Metabolic Syndrome
Conditions
Brief summary
Primary objective: To assess the effect of rimonabant on visceral fat area over a period of 12 months when prescribed with a mild hypocaloric diet in abdominally obese patients with metabolic syndrome Secondary objectives: * To assess the effect of rimonabant over a period of 12 months on: * Liver fat content using CT scan (Computed Tomography scan) * Anthropometric measures (weight, waist circumference, body composition using Dual Energy X-ray Absorptiometry (DEXA)) * Lipid, lipoprotein profile * Glycemia, insulinemia and HbA1c * Adipokines, inflammatory and hemostatic markers * To evaluate the percentage of patients with metabolic syndrome at 12 months * To evaluate the safety and tolerability of rimonabant in these patients In four selected US sites the effect of rimonabant at 12 months will be also assessed on: * Basal lipolysis and insulin suppressed lipolysis (euglycemic hyperinsulinemic clamp). * Resting metabolic rate and substrate oxidation at rest using indirect calorimetry. * Adipose tissue histology and expression of genes involved in glucose and lipid metabolism (superficial adipose tissue biopsy).
Detailed description
The total duration per patient will be approximately 15 months including a 12-month double-blind treatment period.
Interventions
DRUGRimonabant
Tablet, oral administration
Tablet, oral administration
OTHERMild hypocaloric diet
Calculated by the dietitian based on the estimated basal metabolism rate and the physical activity
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
35 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
: * Waist circumference \> 102 cm in men and \> 88 cm in women * Two other components of the metabolic syndrome (NCEP/ATPIII definition) among the following : * Triglyceridemia ≥ 150 mg/dl (or 1.69 mmol/L) * HDL cholesterol \< 50 mg/dL (or 1.29 mmol/L) in women or \< 40 mg/dL (or 1.04 mmol/L) in men * Blood pressure ≥ 130/85 mmHg (systolic blood pressure ≥ 130 mmHg and/or diastolic blood pressure ≥ 85 mmHg) or Treatment with antihypertensive agent(s) for this condition * Fasting blood glucose \> 110 mg/dl (or 6.1 mmol/L)
Exclusion criteria
: * Positive pregnancy test, pregnant or breast-feeding women, or women planning to become pregnant or breastfeed * Absence of medically approved contraceptive methods for female of childbearing potential * History of very low-calorie diet (≤ 800 kcal/day) within 3 months prior to screening visit * History of surgical procedures for weight loss (eg, stomach stapling, bypass). * Presence of any clinically significant endocrine disease according to the investigator. * Weight change \> 5 kg within 3 months prior to screening visit * Obese patients (BMI\> 40 kg/m²) * Established type 1 or 2 diabetes (treated or untreated): at least 2 measures of fasting blood glucose ≥ 126 mg/dl * Severe renal dysfunction (creatinine clearance \< 30 ml/min) or nephrotic syndrome * Chronic hepatitis or clinically significant hepatic disease * Positive test for hepatitis B or C * Marijuana or hashish users * Significant haematology abnormalities (haemoglobin \< 100 g/L and/or neutrophils \< 1.5 G/L and/or platelets \< 100 G/L). * Presence or history of cancer within the past 5 years with the exception of adequately treated basal cell skin cancer or in situ uterine cervical cancer * Presence or history of severe depression that can be defined as depression which necessitated the patient to be hospitalised, or patient with 2 or more recurrent episodes of depression or an history of suicide attempt * Presence or history of bulimia or anorexia nervosa (DSM-IV (Diagnostic and Statistical Manual of Mental Disorders) criteria) or binge eating disorders * Presence of any other condition (eg geographical, social…) current or anticipated that the Investigator feels that would restrict or limit the subject's participation for the duration of the studyRelated to previous or concomitant drugs that could interfere with the evaluation of study drug effects * Administration of any investigational treatment (drug or device) within 30 days prior to screening * Previous participation in a rimonabant study * Administration of any of the following within 3 months prior to screening visit: * anti obesity drugs (eg, sibutramine, orlistat) * other drugs for weight reduction (phentermine, amphetamines) * herbal preparations for weight reduction * thyroid preparations or thyroxin treatment (except in patients on replacement therapy on a stable dose) * Patient treated within the last 3 months with nicotinic acid, fibrates, bile acid sequestrants or ezetimibe (patients treated with statins can be included if the dose received is stable since at least 3 months and should not be modified during the whole study period). * Patient treated with antidiabetic drug(s). * Prolonged use (more than one week) within the last 3 months of systemic corticosteroids, neuroleptics, or antidepressants (including bupropion). The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Relative change in visceral fat area assessed by CT scan | From baseline to Month 12 |
Secondary
| Measure | Time frame |
|---|---|
| Change in Liver fat content measured using CT scan | From baseline to Month 12 |
| Change in anthropometric measures | From baseline to Month 12 |
| Change in specific lipid parameters | From baseline to Month 12 |
| Absolute change in visceral fat area assessed by CT scan | From baseline to Month 12 |
| Change in adipokines, inflammatory and hemostatic markers | From baseline to Month 12 |
| Percentages of patients with a metabolic syndrome | At 12 months |
| Change in glucose control parameters | From baseline to Month 12 |
Countries
Canada, Denmark, Finland, France, Italy, Spain, Sweden, United Kingdom, United States
Outcome results
None listed