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

NCT ID: NCT01147523

Last Updated: 2012-01-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-01-31

Study Completion Date

2011-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Fatty Liver Steatohepatitis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Vitamin E

Vitamin E, capsules 400 mg daily, for 52 weeks

Group Type EXPERIMENTAL

Spironolactone/Vitamin E

Intervention Type DRUG

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

Interventions

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Spironolactone/Vitamin E

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

Intervention Type DRUG

Other Intervention Names

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Aldactone tab 25 Eviol caps 100

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Aristotle University Of Thessaloniki

OTHER

Sponsor Role lead

Responsible Party

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Stergios A. Polyzos

Dr

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Stergios A Polyzos, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

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

Jannis Kountouras, MD, Prof

Role: STUDY_CHAIR

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

Efthimia Zafeiriadou, MD, PhD

Role: STUDY_DIRECTOR

Department of Radiology, Ippokration Hospital, Thessaloniki, Greece

Kalliopi Patsiaoura, MD, PhD

Role: STUDY_DIRECTOR

Department of Pathology, Ippokration Hospital, Thessaloniki, Greece

Evangelia Katsiki, MD

Role: STUDY_DIRECTOR

Department of Pathology, Ippokration Hospital, Thessaloniki, Greece

Aristidis Slavakis, MD, MSc

Role: STUDY_DIRECTOR

Department of Biochemistry, Ippokration Hospital, Thessaloniki, Greece

Locations

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

Thessaloniki, Thessaloniki, Greece

Site Status

Countries

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Greece

References

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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.

Reference Type BACKGROUND
PMID: 19355912 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19162411 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19561788 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19770674 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20080361 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20394676 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20415685 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20717042 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21040935 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21314876 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21435084 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21789399 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22064347 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22082482 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22166563 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22229957 (View on PubMed)

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.

Reference Type RESULT
PMID: 21436212 (View on PubMed)

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.

Reference Type RESULT
PMID: 21974769 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30467685 (View on PubMed)

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.

Reference Type DERIVED
PMID: 28452101 (View on PubMed)

Other Identifiers

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PolyzosKountouras

Identifier Type: -

Identifier Source: org_study_id

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