Low HDL Cholesterol Clinical Trial
Official title:
Association Between HDL Functions and Atherosclerotic Burden in Healthy Individuals
This is a study of HDL function in healthy individuals classified in three groups according to their HDL-cholesterol levels (Low HDL-C, Intermediate HDl-C and High HDL-C), with the purpose of investigating which characteristics of the HDL particle might be associated to atherosclerotic burden, characterized by carotid intima-media thickness above 1mm.
Selection: Study participants are initially selected trough the evaluation of consecutive
lipid profiles from individuals who spontaneously seek governmental primary care centers of
the city of Campinas, Sao Paulo, Brazil. Telephone-based screening interviews are performed,
followed by in-person clinical evaluation and blood exams.
Biochemical analyses: Glucose, triglycerides, HDL-C and c-reactive protein (CRP) are
measured in an automated Modular® Analytics Evo (Roche Diagnostics, Burgess Hill, West
Sussex, UK), using Roche Diagnostics® reagents (Mannheim, Germany). LDL-cholesterol is
calculated by the Friedewald formula. Serum insulin levels are measured using ELISA
(Millipore, Massachusetts, USA). The Homeostasis Model Assessment (HOMA) Calculator version
2.2 (University of Oxford, UK) is used to estimate insulin sensitivity. Apolipoproteins A-I
and B-100 and lipoprotein (a) are determined by nephelometry in an automated system and
reagents from Dade-Behring® (Marburg, Germany).
Carotid artery ultrasound: Carotid artery atherosclerosis is estimated by using
high-resolution B-mode ultrasound, at the posterior wall of the common carotid artery.
Lipoprotein isolation: HDL from each study participant is isolated from plasma, through
ultracentrifugation (Beckman Coulter Inc., Palo Alto, USA).
HDL chemical composition: Using commercially available enzymatic kits, HDL content of total
proteins, total cholesterol, free cholesterol, phospholipids, triglycerides and
apolipoprotein A-I are measured. Cholesteryl ester (CE) is calculated as the difference
between total cholesterol and free cholesterol times 1.67. HDL molar concentration is
estimated based on particle total mass and molecular weight.
HDL physical-chemical characterization: HDL particle size is determined using dynamic light
scattering, and zeta potential using laser Doppler micro-electrophoresis.
Determination of proteins involved in HDL metabolism: Cholesteryl ester transfer protein,
phospholipids transfer protein, lipoprotein lipase, hepatic lipase and lecithin:cholesterol
acyl transferase activities are determined trough radiometric exogenous assays.
HDL functions: Cholesterol efflux capacity, antioxidant activity, susceptibility to
oxidation, anti-inflammatory activity and platelet aggregation inhibition are measured using
straightforward and consolidated methodologies.
Statistical Analyses: Differences between groups are evaluated using ANOVA or
Kruskal-Wallis, with Bonferroni's post-hoc multiple comparison analysis, according to
variable distribution. Chi-Square is used to compare categorical data. Analysis of
covariance (ANCOVA) adjusted for confounding variables is also used, after checking
variables with histograms, normality plots, and residual scatter plots that tested for
linearity, normality, and variance. Pearson's correlation test is used to assess the
relationships between variables. A two-sided p-value of 0.05 is considered significant.
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Observational Model: Case Control, Time Perspective: Cross-Sectional
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT00156169 -
The Effect of the Alga Dunaliella Bardawil as a Source of 9-cis Retinoic Acid on Lipid Profile in Fibrate Treated Patients.
|
Phase 3 |