The Influence of Ezetimibe on Gallbladder Function

NCT ID: NCT00634140

Last Updated: 2015-03-30

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: NA
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-08-31
• Study Completion Date: 2009-08-31

Brief Summary

Ezetimibe is a drug which inhibits the absorption of both dietary and biliary cholesterol in the small intestine. Ezetimibe has been approved for use in humans to lower serum cholesterol.

The primary aim of this study is to determine if ezetimibe normalizes resting and residual volume in patients with chronic acalculous cholecystitis.

Detailed Description

Gallbladder disease continues to be a major healthcare problem in the United States with more than 750,000 cholecystectomies being performed each year. In the last decade, the proportion of elective cholecystectomies performed for chronic acalculous cholecystitis has more than doubled. During this same time, obesity has reached epidemic proportions. In addition, obesity-induced visceral steatosis is known to cause a local inflammatory process resulting in organ dysfunction, with nonalcoholic steatohepatitis being a well established example of this phenomenon. Previous data from our lab also have shown that both congenital and diet-induced obesity result in cholecystosteatosis, an increase in gallbladder wall fats accompanied by altered gallbladder motility and absorption. This phenomenon also has been documented in humans, with patients with chronic acalculous and/or calculous cholecystitis having increased gallbladder fat than nondiseased controls.

Ezetimibe is a drug which inhibits the absorption of both dietary and biliary cholesterol in the small intestine. Ezetimibe has been approved for use in humans to lower serum cholesterol. Moreover, ezetimibe has been shown to ameliorate hepatic steatosis and cholesterol gallstone formation in animal models. Previous data from our lab have documented that ezetimibe lowers serum cholesterol, prevents biliary crystals and ameliorates cholecystosteatosis in lean mice fed a high fat diet. However, the influence of ezetimibe on gallbladder motility, absorption and accumulation of toxic fats, metabolites, cytokines and chemokines, cholecystosteatosis, have not been studied in humans. Therefore, the aims of this study are 1) to determine if ezetimibe normalizes resting and residual volume in patients with chronic acalculous cholecystitis, 2) to determine if ezetimibe normalizes gallbladder ion flux in patients with chronic acalculous cholecystitis and 3) to determine if ezetimibe normalizes gallbladder absorption/secretion modulators as well as gallbladder fat, cytokines and chemkines.

Subjects with typical biliary pain and or ejection fraction less than 30% on a HIDA scan will be identified. Patients will then be randomized with one group given ezetimibe and the other group given placebo. All subjects will have gallbladder ultrasound studies to determine volume before and after a standardized fatty meal both before starting ezetimibe or placebo and after 4 weeks. A cholecystectomy will then be performed. In addition, pieces of the gallbladder taken at cholecystectomy will be analyzed for ion flux, as well as absorption/secretion modulators and accumulation of toxic fats, metabolites, cytokines and chemokines.

Conditions

Chronic Acalculous Cholecystitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

1

ezetimibe

Group Type: EXPERIMENTAL

ezetimibe

Intervention Type: DRUG

ezetimibe 10 mg daily for 4 to 6 weeks

2

placebo for 4-6 weeks

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

placebo for 4-6 weeks

Interventions

ezetimibe

ezetimibe 10 mg daily for 4 to 6 weeks

Intervention Type: DRUG

Placebo

placebo for 4-6 weeks

Intervention Type: DRUG

Other Intervention Names

Zetia

Eligibility Criteria

Inclusion Criteria

• Subjects with typical biliary pain and ejection fraction <30% on a HIDA scan.
• Must be > 18 years of age.

Exclusion Criteria

• Subjects with gallstones seen on HIDA.
• Subjects on statin medication
• Subjects with known allergies to ezetimibe.
• Subjects who are pregnant or breast-feeding.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Indiana University

OTHER

Sponsor Role: lead

Responsible Party

Indiana University

Principal Investigators

Henry A. Pitt, MD

Role: PRINCIPAL_INVESTIGATOR

Indiana University

Locations

Indiana University Hospital

Indianapolis, Indiana, United States

Countries

United States

Other Identifiers

0710-24

Identifier Type: -

Identifier Source: org_study_id