Impact of Fructose on Metabolism, Energy Homeostasis and Magnetic Resonance Biomarkers in Nonalcoholic Fatty Liver Disease

NCT01930123 | Terminated Phase 2 Results

• 1 other identifier: Pro00031687
• Study Type: interventional
• Target: 118
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Nonalcoholic Fatty Liver Disease (NAFLD)

Keywords

Fructose; NASH; advanced fibrosis; biomarker; magnetic resonance

Outcome Measures

Primary Outcomes (2)

• Change in Blood Glucose Level From Pre-fructose Administration to Post-fructose Administration in Control Cohort

  Baseline to approximately one hour post-fructose administration

• Fructose-induced Change in Low Density Lipoproteins (LDL) Level

  Comparison between participants with mild fibrosis and participants with advanced fibrosis per the NAFLD Fibrosis score. The NAFLD Fibrosis score is a non-invasive scoring system based on several laboratory tests that helps to estimate the amount of scarring in the liver. A score of F0 or F1 is considered mild, F2 is indeterminate, and F3 or F4 is considered advanced.

  Baseline to approximately one hour post-fructose administration

Secondary Outcomes (1)

• Dynamic 31P Changes in Liver Beta-ATP Due to Fructose Injection

  6 Baseline measurements (~3 min), fructose injection and then approximately 30-50 minutes of 31P MRS with scans at 90 seconds

Study Arms (2)

Patients with NAFLD

EXPERIMENTAL

70 subjects with biopsy-proven NAFLD; subjects will be challenged with a fructose infusion after a period for 12 hours fasting.

Drug: intravenous fructose challenge; Other: Blood Draw

Health controls

ACTIVE COMPARATOR

15 healthy controls for comparison with NAFLD patients.The 15 subjects will be challenged with a fructose infusion after a period for 12 hours fasting.

Drug: intravenous fructose challenge; Other: Blood Draw

Interventions

intravenous fructose challenge DRUG

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.

Health controls; Patients with NAFLD

Blood Draw OTHER

Fasting bloodwork will be obtained before and after the IV fructose challenge.

Health controls; Patients with NAFLD

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Manal F Abdelmalek: lead

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Brian J. Soher, Ph.D.
• Organization: Duke University

brian.soher@duke.edu

919-684-7350

Study Officials

• Manal F Abdelmalek, MD., MPH

  DUMC - Gastroenterology

  PRINCIPAL INVESTIGATOR

• Brian Soher, PhD

  DUMC -Radiology

  PRINCIPAL INVESTIGATOR

• Mustafa Bashir, MD

  DUMC - Radiology

  PRINCIPAL INVESTIGATOR

• Cynthia Guy, MD

  DUMC- Pathology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: August 23, 2013
• First Posted: August 28, 2013
• Study Start: October 1, 2013
• Primary Completion: January 1, 2020
• Study Completion: January 1, 2020
• Last Updated: August 31, 2022
• Results First Posted: August 31, 2022

Record last verified: 2022-08

Locations

US (1)