Association Between HDL Functions and Atherosclerotic Burden in Healthy Individuals

Low HDL Cholesterol Clinical Trial

Official title:

Association Between HDL Functions and Atherosclerotic Burden in Healthy Individuals

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02106013
• Other study ID #: BHS2
• Status: Completed
• Phase: N/A
• First received: March 30, 2014
• Last updated: April 2, 2014
• Start date: April 2008
• Est. completion date: March 2014

Study information

• Verified date: April 2014
• Source: University of Campinas, Brazil
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: National Committee of Ethics in Research
• Study type: Observational

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 101
• Est. completion date: March 2014
• Est. primary completion date: November 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 20 Years to 75 Years

Eligibility

Inclusion Criteria:

• glucose <100 mg/dL

• Urea <71 mg/dL

• Creatinine < 1.20 mg/dL

• Uric acid <7.0 mg/dL

• Alanine aminotransferase <50 U/L

• Aspartate aminotransferase < 33 U/L

• Gamma-glutamyl transferase <71 U/L

• Alkaline phosphatase <129 U/L

• Thyroid stimulating hormone between 0.41 and 4.50 µUI/mL

• Free thyroxin between 0.9 and 1.8 ng/dL

Exclusion Criteria:

• Symptomatic cardiovascular disease

• LDL-cholesterol =130 mg/dL

• Triglycerides =150 mg/dL

• Metabolic syndrome

• BMI = 30 kg/m2

• Smoking habit

• Daily intake of alcohol >14g

• Regular use of medical treatments

Study Design

Observational Model: Case Control, Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Low HDL Cholesterol

Locations

Country	Name	City	State
Brazil	State University of Campinas	Campinas	Sao Paulo

Sponsors (3)

Lead Sponsor	Collaborator
University of Campinas, Brazil	Conselho Nacional de Desenvolvimento Científico e Tecnológico, Fundação de Amparo à Pesquisa do Estado de São Paulo

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cholesterol efflux capacity of HDL	This is a cross-sectional study and as such the cholesterol efflux capacity will be measured using the plasma sample collected at admission into the study	The analysis will be performed using plasma obtained at admission into the study	No
Secondary	Antioxidant activity of HDL	This is a cross-sectional study and as such the cholesterol efflux capacity will be measured using the plasma sample collected at admission into the study	The analysis will be performed using plasma obtained at admission into the study	No
Secondary	Susceptibility to oxidation of HDL	This is a cross-sectional study and as such the cholesterol efflux capacity will be measured using the plasma sample collected at admission into the study	The analysis will be performed using plasma obtained at admission into the study	No
Secondary	Anti-inflammatory activity of HDL	This is a cross-sectional study and as such the cholesterol efflux capacity will be measured using the plasma sample collected at admission into the study	The analysis will be performed using plasma obtained at admission into the study	No
Secondary	Platelet aggregation inhibition by HDL	This is a cross-sectional study and as such the cholesterol efflux capacity will be measured using the plasma sample collected at admission into the study	The analysis will be performed using plasma obtained at admission into the study	No