Metformin in Non-Alcoholic Fatty Liver Disease

Overview[ - collapse ][ - ]

Purpose The study evaluates the use of the antidiabetic medicine metformin in nonalcoholic fatty liver disease.
ConditionFatty Liver
InterventionDrug: metformin
PhasePhase 2/Phase 3
SponsorUniversity Hospital, Aker
Responsible PartyUniversity Hospital, Aker
ClinicalTrials.gov IdentifierNCT00303537
First ReceivedMarch 16, 2006
Last UpdatedJune 29, 2007
Last verifiedJune 2007

Tracking Information[ + expand ][ + ]

First Received DateMarch 16, 2006
Last Updated DateJune 29, 2007
Start DateNovember 2004
Estimated Primary Completion DateJune 2008
Current Primary Outcome MeasuresGrade of steatosis as judged by repeat biopsy [Time Frame: 6 mo]
Current 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]

Descriptive Information[ + expand ][ + ]

Brief TitleMetformin in Non-Alcoholic Fatty Liver Disease
Official TitleDouble Blind, Randomized, Placebo Controlled Trial With Metformin in Non-Alcoholic Fatty Liver Disease (NAFLD)
Brief Summary
The study evaluates the use of the antidiabetic medicine metformin in nonalcoholic fatty
liver disease.
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).
Study TypeInterventional
Study PhasePhase 2/Phase 3
Study DesignAllocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment
ConditionFatty Liver
InterventionDrug: metformin
Study Arm (s)Not Provided

Recruitment Information[ + expand ][ + ]

Recruitment StatusActive, not recruiting
Estimated Enrollment90
Estimated Completion DateJune 2008
Estimated Primary Completion DateNot Provided
Eligibility 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.
GenderBoth
Ages20 Years
Accepts Healthy VolunteersNo
ContactsNot Provided
Location CountriesNorway

Administrative Information[ + expand ][ + ]

NCT Number NCT00303537
Other Study ID NumbersAkerU3
Has Data Monitoring CommitteeNo
Information Provided ByUniversity Hospital, Aker
Study SponsorUniversity Hospital, Aker
CollaboratorsMerck Sharp & Dohme Corp.
Investigators Study Chair: Kaare Birkeland, Prof./Ph.D Aker University Hospital, Oslo, NorwayStudy Chair: Zbigniew Konopski, Cons./Ph.D Aker University Hospital, Oslo, NorwayStudy Chair: Kristian Bjøro, Cons./Ph.D Rikshospitalet-Radiumhospitalet, Oslo, NorwayPrincipal Investigator: John W Haukeland, Physician University Hospital, Aker
Verification DateJune 2007

Locations[ + expand ][ + ]

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