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

Gregory Graf, PhD

Status and phase: Terminated; Phase 2

Conditions: Nonalcoholic Fatty Liver Disease (NAFLD)

Treatments: Drug: EZ-Urso combination therapy

Study type: Interventional

Funder types: Other

Identifiers

NCT02244944

13-0972-F1V

Details and patient eligibility

About

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).

Full 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

Enrollment: 2 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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2 participants in 1 patient group

EZ-URSO Combination Therapy

Experimental group

Description:

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.

Treatment:

Drug: EZ-Urso combination therapy