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

NCT ID: NCT05725798

Last Updated: 2023-08-22

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 20 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-02-01
• Study Completion Date: 2023-08-01

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.

Conditions

Systemic Inflammatory Response Syndrome

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

DM and Sitagliptin treatment

Cardiac surgery patients who suffer from diabetes mellitus type 2 and take Sitagliptin.

Sitagliptin

Intervention Type: DRUG

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 interventions assigned to this group

No DM

Cardiac surgery patients who do not suffer from diabetes mellitus type 2 and do not take Sitagliptin.

No interventions assigned to this group

Interventions

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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital Muenster

OTHER

Sponsor Role: lead

Responsible Party

Sebastian Kintrup

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Nana-Maria Wagner, Prof. Dr.

Role: STUDY_DIRECTOR

University Hospital Münster

Locations

University Hospital Münster

Münster, North Rhine-Westphalia, Germany

Countries

Germany

References

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.

Reference Type: BACKGROUND

PMID: 10648832 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 35699655 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 11958300 (View on PubMed)

Hellenthal KEM, Kintrup S, Wirth T, Brabenec L, Cursiefen C, Beulen R, Hollmann K, Lehmann M, Burkard P, Roth J, Schughart K, Klotz L, Rossaint J, Meybohm P, Wagner NM. DPP4 inhibition curbs systemic inflammation. Crit Care. 2025 Aug 15;29(1):359. doi: 10.1186/s13054-025-05599-x.

Reference Type: DERIVED

PMID: 40817204 (View on PubMed)

Other Identifiers

02-AnIt-19

Identifier Type: -

Identifier Source: org_study_id