Evaluation of Corticosteroid in Systemic Inflammatory Response Syndrome

Systemic Inflammatory Response Syndrome Clinical Trial

Official title:

Evaluation of Corticosteroid as Modulators of Humeral and Cellular Immune Response in Open Heart Surgery in Egyptian Population

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03876041
• Other study ID #: ASSUITUU
• Status: Completed
• Phase: Phase 4
• Start date: September 1, 2019
• Est. completion date: November 1, 2020

Study information

• Verified date: June 2021
• Source: Assiut University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Cardiac surgery and cardiopulmonary bypass (CPB) initiate a whole-body systemic inflammatory response (SIRS) characterized by the activation of leukocytes, monocytes, and the complement cascade. Multiple mediators of the inflammatory process are released, including cytokines, endothelin, adhesion molecules, and oxygen free radicals. An exaggerated release of these mediators may contribute to numerous postoperative end-organ complications, including myocardial dysfunction, neurologic impairment, respiratory failure, altered renal and hepatic function, bleeding disorders, and multiple organ failure. Although most cardiac surgical patients do not experience major adverse events, it is likely that the inflammatory response impairs clinical recovery to some degree in all patients.

A large number of therapeutic strategies have been developed to attenuate the inflammatory reaction to CPB and thereby enhance recovery of the cardiac surgical patient. Intraoperative corticosteroid administration has been studied extensively as a primary pharmacologic anti-inflammatory treatment option.

Description:

Investigations have shown that clinical outcomes have been improved, worsened, or unaffected by the intraoperative administration of dexamethasone or methylprednisolone Limited data suggest that low-dose corticosteroids may be as effective as high-dose treatment in reducing complications but with fewer potential side effects MicroRNAs (miRNAs) are protein regulators that play an important role in a wide range of cellular functions. There is increasing evidence for the close relationship between miRNA expression, Th17 cell differentiation and disease pathology The miRNA, miR-155, which was the subject of this study, has a range of known biological functions, which include the induction of Toll like receptor (TLR) activation in monocytes /macrophages and the modulation of TLR signaling, facilitating pro-inflammatory cellular responses and initiating systemic inflammatory responses, as well as regulating Treg cell differentiation, maintenance, and function. The expression of this miRNA can be induced by inflammatory cytokines, such as tumor necrosis factor α (TNFα), that are released into the circulation in the initial stages of a systemic inflammatory response. In another study, demonstrated that miR-155 enhanced Treg and Th17 cell differentiation and Th17 cell function by targeting (suppressor of cytokine signaling 1) SOCS1.

In this study, the investigators will compare effect of low dose intra-operative corticosteroid (dexamethasone and methylprednisolone) as anti-inflammatory modulators through detection of T regulatory cells(Tregs) and IL-17 and correlate relation between Treg, IL-17 and micro RNA-155.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: November 1, 2020
• Est. primary completion date: September 1, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• open heart surgery with Cardiopulmonary bypass machine with relatively long bypass time more than 60 minute

• All patients Included in study with normal heart function

Exclusion Criteria:

• Left ventricular ejection fraction less than 40%

• acute infection such as sepsis or pneumonia, hepatic and renal failure, cancer or any autoimmune disease

• the use of steroid within 2 week prior to operation

• coagulation abnormalities

Related Conditions & MeSH terms

• Syndrome
• Systemic Inflammatory Response Syndrome

Intervention

Drug:
• solumedrol
intravenous solution for injection
• Dexamethasone phosphate
intravenous solution for injection

Locations

Country	Name	City	State
Egypt	Assuit university hospital	Assiut	Assuit

Sponsors (1)

Lead Sponsor	Collaborator
Assiut University

Country where clinical trial is conducted

Egypt, 

References & Publications (5)

Bocsi J, Hänzka MC, Osmancik P, Hambsch J, Dähnert I, Sack U, Bellinghausen W, Schneider P, Janoušek J, Kostelka M, Tárnok A. Modulation of the cellular and humoral immune response to pediatric open heart surgery by methylprednisolone. Cytometry B Clin Cytom. 2011 Jul-Aug;80(4):212-20. doi: 10.1002/cyto.b.20587. Epub 2011 Mar 4. — View Citation

Cicarelli DD, Benseñor FE, Vieira JE. Effects of single dose of dexamethasone on patients with systemic inflammatory response. Sao Paulo Med J. 2006 Mar 2;124(2):90-5. — View Citation

Schadenberg AW, Vastert SJ, Evens FC, Kuis W, van Vught AJ, Jansen NJ, Prakken BJ. FOXP3+ CD4+ Tregs lose suppressive potential but remain anergic during transient inflammation in human. Eur J Immunol. 2011 Apr;41(4):1132-42. doi: 10.1002/eji.201040363. Epub 2011 Mar 7. — View Citation

Soltani G, Abbasi Tashnizi M, Moeinipour AA, Ganjifard M, Esfahanizadeh J, Sepehri Shamloo A, Purafzali Firuzabadi SJ, Zirak N. Comparing the effect of preoperative administration of methylprednisolone and its administration before and during surgery on the clinical outcome in pediatric open heart surgeries. Iran Red Crescent Med J. 2013 Jun;15(6):483-7. doi: 10.5812/ircmj.8105. Epub 2013 Jun 5. — View Citation

Wang D, Tang M, Zong P, Liu H, Zhang T, Liu Y, Zhao Y. MiRNA-155 Regulates the Th17/Treg Ratio by Targeting SOCS1 in Severe Acute Pancreatitis. Front Physiol. 2018 Jun 8;9:686. doi: 10.3389/fphys.2018.00686. eCollection 2018. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	measure anti-inflammatory effect through detection T regulatory cell level by4 color flow cytometry analysis to quantify % of Tregs (CD4, CD25,FoxP3)	in blood of all subjects	72 hours post operative
Primary	detect microRNA-155	micro-RNA 155 is measured by RT-PCR	72 hours post operative
Secondary	measure pro-inflammatory cytokines	pro-inflammatory cytokines such as IL-1 and IL-6 by ELISA.	72 hours post operative