Clinical trial NCT00303537: Metformin in Non-Alcoholic Fatty Liver Disease
Official title: Double Blind, Randomized, Placebo Controlled Trial With Metformin in Non-Alcoholic Fatty Liver Disease (NAFLD)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Fatty Liver
Keywords: hepatitis
metformin
non-alcoholic fatty liver (NAFLD)
non-alcoholic steatohepatitis (NASH)
Nonalcoholic fatty liver disease
Lead sponsor: University Hospital, Aker
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2006-03-17
Enrollment: 90
Sex: ALL
Minimum age (years): 20
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: Grade of steatosis as judged by repeat biopsy
timeFrame: 6 mo
Secondary outcomes:
measure: Grade of necroinflammation as judged by repeat biopsy
timeFrame: 6 mo
measure: Liver density obtained by computer scan
timeFrame: 6 mo
measure: Serum alanine transaminase (ALAT)
timeFrame: 6 mo
Other outcomes:
Locations:
city: Bergen
country: Norway
facility: Haukeland Universitetssykehus
city: Oslo
country: Norway
facility: Aker University Hospital
city: Oslo
country: Norway
facility: Akershus University Hospital
city: Tromsø
country: Norway
facility: Universitetssykehuset i Nord-Norge
Study officials:
affiliation: Aker University Hospital, Oslo, Norway
name: Kaare Birkeland, Prof./Ph.D
role: STUDY_CHAIR
affiliation: Aker University Hospital, Oslo, Norway
name: Zbigniew Konopski, Cons./Ph.D
role: STUDY_CHAIR
affiliation: Rikshospitalet-Radiumhospitalet, Oslo, Norway
name: Kristian Bjøro, Cons./Ph.D
role: STUDY_CHAIR
affiliation: University Hospital, Aker
name: John W Haukeland, Physician
role: PRINCIPAL_INVESTIGATOR
References:
citation: Haukeland JW, Dahl TB, Yndestad A, Gladhaug IP, Loberg EM, Haaland T, Konopski Z, Wium C, Aasheim ET, Johansen OE, Aukrust P, Halvorsen B, Birkeland KI. Fetuin A in nonalcoholic fatty liver disease: in vivo and in vitro studies. Eur J Endocrinol. 2012 Mar;166(3):503-10. doi: 10.1530/EJE-11-0864. Epub 2011 Dec 14.
citation: Haukeland JW, Konopski Z, Eggesbo HB, von Volkmann HL, Raschpichler G, Bjoro K, Haaland T, Loberg EM, Birkeland K. Metformin in patients with non-alcoholic fatty liver disease: a randomized, controlled trial. Scand J Gastroenterol. 2009;44(7):853-60. doi: 10.1080/00365520902845268.