Insulin Resistance in Non-alcoholic Fatty Liver Disease

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT01289639
First received: January 21, 2011
Last updated: August 28, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention
Fatty Liver
Drug: fenofibrate
Drug: pioglitazone
Drug: placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Basic Science
Official Title: Insulin Resistance in Non-alcoholic Fatty Liver Disease (Protocol Drug Change From Project CDA-2-044-08S)

Resource links provided by NLM:


Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:
  • liver/spleen ratio [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Peripheral insulin sensitivity Hepatic insulin sensitivity Inflammatory cytokines Lipid profile Glucose tolerance Beta-cell function [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • ALT levels [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • hepatic insulin sensitivity index [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 48
Study Start Date: October 2005
Estimated Study Completion Date: August 2015
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Arm 1
matching placebo 1 po qd
Drug: placebo
placebo 1 capsule po qd
Experimental: Arm 2
micronized fenofibrate 200 mg 1 po qd
Drug: fenofibrate
micronized fenofibrate 200 mg 1 po qd
Experimental: Arm 3
pioglitazone 30 mg po qd
Drug: pioglitazone
pioglitazone 30 mg po qd

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

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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 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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01289639

Locations
United States, Washington
VA Puget Sound Health Care System, Seattle
Seattle, Washington, United States, 98108
Sponsors and Collaborators
Investigators
Principal Investigator: Kristina Marie Utzschneider, MD VA Puget Sound Health Care System, Seattle
  More Information

Additional Information:
Publications:
Responsible Party: Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT01289639     History of Changes
Other Study ID Numbers: CDA-2-044-08S-2
Study First Received: January 21, 2011
Last Updated: August 28, 2014
Health Authority: United States: Federal Government

Keywords provided by Department of Veterans Affairs:
non-alcoholic fatty liver disease
non-alcoholic steatohepatitis
insulin resistance
pioglitazone
fenofibrate

Additional relevant MeSH terms:
Liver Diseases
Insulin Resistance
Fatty Liver
Digestive System Diseases
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Pioglitazone
Insulin
Fenofibrate
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 18, 2014