Insulin Resistance in Non-alcoholic Fatty Liver Disease
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|ClinicalTrials.gov Identifier: NCT00252499|
Recruitment Status : Terminated (Protocol drug change required new clinicaltrails.gov entry)
First Posted : November 11, 2005
Results First Posted : April 11, 2014
Last Update Posted : August 20, 2014
|Condition or disease||Intervention/treatment||Phase|
|Fatty Liver Insulin Resistance||Drug: rosiglitazone Drug: fenofibrate Drug: placebo for rosiglitazone Drug: placebo for fenofibrate||Not Applicable|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||13 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|Primary Purpose:||Basic Science|
|Official Title:||Insulin Resistance in Non-alcoholic Fatty Liver Disease|
|Study Start Date :||October 2005|
|Actual Primary Completion Date :||August 2010|
|Actual Study Completion Date :||August 2010|
U.S. FDA Resources
Placebo Comparator: Placebo Arm
matching placebo for rosiglitazone, 1 po bid and placebo for fenofibrate 1 po qd
Drug: placebo for rosiglitazone
placebo tablets that are matched to look like rosiglitazoneDrug: placebo for fenofibrate
placebo matched to look like fenofibrate tablets
Experimental: Rosiglitazone Arm
rosiglitazone 4 mg po bid and fenofibrate placebo 1 po qd
PPAR-gamma agonist, insulin sensitizerDrug: placebo for fenofibrate
placebo matched to look like fenofibrate tablets
Experimental: Fenofibrate Arm
micronized fenofibrate 200 mg 1 po qd and rosiglitazone placebo 1 po bid
PPAR-alpha agonist, reduces triglyceridesDrug: placebo for rosiglitazone
placebo tablets that are matched to look like rosiglitazone
- Liver/Spleen Ratio at 6 Months [ Time Frame: 6 months ]Liver fat was estimated by non-contrast CT scan measuring the density ratio between the liver and spleen by Hounsfield units (liver/spleen ratio), which has been previously correlated with liver fat quantification by magnetic resonance spectroscopy.Ten separate measurements equally distributed throughout the liver and spleen were obtained and the Hounsfield units averaged. In subjects with more than one slice through the liver and spleen, the values for all slices were averaged.
- Change in Alanine Aminotransferase (ALT) Levels From Baseline to 6 Months [ Time Frame: 6 months ]
- Change in the Liver Spleen Ratio by CT Scan From Baseline to 6 Months as a Measure of Fat in the Liver [ Time Frame: 6 months ]
- Change in Peripheral Insulin Sensitivity From Baseline to 6 Months [ Time Frame: 6 months ]A two-step stable isotope labeled, hyperinsulinemic-euglycemic clamp procedure was performed with a low dose insulin infusion (20 mU/m2/min) for 3 hours followed by a primed high dose insulin infusion (160 mU/m2/min x 5 minutes then 80 mU/m2/min) for two hours. D20 was infused and adjusted to maintain the blood glucose at 90 mg/dl. Samples for glucose, insulin and 6,6 2d glucose were drawn every 15 minutes during the final half hour of the basal, low dose and high dose insulin periods. Whole body insulin sensitivity was calculated as the rate of glucose disposal (Rd)/lean body mass during the high dose insulin infusion.
- Changes in Intra-abdominal Fat Area From Baseline to 6 Months [ Time Frame: 6 months ]Unenhanced CT scan images were obtained on a General Electric Discovery HD750 CT scanner. Intra-abdominal (IAF) areas were measured at the top of the iliac crest and quantified using the Tomovision program (SliceOMatic V4.3) by one trained technologist.
- Change in Hepatic Insulin Sensitivity From Baseline to 6 Months [ Time Frame: 6 months ]Hepatic insulin sensitivity was determined as the percent suppression of endogenous glucose production (EGP) at the end of the low dose insulin clamp.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00252499
|United States, Washington|
|VA Puget Sound Health Care System, Seattle|
|Seattle, Washington, United States, 98108|
|Principal Investigator:||Kristina Marie Utzschneider, MD||VA Puget Sound Health Care System, Seattle|