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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Atorvastatin | Experimental | 20mg atorvastatin daily |
|
| Carnitine | Experimental | 1000mg L-carnitine daily |
|
| Atoral | Experimental | 1000mg L-carnitine and 20mg atorvastatin |
|
| Placebo | Placebo Comparator | Identically looking placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Atorvastatin | Drug | Atorvastatin 20 mg |
| |
| Measure | Description | Time Frame |
|---|---|---|
| improvement in liver stiffness | As measured by Fibroscan | 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| improvement in liver enzyme levels | Difference between last and first measurements | 2 years |
| Adverse drug events | questionnaire | 2 years |
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Inclusion Criteria:
NASH diagnosed on the basis of the following criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Shahin Merat, Professor | Contact | +98 917 117 3966 | merat@tums.ac.ir | |
| Reza Malekzadeh, Professor | Contact | +98 912 111 4139 | malek@ams.ac.ir |
| Name | Affiliation | Role |
|---|---|---|
| Reza Malekzadeh, MD | Tehran University of Medical Sciences | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Pars Cohort Center | Active, not recruiting | Shiraz | Fars | Iran | ||
| Masoud Clinic |
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| ID | Term |
|---|---|
| D065626 | Non-alcoholic Fatty Liver Disease |
| ID | Term |
|---|---|
| D005234 | Fatty Liver |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| D000069059 | Atorvastatin |
| D002331 | Carnitine |
| ID | Term |
|---|---|
| D011758 | Pyrroles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| L-Carnitine |
| Drug |
1000mg L-carnitine |
|
| Placebo | Drug | Identically looking placebo |
|
| Recruiting |
| Tehran |
| 14117 |
| Iran |
|
| D006538 |
| Heptanoic Acids |
| D005227 | Fatty Acids |
| D008055 | Lipids |
| D050337 | Trimethyl Ammonium Compounds |
| D000644 | Quaternary Ammonium Compounds |
| D000588 | Amines |
| D009930 | Organic Chemicals |