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

Insulin Sensitivity Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01216956
• Other study ID #: NIASPAN-C05-36
• Status: Completed
• Phase: N/A
• First received: October 5, 2010
• Last updated: October 6, 2010
• Start date: September 2006
• Est. completion date: March 2010

Study information

• Verified date: October 2010
• Source: Centre de Recherche en Nutrition Humaine Rhone-Alpe
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)France: Institutional Ethical Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: March 2010
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 65 Years

Eligibility

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

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double-Blind, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Dyslipidemias
• Insulin Sensitivity
• Lipid Profile
• Lipoproteins Metabolism
• Non Esterified Fatty Acid Kinetics
• Obesity, Abdominal

Intervention

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.

Locations

Country	Name	City	State
France	Centre de Recherche en Nutrition Humaine	Nantes

Sponsors (3)

Lead Sponsor	Collaborator
Centre de Recherche en Nutrition Humaine Rhone-Alpe	GlaxoSmithKline, Institut National de la Santé Et de la Recherche Médicale, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evolution of non-esterified fatty acid and triglycerides concentrations over time	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.	After 42 and 56 days of placebo or nicotinic acid treatment	No
Secondary	Insulin sensitivity after treatment	Euglycemic Hyperinsulinemic clamp with glucose tracer infusion	After 53 days of placebo or nicotinic acid treatment	No
Secondary	Lipoproteins metabolism	Stable Isotopic tracer infusion (d3-leucine, 13C-acétate, d5-glycerol)	After 53 days of placebo or nicotinic acid treatment	No
Secondary	Lipid profile	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)	Before and after placebo or nicotinic acid treatment	No