Clinical trial NCT00408148: High Density Lipoprotein Turnover
Official title: A Randomized, Double-blind, Two Arm, Parallel, Placebo Controlled Study of Rimonabant 20 mg Effect on High Density Lipoprotein Kinetics in Patients With Abdominal Obesity and Additional Cardiometabolic Risk Factors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Obesity
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2006-12-06
Enrollment: 64
Sex: ALL
Minimum age (years): 35
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: The fractional catabolic rate (FCR) of HDL ApoA-I
timeFrame: After 12 months of treatment.
Secondary outcomes:
measure: Production Rate (PR) of HDL ApoA-I and A-II, (FCR) of HDL ApoA-II
timeFrame: All across the study
measure: PR and FCR of VLDL1 and VLDL2 Apo B, VLDL1 and VLDL2 TG, IDL Apo B and LDL Apo B
timeFrame: All across the study
measure: Variation in ApoA-I, ApoA-II, Lp-AI, Lp-AII, pre-beta-HDL HDL2a, HDL2b, HDL3a, HDL3b, HDL3c, Apo B, Apo C III, TG, LDL-C, HDL-C levels
timeFrame: All across the study
measure: Variation in Glucose, insulin, HbA1c, leptin, adiponectin
timeFrame: All across the study
measure: Variation in hs-CRP, TNF-alpha, CETP, PLTP and LCAT activities, lipoprotein and hepatic lipase activities in post-heparin plasma
timeFrame: All across the study
measure: Variation in whole body fat
timeFrame: All across the study
measure: Variation in abdominal sub-cutaneous and visceral fat
timeFrame: All across the study
measure: Variation in liver fat
timeFrame: All across the study
measure: Variation in blood pressure
timeFrame: All across the study
measure: Variation in body weight, waist circumference, waist/hip ratio
timeFrame: From the beginning to the end of the study
measure: CE/TG ratio in HDL
timeFrame: All across the study
measure: Adverse events
timeFrame: From the beginning to the end of the study
Other outcomes:
Locations:
city: North Ryde
country: Australia
facility: Sanofi-Aventis Administrative Office
city: Helsinki
country: Finland
facility: Sanofi-Aventis Administrative Office
city: Paris
country: France
facility: Sanofi-Aventis Administrative Office
city: Guildford
country: United Kingdom
facility: Sanofi-Aventis Administrative Office
Study officials:
affiliation: Sanofi
name: Valérie Pilorget
role: STUDY_DIRECTOR
References:
citation: Verges B, Adiels M, Boren J, Barrett PH, Watts GF, Chan D, Duvillard L, Soderlund S, Matikainen N, Kahri J, Robin I, Taskinen MR. Interrelationships between the kinetics of VLDL subspecies and HDL catabolism in abdominal obesity: a multicenter tracer kinetic study. J Clin Endocrinol Metab. 2014 Nov;99(11):4281-90. doi: 10.1210/jc.2014-2365. Epub 2014 Jul 31.