Effect of Nicotinic Acid on Adipose Tissue Inflammation in Obese Subjects

Condition(s) targeted: Obesity

Intervention: training (Behavioral); nicotinic acid (Drug); Placebo (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: University Hospital, Toulouse

Official(s) and/or principal investigator(s):
Claire Thalamas, Principal Investigator, Affiliation: University Toulouse Hospital

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.

Official title: Effect of Nicotinic Acid on Adipose Tissue Inflammation in Obese Subjects

Study design: Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Primary outcome: Comparison of changes of AT inflammation will be measured by gene expression analysis

Secondary outcome: Comparison of changes in insulin sensitivity and glucose tolerance

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.

Minimum age: 25 Years. Maximum age: 45 Years. Gender(s): Male.

Criteria:

Inclusion Criteria:

- Signature of informed consent form

- Age 25 to 45 year-old

- Male, insulin resistant obese subjects (30

- 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

Centre d'Investigation Clinique, Purpan University Toulouse Hospital, Toulouse 31059, France

Starting date: January 2010
Last updated: October 22, 2012