Effect of Omega 5 Fatty Acid as an Adyuvant Treatment to Prednisone in Patients With Severe Alcoholic Hepatitis

NCT03732586 | Completed

• 1 other identifier: Hospitalgea
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

In Mexico, alcoholic liver disease is the fourth cause of mortality (INEGI). Patients with severe alcoholic hepatitis have a high mortality at 28 days and 6 months, patients receiving standard therapy with prednisone that are non responders (Lille\> 0.45) have a survival of 53.3 ± 5.1 % to 28 days. At present, there is not a completely effective treatment for non responders patients, with a high mortality, so it is necessary to look for other therapeutic strategies. The omega-5 fatty acid (punicic acid) has been considered a powerful antioxidant, it is an agonist of PPAR gamma, has been shown to reduce lipid peroxidation, and restore levels of antioxidant enzymes such as superoxide dismutase (SOD), catalase and glutathione peroxidase. It has also been shown to inhibit the expression of proinflammatory cytokines (such as IL6, IL8, IL23, IL12 and TNFalpha) through PPAR and modulation delta. The objective of this study is to evaluate the effect of Omega 5 fatty acid on inflammatory markers and antioxidant-oxidant balance markers in patients with severe alcoholic hepatitis treated with prednisone. HYPOTHESIS. Omega 5 fatty acid being a PPARgamma agonist reduces lipid peroxidation and protein damage, restoring reduced glutathione levels, as well as decreasing proinflammatory cytokines, in patients with Severe Alcoholic Hepatitis treated with prednisone and supplementation with fatty acid Omega 5.

Conditions

Alcoholic Hepatitis

Keywords

Severe Alcoholic Hepatitis treatment

Outcome Measures

Primary Outcomes (1)

• 30 Day Survival

  Better survival in patients with omega 5 supplement associated to prednisone

  day 30

Secondary Outcomes (3)

• Rate of reponse to steroids at day 7

  day 7

• Malondialdehyde serum levels

  basal, day 7, day 14 and day 28

• Oxidative Stress molecules serum levels

  basal, day 7, day 14 and day 28

Study Arms (2)

Omega 5 fatty acid supplement

EXPERIMENTAL

20 patients will be assigned to traditional treatment with prednisone 40 mg per day plus dietary supplement with omega 5 fatty acid

Dietary Supplement: Omega 5 fatty acid supplement

PLACEBO

PLACEBO COMPARATOR

20 patients will be assigned to traditional treatment (prednisone 40 mg per day) plus placebo

Other: PLACEBO

Interventions

Omega 5 fatty acid supplement DIETARY_SUPPLEMENT

Patients will be randomized to receive traditional treatment (prednisone 40 mg per day) plus omega 5 fatty acid ( 2 capsules of 0.64g per day) for 28 days.

Omega 5 fatty acid supplement

PLACEBO OTHER

Patients will be randomized to receive the traditional treatment (prednisone 40 mg per day) plus placebo (2 capsules of placebo with identical appereance and size like omega 5 supplement) for 28 days.

Also known as: placebo capsules

PLACEBO

Eligibility Criteria

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

You may qualify if:

• Patients with clinical and biochemical criteria for severe alcoholic hepatitis (Total bilirubin greater than 5 mg/dl in absence of biliary tract obstruction evidenced by ultrasound)
• history of chronic alcohol intake (greater than 50 g / day for at least 3 months),
• leukocytosis (neutrophilia)
• elevation of transaminases with an aspartate aminotransferase / alanine aminotransferase ratio equal or greater than 2)
• discriminant function greater than 32.

You may not qualify if:

• Hepatorenal syndrome (serum creatinine \>2.5mg/dl)
• Hepatocellular carcinoma.
• Hepatitis C virus, hepatitis B virus or human immunodeficiency virus infection.
• Cancer, heart disease, neurological or severe neurological.
• Patients taking pentoxifylline, steroids, S-adenosyl L- methionine or N-Acetylcysteine.

