The Influence of Ezetimibe on Gallbladder Function

March 27, 2015 updated by: Indiana University

Te Influence of Ezetimibe on Gallbladder Function

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1
ezetimibe
Drug: ezetimibe
ezetimibe 10 mg daily for 4 to 6 weeks
Other Names:
  • Zetia
Placebo Comparator: 2
placebo for 4-6 weeks
Drug: Placebo
placebo for 4-6 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Normalization of resting gallbladder volume in patients with chronic acalculous cholecystitis
Time Frame: Approximately 6 weeks after treatment
Approximately 6 weeks after treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Indiana University

Investigators

  • Principal Investigator: Henry A. Pitt, MD, Indiana University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2009

Primary Completion (Anticipated)

August 1, 2009

Study Completion (Anticipated)

August 1, 2009

Study Registration Dates

First Submitted

March 3, 2008

First Submitted That Met QC Criteria

March 10, 2008

First Posted (Estimate)

March 12, 2008

Study Record Updates

Last Update Posted (Estimate)

March 30, 2015

Last Update Submitted That Met QC Criteria

March 27, 2015

Last Verified

March 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0710-24

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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