Eicosanoids in Human Heart Failure

Heart Failure Clinical Trial

Official title:

Plasmatic Levels of Epoxyeicosatrienoic and Dihydroxyeicosatrienoic Acids in Heart Failure

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05305170
• Other study ID #: UHMotol
• Status: Recruiting
• Start date: August 1, 2021
• Est. completion date: December 31, 2024

Study information

• Verified date: March 2022
• Source: University Hospital, Motol
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Our translational project aims to evaluate the role of eicosanoids in human HF.

Description:

Heart failure (HF) is the leading cause of cardiovascular hospitalizations, and with its increasing prevalence, the healthcare systems face a heart failure pandemic. Translational research findings improve our knowledge of pathophysiology and uncover therapeutic targets in HF. Natriuretic peptides represent such examples as routinely used in diagnostics and therapeutics (neprilysin inhibitor). Despite modern pharmacotherapy, including angiotensin receptor-neprilysin inhibitor (ARNI) and sodium-glucose cotransporter-2 inhibitors (SGLT2i), the prognosis of patients, especially with advanced heart failure, remains poor. Furthermore, most medication is limited in the late stages of HF due to their hypotensive effects.

Basic research has been focused on the eicosanoids - metabolites of cytochrome P-450 (CYP)-dependent epoxygenase pathway of arachidonic acid (AA), especially epoxyeicosatrienoic acids (EETs). In the preclinical studies, it was shown that EETs importantly contribute to the regulation of cardiovascular and renal function and exert organ-protective actions. It was also proposed that intrarenal EETs operate as an endogenous compensatory system opposing increased renin-angiotensin system (RAS) activity. EETs are rapidly transformed by soluble epoxide hydrolase (sEH) to biologically inactive dihydroxyeicosatrienoic acids (DHETs). The role of eicosanoids in human HF, however, remains unclear.

Our translational project (Eicosanoids in Human Heart Failure) aims to evaluate the role of eicosanoids in human HF.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Heart failure

Exclusion Criteria:

• None

Related Conditions & MeSH terms

• Heart Failure

Intervention

Diagnostic Test:
• Levels of EETs, DHETs and HETEs
The plasmatic concentration of EETs, DHETs, and HETEs.

Locations

Country	Name	City	State
Czechia	University Hospital Motol	Prague

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Motol

Country where clinical trial is conducted

Czechia, 

References & Publications (12)

Conrad N, Judge A, Tran J, Mohseni H, Hedgecott D, Crespillo AP, Allison M, Hemingway H, Cleland JG, McMurray JJV, Rahimi K. Temporal trends and patterns in heart failure incidence: a population-based study of 4 million individuals. Lancet. 2018 Feb 10;391(10120):572-580. doi: 10.1016/S0140-6736(17)32520-5. Epub 2017 Nov 21. — View Citation

Elmarakby AA. Reno-protective mechanisms of epoxyeicosatrienoic acids in cardiovascular disease. Am J Physiol Regul Integr Comp Physiol. 2012 Feb 1;302(3):R321-30. doi: 10.1152/ajpregu.00606.2011. Epub 2011 Nov 23. Review. — View Citation

Fan F, Roman RJ. Effect of Cytochrome P450 Metabolites of Arachidonic Acid in Nephrology. J Am Soc Nephrol. 2017 Oct;28(10):2845-2855. doi: 10.1681/ASN.2017030252. Epub 2017 Jul 12. Review. — View Citation

Fleming I. The pharmacology of the cytochrome P450 epoxygenase/soluble epoxide hydrolase axis in the vasculature and cardiovascular disease. Pharmacol Rev. 2014 Oct;66(4):1106-40. doi: 10.1124/pr.113.007781. Review. — View Citation

Gawrys O, Husková Z, Baranowska I, Walkowska A, Sadowski J, Kikerlová S, Vanourková Z, Honetschlägerová Z, Škaroupková P, Cervenka L, Falck JR, Imig JD, Kompanowska-Jezierska E. Combined treatment with epoxyeicosatrienoic acid analog and 20-hydroxyeicosatetraenoic acid antagonist provides substantial hypotensive effect in spontaneously hypertensive rats. J Hypertens. 2020 Sep;38(9):1802-1810. doi: 10.1097/HJH.0000000000002462. — View Citation

Imig JD, Cervenka L, Neckar J. Epoxylipids and soluble epoxide hydrolase in heart diseases. Biochem Pharmacol. 2022 Jan;195:114866. doi: 10.1016/j.bcp.2021.114866. Epub 2021 Dec 2. Review. — View Citation

Imig JD, Elmarakby A, Nithipatikom K, Wei S, Capdevila JH, Tuniki VR, Sangras B, Anjaiah S, Manthati VL, Sudarshan Reddy D, Falck JR. Development of epoxyeicosatrienoic acid analogs with in vivo anti-hypertensive actions. Front Physiol. 2010 Dec 3;1:157. doi: 10.3389/fphys.2010.00157. eCollection 2010. — View Citation

Jamieson KL, Endo T, Darwesh AM, Samokhvalov V, Seubert JM. Cytochrome P450-derived eicosanoids and heart function. Pharmacol Ther. 2017 Nov;179:47-83. doi: 10.1016/j.pharmthera.2017.05.005. Epub 2017 May 25. Review. — View Citation

Kala P, Miklovic M, Jíchová Š, Škaroupková P, Vanourková Z, Maxová H, Gawrys O, Kompanowska-Jezierska E, Sadowski J, Imig JD, Falck JR, Veselka J, Cervenka L, Aiglová R, Vícha M, Gloger V, Táborský M. Effects of Epoxyeicosatrienoic Acid-Enhancing Therapy on the Course of Congestive Heart Failure in Angiotensin II-Dependent Rat Hypertension: From mRNA Analysis towards Functional In Vivo Evaluation. Biomedicines. 2021 Aug 20;9(8). pii: 1053. doi: 10.3390/biomedicines9081053. — View Citation

McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, Burri H, Butler J, Celutkiene J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Kathrine Skibelund A; ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021 Sep 21;42(36):3599-3726. doi: 10.1093/eurheartj/ehab368. Erratum in: Eur Heart J. 2021 Oct 14;:. — View Citation

Sporková A, Reddy RN, Falck JR, Imig JD, Kopkan L, Sadowski J, Cervenka L. Interlobular Arteries From 2-Kidney, 1-Clip Goldblatt Hypertensive Rats' Exhibit-Impaired Vasodilator Response to Epoxyeicosatrienoic Acids. Am J Med Sci. 2016 May;351(5):513-9. doi: 10.1016/j.amjms.2016.02.030. Epub 2016 Feb 23. — View Citation

Vaduganathan M, Claggett BL, Jhund PS, Cunningham JW, Pedro Ferreira J, Zannad F, Packer M, Fonarow GC, McMurray JJV, Solomon SD. Estimating lifetime benefits of comprehensive disease-modifying pharmacological therapies in patients with heart failure with reduced ejection fraction: a comparative analysis of three randomised controlled trials. Lancet. 2020 Jul 11;396(10244):121-128. doi: 10.1016/S0140-6736(20)30748-0. Epub 2020 May 21. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasmatic levels of eicosanoids	EET, DHET, 20-HETE	at enrollment
Secondary	Mortality	Overall mortality	2 years