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
  Purpose

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 Intervention Phase
Fatty Liver
Steatohepatitis
Drug: Spironolactone/Vitamin E
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Aristotle University Of Thessaloniki:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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


Enrollment: 30
Study Start Date: January 2010
Study Completion Date: December 2011
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01147523

Locations
Greece
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
  More Information

Publications:

Responsible Party: Stergios A. Polyzos, Dr, Aristotle University Of Thessaloniki
ClinicalTrials.gov Identifier: NCT01147523     History of Changes
Other Study ID Numbers: PolyzosKountouras
Study First Received: June 17, 2010
Last Updated: January 19, 2012
Health Authority: Greece: Ethics Committee

Keywords provided by Aristotle University Of Thessaloniki:
nonalcoholic fatty liver disease
nonalcoholic steatohepatitis
adipokines
spironolactone
vitamin E
adiponectin
visfatin
leptin
resistin
TNF-alpha
IL-6
IL-1

Additional relevant MeSH terms:
Fatty Liver
Liver Diseases
Digestive System Diseases
Spironolactone
Vitamin E
Alpha-Tocopherol
Tocopherols
Tocotrienols
Vitamins
Aldosterone Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Diuretics
Natriuretic Agents
Cardiovascular Agents
Therapeutic Uses
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on July 28, 2014