Genetic-specific Effects of Fructose on Liver Lipogenesis

September 27, 2024 updated by: University of North Carolina, Chapel Hill

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

15

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • North Carolina
      • Kannapolis, North Carolina, United States, 28081
        • UNC Nutrition Research Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years to 40 years (Child, Adult)

Accepts Healthy Volunteers

Yes

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: High GRS group
This group consists of individuals who are in the highest quartile of the genetic risk score (GRS) and will ingest one sugar drink (equal to 2 soft drinks) per day for 3 weeks. The GRS is computed by adding the number of alleles that increase the risk for liver lipogenesis or fatty liver.
Other: Sugar drink
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
Experimental: Low GRS group
This groups consists of individuals who are in the lowest quartile of the genetic risk score (GRS) and will ingest one sugar drink (equal to 2 soft drinks) per day for 3 weeks. The GRS is computed by adding the number of alleles that increase the risk for liver lipogenesis or fatty liver.
Other: Sugar drink
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
between week 0 (Baseline) and week 3
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).
between week 0 (Baseline) and week 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.
between week 0 (Baseline) and week 3
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.
between week 0 (Baseline) and week 3

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
between week 0 (Baseline) and week 3
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.
between week 0 (Baseline) and week 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.
between week 0 (Baseline) and week 3
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.
between week 0 (baseline) and week 3
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
between week 0 (Baseline) and week 3
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.
Week 0 (baseline) and week 3
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
between week 0 (Baseline) and week 3
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.
week 0 and week 3
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
between week 0 (Baseline) and week 3
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.
between week 0 (Baseline) and week 3
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
between week 0 (Baseline) and week 3
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.
between week 0 (Baseline) and week 3
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
between week 0 (Baseline) and week 3
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.
between week 0 (Baseline) and week 3
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
between week 0 (Baseline) and week 3
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.
between week 0 (Baseline) and week 3
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
between week 0 (Baseline) and week 3
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.
between week 0 (Baseline) and week 3

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of North Carolina, Chapel Hill

Collaborators

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

Investigators

  • Principal Investigator: Saroja Voruganti, University of North Carolina, Chapel Hill

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 25, 2019

Primary Completion (Actual)

April 25, 2023

Study Completion (Actual)

April 25, 2023

Study Registration Dates

First Submitted

December 17, 2018

First Submitted That Met QC Criteria

December 19, 2018

First Posted (Actual)

December 20, 2018

Study Record Updates

Last Update Posted (Actual)

October 23, 2024

Last Update Submitted That Met QC Criteria

September 27, 2024

Last Verified

May 1, 2023

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • 17-3348
  • P30DK056336-16S1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with University of North Carolina (UNC).

IPD Sharing Time Frame

9- 36 months following article publication

IPD Sharing Access Criteria

Investigators whose proposed use of the data has been approved by the institutional review board, independent ethics committee or research ethics committee, as applicable and an executed data use agreement with UNC.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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