Lifestyle Versus Ezetimibe Plus Lifestyle in Patients With Non-alcoholic Steatohepatitis

Study Overview
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Brief Summary
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NAFLD (Non-alcoholic fatty liver disease) has become the most common cause of liver disease in Western countries (hepatic manifestation of insulin resistance); NAFLD represents a cardiovascular risk factor; Lifestyle modification(weight loss)is the effective medical treatment recommended for NASH (Non-alcoholic Steatohepatitis); Ezetimibe could represent a novel safe treatment for NAFLD (Patel 2006. Here the investigators propose a Randomized Controlled Pilot Trial to evaluate the addictive effect of ezetimibe on liver histology, biochemical and sonographic parameters in a small (n.40) number of NASH patients randomized for 12 months in two arms: lifestyle vs lifestyle+ezetimibe.

Detailed Description
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to evaluate the addictive effect of ezetimibe on liver histology, biochemical and sonographic parameters in a small (n.40) number of NASH patients randomized for 12 months in two arms: lifestyle vs lifestyle+ezetimibe.

Official Title
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A Randomised Controlled Trial of Lifestyle Versus Ezetimibe Plus Lifestyle in Patients With Non-alcoholic Steatohepatitis

Conditions
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•Non-alcoholic Steatohepatitis (NASH)

Intervention / Treatment
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* Drug: Ezetimibe
* Behavioral: Lifestyle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1.Patients older 18 years 2.Histological diagnosis of possible or definite NASH, according to Kleiner scorw, within 6 months before randomization - Exclusion Criteria: 1)Average alcohol consumption > 20 g per day in women and > 30 g per day in men 2)other causes of chronic liver disease 3) History of or planned gastrointestinal bypass or any additional bariatric surgery/intervention 4)Hepatic cirrhosis with Child-Pugh score of B or C, and/or concomitant HCC 5)Recent(within 6 months) or concomitant use of agents known to cause hepatic steatosis 7)Recent(within 6 months)change in dose/regimen or first treatment with vitamin E, C, betaine, s-adenosylmethionine, ursodeoxycholate, sylimarin, fibrate, statin, pentoxyfilline, angiotensin II inhibitors, orlistat, sibutramine 8)Ongoing or recent therapy (within 6 months) with vitamin D or with medications known to affect vitamin D3 metabolism 9)Any additional condition that might interfere with optimal partecipation in the study, according to Investigators opinion; 10)Be pregnant or breastfeeding.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ezetimibe<br>Ezetimibe tablets plus lifestyle | Drug: Ezetimibe<br>* Ezetimibe tablets<br>Behavioral: Lifestyle<br>* lifestyle<br>|
| Active Comparator: lifestyle<br>lifestyle | Behavioral: Lifestyle<br>* lifestyle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HISTOLOGICAL IMPROVEMENT IN THE SEVERITY OF NASH | either improvement in NAS by at least 2 points spread across at least 2 of the NAS components or post-treatment NAS of 3 points or less; at least 1 point improvement in the score for ballooning degeneration; no worsening of the fibrosis score. | 52 WEEKS | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in individual components of NAS score | Changes in: steatosis, lobular inflammation and hepatocellular balloonin; fibrosis; serum aminotransferase levels anthropometric measures, visceral adiposity index (VAI), insulin resistence, lipid profile and liver elastometry. | 6 weeks, 24 weeks, 52 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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•Non-alcoholic Steatohepatitis (NASH)