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

Phase 2
Completed
Conditions
Fatty Liver
Steatohepatitis
Interventions
Drug: Spironolactone/Vitamin E
Registration Number
NCT01147523
Lead Sponsor
Aristotle University Of Thessaloniki
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
30
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Vitamin ESpironolactone/Vitamin EVitamin E, capsules 400 mg daily, for 52 weeks
Primary Outcome Measures
NameTimeMethod
Serum adipocytokines levels52 weeks

Adiponectin; visfatin; leptin; resistin; omentin; vaspin; RBP4; TNF-alpha, IL-6; IL-1

Secondary Outcome Measures
NameTimeMethod
Insulin resistance52 weeks

Serum insulin; serum glucose; HOMA and QUICKI indexes

Hormonal profile52 weeks

DHEAS; testosterone; estradiol; TSH; free T4; cortisol (serum levels)

Serum homocysteine levels52 weeks

Homocysteine; vitamin B12; folate

Liver histology52 weeks

Repeat biopsy, if patients provide their consent

Serum biochemistry52 weeks

ALT; AST; ggt; Potassium; Sodium; urea; creatinin; cholesterol; triglycerides; HDL; LDL

Reactive Oxygen Metabolites (ROMs)52 weeks

Serum dROMs leves

Trial Locations

Locations (1)

Second Medical Clinic, Medical School, Aristotle University of Thessaloniki, Ippokration Hospital

🇬🇷

Thessaloniki, Greece

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