SGLT2 Inhibitors as a Novel Treatment for Pediatric Non-Alcoholic Fatty Liver Disease
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- Justin Ryder
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Efficacy as Measured by Change in Hepatic Fat Fraction (HFF)
研究概览
简要总结
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.
详细描述
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, stool sample, OGTT, CGM sensor placement and removal, MRI scan (MRS-Liver), BMI/anthropometrics, urine pregnancy test for female participants, iDXA scan (body fat and bone density), arterial stiffness and blood pressure.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
This is a double blind clinical trial in which the study team and the participants are blinded to whether the subject received placebo or study drug.
入排标准
- 年龄范围
- 12 Years 至 20 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •For clinical referral to screening visit:
- •Age: 12 to <20 years old
- •Diagnosis of Obesity: BMI-percentile >95th (using age- and sex- based Center for Disease Control definitions) or BMI ≥30 kg/m2
- •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
- •History of lifestyle modification to treat obesity or NAFLD
- •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 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%
- •Willingness to adhere to lifestyle considerations throughout the study
排除标准
- •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
- •Previous bariatric surgery
- •Use of metformin
- •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 protected by an effective method of birth control (e.g. IUD 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
- •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).
研究组 & 干预措施
Study intervention
Empagliflozin 10 mg will be taken daily
干预措施: Empagliflozin 10 MG (Drug)
Control arm
Placebo oral tablet will be taken daily
干预措施: Placebo Oral Tablet (Drug)
结局指标
主要结局
Efficacy as Measured by Change in Hepatic Fat Fraction (HFF)
时间窗: Baseline to 26 weeks
HFF is measured by MRI via 1H- magnetic resonance spectroscopy (MRS). HFF will be measured with single-voxel 1H-MRS on a 3.0 T Trio whole body MRI scanner, using the software package provided by the vendor. The MR elastography measurement will consist of a phase-contrast 2D GRE scan (TR/TE = 50/25 ms, matrix 256 x 90, GRAPPA R=3, slice thickness 7mm) with motion encoding in the z-direction, and acoustic excitation at 60 Hz. Four axial slices will be acquired, each with a single breath-hold. Manual ROIs covering the liver will be drawn on the stiffness maps (in kPa units) generated by the system software. Fibrosis staging will be determined following previously published guidelines.
次要结局
- Change in Body Measurements: Body mass index (BMI)(Baseline to 26 weeks)
- Change in Body Measurements: Visceral Fat %(Baseline to 26 weeks)
- Change in Biomarkers of NAFLD: Alanine transaminase (ALT)(Baseline to 26 weeks)
- Change in Glycemic Control(Baseline to 26 weeks)
- Change in Body Measurements: Body Fat %(Baseline to 26 weeks)
- Change in Biomarkers of NAFLD: Cytokeratin (CK)-18(Baseline to 26 weeks)
- Change in Proton Density Fat Fraction (PDFF) from MRI(Baseline to 26 weeks)
- Change in Blood Pressure(Baseline to 26 weeks)
- Change in Arterial Stiffness(Baseline to 26 weeks)
研究者
Justin Ryder
Vice Chair of Research for the Department of Surgery
Ann & Robert H Lurie Children's Hospital of Chicago