Outcome
Type |
Measure |
Description |
Time frame |
Safety issue |
Primary |
Percent Change in Alanine Aminotransferase (ALT) |
Percent change in alanine aminotransferase (ALT) from baseline to 12 weeks was examined. ALT elevation is the most common screening test used for detecting NAFLD. The normal range for ALT varies by age, sex, and the specific assay used but is approximately 9-23 units/Liter (U/L) for boys and girls aged 1-18. Children with a sustained ALT = 80 U/L are twice as likely to have nonalcoholic steatohepatitis (NASH), which is a severe form of NAFLD characterized by inflammation and liver cell damage. |
Baseline, Week 12 |
|
Secondary |
Absolute Change in ALT |
Absolute change in ALT among study participants is reported here. ALT elevation is the most common screening test used for detecting NAFLD. ALT elevation is the most common screening test used for detecting NAFLD. The normal range for ALT varies by age, sex, and the specific assay used but is approximately 9-23 U/L for boys and girls aged 1-18. Children with a sustained ALT = 80 U/L are twice as likely to have nonalcoholic steatohepatitis (NASH), which is a severe form of NAFLD characterized by inflammation and liver cell damage. |
Baseline, Week 6, Week 12 |
|
Secondary |
Percent Change in ALT Between Study Visits |
Percent change in ALT from baseline to week 6 and the mean of week 6 and week 12 was examined. ALT elevation is the most common screening test used for detecting NAFLD. The normal range for ALT varies by age, sex, and the specific assay used but is approximately 9-23 U/L for boys and girls aged 1-18. Children with a sustained ALT = 80 U/L are twice as likely to have nonalcoholic steatohepatitis (NASH), which is a severe form of NAFLD characterized by inflammation and liver cell damage. |
Baseline, Week 6, Week 12 |
|
Secondary |
Absolute Change in Hepatic Steatosis |
Hepatic steatosis (fat accumulation in the liver) was measured by MRI using liver fat fraction (HepaFat-Scan by Resonance Health). NAFLD is characterized by an accumulation of fat in the liver. Having a fat percentage greater than 5% of the weight of the liver is a typical cut point to indicate NAFLD. The HepaFat-Scan software is a non-invasive method of measuring the volumetric liver fat fraction and is validated in children. |
Baseline, Week 12 |
|
Secondary |
Absolute Change in Pancreatic Fat |
Pancreatic fat was measured by MRI (HepaFat). Increased pancreatic fat is associated with more severe liver disease in children with NAFLD. |
Baseline, Week 12 |
|
Secondary |
Absolute Change in Aspartate Aminotransferase (AST) |
AST is a common screening test used for detecting NAFLD. The normal range for AST varies by age, sex, and the specific assay used but is approximately 13-32 U/L for boys and 12-24 units/Liter for girls aged 7-18. Elevated AST levels indicate increased liver disease. |
Baseline, Week 6, Week 12 |
|
Secondary |
Change in Fasting Insulin |
Insulin sensitivity was determined by assessment of fasting insulin. Fasting insulin increases with insulin resistance and tends to occur with NAFLD. |
Baseline, Week 6, Week 12 |
|
Secondary |
Change in Fasting Glucose |
Insulin sensitivity was determined by assessment of fasting glucose. The normal range for fasting glucose in children is 70-99 mg/dL. Diabetes mellitus is indicated with fasting glucose levels of 126 or greater. |
Baseline, Week 6, Week 12 |
|
Secondary |
Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) Score |
The HOMA-IR score is calculated as fasting blood glucose level (nmol/L) multiplied by fasting insulin level (microU/L), divided by 22.5. Higher scores indicate increasing insulin resistance, although pediatric cut-points for HOMA-IR scores vary by gender and age. |
Baseline, Week 6, Week 12 |
|
Secondary |
Absolute Change in Gamma-glutamyltransferase (GGT) |
Gamma-glutamyl transferase (GGT) is a biomarker for NAFLD. Normal GGT values vary by age and the specific assay used. The normal range for males and females aged 11-18 is approximately 5-15 U/L. Increased GGT is associated with more severe NAFLD. |
Baseline, Week 6, Week 12 |
|
Secondary |
Absolute Change in Total Cholesterol |
Blood was drawn for a clinical lipid profile, including total cholesterol. Cholesterol is waxy substance which is produced by the liver or comes from food consumed. Cholesterol concentrations are commonly used as a marker for cardiovascular disease risk in adulthood Total cholesterol levels below 170 mg/100 milliliters (mL) of blood are in the normal range while levels at 200 and above are considered high. |
Baseline, Week 6, Week 12 |
|
Secondary |
