Systemic Inflammatory Response SyndromeSiCa-FlamNCT05725798
Perioperative Sitagliptin Medication for Reduction of the Inflammatory Response Associated With Cardiopulmonary Bypass
An observational study of Systemic Inflammatory Response Syndrome, run by University Hospital Muenster at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Systemic Inflammatory Response Syndrome
- What is being tested?
- Sitagliptin
- How many people
- 20 participants
- Where
- 1 siteGermany
- Study dates
- 1 Feb 2022to 1 Aug 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Adult, Older adult
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
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Germany1 site
University Hospital Münster
Münster, North Rhine-Westphalia, 48147
About this study
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
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.
Read the 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
- Being tested
- Sitagliptin
- Keywords
- SIRS, Cardiac surgery, DPP4
- Medical subject headings
- Systemic Inflammatory Response Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SitagliptinDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| DM and Sitagliptin treatment | Cardiac surgery patients who suffer from diabetes mellitus type 2 and take Sitagliptin. Receives: Drug: 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 being measured
The primary outcome is the main question the study is designed to answer.
Total norepinephrine-requirement within 24 hours after surgery
Retrospective data collection from the hospital information system
Measured: Retrospective data collection 24 hours after surgery
Total crystalloid volume-requirement within 24 hours after surgery
Retrospective data collection from the hospital information system
Measured: Retrospective data collection 24 hours after surgery
Secondary outcomes (3)
Immune cells surface markers
Measured by using Cytec Aurora Flow Cytometry
Measured: Measured 24 hours after surgery
Cytokine-levels
Measured by using multiplex immunoassay analysis.
Measured: 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: Measured immediately after surgery and 24 hours after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2023
- Study start1 Feb 2022
- Primary completion1 May 2023
- Study completion1 Aug 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Systemic Inflammatory Response SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Muenster
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sebastian Kintrup, University Hospital Muenster
- Investigators
- Nana-Maria Wagner, Prof. Dr., Study director, University Hospital Münster
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05725798
- Sponsor's protocol ID
- 02-AnIt-19
- Acronym
- SiCa-Flam
- Status last verified
- Aug 2023
- First submitted
- 19 Jan 2023
- Last updated
- 22 Aug 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 10648832Brabenec 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.
PubMed 35699655Sablotzki 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.
PubMed 11958300Hellenthal 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.
PubMed 40817204
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05725798
- Acronym / sponsor ID
- SiCa-Flam / 02-AnIt-19
- Conditions
- Systemic Inflammatory Response Syndrome
- Keywords
- SIRS, Cardiac surgery, DPP4
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University Hospital MuensterUniversity, hospital or other
- Study start
- 1 Feb 2022 (actual)
- Primary completion
- 1 May 2023 (actual)
- Study completion
- 1 Aug 2023 (actual)
- First posted
- 13 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| DM and Sitagliptin treatment | – | Drug: SitagliptinCardiac surgery patients who suffer from diabetes mellitus type 2 and 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Age groups
- Adult, Older adult
- 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
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (8 listed)
- Diabetes mellitus type 1
- Treatment with another DPP4-inhibitor
- Treatment with GLP-1-analoga
- Emergency surgery
- Chronic or acute infection
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SitagliptinGroup 1 who regularly takes Sitagliptin due to diabetes mellitus type 2 continues the treatment perioperatively. Group 2 and group 3 do not take Sitagliptin. | Drug | DM and Sitagliptin treatment |
Primary outcome
Total norepinephrine-requirement within 24 hours after surgery
Time frame: Retrospective data collection 24 hours after surgery
Retrospective data collection from the hospital information system
Total crystalloid volume-requirement within 24 hours after surgery
Time frame: Retrospective data collection 24 hours after surgery
Retrospective data collection from the hospital information system
3 secondary outcomes
Immune cells surface markers
Time frame: Measured 24 hours after surgery
Cytokine-levels
Time frame: Measured 24 hours after surgery
Sublingual microcirculatory parameters: Total vessel density, Proportion of Perfused Vessels, Perfused Vessel Density, Microvascular Flow Index
Time frame: Measured immediately after surgery and 24 hours after surgery
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2023.
- Background: PubMed 10648832Wrenger 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.
- Background: PubMed 35699655Brabenec 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.
- Background: PubMed 11958300Sablotzki 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.
- Derived from this study: PubMed 40817204Hellenthal 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nana-Maria Wagner, Prof. Dr. study director
University Hospital Münster
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Systemic Inflammatory Response Syndrome, run by University Hospital Muenster at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Total norepinephrine-requirement within 24 hours after surgery (time frame: Retrospective data collection 24 hours after surgery). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05725798, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2023.