Effect of Lipid Modifying Drugs on HDL Function in Patients With Hyperlipidemia

Study Overview
=================
Brief Summary
-----------------
1) to test HDL function comprehensively in healthy and diseased individuals; 2) to evaluate if this test correlates with cardiovascular risk, independent of traditional risk factors; 3) and to differentiate effects of lipid-modifying or antiatherosclerotic drugs on HDL function and composition

Conditions
-----------------
Hyperlipidemia

Intervention / Treatment
-----------------
* Drug: Atorvastatin 20 mg
* Drug: Cholestyramine 8 g
* Drug: Omega-3 2g
* Drug: Concurrent with Atorvastatin 5 mg + Ezetimibe 10 mg
* Behavioral: Lifestyle modification


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: The patients who meet the 2013 American College of Cardiology/American Heart Association criteria for receiving lipid-lowering therapy Aged over 20 Consent form signed Exclusion Criteria: pregnant or lactating women subjects with familial hypercholesterolemia uncontrolled hypertension or DM Thyroid dysfunction Active liver disease (transaminase or bilirubin > 1.5 x NL) Serum creatinine > 2 mg/dL Included in other clinical trials within 3 months using of other medication: fish oil, fibric acid derivatives, niacin, systemic corticosteroid, thiazolidinedione

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Atorvastatin 20 mg<br>lipid lowering treatment | Drug: Atorvastatin 20 mg<br>* The patients who meet the 2013 American College of Cardiology/American Heart Association criteria for receiving lipid-lowering therapy will be randomized into 5 groups.<br>|
| Experimental: Cholestyramine 8 g<br>lipid lowering treatment | Drug: Cholestyramine 8 g<br>* The patients who meet the 2013 American College of Cardiology/American Heart Association criteria for receiving lipid-lowering therapy will be randomized into 5 groups.<br>|
| Experimental: Omega-3 (EPA+DHA) 2 g<br>lipid lowering treatment | Drug: Omega-3 2g<br>* The patients who meet the 2013 American College of Cardiology/American Heart Association criteria for receiving lipid-lowering therapy will be randomized into 5 groups.<br>|
| Experimental: Atorvastatin 5 mg + Ezetimibe 10 mg<br>lipid lowering treatment | Drug: Concurrent with Atorvastatin 5 mg + Ezetimibe 10 mg<br>* The patients who meet the 2013 American College of Cardiology/American Heart Association criteria for receiving lipid-lowering therapy will be randomized into 5 groups.<br>|
| Active Comparator: Life style modification for management of dyslipidemia<br> | Behavioral: Lifestyle modification<br>* The patients who meet the 2013 American College of Cardiology/American Heart Association criteria for receiving lipid-lowering therapy will be randomized into 5 groups.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cholesterol efflux capacity (%) | [3H-cholesterol (µCi) in medium containing HDL/(3H-cholesterol {µCi} in medium containing HDL+µCi of 3H-cholesterol {µCi} in cells)] x 100 | Change of HDL functions from baseline to 8 weeks | 
| Endothelial NO production (Arbitrary unit) | measured with nitrate assay kit and expressed as relative amount compared to control (no HDL treatment sample) | up to 8 weeks | 
| VCAM-1 expression (Arbitrary unit) | western blotting of VCAM-1 protein and expressed as relative amount compared to control (no HDL treatment sample) | up to 8 weeks | 
| ROS generation (Arbitrary unit) | fluorescence intensity measurement using dichlorodihydrofluorescein diacetate and expressed as relative amount compared to control (no HDL treatment sample) | up to 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ApoA-I | quantitation of intensity of western blot and expresses as relative amount to control (no HDL treatment sample) | Change of HDL associated proteins from each patient at baseline and at 8 weeks | 
| ApoA-II | quantitation of intensity of western blot and expresses as relative amount to control (no HDL treatment sample) | Change of HDL associated proteins from each patient at baseline and at 8 weeks | 
| ApoC-I | quantitation of intensity of western blot and expresses as relative amount to control (no HDL treatment sample) | Change of HDL associated proteins from each patient at baseline and at 8 weeks | 
| ApoC-II | quantitation of intensity of western blot and expresses as relative amount to control (no HDL treatment sample) | Change of HDL associated proteins from each patient at baseline and at 8 weeks | 
| ApoC-III | quantitation of intensity of western blot and expresses as relative amount to control (no HDL treatment sample) | Change of HDL associated proteins from each patient at baseline and at 8 weeks |