Sponsors & Collaborators

• Hospital General Dr. Manuel Gea González: lead
• Universidad Nacional Autonoma de Mexico: collaborator

Study Sites (2)

Laboratorio de Higado, Pancreas y Motilidad Intestinal. UNIVERSIDAD AUTONOMA DE MEXICO

Mexico City, Cuauhtemoc, 06720, Mexico

Location

Hospital General Dr. Manuel Gea Gonzalez

Mexico City, Tlalpan, 14080, Mexico

Location

Related Publications (44)

• European Association for the Study of Liver. EASL clinical practical guidelines: management of alcoholic liver disease. J Hepatol. 2012 Aug;57(2):399-420. doi: 10.1016/j.jhep.2012.04.004. Epub 2012 May 26. No abstract available.

  PMID: 22633836 BACKGROUND

• Mendez-Sanchez N, Villa AR, Chavez-Tapia NC, Ponciano-Rodriguez G, Almeda-Valdes P, Gonzalez D, Uribe M. Trends in liver disease prevalence in Mexico from 2005 to 2050 through mortality data. Ann Hepatol. 2005 Jan-Mar;4(1):52-5.

  PMID: 15798662 BACKGROUND

• Amini M, Runyon BA. Alcoholic hepatitis 2010: a clinician's guide to diagnosis and therapy. World J Gastroenterol. 2010 Oct 21;16(39):4905-12. doi: 10.3748/wjg.v16.i39.4905.

  PMID: 20954276 BACKGROUND

• Lucey MR, Mathurin P, Morgan TR. Alcoholic hepatitis. N Engl J Med. 2009 Jun 25;360(26):2758-69. doi: 10.1056/NEJMra0805786. No abstract available.

  PMID: 19553649 BACKGROUND

• Nguyen-Khac E, Thevenot T, Piquet MA, Benferhat S, Goria O, Chatelain D, Tramier B, Dewaele F, Ghrib S, Rudler M, Carbonell N, Tossou H, Bental A, Bernard-Chabert B, Dupas JL; AAH-NAC Study Group. Glucocorticoids plus N-acetylcysteine in severe alcoholic hepatitis. N Engl J Med. 2011 Nov 10;365(19):1781-9. doi: 10.1056/NEJMoa1101214.

  PMID: 22070475 BACKGROUND

• Thursz MR, Richardson P, Allison M, Austin A, Bowers M, Day CP, Downs N, Gleeson D, MacGilchrist A, Grant A, Hood S, Masson S, McCune A, Mellor J, O'Grady J, Patch D, Ratcliffe I, Roderick P, Stanton L, Vergis N, Wright M, Ryder S, Forrest EH; STOPAH Trial. Prednisolone or pentoxifylline for alcoholic hepatitis. N Engl J Med. 2015 Apr 23;372(17):1619-28. doi: 10.1056/NEJMoa1412278.

  PMID: 25901427 BACKGROUND

• Basra G, Basra S, Parupudi S. Symptoms and signs of acute alcoholic hepatitis. World J Hepatol. 2011 May 27;3(5):118-20. doi: 10.4254/wjh.v3.i5.118.

  PMID: 21731904 BACKGROUND

• Sass DA, Shaikh OS. Alcoholic hepatitis. Clin Liver Dis. 2006 May;10(2):219-37, vii. doi: 10.1016/j.cld.2006.05.011.

  PMID: 16971259 BACKGROUND

• Ambade A, Mandrekar P. Oxidative stress and inflammation: essential partners in alcoholic liver disease. Int J Hepatol. 2012;2012:853175. doi: 10.1155/2012/853175. Epub 2012 Mar 1.

  PMID: 22500241 BACKGROUND

• Lefkowitch JH. Morphology of alcoholic liver disease. Clin Liver Dis. 2005 Feb;9(1):37-53. doi: 10.1016/j.cld.2004.11.001.

  PMID: 15763228 BACKGROUND

• Dugum MF, McCullough AJ. Acute Alcoholic Hepatitis, the Clinical Aspects. Clin Liver Dis. 2016 Aug;20(3):499-508. doi: 10.1016/j.cld.2016.02.008. Epub 2016 May 14.

  PMID: 27373612 BACKGROUND

• Cohen SM, Ahn J. Review article: the diagnosis and management of alcoholic hepatitis. Aliment Pharmacol Ther. 2009 Jul;30(1):3-13. doi: 10.1111/j.1365-2036.2009.04002.x. Epub 2009 Mar 26.

  PMID: 19416132 BACKGROUND

• Gholam PM. Prognosis and Prognostic Scoring Models for Alcoholic Liver Disease and Acute Alcoholic Hepatitis. Clin Liver Dis. 2016 Aug;20(3):491-7. doi: 10.1016/j.cld.2016.02.007. Epub 2016 May 14.

  PMID: 27373611 BACKGROUND

• Sheth M, Riggs M, Patel T. Utility of the Mayo End-Stage Liver Disease (MELD) score in assessing prognosis of patients with alcoholic hepatitis. BMC Gastroenterol. 2002;2:2. doi: 10.1186/1471-230x-2-2. Epub 2002 Jan 22.

  PMID: 11835693 BACKGROUND

• Dominguez M, Rincon D, Abraldes JG, Miquel R, Colmenero J, Bellot P, Garcia-Pagan JC, Fernandez R, Moreno M, Banares R, Arroyo V, Caballeria J, Gines P, Bataller R. A new scoring system for prognostic stratification of patients with alcoholic hepatitis. Am J Gastroenterol. 2008 Nov;103(11):2747-56. doi: 10.1111/j.1572-0241.2008.02104.x. Epub 2008 Aug 21.

  PMID: 18721242 BACKGROUND

• Higuera-de la Tijera MF, Perez-Hernandez JL, Serralde-Zuniga AE, Servin-Caamano AI, Cruz-Palacios A, Bernal-Sahagun F, Salas-Gordillo F. [Three prognostic utility scales to determine early mortality in patients with alcoholic hepatitis in the General Hospital of Mexico]. Rev Gastroenterol Mex. 2010;75(3):281-6. Spanish.

  PMID: 20959177 BACKGROUND

• Altamirano J, Higuera-de laTijera F, Duarte-Rojo A, Martinez-Vazquez MA, Abraldes JG, Herrera-Jimenez LE, Michelena J, Zapata L, Perez-Hernandez J, Torre A, Gonzales-Gonzalez JA, Cardenas A, Dominguez M, Arroyo V, Gines P, Caballeria J, Bataller R. The amount of alcohol consumption negatively impacts short-term mortality in Mexican patients with alcoholic hepatitis. Am J Gastroenterol. 2011 Aug;106(8):1472-80. doi: 10.1038/ajg.2011.141. Epub 2011 May 10.

  PMID: 21556041 BACKGROUND

• Higuera-de la Tijera MF, Perez-Hernandez JL, Servin-Caamano AL, Serralde-Zuniga AE, Cruz-Palacios A. [The amount of alcohol intake, upper gastrointestinal bleeding, acute renal failure and hepatic encephalopathy as the risk factors implied in the increase of patients with alcoholic hepatitis]. Rev Gastroenterol Mex. 2009 Oct-Dec;74(4):306-13. Spanish.

  PMID: 20423759 BACKGROUND

• Louvet A, Wartel F, Castel H, Dharancy S, Hollebecque A, Canva-Delcambre V, Deltenre P, Mathurin P. Infection in patients with severe alcoholic hepatitis treated with steroids: early response to therapy is the key factor. Gastroenterology. 2009 Aug;137(2):541-8. doi: 10.1053/j.gastro.2009.04.062. Epub 2009 May 13.

  PMID: 19445945 BACKGROUND

• Louvet A, Naveau S, Abdelnour M, Ramond MJ, Diaz E, Fartoux L, Dharancy S, Texier F, Hollebecque A, Serfaty L, Boleslawski E, Deltenre P, Canva V, Pruvot FR, Mathurin P. The Lille model: a new tool for therapeutic strategy in patients with severe alcoholic hepatitis treated with steroids. Hepatology. 2007 Jun;45(6):1348-54. doi: 10.1002/hep.21607.

  PMID: 17518367 BACKGROUND

• Phillips PK, Lucey MR. Acute Alcoholic Hepatitis: Therapy. Clin Liver Dis. 2016 Aug;20(3):509-19. doi: 10.1016/j.cld.2016.02.015. Epub 2016 May 31.

  PMID: 27373613 BACKGROUND

• Higuera-de la Tijera F, Servin-Caamano AI, Serralde-Zuniga AE, Cruz-Herrera J, Perez-Torres E, Abdo-Francis JM, Salas-Gordillo F, Perez-Hernandez JL. Metadoxine improves the three- and six-month survival rates in patients with severe alcoholic hepatitis. World J Gastroenterol. 2015 Apr 28;21(16):4975-85. doi: 10.3748/wjg.v21.i16.4975.

  PMID: 25945012 BACKGROUND

• Mathurin P, O'Grady J, Carithers RL, Phillips M, Louvet A, Mendenhall CL, Ramond MJ, Naveau S, Maddrey WC, Morgan TR. Corticosteroids improve short-term survival in patients with severe alcoholic hepatitis: meta-analysis of individual patient data. Gut. 2011 Feb;60(2):255-60. doi: 10.1136/gut.2010.224097. Epub 2010 Oct 12.

  PMID: 20940288 BACKGROUND

• Bihamta M, Hosseini A, Ghorbani A, Boroushaki MT. Protective effect of pomegranate seed oil against H2O2 -induced oxidative stress in cardiomyocytes. Avicenna J Phytomed. 2017 Jan-Feb;7(1):46-53.

  PMID: 28265546 RESULT

• Boroushaki MT, Hosseini A, Dolati K, Mollazadeh H, Rajabian A. PROTECTIVE EFFECT OF POMEGRANATE SEED OIL AGAINST MERCURIC CHLORIDE-INDUCED HEPATOTOXICITY IN RAT. Acta Pol Pharm. 2016 Jul;73(4):991-997.

  PMID: 29648725 RESULT

• Boroushaki MT, Rajabian A, Farzadnia M, Hoseini A, Poorlashkari M, Taghavi A, Dolati K, Bazmandegan G. Protective effect of pomegranate seed oil against cisplatin-induced nephrotoxicity in rat. Ren Fail. 2015;37(8):1338-43. doi: 10.3109/0886022X.2015.1073496. Epub 2015 Aug 14.

  PMID: 26288026 RESULT

• Nematbakhsh M. Cisplatin and herbal antioxidants: protective effect of pomegranate seed oil against cisplatin-induced nephrotoxicity in rat. Ren Fail. 2016;38(2):344-5. doi: 10.3109/0886022X.2015.1127740. Epub 2015 Dec 27. No abstract available.

  PMID: 26707061 RESULT

• Boroushaki MT, Mollazadeh H, Rajabian A, Dolati K, Hoseini A, Paseban M, Farzadnia M. Protective effect of pomegranate seed oil against mercuric chloride-induced nephrotoxicity in rat. Ren Fail. 2014 Nov;36(10):1581-6. doi: 10.3109/0886022X.2014.949770. Epub 2014 Aug 26.

  PMID: 25154291 RESULT

• Boroushaki MT, Rajabian A, Farzadnia M, Hoseini A, Poorlashkari M, Taghavi A, Dolati K, Bazmandegan G. Protective effect of pomegranate seed oil against cisplatin-induced nephrotoxicity in rat. Ren Fail. 2015 Aug 14:1-6. Online ahead of print.

  PMID: 26275112 RESULT

• Mollazadeh H, Sadeghnia HR, Hoseini A, Farzadnia M, Boroushaki MT. Effects of pomegranate seed oil on oxidative stress markers, serum biochemical parameters and pathological findings in kidney and heart of streptozotocin-induced diabetic rats. Ren Fail. 2016 Sep;38(8):1256-66. doi: 10.1080/0886022X.2016.1207053. Epub 2016 Jul 25.

  PMID: 27453190 RESULT

• Boroushaki MT, Arshadi D, Jalili-Rasti H, Asadpour E, Hosseini A. Protective effect of pomegranate seed oil against acute toxicity of diazinon in rat kidney. Iran J Pharm Res. 2013 Fall;12(4):821-7.

  PMID: 24523762 RESULT

• Shaban NZ, El-Kersh MA, El-Rashidy FH, Habashy NH. Protective role of Punica granatum (pomegranate) peel and seed oil extracts on diethylnitrosamine and phenobarbital-induced hepatic injury in male rats. Food Chem. 2013 Dec 1;141(3):1587-96. doi: 10.1016/j.foodchem.2013.04.134. Epub 2013 May 23.

  PMID: 23870864 RESULT

• Coursodon-Boyiddle CF, Snarrenberg CL, Adkins-Rieck CK, Bassaganya-Riera J, Hontecillas R, Lawrence P, Brenna JT, Jouni ZE, Dvorak B. Pomegranate seed oil reduces intestinal damage in a rat model of necrotizing enterocolitis. Am J Physiol Gastrointest Liver Physiol. 2012 Sep 15;303(6):G744-51. doi: 10.1152/ajpgi.00248.2012. Epub 2012 Jul 19.

  PMID: 22821948 RESULT

• Mollazadeh H, Boroushaki MT, Soukhtanloo M, Afshari AR, Vahedi MM. Effects of pomegranate seed oil on oxidant/antioxidant balance in heart and kidney homogenates and mitochondria of diabetic rats and high glucose-treated H9c2 cell line. Avicenna J Phytomed. 2017 Jul-Aug;7(4):317-333.

  PMID: 28884082 RESULT

• Cao Y, Yang L, Gao HL, Chen JN, Chen ZY, Ren QS. Re-characterization of three conjugated linolenic acid isomers by GC-MS and NMR. Chem Phys Lipids. 2007 Feb;145(2):128-33. doi: 10.1016/j.chemphyslip.2006.11.005. Epub 2006 Dec 1.

  PMID: 17204261 RESULT

• Baccarin T, Mitjans M, Ramos D, Lemos-Senna E, Vinardell MP. Photoprotection by Punica granatum seed oil nanoemulsion entrapping polyphenol-rich ethyl acetate fraction against UVB-induced DNA damage in human keratinocyte (HaCaT) cell line. J Photochem Photobiol B. 2015 Dec;153:127-36. doi: 10.1016/j.jphotobiol.2015.09.005. Epub 2015 Sep 4.

  PMID: 26406978 RESULT

• Mirmiran P, Fazeli MR, Asghari G, Shafiee A, Azizi F. Effect of pomegranate seed oil on hyperlipidaemic subjects: a double-blind placebo-controlled clinical trial. Br J Nutr. 2010 Aug;104(3):402-6. doi: 10.1017/S0007114510000504. Epub 2010 Mar 25.

  PMID: 20334708 RESULT

• Viladomiu M, Hontecillas R, Lu P, Bassaganya-Riera J. Preventive and prophylactic mechanisms of action of pomegranate bioactive constituents. Evid Based Complement Alternat Med. 2013;2013:789764. doi: 10.1155/2013/789764. Epub 2013 Apr 30.

  PMID: 23737845 RESULT

• Arao K, Yotsumoto H, Han SY, Nagao K, Yanagita T. The 9cis,11trans,13cis isomer of conjugated linolenic acid reduces apolipoprotein B100 secretion and triacylglycerol synthesis in HepG2 cells. Biosci Biotechnol Biochem. 2004 Dec;68(12):2643-5. doi: 10.1271/bbb.68.2643.

  PMID: 15618643 RESULT

• Baccarin T, Mitjans M, Lemos-Senna E, Vinardell MP. Protection against oxidative damage in human erythrocytes and preliminary photosafety assessment of Punica granatum seed oil nanoemulsions entrapping polyphenol-rich ethyl acetate fraction. Toxicol In Vitro. 2015 Dec 25;30(1 Pt B):421-8. doi: 10.1016/j.tiv.2015.09.020. Epub 2015 Sep 25.

  PMID: 26407526 RESULT

• Mizrahi M, Friedman-Levi Y, Larush L, Frid K, Binyamin O, Dori D, Fainstein N, Ovadia H, Ben-Hur T, Magdassi S, Gabizon R. Pomegranate seed oil nanoemulsions for the prevention and treatment of neurodegenerative diseases: the case of genetic CJD. Nanomedicine. 2014 Aug;10(6):1353-63. doi: 10.1016/j.nano.2014.03.015. Epub 2014 Apr 2.

  PMID: 24704590 RESULT

• Harzallah A, Hammami M, Kepczynska MA, Hislop DC, Arch JR, Cawthorne MA, Zaibi MS. Comparison of potential preventive effects of pomegranate flower, peel and seed oil on insulin resistance and inflammation in high-fat and high-sucrose diet-induced obesity mice model. Arch Physiol Biochem. 2016;122(2):75-87. doi: 10.3109/13813455.2016.1148053. Epub 2016 Feb 26.

  PMID: 26822470 RESULT

• Miranda J, Arias N, Fernandez-Quintela A, del Puy Portillo M. Are conjugated linolenic acid isomers an alternative to conjugated linoleic acid isomers in obesity prevention? Endocrinol Nutr. 2014 Apr;61(4):209-19. doi: 10.1016/j.endonu.2013.04.016. Epub 2013 Sep 10. English, Spanish.

  PMID: 24029409 RESULT

• Holic R, Xu Y, Caldo KMP, Singer SD, Field CJ, Weselake RJ, Chen G. Bioactivity and biotechnological production of punicic acid. Appl Microbiol Biotechnol. 2018 Apr;102(8):3537-3549. doi: 10.1007/s00253-018-8883-y. Epub 2018 Mar 3.

  PMID: 29502183 RESULT

MeSH Terms

Conditions

Hepatitis, Alcoholic

Condition Hierarchy (Ancestors)

Hepatitis; Liver Diseases; Digestive System Diseases; Liver Diseases, Alcoholic; Alcohol-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders

Study Officials

• Jacqueline Cordova-Gallardo, MD

  Hospital General Dr. Manuel Gea Gonzalez

  PRINCIPAL INVESTIGATOR

• Gabriela Gutierrez-Reyes, DSc

  Universidad Autonoma de México

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Subjects will be randomly assigned to one of the two treatments. The randomization is done through a computer generated system. The labelling will be done by a pharmacist or similar. Envelopes with randomization listings will be stored in a secure environment within the Hospital. Blinding should be maintained throughout the study. The randomization code should not be broken during the course of the study unless it is necessary for the safety of the subjects, as judged by the investigator. The date, time and reason for unmasking must be recorded, along with the researcher's signature. The rupture of the study blind will be done once the database has been blocked. The study will be double-blind, which means that neither the patients nor the study site staff will have access to the randomization code until the code is broken.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Hepatologist

Model Details: Randomized, Double-blind clinical trial.

Study Record Dates

• First Submitted: October 30, 2018
• First Posted: November 6, 2018
• Study Start: September 30, 2018
• Primary Completion: January 1, 2023
• Study Completion: May 22, 2023
• Last Updated: May 23, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

ME (2)