Weight Loss in Response to Sibutramine (MERIDIA) is Influenced by the Inherited Genes
Control of food intake, size and frequency of meals are critical to the development of obesity. The stomach signals feelings of fullness after a meal and therefore plays a role in control of calorie intake. It is unclear whether the approved appetite reducing drug sibutramine changes the function of the stomach. Differences in the way individuals respond to treatment with the appetite suppressant sibutramine may also explain why some people lose weight while others do not.
In a previous study of 48 overweight or obese participants, we preliminarily observed that variation in the gene for the promoter of the serotonin transporter protein was significantly associated with degree of weight loss.
This new single center clinical study aims to evaluate the effects of the FDA-approved appetite suppressing medication, sibutramine (MERIDIA)on weight loss and stomach emptying in patients who are overweight or obese. The effect of individual differences in inherited genes that modify serrotonin and noradrenergic receptors on weight reduction with sibutramine will be tested.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Pharmacogenomics of Weight Loss With Sibutramine in Obese and Overweight Patients|
- Association of weight loss with candidate genotypes [ Time Frame: 2006-2007 ] [ Designated as safety issue: No ]
- T1/2 gastric emptying of solids [ Time Frame: 2006-2007 ] [ Designated as safety issue: No ]
- body composition (fat) [ Time Frame: 2006-2007 ] [ Designated as safety issue: No ]
|Study Start Date:||July 2006|
|Study Completion Date:||November 2007|
|Primary Completion Date:||November 2007 (Final data collection date for primary outcome measure)|
Placebo Comparator: 1
Other Name: meridia
oral sibutramine 10 mg once per day
Other Name: MERIDIA
oral 15 mg sibutramine once per day
Other Name: MERIDIA
Background:. Genetic variations are potentially key to inter-individual differences in responses to treatment with the appetite suppressant sibutramine.
Overall Aims: To evaluate influence of genetic variation in candidate adrenergic and serotonergic control mechanisms on weight loss and gastric emptying response to sibutramine in obesity.
Methods: 180 overweight or obese (respectively BMI of 25-29.9 or 30 kg/m2) people treated with sibutramine (10 or 15 mg/day) or placebo for 12 wks. We shall collect DNA from venous blood sample at study entry, and use SERT-P genotype at baseline to stratify patients according to LL vs LS/SS genotype in both obese and overweight groups. The primary outcome measurement will be the association of clinical response (weight loss) and the influence of SERT-P and 2-MSP variation. A secondary outcome for descriptive purposes is the gastric emptying response to sibutramine treatment. Gastric emptying of solids will be measured using stable isotope method.
Anticipated Results: SERT-P genotype is significantly associated with the magnitude of weight loss in obese and overweight individuals.
Significance: Our study will provide the first evidence of the pharmacogenomic effects of sibutramine on weight loss in obesity and appraise the association of weight loss with change in gastric emptying.
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Principal Investigator:||Michael L. Camilleri, M.D.||Mayo Clinic|