (ALT) more than twice the upper limit of normal by gender (≥44 U/L for girls, ≥50 U/L for boys) 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 moths of screening
• History of lifestyle modification to treat obesity or NAFLD To be obtained at screening visit:
• Confirmation of Obesity
• Tanner stage 2
• 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 screened 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
• Previous bariatric surgery
• Use of metformin
• 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
• Current pregnancy or plans to become pregnant.Females unwilling to be tested for pregnancy. Females will be tested for pregnancy. Females who are sexually active and not protected 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] < 90 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)

Drug: Empagliflozin 10 MG, Drug: Placebo Oral Tablet

Non-Alcoholic Fatty Liver Disease, NAFLD, Pediatric NAFLD

Patti Laqua - laqua001@umn.edu
Justin Ryder
Phase 2
STUDY00003825
NCT03867487
See this study on ClinicalTrials.gov

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