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

Primary Purpose

Obesity

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

sibutramine

About this trial

This is an interventional treatment trial for Obesity focused on measuring obesity, pharmacogenetics, sibutramine, adrenergic, serotonergic, body composition, gastric emptying

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

Mayo Clinic

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Experimental

Arm Label

Arm Description

placebo tablet

sibutramine

Outcomes

Primary Outcome Measures

Association of weight loss with candidate genotypes

Secondary Outcome Measures

T1/2 gastric emptying of solids

body composition (fat)

Full Information

NCT ID

NCT00433641

First Posted

February 8, 2007

Last Updated

March 10, 2011

Sponsor

Mayo Clinic

Collaborators

National Institutes of Health (NIH)

1. Study Identification

Unique Protocol Identification Number

NCT00433641

Brief Title

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

Official Title

Pharmacogenomics of Weight Loss With Sibutramine in Obese and Overweight Patients

Study Type

Interventional

2. Study Status

Record Verification Date

March 2011

Overall Recruitment Status

Completed

Study Start Date

July 2006 (undefined)

Primary Completion Date

November 2007 (Actual)

Study Completion Date

November 2007 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

Mayo Clinic

Collaborators

National Institutes of Health (NIH)

4. Oversight

Data Monitoring Committee

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Obesity

Keywords

obesity, pharmacogenetics, sibutramine, adrenergic, serotonergic, body composition, gastric emptying

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

181 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Placebo Comparator

Arm Description

placebo tablet

Arm Title

Arm Type

Experimental

Arm Description

sibutramine

Arm Title

Arm Type

Experimental

Arm Description

sibutramine

Intervention Type

Drug

Intervention Name(s)

sibutramine

Other Intervention Name(s)

meridia

Intervention Description

placebo

Intervention Type

Drug

Intervention Name(s)

sibutramine

Other Intervention Name(s)

MERIDIA

Intervention Description

oral 15 mg sibutramine once per day

Intervention Type

Drug

Intervention Name(s)

sibutramine

Other Intervention Name(s)

MERIDIA

Intervention Description

oral sibutramine 10 mg once per day

Primary Outcome Measure Information:

Title

Association of weight loss with candidate genotypes

Time Frame

2006-2007

Secondary Outcome Measure Information:

Title

T1/2 gastric emptying of solids

Time Frame

2006-2007

Title

body composition (fat)

Time Frame

2006-2007

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

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).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Michael L. Camilleri, M.D.

Organizational Affiliation

Mayo Clinic

Official's Role

Principal Investigator

Facility Information:

Facility Name

Mayo Clinic

City

Rochester

State/Province

Minnesota

ZIP/Postal Code

55905

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

18725220

Citation

Grudell AB, Sweetser S, Camilleri M, Eckert DJ, Vazquez-Roque MI, Carlson PJ, Burton DD, Braddock AE, Clark MM, Graszer KM, Kalsy SA, Zinsmeister AR. A controlled pharmacogenetic trial of sibutramine on weight loss and body composition in obese or overweight adults. Gastroenterology. 2008 Oct;135(4):1142-54. doi: 10.1053/j.gastro.2008.07.009. Epub 2008 Jul 16.

Results Reference

derived

Links:

URL

http://clinicaltrials.mayo.edu

Description

Mayo Clinic Clinical Trials

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

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