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

NCT ID: NCT01544751

Last Updated: 2014-05-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

150 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-09-30

Study Completion Date

2015-06-30

Brief Summary

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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

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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.

Conditions

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Nonalcoholic Fatty Liver Disease (NAFLD)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Low dose Metformin

500 mg twice a day for one year

Group Type ACTIVE_COMPARATOR

Low dose metformin

Intervention Type DRUG

500 mg twice a day

Metformin

1000 mg twice a day for one year

Group Type ACTIVE_COMPARATOR

Metformin

Intervention Type DRUG

1000 mg twice a day

Atorvastatin

20 mg day

Group Type ACTIVE_COMPARATOR

Atorvastatin

Intervention Type DRUG

20 mg/day

Interventions

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Low dose metformin

500 mg twice a day

Intervention Type DRUG

Metformin

1000 mg twice a day

Intervention Type DRUG

Atorvastatin

20 mg/day

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Prof Antonino Belfiore

OTHER

Sponsor Role lead

Responsible Party

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Prof Antonino Belfiore

Full Professor

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Antonino Belfiore, Director

Role: STUDY_DIRECTOR

Endocrinology Unit

Locations

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Endocrinology Unit

Catanzaro, Catanzaro, Italy

Site Status RECRUITING

Countries

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Italy

Central Contacts

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Giovanbattista De sarro, Professor

Role: CONTACT

+03909613647110

Facility Contacts

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Angela Mazza, Post doc

Role: primary

+03909613647110

Barbara Fruci, Doctor

Role: backup

+03909613647110

Other Identifiers

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2010.42

Identifier Type: -

Identifier Source: org_study_id

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