Nonalcoholic Fatty Liver Disease (NAFLD)
Conditions
Keywords
nonalcoholic fatty liver disease, NAFLD
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
Interventions
DRUGEZ-Urso combination therapy
Ursodiol 13-15 mg per kg per day combined with Ezetimibe (Zetia) 10 mg per day
Sponsors
Gregory Graf, PhD
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Reduction in Serum Alanine Transaminase (ALT) | 6 months | Determine if Ezetimibe-Ursodiol combination therapy improves liver function tests (ALT) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
EZ-Urso combination therapy: Ursodiol 13-15 mg per kg per day combined with Ezetimibe (Zetia) 10 mg per day | 2 |
| Total | 2 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Study Terminated | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | EZ-URSO Combination Therapy |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Age, Continuous | 43.5 years |
| Region of Enrollment United States | 2 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 1 / 2 |
| serious Total, serious adverse events | 0 / 2 |
Outcome results
Primary
Reduction in Serum Alanine Transaminase (ALT)
Determine if Ezetimibe-Ursodiol combination therapy improves liver function tests (ALT)
Time frame: 6 months
Population: The trial was terminated early. No data was collected to analyze the primary outcome measure.
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.
Time frame: 6 months
Population: The trial was terminated early. No data was collected to analyze the secondary outcome measure.
Secondary
Reduction in Hepatic Fat Fraction
Determine if Ezetimibe-Ursodiol combination therapy reduces total fat in the liver as assessed by MRI
Time frame: 6 months
Population: The trial was terminated early. No data was collected to analyze the primary outcome measure.