Clinical trial NCT05703802: Establishment of an ELISA for the Recognition of Procalcitonin Variants in Patients With Hyperprocalcitonemia.
Official title: Establishment of an Enzyme-linked Immunosorbent Assay for the Recognition of Procalcitonin Variants and Characterization of Procalcitonin Variants in Patients With Hyperprocalcitonemia.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Sepsis
Pre-Eclampsia
Granulomatosis With Polyangiitis
Microscopic Polyangiitis
Adiposity
SIRS
Procalcitonin
Lead sponsor: University Hospital Muenster
Sponsor class: OTHER
First posted: 2023-01-30
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients from the University Hospital Münster who suffer from different diseases which are accompanied by hyperprocalcitoninemia.

Brief summary: Procalcitonin is a protein consisting of 116 amino-acids which can rapidly rise under inflammatory conditions and sepsis. More than 20 years ago it has been shown that dipeptidylpeptidase-4 (DPP-4) cleaves procalcitonin from the n-terminus, resulting in a truncated procalcitonin-variant which consists of 114 aminoacids. Within their workgroup the investigators found that the truncated procalcitonin-variant had deleterious effects on vascular integrity during sepsis in mice. However, it is unknown if this applies also in humans. By using an ELISA-assay the investigators want to examine the ratio between native and truncated human procalcitonin during diseases accompanied with hyperprocalcitoninemia and correlate the results with clinical data.

Detailed description: Procalcitonin is a protein consisting of 116 amino-acids which can rapidly rise under inflammatory conditions and sepsis. More than 20 years ago it has been shown that dipeptidylpeptidase-4 (DPP-4) cleaves procalcitonin from the n-terminus, resulting in a truncated procalcitonin-variant which consists of 114 aminoacids.

Within their workgroup the investigators found that the truncated procalcitonin-variant had deleterious effects on vascular integrity during sepsis in mice: They observed that binding of truncated procalcitonin to the CRLR/RAMP1-receptor on vascular endothelium lead to phosphorylation and destruction of VE-cadherin, an essential part of adherens junctions. Consequently, paracellular leakage of proteins and fluid from blood vessels developed.

It is unknown if these effects also apply to humans. By using an ELISA-assay the investigators want to examine the ratio between native and truncated human procalcitonin during diseases accompanied with hyperprocalcitoninemia and correlate the results with clinical data. Futhermore, they want to examine if the procalcitonin-variants have influence on cytokine levels and surface antigens on immune cells by performing multiplex immunoassays and FACS-analysis.

Eligibility criteria: Inclusion Criteria:

* Age \>18
* Patients with diagnosis...
* Sepsis or,
* SIRS after cardiothoracic surgery or,
* adipositas or,
* granulomatosis with polyangiitis/microscopic polyangiitis or,
* pre-eclampsia
* healthy control subjects
* written informed consent

Exclusion Criteria:

* participation in an interventional study trial within the last 3 months
* relationship to study investigator

Primary outcomes:
measure: Ratio between native and truncated procalcitonin during different conditions of hyperprocalcitoninemia
timeFrame: Blood withdrawal takes approximately 5 minutes per patient
Secondary outcomes:
measure: DPP-4-activity
timeFrame: Blood withdrawal takes approximately 5 minutes per patient
measure: Proinflammatory cytokines
timeFrame: Blood withdrawal takes approximately 5 minutes per patient
measure: Immun cell surface-antigens
timeFrame: Blood withdrawal takes approximately 5 minutes per patient
Other outcomes:
Locations:
city: Münster
country: Germany
facility: University Hospital Münster
state: North Rhine-Westphalia
Study officials:
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: Weglohner W, Struck J, Fischer-Schulz C, Morgenthaler NG, Otto A, Bohuon C, Bergmann A. Isolation and characterization of serum procalcitonin from patients with sepsis. Peptides. 2001 Dec;22(12):2099-103. doi: 10.1016/s0196-9781(01)00541-1.