Metabolic Effects of an 8 Week Niaspan Treatment in Patients With Abdominal Obesity and Mixed Dyslipidemia
Condition: Insulin Sensitivity; Lipoproteins Metabolism; Non Esterified Fatty Acid Kinetics; Lipid Profile
MeSH terms: Dyslipidemias; Insulin Resistance; Obesity, Abdominal
Study type: Interventional

Summary: 
      Nicotinic acid (Niacin) has been used for many years for the treatment of dyslipidemia.
      Indeed Niacin decreases triglycerides (TG) and low density lipoprotein cholesterol (LDL-c)
      but more importantly increases high density lipoprotein cholesterol (HDL-c). Although the
      drug has been used for so long, its precise mechanism of action remains elusive. The aim of
      this study was to characterise the metabolic changes induced by 8 week treatment with Niacin
      in dyslipidemic, overweight patients. The importance of the inhibition of lipolysis on the
      overall lipid effects of niacin will be studied. In order to get a very comprehensive view of
      all metabolic activities of niacin, this study will investigate the potential effects of
      niacin on Glucose metabolism, lipid and lipoprotein turnover, quantitative changes in
      lipoproteins and key enzymes involved in lipid metabolism.
    

Detailed description: 
      24 patients will be included in a double blind placebo controlled cross-over 8 week study
      comparing placebo to Niaspan (a long release formulation of niacin). In order to prevent any
      drop out linked to the flushing side effect of niacin, patient will take aspirin (300mg)
      prior to treatment throughout the study duration. The study will include at start and end of
      each arm, a full lipoproteins quantification as well as a measure of enzymes involved in
      lipid metabolism. On day 42 and 56 of each period, after an administration of either placebo
      or 500mg of immediate release niacin respectively, changes in plasma free fatty acid levels
      will be measured for 8hours in order to assess potential loss of activity of niacin over time
      upon chronic treatment with niaspan. Half of the patient will have an exploration of their
      glucose metabolism using hyperinsulinic clamp technique, whereas in the other half a
      metabolic turnover study using stable isotopes will focus on their lipoproteins,
      triglycerides and cholesterol handling. These explorations will be done at the end of each
      treatment period.
    

Intervention name(s): Extended-release nicotinic acid versus placebo
Intervention type(s): Drug
Intervention description(s): Voluntary men with mixed dyslipidemia and abdominal obesity will receive extended release nicotinic acid. The dose of niaspan will be up-titrated for 3 weeks starting at 500 mg/d in order to reach 2g/d at start of week 4 dose which will be continued until the end of week 8. After a wash-out period of 3 weeks, they will receive placebo for 8 weeks. According to their randomization arm, subjects will receive either in first place placebo followed by extended release nicotinic acid or the opposite.
Intervention MeSH terms: Nicotinic Acids; Niacin; Niacinamide
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double
Primary purpose: Basic Science
Keywords: extended release nicotinic acid; non esterified fatty acid (NEFA); insulin resistance; Cholesteryl ester transfer protein (CETP); High density lipoprotein cholesterol