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

Nonalcoholic Fatty Liver Disease (NAFLD) Clinical Trial

Official title:

Metformin Versus Atorvastatin in Nonalcoholic Hepatic Steatosis: a Randomized Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01544751
• Other study ID #: 2010.42
• Status: Recruiting
• Phase: N/A
• First received: February 16, 2012
• Last updated: May 27, 2014
• Start date: September 2011
• Est. completion date: June 2015

Study information

• Verified date: May 2014
• Source: University Magna Graecia
• Contact: Giovanbattista De sarro, Professor
• Phone: +03909613647110
• Email: desarro[@]unicz.it
• Is FDA regulated: No
• Health authority: Italy: National Bioethics Committee
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: June 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fatty Liver
• Liver Diseases
• Nonalcoholic Fatty Liver Disease (NAFLD)

Intervention

Drug:
• Low dose metformin
500 mg twice a day
• Metformin
1000 mg twice a day
• Atorvastatin
20 mg/day

Locations

Country	Name	City	State
Italy	Endocrinology Unit	Catanzaro

Sponsors (1)

Lead Sponsor	Collaborator
Prof Antonino Belfiore

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No