Effect of Nicotinic Acid on Adipose Tissue Inflammation in Obese Subjects
Information source: University Hospital, Toulouse
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
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
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.
Clinical Details
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.
Eligibility
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
Locations and Contacts
Centre d'Investigation Clinique, Purpan University Toulouse Hospital, Toulouse 31059, France
Additional Information
Starting date: January 2010
Last updated: October 22, 2012
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