Clinical trial NCT01083329: Effect of Nicotinic Acid on Adipose Tissue Inflammation in Obese Subjects
Official title: Effect of Nicotinic Acid on Adipose Tissue Inflammation in Obese Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Obesity
Keywords: nicotinic acid
lipolysis
training program
adipose tissue inflammation
obese
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
First posted: 2010-03-09
Enrollment: 24
Sex: MALE
Minimum age (years): 25
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

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 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

Primary outcomes:
measure: Comparison of changes of AT inflammation will be measured by gene expression analysis
timeFrame: Visit 1(T0), Visit 2 (T+8 weeks of treatment) and Visit 3 (T+16 weeks of treatment)
Secondary outcomes:
measure: Comparison of changes in insulin sensitivity and glucose tolerance
timeFrame: Visit 1(T0), Visit 2 (T+8 weeks of treatment) and Visit 3 (T+16 weeks of treatment)
Other outcomes:
Locations:
city: Toulouse
country: France
facility: Centre d'Investigation Clinique, Purpan University Toulouse Hospital
Study officials:
affiliation: University Toulouse Hospital
name: Claire Thalamas
role: PRINCIPAL_INVESTIGATOR
References:
citation: Montastier E, Beuzelin D, Martins F, Mir L, Marques MA, Thalamas C, Iacovoni J, Langin D, Viguerie N. Niacin induces miR-502-3p expression which impairs insulin sensitivity in human adipocytes. Int J Obes (Lond). 2019 Jul;43(7):1485-1490. doi: 10.1038/s41366-018-0260-5. Epub 2018 Nov 27.
citation: Bourlier V, Saint-Laurent C, Louche K, Badin PM, Thalamas C, de Glisezinski I, Langin D, Sengenes C, Moro C. Enhanced glucose metabolism is preserved in cultured primary myotubes from obese donors in response to exercise training. J Clin Endocrinol Metab. 2013 Sep;98(9):3739-47. doi: 10.1210/jc.2013-1727. Epub 2013 Jul 24.