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

Obesity Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00584389
• Other study ID #: EC/2006/117/PGMS
• Secondary ID: Eudract 2006-006
• Status: Terminated
• Phase: Phase 4
• First received: December 11, 2007
• Last updated: April 16, 2010
• Start date: July 2007
• Est. completion date: May 2010

Study information

• Verified date: April 2010
• Source: University of Surrey
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 14
• Est. completion date: May 2010
• Est. primary completion date: April 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 50 Years to 70 Years

Eligibility

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

• ß-blockers, fibrates and metformin

• Severe under-reporting of food intake based on a 4 day food diary

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Obesity

Intervention

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.

Locations

Country	Name	City	State
United Kingdom	Royal Surrey County Hospital	Guildford	Surrey

Sponsors (3)

Lead Sponsor	Collaborator
University of Surrey	European Foundation for the Study of Diabetes, Royal Surrey County Hospital

Country where clinical trial is conducted

United Kingdom, 

References & Publications (3)

Després JP, Golay A, Sjöström L; Rimonabant in Obesity-Lipids Study Group. Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N Engl J Med. 2005 Nov 17;353(20):2121-34. — View Citation

Pi-Sunyer FX, Aronne LJ, Heshmati HM, Devin J, Rosenstock J; RIO-North America Study Group. Effect of rimonabant, a cannabinoid-1 receptor blocker, on weight and cardiometabolic risk factors in overweight or obese patients: RIO-North America: a randomized controlled trial. JAMA. 2006 Feb 15;295(7):761-75. Erratum in: JAMA. 2006 Mar 15;295(11):1252. — View Citation

Van Gaal LF, Rissanen AM, Scheen AJ, Ziegler O, Rössner S; RIO-Europe Study Group. Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study. Lancet. 2005 Apr 16-22;365(9468):1389-97. Erratum in: Lancet. 2005 Jul 30-Aug 5;366(9483):370. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The direct effect of rimonabant on energy expenditure		12 weeks	No
Secondary	Whole body fatty acid production and oxidation rate.		12 weeks	No
Secondary	Triglyceride synthesis and clearance rate.		12 weeks	No
Secondary	Whole body fat distribution.		12 weeks	No
Secondary	Adipose tissue and muscle mRNA levels of key regulators of fatty acid metabolism.		12 weeks	No
Secondary	Insulin sensitivity.		12 weeks	No