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

This study has been terminated.
(Suspension of licence for rimonabant by European Medicines Agency)
Sponsor:
Collaborators:
European Foundation for the Study of Diabetes
Royal Surrey County Hospital
Information provided by:
University of Surrey
ClinicalTrials.gov Identifier:
NCT00584389
First received: December 11, 2007
Last updated: April 16, 2010
Last verified: April 2010
  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:


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.

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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
Body Weight
Nutrition Disorders
Overnutrition
Overweight
Signs and Symptoms
Rimonabant
Cannabinoid Receptor Antagonists
Cannabinoid Receptor Modulators
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 27, 2014