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Comparing Tricor, Avandia, or Weight Loss to Lower Cardiovascular Risk Factors in People With High Triglycerides.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00186537
Recruitment Status : Completed
First Posted : September 16, 2005
Results First Posted : May 5, 2016
Last Update Posted : January 12, 2017
Information provided by (Responsible Party):
Gerald M Reaven, Stanford University

Brief Summary:
Approximately 1/4 of the US population has insulin resistance and the associated risk factors such as elevated lipid levels -triglycerides (type of fat from what we eat and what the liver produces and low HDL cholesterol which is the good cholesterol helping to protect against heart disease. Currently one known treatment for this a medication called fenofibrate, another medication that can improve insulin resistance is rosiglitazone, a third treatment known to improve insulin resistance an decrease triglycerides is weight loss. In this study insulin resistant individuals with elevated triglycerides and or a ratio of triglycerides to HDL cholesterol of 3:1 or greater will be randomized (selected by chance) to receive one of these treatments and results of insulin sensitivity and cardiac risk profiles will be compared at the end of the study.

Condition or disease Intervention/treatment Phase
Insulin Resistance Hypertriglyceridemia Drug: Rosiglitazone Drug: Fenofibrate Behavioral: Weight Loss Not Applicable

Detailed Description:

It has been estimated that approximately ¼ of the US population has the Insulin Resistant Syndrome (IRS). The notion that insulin resistance and compensatory hyperinsulinemia lead to a cluster of abnormalities that increase CVD risk was first introduced in 1988, and central to the changes identified was a dyslipidemia characterized by a high plasma triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) concentration. The atherogenic lipoprotein pattern associated with the IRS has grown to include enhanced postprandial lipemia and smaller and denser low-density lipoprotein (LDL) particles. In addition to being associated with insulin resistance and compensatory hyperinsulinemia, these changes in lipoprotein metabolism have been identified as increasing CVD risk. The power of the dyslipidemia associated with the IRS is reinforced by reports that the plasma TG/HDL-C concentration ratio is as powerful a predictor of CVD, if not more so, than the more conventional total plasma cholesterol/LDL-C concentration ratio, and evidence from the Copenhagen Male Study of the interaction between the plasma TG and HDL-C concentrations, "conventional" CVD risk factors, and CVD events. Specifically, these latter investigators were able to show in a prospective study (11) that CVD events were substantially attenuated in: 1) smokers; 2) patients with high blood pressure; 3) individuals with a high LDL-C concentration; and 4) subjects who were sedentary; as long as they were in the lowest 1/3rd of the population with the lowest TG/HDL-C concentration ratio and presumably insulin sensitive. Conversely, if they were in the tertile with the highest plasma TG/HDL-C concentration ratio, and presumably insulin resistant, they had a significant increase in CVD events in the absence of the four conventional CVD risk factors evaluated.

An obvious alternative therapeutic approach to decreasing CVD risk in patients with the IRS would be to administer a thiazolidinedione (TZD) compound in an effort to directly treat the basic defect of the syndrome. However, based upon our own results with rosiglitazone (ROSI) in several different patient populations, improvements in insulin sensitivity were not associated with a significant improvement in dyslipidemia. For example, in a recent study (unpublished) of ROSI-treated patients with type 2 diabetes, neither plasma TG (358 to 347 mg/dL) nor HDL-C (40 to 42 mg/dL) concentrations improved, and both total (215 to 239 mg/dL and LDL-C (118-142mg/dL) concentrations actually increased. Since the patients in this study became more insulin sensitive with treatment, and had lower daylong plasma glucose, insulin, and free fatty acid concentrations, the reason for the lack of a beneficial effect of ROSI on lipoprotein metabolism is not clear. On the other hand, given evidence of the importance of dyslipidemia in increasing CVD risk in insulin resistant individuals, it seems reasonable to question the notion that TZD compounds provide the most beneficial approach to decreasing CVD risk in the dyslipidemic patient with the IRS.

With this background in mind, we propose to initiate a study in which insulin resistant individuals with the dyslipidemia characteristic of the IRS will be randomized to treatment with fenofibrate,ROSI, or weight loss and the effect of these three treatments on CVD risk factors compared. It is postulated that although insulin resistance will improve to a greater degree with ROSI treatment, the atherogenic lipoprotein profile known to link IRS and CVD will only significantly improve following treatment with fenofibrate and effects of weight loss can effect both of these.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 47 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Comparison Fenofibrate, Rosiglitazone, or Weight Loss to Decrease Cardiovascular Risk in Insulin Resistant Dyslipidemic Individuals.
Study Start Date : September 2003
Actual Primary Completion Date : September 2008
Actual Study Completion Date : September 2008

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: fenofibrate
160 mg daily for 12 weeks
Drug: Fenofibrate
Other Name: tricor

Active Comparator: rosiglitazone
4 mg/daily 4 weeks followed by 4 mg 2 x daily for 8 weeks
Drug: Rosiglitazone
Other Name: avandia

Active Comparator: calorie restricted diet
calorie restricted to achieve 0.5 kg weight loss/week x 12 weeks
Behavioral: Weight Loss

Primary Outcome Measures :
  1. Pre- and Post-Intervention Triglyceride Levels [ Time Frame: Baseline, 12 weeks ]
    Compare the change in mean triglyceride levels between groups after the interventions

  2. Pre- and Post-Intervention LDL Cholesterol Levels [ Time Frame: Baseline, 12 weeks ]
    Compare the change in mean LDL Cholesterol levels between groups after the interventions

  3. Pre- and Post-Intervention HDL Cholesterol Levels [ Time Frame: Baseline, 12 weeks ]
    Compare the change in mean HDL Cholesterol levels between groups after the interventions

Information from the National Library of Medicine

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Ages Eligible for Study:   30 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

Insulin Resistant Triglyceride 150 mg/dL or greater or triglyceride HDL-C ratio 3 or greater BMI 25-35

Exclusion Criteria:

Diabetes Mellitus History of gall stones History of CHF History of CAD Severe anemia,kidney, or liver disease

Information from the National Library of Medicine

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 identifier (NCT number): NCT00186537

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United States, California
Stanford University Medical Center
Stanford, California, United States, 94305
Sponsors and Collaborators
Stanford University
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Principal Investigator: Gerald M Reaven, MD Stanford University
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Responsible Party: Gerald M Reaven, Professor Emeritus, Stanford University Identifier: NCT00186537    
Other Study ID Numbers: 79301
SPO 28829
First Posted: September 16, 2005    Key Record Dates
Results First Posted: May 5, 2016
Last Update Posted: January 12, 2017
Last Verified: November 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Gerald M Reaven, Stanford University:
Insulin resistance
Insulin resistance syndrome
atherogenic dyslipidemia
triglyceride/HDL-C ratio
Additional relevant MeSH terms:
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Insulin Resistance
Weight Loss
Body Weight Changes
Body Weight
Glucose Metabolism Disorders
Metabolic Diseases
Lipid Metabolism Disorders
Hypoglycemic Agents
Physiological Effects of Drugs
Hypolipidemic Agents
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents