Atorvastatin, L-Carnitine and Non-Alcoholic Steatohepatitis (NALCAT)

Tehran University of Medical Sciences

Status and phase: Unknown; Phase 2

Conditions: Non-alcoholic Steatohepatitis

Treatments: Drug: L-Carnitine; Drug: Placebo; Drug: Atorvastatin

Study type: Interventional

Funder types: Other

Identifiers

NCT01617772

90-03-37-15428

Details and patient eligibility

About

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.

Full 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.

Enrollment: 440 estimated patients

Sex: All

Ages: 40 to 60 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Quadruple Blind

---

440 participants in 4 patient groups, including a placebo group

Atorvastatin

Experimental group

Description:

20mg atorvastatin daily

Treatment:

Drug: Atorvastatin

Carnitine

Experimental group

Description:

1000mg L-carnitine daily

Treatment:

Drug: L-Carnitine

Atoral

Experimental group

Description:

1000mg L-carnitine and 20mg atorvastatin

Treatment:

Drug: L-Carnitine

Drug: Atorvastatin

Placebo

Placebo Comparator group

Description:

Identically looking placebo

Treatment:

Drug: Placebo