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

Nonalcoholic Fatty Liver Disease (NAFLD) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02244944
• Other study ID #: 13-0972-F1V
• Status: Terminated
• Phase: Phase 2
• First received: September 10, 2014
• Last updated: January 11, 2018
• Start date: September 2014
• Est. completion date: September 2015

Study information

• Verified date: January 2018
• Source: University of Kentucky
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: September 2015
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Fatty Liver
• Liver Diseases
• Non-alcoholic Fatty Liver Disease
• Nonalcoholic Fatty Liver Disease (NAFLD)

Intervention

Drug:
• EZ-Urso combination therapy
Ursodiol 13-15 mg per kg per day combined with Ezetimibe (Zetia) 10 mg per day

Locations

Country	Name	City	State
United States	University of Kentucky Medical Center	Lexington	Kentucky

Sponsors (1)

Lead Sponsor	Collaborator
Gregory Graf, PhD

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Reduction in Serum Alanine Transaminase (ALT)	Determine if Ezetimibe-Ursodiol combination therapy improves liver function tests (ALT)	6 months
Secondary	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
Secondary	Reduction in Hepatic Fat Fraction	Determine if Ezetimibe-Ursodiol combination therapy reduces total fat in the liver as assessed by MRI	6 months