Clinical trial NCT01617772: Atorvastatin, L-Carnitine and Non-Alcoholic Steatohepatitis
Official title: Comparison the Effectiveness of L-Carnitine With Atorvastatin in Non-Alcoholic Steatohepatitis (NASH)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Non-alcoholic Steatohepatitis
Keywords: Non-alcoholic steatohepatitis, Atorvastatin, L-Carnitine
Lead sponsor: Tehran University of Medical Sciences
Sponsor class: OTHER
First posted: 2012-06-12
Enrollment: 440
Sex: ALL
Minimum age (years): 40
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

* NASH diagnosed on the basis of the following criteria:

  1. Imaging techniques showing evidence of hepatic steatosis
  2. 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

Primary outcomes:
measure: improvement in liver stiffness
timeFrame: 2 years
Secondary outcomes:
measure: improvement in liver enzyme levels
timeFrame: 2 years
measure: Adverse drug events
timeFrame: 2 years
Other outcomes:
Locations:
city: Shiraz
country: Iran, Islamic Republic of
facility: Pars Cohort Center
state: Fars
city: Tehran
country: Iran, Islamic Republic of
facility: Masoud Clinic
Study officials:
affiliation: Tehran University of Medical Sciences
name: Reza Malekzadeh, MD
role: STUDY_CHAIR
References: