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

This study is currently recruiting participants.
Verified June 2012 by University Magna Graecia
Sponsor:
Information provided by (Responsible Party):
Prof Antonino Belfiore, University Magna Graecia
ClinicalTrials.gov Identifier:
NCT01544751
First received: February 16, 2012
Last updated: June 13, 2012
Last verified: June 2012

February 16, 2012
June 13, 2012
September 2011
March 2013   (final data collection date for primary outcome measure)
Number of Participants with improvement of liver hyperechogenicity [ Time Frame: one year ] [ Designated as safety issue: No ]
We will investigate efficacy of metformin and atorvastatin in amelioration of liver hyperechogenicity and fibrosis scores.
Same as current
Complete list of historical versions of study NCT01544751 on ClinicalTrials.gov Archive Site
Number of Participants with amelioration of metabolic syndrome and HOMA-Index [ Time Frame: one years ] [ Designated as safety issue: No ]
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).
Same as current
Not Provided
Not Provided
 
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.

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.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Nonalcoholic Fatty Liver Disease (NAFLD)
  • Drug: Low dose metformin
    500 mg twice a day
  • Drug: Metformin
    1000 mg twice a day
  • Drug: Atorvastatin
    20 mg/day
  • Active Comparator: Low dose Metformin
    500 mg twice a day for one year
    Intervention: Drug: Low dose metformin
  • Active Comparator: Metformin
    1000 mg twice a day for one year
    Intervention: Drug: Metformin
  • Active Comparator: Atorvastatin
    20 mg day
    Intervention: Drug: Atorvastatin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
150
September 2013
March 2013   (final data collection date for primary outcome measure)

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
Both
18 Years to 55 Years
No
Contact: Giovanbattista De sarro, Professor +03909613647110 desarro@unicz.it
Italy
 
NCT01544751
2010.42
No
Prof Antonino Belfiore, University Magna Graecia
Prof Antonino Belfiore
Not Provided
Study Director: Antonino Belfiore, Director Endocrinology Unit
University Magna Graecia
June 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP