Short-term Effect of Extended-release Niacin on Endothelial Function.
Condition: Hypoalphalipoproteinemia
MeSH terms: Hypoalphalipoproteinemias
Study type: Interventional
Phase: Phase 4

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 description: 
      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.
    

Intervention name(s): Niacin
Intervention type(s): Drug
Intervention description(s): 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).
Other intervention name(s): Nicotinic acid; Vitamin B3
Intervention MeSH terms: Niacin; Nicotinic Acids
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science
Keywords: Niacin; Endothelial function; Laropiprant; HDL