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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Systemic Inflammatory Response Syndrome

Intervention / Treatment
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* Drug: Sitagliptin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| DM and Sitagliptin treatment<br>Cardiac surgery patients who suffer from diabetes mellitus type 2 and take Sitagliptin. | Drug: Sitagliptin<br>* 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.<br>|
| DM without Sitagliptin treatment<br>Cardiac surgery patients who suffer from diabetes mellitus type 2 and do not take Sitagliptin. | |
| No DM<br>Cardiac surgery patients who do not suffer from diabetes mellitus type 2 and do not take Sitagliptin. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total norepinephrine-requirement within 24 hours after surgery | Retrospective data collection from the hospital information system | Retrospective data collection 24 hours after surgery | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immune cells surface markers | Measured by using Cytec Aurora Flow Cytometry | Measured 24 hours after surgery | 
| Cytokine-levels | Measured by using multiplex immunoassay analysis. | Measured 24 hours after surgery | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SIRS, Cardiac surgery, DPP4