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Completed

NCT Number: NCT03783195

Genetic-specific Effects of Fructose on Liver Lipogenesis

The primary goal of this study is to identify a set of genotypes that increase the risk for nonalcoholic fatty liver disease (NAFLD) and predispose individuals to increased de novo lipogenesis (DNL) and liver fat accumulation when exposed to fructose intake. The proposed goal will be achieved through the completion of following aims:

1. To determine the impact of prolonged exposure of fructose on hepatic lipid accumulation in Caucasian individuals with high and low genetic risk for NAFLD, 2. to determine the impact of acute exposure of fructose on hepatic DNL, and 3. to determine the relationship between markers of DNL, liver fat accumulation and serum concentrations of lipids, uric acid and liver function markers before and after the fructose challenge.

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Key information

Conditions

NAFLD Digestive System Diseases Fatty Liver Liver Diseases Non-alcoholic Fatty Liver Disease

Age range

12 year–40 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

UNC Nutrition Research Institute

Kannapolis, North Carolina, 28081, United States

About this study

BACKGROUND AND RATIONALE Non-alcoholic fatty liver disease (NAFLD) is characterized by fat accumulation in liver cells not caused by alcohol. A leading cause of chronic liver disease in the US, NAFLD represents a group of disorders including steatosis, nonalcoholic steatohepatitis with fibrosis. It has substantially risen in prevalence over the last two decades with the estimated prevalence being 20% among US adults and 25% in young adults (18-39 years). Over 64 million individuals are believed to have NAFLD with annual medical costs rising to more $100 billion. More common in individuals who are obese or diabetic and/or have metabolic syndrome, NAFLD has been associated with increased cirrhosis, liver-related mortality and hepatocellular carcinoma.

Both genetic and environmental, including nutritional, factors contribute to the onset and progression of NAFLD. Increased consumption of sugar-sweetened, fructose-rich beverages has been linked to NAFLD. Fructose, commonly found in soft drinks, fruit juices and energy drinks, affects many metabolic processes, foremost being an increase in fat accumulation in the liver and hence, NAFLD. Genome-wide and candidate gene studies have identified several genes associated with NAFLD. However, none of these studies have shown the cumulative effects of single nucleotide polymorphisms (SNPs) on changes in liver fat when exposed to fructose. The results from this study can be extrapolated to larger cohorts and other ethnicities and are therefore, expected to lay the foundation for developing personalized nutritional plans.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Subjects 12 - 40 years
  • No history of alcohol abuse (> 7 drinks per week)
  • History of fructose intake of < 14 drinks per week
  • Caucasian ethnicity
  • BMI > 25kg/m² - 32kg/m² or 85th -99th percentile but otherwise healthy

Exclusion criteria

  • ages < 12 and > 40 years
  • Pregnant/lactating
  • known alcohol abuse or fructose intake > 14 drinks per week
  • not of Caucasian ethnicity
  • glucose levels > 100 mg/dL if fasting, > 140mg/dL if within 2 hours post meal and > 200 mg/dL if random sample
  • taking anti-hypertensive, anti-diabetic, uric acid and/or lipid-lowering medications
  • known diagnosis of diabetes, fructose intolerance, chronic kidney disease, NAFLD or any liver-related disease, hypertriglyceridemia, polycystic ovary syndrome, hypothyroidism, obstructive sleep apnea, hypopituitarism and hypogonadism
  • BMI < 25kg/m² or > 32 kg/m² or < 85th or > 99th percentile
  • Liver fat fraction >5% as per baseline MRI scan

Treatment and study plan

Sugar drink

Other

A sugar drink made with 1.2 g/kg body weight of added sugar( 0.75g/kg body weight of fructose + 0.45g/kg body weight of glucose) and 24oz water

Primary outcomes

  1. Mean Change in Liver Fat Content Based on Elastography

    Time frame: between week 0 (Baseline) and week 3

    Elastography (Fibroscan) will be used to measure changes in liver fat.

  2. Mean Percent Change in Liver Fat Content Based on MRI

    Time frame: between week 0 (Baseline) and week 3

    Magnetic resonance imaging (MRI) will be used to measure changes in liver fat (% change in fat fraction).

  3. Mean Change in Serum Concentrations of Very Low Density Lipoprotein-triglycerides (VLDL-TG)

    Time frame: between week 0 (Baseline) and week 3

    VLDL-TG measurement in serum (mg/dl) at week 0 and Week 3.

  4. Mean Change in AUC of Serum Very Low Density Lipoprotein-triglycerides (VLDL-TG)

    Time frame: between week 0 (Baseline) and week 3

    Area under curve (AUC) (mg*hr/dl) of serum VLDL-TG for baseline and 3hr time points at week 0 and Week 3.

