Ignite Creation Date:
2024-05-05 @ 11:56 AM
Last Modification Date:
2024-10-26 @ 9:17 AM
Study NCT ID:
NCT00186537
Status:
COMPLETED
Last Update Posted:
2017-01-12
First Post:
2005-09-14
Brief Title:
Comparing Tricor Avandia or Weight Loss to Lower Cardiovascular Risk Factors in People With High Triglycerides
Sponsor:
Stanford University
Organization:
Stanford University
Study Overview
Official Title:
Comparison Fenofibrate Rosiglitazone or Weight Loss to Decrease Cardiovascular Risk in Insulin Resistant Dyslipidemic Individuals
Status:
COMPLETED
Status Verified Date:
2016-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Approximately 14 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 31 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 ΒΌ 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 TGHDL-C concentration ratio is as powerful a predictor of CVD if not more so than the more conventional total plasma cholesterolLDL-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 13rd of the population with the lowest TGHDL-C concentration ratio and presumably insulin sensitive Conversely if they were in the tertile with the highest plasma TGHDL-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 mgdL nor HDL-C 40 to 42 mgdL concentrations improved and both total 215 to 239 mgdL and LDL-C 118-142mgdL 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 fenofibrateROSI 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
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 mgdL nor HDL-C 40 to 42 mgdL concentrations improved and both total 215 to 239 mgdL and LDL-C 118-142mgdL 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 fenofibrateROSI 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| SPO 28829 | None | None | None |