Atorvastatin, L-Carnitine and Non-Alcoholic Steatohepatitis

Study Overview
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Brief Summary
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The aim of the present study was to compare the effects of simvastatin and L-carnitine coadministration versus simvastatin, L-Carnitine monotherapy on liver transaminases and liver elasticity in NASH patients.

Detailed Description
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Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of disease ranging from steatosis to steatohepatitis (nonalcoholic steatohepatitis, NASH) to cirrhosis. Statins are competitive inhibitors of Hydroxymethylglutaryl-CoA reductase, the rate-limiting step in cholesterol biosynthesis. They occupy a portion of the binding site of Hydroxymethylglutaryl-CoA, blocking access of this substrate to the active site on the enzyme. A reduction in intrahepatic cholesterol leads to an increase in LDL receptor turnover that results from an enhanced rate of hepatic LDL receptor cycling. On the other hand recent studies have implicated several important cellular processes and signaling pathways that are affected by abnormal lipid metabolism, resulting in specific biochemical, histological, and clinical changes associated with NAFLD. Maybe statins, as lipid lowering agents, and through their effect in reduction of intrahepatic cholesterol, can affect the abnormal lipid metabolism in NASH. L- carnitine, can improve the outcome of NASH, because it reduces lipid levels, limits oxidative stress, and modulates inflammatory responses . It performs a number of essential intracellular and metabolic functions, such as fatty acid transport, detoxification of potentially toxic metabolites, regulation of the mitochondrial acyl-CoA / CoA ratio, and stabilization of cell membranes. It has a pivotal role in the transport of long chain fatty acids across the inner mitochondrial membrane.

Official Title
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Comparison the Effectiveness of L-Carnitine With Atorvastatin in Non-Alcoholic Steatohepatitis (NASH)

Conditions
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Non-alcoholic Steatohepatitis

Intervention / Treatment
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* Drug: Atorvastatin
* Drug: L-Carnitine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: NASH diagnosed on the basis of the following criteria: Imaging techniques showing evidence of hepatic steatosis Increased alanine transaminase above 1.5 times normal (normal: 20 IU/L for women, 30 for men) on two occasions three months apart. Exclusion Criteria: Patients with hepatitis B or C alanine transaminase > 300 IU/L Participants presenting one or more causes commonly associated with secondary NAFLD (drugs, surgical procedures, environmental toxins, or total parenteral nutrition) Alcohol ingestion greater than 40 gr per week Abnormal Lipid profile (TG>500 , LDL>160) Patients with hypertension, diabetes mellitus, coronary heart disease Fibroscan score more than 14 kp pregnancy, lactation Drug addiction Reynolds Risk Score > 10% Not consenting to the study

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 60 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: Factorial Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Atorvastatin<br>20mg atorvastatin daily | Drug: Atorvastatin<br>* Atorvastatin 20 mg<br>|
| Experimental: Carnitine<br>1000mg L-carnitine daily | Drug: L-Carnitine<br>* 1000mg L-carnitine<br>|
| Experimental: Atoral<br>1000mg L-carnitine and 20mg atorvastatin | Drug: Atorvastatin<br>* Atorvastatin 20 mg<br>Drug: L-Carnitine<br>* 1000mg L-carnitine<br>|
| Placebo Comparator: Placebo<br>Identically looking placebo | Drug: Placebo<br>* Identically looking placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| improvement in liver stiffness | As measured by Fibroscan | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| improvement in liver enzyme levels | Difference between last and first measurements | 2 years | 
| Adverse drug events | questionnaire | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-alcoholic steatohepatitis, Atorvastatin, L-Carnitine