The Effect of Rimonabant on Energy Expenditure, Fat Metabolism and Body Composition - Full Text View

Purpose

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.

Condition	Intervention	Phase
Obesity	Drug: rimonabant Behavioral: Dietary intervention	Phase 4

Study Type:	Interventional
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

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Medicines Obesity Weight Control

U.S. FDA Resources

Further study details as provided by University of Surrey:

Primary Outcome Measures:

The direct effect of rimonabant on energy expenditure [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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 ]

Enrollment:	14
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)

Arms	Assigned Interventions
Experimental: 1 Rimonabant treatment (20mg/d) for 12 weeks	Drug: rimonabant 20mg/d (oral) once daily for 12 weeks Other Name: Acomplia
2 Dietary intervention	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

Assigned Interventions

Experimental: 1

Rimonabant treatment (20mg/d) for 12 weeks

Drug: rimonabant

20mg/d (oral) once daily for 12 weeks

Other Name: Acomplia

2

Dietary intervention

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.

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.

Eligibility

Ages Eligible for Study:	50 Years to 70 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00584389

Locations

United Kingdom
Royal Surrey County Hospital
Guildford, Surrey, United Kingdom, GU2 7XX

Sponsors and Collaborators

University of Surrey

European Foundation for the Study of Diabetes

Royal Surrey County Hospital

Investigators

Study Director:	David L Russell-Jones, MBBS,MD,FRCP	UK National Health Service
Principal Investigator:	Margot Umpleby, BA, PhD	University of Surrey

More Information

Publications:

Despres JP, Golay A, Sjostrom 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.

Van Gaal LF, Rissanen AM, Scheen AJ, Ziegler O, Rossner 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.

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.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Backhouse K, Sarac I, Shojaee-Moradie F, Stolinski M, Robertson MD, Frost GS, Bell JD, Thomas EL, Wright J, Russell-Jones D, Umpleby AM. Fatty acid flux and oxidation are increased by rimonabant in obese women. Metabolism. 2012 Sep;61(9):1220-3. doi: 10.1016/j.metabol.2012.02.012. Epub 2012 Mar 24.

Responsible Party:	Professor Margot Umpleby, University of Surrey
ClinicalTrials.gov Identifier:	NCT00584389 History of Changes
Other Study ID Numbers:	EC/2006/117/PGMS, Eudract 2006-006424-18
Study First Received:	December 11, 2007
Last Updated:	April 16, 2010
Health Authority:	United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by University of Surrey:

Obesity
Energy expenditure
Fatty acid
Triglyceride

Additional relevant MeSH terms:

Obesity
Overnutrition
Nutrition Disorders

Overweight
Body Weight
Signs and Symptoms

ClinicalTrials.gov processed this record on May 21, 2013