Pharmacodynamic Effects of Sibutramine on Gastric Function in Obesity - Full Text View

Sponsor:	Mayo Clinic
Information provided by:	Mayo Clinic
ClinicalTrials.gov Identifier:	NCT00330525

Purpose

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.

This single center clinical study aims to compare functions of the stomach in healthy, overweight and obese individuals, and to evaluate the effects of the FDA-approved appetite suppressing medication sibutramine on weight loss and stomach functions in patients who are overweight or obese. The effect of individual differences in inherited genes on weight reduction with sibutramine will be tested.

Condition	Intervention	Phase
Obesity Overweight	Drug: sibutramine	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Pharmacodynamics Study
Official Title:	Pharmacodynamic Effects of Sibutramine on Gastric Function in Obesity

Resource links provided by NLM:

MedlinePlus related topics: Obesity Weight Control

Drug Information available for: Sibutramine Sibutramine hydrochloride monohydrate

U.S. FDA Resources

Further study details as provided by Mayo Clinic:

Primary Outcome Measures:

T1/2 gastric emptying of solids and liquids
Fasting whole gastric volume
Maximum volume of Ensure ingested (satiety testing)
weight loss in kg
effect of candidate SNPs/gene deletions on response to sibutramine

Secondary Outcome Measures:

Ghrelin, leptin, insulin, GLP-1, and PYY levels integrated over the 8 hours after the meal.
Aggregate symptom score 30 min after ingestion of Ensure
Body fat
Gastric residual at 2 and 4 hours; gastric emptying T10%, and parameters from power exponential analysis will also be described
Caloric intake from a standard ad libitum meal

Enrollment:	72
Study Start Date:	January 2005
Study Completion Date:	March 2006
Primary Completion Date:	March 2006 (Final data collection date for primary outcome measure)

Detailed Description:

Background: Control of food intake, size and frequency of meals are critical to the development of obesity. The stomach signals satiation in response to calories and volume ingested, playing a role in control of calorie intake. It is unclear whether the approved appetite reducing drug sibutramine alters gastric physiology. Genetic variations are potentially key to inter-individual differences in responses to treatment with the appetite suppressant sibutramine.

Aims: 1. To compare gastric functions in healthy, overweight and obese individuals. 2. To evaluate effects of sibutramine on gastric functions and weight in patients who are overweight or obese. 3. To obtain preliminary data on the effect of genetic variation on responses to sibutramine.

Methods: We shall measure gastric emptying, fasting and postprandial gastric volumes (using validated, non-invasive imaging methods), postprandial satiation and satiety, and integrated plasma ghrelin, leptin, insulin, GLP-1 and peptide YY levels before and after 12 weeks of sibutramine 15mg vs. placebo. We shall also collect DNA, to eventually study effects of candidate genes on response to sibutramine.

Significance: Our study will provide the first evidence of the effects of sibutramine on gastric function.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

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).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00330525

Locations

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

Sponsors and Collaborators

Mayo Clinic

Investigators

Principal Investigator:

Michael Camilleri, M.D.

Mayo Clinic

More Information

No publications provided

Study ID Numbers:	1723-04
Study First Received:	May 25, 2006
Last Updated:	January 19, 2010
ClinicalTrials.gov Identifier:	NCT00330525 History of Changes
Health Authority:	United States: Institutional Review Board

Additional relevant MeSH terms:

Obesity
Psychotropic Drugs
Overweight
Pharmacologic Actions
Body Weight
Sibutramine
Signs and Symptoms

Anti-Obesity Agents
Therapeutic Uses
Nutrition Disorders
Appetite Depressants
Overnutrition
Central Nervous System Agents
Antidepressive Agents

ClinicalTrials.gov processed this record on February 08, 2010