Weight Loss in Response to Sibutramine (MERIDIA) is Influenced by the Inherited Genes

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00433641
Recruitment Status : Completed
First Posted : February 12, 2007
Last Update Posted : March 14, 2011
National Institutes of Health (NIH)
Information provided by:
Mayo Clinic

Brief 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.

Condition or disease Intervention/treatment Phase
Obesity Drug: sibutramine Phase 4

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 181 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Pharmacogenomics of Weight Loss With Sibutramine in Obese and Overweight Patients
Study Start Date : July 2006
Primary Completion Date : November 2007
Study Completion Date : November 2007

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Placebo Comparator: 1
placebo tablet
Drug: sibutramine
Other Name: meridia
Experimental: 2
Drug: sibutramine
oral sibutramine 10 mg once per day
Other Name: MERIDIA
Experimental: 3
Drug: sibutramine
oral 15 mg sibutramine once per day
Other Name: MERIDIA

Primary Outcome Measures :
  1. Association of weight loss with candidate genotypes [ Time Frame: 2006-2007 ]

Secondary Outcome Measures :
  1. T1/2 gastric emptying of solids [ Time Frame: 2006-2007 ]
  2. body composition (fat) [ Time Frame: 2006-2007 ]

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Normal weight, overweight and obese subjects with BMI> 18 Kg/m2 residing in Olmsted County, MN: Otherwise healthy individuals who are not currently on treatment for cardiac, pulmonary, gastrointestinal, hepatic, renal, hematological, neurological, endocrine (other than hyperglycemia not requiring medical therapy) and unstable psychiatric disease.
  • Age: 18-65 years
  • Gender: Men or women. Women of childbearing potential will have negative pregnancy test within 48 h of enrollment and before each radiation exposure.

Exclusion Criteria:

  • Weight exceeding 300 pounds or 137 kilograms (due to limitations regarding SPECT imaging studies).
  • Abdominal surgery other than appendectomy, Caesarian section or tubal ligation.
  • Positive history of chronic gastrointestinal diseases, systemic disease that could affect gastrointestinal motility or use of medications that may alter gastrointestinal motility, appetite or absorption e.g., orlistat (Xenical).
  • Significant psychiatric dysfunction based upon screening with the Hospital Anxiety and Depression Scale [HADS] self-administered alcoholism screening test (substance abuse) and the questionnaire on eating and weight patterns (binge eating disorders and bulimia). If such a dysfunction is identified by a HADS score >8 or difficulties with substance or eating disorders, the participant will be excluded and given a referral letter to his/her primary care doctor for further appraisal and follow-up.
  • Intake of medication, whether prescribed or OTC medication (except multivitamins) within 7 days of the study. Exceptions are birth control pill, estrogen replacement therapy, and thyroxine replacement.
  • Concomitant use of MAOI inhibitors and other centrally acting appetite suppressants (since this would make them ineligible for sibutramine treatment).
  • Hypersensitivity to sibutramine (since this would make them ineligible for sibutramine treatment).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00433641

United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
National Institutes of Health (NIH)
Principal Investigator: Michael L. Camilleri, M.D. Mayo Clinic

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Michael Camilleri, Mayo Clinic Identifier: NCT00433641     History of Changes
Other Study ID Numbers: 06-003371
NIH DK67071
First Posted: February 12, 2007    Key Record Dates
Last Update Posted: March 14, 2011
Last Verified: March 2011

Keywords provided by Mayo Clinic:
body composition
gastric emptying

Additional relevant MeSH terms:
Weight Loss
Body Weight Changes
Body Weight
Signs and Symptoms
Antidepressive Agents
Psychotropic Drugs
Appetite Depressants
Anti-Obesity Agents