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

Completed
Conditions
Systemic Inflammatory Response Syndrome
Interventions
Registration Number
NCT05725798
Lead Sponsor
University Hospital Muenster
Brief 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.

Detailed 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 & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
20
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

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
DM and Sitagliptin treatmentSitagliptinCardiac surgery patients who suffer from diabetes mellitus type 2 and take Sitagliptin.
Primary Outcome Measures
NameTimeMethod
Total crystalloid volume-requirement within 24 hours after surgeryRetrospective data collection 24 hours after surgery

Retrospective data collection from the hospital information system

Total norepinephrine-requirement within 24 hours after surgeryRetrospective data collection 24 hours after surgery

Retrospective data collection from the hospital information system

Secondary Outcome Measures
NameTimeMethod
Immune cells surface markersMeasured 24 hours after surgery

Measured by using Cytec Aurora Flow Cytometry

Cytokine-levelsMeasured 24 hours after surgery

Measured by using multiplex immunoassay analysis.

Sublingual microcirculatory parameters: Total vessel density, Proportion of Perfused Vessels, Perfused Vessel Density, Microvascular Flow IndexMeasured immediately after surgery and 24 hours after surgery

Measured by using videomicroscopy to generate sublingual microcirculatory images.

Trial Locations

Locations (1)

University Hospital Münster

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Münster, North Rhine-Westphalia, Germany

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