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

Not Applicable

Completed

• Conditions: Insulin Sensitivity; Lipoproteins Metabolism; Non Esterified Fatty Acid Kinetics; Lipid Profile
• Interventions: Drug: Extended-release nicotinic acid versus placebo

• Registration Number: NCT01216956
• Lead Sponsor: Centre de Recherche en Nutrition Humaine Rhone-Alpe

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.

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 Timeline

• Study Start: 2006-09
• Primary Completion: 2009-06
• Study Completion: 2010-03
• Status Verified: 2010-10
• Study First Submitted: 2010-10-05
• Study First Submitted QC: 2010-10-06
• Last Update Submitted: 2010-10-06
• Study First Posted: 2010-10-07
• Last Update Posted: 2010-10-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 24

Inclusion Criteria

• Waist circumference > 94cm
• Triglyceride concentration between 150mg/dL and 400mg/dL
• HDL-c < 60mg/dL
• Body mass index: 27 to 35 kg/m²

Exclusion Criteria

• cancer
• diabetes mellitus
• hepatic, renal or digestive disorder
• hypertension
• chronic medical treatment interfering on lipids parameters

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Extended release nicotinic acid	Extended-release nicotinic acid versus placebo	-
Placebo	Extended-release nicotinic acid versus placebo	-

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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)

Trial Locations

Locations (1)

Centre de Recherche en Nutrition Humaine; 🇫🇷 Nantes, France