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

Phase 1
Completed
Conditions
Hypercholesterolemia, Dyslipidemia
Interventions
Drug: Placebo
Registration Number
NCT00935259
Lead Sponsor
Merck Sharp & Dohme LLC
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
31
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 & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Simvastatin 40 mg first, then placeboSimvastatinSimvastatin 40 mg tablets once daily for 2 weeks followed by placebo for 2 weeks
Simvastatin 40 mg first, then placeboPlaceboSimvastatin 40 mg tablets once daily for 2 weeks followed by placebo for 2 weeks
Placebo first, then simvastatin 40 mg once dailyPlaceboPlacebo for 2 weeks followed by simvastatin 40 mg once daily for 2 weeks
Placebo first, then simvastatin 40 mg once dailySimvastatinPlacebo for 2 weeks followed by simvastatin 40 mg once daily for 2 weeks
Primary Outcome Measures
NameTimeMethod
Arachidonic Acid Level After 2 Weeks of Treatment2 weeks

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.

Secondary Outcome Measures
NameTimeMethod
Blood Linoleic Acid Levels2 weeks

Change in blood linoleic acid levels for Cholesterol Ester compared to placebo.

Change in Fasting Delta 5 Desaturase Enzyme Activity Compared to Placebo2 weeks

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.

Serum Proprotein Convertase Subtilisin-like/Kexin Type 9 (PCSK9) Level2 weeks

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).

Fasting Blood Lipidomic Levels After 2 Weeks of Treatment2 weeks

Change in fasting blood cholesterol ester, lysophosphatidylcholine, phosphatidylcholine, phosphatidylethanolamine, and triacylglycerol levels compared to placebo.

The mean reported was an adjusted mean.

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