Ezetimibe-Ursodiol Combination Therapy on Biomarkers of Liver Function and Sterol Balance in Subjects With NAFLD

Study Overview
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Brief Summary
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The purpose of this research is to gather information on the combination Zetia® (Ezetimibe) and Urso Forte® with respect to sterol balance and their effects on biomarkers of liver function in subjects with nonalcoholic fatty liver disease (NAFLD).

Detailed Description
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The study will be conducted as a prospective open label trial with pre- and post-treatment measures for all dependent variables. This trial will enroll subjects with a clinical diagnosis of nonalcoholic fatty liver disease (NAFLD) by magnetic resonance imaging (MRI), computed tomography (CT) or ultrasound, including those diagnosed with nonalcoholic steatohepatitis (NASH). Subjects will be consented, blood collected and a MRI conducted on the first visit. Patients will be advised on the proper use of the study drug and given the first three month's supply of the study drug to take home with them. For the remaining three months, study drug will be delivered by US mail along with return packaging for the prior three month's study medication in order to monitor compliance. Patients will be called routinely to encourage compliance, retention, and monitor side effects or adverse events. After six months of study drug administration, subjects will return for a follow-up visit. Blood will be drawn, an MRI will be obtained and a post-study questionnaire will be administered. Duration of Patient Enrollment: 6 months Duration of Study: 18 months

Official Title
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The Effect of Ezetimibe-Ursodiol Combination Therapy on Biomarkers of Liver Function and Sterol Balance in Subjects With NAFLD

Conditions
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Nonalcoholic Fatty Liver Disease (NAFLD)

Intervention / Treatment
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* Drug: EZ-Urso combination therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Steatosis ALT >1.5 times normal ALT/AST ratio >1.0 Normal Kidney Function Exclusion Criteria: Normal ALT within last 6 months Advanced fibrosis based on 1) biopsy, if available (Stage 3 or 4 NAFLD), 2) imaging, or 3) lab (platelet count <150,000) Daily alcohol use above 20 g/day for women and 30 g/day for men Prescription use of ursodiol, ezetimibe, vitamin E, fish oils, thiazolidinediones, insulin, sulfonylureas, HMG-CoA reductase inhibitors Weight loss greater than 15% in past 12 months Pregnant or breastfeeding Body Mass index greater than 50 Largest body circumference greater than 160 cm Claustrophobia Allergy to ezetimibe or ursodiol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EZ-URSO Combination Therapy<br>Ursodiol (URSO Forte) 13-15 mg per kg (250-500 mg b.i.d. or t.i.d depending on body weight) combined with Ezetimibe (Zetia) 10 mg o.p.d. | Drug: EZ-Urso combination therapy<br>* Ursodiol 13-15 mg per kg per day combined with Ezetimibe (Zetia) 10 mg per day<br>* Other names: Ursoldiol (URSO Forte);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in Serum Alanine Transaminase (ALT) | Determine if Ezetimibe-Ursodiol combination therapy improves liver function tests (ALT) | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Increase in Plasma Lathosterol | Determine if Ezetimibe-Ursodiol combination therapy promotes a net-negative sterol balance as evidenced by an increase in the cholesterol synthesis intermediate, lathosterol, in plasma. | 6 months | 
| Reduction in Hepatic Fat Fraction | Determine if Ezetimibe-Ursodiol combination therapy reduces total fat in the liver as assessed by MRI | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nonalcoholic fatty liver disease, NAFLD