The Influence of Ezetimibe on Gallbladder Function
Information source: Indiana University
Information obtained from ClinicalTrials.gov on February 12, 2009
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Chronic Acalculous Cholecystitis
Intervention: ezetimibe (Drug); Placebo (Drug)
Phase: N/A
Status: Not yet recruiting
Sponsored by: Indiana University Official(s) and/or principal investigator(s):
Henry A. Pitt, MD, Principal Investigator, Affiliation: Indiana University
Overall contact:
Henry A. Pitt, MD, Phone: 317-274-2304, Email: hapitt@iupui.edu
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.
Clinical Details
Official title: Te Influence of Ezetimibe on Gallbladder Function
Study design: Basic Science, Randomized, Double Blind (Subject, Investigator), Parallel Assignment, Efficacy Study
Primary outcome: Normalization of resting gallbladder 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.
Eligibility
Minimum age: 18 Years.
Maximum age: 90 Years.
Gender(s): Both.
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.
Locations and Contacts
Henry A. Pitt, MD, Phone: 317-274-2304, Email: hapitt@iupui.edu
Indiana University Hospital, Indianapolis, Indiana 46202, United States
Additional Information
Starting date: April 2010
Ending date: August 2020
Last updated: January 27, 2009
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