The Influence of Ezetimibe on Gallbladder Function

Study Overview
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Brief Summary
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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
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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.

Official Title
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Te Influence of Ezetimibe on Gallbladder Function

Conditions
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Chronic Acalculous Cholecystitis

Intervention / Treatment
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* Drug: ezetimibe
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>ezetimibe | Drug: ezetimibe<br>* ezetimibe 10 mg daily for 4 to 6 weeks<br>* Other names: Zetia;|
| Placebo Comparator: 2<br>placebo for 4-6 weeks | Drug: Placebo<br>* placebo for 4-6 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gallbladder, ezetimibe for 4 to 6 weeks prior to gallbladder removal