Effect of Nicotinic Acid on Adipose Tissue Inflammation in Obese Subjects (ANITA)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University Hospital, Toulouse
ClinicalTrials.gov Identifier:
NCT01083329
First received: February 25, 2010
Last updated: October 22, 2012
Last verified: October 2012
  Purpose

Our working hypothesis postulates that lipolysis is a determinant of inflammation in adipose tissue (AT). Inhibition of lipolysis, e.g. using the oldest normolipidemic drug, nicotinic acid, has proved valuable to combat the metabolic syndrome. Our proposal will determine whether part of the beneficial effects of this antilipolytic compound is due to a diminution of AT inflammation.

To this aim, the effect of nicotinic acid or placebo will be studied in male obese subjects with or without a training program which goal is to enhance lipolysis.


Condition Intervention Phase
Obesity
Behavioral: training
Drug: nicotinic acid
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Effect of Nicotinic Acid on Adipose Tissue Inflammation in Obese Subjects

Resource links provided by NLM:


Further study details as provided by University Hospital, Toulouse:

Primary Outcome Measures:
  • Comparison of changes of AT inflammation will be measured by gene expression analysis [ Time Frame: Visit 1(T0), Visit 2 (T+8 weeks of treatment) and Visit 3 (T+16 weeks of treatment) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Comparison of changes in insulin sensitivity and glucose tolerance [ Time Frame: Visit 1(T0), Visit 2 (T+8 weeks of treatment) and Visit 3 (T+16 weeks of treatment) ] [ Designated as safety issue: No ]

Enrollment: 24
Study Start Date: January 2010
Study Completion Date: June 2012
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: placebo
for 16 weeks
Behavioral: training
the last 8 weeks, the subjects will follow a training program calculated to optimize use of lipid
Drug: Placebo
Obese subjects will receive nicotinic acid or placebo for 16 weeks
Active Comparator: nicotinic acid

for 16 weeks :

  • week 1 = 375 mg per day,
  • week 2 = 500 mg per day,
  • week 3 = 750 mg per day,
  • week 4 = 1000 mg per day,
  • week 5 = 1500 mg per day,
  • weeks 6 to 16 = 2000 mg per day.
Behavioral: training
the last 8 weeks, the subjects will follow a training program calculated to optimize use of lipid
Drug: nicotinic acid
Obese subjects will receive nicotinic acid or placebo for 16 weeks

Detailed Description:

24 male obese insulin resistant subjects will receive nicotinic acid or placebo for 16 weeks. The last 8 weeks, the subjects will follow a training program calculated to optimize use of lipid. Insulin sensitivity and glucose tolerance will be assessed using, respectively, fasting-based estimates of insulin sensitivity (plasma and muscle) and oral glucose tolerance test. Plasma parameters of adipokines and, inflammatory and metabolic parameters will be determined. As an index of AT inflammation, the percentage and the phenotype of macrophages will be determined using flow cytometry of cells of the stromavascular fraction of subcutaneous AT. Macrophage infiltration will be investigated by light microscopy. The characterization of the inflammatory profile of AT will be completed by measurements of the expression of genes that are either specific markers of human AT macrophages or inflammatory and anti-inflammatory adipokines. This combination of approaches has never been carried out during a pharmacological intervention in humans. The following points will be addressed:

  • determine the influence of lipolysis on AT inflammation, specifically on macrophage activation and adipokine production.
  • examine the causal relationship between adipocyte FA metabolism, AT inflammation and insulin sensitivity.
  • establish whether the beneficial effect of antilipolytic drugs may be attributable at least in part to a decrease in AT inflammation.
  Eligibility

Ages Eligible for Study:   25 Years to 45 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signature of informed consent form
  • Age 25 to 45 year-old
  • Male, insulin resistant obese subjects (30<BMI<40 kg/m2),
  • Blood arterial pressure<140/90 mmHg

Exclusion Criteria:

  • History of cardiovascular disease
  • Treatment with drugs which can interfere with cardiovascular system and autonomic nervous system (i.e. beta blockers).
  • Treatment with nicotinic acid
  • Treatment with fibrates, statins, cholestyramine and ezetimibe
  • Treatment with thiazidics
  • Fasted hyperglycaemia > 1,26 g/l (Diabetes)
  • Triglycerides >5 g/l
  • Blood arterial pressure > 140/90 mm Hg
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01083329

Locations
France
Centre d'Investigation Clinique, Purpan University Toulouse Hospital
Toulouse, France, 31059
Sponsors and Collaborators
University Hospital, Toulouse
Investigators
Principal Investigator: Claire Thalamas University Toulouse Hospital
  More Information

No publications provided by University Hospital, Toulouse

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University Hospital, Toulouse
ClinicalTrials.gov Identifier: NCT01083329     History of Changes
Other Study ID Numbers: 0816302
Study First Received: February 25, 2010
Last Updated: October 22, 2012
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Toulouse:
nicotinic acid
lipolysis
training program
adipose tissue inflammation
obese

Additional relevant MeSH terms:
Inflammation
Pathologic Processes
Nicotinic Acids
Niacin
Niacinamide
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Therapeutic Uses
Vasodilator Agents
Cardiovascular Agents

ClinicalTrials.gov processed this record on September 16, 2014