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

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ClinicalTrials.gov Identifier: NCT01544751
Recruitment Status : Unknown
Verified May 2014 by Prof Antonino Belfiore, University Magna Graecia.
Recruitment status was:  Recruiting
First Posted : March 6, 2012
Last Update Posted : May 28, 2014
Sponsor:
Information provided by (Responsible Party):
Prof Antonino Belfiore, University Magna Graecia

Brief 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.

Condition or disease Intervention/treatment Phase
Nonalcoholic Fatty Liver Disease (NAFLD) Drug: Low dose metformin Drug: Metformin Drug: Atorvastatin Not Applicable

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  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Metformin Versus Atorvastatin in Nonalcoholic Hepatic Steatosis: a Randomized Study
Study Start Date : September 2011
Estimated Primary Completion Date : June 2015
Estimated Study Completion Date : June 2015


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



Primary Outcome Measures :
  1. Number of Participants with improvement of liver hyperechogenicity [ Time Frame: one year ]
    We will investigate efficacy of metformin and atorvastatin in amelioration of liver hyperechogenicity and fibrosis scores.


Secondary Outcome Measures :
  1. Number of Participants with amelioration of metabolic syndrome and HOMA-Index [ Time Frame: one years ]
    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).



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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01544751


Contacts
Contact: Giovanbattista De sarro, Professor +03909613647110 desarro@unicz.it

Locations
Italy
Endocrinology Unit Recruiting
Catanzaro, Italy, 88100
Contact: Angela Mazza, Post doc    +03909613647110    angela_mazza@libero.it   
Contact: Barbara Fruci, Doctor    +03909613647110    barbara.fruci@yahoo.it   
Principal Investigator: Antonino Belfiore, Professor         
Sponsors and Collaborators
Prof Antonino Belfiore
Investigators
Study Director: Antonino Belfiore, Director Endocrinology Unit

Responsible Party: Prof Antonino Belfiore, Full Professor, University Magna Graecia
ClinicalTrials.gov Identifier: NCT01544751     History of Changes
Other Study ID Numbers: 2010.42
First Posted: March 6, 2012    Key Record Dates
Last Update Posted: May 28, 2014
Last Verified: May 2014

Keywords provided by Prof Antonino Belfiore, University Magna Graecia:
NAFLD
metformin
atorvastatin
metabolic syndrome

Additional relevant MeSH terms:
Liver Diseases
Fatty Liver
Non-alcoholic Fatty Liver Disease
Digestive System Diseases
Metformin
Atorvastatin Calcium
Hypoglycemic Agents
Physiological Effects of Drugs
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors