Establishment of an ELISA for the Recognition of Procalcitonin Variants in Patients With Hyperprocalcitonemia.

Sepsis Clinical Trial

Official title:

Establishment of an Enzyme-linked Immunosorbent Assay for the Recognition of Procalcitonin Variants and Characterization of Procalcitonin Variants in Patients With Hyperprocalcitonemia.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05703802
• Other study ID #: 10-AnIt-19
• Status: Recruiting
• Start date: July 1, 2022
• Est. completion date: March 1, 2023

Study information

• Verified date: January 2023
• Source: University Hospital Muenster
• Contact: Sebastian Kintrup, Dr.
• Phone: 015120533081
• Email: Sebastian.Kintrup[@]ukmuenster.de
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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 our workgroup we 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 we want to examine the ratio between native and truncated human procalcitonin during diseases accompanied with hyperprocalcitoninemia and correlate the results with clinical data.

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 our workgroup we found that the truncated procalcitonin-variant had deleterious effects on vascular integrity during sepsis in mice: We 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 we want to examine the ratio between native and truncated human procalcitonin during diseases accompanied with hyperprocalcitoninemia and correlate the results with clinical data. Futhermore, we 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: March 1, 2023
• Est. primary completion date: February 1, 2023
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adiposity
• Eclampsia
• Granulomatosis with Polyangiitis
• Microscopic Polyangiitis
• Pre-Eclampsia
• Procalcitonin
• Sepsis
• SIRS
• Systemic Vasculitis

Intervention

Diagnostic Test:
• Procalcitonin-variants ELISA-Assay
Observational study measuring procalcitonin-variants in different patient collectives by obtaining 3 blood collection tubes per patient.

Locations

Country	Name	City	State
Germany	University Hospital Münster	Münster	North Rhine-Westphalia

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Muenster

Country where clinical trial is conducted

Germany, 

References & Publications (3)

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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ratio between native and truncated procalcitonin during different conditions of hyperprocalcitoninemia	Measurement performed by using ELISA-assay.	Blood withdrawal takes approximately 5 minutes per patient
Secondary	DPP-4-activity	Measurement performed by using a commercial DPP4-ELISA-kit.	Blood withdrawal takes approximately 5 minutes per patient
Secondary	Proinflammatory cytokines	Measurement performed by using a commercial multiplex immunoassay kit.	Blood withdrawal takes approximately 5 minutes per patient
Secondary	Immun cell surface-antigens	Measurement performed by using fluorescence-acivated cell sorting (FACS).	Blood withdrawal takes approximately 5 minutes per patient