Multiparametric Assessment of Maternal Vascular Function in the Prediction of Hypertensive Disorders of Pregnancy

Not Applicable

Not yet recruiting

• Conditions: Preeclampsia; Hypertensive Disorder of Pregnancy
• Interventions: Device: Arterial applanation tonometry; Device: In vivo endothelial glycocalyx measurement; Diagnostic Test: Serum markers of angiogenesis and endothelial dysfunction; Diagnostic Test: Blood chemistry test; Diagnostic Test: Serum xanthine oxidase activity

• Registration Number: NCT05999851
• Lead Sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna

Brief Summary

The present study is a single-centre prospective study that will enrol pregnant women during their first trimester of pregnancy (11+0 - 13+6 weeks of gestation).

During pregnancy, women will undergo standard clinical evaluation and management. During the two study visits (enrollment and 24+0 - 27+6 weeks of gestation) the investigators will perform arterial tonometry (Pulsepen) and in vivo darkfield microscopy (Glycocheck) to evaluate endothelial and vascular function. A urine sample and a blood sample for specific study analyses on metabolic profile, endothelial and angiogenic markers will be collected. Pregnancy outcomes will be collected at delivery and five years after delivery all the participants will be interview to collect long-term cardiovascular outcomes. Serum endothelial and angiogenic markers will be evaluated only in participants who will develop hypertensive disorders of pregnancy and in an equal number of controls matched for age and body mass index at the time of conception.

Detailed Description

Primary aim:

To determine the role of the combination of arterial tonometry and endothelial glycocalyx measurement in predicting the risk of developing hypertensive disorders in pregnancy.

Secondary aims:

* To determine the association between circulating markers of angiogenesis and endothelial dysfunction (ANG-1, ANG-2, ET-1, ICAM-1 and VCAM-1) and the development of hypertensive disorders of pregnancy.

* To define the trends of serum uric acid, lipids and xanthine oxidase activity in normotensive and hypertensive pregnancies.

* To determine the ability of the combination of arterial tonometry and endothelial glycocalyx measurement, performed in the two study visits during pregnancy, in predicting the risk of long-term maternal cardiovascular disease.

Study Timeline

• Status Verified: 2023-06
• Study First Submitted: 2023-06-15
• Study First Submitted QC: 2023-08-17
• Last Update Submitted: 2023-08-17
• Study First Posted: 2023-08-21
• Last Update Posted: 2023-08-21
• Study Start: 2023-09
• Primary Completion: 2026-05
• Study Completion: 2031-09

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Female
• Target Recruitment: 400

Inclusion Criteria

• Age greater than or equal to 18 years
• Single pregnancy
• No previous pregnancies lasting more than 12 weeks
• Participant willing and able to give informed consent for participation in the study

Exclusion Criteria

• Intermediate-high risk of genetic abnormalities and/or need to perform invasive tests (amniocentesis, villocentesis)
• History of solid organ or hematopoietic stem cell transplantation
• Chronic renal failure (eGFR≤45ml/min/1.73m2)
• Chronic treatment with antihypertensive drugs and/or xanthine oxidase (XO) inhibitors

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Principal arm	In vivo endothelial glycocalyx measurement	The entire cohort of participants will undergo all experimental procedures. Participants who will develop hypertensive disorders of pregnancy and matched participants with healthy pregnancies will also undergo serum endothelial and angiogenic markers assessment.
Principal arm	Serum markers of angiogenesis and endothelial dysfunction	The entire cohort of participants will undergo all experimental procedures. Participants who will develop hypertensive disorders of pregnancy and matched participants with healthy pregnancies will also undergo serum endothelial and angiogenic markers assessment.
Principal arm	Arterial applanation tonometry	The entire cohort of participants will undergo all experimental procedures. Participants who will develop hypertensive disorders of pregnancy and matched participants with healthy pregnancies will also undergo serum endothelial and angiogenic markers assessment.
Principal arm	Serum xanthine oxidase activity	The entire cohort of participants will undergo all experimental procedures. Participants who will develop hypertensive disorders of pregnancy and matched participants with healthy pregnancies will also undergo serum endothelial and angiogenic markers assessment.
Principal arm	Blood chemistry test	The entire cohort of participants will undergo all experimental procedures. Participants who will develop hypertensive disorders of pregnancy and matched participants with healthy pregnancies will also undergo serum endothelial and angiogenic markers assessment.

Primary Outcome Measures

Name	Time	Method
Perfused Boundary Region (PBR)	Follow-up visit (24/27+6 weeks of pregnancy)	Micron
Number of participants with hypertensive disorders of pregnancy	From date of enrolment until the date of first documented diagnosis of hypertensive disorder of pregnancy, according to the International Society for the Study of Hypertension in Pregnancy Criteria, assessed up to one week after delivery	Number of participants diagnosed during pregnancy with any hypertensive disorder of pregnancy
Carotid-femoral pulse wave velocity (cf-PWV)	Follow-up visit (24/27+6 weeks of pregnancy)	m/s
Number of participants with preeclampsia	From date of enrolment until the date of first documented diagnosis of preeclampsia, according to the International Society for the Study of Hypertension in Pregnancy Criteria, assessed up to one week after delivery	Number of participants diagnosed during pregnancy with preeclampsia according to the International Society for the Study of Hypertension in Pregnancy (ISSHP) criteria.

Secondary Outcome Measures

Name	Time	Method
Serum Angiopoietin 1 (ANG-1)	Follow-up visit (24/27+6 weeks of pregnancy)	ng/ml
Serum Vascular Cell Adhesion Molecule-1 (VCAM-1)	Follow-up visit (24/27+6 weeks of pregnancy)	ng/ml
Number of participants with long-term cardiovascular outcomes	Interview 5 years after delivery	Number of participants diagnosed with stroke, myocardial infarction, heart failure or hospitalized for cardiovascular disease in the 5 years after delivery
Serum Angiopoietin 2 (ANG-2)	Follow-up visit (24/27+6 weeks of pregnancy)	ng/ml
Serum Endothelin-1 (ET-1)	Follow-up visit (24/27+6 weeks of pregnancy)	pg/ml
Serum Intercellular adhesion molecule-1 (ICAM-1)	Follow-up visit (24/27+6 weeks of pregnancy)	ng/ml

Trial Locations

Locations (1)

Cardiovascular Internal Medicine Unit, IRCCS University Hospital of Bologna, Bologna, Italy; 🇮🇹 Bologna, Italy