Effect of a Fibrate and a Statin on Endothelial Dysfunction

Study Overview
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Brief Summary
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The study will compare the effect of atorvastatin to the effect of fenofibrate on endothelial function in patients with diabetes mellitus or the metabolic syndrome.

Detailed Description
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The study will compare the effect of atorvastatin to the effect of fenofibrate on endothelial function in patients with diabetes mellitus or the metabolic syndrome. The study is a double blind, placebo controlled, crossover study with the order of treatment randomized. Patients will receive each treatment for 8 weeks with a 1 week rest period between treatment periods. Endothelial function will be tested using non-invasive techniques before and after each treatments. A total of 40 subjects with diabetes or the metabolic syndrome will be enrolled at Boston Medical Center.

Official Title
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Effect of a Fibrate (Fenofibrate) and a Statin (Atorvastatin) and on Endothelial Dysfunction in Diabetes Mellitus and the Metabolic Syndrome

Conditions
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Diabetes Mellitus, Metabolic Syndrome

Intervention / Treatment
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* Drug: Fenofibrate
* Drug: Atorvastatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age greater than 30 years Adult-onset DM (defined as fasting glucose greater than 125 mg/dl or by ongoing treatment with an oral hypoglycemic agent) or metabolic syndrome (defined as at least 3 of the following: 1. HDL less than 40 mg/dl for men or less than 50 mg/dl for women; 2. triglycerides greater than 150 mg/dl; 3. waist circumference greater than 40 inches for men and greater than 35 inches for women; 4. fasting glucose greater than 100 mg/dl). LDL cholesterol level less than 140 mg/dl Able to provide informed consent and complete study procedures Exclusion Criteria: Change in therapy for glucose control or blood pressure less than 1 month before entry Hemoglobin A1C greater than 8.0%. Renal insufficiency (serum creatinine greater than 1.6 mg/dl in men or 1.5 mg/dl in women. Any investigational drug less than 1 month before entry. Pregnancy (excluded by urine pregnancy test at study entry with ongoing use of reliable form of birth control) or lactation Liver function tests or serum creatinine kinase (CK) greater than 3 times upper limit of normal. Clinically evident major illnesses or other problem that would make participation inappropriate Clinical history of symptomatic cholelithiasis Patients with coronary artery disease, peripheral arterial disease, or cerebral vascular disease will not be enrolled if they are currently taking lipid-lowering therapy Patients taking more than 40 mg/day of atorvastatin will be excluded. There is no ceiling level for patients taking fibrates.

Ages Eligible for Study
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Minimum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Fenofibrate First<br>Fenofibrate 145 mg/day for 8 weeks First and Atorvastatin 20 mg/day for 8 weeks Second | Drug: Fenofibrate<br>* 140 mg/day for 8 weeks<br>* Other names: Tricor;Drug: Atorvastatin<br>* 20 mg/day for 8 weeks<br>* Other names: Lipitor;|
| Active Comparator: Atorvastatin First<br>Atorvastatin 20 mg/day for 8 weeks First and Fenofibrate 145 mg/day for 8 weeks Second | Drug: Fenofibrate<br>* 140 mg/day for 8 weeks<br>* Other names: Tricor;Drug: Atorvastatin<br>* 20 mg/day for 8 weeks<br>* Other names: Lipitor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brachial Artery Flow-mediated Dilation | Endothelial function was assessed as brachial artery flow-mediated dilation (FMD) using ultrasound. FMD is calculated as the difference in brachial diameter during hyperemic flow and brachial diameter at baseline divided by brachial diameter at baseline and expressed as percent dilation. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Lipids | Effect of the intervention on total cholesterol, HDL, and triglycerides | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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endothelium, obesity, diabetes mellitus, dyslipidemia