Secondary outcomes

  1. Mean Change in Serum Concentrations of Triglycerides

    Time frame: between week 0 (Baseline) and week 3

    Fasting concentrations of serum triglycerides (mg/dl) will be measured at week 0 and 3

  2. Mean Change in AUC of Serum Triglycerides

    Time frame: between week 0 (Baseline) and week 3

    Area under curve (AUC) (mg*hr/dl) of serum VLDL-TG for baseline and 3hr time points at week 0 and Week 3.

  3. Mean Change in Serum Concentrations of HDL Cholesterol

    Time frame: between week 0 (Baseline) and week 3

    Fasting concentrations of serum HDL cholesterol (mg/dl) will be measured at week 0 and week 3.

  4. Mean Change in AUC of Serum HDL Cholesterol

    Time frame: between week 0 (baseline) and week 3

    Area under curve (AUC) (mg*hr/dl) of serum HDL cholesterol for baseline and 3hr time points at week 0 and Week 3.

  5. Mean Change in Serum Concentrations of LDL Cholesterol

    Time frame: between week 0 (Baseline) and week 3

    Fasting concentrations of serum LDL cholesterol (mg/dl) will be measured.at week 0 and week 3

  6. Mean Change in AUC of Serum LDL Cholesterol

    Time frame: Week 0 (baseline) and week 3

    Area under curve (AUC) (mg*hr/dl) of serum LDL cholesterol for baseline and 3hr time points at week 0 and Week 3.

  7. Mean Change in Serum Concentrations of Total Cholesterol

    Time frame: between week 0 (Baseline) and week 3

    Fasting serum concentrations of total cholesterol (mg/dl) will be measured at week 0 and week 3

  8. Mean Change in AUC of Serum Total Cholesterol

    Time frame: week 0 and week 3

    Area under curve (AUC) (mg*hr/dl) of serum total cholesterol for baseline and 3hr time points at week 0 and Week 3.

  9. Mean Changes in Serum Concentrations of Uric Acid

    Time frame: between week 0 (Baseline) and week 3

    Fasting concentrations of serum uric acid (ng/ml) will be measured at week 0 and week 3

  10. Mean Changes in AUC of Serum Uric Acid

    Time frame: between week 0 (Baseline) and week 3

    Area under curve (AUC) (ng*hr/ml) of serum uric acid for baseline and 3hr time points at week 0 and Week 3.

  11. Mean Change in Serum Concentrations of Liver Function Marker (Alanine Transaminase- ALT).

    Time frame: between week 0 (Baseline) and week 3

    Fasting concentrations of serum ALT (nmol) will be measured at week 0 and week 3

  12. Mean Change in AUC of Serum Alanine Transaminase (ALT)

    Time frame: between week 0 (Baseline) and week 3

    Area under curve (AUC) (nmol/hr) of serum ALT for baseline and 3hr time points at week 0 and Week 3.

  13. Mean Change in Serum Concentrations of Liver Function Marker (Aspartate Transaminase-AST).

    Time frame: between week 0 (Baseline) and week 3

    Serum concentrations of serum AST will be measured at week 0 and week 3

  14. Mean Change in AUC of Serum Aspartate Transaminase (AST).

    Time frame: between week 0 (Baseline) and week 3

    Area under curve (AUC) (IU*hr/L) of serum AST for baseline and 3hr time points at week 0 and Week 3.

  15. Mean Change in Serum Concentrations of Liver Function Marker (Alkaline Phosphatase-ALP)

    Time frame: between week 0 (Baseline) and week 3

    Fasting concentrations of serum ALP (nmol) will be measured at week 0 and week3

  16. Mean Change in AUC of Serum Alkaline Phosphatase (ALP)

    Time frame: between week 0 (Baseline) and week 3

    Area under curve (AUC) (nmol/hr) of serum ALP for baseline and 3hr time points at week 0 and Week 3.

  17. Mean Change in Serum Concentrations of Liver Function Marker (Gamma Glutamyl Transpeptidase-GGT)

    Time frame: between week 0 (Baseline) and week 3

    Serum concentrations of GGT will be measured at week 0 and week 3

  18. Mean Change in AUC of Serum Gamma Glutamyl Transpeptidase (GGT)

    Time frame: between week 0 (Baseline) and week 3

    Area under curve (AUC) (IU*hr/dl) of serum VLDL-TG for baseline and 3hr time points at week 0 and Week 3.

Sponsors and collaborators

Lead sponsor

University of North Carolina, Chapel Hill

Other

Collaborators

  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Registry information

Important dates

Study start
2019
Primary completion
2023
Study completion
2023
First posted
Dec 20, 2018
Registry last updated
Oct 23, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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