Hypoalphalipoproteinemia Clinical Trial
Official title:
Short-term Effect of Extended-release Niacin With and Without the Addition of Laropiprant on Endothelial Function
Individuals with reduced plasma concentration of high-density lipoprotein (HDL) cholesterol are more susceptible to oxidative stress and often present reduced endothelial function, which has been mainly related to this susceptibility. Studies in animal and cell models have demonstrated that niacin activates both GPR-109A in leukocytes and heme oxygenase-1 (HO-1) pathway promoting strong anti-inflammatory and anti-oxidative effects. . In this context, the aim of this study was to investigate the short-term effect of niacin on endothelial function and verify the existence of interaction of PGD2 receptor antagonist, i.e. laropiprant (LRPT), in subjects with low HDL-cholesterol (HDL -C).
Study design and treatments The study was randomized, double-blind, controlled, using a
2-way crossover design with both treatment periods and washout time lasting 7 days. Subjects
were allocated by simple randomization to extended-release niacin 1g/day alone (ERN, Metri,
Libbs Farmacêutica, São Paulo, Brazil) or niacin associated with LRPT 1g/20mg (ERN/LRPT,
Cordaptive, Merck, São Paulo, Brazil). Medications were kindly supplied by Libbs and Merck.
Plasma samples and brachial artery reactivity were obtained at baseline, 7th day of
treatment 1, 7th day after washout and 7th day of treatment 2.
Study Measurements The following blood measurements were performed using the Modular Hitachi
system and Roche Diagnostics (Mannheim, Germany) reagents: glucose (GOD-PAP), triglycerides
(TG)(GPO-PAP), HDL-C (HDL-C plus 3rd generation) and C-reactive protein (CRP)
(high-sensitivity CRP, Cardiophase, Dade Behring, Marburg, Germany). LDL cholesterol was
calculated by the Friedewald formula. HDL size was measured by laser scattering (Zetasizer -
Nanoseries DTS 1060, Malvern Instruments, Worcestershire, UK). Total and direct bilirrubin
was measured by the Jendrassik-Grof method (Roche/Hitachi analyzer).
The cholesteryl ester transfer protein activity was measured by an endogenous assay.
Aliquots of the whole plasma (in which LCAT activity was inhibited by DTNB 9 μL/mL) were
added to HDL-[3H]cholesteryl ester fractions and simultaneously incubated at 4°C and 37°C
for 4h. Apo-B containing lipoproteins, present in the incubation mixture, were then
precipitated; the CE radioactivity in the supernatant represented the net rate at which CE
mass was transferred and values expressed as percent of [3H] cholesteryl ester transferred/4
hours depended upon the plasma concentrations of HDL, TG-rich lipoproteins and CETP
simultaneously.
Endothelial-dependent vasodilation was assessed by ischemia-induced reactive hyperemia.
Briefly, after 12-hour overnight fasting patients were examined at 8 a.m. in a quiet room at
22ºC by using a ultrasound equipment Vivid i (GE Healthcare, Wauwatosa, WI, USA) with a
high-resolution (up to 13 MHz) vascular probe (12l-RS, GE Healthcare, Wauwatosa, WI, USA) in
B-mode. The cardiac cycles were monitored simultaneously by electrocardiography coupled to
the equipment. Flow-mediated dilation (FMD) was assessed after 5-minutes inflation of a cuff
placed below the transducer, 50 mm Hg above the systolic blood pressure. Two-dimensional
images of the brachial artery were obtained during 5 minutes from the longitudinal axis
approximately 5-10 cm above the antecubital fossa. The maximum expansion of the diameter of
the brachial artery was measured in triplicate at the peak of the T wave of the cardiac
cycle before the interruption of the flow and post deflation.
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Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT01342666 -
Tomato Consumption and High Density Lipoprotein-cholesterol
|
N/A |