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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01147523
First Posted: June 22, 2010
Last Update Posted: January 20, 2012
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Stergios A. Polyzos, Aristotle University Of Thessaloniki
  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
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

Resource links provided by NLM:


Further study details as provided by Stergios A. Polyzos, Aristotle University Of Thessaloniki:

Primary Outcome Measures:
  • Serum adipocytokines levels [ Time Frame: 52 weeks ]
    Adiponectin; visfatin; leptin; resistin; omentin; vaspin; RBP4; TNF-alpha, IL-6; IL-1


Secondary Outcome Measures:
  • Serum homocysteine levels [ Time Frame: 52 weeks ]
    Homocysteine; vitamin B12; folate

  • Liver histology [ Time Frame: 52 weeks ]
    Repeat biopsy, if patients provide their consent

  • Insulin resistance [ Time Frame: 52 weeks ]
    Serum insulin; serum glucose; HOMA and QUICKI indexes

  • Hormonal profile [ Time Frame: 52 weeks ]
    DHEAS; testosterone; estradiol; TSH; free T4; cortisol (serum levels)

  • Serum biochemistry [ Time Frame: 52 weeks ]
    ALT; AST; ggt; Potassium; Sodium; urea; creatinin; cholesterol; triglycerides; HDL; LDL

  • Reactive Oxygen Metabolites (ROMs) [ Time Frame: 52 weeks ]
    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

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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:
Polyzos SA, Kountouras J, Zafeiriadou E, Patsiaoura K, Katsiki E, Deretzi G, Zavos C, Tsarouchas G, Rakitzi P, Slavakis A. Effect of spironolactone and vitamin E on serum metabolic parameters and insulin resistance in patients with nonalcoholic fatty liver disease. J Renin Angiotensin Aldosterone Syst. 2011 Dec;12(4):498-503. doi: 10.1177/1470320311402110. Epub 2011 Mar 24.
Polyzos SA, Kountouras J, Zavos C, Deretzi G. Spironolactone revisited. J Clin Hypertens (Greenwich). 2011 Oct;13(10):783-4. doi: 10.1111/j.1751-7176.2011.00484.x. Epub 2011 Jul 18.
Polyzos SA, Kountouras J, Zavos C. Nonalcoholic fatty liver disease: the pathogenetic roles of insulin resistance and adipocytokines. Curr Mol Med. 2009 Apr;9(3):299-314. Review.
Polyzos SA, Kountouras J, Zavos C. Insulin resistance and therapy: cross-talk between phosphatidylinositol-3 kinase and mitogen-activated protein kinase pathways. Med Hypotheses. 2009 May;72(5):610. doi: 10.1016/j.mehy.2008.12.019. Epub 2009 Jan 21.
Polyzos SA, Kountouras J, Zavos Ch. The multi-hit process and the antagonistic roles of tumor necrosis factor-alpha and adiponectin in non alcoholic fatty liver disease. Hippokratia. 2009 Apr;13(2):127; author reply 128.
Polyzos SA, Kountouras J, Zavos C. Nonlinear distribution of adiponectin in patients with nonalcoholic fatty liver disease limits its use in linear regression analysis. J Clin Gastroenterol. 2010 Mar;44(3):229-30; author reply 230-1. doi: 10.1097/MCG.0b013e3181b5ce68.
Polyzos SA, Kountouras J, Zavos C, Stergiopoulos C. Adipocytokines in insulin resistance and non-alcoholic fatty liver disease: the two sides of the same coin. Med Hypotheses. 2010 Jun;74(6):1089-90. doi: 10.1016/j.mehy.2009.12.028. Epub 2010 Jan 18.
Polyzos SA, Kountouras J, Zavos C. Adiponectin as a potential therapeutic agent for nonalcoholic steatohepatitis. Hepatol Res. 2010 Apr;40(4):446-7. doi: 10.1111/j.1872-034X.2010.00632.x.
Polyzos SA, Kountouras J, Zavos C, Tsiaousi E. The role of adiponectin in the pathogenesis and treatment of non-alcoholic fatty liver disease. Diabetes Obes Metab. 2010 May;12(5):365-83. doi: 10.1111/j.1463-1326.2009.01176.x. Review.
Polyzos SA, Kountouras J, Zavos C, Deretzi G. The potential adverse role of leptin resistance in nonalcoholic fatty liver disease: a hypothesis based on critical review of the literature. J Clin Gastroenterol. 2011 Jan;45(1):50-4. doi: 10.1097/MCG.0b013e3181ec5c66. Review.
Polyzos SA, Toulis KA, Goulis DG, Zavos C, Kountouras J. Serum total adiponectin in nonalcoholic fatty liver disease: a systematic review and meta-analysis. Metabolism. 2011 Mar;60(3):313-26. doi: 10.1016/j.metabol.2010.09.003. Epub 2010 Oct 30. Review.
Polyzos SA, Kountouras J, Zavos C. Adiponectin in non-alcoholic fatty liver disease treatment: therapeutic perspectives and unresolved dilemmas. Int J Clin Pract. 2011 Mar;65(3):373-4. doi: 10.1111/j.1742-1241.2010.02594.x.
Polyzos SA, Kountouras J, Zavos C, Deretzi G. The association between Helicobacter pylori infection and insulin resistance: a systematic review. Helicobacter. 2011 Apr;16(2):79-88. doi: 10.1111/j.1523-5378.2011.00822.x. Review.
Polyzos SA, Kountouras J, Zavos C, Deretzi G. The potentially dual-faceted nature of fetuin-A in Helicobacter pylori infection and insulin resistance. Clinics (Sao Paulo). 2011;66(5):911-2.
Polyzos SA, Kountouras J, Zavos C, Deretzi G. Helicobacter pylori and insulin resistance association: not just a myth, not yet a fact. Saudi J Gastroenterol. 2011 Nov-Dec;17(6):425-6. doi: 10.4103/1319-3767.87190.
Polyzos SA, Kountouras J, Deretzi G, Zavos C, Mantzoros CS. The emerging role of endocrine disruptors in pathogenesis of insulin resistance: a concept implicating nonalcoholic fatty liver disease. Curr Mol Med. 2012 Jan;12(1):68-82. Review.
Polyzos SA, Kountouras J, Patsiaoura K, Katsiki E, Zafeiriadou E, Deretzi G, Zavos C, Gavalas E, Katsinelos P, Mane V, Slavakis A. Serum homocysteine levels in patients with nonalcoholic fatty liver disease. Ann Hepatol. 2012 Jan-Feb;11(1):68-76.
Polyzos SA, Kountouras J, Patsiaoura K, Katsiki E, Zafeiriadou E, Zavos C, Deretzi G, Tsiaousi E, Slavakis A. Serum vitamin B12 and folate levels in patients with non-alcoholic fatty liver disease. Int J Food Sci Nutr. 2012 Sep;63(6):659-66. doi: 10.3109/09637486.2011.649249. Epub 2012 Jan 9.

Responsible Party: Stergios A. Polyzos, Dr, Aristotle University Of Thessaloniki
ClinicalTrials.gov Identifier: NCT01147523     History of Changes
Other Study ID Numbers: PolyzosKountouras
First Submitted: June 17, 2010
First Posted: June 22, 2010
Last Update Posted: January 20, 2012
Last Verified: January 2012

Keywords provided by Stergios A. Polyzos, 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:
Liver Diseases
Fatty Liver
Non-alcoholic Fatty Liver Disease
Digestive System Diseases
Vitamins
Vitamin E
Tocopherols
Tocotrienols
alpha-Tocopherol
Spironolactone
Micronutrients
Growth Substances
Physiological Effects of Drugs
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Mineralocorticoid Receptor Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Diuretics, Potassium Sparing
Diuretics
Natriuretic Agents


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