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

Phase 2

Terminated

• Conditions: Nonalcoholic Fatty Liver Disease (NAFLD)
• Interventions: Drug: EZ-Urso combination therapy

• Registration Number: NCT02244944
• Lead Sponsor: Gregory Graf, PhD

Brief Summary

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

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 Timeline

• Study Start: 2014-09
• Study First Submitted: 2014-09-10
• Study First Submitted QC: 2014-09-17
• Study First Posted: 2014-09-19
• Primary Completion: 2015-09
• Study Completion: 2015-09
• Results First Submitted: 2017-09-20
• Status Verified: 2018-01
• Results First Submitted QC: 2018-01-11
• Last Update Submitted: 2018-01-11
• Results First Posted: 2018-02-07
• Last Update Posted: 2018-02-07

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 2

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
EZ-URSO Combination Therapy	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.

Primary Outcome Measures

Name	Time	Method
Reduction in Serum Alanine Transaminase (ALT)	6 months	Determine if Ezetimibe-Ursodiol combination therapy improves liver function tests (ALT)

Secondary Outcome Measures

Name	Time	Method
Increase in Plasma Lathosterol	6 months	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.
Reduction in Hepatic Fat Fraction	6 months	Determine if Ezetimibe-Ursodiol combination therapy reduces total fat in the liver as assessed by MRI

Trial Locations

Locations (1)

University of Kentucky Medical Center; 🇺🇸 Lexington, Kentucky, United States