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

October 6, 2010 updated by: Centre de Recherche en Nutrition Humaine Rhone-Alpe
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

24

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Nantes, France
        • Centre de Recherche en Nutrition Humaine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: BASIC_SCIENCE
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evolution of non-esterified fatty acid and triglycerides concentrations over time
Time Frame: 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.
After 42 and 56 days of placebo or nicotinic acid treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Insulin sensitivity after treatment
Time Frame: After 53 days of placebo or nicotinic acid treatment
Euglycemic Hyperinsulinemic clamp with glucose tracer infusion
After 53 days of placebo or nicotinic acid treatment
Lipoproteins metabolism
Time Frame: After 53 days of placebo or nicotinic acid treatment
Stable Isotopic tracer infusion (d3-leucine, 13C-acétate, d5-glycerol)
After 53 days of placebo or nicotinic acid treatment
Lipid profile
Time Frame: 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)
Before and after placebo or nicotinic acid treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centre de Recherche en Nutrition Humaine Rhone-Alpe

Collaborators

GlaxoSmithKline
Institut National de la Santé Et de la Recherche Médicale, France

Investigators

  • Principal Investigator: Michel Krempf, PhD, MD, Institut National de la Santé Et de la Recheche Médiacle

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2006

Primary Completion (ACTUAL)

June 1, 2009

Study Completion (ACTUAL)

March 1, 2010

Study Registration Dates

First Submitted

October 5, 2010

First Submitted That Met QC Criteria

October 6, 2010

First Posted (ESTIMATE)

October 7, 2010

Study Record Updates

Last Update Posted (ESTIMATE)

October 7, 2010

Last Update Submitted That Met QC Criteria

October 6, 2010

Last Verified

October 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NIASPAN-C05-36

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Insulin Sensitivity

Clinical Trials on Extended-release nicotinic acid versus placebo

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Bahamas

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe