None listed
Conditions
Brief summary
Hepatic steatosis (fatty liver) is now the most common liver disease in western countries and NASH (fatty liver with inflammation) related cirrhosis and its complications is set to become one of the most important causes of liver related morbidity and mortality. It is clear that treatment and control of predisposing factors such as obesity and diabetes can lead to improvement in liver fibrosis (scarring) in patients with NASH however this is not possible in many patients. At present there are no established drug treatments which have been able to prevent liver fibrosis due to NASH. The renin-angiotensin sysytem (RAS) plays a central role in controlling blood pressure and sodium balance. Angiotensin II (the effector molecule) is a regarded as a key player in the general response to tissue injury in a number of organ systems, including the liver. A number of studies (experimental and human) have shown an improvement in fibrosis when the effects of AII are blocked. This study will assess the ability of telmisartan therapy to decrease the formation of fat and scar tissue in the liver in patients with fatty liver disease. It will also study the effects of telmisartan on other factors commonly found in patients with fatty liver including obesity and insulin resistance. Telmisartan will be given for a period of 12 months. A liver biopsy will be performed prior to enrolment and then at 12 months. At each visit (3 monthly after the first month) a blood sample and medical consultation will be performed.
Interventions
12 months of oral telmisartan therapy (20-80mg per day). Participants will begin at 20mg and this dose will be increased in 20mg increments until the maximum tolerated dose is reached up to 80mg per day.
Sponsors
Professor Peter Angus
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Stable body weight ( change of < 3%) for the last 6 months• Undergone 6 months of a diet and exercise regimen to help improve liver function tests• Non diabetic or well controlled diabetes • Abnormal liver function tests in patients with fatty liver disease• Haemaglobin > 10g/dL• Platelets >70,000/mm3• Prothrombin time < 2 sec prolonged • Serum creatinine < .15 mmol/l
Exclusion criteria
Female patients of child bearing potential who are not using an accepted method of birth control (surgically sterile, intra-uterine device, oral contraceptives, hormone delivery systems, diaphragm or condom in combination with contraceptive cream or foam), or female patients who are pregnant or breastfeeding. A pre-enrolment serum or urinary HCG (human chorionic gonadotrophin) must be negative;• Infection with Hepatitis B virus (HBV), Hepatitis C virus (HCV) or Human Immunodeficiency Virus (HIV)• Other chronic liver diseases• Significant weight gain or loss in the 3 months prior to study• Unstable diabetes• Patients with significant renal impairment (creatinine > .15 mm/l)• Patients with systolic BP <110 mmHg• Patients with decompensated liver disease ( Childs Pugh score >6 )• Patients who have participated in a clinical trial for an investigational drug (a new chemical not registered for clinical use) within 30 days preceding entry into the study, or who are due to enter such a trial during the treatment period• Substance abuse such as alcohol (>30g/day for males, >20g/day for females), IV and inhaled drugs. If there has been a history of substance abuse, the subject must have abstained from using for at least 2 years.
Outcome results
None listed