Use of Fish Oil to Reduce Inflammation During Endovascular Abdominal Aortic Repair

Abdominal Aortic Aneurysm Clinical Trial

— Omega-EVAR  

Official title:

Omega EVAR: Use of Fish Oil to Reduce Inflammation During Endovascular Abdominal Aortic Repair.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03208920
• Other study ID #: 15-16505
• Status: Completed
• Phase: N/A
• Start date: December 2016
• Est. completion date: August 28, 2018

Study information

• Verified date: July 2021
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine if high-dose PUFA supplementation in patients undergoing EVAR for infra-renal AAA reduces the peri-operative inflammation.

Description:

In this 2:1 double-blind, randomized, placebo controlled trial, subjects will be given an active drug of n-3 polyunsaturated fatty acids (PUFAs) or a placebo soybean oil for about two weeks prior to an endovascular abdominal aortic repair (EVAR) and subsequently six months after the procedure. An EVAR is known to produce a systemic inflammatory response with an increased risk of prolonged hospitalization and complicated post-operative recovery with cardiac events, renal and pulmonary dysfunction, and multiple organ failure. The study proposed here has the potential to provide valuable insight on the role of nutritional intervention to improve outcomes related to surgical revascularization.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2
• Est. completion date: August 28, 2018
• Est. primary completion date: March 28, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 90 Years

Eligibility

Inclusion Criteria:

• Undergoing EVAR for infra-renal AAA and/or iliac artery aneurysm

Exclusion Criteria:

• Age < 40 or > 90 years
• On dual antiplatelet therapy or anticoagulation
• Evidence of active infection
• Diagnosed hypercoagulable state
• Non-atherosclerotic/aneurysmal disease as indication for procedure
• Chronic liver disease or myopathy
• End-stage renal disease (CKD 5)
• Poorly controlled diabetes (HbA1C > 8%)
• Recent other major surgery or illness within 6 weeks
• Use of immunosuppressive medication or extant chronic inflammatory disorders
• History of organ transplantation
• Pregnancy or plans to become pregnant
• Condition in which patient life expectancy is less than one year
• Known allergy to fish or fish products
• Presence of symptomatic or ruptured AAA

Related Conditions & MeSH terms

• Abdominal Aortic Aneurysm
• Aneurysm
• Aortic Aneurysm
• Aortic Aneurysm, Abdominal
• Inflammation
• PAD

Intervention

Dietary Supplement:
• Pro-Omega
Pro-Omega (Nordic Naturals, Watsonville, CA, USA). Each Pro-Omega capsule is 550 mg. Must take 4400 mg/day x 6 months.

Other:
• ProOmega Placebo
Placebo Comparator: soybean (Nordic Naturals, Watsonville, CA, USA). Each soybean capsule is 550 mg. Must take 4400 mg/day x 6 months.

Locations

Country	Name	City	State
United States	San Francisco Veteran Affairs Medical Center	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, San Francisco

Country where clinical trial is conducted

United States, 

References & Publications (31)

Bannenberg GL, Chiang N, Ariel A, Arita M, Tjonahen E, Gotlinger KH, Hong S, Serhan CN. Molecular circuits of resolution: formation and actions of resolvins and protectins. J Immunol. 2005 Apr 1;174(7):4345-55. Erratum in: J Immunol. 2005 May 1;174(9):5884. — View Citation

Boyle JR, Goodall S, Thompson JP, Bell PR, Thompson MM. Endovascular AAA repair attenuates the inflammatory and renal responses associated with conventional surgery. J Endovasc Ther. 2000 Oct;7(5):359-71. — View Citation

Chang CK, Chuter TA, Niemann CU, Shlipak MG, Cohen MJ, Reilly LM, Hiramoto JS. Systemic inflammation, coagulopathy, and acute renal insufficiency following endovascular thoracoabdominal aortic aneurysm repair. J Vasc Surg. 2009 May;49(5):1140-6. doi: 10.1016/j.jvs.2008.11.102. — View Citation

Freidlin B, Korn EL, George SL. Data monitoring committees and interim monitoring guidelines. Control Clin Trials. 1999 Oct;20(5):395-407. Review. — View Citation

