Clinical trial NCT06355310: Mechanisms of SGLT2 Inhibition in Pediatric Steatotic Liver Disease
Official title: Mechanisms of SGLT2 Inhibition in Pediatric Steatotic Liver Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Non-Alcoholic Fatty Liver Disease
Lead sponsor: Ann & Robert H Lurie Children's Hospital of Chicago
Sponsor class: OTHER
First posted: 2024-04-09
Enrollment: 40
Sex: ALL
Minimum age (years): 16
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 1:1 randomization
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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

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
  * 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).

Primary outcomes:
measure: Hepatic Fat
timeFrame: 26-Weeks
Secondary outcomes:
measure: Body mass index
timeFrame: 26-Weeks
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Ann & Robert H Lurie Children's Hospital of Chicago
state: Illinois
Study officials:
References: