Lipid Biomarker Study in Men With Dyslipidemia After Simvastatin Treatment (Study MK-0000-140)(COMPLETED)

A Randomized, Placebo Controlled Clinical Trial to Evaluate the Effects of Simvastatin Treatment on Measurements of Lipidomic Biomarkers in Men With Dyslipidemia

The purpose of this study was to provide human lipidomics standards with simvastatin treatment that were to be used for comparison with similar preclinical studies.

Study Overview

• Status: Completed
• Conditions: Hypercholesterolemia, Dyslipidemia
• Intervention / Treatment: Drug: Simvastatin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Participant is a Caucasian (including Hispanic) male
• Participant has a maximum waist size of 40 inches
• Participant does not currently use any lipid-altering medications
• Participant is in good health other than the diagnosis of dyslipidemia

Exclusion Criteria:

• Participant has had stomach ulcers within the last 3 months
• Participant has had a heart attack in the last 6 months or has angina
• Participant has chronic heart failure
• Participant has a history of stroke, seizures, or major neurological disorder
• Participant has a history of cancer
• Participant has a gastrointestinal condition that affects bowel movements
• Participant has type 1 or 2 diabetes

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Simvastatin 40 mg first, then placebo; Simvastatin 40 mg tablets once daily for 2 weeks followed by placebo for 2 weeks	Drug: Simvastatin; 40 mg once daily for 2 weeks; Other Names: Zocor; Drug: Placebo; Placebo, matching the simvastatin (40 mg) tablet as a single oral daily dose for 2 weeks
Placebo Comparator: Placebo first, then simvastatin 40 mg once daily; Placebo for 2 weeks followed by simvastatin 40 mg once daily for 2 weeks	Drug: Simvastatin; 40 mg once daily for 2 weeks; Other Names: Zocor; Drug: Placebo; Placebo, matching the simvastatin (40 mg) tablet as a single oral daily dose for 2 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Arachidonic Acid Level After 2 Weeks of Treatment	Arachidonic acid level (20:4n6) in the cholesterol ester lipid class. The mean reported was an adjusted mean, which was obtained from running a 2-period crossover model that had fixed treatment and period terms and a random participant term.	2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fasting Blood Lipidomic Levels After 2 Weeks of Treatment	Change in fasting blood cholesterol ester, lysophosphatidylcholine, phosphatidylcholine, phosphatidylethanolamine, and triacylglycerol levels compared to placebo. The mean reported was an adjusted mean.	2 weeks
Serum Proprotein Convertase Subtilisin-like/Kexin Type 9 (PCSK9) Level	Two days of standardized, pre-packaged meals were provided prior to the 10-hour fast required before blood collection. To assess how consumption of a meal would affect levels of plasma PCSK9, following each of the fasting blood draws, participants were asked to consume a high fat meal (heavy whipping cream + vanilla ice cream in a 1:4 ratio [dose = 162 g/m^2]) within 20 minutes. For the duration of the test, participants were to remain seated or recumbent until blood samples were drawn 4 h after meal completion. The mean reported was an adjusted mean (defined in first outcome measure).	2 weeks
Blood Linoleic Acid Levels	Change in blood linoleic acid levels for Cholesterol Ester compared to placebo.	2 weeks
Change in Fasting Delta 5 Desaturase Enzyme Activity Compared to Placebo	Change in fasting delta 5 desaturase enzyme activity compared to placebo. Delta 5 desaturase enzyme activity is defined as the ratios of C20:4n-6 to C20:3n-6 and C20:5n-3 to C20:4n-3.	2 weeks

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Chen F, Maridakis V, O'Neill EA, Hubbard BK, Strack A, Beals C, Herman GA, Wong P. The effects of simvastatin treatment on plasma lipid-related biomarkers in men with dyslipidaemia. Biomarkers. 2011 Jun;16(4):321-33. doi: 10.3109/1354750X.2011.561367. Epub 2011 Mar 21.

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Actual): October 1, 2009
• Study Completion (Actual): October 1, 2009

Study Registration Dates

• First Submitted: July 7, 2009
• First Submitted That Met QC Criteria: July 7, 2009
• First Posted (Estimate): July 8, 2009

Study Record Updates

• Last Update Posted (Estimate): October 8, 2015
• Last Update Submitted That Met QC Criteria: October 7, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: Hypercholesterolemia, Dyslipidemia, simvastatin, Zocor
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Simvastatin
• Other Study ID Numbers: 0000-140; 2009_609