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

This study has been completed.
Sponsor:
Collaborators:
Institut National de la Santé Et de la Recherche Médicale, France
GlaxoSmithKline
Information provided by:
Centre de Recherche en Nutrition Humaine Rhone-Alpe
ClinicalTrials.gov Identifier:
NCT01216956
First received: October 5, 2010
Last updated: October 6, 2010
Last verified: October 2010
  Purpose

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

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double-Blind
Primary Purpose: Basic Science
Official Title: Metabolic Effects of an 8 Week Niaspan Treatment in Patients With Abdominal Obesity and Mixed Dyslipidemia

Resource links provided by NLM:


Further study details as provided by Centre de Recherche en Nutrition Humaine Rhone-Alpe:

Primary Outcome Measures:
  • Evolution of non-esterified fatty acid and triglycerides concentrations over time [ Time Frame: After 42 and 56 days of placebo or nicotinic acid treatment ] [ Designated as safety issue: No ]

    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 [ Time Frame: After 53 days of placebo or nicotinic acid treatment ] [ Designated as safety issue: No ]
    Euglycemic Hyperinsulinemic clamp with glucose tracer infusion

  • Lipoproteins metabolism [ Time Frame: After 53 days of placebo or nicotinic acid treatment ] [ Designated as safety issue: No ]
    Stable Isotopic tracer infusion (d3-leucine, 13C-acétate, d5-glycerol)

  • Lipid profile [ Time Frame: Before and after placebo or nicotinic acid treatment ] [ Designated as safety issue: No ]
    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)


Enrollment: 24
Study Start Date: September 2006
Study Completion Date: March 2010
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01216956

Locations
France
Centre de Recherche en Nutrition Humaine
Nantes, France
Sponsors and Collaborators
Centre de Recherche en Nutrition Humaine Rhone-Alpe
Institut National de la Santé Et de la Recherche Médicale, France
GlaxoSmithKline
Investigators
Principal Investigator: Michel Krempf, PhD, MD Institut National de la Santé Et de la Recheche Médiacle
  More Information

No publications provided

Responsible Party: Michel Krempf, Institut National de la Santé Et de la Recherche Médicale, France
ClinicalTrials.gov Identifier: NCT01216956     History of Changes
Other Study ID Numbers: NIASPAN-C05-36
Study First Received: October 5, 2010
Last Updated: October 6, 2010
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: Institutional Ethical Committee

Keywords provided by Centre de Recherche en Nutrition Humaine Rhone-Alpe:
extended release nicotinic acid
non esterified fatty acid (NEFA)
insulin resistance
Cholesteryl ester transfer protein (CETP)
High density lipoprotein cholesterol

Additional relevant MeSH terms:
Dyslipidemias
Obesity, Abdominal
Insulin Resistance
Lipid Metabolism Disorders
Metabolic Diseases
Obesity
Overnutrition
Nutrition Disorders
Hyperinsulinism
Glucose Metabolism Disorders
Nicotinic Acids
Niacin
Niacinamide
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Vasodilator Agents
Cardiovascular Agents
Therapeutic Uses
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents

ClinicalTrials.gov processed this record on April 17, 2014