The Influence of Ezetimibe on Gallbladder Function
The 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.
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.
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.