Absolute Change in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) |
Blood was drawn for a clinical lipid profile, including total non-HDL-C. A measurement of non-HDL-C is obtained by subtracting high-density lipoprotein (HDL) level from total cholesterol. Non-HDL-C can predict atherosclerosis with as much accuracy as other lipoproteins can. Non-HDL-C values of 129 mg/dL or greater are considered high. |
Baseline, Week 6, Week 12 |
|
Secondary |
Absolute Change in High-density Lipoprotein (HDL) Cholesterol |
Blood was drawn for a clinical lipid profile, including total HDL cholesterol. HDL cholesterol is the "good" cholesterol because it is a type of fat that removes cholesterol from blood, thereby preventing build up. A healthy value for HDL cholesterol is 35 mg/dL and higher. Values under 35 mg/dL mean the child has a higher risk of developing heart disease. |
Baseline, Week 6, Week 12 |
|
Secondary |
Absolute Change in Very-low-density Lipoprotein Cholesterol (VLDL-C) |
Blood was drawn for a clinical lipid profile, including total VLDL cholesterol. VLDL cholesterol is produced in the liver and high levels are associated with increased plaque buildup in arteries. Values of VLDL-C that are 29 mg/dL or greater are considered high. |
Baseline, Week 6, Week 12 |
|
Secondary |
Absolute Change in Low-density Lipoprotein (LDL) Cholesterol |
Blood was drawn for a clinical lipid profile, including LDL cholesterol. LDL cholesterol levels below 110 mg/100 mL of blood are in the normal range while levels at 130 and above are considered high. |
Baseline, Week 6, Week 12 |
|
Secondary |
Absolute Change in Triglycerides (TG) |
Blood was drawn for a clinical lipid profile, including triglycerides. Triglycerides are made by the body and come from food consumed. High triglyceride levels increases the risk of heart disease and stroke. Triglyceride levels below 150 mg/dL are considered acceptable while levels greater than 200 mg/dL are considered high. |
Baseline, Week 6, Week 12 |
|
Secondary |
Absolute Change in Apolipoprotein A-1 (ApoA-1) |
Apolipoproteins transport lipids through the body by binding with fat and cholesterol to form lipoproteins. ApoA-1 is a component of HDL ("good cholesterol") which transports cholesterol and phospholipids through the body to the liver. Among children aged 2 to 17 years, an ApoA-1 level of less than 115 mg/dL is considered low and levels greater than 120 mg/dL are considered acceptable. |
Baseline, Week 6, Week 12 |
|
Secondary |
Absolute Change in Apolipoprotein B (ApoB) |
Apolipoproteins transport lipids through the body by binding with fat and cholesterol to form lipoproteins. ApoB is a component of VLDL, intermediate-density lipoproteins (IDL), LDL, and chylomicrons. Among children aged 2 to 17 years, an ApoB level of less than 90 mg/dL is considered acceptable and levels of 100 mg/dL and greater are considered high. |
Baseline, Week 6, Week 12 |
|
Secondary |
Absolute Change in Apolipoprotein C-II (ApoC-II) |
Apolipoproteins transport lipids through the body by binding with fat and cholesterol to form lipoproteins. ApoC-II is a component of VLDL and chylomicrons. Normal values are between 3-5 mg/dL and abnormal values may be caused by a lipoprotein lipase deficiency resulting in fats not being broken down normally. Abnormal ApoC-II measurements may explain elevated levels of cholesterol and triglycerides. |
Baseline, Week 6, Week 12 |
|
Secondary |
Absolute Change in Apolipoprotein E (ApoE) |
Apolipoproteins transport lipids through the body by binding with fat and cholesterol to form lipoproteins. ApoE is a component of IDL and chylomicrons and carry cholesterol to the brain. Normal values of ApoE are between 3-7 mg/dL. Elevated ApoE may be associated with increased risk of dyslipidemia and atherosclerosis. |
Baseline, Week 6, Week 12 |
|
Secondary |
Absolute Change in Apolipoprotein CIII (ApoCIII) |
Apolipoproteins transport lipids through the body by binding with fat and cholesterol to form lipoproteins. ApoCIII is a component of VLDL, HDL, and triglyceride-rich chylomicrons and regulates lipid metabolism. Elevated ApoCIII is associated with atherosclerosis and cardiovascular disease. |
Baseline, Week 6, Week 12 |
|
Secondary |
Absolute Change in High Sensitivity C-Reactive Protein (hsCRP) |
High Sensitivity C-Reactive Protein (hsCRP) is a measurement assessing inflammation. Increased levels of hsCRP are associated with increased risk of cardiovascular disease or cardiovascular events such as stroke or heart attack. Values of hsCRP that are less than 1.0 mg/L are considered low risk, 1.0 to 3.0 mg/L indicates average risk, and values greater than 3.0 mg/L are considered high risk. |
