Atorvastatin, L-Carnitine and Non-Alcoholic Steatohepatitis

Phase 2

• Conditions: Non-alcoholic Steatohepatitis
• Interventions: Drug: Atorvastatin; Drug: Placebo; Drug: L-Carnitine

• Registration Number: NCT01617772
• Lead Sponsor: Tehran University of Medical Sciences

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.

Study Timeline

• Study First Submitted: 2012-06-08
• Study First Submitted QC: 2012-06-08
• Study First Posted: 2012-06-12
• Study Start: 2016-01-01
• Status Verified: 2018-05
• Last Update Submitted: 2018-05-05
• Last Update Posted: 2018-05-11
• Primary Completion: 2019-10
• Study Completion: 2019-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 440

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Atorvastatin	Atorvastatin	20mg atorvastatin daily
Placebo	Placebo	Identically looking placebo
Carnitine	L-Carnitine	1000mg L-carnitine daily
Atoral	Atorvastatin	1000mg L-carnitine and 20mg atorvastatin
Atoral	L-Carnitine	1000mg L-carnitine and 20mg atorvastatin

Primary Outcome Measures

Name	Time	Method
improvement in liver stiffness	2 years	As measured by Fibroscan

Secondary Outcome Measures

Name	Time	Method
improvement in liver enzyme levels	2 years	Difference between last and first measurements
Adverse drug events	2 years	questionnaire

Trial Locations

Locations (2)

Masoud Clinic; 🇮🇷 Tehran, Iran, Islamic Republic of

Pars Cohort Center; 🇮🇷 Shiraz, Fars, Iran, Islamic Republic of