Perioperative Sitagliptin Medication for Reduction of the Inflammatory Response Associated With Cardiopulmonary Bypass (SiCa-Flam)

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

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.

Study Overview

• Status: Completed
• Conditions: Systemic Inflammatory Response Syndrome
• Intervention / Treatment: Drug: Sitagliptin

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.

• Study Type: Observational
• Enrollment (Actual): 20

Contacts and Locations

Study Locations

• Germany
  • North Rhine-Westphalia
    • Münster, North Rhine-Westphalia, Germany, 48147
      • University Hospital Münster

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Adult cardiac surgery patients from University Hospital Münster who suffer from...

• Diabetes mellitus type 2 with Sitagliptin treatment or,
• Diabetes mellitus type 2 without Sitagliptin treatment or,
• No diabetes mellitus

Description

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 Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
DM and Sitagliptin treatment; Cardiac surgery patients who suffer from diabetes mellitus type 2 and take Sitagliptin.	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.
DM without Sitagliptin treatment; Cardiac surgery patients who suffer from diabetes mellitus type 2 and do not take Sitagliptin.
No DM; Cardiac surgery patients who do not suffer from diabetes mellitus type 2 and do not take Sitagliptin.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital Muenster
• Investigators: Study Director: Nana-Maria Wagner, Prof. Dr., University Hospital Münster

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2022
• Primary Completion (Actual): May 1, 2023
• Study Completion (Actual): August 1, 2023

Study Registration Dates

• First Submitted: January 19, 2023
• First Submitted That Met QC Criteria: February 10, 2023
• First Posted (Actual): February 13, 2023

Study Record Updates

• Last Update Posted (Actual): August 22, 2023
• Last Update Submitted That Met QC Criteria: August 19, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: SIRS, Cardiac surgery, DPP4
• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation; Shock; Systemic Inflammatory Response Syndrome; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Sitagliptin Phosphate
• Other Study ID Numbers: 02-AnIt-19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No