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

January 19, 2012 updated by: Stergios A. Polyzos, Aristotle University Of Thessaloniki

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

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 Overview

Status

Completed

Conditions

Intervention / 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.

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Greece
      • Thessaloniki, Greece, 54642
        • Second Medical Clinic, Medical School, Aristotle University of Thessaloniki, Ippokration Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 71 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2010

Primary Completion (Actual)

November 1, 2010

Study Completion (Actual)

December 1, 2011

Study Registration Dates

First Submitted

June 17, 2010

First Submitted That Met QC Criteria

June 18, 2010

First Posted (Estimate)

June 22, 2010

Study Record Updates

Last Update Posted (Estimate)

January 20, 2012

Last Update Submitted That Met QC Criteria

January 19, 2012

Last Verified

January 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PolyzosKountouras

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe