Fatty Liver, Steatohepatitis
Conditions
Keywords
nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, adipokines, spironolactone, vitamin E, adiponectin, visfatin, leptin, resistin, TNF-alpha, IL-6, IL-1
Brief summary
The primary aim of the study is the effect of spironolactone and vitamin E versus vitamin E on serum levels of adipokines 52 weeks post-treatment.
Detailed description
Unlike other chronic liver diseases (e.g., hepatitis C), there are no effective treatment strategy for NAFLD. Currently, the management of NAFLD includes modification of underlying risk factors, detection of patients that have progressed to cirrhosis, management of cirrhosis-related morbidity and transplantation in patients with end-stage liver disease. Diet, exercise, bariatric surgery and pharmacologic treatment, including weight loss agents, insulin sensitizers, lipid-lowering agents, ursodeoxycholic acid and vitamin E have been investigated with some promising results. The renin-angiotensin-aldosterone system (RAAS) has been implicated in the pathogenesis of insulin resistance (IR) and nonalcoholic fatty liver disease (NAFLD). Recently, low-dose (25-50 mg/day) aldosterone antagonists in patients with heart failure diminish mortality, possibly by reducing cardiac and vascular fibrosis. Moreover, the beneficial effect of spironolactone in a mouse model with diet-induced diabetes and NAFLD has been reported. However, to our knowledge, the role of spironolactone in NAFLD patients has not been investigated yet. The primary aim of the study is the effect of spironolactone and vitamin E versus vitamin E on serum levels of adipokines 52 weeks post-treatment.
Interventions
DRUGSpironolactone/Vitamin E
Spironolactone, tablets, 25 mg daily plus Vitamin E, capsules, 400 mg daily, for 52 weeks
Sponsors
Aristotle University Of Thessaloniki
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Bright liver on ultrasound imaging and increased liver function tests for at least 6 months before liver biopsy * Biopsy-proven NAFLD (either NAFL or NASH) according to NAFLD Activity Score (NAS)
Exclusion criteria
* Ethanol consumption more than 20 g/day * Known intolerance to spironolactone or vitamin E * History of liver disease (chronic viral hepatitis, autoimmune hepatitis, drug-induced liver disease, primary biliary cirrhosis, hemochromatosis, Wilson's disease and α1-antitrypsin deficiency) * Previous exposure to hepatotoxic drugs * Spironolactone or vitamin E administration within one year before screening * Type I Diabetes Mellitus * Pancreatitis * Uncontrolled hypothyroidism or hyperthyroidism * Adrenal Insufficiency * Renal Failure * Cancer * Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum adipocytokines levels | 52 weeks | Adiponectin; visfatin; leptin; resistin; omentin; vaspin; RBP4; TNF-alpha, IL-6; IL-1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Liver histology | 52 weeks | Repeat biopsy, if patients provide their consent |
| Insulin resistance | 52 weeks | Serum insulin; serum glucose; HOMA and QUICKI indexes |
| Serum homocysteine levels | 52 weeks | Homocysteine; vitamin B12; folate |
| Serum biochemistry | 52 weeks | ALT; AST; ggt; Potassium; Sodium; urea; creatinin; cholesterol; triglycerides; HDL; LDL |
| Reactive Oxygen Metabolites (ROMs) | 52 weeks | Serum dROMs leves |
| Hormonal profile | 52 weeks | DHEAS; testosterone; estradiol; TSH; free T4; cortisol (serum levels) |
Countries
Greece
Outcome results
None listed