Impact of Fructose on Metabolism, Energy Homeostasis and Magnetic Resonance Biomarkers in Nonalcoholic Fatty Liver Disease
Condition: Nonalcoholic Fatty Liver Disease (NAFLD)
MeSH terms: Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
Intervention: intravenous fructose challenge; Blood Draw
Intervention description: Patients will be admitted to our Duke Clinical Research Unit (DCRU) at least 12 hours prior to morning intravenous fructose challenge. All patients will have a "standard" meal in order to control for dietary composition and calorie intake prior to intravenous fructose challenge. Patients will be NPO (nothing by mouth) after midnight for morning IV fructose MR biomarker measures. Patients with suspected NAFLD will have had an historical standard of care liver biopsy in the past and will have IV fructose Magnetic Resonance biomarker measures in the morning.; Fasting bloodwork will be obtained before and after the IV fructose challenge.
Phase: Phase 2
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 118.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Fructose; NASH; advanced fibrosis; biomarker; magnetic resonance

Summary:

      This study will advance several goals of the NIH Action Plan: 1) establish a
      multidisciplinary team to develop quantitative methodologies and imaging protocols for liver,
      2) validate diagnostic criteria and methodologies for imaging in liver in both a
      cross-sectional and a longitudinal dietary intervention study of patients with Nonalcoholic
      Fatty Liver Disease (NAFLD), 3) create a liver tissue bank with correlative imaging data, 4)
      develop reliable non-invasive MR markers to distinguish simple steatosis from Nonalcoholic
      Steatohepatitis (NASH), and 5) define the dynamic changes in metabolism, energy homeostasis,
      and MR biomarkers as they relate to fructose-related liver injury.
    

Eligibility criteria:

        Inclusion Criteria:

        Patients must satisfy all of the following criteria to be eligible for enrollment:

          -  Age greater than 18 years as of the initial screening interview and provision of
             consent

          -  Healthy control as defined by:

               -  normal liver aminotransferases AND

               -  no evidence of NAFLD on radiologic imaging studies AND

               -  no history of chronic liver disease OR

               -  liver biopsy (if one had been historically performed for evaluation of suspected
                  liver disease).

        OR • Patient with clinically suspected NAFLD as assessed by standard of care measures (risk
        factors for NAFLD, abnormal liver enzymes and/or fatty liver on imaging studies) who are
        scheduled to will undergo liver biopsy for the purpose of grading / staging the severity of
        their underlying liver disease

        Exclusion Criteria:

        Patients who satisfy any of the following exclusion criteria will be ineligible for
        enrollment:

          -  Current or history of significant alcohol consumption for a period of more than 3
             consecutive months within 1 year prior to screening (significant alcohol consumption
             is defined as more than 20 g/day in females and more than 30 g/day in males, on
             average)

          -  Inability to reliably quantify alcohol consumption based upon local study physician
             judgment

          -  Use of drugs historically associated with NAFLD (amiodarone, methotrexate, systemic
             glucocorticoids, tetracyclines, tamoxifen, estrogens at doses greater than those used
             for hormone replacement, anabolic steroids, valproic acid, and other known
             hepatotoxins) for more than 2 weeks in the past year prior to randomization

          -  Prior or planned (during the study period) bariatric surgery

          -  Uncontrolled diabetes defined as HbA1c 9.5% or higher within 60 days prior to
             enrollment

          -  A platelet count below 90,000/mm3

          -  Clinical evidence of hepatic decompensation as defined by the presence of any of the
             following abnormalities:

               -  Serum albumin greater than 3.2 g/dL, INR (international normalized ratio) greater
                  than 1.3, bilirubin greater than 2.0 mg/dL

               -  History of esophageal varices, ascites or hepatic encephalopathy

          -  Evidence of other forms of chronic liver disease

          -  Serum alanine aminotransferase (ALT) greater than 300 U/L

          -  Serum creatinine of 2.0 mg/dL or greater

          -  Unstable therapy for components of the metabolic syndrome (ie. recent starting or
             stopping of insulin sensitizing agent, lipid lowering agent, and/or antioxidant
             therapy) . Recent starting or stopping (for more than 7 days) the use of a
             thiazolidinedione (pioglitazone or rosiglitazone) 90 days before the entry biopsy or
             anytime thereafter

          -  Use of any prescription or over-the-counter medication or herbal remedy that are
             believed to improve or treat NASH or liver disease or obesity for the 90 days prior to
             baseline liver biopsy or prior to randomization

             - Patients must not take any other agent to treat NASH except the treatment assigned
             after randomization.

          -  Inability to safely obtain a liver biopsy

          -  Active substance abuse including inhaled or injection drugs in the year prior to
             screening

          -  Pregnancy, planned pregnancy, potential for pregnancy and unwillingness to use
             effective birth control during the trial, breast feeding

          -  Any other condition which, in the opinion of the investigator, would impede compliance
             or hinder completion of the study

          -  A contraindication to MRI examinations

          -  Extreme claustrophobia

          -  Weight or girth exceeds the scanner capabilities

          -  Any condition or circumstance that, in the opinion of the site investigator, would
             interfere with completion of MR examinations

          -  Failure to give informed consent