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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT00186537
Other study ID # 79301
Secondary ID SPO 28829
Status Recruiting
Phase N/A
First received September 14, 2005
Last updated December 1, 2006
Start date September 2003
Est. completion date September 2010

Study information

Verified date December 2006
Source Stanford University
Contact Cynthia A Lamendola, MSN/ ANP
Phone 650-723-7024
Is FDA regulated No
Health authority United States: Food and Drug Administration
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 45
Est. completion date September 2010
Est. primary completion date
Accepts healthy volunteers Accepts Healthy Volunteers
Gender Both
Age group 30 Years to 65 Years
Eligibility 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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment


Related Conditions & MeSH terms


Intervention

Drug:
Rosiglitazone

Fenofibrate

Behavioral:
Weight Loss


Locations

Country Name City State
United States Stanford University Medical Center Stanford California

Sponsors (2)

Lead Sponsor Collaborator
Stanford University Abbott

Country where clinical trial is conducted

United States, 

References & Publications (3)

Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA. 2002 Jan 16;287(3):356-9. — View Citation

Laws A, Reaven GM. Evidence for an independent relationship between insulin resistance and fasting plasma HDL-cholesterol, triglyceride and insulin concentrations. J Intern Med. 1992 Jan;231(1):25-30. — View Citation

Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes. 1988 Dec;37(12):1595-607. Review. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Compare the effect of these three treatments on CVD risk factors.
Secondary Compare the effect of these three treatments on changes in endothelial function
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