Weight Loss in Response to Sibutramine (MERIDIA) is Influenced by the Inherited Genes
Information source: Mayo Clinic
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Obesity
Intervention: sibutramine (Drug); sibutramine (Drug); sibutramine (Drug)
Phase: Phase 4
Status: Completed
Sponsored by: Mayo Clinic Official(s) and/or principal investigator(s): Michael L. Camilleri, M.D., Principal Investigator, Affiliation: Mayo Clinic
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.
Clinical Details
Official title: Pharmacogenomics of Weight Loss With Sibutramine in Obese and Overweight Patients
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Association of weight loss with candidate genotypes
Secondary outcome: T1/2 gastric emptying of solidsbody composition (fat)
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.
Eligibility
Minimum age: 18 Years.
Maximum age: 65 Years.
Gender(s): Both.
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).
Locations and Contacts
Mayo Clinic, Rochester, Minnesota 55905, United States
Additional Information
Mayo Clinic Clinical Trials
Starting date: July 2006
Last updated: March 10, 2011
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