Insulin Resistance in Non-Alcoholic Fatty Liver Disease - Full Text View

Sponsored by:	Department of Veterans Affairs
Information provided by:	Department of Veterans Affairs
ClinicalTrials.gov Identifier:	NCT00252499

Purpose

The purpose of this study is to determine whether nonalcoholic fatty liver disease (NAFLD) is associated with altered peripheral and hepatic insulin sensitivity 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 Insulin Resistance	Drug: rosiglitazone Drug: fenofibrate

Study Type:	Interventional
Study Design:	Basic Science, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Efficacy Study
Official Title:	Insulin Resistance in Non-Alcoholic Fatty Liver Disease

Resource links provided by NLM:

MedlinePlus related topics: Liver Diseases

Drug Information available for: Insulin Procetofen Rosiglitazone Rosiglitazone Maleate

U.S. FDA Resources

Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:

The 2 primary outcome measures are: change in ALT levels and liver/spleen ratio [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

1.Change in alanine aminotransferase (ALT) levels as a marker of hepatic inflammation [ Time Frame: 6 months ] [ Designated as safety issue: No ]
2.Change in the liver spleen ration by CT scan as a measure of fat in the liver [ Time Frame: 6 months ] [ Designated as safety issue: No ]
3. Peripheral insulin sensitivityHepatic insulin sensitivityInflammatory cytokinesLipid profileGlucose toleranceBeta-cell function [ Time Frame: 6 months ] [ Designated as safety issue: No ]
4. Changes in body fat distribution [ Time Frame: 6 months ] [ Designated as safety issue: No ]
5. Changes in beta-cell function [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	48
Study Start Date:	October 2005
Estimated Study Completion Date:	August 2015
Estimated Primary Completion Date:	August 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: No Intervention matching placebo for rosiglitazone, 1 po bid and placebo for fenofibrate 1 po qd
2: Experimental rosiglitazone 4 mg po bid and fenofibrate placebo 1 po qd	Drug: rosiglitazone PPAR-gamma agonist, insulin sensitizer
3: Experimental micronized fenofibrate 200 mg 1 po qd and rosiglitazone placebo 1 po bid	Drug: fenofibrate PPAR-alpha agonist, reduces triglycerides

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, -cell function and body fat distribution. Specific Aim 2: To determine in a 6 month placebo-controlled double-blinded treatment study if treatment with rosiglitazone, 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:

Age 18-80 years oldControls: otherwise healthyCase subjects: NAFLD on liver biopsy within the past 3 years or presumed NAFLD with otherwise unexplained elevated ALT and fatty liver by CT or ultrasound
Able to comply with taking 3 pills a day for 6 months and follow-up safety visits

Exclusion Criteria:

Controls: history or evidence of hepatic steatosis; 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: Cases: ALT >5x upper limit of normal Controls: ALT or AST above the normal range, 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 for controls, or since the liver biopsy for case subjects, history of significant coronary artery disease or congestive heart failure, retinopathy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00252499

Contacts

Contact: Kristina M Utzschneider, MD

(206) 277-3568

kutzschn@u.washington.edu

Locations

United States, Washington
VA Puget Sound Health Care System, Seattle	Recruiting
Seattle, Washington, United States, 98108
Contact: Kristina M Utzschneider, MD (206) 277-3568 kutzschn@u.washington.edu
Principal Investigator: Kristina Marie Utzschneider, MD

Sponsors and Collaborators

Department of Veterans Affairs

Investigators

Principal Investigator:

Kristina Marie Utzschneider, MD

VA Puget Sound Health Care System, Seattle

More Information

Additional Information:

Related Info This link exits the ClinicalTrials.gov site

Click here for more information about this study: Insulin resistance in non-alcoholic fatty liver disease This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Department of Veterans Affairs ( Utzschneider, Kristina - Principal Investigator )
Study ID Numbers:	CDA-2-044-08S
Study First Received:	November 9, 2005
Last Updated:	March 19, 2009
ClinicalTrials.gov Identifier:	NCT00252499 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by Department of Veterans Affairs:

beta cell function
fenofibrate
non-alcoholic steatohepatitis
rosiglitazone
insulin sensitivity

Study placed in the following topic categories:

Antimetabolites
Liver Diseases
Metabolic Diseases
Non-alcoholic Steatohepatitis (NASH)
Antilipemic Agents
Fatty Liver
Procetofen
Insulin

Hyperinsulinism
Digestive System Diseases
Hypoglycemic Agents
Insulin Resistance
Glucose Metabolism Disorders
Metabolic Disorder
Rosiglitazone

Additional relevant MeSH terms:

Antimetabolites
Liver Diseases
Metabolic Diseases
Molecular Mechanisms of Pharmacological Action
Antilipemic Agents
Physiological Effects of Drugs
Fatty Liver
Procetofen
Insulin

Pharmacologic Actions
Hyperinsulinism
Digestive System Diseases
Hypoglycemic Agents
Therapeutic Uses
Insulin Resistance
Glucose Metabolism Disorders
Rosiglitazone

ClinicalTrials.gov processed this record on July 06, 2009