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

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

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).

Study Overview

• Status: Terminated
• Conditions: Nonalcoholic Fatty Liver Disease (NAFLD)
• Intervention / Treatment: Drug: EZ-Urso combination therapy

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EZ-URSO Combination Therapy; 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; Ursodiol 13-15 mg per kg per day combined with Ezetimibe (Zetia) 10 mg per day; Other Names: Ezetimibe (Zetia); Ursoldiol (URSO Forte)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Gregory Graf, PhD
• Investigators: Principal Investigator: Gregory Graf, PhD, University of Kentucky

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: September 10, 2014
• First Submitted That Met QC Criteria: September 17, 2014
• First Posted (Estimate): September 19, 2014

Study Record Updates

• Last Update Posted (Actual): February 7, 2018
• Last Update Submitted That Met QC Criteria: January 11, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: NAFLD; nonalcoholic fatty liver disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Ezetimibe
• Other Study ID Numbers: 13-0972-F1V