Metabolic Effects of an 8 Week Niaspan Treatment in Patients With Abdominal Obesity and Mixed Dyslipidemia

Sponsor

Centre de Recherche en Nutrition Humaine Rhone-Alpe (Other)

Overall Status

Completed

CT.gov ID

NCT01216956

Collaborator

Institut National de la Santé Et de la Recherche Médicale, France (Other), GlaxoSmithKline (Industry)

Enrollment

Location

Arms

Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Insulin Sensitivity Lipoproteins Metabolism Non Esterified Fatty Acid Kinetics Lipid Profile	Drug: Extended-release nicotinic acid versus placebo	N/A

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

24 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Double

Primary Purpose:

Basic Science

Official Title:

Metabolic Effects of an 8 Week Niaspan Treatment in Patients With Abdominal Obesity and Mixed Dyslipidemia

Study Start Date :

Sep 1, 2006

Actual Primary Completion Date :

Jun 1, 2009

Actual Study Completion Date :

Mar 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Extended release nicotinic acid	Drug: Extended-release nicotinic acid versus placebo 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.
Placebo Comparator: Placebo	Drug: Extended-release nicotinic acid versus placebo 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.

Arm

Intervention/Treatment

Experimental: Extended release nicotinic acid

Drug: Extended-release nicotinic acid versus placebo

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.

Placebo Comparator: Placebo

Drug: Extended-release nicotinic acid versus placebo

Outcome Measures

Primary Outcome Measures

Evolution of non-esterified fatty acid and triglycerides concentrations over time [After 42 and 56 days of placebo or nicotinic acid treatment]
Twelve hours after ingestion of chronic treatment, measures of non esterified fatty acid and triglycerides concentrations were carried out during 480 minutes to assess acute and chronic treatment effect on lipolysis and on triglyceride concentration. To appreciate both acute and chronic effects, subjects received medicinal supplements in addition to their chronic treatment: On day 42, 500 mg of placebo to assess chronic nicotinic acid effect versus placebo effect On day 56, 500 mg of immediate-release nicotinic acid (INA) to assess acute versus chronic nicotinic acid effect.

Secondary Outcome Measures

Insulin sensitivity after treatment [After 53 days of placebo or nicotinic acid treatment]
Euglycemic Hyperinsulinemic clamp with glucose tracer infusion
Lipoproteins metabolism [After 53 days of placebo or nicotinic acid treatment]
Stable Isotopic tracer infusion (d3-leucine, 13C-acétate, d5-glycerol)
Lipid profile [Before and after placebo or nicotinic acid treatment]
Measure of lipoproteins (VLDL, IDL, LDL, HDL) - characterization of lipoprotein's subfraction Measure of enzymatic activity of cholesteryl ester transfer protein (CETP), phospholipid transfer protein (PLTP) and lecithin cholesterol acyl transferase (LCAT)