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

NCT01147523 | Completed Phase 2 DMC

• 1 other identifier: PolyzosKountouras
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Fatty Liver; Steatohepatitis

Keywords

nonalcoholic fatty liver disease; nonalcoholic steatohepatitis; adipokines; spironolactone; vitamin E; adiponectin; visfatin; leptin; resistin; TNF-alpha; IL-6; IL-1

Outcome Measures

Primary Outcomes (1)

• Serum adipocytokines levels

  Adiponectin; visfatin; leptin; resistin; omentin; vaspin; RBP4; TNF-alpha, IL-6; IL-1

  52 weeks

Secondary Outcomes (6)

• Serum homocysteine levels

  52 weeks

• Liver histology

  52 weeks

• Insulin resistance

  52 weeks

• Hormonal profile

  52 weeks

• Serum biochemistry

  52 weeks

Study Arms (1)

Vitamin E

EXPERIMENTAL

Vitamin E, capsules 400 mg daily, for 52 weeks

Drug: Spironolactone/Vitamin E

Interventions

Spironolactone/Vitamin E DRUG

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

Also known as: Aldactone tab 25, Eviol caps 100

Vitamin E

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Aristotle University Of Thessaloniki: lead

Study Sites (1)

Second Medical Clinic, Medical School, Aristotle University of Thessaloniki, Ippokration Hospital

Thessaloniki, Thessaloniki, 54642, Greece

Location

Related Publications (20)

• 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. doi: 10.2174/156652409787847191.

  PMID: 19355912 BACKGROUND

• 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. No abstract available.

  PMID: 19162411 BACKGROUND

• 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. No abstract available.

  PMID: 19561788 BACKGROUND

• 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. No abstract available.

  PMID: 19770674 BACKGROUND

• 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. No abstract available.

  PMID: 20080361 BACKGROUND

• 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. No abstract available.

  PMID: 20394676 BACKGROUND

• 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.

  PMID: 20415685 BACKGROUND

• 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.

  PMID: 20717042 BACKGROUND

• 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.

  PMID: 21040935 BACKGROUND

• 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. No abstract available.

  PMID: 21314876 BACKGROUND

• 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.

  PMID: 21435084 BACKGROUND

• 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. doi: 10.1590/s1807-59322011000500031. No abstract available.

  PMID: 21789399 BACKGROUND

• 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. No abstract available.

  PMID: 22064347 BACKGROUND

• 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. doi: 10.2174/156652412798376161.

  PMID: 22082482 BACKGROUND

• 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.

  PMID: 22166563 BACKGROUND

• 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.

  PMID: 22229957 BACKGROUND

• 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.

  PMID: 21436212 RESULT

• 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. No abstract available.

  PMID: 21974769 RESULT

• Polyzos SA, Kountouras J, Anastasilakis AD, Makras P, Hawa G, Sonnleitner L, Missbichler A, Doulberis M, Katsinelos P, Terpos E. Noggin levels in nonalcoholic fatty liver disease: the effect of vitamin E treatment. Hormones (Athens). 2018 Dec;17(4):573-579. doi: 10.1007/s42000-018-0083-8. Epub 2018 Nov 22.

  PMID: 30467685 DERIVED

• Polyzos SA, Kountouras J, Mantzoros CS, Polymerou V, Katsinelos P. Effects of combined low-dose spironolactone plus vitamin E vs vitamin E monotherapy on insulin resistance, non-invasive indices of steatosis and fibrosis, and adipokine levels in non-alcoholic fatty liver disease: a randomized controlled trial. Diabetes Obes Metab. 2017 Dec;19(12):1805-1809. doi: 10.1111/dom.12989. Epub 2017 Jul 10.

  PMID: 28452101 DERIVED

MeSH Terms

Conditions

Fatty Liver; Non-alcoholic Fatty Liver Disease

Interventions

Spironolactone; Vitamin E

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Stergios A Polyzos, MD, MSc

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

  PRINCIPAL INVESTIGATOR

• Jannis Kountouras, MD, Prof

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

  STUDY CHAIR

• 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

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr

Study Record Dates

• First Submitted: June 17, 2010
• First Posted: June 22, 2010
• Study Start: January 1, 2010
• Primary Completion: November 1, 2010
• Study Completion: December 1, 2011
• Last Updated: January 20, 2012

Record last verified: 2012-01

Locations

GR (1)