Effect of Nicotinic Acid on Adipose Tissue Inflammation in Obese Subjects

NCT ID: NCT01083329

Last Updated: 2020-07-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-01-31
• Study Completion Date: 2012-06-30

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.

Conditions

Obesity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

placebo

for 16 weeks

Group Type: PLACEBO_COMPARATOR

training

Intervention Type: BEHAVIORAL

the last 8 weeks, the subjects will follow a training program calculated to optimize use of lipid

Placebo

Intervention Type: DRUG

Obese subjects will receive nicotinic acid or placebo for 16 weeks

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.

Group Type: ACTIVE_COMPARATOR

training

Intervention Type: BEHAVIORAL

the last 8 weeks, the subjects will follow a training program calculated to optimize use of lipid

nicotinic acid

Intervention Type: DRUG

Obese subjects will receive nicotinic acid or placebo for 16 weeks

Interventions

training

the last 8 weeks, the subjects will follow a training program calculated to optimize use of lipid

Intervention Type: BEHAVIORAL

nicotinic acid

Obese subjects will receive nicotinic acid or placebo for 16 weeks

Intervention Type: DRUG

Placebo

Obese subjects will receive nicotinic acid or placebo for 16 weeks

Intervention Type: DRUG

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

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Toulouse

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Claire Thalamas

Role: PRINCIPAL_INVESTIGATOR

University Toulouse Hospital

Locations

Centre d'Investigation Clinique, Purpan University Toulouse Hospital

Toulouse, , France

Countries

France

References

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.

Reference Type: RESULT

PMID: 30482933 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 23884778 (View on PubMed)

Other Identifiers

0816302

Identifier Type: -

Identifier Source: org_study_id