Perioperative Sitagliptin Medication for Reduction of the Inflammatory Response Associated With Cardiopulmonary Bypass

Systemic Inflammatory Response Syndrome Clinical Trial

— SiCa-Flam  

Official title:

Perioperative Sitagliptin Medication for Reduction of the Inflammatory Response Associated With Cardiopulmonary Bypass and Postoperative Glucose Control in Diabetic Patients Undergoing Elective Cardiac Surgery - a Pilot Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05725798
• Other study ID #: 02-AnIt-19
• Status: Completed
• Start date: February 1, 2022
• Est. completion date: August 1, 2023

Study information

• Verified date: August 2023
• Source: University Hospital Muenster
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Sitagliptin is an inhibitor of the enzyme dipeptidylpeptidase-4 (DPP-4) and represents an established drug in type 2 diabetes mellitus treatment. However, Sitagliptin may also have several antiinflammatory properties. Within this study the investigators examine the effects of perioperative Sitagliptin intake on the inflammatory response after cardiopulmonary bypass.

Description:

Sitagliptin is an inhibitor of the enzyme dipeptidylpeptidase-4 (DPP-4) and represents an established drug in type 2 diabetes mellitus treatment. However, Sitagliptin may also have several antiinflammatory properties. For example, it is known that DPP-4-inhibition prevents procalcitonin from being cleaved to a truncated form that lacks 2 amino acids. As the investigators described recently, truncated procalcitonin targets the CRLR-RAMP1-receptor on vascular endothelium and induces VE-cadherin-phosphorylation which leads to leakage of fluids and proteins from vessels. Furthermore, many other immunoregulatory targets such as substance p, CXCL10 or NF-kB have been reported to be modified by DPP-4. Therefore, it can be assumed that Sitagliptin possibly represents a powerful drug in inflammatory circumstances.

The aim of this study is to prove possible antiinflammatory properties by conducting an observational trial in cardiac surgery patients. All patients undergo cardiac surgery with the use of cardiopulmonary bypass (CBP) which is known to trigger a systemic inflammatory response syndrome (SIRS). Group 1 suffers from diabetes mellitus type two and regularly takes Sitagliptin which is continued perioperatively. Group 2 also suffers from diabetes mellitus type 2 but does not take Sitagliptin. Group 3 has no diabetes mellitus but also undergoes cardiac surgery. To determine the effect of Sitagliptin under inflammatory conditions deep immune phenotyping and a cytokine assay is performed from blood withdrawals 24h after surgery. Moreover, the sublingual microcirculation is measured two times after the operation.

Taking all measurements of the cellular immune system, the humoral immune system and the vasculature into account it should be possible to define the immunoregulatory effects of Sitagliptin treatment more properly.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: August 1, 2023
• Est. primary completion date: May 1, 2023
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age >18 years

• Patients undergoing cardiac surgery with use of CBP and...

• Diabetes mellitus type 2 with Sitagliptin treatment or,

• Diabetes mellitus type 2 without Sitagliptin treatmet or,

• No diabetes mellitus

• Written informed consent

Exclusion Criteria:

• Diabetes mellitus type 1

• Treatment with another DPP4-inhibitor

• Treatment with GLP-1-analoga

• Emergency surgery

• Chronic or acute infection

• Pregnancy

• Participation in an interventional study trial within last 3 months

• Relationship to study investigators

Related Conditions & MeSH terms

• Systemic Inflammatory Response Syndrome

Intervention

Drug:
• Sitagliptin
Group 1 who regularly takes Sitagliptin due to diabetes mellitus type 2 continues the treatment perioperatively. Group 2 and group 3 do not take Sitagliptin.

Locations

Country	Name	City	State
Germany	University Hospital Münster	Münster	North Rhine-Westphalia

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Muenster

Country where clinical trial is conducted

Germany, 

References & Publications (3)

Brabenec L, Muller M, Hellenthal KEM, Karsten OS, Pryvalov H, Otto M, Holthenrich A, Matos ALL, Weiss R, Kintrup S, Hessler M, Dell'Aquila A, Thomas K, Nass J, Margraf A, Nottebaum AF, Rossaint J, Zarbock A, Vestweber D, Gerke V, Wagner NM. Targeting Procalcitonin Protects Vascular Barrier Integrity. Am J Respir Crit Care Med. 2022 Aug 15;206(4):488-500. doi: 10.1164/rccm.202201-0054OC. — View Citation

Sablotzki A, Friedrich I, Muhling J, Dehne MG, Spillner J, Silber RE, Czeslik E. The systemic inflammatory response syndrome following cardiac surgery: different expression of proinflammatory cytokines and procalcitonin in patients with and without multiorgan dysfunctions. Perfusion. 2002 Mar;17(2):103-9. doi: 10.1177/026765910201700206. — View Citation

Wrenger S, Kahne T, Bohuon C, Weglohner W, Ansorge S, Reinhold D. Amino-terminal truncation of procalcitonin, a marker for systemic bacterial infections, by dipeptidyl peptidase IV (DP IV). FEBS Lett. 2000 Jan 21;466(1):155-9. doi: 10.1016/s0014-5793(99)01779-2. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total norepinephrine-requirement within 24 hours after surgery	Retrospective data collection from the hospital information system	Retrospective data collection 24 hours after surgery
Primary	Total crystalloid volume-requirement within 24 hours after surgery	Retrospective data collection from the hospital information system	Retrospective data collection 24 hours after surgery
Secondary	Immune cells surface markers	Measured by using Cytec Aurora Flow Cytometry	Measured 24 hours after surgery
Secondary	Cytokine-levels	Measured by using multiplex immunoassay analysis.	Measured 24 hours after surgery
Secondary	Sublingual microcirculatory parameters: Total vessel density, Proportion of Perfused Vessels, Perfused Vessel Density, Microvascular Flow Index	Measured by using videomicroscopy to generate sublingual microcirculatory images.	Measured immediately after surgery and 24 hours after surgery