Clinical trial NCT01216956: Metabolic Effects of an 8 Week Niaspan Treatment in Patients With Abdominal Obesity and Mixed Dyslipidemia
Official title: Metabolic Effects of an 8 Week Niaspan Treatment in Patients With Abdominal Obesity and Mixed Dyslipidemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Insulin Sensitivity
Lipoproteins Metabolism
Non Esterified Fatty Acid Kinetics
Lipid Profile
Keywords: extended release nicotinic acid
non esterified fatty acid (NEFA)
insulin resistance
Cholesteryl ester transfer protein (CETP)
High density lipoprotein cholesterol
Lead sponsor: Centre de Recherche en Nutrition Humaine Rhone-Alpe
Sponsor class: OTHER
Collaborators: name: Institut National de la Santé Et de la Recherche Médicale, France
name: GlaxoSmithKline
First posted: 2010-10-07
Enrollment: 24
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Evolution of non-esterified fatty acid and triglycerides concentrations over time
timeFrame: After 42 and 56 days of placebo or nicotinic acid treatment
Secondary outcomes:
measure: Insulin sensitivity after treatment
timeFrame: After 53 days of placebo or nicotinic acid treatment
measure: Lipoproteins metabolism
timeFrame: After 53 days of placebo or nicotinic acid treatment
measure: Lipid profile
timeFrame: Before and after placebo or nicotinic acid treatment
Other outcomes:
Locations:
city: Nantes
country: France
facility: Centre de Recherche en Nutrition Humaine
Study officials:
affiliation: Institut National de la Santé Et de la Recheche Médiacle
name: Michel Krempf, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Blanchard V, Ramin-Mangata S, Billon-Crossouard S, Aguesse A, Durand M, Chemello K, Nativel B, Flet L, Chetiveaux M, Jacobi D, Bard JM, Ouguerram K, Lambert G, Krempf M, Croyal M. Kinetics of plasma apolipoprotein E isoforms by LC-MS/MS: a pilot study. J Lipid Res. 2018 May;59(5):892-900. doi: 10.1194/jlr.P083576. Epub 2018 Mar 14.
citation: Ferchaud-Roucher V, Croyal M, Moyon T, Zair Y, Krempf M, Ouguerram K. Plasma Lipidome Analysis by Liquid Chromatography-High Resolution Mass Spectrometry and Ion Mobility of Hypertriglyceridemic Patients on Extended-Release Nicotinic Acid: a Pilot Study. Cardiovasc Drugs Ther. 2017 Jun;31(3):269-279. doi: 10.1007/s10557-017-6737-y.