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

Phase 4

Terminated

• Conditions: Obesity
• Interventions: Drug: rimonabant; Behavioral: Dietary intervention

• Registration Number: NCT00584389
• Lead Sponsor: University of Surrey

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study Start: 2007-07
• Study First Submitted: 2007-12-11
• Study First Submitted QC: 2007-12-31
• Study First Posted: 2008-01-02
• Primary Completion: 2009-04
• Status Verified: 2010-04
• Last Update Submitted: 2010-04-16
• Last Update Posted: 2010-04-19
• Study Completion: 2010-05

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Female
• Target Recruitment: 14

Inclusion Criteria

• Healthy Caucasian postmenopausal women
• BMI 30-38

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	rimonabant	Rimonabant treatment (20mg/d) for 12 weeks
2	Dietary intervention	Dietary intervention

Primary Outcome Measures

Name	Time	Method
The direct effect of rimonabant on energy expenditure	12 weeks

Secondary Outcome Measures

Name	Time	Method
Whole body fatty acid production and oxidation rate.	12 weeks
Triglyceride synthesis and clearance rate.	12 weeks
Whole body fat distribution.	12 weeks
Adipose tissue and muscle mRNA levels of key regulators of fatty acid metabolism.	12 weeks
Insulin sensitivity.	12 weeks

Trial Locations

Locations (1)

Royal Surrey County Hospital; 🇬🇧 Guildford, Surrey, United Kingdom