<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03783195</url>
  </required_header>
  <id_info>
    <org_study_id>17-3348</org_study_id>
    <secondary_id>P30DK056336-16S1</secondary_id>
    <nct_id>NCT03783195</nct_id>
  </id_info>
  <brief_title>Genetic-specific Effects of Fructose on Liver Lipogenesis</brief_title>
  <official_title>Genetic-specific Effects of Fructose on Liver Lipogenesis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of North Carolina, Chapel Hill</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of North Carolina, Chapel Hill</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary goal of this study is to identify a set of genotypes that increase the risk for&#xD;
      nonalcoholic fatty liver disease (NAFLD) and predispose individuals to increased de novo&#xD;
      lipogenesis (DNL) and liver fat accumulation when exposed to fructose intake. The proposed&#xD;
      goal will be achieved through the completion of following aims:&#xD;
&#xD;
        1. To determine the impact of prolonged exposure of fructose on hepatic lipid accumulation&#xD;
           in Caucasian individuals with high and low genetic risk for NAFLD,&#xD;
&#xD;
        2. to determine the impact of acute exposure of fructose on hepatic DNL, and&#xD;
&#xD;
        3. to determine the relationship between markers of DNL, liver fat accumulation and serum&#xD;
           concentrations of lipids, uric acid and liver function markers before and after the&#xD;
           fructose challenge.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      BACKGROUND AND RATIONALE Non-alcoholic fatty liver disease (NAFLD) is characterized by fat&#xD;
      accumulation in liver cells not caused by alcohol. A leading cause of chronic liver disease&#xD;
      in the US, NAFLD represents a group of disorders including steatosis, nonalcoholic&#xD;
      steatohepatitis with fibrosis. It has substantially risen in prevalence over the last two&#xD;
      decades with the estimated prevalence being 20% among US adults and 25% in young adults&#xD;
      (18-39 years). Over 64 million individuals are believed to have NAFLD with annual medical&#xD;
      costs rising to more $100 billion. More common in individuals who are obese or diabetic&#xD;
      and/or have metabolic syndrome, NAFLD has been associated with increased cirrhosis,&#xD;
      liver-related mortality and hepatocellular carcinoma.&#xD;
&#xD;
      Both genetic and environmental, including nutritional, factors contribute to the onset and&#xD;
      progression of NAFLD. Increased consumption of sugar-sweetened, fructose-rich beverages has&#xD;
      been linked to NAFLD. Fructose, commonly found in soft drinks, fruit juices and energy&#xD;
      drinks, affects many metabolic processes, foremost being an increase in fat accumulation in&#xD;
      the liver and hence, NAFLD. Genome-wide and candidate gene studies have identified several&#xD;
      genes associated with NAFLD. However, none of these studies have shown the cumulative effects&#xD;
      of single nucleotide polymorphisms (SNPs) on changes in liver fat when exposed to fructose.&#xD;
      The results from this study can be extrapolated to larger cohorts and other ethnicities and&#xD;
      are therefore, expected to lay the foundation for developing personalized nutritional plans.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 25, 2019</start_date>
  <completion_date type="Actual">April 25, 2023</completion_date>
  <primary_completion_date type="Actual">April 25, 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Participants are assigned to high genetic risk score group in parallel to low genetic risk score group</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Liver fat content (%)</measure>
    <time_frame>at week 0 and 3</time_frame>
    <description>Magnetic resonance imaging (MRI) and transient elastography (Fibroscan) will be used to measure changes in liver fat.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Serum concentrations of low density lipoprotein-triglycerides (VLDL-TG)</measure>
    <time_frame>0, 1 and 3 hours at week 0 and week 3</time_frame>
    <description>VLDL-TG measurement in serum (mg/dl)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Serum concentrations of triglycerides</measure>
    <time_frame>at week 0 and week 3</time_frame>
    <description>Fasting concentrations of serum triglycerides (mg/dl) will be measured.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum concentrations of HDL cholesterol</measure>
    <time_frame>at week 0 and week 3</time_frame>
    <description>Fasting concentrations of serum HDL cholesterol (mg/dl) will be measured.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum concentrations of LDL cholesterol</measure>
    <time_frame>at week 0 and week 3</time_frame>
    <description>Fasting concentrations of serum LDL cholesterol (mg/dl) will be measured.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum concentrations of total cholesterol</measure>
    <time_frame>at week 0 and week 3</time_frame>
    <description>Fasting serum concentrations of total cholesterol (mg/dl) will be measured.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum concentrations of uric acid</measure>
    <time_frame>at week 0 and week 3</time_frame>
    <description>Fasting concentrations of serum uric acid (ng/ml) will be measured.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum concentrations of liver function marker (Alanine transaminase- ALT).</measure>
    <time_frame>at week 0 and week 3</time_frame>
    <description>Fasting concentrations of serum ALT (IU/L) will be measured.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum concentrations of liver function marker (Aspartate transaminase-AST).</measure>
    <time_frame>at week 0 and week 3</time_frame>
    <description>Fasting concentrations of serum AST (IU/L) will be measured.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum concentrations of liver function marker (Alkaline phosphatase-ALP)</measure>
    <time_frame>at week 0 and week 3</time_frame>
    <description>Fasting concentrations of serum ALP (IU/L) will be measured.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum concentrations of liver function marker (Gamma glutamyl transpeptidase-GGT)</measure>
    <time_frame>at week 0 and week 3</time_frame>
    <description>Fasting concentrations of serum GGT will be measured.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">15</enrollment>
  <condition>NAFLD</condition>
  <arm_group>
    <arm_group_label>High GRS group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Low GRS group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Sugar drink</intervention_name>
