The Effect of Rimonabant on Energy Expenditure, Fat Metabolism and Body Composition

Official Title: “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.

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.

Intervention(s) in this Clinical Trial

• Drug: rimonabant
  • 20mg/d (oral) once daily for 12 weeks
• 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.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Rimonabant treatment (20mg/d) for 12 weeks
• Other: 2
  • Dietary intervention

Primary Measures

• The direct effect of rimonabant on energy expenditure
  • Time Frame: 12 weeks
    Safety Issue?: No

Secondary Measures

• Whole body fatty acid production and oxidation rate.
  • Time Frame: 12 weeks
    Safety Issue?: No
• Triglyceride synthesis and clearance rate.
  • Time Frame: 12 weeks
    Safety Issue?: No
• Whole body fat distribution.
  • Time Frame: 12 weeks
    Safety Issue?: No
• Adipose tissue and muscle mRNA levels of key regulators of fatty acid metabolism.
  • Time Frame: 12 weeks
    Safety Issue?: No
• Insulin sensitivity.
  • Time Frame: 12 weeks
    Safety Issue?: No

Inclusion Criteria:

• Healthy Caucasian postmenopausal women
• BMI 30-38

Exclusion Criteria:

• Not currently weight-stable
• Diagnosed with diabetes
• Cardiovascular disease
• Endocrine disease
• Hepatic and renal disorders
• Neurological/psychological illness/history of depression
• Previous surgical procedures for weight loss
• Medications known to alter body weight or appetite
• β-blockers, fibrates and metformin
• Severe under-reporting of food intake based on a 4 day food diary

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 50 Years

Maximum Age for this Clinical Trial: 70 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Investigator: University of Surrey Other

Overall Clinical Trial Officials and Contacts

David L Russell-Jones, MBBS,MD,FRCP Study Director UK National Health Service  

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00584389

Study ID Number: EC/2006/117/PGMS

ClinicalTrials.gov Identifier: NCT00584389

Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency