Clinical Trial: Short-term Effect of Extended-release Niacin on Endothelial Function.

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Short-term Effect of Extended-release Niacin With and Without the Addition of Laropiprant on Endothelial Function

Brief Summary: 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).

Detailed Summary:

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 si
Sponsor: University of Campinas, Brazil

Current Primary Outcome: The short-term effect of niacin on endothelial function. [ Time Frame: 7 days ]

Endothelial-dependent vasodilation was assessed by ischemia-induced reactive hyperemia of the brachial artery by using an ultrasound equipment


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Plasma C-reactive protein levels [ Time Frame: 7 days ]
    Systemic inflammatory activity as estimated by the plasma concentration of C-reactive protein
  • HDL-C and HDL size [ Time Frame: 7 days ]
    Plasma concentration of high-density lipoprotein (HDL) cholesterol and HDL size


Original Secondary Outcome: Same as current

Information By: University of Campinas, Brazil

Dates:
Date Received: September 10, 2013
Date Started: March 2012
Date Completion:
Last Updated: September 10, 2013
Last Verified: September 2013