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

Primary Purpose

Nonalcoholic Fatty Liver Disease (NAFLD)

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
EZ-Urso combination therapy
Sponsored by
Gregory Graf, PhD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Nonalcoholic Fatty Liver Disease (NAFLD) focused on measuring nonalcoholic fatty liver disease, NAFLD

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • University of Kentucky Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

EZ-URSO Combination Therapy

Arm 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.

Outcomes

Primary Outcome Measures

Reduction in Serum Alanine Transaminase (ALT)
Determine if Ezetimibe-Ursodiol combination therapy improves liver function tests (ALT)

Secondary Outcome Measures

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.
Reduction in Hepatic Fat Fraction
Determine if Ezetimibe-Ursodiol combination therapy reduces total fat in the liver as assessed by MRI

Full Information

First Posted
September 10, 2014
Last Updated
January 11, 2018
Sponsor
Gregory Graf, PhD
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1. Study Identification

Unique Protocol Identification Number
NCT02244944
Brief Title
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

2. Study Status

Record Verification Date
January 2018
Overall Recruitment Status
Terminated
Why Stopped
Failure to recruit
Study Start Date
September 2014 (undefined)
Primary Completion Date
September 2015 (Actual)
Study Completion Date
September 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Gregory Graf, PhD

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nonalcoholic Fatty Liver Disease (NAFLD)
Keywords
nonalcoholic fatty liver disease, NAFLD

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
2 (Actual)

8. Arms, Groups, and Interventions

Arm Title
EZ-URSO Combination Therapy
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
EZ-Urso combination therapy
Other Intervention Name(s)
Ezetimibe (Zetia), Ursoldiol (URSO Forte)
Intervention Description
Ursodiol 13-15 mg per kg per day combined with Ezetimibe (Zetia) 10 mg per day
Primary Outcome Measure Information:
Title
Reduction in Serum Alanine Transaminase (ALT)
Description
Determine if Ezetimibe-Ursodiol combination therapy improves liver function tests (ALT)
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Increase in Plasma Lathosterol
Description
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.
Time Frame
6 months
Title
Reduction in Hepatic Fat Fraction
Description
Determine if Ezetimibe-Ursodiol combination therapy reduces total fat in the liver as assessed by MRI
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gregory Graf, PhD
Organizational Affiliation
University of Kentucky
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Kentucky Medical Center
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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