Metformin in Non-Alcoholic Fatty Liver Disease

Fatty Liver Clinical Trial

Official title:

Double Blind, Randomized, Placebo Controlled Trial With Metformin in Non-Alcoholic Fatty Liver Disease (NAFLD)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00303537
• Other study ID #: AkerU3
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• First received: March 16, 2006
• Last updated: June 29, 2007
• Start date: November 2004
• Est. completion date: June 2008

Study information

• Verified date: June 2007
• Source: University Hospital, Aker
• Contact: n/a
• Is FDA regulated: No
• Health authority: Norway:National Committee for Medical and Health Research EthicsNorway: Norwegian Medicines Agency
• Study type: Interventional

Clinical Trial Summary

The study evaluates the use of the antidiabetic medicine metformin in nonalcoholic fatty liver disease.

Description:

Nonalcoholic fatty liver disease (NAFLD) is a prevalent disorder associated with insulin resistance. Metformin is a drug that has been used for several decades in the treatment of diabetes mellitus. Metformin is known to improve insulin sensitivity. Some authors have reported beneficial effects of metformin in NAFLD, others have not been able to reproduce these findings. Only a few randomized controlled studies have been published so far, and there is still need for controlled trials with sufficient power to assess the efficacy of metformin in this condition.

The aim of this study is to see whether treatment with metformin for 26 weeks results in reduction of liver steatosis (primary endpoint) and reduction in grade of inflammation in those with non-alcoholic steatohepatitis (NASH) (secondary endpoint).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 90
• Est. completion date: June 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 70 Years

Eligibility

Inclusion Criteria:

• Histologically proven NAFLD less than 18 months prior to inclusion. For those with pure steatosis, ALAT or aspartate aminotransferase (ASAT) must be elevated above the upper limits of normal, and impaired glucose tolerance or diabetes mellitus type 2 must be present.

• Body weight within +/- 5 kg compared with the weight at the time of biopsy.

Exclusion Criteria:

• Treatment for more than 1 week with metformin or glitazones the last 6 months before inclusion.

• Treatment with insulin.

• Hypersensitivity to metformin.

• Treatment with cimetidine.

• Heart failure requiring pharmacological treatment.

• Coronary heart disease (New York Heart Association [NYHA] class 3 or 4).

• Chronic obstructive lung disease (moderate or severe).

• Breast-feeding or pregnant.

• Metabolic acidosis.

• Renal failure (male [?]: creatinine > 135 micromol/L, female [?] > 110 micromol/L).

• Average alcohol consumption > 24 g/day the last year.

• Serum ALAT or serum ASAT > 5 x upper limit of normal (ULN) at screening.

• Cirrhosis.

• Platelets < 100 000.

• Haemochromatosis.

• Alfa-1-antitrypsin-deficiency.

• Wilson's disease.

• Thyroid dysfunction (0.2 mU/L < thyroid stimulating hormone [TSH] < 5.0 mU/L).

• Chronic infection with hepatitis B or C virus or HIV.

• Autoimmune hepatitis (antinuclear antibodies [ANA] > 1/256 or smooth muscle antibodies [SMA] > 1/128).

• Primary biliary cirrhosis (antimitochondrial antibodies [AMA] > 1/64).

• Primary sclerosing cholangitis.

• Previous participation in another clinical trial the last 6 months.

• Legal incapability.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fatty Liver
• Liver Diseases

Intervention

Drug:
• metformin

Locations

Country	Name	City	State
Norway	Haukeland Universitetssykehus	Bergen
Norway	Aker University Hospital	Oslo
Norway	Akershus University Hospital	Oslo
Norway	Universitetssykehuset i Nord-Norge	Tromsø

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Aker	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

Norway, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Grade of steatosis as judged by repeat biopsy		6 mo
Secondary	Grade of necroinflammation as judged by repeat biopsy		6 mo
Secondary	Liver density obtained by computer scan		6 mo
Secondary	Serum alanine transaminase (ALAT)		6 mo