Clinical trial NCT01544751: Nonalcoholic Fatty Liver Disease (NAFLD) Pharmacological Treatment: Metformin Versus Atorvastatin
Official title: Metformin Versus Atorvastatin in Nonalcoholic Hepatic Steatosis: a Randomized Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Nonalcoholic Fatty Liver Disease (NAFLD)
Keywords: NAFLD
metformin
atorvastatin
metabolic syndrome
Lead sponsor: University Magna Graecia
Sponsor class: OTHER
First posted: 2012-03-06
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Participants with improvement of liver hyperechogenicity
timeFrame: one year
Secondary outcomes:
measure: Number of Participants with amelioration of metabolic syndrome and HOMA-Index
timeFrame: one years
Other outcomes:
Locations:
city: Catanzaro
country: Italy
facility: Endocrinology Unit
Study officials:
affiliation: Endocrinology Unit
name: Antonino Belfiore, Director
role: STUDY_DIRECTOR
References: