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

March 10, 2011 updated by: Mayo Clinic

Pharmacogenomics of Weight Loss With Sibutramine in Obese and Overweight Patients

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 Overview

Status

Completed

Conditions

Intervention / Treatment

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

Enrollment (Actual)

181

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 61 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: 1
placebo tablet
Drug: sibutramine
placebo
Other Names:
  • meridia
Drug: sibutramine
oral 15 mg sibutramine once per day
Other Names:
  • MERIDIA
Drug: sibutramine
oral sibutramine 10 mg once per day
Other Names:
  • MERIDIA
Experimental: 2
sibutramine
Drug: sibutramine
placebo
Other Names:
  • meridia
Drug: sibutramine
oral 15 mg sibutramine once per day
Other Names:
  • MERIDIA
Drug: sibutramine
oral sibutramine 10 mg once per day
Other Names:
  • MERIDIA
Experimental: 3
sibutramine
Drug: sibutramine
placebo
Other Names:
  • meridia
Drug: sibutramine
oral 15 mg sibutramine once per day
Other Names:
  • MERIDIA
Drug: sibutramine
oral sibutramine 10 mg once per day
Other Names:
  • MERIDIA

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Association of weight loss with candidate genotypes
Time Frame: 2006-2007
2006-2007

Secondary Outcome Measures

Outcome Measure
Time Frame
T1/2 gastric emptying of solids
Time Frame: 2006-2007
2006-2007
body composition (fat)
Time Frame: 2006-2007
2006-2007

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mayo Clinic

Collaborators

National Institutes of Health (NIH)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2006

Primary Completion (Actual)

November 1, 2007

Study Completion (Actual)

November 1, 2007

Study Registration Dates

First Submitted

February 8, 2007

First Submitted That Met QC Criteria

February 9, 2007

First Posted (Estimate)

February 12, 2007

Study Record Updates

Last Update Posted (Estimate)

March 14, 2011

Last Update Submitted That Met QC Criteria

March 10, 2011

Last Verified

March 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 06-003371
  • NIH DK67071

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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