Pharmacological Regulation of Fat Transport in Metabolic Syndrome

Study Overview
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Brief Summary
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The purpose of this study is to determine whether atorvastatin and fenofibrate are effective in the treatment of lipid disorders in obese, insulin resistant subjects.

Detailed Description
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Insulin resistance is a heterogeneous metabolic disorder of complex etiology. It underpins dyslipoproteinemia, a key feature of the metabolic syndrome (MetS) that independently predicts cardiovascular disease (CVD). Hypertriglyceridemia, the most consistent lipid disorder in subjects with obesity and type 2 diabetes mellitus, is chiefly a consequence of overproduction and delayed clearance of triglyceride-rich lipoproteins (TRLs). Although the precise mechanisms involved are incompletely understood, experimental and clinical evidence suggests that elevated apolipoprotein (apo) C-III may play a crucial role in the dysregulation of TRL metabolism. investigating the effects of these agents on VLDL-apoC-III kinetics. In this study, we aimed to examine the effect of two lipid-regulating agents, atorvastatin and fenofibrate on VLDL-apoC-III transport. We hypothesized that atorvastatin and fenofibrate would have similar effects on apoC-III transport by decreasing the production and increasing the catabolism of VLDL-apoC-III.

Official Title
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Regulation of Lipoprotein Kinetics by Atorvastatin and Fenofibrate With the Metabolic Syndrome

Conditions
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Obesity, Lipid Disorders, Hypertriglyceridemia, Cardiovascular Disease

Intervention / Treatment
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* Drug: Atorvastatin and fenofibrate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: any three of the followings waist circumference >102cm triglycerides >1.7 mmol/L HDL-cholesterol <1.05 mmol/L blood glucose >6.1 mmol/L blood pressure >130/85mmHg Exclusion Criteria: plasma cholesterol >7mmo/L triglycerides >4.5mmo/L diabetes mellitus (defined by oral glucose tolerance test) CVD consumption of >30g alcohol/day use of agents affecting lipid metabolism APOE2/E2 genotype, macroproteinuria creatinaemia (>120umol/L) hypothyroidism abnormal liver and muscle enzymes.

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Male

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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: P<br>placebo group | Drug: Atorvastatin and fenofibrate<br>* atorvastatin (40mg/day) fenofibrate (200mg/day)<br>* Other names: Lofibra;|
| Active Comparator: Feno<br>Fenofibrate | Drug: Atorvastatin and fenofibrate<br>* atorvastatin (40mg/day) fenofibrate (200mg/day)<br>* Other names: Lofibra;|
| Active Comparator: ATV<br>Atorvastatin | Drug: Atorvastatin and fenofibrate<br>* atorvastatin (40mg/day) fenofibrate (200mg/day)<br>* Other names: Lofibra;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| VLDL-apoC-III transport rate |  | 5 weeks |