Mechanisms of SGLT2 Inhibition in Pediatric Steatotic Liver Disease

NCT ID: NCT06355310

Last Updated: 2025-02-19

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-01-27
• Study Completion Date: 2028-02-01

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.

Conditions

Non-Alcoholic Fatty Liver Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Study intervention

Empagliflozin 10 mg will be taken daily

Group Type: EXPERIMENTAL

Empagliflozin 10 MG

Intervention Type: DRUG

Participants will take a 10 mg oral tablet of empagliflozin, an orally-active inhibitor of sodium-glucose co-transporter 2 (SGLT2)

Control arm

Placebo oral tablet will be taken daily

Group Type: PLACEBO_COMPARATOR

Placebo Oral Tablet

Intervention Type: DRUG

Participants will take an identical appearing oral tablet with zero active ingredient.

Interventions

Empagliflozin 10 MG

Participants will take a 10 mg oral tablet of empagliflozin, an orally-active inhibitor of sodium-glucose co-transporter 2 (SGLT2)

Intervention Type: DRUG

Placebo Oral Tablet

Participants will take an identical appearing oral tablet with zero active ingredient.

Intervention Type: DRUG

Other Intervention Names

Jardiance; Control group

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);
• 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).

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ann & Robert H Lurie Children's Hospital of Chicago

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Ann & Robert H Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Angie Figueroa, MS, CCRP

Role: CONTACT

SHIELD@luriechildrens.org

773-550-0749

Facility Contacts

Angie Figueroa

Role: primary

SHIELD@luriechildrens.org

773-550-0749 ext. 312-227-4757

Other Identifiers

IRB 2023-6429

Identifier Type: -

Identifier Source: org_study_id