Mechanisms of SGLT2 Inhibition in Pediatric Steatotic Liver Disease
- Conditions
- Non-Alcoholic Fatty Liver Disease
- Interventions
- Drug: Placebo Oral Tablet
- Registration Number
- NCT06355310
- 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 adolescents with obesity.
- 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-percentile ≥95th) who have MRI-confirmed NAFLD (hepatic fat fraction ≥ 5.5%) and have normal fasting glucose.
Participants will take empagliflozin, once daily, in the morning, with or without food, in addition to receiving lifestyle/behavioral counseling throughout the study.
The following data will be collected throughout the course of the study: Physical exam with tanner staging, safety and fasting labs, fasting blood draw (biomarkers), urine sample, 2-stage clamp (overnight Stay),Stable isotope tracers (overnight Stay), MRI scan (MRS-Liver), BMI/anthropometrics, urine pregnancy test for female participants, iDXA scan (body fat and bone density), arterial stiffness and blood pressure.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 40
- For clinical referral to screening visit:
- BMI >30 kg/m2 or >95th BMI-Percentile
- 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
-
•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
- 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)
- 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).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Study intervention Empagliflozin 10 MG Empagliflozin 10 mg will be taken daily Control arm Placebo Oral Tablet Placebo oral tablet will be taken daily
- Primary Outcome Measures
Name Time Method Hepatic Fat 26-Weeks change in hepatic fat fraction (Hepatic fat will be measured by MRI via proton density fat fraction (PDFF)) from baseline (first measurement time point) to 26-weeks.
- Secondary Outcome Measures
Name Time Method Body mass index 26-Weeks * BMI
* body fat% (total and visceral fat)
* ALT
* biomarkers of NAFLD oCK-18 ototal and activated PAI-1 oIL-8
* biomarkers of bone health (additional safety outcome) oN-terminal collagen type I extension propeptide (PINP) oOsteocalcin oC-terminal cross-linking telopeptide of type I collagen (CTX)
* Systolic and diastolic blood pressure
* glycemic control (from oral glucose tolerance test)
* Insulin sensitivity (from oral glucose tolerance test) by the whole-body insulin sensitivity index
Trial Locations
- Locations (1)
Ann & Robert H Lurie Children's Hospital of Chicago
🇺🇸Chicago, Illinois, United States