Insulin Resistance in Non-alcoholic Fatty Liver Disease
Information source: Department of Veterans Affairs
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Fatty Liver
Intervention: fenofibrate (Drug); pioglitazone (Drug); placebo (Drug)
Phase: N/A
Status: Terminated
Sponsored by: Department of Veterans Affairs Official(s) and/or principal investigator(s): Kristina M Utzschneider, MD, Principal Investigator, Affiliation: VA Puget Sound Health Care System, Seattle
Summary
The study is designed to investigate the relationship between insulin resistance and
non-alcoholic fatty liver disease (NAFLD) and to investigate potential mechanisms underlying
insulin resistance in NAFLD by determining associations between hepatic and peripheral
insulin sensitivity, hepatic steatosis, dyslipidemia, inflammatory cytokines, glucose
metabolism, beta-cell function and body fat distribution.
Clinical Details
Official title: Insulin Resistance in Non-alcoholic Fatty Liver Disease (Protocol Drug Change From Project Career Development Award (CDA)-2-044-08S)
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science
Primary outcome: Liver/Spleen Ratio Measured as the Ratio in Hounsfield Units Between the Liver and the Spleen on Computed Tomography (CT) Scan
Secondary outcome: Change in Alanine Aminotransferase (ALT) LevelsChange in Liver/Spleen Ratio Measure by the Density Ratio in Hounsfield Units Between the Liver and the Spleen by CT Change in Peripheral Insulin Sensitivity Change in Intra-abdominal Fat Area by CT Scan Change in Hepatic Insulin Sensitivity
Detailed description:
NAFLD and nonalcoholic steatohepatitis (NASH) are common liver disorders that are strongly
associated with obesity, type 2 diabetes and dyslipidemia. The underlying pathophysiology of
fatty infiltration of the liver is thought to be related to insulin resistance, which is an
almost universal finding in patients with NAFLD. It is also possible that fat infiltration
and inflammation in the liver may impair insulin sensitivity, either locally in the liver,
or peripherally via the actions of inflammatory cytokines. We hypothesize that insulin
resistance is a major causal factor leading to fat deposition in the liver and NAFLD, and
thus interventions aimed at improving insulin sensitivity will result in a reduction of
hepatic inflammation and steatosis.
Specific Aim 1: To determine in a cross-sectional study whether NAFLD is associated with
altered peripheral and hepatic insulin sensitivity and to study their relationships with
hepatic steatosis, dyslipidemia, inflammatory cytokines, glucose metabolism, beta-cell
function and body fat distribution. Specific Aim 2: To determine in a 6 month
placebo-controlled double-blinded treatment study if treatment with pioglitazone, an insulin
sensitizer, or fenofibrate, a triglyceride lowering agent, will improve both hepatic as well
as peripheral insulin sensitivity and thereby improve hepatic steatosis and inflammation in
subjects with NAFLD.
The results of the proposed study will have important implications for our understanding of
the mechanisms underlying insulin resistance and abnormalities in lipid and glucose
metabolism in subjects with NAFLD and for the design of future studies aimed at the
prevention and treatment of this condition.
Eligibility
Minimum age: 18 Years.
Maximum age: 80 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
Control subjects: nl liver enzymes and no history of liver disease Case subjects: NAFLD on
liver biopsy within the past 3 years or presumed NAFLD with otherwise unexplained elevated
alanine aminotransferase (ALT) and fatty liver by computerized tomography (CT) scan or
ultrasound
- Able to comply with taking 1 pill a day for 6 months and follow-up safety visits
Exclusion Criteria:
- Cases: cirrhosis on liver biopsy or by clinical exam or fibrosis score
- Causes of liver dysfunction other than NASH
- Use of medications associated with hepatic steatosis:
- glucocorticoids
- estrogens
- tamoxifen
- amiodarone
- accutane
- sertraline
- Use of medications that cause insulin resistance:
- niacin
- glucocorticoids
- anti-HIV drugs or atypical antipsychotics
- Use of lipid-lowering medications except stable dose statin
- Use of anti-NASH drugs such as ursodeoxycholic acid, betaine milk thistle
- Use of coumadin
- Use of nitrates
- Significant alcohol consumption: Average >20 grams/day
- In subjects with diabetes, a hemoglobin A1c (HbA1c) >7. 5% or use of insulin,
metformin, rosiglitazone or pioglitazone
- Liver transaminases: ALT >5x upper limit of normal,
- Iron saturation >50%
- Creatinine >1. 5 mg/dl for men and >1. 4 mg/dl for women
- Hematocrit <33%
- Pregnancy or lactation
- Significant weight loss within the past 6 months or since the liver biopsy
- History of significant coronary artery disease or congestive heart failure,
retinopathy
Locations and Contacts
VA Puget Sound Health Care System, Seattle, Seattle, Washington 98108, United States
Additional Information
Starting date: October 2005
Last updated: October 10, 2014
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