Preeclampsia and Contact Activation

Completed

• Conditions: Misfolding Disease, Protein; CAS; Preeclampsia
• Interventions: Other: Pregnancy

• Registration Number: NCT04825145
• Lead Sponsor: University of Southern Denmark

Brief Summary

Preeclampsia (PE) affects approximately 5% of all pregnancies with 2,500 cases registered annually in Denmark. PE is characterized by incomplete modelling of the spiral arteries of the uterus, hypertension, inflammation, hypercoagulability and proteinuria. Neonatal complications and increased cardiovascular risk are common features of the syndrome.

PE shares pathophysiologic features with recognized protein misfolding disorders and misfolded proteins are present in urine from women with PE. Misfolded proteins are potent activators of the contact system (CAS) which is involved in inflammation, coagulation and fibrinolysis.

Plasminogen activator inhibitor 2 (PAI-2) regulates important fibrinolytic processes in the placenta. The oxidative milieu characterizing PE may trigger misfolding of PAI-2 which then loose inhibitory capacity, but gain CAS-activating capacity. Thus, misfolding of PAI-2 may affect the fibrinolytic system in the placenta and compromise the modelling of the spiral arteries. Moreover, misfolded PAI-2 may contribute to the hypercoagulability and the inflammatory conditions characterizing women with PE.

The aim of the present study is i) to characterize CAS in women with PE, ii) to study the CAS-activating capacity of misfolded PAI-2 and iii) to develop and apply immunochemical methods for determination of native and misfolded PAI-2 in plasma.

Detailed Description

Not available

Study Timeline

• Study Start: 2020-01-20
• Study First Submitted: 2021-03-25
• Study First Submitted QC: 2021-03-30
• Study First Posted: 2021-04-01
• Primary Completion: 2021-11-30
• Study Completion: 2021-11-30
• Status Verified: 2022-11
• Last Update Submitted: 2022-11-01
• Last Update Posted: 2022-11-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 234

Inclusion Criteria

• Pregnant women developing preeclampsia

Exclusion Criteria

• Healthy pregnant women

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Preeclamptic women	Pregnancy	Pregnant women who is diagnosed with preeclampsia during anytime of pregnancy.

Primary Outcome Measures

Name	Time	Method
The Contact Activation System (CAS)	3 years	Biomarkers for the CAS in plasma Coagulation factor XII antigen/activity, High molecular weight kininogen (HK), Truncated (HK), Prekallikrein antigen, kallikrein generation, C1-esterase inhibitor, alpha-2-macroglobulin, Fast form alpha-2-macroglobulin, Thrombin generation,
Misfolded Plasminogen activator inhibitor 2 (PAI-2)	3 years	Biomarkers for misfolded PAI-2 in plasma Native PAI-2 antigen, Misfolded PAI-2, Native PAI-1 antigen,

Trial Locations

Locations (1)

The Unit for Thrombosis Research, University of Southern Denmark; 🇩🇰 Esbjerg, Denmark