Status:

NOT_YET_RECRUITING

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

Lead Sponsor:

Ann & Robert H Lurie Children's Hospital of Chicago

Conditions:

Non-Alcoholic Fatty Liver Disease

NAFLD

Eligibility:

All Genders

12-17 years

Phase:

PHASE2

Brief Summary

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 ...

Detailed Description

The overall aim of this pilot study is to evaluate the feasibility and obtain a preliminary estimate of efficacy and safety of the SGLT2 inhibitor, empagliflozin, in adolescents with obesity (BMI-perc...

Eligibility Criteria

Inclusion

  • 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

  • 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)

Key Trial Info

Start Date :

May 1 2025

Trial Type :

INTERVENTIONAL

Allocation :

ESTIMATED

End Date :

February 1 2028

Estimated Enrollment :

40 Patients enrolled

Trial Details

Trial ID

NCT03867487

Start Date

May 1 2025

End Date

February 1 2028

Last Update

November 12 2024

Active Locations (1)

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Ann & Robert H Lurie Children's Hospital of Chicago

Chicago, Illinois, United States, 60601