Pharmacodynamic Effects of Sibutramine on Gastric Function in Obesity

Obesity Clinical Trial

Official title:

Pharmacodynamic Effects of Sibutramine on Gastric Function in Obesity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00330525
• Other study ID #: 1723-04
• Status: Completed
• Phase: Phase 2
• First received: May 25, 2006
• Last updated: January 19, 2010
• Start date: January 2005
• Est. completion date: March 2006

Study information

• Verified date: January 2010
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 72
• Est. completion date: March 2006
• Est. primary completion date: March 2006
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria

1. 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.

2. Age: 18-65 years

3. 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

1. Weight exceeding 300 pounds or 137 kilograms (due to limitations regarding SPECT imaging studies).

2. Abdominal surgery other than appendectomy, Caesarian section or tubal ligation.

3. 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).

4. 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.

5. 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.

6. Concomitant use of MAOI inhibitors and other centrally acting appetite suppressants (since this would make them ineligible for sibutramine treatment).

7. Hypersensitivity to sibutramine (since this would make them ineligible for sibutramine treatment).

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Obesity
• Overweight

Intervention

Drug:
• sibutramine

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Mayo Clinic

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	T1/2 gastric emptying of solids and liquids
Primary	Fasting whole gastric volume
Primary	Maximum volume of Ensure ingested (satiety testing)
Primary	weight loss in kg
Primary	effect of candidate SNPs/gene deletions on response to sibutramine
Secondary	Ghrelin, leptin, insulin, GLP-1, and PYY levels integrated over the 8 hours after the meal.
Secondary	Aggregate symptom score 30 min after ingestion of Ensure
Secondary	Body fat
Secondary	Gastric residual at 2 and 4 hours; gastric emptying T10%, and parameters from power exponential analysis will also be described
Secondary	Caloric intake from a standard ad libitum meal