Effect of Spironolactone and Vitamin E in Patients With Nonalcoholic Fatty Liver Disease

Study Overview
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Brief Summary
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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
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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.

Official Title
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The Effect of Spironolactone and Vitamin E Versus Vitamin E on Serum Adipocytokines Levels in Patients With Biopsy-proven Nonalcoholic Fatty Liver Disease-A Phase II Study

Conditions
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Fatty Liver, Steatohepatitis

Intervention / Treatment
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* Drug: Spironolactone/Vitamin E


Participation Criteria
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Eligibility Criteria
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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 Exclusion criteria were generally the same as those proposed for PIVENS trial design with two modifications: a) known intolerance to spironolactone as an exclusion criterion and b) the inclusion of patients with T2DM not receiving thiazolidinediones or insulin.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin E<br>Vitamin E, capsules 400 mg daily, for 52 weeks | Drug: Spironolactone/Vitamin E<br>* Spironolactone, tablets, 25 mg daily plus Vitamin E, capsules, 400 mg daily, for 52 weeks<br>* Other names: Eviol caps 100;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum adipocytokines levels | Adiponectin; visfatin; leptin; resistin; omentin; vaspin; RBP4; TNF-alpha, IL-6; IL-1 | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum homocysteine levels | Homocysteine; vitamin B12; folate | 52 weeks | 
| Liver histology | Repeat biopsy, if patients provide their consent | 52 weeks | 
| Insulin resistance | Serum insulin; serum glucose; HOMA and QUICKI indexes | 52 weeks | 
| Hormonal profile | DHEAS; testosterone; estradiol; TSH; free T4; cortisol (serum levels) | 52 weeks | 
| Serum biochemistry | ALT; AST; ggt; Potassium; Sodium; urea; creatinin; cholesterol; triglycerides; HDL; LDL | 52 weeks | 
| Reactive Oxygen Metabolites (ROMs) | Serum dROMs leves | 52 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, adipokines, spironolactone, vitamin E, adiponectin, visfatin, leptin, resistin, TNF-alpha, IL-6, IL-1