Clinical trial NCT02244944: Ezetimibe-Ursodiol Combination Therapy on Biomarkers of Liver Function and Sterol Balance in Subjects With NAFLD
Official title: The Effect of Ezetimibe-Ursodiol Combination Therapy on Biomarkers of Liver Function and Sterol Balance in Subjects With NAFLD
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Nonalcoholic Fatty Liver Disease (NAFLD)
Keywords: nonalcoholic fatty liver disease
NAFLD
Lead sponsor: University of Kentucky
Sponsor class: OTHER
First posted: 2014-09-19
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Reduction in Serum Alanine Transaminase (ALT)
timeFrame: 6 months
Secondary outcomes:
measure: Increase in Plasma Lathosterol
timeFrame: 6 months
measure: Reduction in Hepatic Fat Fraction
timeFrame: 6 months
Other outcomes:
Locations:
city: Lexington
country: United States
facility: University of Kentucky Medical Center
state: Kentucky
Study officials:
affiliation: University of Kentucky
name: Gregory Graf, PhD
role: PRINCIPAL_INVESTIGATOR
References: