Nonalcoholic Fatty Liver Disease (NAFLD) Pharmacological Treatment: Metformin Versus Atorvastatin

Metformin Versus Atorvastatin in Nonalcoholic Hepatic Steatosis: a Randomized Study

The first line approach to NAFLD is currently based on diet and lifestyle modification. Aim of our Unit is to compare the efficacy of two different doses of metformin (1 g/day and 2 g/day) with atorvastatin (20 mg/day) on amelioration of inflammatory and cardiometabolic parameters, ultrasound signs and clinical scores associated with liver fibrosis in early-stage NAFLD non-diabetic patients.

Study Overview

• Status: Unknown
• Conditions: Nonalcoholic Fatty Liver Disease (NAFLD)
• Intervention / Treatment: Drug: Atorvastatin; Drug: Metformin; Drug: Low dose metformin

Detailed Description

Non alcoholic fatty liver disease (NAFLD) is a common liver disease that encompasses both simple steatosis and non alcoholic steatohepatitis (NASH.

There is currently no therapy that is of proven benefit for these liver disorders both of which are closely associated with insulin resistance and features of the metabolic syndrome such as obesity, hyperlipidaemia and type 2 diabetes mellitus. The first line approach to NAFLD is currently based on diet and lifestyle modification. However, dietary treatment is limited by the lack of compliance and the frequent regain of weight at follow-up.

Aim of our Unit is to compare the efficacy of two different doses of metformin (1 g/day and 2 g/day) with atorvastatin (20 mg/day) on amelioration of inflammatory and cardiometabolic parameters, ultrasound signs and clinical scores associated with liver fibrosis in early-stage NAFLD non-diabetic patients.

The investigators will enrol obese or overweight non-diabetic patients with ultrasonographic diagnosis of hepatic steatosis at early stage (NAFLD). The investigators will exclude from the study patients with clinical-biochemical and ultrasound markers of disease severity (age, BMI, lipid profile, AST, ALT, Angulo, BAAT and HAIR clinical fibrosis scores, signs of portal hypertension and posterior attenuation of the deep liver parenchyma at US). Patients who meet all eligibility criteria will be randomly assigned to one of three groups for 12 months of study treatment. The first group (n=50) will receive metformin (1g/day) plus dietary treatment; the second group (n=50) will be given metformin (2 g/day) and the third group (n=50) will be treated with atorvastatin (20 mg/day). All participants will be followed-up at 3, 6, 9, 12 months intervals after randomization. We will compare the effects of two doses of metformin with atorvastatin on the amelioration of both inflammatory (PCR, TNF-a , IL-6) and metabolic parameters (lipid profile, BMI, waist circumference, fasting glucose, 2-h glucose tolerance test, insulin, transaminases, adiponectin,leptin, HOMA-IR index and VAI index). Furthermore, we will assess the improvement under drug treatment of liver steatosis on the basis of US signs (liver echogenicity and stiffness) and of fibrosis scoring systems (Angulo, BAAT and HAIR scores).

In conclusion, considering the increasing prevalence of NAFLD and its strong association with cardiovascular diseases and cancer, the investigators expect to identify a safe pharmacological regimen that, in addition to dietary treatment, may ameliorate or even reverse this liver disease and the underlying risk factors. This study could have an important social impact in terms of both preventive and therapeutic interventions.

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Giovanbattista De sarro, Professor; Phone Number: +03909613647110; Email: desarro@unicz.it

Study Locations

• Italy
  • Catanzaro, Italy, 88100
    • Recruiting
    • Endocrinology Unit
    • Contact: Angela Mazza, Post doc; Phone Number: +03909613647110; Email: angela_mazza@libero.it
    • Contact: Barbara Fruci, Doctor; Phone Number: +03909613647110; Email: barbara.fruci@yahoo.it
    • Principal Investigator: Antonino Belfiore, Professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age <=55
• BMI <=40
• Total cholesterol <=280 mg/dl
• LDL <=180 mg/dl
• Triglycerides <=200 mg/dl
• AST and ALT in the normal range
• Signs of simple liver steatosis at ultrasonorography.

Exclusion criteria:

• Type 2 diabetes
• Heart disease
• Renal failure
• Smoking habit
• Alcohol intake of more than 20 g per day in the case of women and more than 30 g per day in the case of men
• Hepatic virus infection
• Autoimmune, metabolic or genetic liver diseases
• Use of drugs known to induce liver steatosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Low dose Metformin; 500 mg twice a day for one year	Drug: Low dose metformin; 500 mg twice a day
Active Comparator: Metformin; 1000 mg twice a day for one year	Drug: Metformin; 1000 mg twice a day
Active Comparator: Atorvastatin; 20 mg day	Drug: Atorvastatin; 20 mg/day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with improvement of liver hyperechogenicity	We will investigate efficacy of metformin and atorvastatin in amelioration of liver hyperechogenicity and fibrosis scores.	one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with amelioration of metabolic syndrome and HOMA-Index	We will investigate efficacy of metformin and atorvastatin in amelioration of metabolic parameters (change in the number of patients with metabolic syndrome from baseline and after treatment and amelioration of HOMA-Index from Baseline at one years).	one years

Collaborators and Investigators

• Sponsor: Prof Antonino Belfiore
• Investigators: Study Director: Antonino Belfiore, Director, Endocrinology Unit

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Anticipated): June 1, 2015
• Study Completion (Anticipated): June 1, 2015

Study Registration Dates

• First Submitted: February 16, 2012
• First Submitted That Met QC Criteria: March 5, 2012
• First Posted (Estimate): March 6, 2012

Study Record Updates

• Last Update Posted (Estimate): May 28, 2014
• Last Update Submitted That Met QC Criteria: May 27, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Keywords: NAFLD; metformin; metabolic syndrome; atorvastatin
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin; Metformin
• Other Study ID Numbers: 2010.42