Using SGLT2 inhibitors to treat fatty liver disease in obese adolescents

Mechanisms of SGLT2 Inhibition in Pediatric Steatotic Liver Disease

This study is testing if a medication called empagliflozin can help obese teenagers with fatty liver disease improve their liver health and overall well-being.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 16 Years to 20 Years
• Sex: All
• Sponsor: Ann & Robert H Lurie Children's Hospital of Chicago (Academic / other)
• Locations: 1 site (Chicago, Illinois)
• Trial ID: NCT06355310 on ClinicalTrials.gov

What this trial studies

This pilot study is a randomized, double-blind, placebo-controlled trial aimed at evaluating the feasibility, initial efficacy, and safety of the SGLT2 inhibitor empagliflozin in adolescents with obesity and non-alcoholic fatty liver disease (NAFLD). Participants aged 16 to 21 with a BMI in the 95th percentile or higher will receive either empagliflozin or a placebo, alongside lifestyle and behavioral counseling. The study will collect various health data, including physical exams, lab tests, and MRI scans, to assess the treatment's impact on liver health and overall well-being.

Who should consider this trial

Good fit: Ideal candidates are adolescents aged 16 to 21 with obesity and MRI-confirmed NAFLD.

Not a fit: Patients with normal liver function and those without obesity or NAFLD may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for adolescents suffering from NAFLD, potentially improving liver health and reducing obesity-related complications.

How similar studies have performed: While this approach is relatively novel in the pediatric population, previous studies in adults have shown promise with SGLT2 inhibitors for metabolic conditions.

Eligibility criteria

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).

Where this trial is running

Chicago, Illinois

• Ann & Robert H Lurie Children's Hospital of Chicago — Chicago, Illinois, United States (Recruiting)

Study contacts

• Principal investigator: Justin Ryder, PhD — Ann & Robert H Lurie Children's Hospital of Chicago
• Study coordinator: Farah Salim, M.S.

Conditions Non-Alcoholic Fatty Liver Disease