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

University of Surrey

Status and phase: Terminated; Phase 4

Conditions: Obesity

Treatments: Behavioral: Dietary intervention; Drug: rimonabant

Study type: Interventional

Funder types: Other

Identifiers

NCT00584389

EC/2006/117/PGMS

Eudract 2006-006424-18

Details and patient eligibility

About

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.

Full 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.

Enrollment: 14 patients

Sex: Female

Ages: 50 to 70 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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14 participants in 2 patient groups

1

Experimental group

Description:

Rimonabant treatment (20mg/d) for 12 weeks

Treatment:

Drug: rimonabant

2

Other group

Description:

Dietary intervention

Treatment:

Behavioral: Dietary intervention