Preeclampsia and Contact Activation

NCT04825145 | Completed DMC

• 1 other identifier: s-20190142
• Study Type: observational
• Target: 234
• Locations: 1 country
• Sites: 1

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.

Conditions

Preeclampsia; CAS; Misfolding Disease, Protein

Keywords

Contact activation system, PAI-2

Outcome Measures

Primary Outcomes (2)

• The Contact Activation System (CAS)

  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,

  3 years

• Misfolded Plasminogen activator inhibitor 2 (PAI-2)

  Biomarkers for misfolded PAI-2 in plasma Native PAI-2 antigen, Misfolded PAI-2, Native PAI-1 antigen,

  3 years

Study Arms (2)

Preeclamptic women

Pregnant women who is diagnosed with preeclampsia during anytime of pregnancy.

Other: Pregnancy

Healthy pregnant women

Pregnant women without preeclampsia. Will be matched for body mass index, gestational age and age.

Interventions

Pregnancy OTHER

Pregnancies complicated by preeclampsia

Preeclamptic women

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Preeclamptic women anytime of pregnancy compared to healthy pregnant women (control) at the same gestational age, with matching BMI and age.

You may qualify if:

• Pregnant women developing preeclampsia

You may not qualify if:

• Healthy pregnant women

Sponsors & Collaborators

• University of Southern Denmark: lead
• Region of Southern Denmark: collaborator
• OPEN: collaborator
• Lida og Oskar Nielsens Fond: collaborator
• Esbjerg Fonden: collaborator
• Gangsted Fonden: collaborator

Study Sites (1)

The Unit for Thrombosis Research, University of Southern Denmark

Esbjerg, 6700, Denmark

Location

Related Publications (1)

• Godtfredsen AC, Palarasah Y, Dolleris BB, Jorgensen JS, Sidelmann JJ, Gram JB. Increased contact activated endogenous thrombin potential in pregnant women with preeclampsia. Blood Coagul Fibrinolysis. 2024 Jan 1;35(1):1-7. doi: 10.1097/MBC.0000000000001269. Epub 2023 Nov 30.

  PMID: 38051647 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Plasma

MeSH Terms

Conditions

Pre-Eclampsia; Proteostasis Deficiencies

Interventions

Pregnancy

Condition Hierarchy (Ancestors)

Hypertension, Pregnancy-Induced; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Reproduction; Reproductive Physiological Phenomena; Reproductive and Urinary Physiological Phenomena

Study Officials

• Jørgen B Gram, Professor

  University of Southern Denmark

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator, medical doctor, phd student

Study Record Dates

• First Submitted: March 25, 2021
• First Posted: April 1, 2021
• Study Start: January 20, 2020
• Primary Completion: November 30, 2021
• Study Completion: November 30, 2021
• Last Updated: November 2, 2022

Record last verified: 2022-11

Locations

DK (1)