Clinical trial NCT05725798: Perioperative Sitagliptin Medication for Reduction of the Inflammatory Response Associated With Cardiopulmonary Bypass
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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Systemic Inflammatory Response Syndrome
Keywords: SIRS, Cardiac surgery, DPP4
Lead sponsor: University Hospital Muenster
Sponsor class: OTHER
First posted: 2023-02-13
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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

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.

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

Primary outcomes:
measure: Total norepinephrine-requirement within 24 hours after surgery
timeFrame: Retrospective data collection 24 hours after surgery
measure: Total crystalloid volume-requirement within 24 hours after surgery
timeFrame: Retrospective data collection 24 hours after surgery
Secondary outcomes:
measure: Immune cells surface markers
timeFrame: Measured 24 hours after surgery
measure: Cytokine-levels
timeFrame: Measured 24 hours after surgery
measure: Sublingual microcirculatory parameters: Total vessel density, Proportion of Perfused Vessels, Perfused Vessel Density, Microvascular Flow Index
timeFrame: Measured immediately after surgery and 24 hours after surgery
Other outcomes:
Locations:
city: Münster
country: Germany
facility: University Hospital Münster
state: North Rhine-Westphalia
Study officials:
affiliation: University Hospital Münster
name: Nana-Maria Wagner, Prof. Dr.
role: STUDY_DIRECTOR
References:
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.
citation: 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.
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.