Metformin in Non-Alcoholic Fatty Liver Disease

Condition(s) targeted: Fatty Liver

Intervention: metformin (Drug)

Phase: Phase 2/Phase 3

Status: No longer recruiting

Sponsored by: University Hospital, Aker

Official(s) and/or principal investigator(s):
Kaare Birkeland, Prof./Ph.D, Study Chair, Affiliation: Aker University Hospital, Oslo, Norway
Zbigniew Konopski, Cons./Ph.D, Study Chair, Affiliation: Aker University Hospital, Oslo, Norway
Kristian Bjøro, Cons./Ph.D, Study Chair, Affiliation: Rikshospitalet-Radiumhospitalet, Oslo, Norway
John W Haukeland, Physician, Principal Investigator, Affiliation: University Hospital, Aker

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

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

Study design: Interventional, Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Efficacy Study

Primary outcome: Grade of steatosis as judged by repeat biopsy

Secondary outcome:

Grade of necroinflammation as judged by repeat biopsy

Liver density obtained by computer scan

Serum alanine transaminase (ALAT)

Detailed 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).

Minimum age: 20 Years. Maximum age: 70 Years. Gender(s): Both.

Criteria:

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.

Aker University Hospital, Oslo, Norway

Akershus University Hospital, Oslo, Norway

Haukeland Universitetssykehus, Bergen, Norway

Universitetssykehuset i Nord-Norge, Tromsø, Norway

Starting date: November 2004
Ending date: June 2008
Last updated: June 29, 2007