Overview

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

Status:
Suspended
Trial end date:
2024-12-01
Target enrollment:
0
Participant gender:
All
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 adolescents with obesity.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
University of Minnesota
University of Minnesota - Clinical and Translational Science Institute
Treatments:
Empagliflozin
Sodium-Glucose Transporter 2 Inhibitors
Criteria
Inclusion Criteria:

For clinical referral to screening visit:

1. Age: 12 to <20 years old

2. Diagnosis of Obesity: BMI-percentile ≥95th (using age- and sex- based Center for
Disease Control definitions) or BMI ≥30 kg/m2

3. 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

4. History of lifestyle modification to treat obesity or NAFLD

To be obtained at screening visit:

1. Confirmation of Obesity

2. Tanner stage 2

3. Normal fasting glucose tolerance (fasting blood glucose <100 mg/dL)

4. 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%

5. Willingness to adhere to lifestyle considerations throughout the study

Exclusion Criteria:

1. ALT > 250U/L at screening

2. History of significant alcohol intake or current use

3. Impaired fasting glucose (>100 mg/dL)

4. Diabetes (type 1 or 2)

5. Current or recent (<6 months prior to enrollment) use of weight loss medication(s)

6. Vitamin E supplementation

7. Previous bariatric surgery

8. Use of metformin

9. Prior use of empagliflozin

10. Lower limb infection/ulceration within 3 months of screening

11. Metal or magnetic implants, devices or objects inside of or on the body, which are not
MRI compatible

12. Structural and functional urogenital abnormalities, that predispose for urogenital
infections

13. Recent initiation (<3 months prior to enrollment) of anti-hypertensive or lipid
medication(s)

14. Major psychiatric disorder

15. 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)

16. Tobacco use

17. 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)

18. Platelets < 150,000 cells/mm3

19. Total bilirubin 1.3 mg/dL

20. INR 1.3

21. Albumin <3.2 g/dL

22. Gilbert's Syndrome

23. Any known causes of liver disease (except NAFLD and NASH)

24. Significant renal dysfunction (estimated glomerular filtration rate [eGFR] < 90
mL/min/1.73 m2),

25. Diagnosed monogenic obesity

26. History of cancer

27. Untreated thyroid disorder

28. History of decompensation events (ascites, variceal bleeding, hepatic encephalopathy,
or hepatocellular carcinoma)

29. Current or recent (<6 months prior to enrollment) use of medication(s) associated with
weight gain (e.g. atypical anti-psychotics)