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

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

Study Overview

• Status: Completed
• 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

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 03722
    • Division of Cardiology, Department of Internal Medicine,

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Atorvastatin 20 mg; lipid lowering treatment	Drug: Atorvastatin 20 mg; 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.
Experimental: Cholestyramine 8 g; lipid lowering treatment	Drug: Cholestyramine 8 g; 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.
Experimental: Omega-3 (EPA+DHA) 2 g; lipid lowering treatment	Drug: Omega-3 2g; 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.
Experimental: Atorvastatin 5 mg + Ezetimibe 10 mg; lipid lowering treatment	Drug: Concurrent with Atorvastatin 5 mg + Ezetimibe 10 mg; 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.
Active Comparator: Life style modification for management of dyslipidemia	Behavioral: Lifestyle modification; 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.

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

Collaborators and Investigators

• Sponsor: Yonsei University

Publications and helpful links

General Publications

• Lee CJ, Choi S, Cheon DH, Kim KY, Cheon EJ, Ann SJ, Noh HM, Park S, Kang SM, Choi D, Lee JE, Lee SH. Effect of two lipid-lowering strategies on high-density lipoprotein function and some HDL-related proteins: a randomized clinical trial. Lipids Health Dis. 2017 Feb 28;16(1):49. doi: 10.1186/s12944-017-0433-6.

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2014
• Primary Completion (Actual): May 23, 2016
• Study Completion (Actual): May 23, 2016

Study Registration Dates

• First Submitted: October 17, 2016
• First Submitted That Met QC Criteria: October 21, 2016
• First Posted (Estimate): October 24, 2016

Study Record Updates

• Last Update Posted (Actual): July 18, 2018
• Last Update Submitted That Met QC Criteria: July 15, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Dyslipidemias; Hyperlipidemias; Hyperlipoproteinemias; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin; Ezetimibe; Cholestyramine Resin
• Other Study ID Numbers: 4-2013-0281

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO