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

Sponsor

University Hospital, Toulouse (Other)

Overall Status

Completed

CT.gov ID

NCT01083329

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Obesity	Behavioral: training Drug: nicotinic acid Drug: Placebo	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

24 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Basic Science

Official Title:

Effect of Nicotinic Acid on Adipose Tissue Inflammation in Obese Subjects

Study Start Date :

Jan 1, 2010

Actual Primary Completion Date :

Jun 1, 2010

Actual Study Completion Date :

Jun 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

Comparison of changes of AT inflammation will be measured by gene expression analysis [Visit 1(T0), Visit 2 (T+8 weeks of treatment) and Visit 3 (T+16 weeks of treatment)]

Secondary Outcome Measures

Comparison of changes in insulin sensitivity and glucose tolerance [Visit 1(T0), Visit 2 (T+8 weeks of treatment) and Visit 3 (T+16 weeks of treatment)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

25 Years to 45 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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