Weight Loss in Response to Sibutramine (MERIDIA) is Influenced by the Inherited Genes
Condition: Obesity
MeSH terms: Weight Loss
Study type: Interventional
Phase: Phase 4

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): sibutramine; sibutramine; sibutramine
Intervention type(s): Drug; Drug; Drug
Intervention description(s): placebo; oral 15 mg sibutramine once per day; oral sibutramine 10 mg once per day
Other intervention name(s): meridia; MERIDIA; MERIDIA
Intervention MeSH terms: Sibutramine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: obesity; pharmacogenetics; sibutramine; adrenergic; serotonergic; body composition; gastric emptying