Clinical trial NCT00584389: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Obesity
Keywords: Obesity
Energy expenditure
Fatty acid
Triglyceride
Lead sponsor: University of Surrey
Sponsor class: OTHER
Collaborators: name: European Foundation for the Study of Diabetes
name: Royal Surrey County Hospital NHS Foundation Trust
First posted: 2008-01-02
Enrollment: 14
Sex: FEMALE
Minimum age (years): 50
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

Eligibility 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

Primary outcomes:
measure: The direct effect of rimonabant on energy expenditure
timeFrame: 12 weeks
Secondary outcomes:
measure: Whole body fatty acid production and oxidation rate.
timeFrame: 12 weeks
measure: Triglyceride synthesis and clearance rate.
timeFrame: 12 weeks
measure: Whole body fat distribution.
timeFrame: 12 weeks
measure: Adipose tissue and muscle mRNA levels of key regulators of fatty acid metabolism.
timeFrame: 12 weeks
measure: Insulin sensitivity.
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Guildford
country: United Kingdom
facility: Royal Surrey County Hospital
state: Surrey
Study officials:
affiliation: UK National Health Service
name: David L Russell-Jones, MBBS,MD,FRCP
role: STUDY_DIRECTOR
affiliation: University of Surrey
name: Margot Umpleby, BA, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1056/NEJMoa044537.
citation: 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. doi: 10.1016/S0140-6736(05)66374-X.
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. doi: 10.1001/jama.295.7.761.
citation: 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.