Clinical trial NCT03783195: Genetic-specific Effects of Fructose on Liver Lipogenesis
Official title: Genetic-specific Effects of Fructose on Liver Lipogenesis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: NAFLD
Keywords: Glucose
Fructose
Fatty-liver
Polymorphisms
Imaging
Fibroscan
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2018-12-20
Enrollment: 15
Sex: ALL
Minimum age (years): 12
Maximum age (years): 40
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants are assigned to high genetic risk score group in parallel to low genetic risk score group
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

1. ages \< 12 and \> 40 years
2. Pregnant/lactating
3. known alcohol abuse or fructose intake \> 14 drinks per week
4. not of Caucasian ethnicity
5. glucose levels \> 100 mg/dL if fasting, \> 140mg/dL if within 2 hours post meal and \> 200 mg/dL if random sample
6. taking anti-hypertensive, anti-diabetic, uric acid and/or lipid-lowering medications
7. 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
8. BMI \< 25kg/m² or \> 32 kg/m² or \< 85th or \> 99th percentile
9. Liver fat fraction \>5% as per baseline MRI scan

Primary outcomes:
measure: Mean Change in Liver Fat Content Based on Elastography
timeFrame: between week 0 (Baseline) and week 3
measure: Mean Percent Change in Liver Fat Content Based on MRI
timeFrame: between week 0 (Baseline) and week 3
measure: Mean Change in Serum Concentrations of Very Low Density Lipoprotein-triglycerides (VLDL-TG)
timeFrame: between week 0 (Baseline) and week 3
measure: Mean Change in AUC of Serum Very Low Density Lipoprotein-triglycerides (VLDL-TG)
timeFrame: between week 0 (Baseline) and week 3
Secondary outcomes:
measure: Mean Change in Serum Concentrations of Triglycerides
timeFrame: between week 0 (Baseline) and week 3
measure: Mean Change in AUC of Serum Triglycerides
timeFrame: between week 0 (Baseline) and week 3
measure: Mean Change in Serum Concentrations of HDL Cholesterol
timeFrame: between week 0 (Baseline) and week 3
measure: Mean Change in AUC of Serum HDL Cholesterol
timeFrame: between week 0 (baseline) and week 3
measure: Mean Change in Serum Concentrations of LDL Cholesterol
timeFrame: between week 0 (Baseline) and week 3
measure: Mean Change in AUC of Serum LDL Cholesterol
timeFrame: Week 0 (baseline) and week 3
measure: Mean Change in Serum Concentrations of Total Cholesterol
timeFrame: between week 0 (Baseline) and week 3
measure: Mean Change in AUC of Serum Total Cholesterol
timeFrame: week 0 and week 3
measure: Mean Changes in Serum Concentrations of Uric Acid
timeFrame: between week 0 (Baseline) and week 3
measure: Mean Changes in AUC of Serum Uric Acid
timeFrame: between week 0 (Baseline) and week 3
measure: Mean Change in Serum Concentrations of Liver Function Marker (Alanine Transaminase- ALT).
timeFrame: between week 0 (Baseline) and week 3
measure: Mean Change in AUC of Serum Alanine Transaminase (ALT)
timeFrame: between week 0 (Baseline) and week 3
measure: Mean Change in Serum Concentrations of Liver Function Marker (Aspartate Transaminase-AST).
timeFrame: between week 0 (Baseline) and week 3
measure: Mean Change in AUC of Serum Aspartate Transaminase (AST).
timeFrame: between week 0 (Baseline) and week 3
measure: Mean Change in Serum Concentrations of Liver Function Marker (Alkaline Phosphatase-ALP)
timeFrame: between week 0 (Baseline) and week 3
measure: Mean Change in AUC of Serum Alkaline Phosphatase (ALP)
timeFrame: between week 0 (Baseline) and week 3
measure: Mean Change in Serum Concentrations of Liver Function Marker (Gamma Glutamyl Transpeptidase-GGT)
timeFrame: between week 0 (Baseline) and week 3
measure: Mean Change in AUC of Serum Gamma Glutamyl Transpeptidase (GGT)
timeFrame: between week 0 (Baseline) and week 3
Other outcomes:
Locations:
city: Kannapolis
country: United States
facility: UNC Nutrition Research Institute
state: North Carolina
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Saroja Voruganti
role: PRINCIPAL_INVESTIGATOR
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