high density lipoprotein turnover

Conditions: Obesity

Summary: the objective of the study is to evaluate the effect of rimonabant 20mg in comparison to placebo, on hdl and vldl lipoprotein kinetics, over a 12 months period. primary objectives: * to assess effect of rimonabant on hdl apoa-i fractional catabolic rate (fcr). secondary objectives: * to assess effect of rimonabant on hdl apoa-i production rate (pr) and on other lipoprotein kinetics. * to assess effect of rimonabant on lipids, glycemic and inflammatory parameters * to assess effect of rimonabant on body composition * to assess safety of rimonabant


Eligibility criteria:
inclusion criteria: * abdominally obese patients with additional cardiometabolic risk factors * females must be post-menopausal * bmi \> 27 kg/m² and \< 40 kg/m² * men or women with abdominal obesity according to ncep/atpiii criteria: waist circumference \> 88 cm in women; \> 102 cm in men * with at least one lipid abnormality defined as: * fasting triglycerides level \> 1.7 mmol/l (150 mg/dl) and \< 4.5 mmol/l (400 mg/dl) * hdl \< 1.03 mmol/l (40 mg/dl) in men and \< 1.29 mmol/l (50 mg/dl) in women exclusion criteria: * hdl ≤ 0.60 mmol/l (23 mg/dl) * plasma ldl-cholesterol \> 155 mg/dl (4.00 mmol/l) or total cholesterol 250 mg/dl (\> 6.5mmol/l) or genetic hyperlipidaemia * fasting triglycerides \> 400 mg/dl (4.5 mmol/l) * known heterozygous or homozygous familial hypercholesterolaemia or know type iii hyperlipoproteinaemia (familial dysbetalipoproteinaemia) * apoe2/e2 homozygosity, apo e4/e4 homozygosity * type 2 diabetes treated with oral agents and/or insulin * diet treated type 2 diabetic patients with hba1c ≥ 7% * history of cardio vascular disease * systolic blood pressure ≥ 160 mmhg or diastolic blood pressure ≥ 95 mmhg. * very low-calorie diet (1200 calories a day or less) or history of surgical procedures for weight loss (e.g., stomach stapling, bypass) * body weight fluctuation \> 5 kg during the previous 3 months * history of bulimia or anorexia nervosa by dsm-iv criteria * presence of any clinically significant endocrine disease according to the investigator, cushing syndrome, obesity secondary to hypothalamic/pituitary disorder. * abnormal tsh and free t4 at baseline (patients treated with thyroid replacement therapy must be on fixed and stable dose for at least 3 months prior to screening and must be in euthyroïd status.) * severe hepatic impairment known by the investigator or ast or alt \> 3 times the uln at screening. * known severe renal dysfunction (creatinine clearance \< 30 ml/min) or urine analysis (performed at screening by dipstick) showing 2+ or more protein * presence of any condition (medical, including clinically significant abnormal laboratory test, psychological, social or geographical) actual or anticipated that the investigator feels would compromise the patient safety or limit his/her successful participation to the study * patient treated for epilepsy * ongoing major depressive illness * uncontrolled psychiatric illness * history of alcohol and/or drug abuse * smoker or smoking cessation within the past 3 months * marijuana or hashish users * previous participation in a rimonabant study or to any other clinical trial within 4 weeks to study start * hypersensitivity/intolerance to the active substance or to any of the excipients such as lactose * blood donation within the past 3 months prior to the study or planned during the study or within the 3 months from the study completing * recent history of active peptic ulcer * willebrand disease or other hemorrhagic diatheses * administration of any of the following within 3 months prior to screening visit and susceptible to be prescribed during the study treatment period: * lipid-lowering drugs intake * anti obesity drugs * other drugs for weight reduction (phentermine, amphetamines) * herbal preparations for weight reduction * other drugs known to affect lipid metabolism: retinoids, antiretroviral, estrogens and hormone replacement therapy, cyclosporine, glitazones, benfluorex, fish oils, plant sterols. * thiazids (including fixed combination) at daily dose higher than 12.5 mg * unselective beta-blockers * prolonged use (more than one week) of systemic corticosteroids, neuroleptics * anticoagulants * ongoing antidepressive treatment the above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.