NALCAT: Atorvastatin, L-Carnitine and Non-Alcoholic Steatohepatitis

• Sponsor: Tehran University of Medical Sciences (Other)
• Overall Status: Unknown status
• CT.gov ID: NCT01617772
• Collaborator: (none)
• Enrollment: 440
• Locations: 2
• Arms: 4
• Anticipated Duration (Months): 47
• Patients Per Site: 220
• Patients Per Site Per Month: 4.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Non-alcoholic Steatohepatitis	Drug: Atorvastatin; Drug: L-Carnitine; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 440 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Comparison the Effectiveness of L-Carnitine With Atorvastatin in Non-Alcoholic Steatohepatitis (NASH)
• Actual Study Start Date: Jan 1, 2016
• Anticipated Primary Completion Date: Oct 1, 2019
• Anticipated Study Completion Date: Dec 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Atorvastatin 20mg atorvastatin daily	Drug: Atorvastatin; Atorvastatin 20 mg
Experimental: Carnitine 1000mg L-carnitine daily	Drug: L-Carnitine; 1000mg L-carnitine
Experimental: Atoral 1000mg L-carnitine and 20mg atorvastatin	Drug: Atorvastatin; Atorvastatin 20 mg; Drug: L-Carnitine; 1000mg L-carnitine
Placebo Comparator: Placebo Identically looking placebo	Drug: Placebo; Identically looking placebo

Outcome Measures

Primary Outcome Measures

1. improvement in liver stiffness [2 years]

   As measured by Fibroscan

Secondary Outcome Measures

1. improvement in liver enzyme levels [2 years]

   Difference between last and first measurements

2. Adverse drug events [2 years]

   questionnaire

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pars Cohort Center	Shiraz	Fars	Iran, Islamic Republic of
2	Masoud Clinic	Tehran		Iran, Islamic Republic of	14117

Sponsors and Collaborators

• Tehran University of Medical Sciences

Investigators

• Study Chair: Reza Malekzadeh, MD, Tehran University of Medical Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Tehran University of Medical Sciences
• ClinicalTrials.gov Identifier: NCT01617772
• Other Study ID Numbers: 90-03-37-15428
• First Posted: Jun 12, 2012
• Last Update Posted: May 11, 2018
• Last Verified: May 1, 2018

• Keywords provided by Tehran University of Medical Sciences: Non-alcoholic steatohepatitis, Atorvastatin, L-Carnitine
• Additional relevant MeSH terms: Fatty Liver; Non-alcoholic Fatty Liver Disease; Atorvastatin

Study Results

No Results Posted as of May 11, 2018