Galle C, De Maertelaer V, Motte S, Zhou L, Stordeur P, Delville JP, Li R, Ferreira J, Goldman M, Capel P, Wautrecht JC, Pradier O, Dereume JP. Early inflammatory response after elective abdominal aortic aneurysm repair: a comparison between endovascular procedure and conventional surgery. J Vasc Surg. 2000 Aug;32(2):234-46. — View Citation

Gerasimidis T, Sfyroeras G, Trellopoulos G, Skoura L, Papazoglou K, Konstantinidis K, Karamanos D, Filaktou A, Parapanisiou E. Impact of endograft material on the inflammatory response after elective endovascular abdominal aortic aneurysm repair. Angiology. 2005 Nov-Dec;56(6):743-53. — View Citation

Grenon SM, Aguado-Zuniga J, Hatton JP, Owens CD, Conte MS, Hughes-Fulford M. Effects of fatty acids on endothelial cells: inflammation and monocyte adhesion. J Surg Res. 2012 Sep;177(1):e35-43. doi: 10.1016/j.jss.2012.04.010. Epub 2012 Apr 27. — View Citation

Grenon SM, Conte MS, Nosova E, Alley H, Chong K, Harris WS, Vittinghoff E, Owens CD. Association between n-3 polyunsaturated fatty acid content of red blood cells and inflammatory biomarkers in patients with peripheral artery disease. J Vasc Surg. 2013 Nov;58(5):1283-90. doi: 10.1016/j.jvs.2013.05.024. Epub 2013 Jul 2. — View Citation

Harris WS. The omega-3 index as a risk factor for coronary heart disease. Am J Clin Nutr. 2008 Jun;87(6):1997S-2002S. — View Citation

Ho KJ, Spite M, Owens CD, Lancero H, Kroemer AH, Pande R, Creager MA, Serhan CN, Conte MS. Aspirin-triggered lipoxin and resolvin E1 modulate vascular smooth muscle phenotype and correlate with peripheral atherosclerosis. Am J Pathol. 2010 Oct;177(4):2116-23. doi: 10.2353/ajpath.2010.091082. Epub 2010 Aug 13. — View Citation

Lindeman JH, Abdul-Hussien H, Schaapherder AF, Van Bockel JH, Von der Thüsen JH, Roelen DL, Kleemann R. Enhanced expression and activation of pro-inflammatory transcription factors distinguish aneurysmal from atherosclerotic aorta: IL-6- and IL-8-dominated inflammatory responses prevail in the human aneurysm. Clin Sci (Lond). 2008 Jun;114(11):687-97. — View Citation

Morikage N, Esato K, Zenpo N, Fujioka K, Takenaka H. Is endovascular treatment of abdominal aortic aneurysms less invasive regarding the biological responses? Surg Today. 2000;30(2):142-6. — View Citation

Morse MA, Califf RM, Sugarman J. Monitoring and ensuring safety during clinical research. JAMA. 2001 Mar 7;285(9):1201-5. — View Citation

Moulakakis KG, Alepaki M, Sfyroeras GS, Antonopoulos CN, Giannakopoulos TG, Kakisis J, Karakitsos P, Liapis CD. The impact of endograft type on inflammatory response after endovascular treatment of abdominal aortic aneurysm. J Vasc Surg. 2013 Mar;57(3):668-77. doi: 10.1016/j.jvs.2012.09.034. Epub 2013 Jan 11. — View Citation

Rizas KD, Ippagunta N, Tilson MD 3rd. Immune cells and molecular mediators in the pathogenesis of the abdominal aortic aneurysm. Cardiol Rev. 2009 Sep-Oct;17(5):201-10. doi: 10.1097/CRD.0b013e3181b04698. Review. — View Citation

Serhan CN, Brain SD, Buckley CD, Gilroy DW, Haslett C, O'Neill LA, Perretti M, Rossi AG, Wallace JL. Resolution of inflammation: state of the art, definitions and terms. FASEB J. 2007 Feb;21(2):325-32. Review. — View Citation

Serhan CN, Chiang N, Van Dyke TE. Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nat Rev Immunol. 2008 May;8(5):349-61. doi: 10.1038/nri2294. Review. — View Citation

Serhan CN, Clish CB, Brannon J, Colgan SP, Chiang N, Gronert K. Novel functional sets of lipid-derived mediators with antiinflammatory actions generated from omega-3 fatty acids via cyclooxygenase 2-nonsteroidal antiinflammatory drugs and transcellular processing. J Exp Med. 2000 Oct 16;192(8):1197-204. — View Citation

Serhan CN, Hong S, Gronert K, Colgan SP, Devchand PR, Mirick G, Moussignac RL. Resolvins: a family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signals. J Exp Med. 2002 Oct 21;196(8):1025-37. — View Citation

Serhan CN, Savill J. Resolution of inflammation: the beginning programs the end. Nat Immunol. 2005 Dec;6(12):1191-7. Review. — View Citation

Serhan CN, Yang R, Martinod K, Kasuga K, Pillai PS, Porter TF, Oh SF, Spite M. Maresins: novel macrophage mediators with potent antiinflammatory and proresolving actions. J Exp Med. 2009 Jan 16;206(1):15-23. doi: 10.1084/jem.20081880. Epub 2008 Dec 22. — View Citation

Serhan CN. Resolution phase of inflammation: novel endogenous anti-inflammatory and proresolving lipid mediators and pathways. Annu Rev Immunol. 2007;25:101-37. Review. — View Citation

Spite M, Serhan CN. Novel lipid mediators promote resolution of acute inflammation: impact of aspirin and statins. Circ Res. 2010 Nov 12;107(10):1170-84. doi: 10.1161/CIRCRESAHA.110.223883. Review. — View Citation

Storck M, Scharrer-Pamler R, Kapfer X, Gallmeier U, Görich J, Sunder-Plassmann L, Brückner U, Mickley V. Does a postimplantation syndrome following endovascular treatment of aortic aneurysms exist? Vasc Surg. 2001 Jan-Feb;35(1):23-9. — View Citation

Swartbol P, Truedsson L, Norgren L. Adverse reactions during endovascular treatment of aortic aneurysms may be triggered by interleukin 6 release from the thrombotic content. J Vasc Surg. 1998 Oct;28(4):664-8. — View Citation

Tang Y, Zhang MJ, Hellmann J, Kosuri M, Bhatnagar A, Spite M. Proresolution therapy for the treatment of delayed healing of diabetic wounds. Diabetes. 2013 Feb;62(2):618-27. doi: 10.2337/db12-0684. Epub 2012 Oct 5. — View Citation

Velázquez OC, Carpenter JP, Baum RA, Barker CF, Golden M, Criado F, Pyeron A, Fairman RM. Perigraft air, fever, and leukocytosis after endovascular repair of abdominal aortic aneurysms. Am J Surg. 1999 Sep;178(3):185-9. — View Citation

Wang JH, Eguchi K, Matsumoto S, Fujiu K, Komuro I, Nagai R, Manabe I. The ?-3 polyunsaturated fatty acid, eicosapentaenoic acid, attenuates abdominal aortic aneurysm development via suppression of tissue remodeling. PLoS One. 2014 May 5;9(5):e96286. doi: 10.1371/journal.pone.0096286. eCollection 2014. — View Citation

Whitehead J. Monitoring and evaluating clinical trials data. Intensive Care Med. 2000;26 Suppl 1:S84-8. — View Citation

Yang R, Chiang N, Oh SF, Serhan CN. Metabolomics-lipidomics of eicosanoids and docosanoids generated by phagocytes. Curr Protoc Immunol. 2011 Nov;Chapter 14:Unit 14.26. doi: 10.1002/0471142735.im1426s95. — View Citation

Zimmer S, Heiss MM, Schardey HM, Weilbach C, Faist E, Lauterjung L. [Inflammatory syndrome after endovascular implantation of an aortic stent--a comparative study]. Langenbecks Arch Chir Suppl Kongressbd. 1998;115(Suppl I):13-7. German. — View Citation

* Note: There are 31 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Highly Sensitive C-Reactive Protein	Blunting of the peri-PVI inflammatory response as measured by the area under the curve (AUC) of the inflammatory biomarker high sensitivity C reactive protein (CRP)	6 months
Secondary	Systemic Inflammatory Markers	Reduce circulating pro-inflammatory markers (PIMs) and increase pro-resolution mediators (PRMs) assayed using targeted metabolo-lipidomics, increase PRM production within peripheral circulating monocytes.	6 months