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

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

Overview[ - collapse ][ - ]

Purpose	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	Nonalcoholic Fatty Liver Disease (NAFLD)
Intervention	Drug: Low dose metformin Drug: Metformin Drug: Atorvastatin
Phase	N/A
Sponsor	Prof Antonino Belfiore
Responsible Party	University Magna Graecia
ClinicalTrials.gov Identifier	NCT01544751
First Received	February 16, 2012
Last Updated	June 13, 2012
Last verified	June 2012

Tracking Information[ + expand ][ + ]

First Received Date	February 16, 2012
Last Updated Date	June 13, 2012
Start Date	September 2011
Estimated Primary Completion Date	September 2013
Current Primary Outcome Measures	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.
Current Secondary Outcome Measures	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).

Descriptive Information[ + expand ][ + ]

Brief Title	Nonalcoholic Fatty Liver Disease (NAFLD) Pharmacological Treatment: Metformin Versus Atorvastatin
Official Title	Metformin Versus Atorvastatin in Nonalcoholic Hepatic Steatosis: a Randomized Study
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.
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
Study Phase	N/A
Study Design	Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Condition	Nonalcoholic Fatty Liver Disease (NAFLD)
Intervention	Drug: Low dose metformin 500 mg twice a day Drug: Metformin 1000 mg twice a day Drug: Atorvastatin 20 mg/day
Study Arm (s)	Active Comparator: Low dose Metformin 500 mg twice a day for one year Active Comparator: Metformin 1000 mg twice a day for one year Active Comparator: Atorvastatin 20 mg day

Recruitment Information[ + expand ][ + ]

Recruitment Status	Recruiting
Estimated Enrollment	150
Estimated Completion Date	September 2013
Estimated Primary Completion Date	March 2013
Eligibility 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
Gender	Both
Ages	18 Years
Accepts Healthy Volunteers	No
Contacts	Contact: Giovanbattista De sarro, Professor +03909613647110 desarro@unicz.it
Location Countries	Italy

Administrative Information[ + expand ][ + ]

NCT Number	NCT01544751
Other Study ID Numbers	2010.42
Has Data Monitoring Committee	No
Information Provided By	University Magna Graecia
Study Sponsor	Prof Antonino Belfiore
Collaborators	Not Provided
Investigators	Study Director: Antonino Belfiore, Director Endocrinology Unit
Verification Date	June 2012

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