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

Study Overview
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Brief Summary
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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.

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

Conditions
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Hypercholesterolemia, Dyslipidemia

Intervention / Treatment
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* Drug: Simvastatin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 30 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: Double


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypercholesterolemia, Dyslipidemia, simvastatin, Zocor