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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Stergios A. Polyzos, Aristotle University Of Thessaloniki
ClinicalTrials.gov Identifier:
NCT01147523
First received: June 17, 2010
Last updated: January 19, 2012
Last verified: January 2012

June 17, 2010
January 19, 2012
January 2010
November 2010   (final data collection date for primary outcome measure)
Serum adipocytokines levels [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
Adiponectin; visfatin; leptin; resistin; omentin; vaspin; RBP4; TNF-alpha, IL-6; IL-1
Same as current
Complete list of historical versions of study NCT01147523 on ClinicalTrials.gov Archive Site
  • Serum homocysteine levels [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Homocysteine; vitamin B12; folate
  • Liver histology [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Repeat biopsy, if patients provide their consent
  • Insulin resistance [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Serum insulin; serum glucose; HOMA and QUICKI indexes
  • Hormonal profile [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    DHEAS; testosterone; estradiol; TSH; free T4; cortisol (serum levels)
  • Serum biochemistry [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
    ALT; AST; ggt; Potassium; Sodium; urea; creatinin; cholesterol; triglycerides; HDL; LDL
  • Reactive Oxygen Metabolites (ROMs) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Serum dROMs leves
Same as current
Not Provided
Not Provided
 
Effect of Spironolactone and Vitamin E in Patients With Nonalcoholic Fatty Liver Disease
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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Fatty Liver
  • Steatohepatitis
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
Experimental: Vitamin E
Vitamin E, capsules 400 mg daily, for 52 weeks
Intervention: Drug: Spironolactone/Vitamin E

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
30
December 2011
November 2010   (final data collection date for primary outcome measure)

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.

Both
18 Years to 75 Years
No
Contact information is only displayed when the study is recruiting subjects
Greece
 
NCT01147523
PolyzosKountouras
Yes
Stergios A. Polyzos, Aristotle University Of Thessaloniki
Aristotle University Of Thessaloniki
Not Provided
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
Aristotle University Of Thessaloniki
January 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP