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

Sponsor

Aristotle University Of Thessaloniki (Other)

Overall Status

Completed

CT.gov ID

NCT01147523

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

1.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Fatty Liver Steatohepatitis	Drug: Spironolactone/Vitamin E	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jan 1, 2010

Actual Primary Completion Date :

Nov 1, 2010

Actual Study Completion Date :

Dec 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vitamin E Vitamin E, capsules 400 mg daily, for 52 weeks	Drug: Spironolactone/Vitamin E Spironolactone, tablets, 25 mg daily plus Vitamin E, capsules, 400 mg daily, for 52 weeks Other Names: Aldactone tab 25 Eviol caps 100

Arm

Intervention/Treatment

Experimental: Vitamin E

Vitamin E, capsules 400 mg daily, for 52 weeks

Drug: Spironolactone/Vitamin E

Spironolactone, tablets, 25 mg daily plus Vitamin E, capsules, 400 mg daily, for 52 weeks

Other Names:

Aldactone tab 25

Eviol caps 100

Outcome Measures

Primary Outcome Measures

Serum adipocytokines levels [52 weeks]
Adiponectin; visfatin; leptin; resistin; omentin; vaspin; RBP4; TNF-alpha, IL-6; IL-1

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Second Medical Clinic, Medical School, Aristotle University of Thessaloniki, Ippokration Hospital	Thessaloniki		Greece	54642

Sponsors and Collaborators

Aristotle University Of Thessaloniki

Investigators

Principal Investigator: Stergios A Polyzos, MD, MSc, Second Medical Clinic, Medical School, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Greece
Study Chair: Jannis Kountouras, MD, Prof, Second Medical Clinic, Medical School, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Greece
Study Director: Efthimia Zafeiriadou, MD, PhD, Department of Radiology, Ippokration Hospital, Thessaloniki, Greece
Study Director: Kalliopi Patsiaoura, MD, PhD, Department of Pathology, Ippokration Hospital, Thessaloniki, Greece
Study Director: Evangelia Katsiki, MD, Department of Pathology, Ippokration Hospital, Thessaloniki, Greece
Study Director: Aristidis Slavakis, MD, MSc, Department of Biochemistry, Ippokration Hospital, Thessaloniki, Greece