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

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ClinicalTrials.gov Identifier: NCT00186537
Recruitment Status : Completed
First Posted : September 16, 2005
Results First Posted : May 5, 2016
Last Update Posted : January 12, 2017
Sponsor:
Collaborator:
Abbott
Information provided by (Responsible Party):
Gerald M Reaven, Stanford University

Tracking Information
First Submitted Date  ICMJE September 14, 2005
First Posted Date  ICMJE September 16, 2005
Results First Submitted Date  ICMJE April 1, 2016
Results First Posted Date  ICMJE May 5, 2016
Last Update Posted Date January 12, 2017
Study Start Date  ICMJE September 2003
Actual Primary Completion Date September 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 21, 2016)
  • Pre- and Post-Intervention Triglyceride Levels [ Time Frame: Baseline, 12 weeks ]
    Compare the change in mean triglyceride levels between groups after the interventions
  • 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
  • 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
Original Primary Outcome Measures  ICMJE
 (submitted: September 14, 2005)
Compare the effect of these three treatments on CVD risk factors.
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: September 14, 2005)
Compare the effect of these three treatments on changes in endothelial function
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Comparing Tricor, Avandia, or Weight Loss to Lower Cardiovascular Risk Factors in People With High Triglycerides.
Official Title  ICMJE Comparison Fenofibrate, Rosiglitazone, or Weight Loss to Decrease Cardiovascular Risk in Insulin Resistant Dyslipidemic Individuals.
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Insulin Resistance
  • Hypertriglyceridemia
Intervention  ICMJE
  • Drug: Rosiglitazone
    Other Name: avandia
  • Drug: Fenofibrate
    Other Name: tricor
  • Behavioral: Weight Loss
Study Arms  ICMJE
  • Active Comparator: fenofibrate
    160 mg daily for 12 weeks
    Intervention: Drug: Fenofibrate
  • Active Comparator: rosiglitazone
    4 mg/daily 4 weeks followed by 4 mg 2 x daily for 8 weeks
    Intervention: Drug: Rosiglitazone
  • Active Comparator: calorie restricted diet
    calorie restricted to achieve 0.5 kg weight loss/week x 12 weeks
    Intervention: Behavioral: Weight Loss
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 21, 2016)
47
Original Enrollment  ICMJE
 (submitted: September 14, 2005)
45
Actual Study Completion Date  ICMJE September 2008
Actual Primary Completion Date September 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 30 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00186537
Other Study ID Numbers  ICMJE 79301
SPO 28829
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Gerald M Reaven, Stanford University
Study Sponsor  ICMJE Stanford University
Collaborators  ICMJE Abbott
Investigators  ICMJE
Principal Investigator: Gerald M Reaven, MD Stanford University
PRS Account Stanford University
Verification Date November 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP