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

Fatty Liver Clinical Trial

— NAFLD  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01147523
• Other study ID #: PolyzosKountouras
• Status: Completed
• Phase: Phase 2
• First received: June 17, 2010
• Last updated: January 19, 2012
• Start date: January 2010
• Est. completion date: December 2011

Study information

• Verified date: January 2012
• Source: Aristotle University Of Thessaloniki
• Contact: n/a
• Is FDA regulated: No
• Health authority: Greece: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: December 2011
• Est. primary completion date: November 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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 a1-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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fatty Liver
• Liver Diseases
• Steatohepatitis

Intervention

Drug:
• Spironolactone/Vitamin E
Spironolactone, tablets, 25 mg daily plus Vitamin E, capsules, 400 mg daily, for 52 weeks

Locations

Country	Name	City	State
Greece	Second Medical Clinic, Medical School, Aristotle University of Thessaloniki, Ippokration Hospital	Thessaloniki

Sponsors (1)

Lead Sponsor	Collaborator
Aristotle University Of Thessaloniki

Country where clinical trial is conducted

Greece, 

References & Publications (18)

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. — View Citation

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. — View Citation

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. — View Citation

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 live — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serum adipocytokines levels	Adiponectin; visfatin; leptin; resistin; omentin; vaspin; RBP4; TNF-alpha, IL-6; IL-1	52 weeks	No
Secondary	Serum homocysteine levels	Homocysteine; vitamin B12; folate	52 weeks	No
Secondary	Liver histology	Repeat biopsy, if patients provide their consent	52 weeks	No
Secondary	Insulin resistance	Serum insulin; serum glucose; HOMA and QUICKI indexes	52 weeks	No
Secondary	Hormonal profile	DHEAS; testosterone; estradiol; TSH; free T4; cortisol (serum levels)	52 weeks	No
Secondary	Serum biochemistry	ALT; AST; ggt; Potassium; Sodium; urea; creatinin; cholesterol; triglycerides; HDL; LDL	52 weeks	Yes
Secondary	Reactive Oxygen Metabolites (ROMs)	Serum dROMs leves	52 weeks	No