Baseline, Week 6, Week 12 |
|
Secondary |
Change in Interleukin 1 Beta (IL-1B) |
Interleukin 1 beta is a cytokine protein involved in inflammatory response. A normal value for IL-1B is less than 3.9 picograms per milliliter (pg/mL). Increased IL-1B levels have been found to be associated with congestive heart failure. |
Baseline, Week 6, Week 12 |
|
Secondary |
Change in Interleukin 6 (IL-6) |
Interleukin 6 is a cytokine protein involved in the pro-inflammatory and anti-inflammatory response and stimulates an inflammatory response in many diseases, including atherosclerosis. Higher levels are generally interpreted as worsening of a disease condition. |
Baseline, Week 6, Week 12 |
|
Secondary |
Change in Procollagen III |
Procollagen III peptide levels can be used to assess the degree of collagen turnover and liver fibrosis. Increases in serum concentrations of procollagen III indicate a worsening disease state. |
Baseline, Week 6, Week 12 |
|
Secondary |
Change in Particle Size of VLDL |
Lipoprotein particle size will be assessed by Nuclear Magnetic Resonance (NMR). VLDL size ranges from 30-90 nanometers (nm) and is impacted by eating a meal high in fat. A linear relationship has been seen between VLDL particle size and NAFLD degree of severity. |
Baseline, Week 6, Week 12 |
|
Secondary |
Change in Particle Size of HDL |
Lipoprotein particle size will be assessed by Nuclear Magnetic Resonance (NMR). HDL size ranges from 7-13 nanometers (nm). Different sizes of HDL perform different functions in the body and this study will examine how HDL particle size is altered over time by the study treatment. |
Baseline, Week 6, Week 12 |
|
Secondary |
Change in Particle Size of LDL |
Lipoprotein particle size will be assessed by Nuclear Magnetic Resonance (NMR). LDL size ranges from 21-27 nanometers (nm) and is impacted by metabolic factors. This study will examine how LDL particle size is altered over time by the study treatment. |
Baseline, Week 6, Week 12 |
|
Secondary |
Change in Particle Size of Chylomicrons |
The size of chylomicrons in blood will be assessed throughout the study period. Chylomicrons are lipoprotein particles comprised of primarily of triglycerides and also contain phospholipids, and proteins. The size of chylomicrons varies and typically range from 75 to 600 nanometers (nm) in diameter. Chylomicrons are larger immediately following a meal. |
Baseline, Week 6, Week 12 |
|
Secondary |
Change in Rate of de Novo Lipogenesis (DNL) |
Rate of de novo lipogenesis (DNL) will be measured using stable isotope tracers. DNL is a biochemical process occurring in the liver where fatty acids are synthesized into carbohydrates. This study will examine how the rate of DNL is altered over time by the study treatment. |
Baseline, Week 6, Week 12 |
|
Secondary |
Absolute Change in Abdominal Visceral Fat |
Abdominal visceral fat was measured with the AMRA Medical body composition profile calculated from MRI images. |
Baseline, Week 12 |
|
Secondary |
Absolute Change in Abdominal Subcutaneous Fat |
Abdominal subcutaneous fat was measured with the AMRA Body composition profile calculated from MRI images. |
Baseline, Week 12 |
|
Secondary |
Change in Liver Inflammation and Fibrosis (LIF) Score |
LiverMultiScan by Perspectum Diagnostics is an imaging software tool that works with MRI providing a non-invasive way to diagnose liver disease. A LIF score of <1 represents a normal liver, 1-1.99 represents mild liver disease, 2-2.99 represents moderate liver disease, and a score ?3 represents severe liver disease. |
Baseline, Week 12 |
|
Secondary |
Absolute Change in Height |
Height in centimeters was measured at each study visit. |
Baseline, Week 12 |
|
Secondary |
Absolute Change in Weight |
Weight in kilograms was measured at each study visit. |
Baseline, Week 12 |
|
Secondary |
Absolute Change in Body Mass Index (BMI) |
Body mass index (BMI) was calculated as weight (in kilograms) divided by height (in meters) squared (kg/m^2). The change in BMI between Baseline and Week 12 is presented here. |
Baseline, Week 12 |
|
Secondary |
Absolute Change in Waist Circumference |
Waist circumference was measured in centimeters at each study visit. The change is waist circumference between Baseline and Week 12 is presented here. |
Baseline, Week 12 |
|
Secondary |
Pill Count |
Adherence was assessed by pill counts of returned bottles. A total of 120 pills were dispensed for the 12 week study period. Taking one pill per day for 12 weeks means that 36 pills would be returned if the participant had perfect adherence. Pill counts greater than 36 mean that doses were skipped. |
Week 12 |
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