The Effect of Rimonabant on Energy Expenditure, Fat Metabolism and Body Composition
This study will determine in obese subjects the direct effects of the weight loss drug rimonabant (ie independent of weight loss) on energy expenditure, fat metabolism and and body fat distribution. We hypothesise that rimonabant will increase energy expenditure. The fuel for the increased energy expenditure will come from fat. As a result of burning more fat there will be a decrease in fat in blood and an improvement in the body's response to insulin.
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
|Official Title:||The Effect of Rimonabant on Energy Expenditure, Fat Metabolism and Body Composition|
- The direct effect of rimonabant on energy expenditure [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
- Whole body fatty acid production and oxidation rate. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
- Triglyceride synthesis and clearance rate. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
- Whole body fat distribution. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
- Adipose tissue and muscle mRNA levels of key regulators of fatty acid metabolism. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
- Insulin sensitivity. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
|Study Start Date:||July 2007|
|Estimated Study Completion Date:||May 2010|
|Estimated Primary Completion Date:||April 2009 (Final data collection date for primary outcome measure)|
Rimonabant treatment (20mg/d) for 12 weeks
20mg/d (oral) once daily for 12 weeks
Other Name: Acomplia
Behavioral: Dietary intervention
Dietary intervention to match weight loss in group 1. The energy prescription will be based on the estimate of the energy deficit estimated from the weight loss in group one. For example a weight loss of 5kg over 12 weeks equates to an approximate energy deficit of 30,000 kcal or a daily energy reduction of approximately 357 kcal. If this is achieved in group 1 the daily energy target for subjects in group 2 will be daily energy expenditure minus 357 kcal.For the subjects randomised to the dietary intervention group there will be a delay until group 1 subjects have completed the study.
In obese subjects (BMI 33-38kg/m2) completing 12 months of treatment with the CB1 antagonist rimonabant (SR141716) there was an average weight loss from baseline of approximately 8.5 kg. These studies also showed the weight loss was accompanied by a decrease in plasma triglyceride (TG), an increase in HDL cholesterol and an improvement in insulin sensitivity measured by HOMA-IR. When adjusted for weight loss 50% of the improvements in TG, HDL cholesterol, and insulin sensitivity was not attributable to weight loss. This suggests that rimonabant has direct effects on fat metabolism.
This study will investigate the direct effects of rimonabant (ie independent of weight loss) in a 2 group randomised study. One group will receive rimonabant for 12 weeks and the other group will have a dietary intervention to match the weight loss in the rimonabant group. Measurements of energy expenditure (using indirect calorimetry and Actiheart monitors),fatty acid and triglyceride metabolism (using stable isotope techniques) and body fat distribution (by magnetic resonance imaging) will be made before and after the intervention. To determine the possible mechanisms of the changes in metabolism, gene expression of key regulators of fatty acid metabolism in adipose and muscle tissue and circulating levels of adipokines will be measured.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00584389
|Royal Surrey County Hospital|
|Guildford, Surrey, United Kingdom, GU2 7XX|
|Study Director:||David L Russell-Jones, MBBS,MD,FRCP||UK National Health Service|
|Principal Investigator:||Margot Umpleby, BA, PhD||University of Surrey|