Metformin in Non-Alcoholic Fatty Liver Disease - Full Text View

Sponsors and Collaborators:	University Hospital, Aker Merck
Information provided by:	University Hospital, Aker
ClinicalTrials.gov Identifier:	NCT00303537

Purpose

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

Condition	Intervention	Phase
Fatty Liver	Drug: metformin	Phase II Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Efficacy Study
Official Title:	Double Blind, Randomized, Placebo Controlled Trial With Metformin in Non-Alcoholic Fatty Liver Disease (NAFLD)

Resource links provided by NLM:

MedlinePlus related topics: Liver Diseases

Drug Information available for: Metformin Metformin hydrochloride

U.S. FDA Resources

Further study details as provided by University Hospital, Aker:

Primary Outcome Measures:

Grade of steatosis as judged by repeat biopsy [ Time Frame: 6 mo ]

Secondary Outcome Measures:

Grade of necroinflammation as judged by repeat biopsy [ Time Frame: 6 mo ]
Liver density obtained by computer scan [ Time Frame: 6 mo ]
Serum alanine transaminase (ALAT) [ Time Frame: 6 mo ]

Estimated Enrollment:	90
Study Start Date:	November 2004
Estimated Study Completion Date:	June 2008

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).

Eligibility

Ages Eligible for Study:	20 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00303537

Locations

Norway
Aker University Hospital
Oslo, Norway
Akershus University Hospital
Oslo, Norway
Universitetssykehuset i Nord-Norge
Tromsø, Norway
Haukeland Universitetssykehus
Bergen, Norway

Sponsors and Collaborators

University Hospital, Aker

Merck

Investigators

Study Chair:	Kaare Birkeland, Prof./Ph.D	Aker University Hospital, Oslo, Norway
Study Chair:	Zbigniew Konopski, Cons./Ph.D	Aker University Hospital, Oslo, Norway
Study Chair:	Kristian Bjøro, Cons./Ph.D	Rikshospitalet-Radiumhospitalet, Oslo, Norway
Principal Investigator:	John W Haukeland, Physician	University Hospital, Aker

More Information

No publications provided

Study ID Numbers:	AkerU3
Study First Received:	March 16, 2006
Last Updated:	June 29, 2007
ClinicalTrials.gov Identifier:	NCT00303537 History of Changes
Health Authority:	Norway: The National Committees for Research Ethics in Norway; Norway: Norwegian Medicines Agency

Keywords provided by University Hospital, Aker:

hepatitis
metformin
non-alcoholic fatty liver (NAFLD)
non-alcoholic steatohepatitis (NASH)
Nonalcoholic fatty liver disease

Study placed in the following topic categories:

Hepatitis
Liver Diseases
Hypoglycemic Agents
Non-alcoholic Steatohepatitis (NASH)

Digestive System Diseases
Metformin
Fatty Liver

Additional relevant MeSH terms:

Liver Diseases
Hypoglycemic Agents
Digestive System Diseases
Physiological Effects of Drugs

Metformin
Fatty Liver
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 02, 2009