    <description>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</description>
    <arm_group_label>High GRS group</arm_group_label>
    <arm_group_label>Low GRS group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Subjects 12 - 40 years&#xD;
&#xD;
          2. No history of alcohol abuse (&gt; 7 drinks per week)&#xD;
&#xD;
          3. History of fructose intake of &lt; 14 drinks per week&#xD;
&#xD;
          4. Caucasian ethnicity&#xD;
&#xD;
          5. BMI &gt; 25kg/m² - 32kg/m² or 85th -99th percentile but otherwise healthy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. ages &lt; 12 and &gt; 40 years&#xD;
&#xD;
          2. Pregnant/lactating&#xD;
&#xD;
          3. known alcohol abuse or fructose intake &gt; 14 drinks per week&#xD;
&#xD;
          4. not of Caucasian ethnicity&#xD;
&#xD;
          5. glucose levels &gt; 100 mg/dL if fasting, &gt; 140mg/dL if within 2 hours post meal and &gt;&#xD;
             200 mg/dL if random sample&#xD;
&#xD;
          6. taking anti-hypertensive, anti-diabetic, uric acid and/or lipid-lowering medications&#xD;
&#xD;
          7. known diagnosis of diabetes, fructose intolerance, chronic kidney disease, NAFLD or&#xD;
             any liver-related disease, hypertriglyceridemia, polycystic ovary syndrome,&#xD;
             hypothyroidism, obstructive sleep apnea, hypopituitarism and hypogonadism&#xD;
&#xD;
          8. BMI &lt; 25kg/m² or &gt; 32 kg/m² or &lt; 85th or &gt; 99th percentile&#xD;
&#xD;
          9. Liver fat fraction &gt;5% as per baseline MRI scan&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Saroja Voruganti</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of North Carolina, Chapel Hill</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UNC Nutrition Research Institute</name>
      <address>
        <city>Kannapolis</city>
        <state>North Carolina</state>
        <zip>28081</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
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  <verification_date>May 2023</verification_date>
  <study_first_submitted>December 17, 2018</study_first_submitted>
  <study_first_submitted_qc>December 19, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 20, 2018</study_first_posted>
  <last_update_submitted>June 19, 2023</last_update_submitted>
  <last_update_submitted_qc>June 19, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 22, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Glucose</keyword>
  <keyword>Fructose</keyword>
  <keyword>Fatty-liver</keyword>
  <keyword>Polymorphisms</keyword>
  <keyword>Imaging</keyword>
  <keyword>Fibroscan</keyword>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_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_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_time_frame>9- 36 months following article publication</ipd_time_frame>
    <ipd_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_access_criteria>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>March 9, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/95/NCT03783195/ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03783195
org study id: 17-3348
secondary id: P30DK056336-16S1
nct id: NCT03783195
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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.
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.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: Participants are assigned to high genetic risk score group in parallel to low genetic risk score group
primary purpose: Basic Science
masking: None (Open Label)
measure: Liver fat content (%)
time frame: at week 0 and 3
description: Magnetic resonance imaging (MRI) and transient elastography (Fibroscan) will be used to measure changes in liver fat.
measure: Serum concentrations of low density lipoprotein-triglycerides (VLDL-TG)
time frame: 0, 1 and 3 hours at week 0 and week 3
description: VLDL-TG measurement in serum (mg/dl)
measure: Serum concentrations of triglycerides
time frame: at week 0 and week 3
description: Fasting concentrations of serum triglycerides (mg/dl) will be measured.
measure: Serum concentrations of HDL cholesterol
time frame: at week 0 and week 3
description: Fasting concentrations of serum HDL cholesterol (mg/dl) will be measured.
measure: Serum concentrations of LDL cholesterol
time frame: at week 0 and week 3
description: Fasting concentrations of serum LDL cholesterol (mg/dl) will be measured.
measure: Serum concentrations of total cholesterol
time frame: at week 0 and week 3
description: Fasting serum concentrations of total cholesterol (mg/dl) will be measured.
measure: Serum concentrations of uric acid
time frame: at week 0 and week 3
description: Fasting concentrations of serum uric acid (ng/ml) will be measured.
measure: Serum concentrations of liver function marker (Alanine transaminase- ALT).
time frame: at week 0 and week 3
description: Fasting concentrations of serum ALT (IU/L) will be measured.
measure: Serum concentrations of liver function marker (Aspartate transaminase-AST).
time frame: at week 0 and week 3
description: Fasting concentrations of serum AST (IU/L) will be measured.
measure: Serum concentrations of liver function marker (Alkaline phosphatase-ALP)
time frame: at week 0 and week 3
description: Fasting concentrations of serum ALP (IU/L) will be measured.
measure: Serum concentrations of liver function marker (Gamma glutamyl transpeptidase-GGT)
time frame: at week 0 and week 3
description: Fasting concentrations of serum GGT will be measured.
arm group label: High GRS group
arm group type: Experimental
description: 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.
arm group label: Low GRS group
arm group type: Experimental
description: 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.
intervention type: Other
intervention name: Sugar drink
description: 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
arm group label: High GRS group
arm group label: Low GRS group
criteria: 
gender: All
minimum age: 12 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Saroja Voruganti
role: Principal Investigator
affiliation: University of North Carolina, Chapel Hill
facility: 
country: United States
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responsible party type: Sponsor
sharing ipd: Yes
ipd 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 info type: Study Protocol
ipd time frame: 9- 36 months following article publication
ipd 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.
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