Clinical trial NCT05999851: Multiparametric Assessment of Maternal Vascular Function in the Prediction of Hypertensive Disorders of Pregnancy
Official title: Multiparametric Assessment of Maternal Vascular Function as a New Diagnostic and Prognostic Tool for Hypertensive Disorders of Pregnancy and Preeclampsia - EDIPE Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Preeclampsia
Hypertensive Disorder of Pregnancy
Keywords: Preeclampsia
Hypertensive Disorders of Pregnancy
Hypertension
Obstetric Medicine
Cardio-Obstetrics
Cardiovascular outcomes
Pregnancy complications
Arterial Stiffness
Endothelial Glycocalyx
Endothelial dysfunction
Uric Acid
Oxidative stress
Xanthine oxidase
Lipids
Lead sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna
Sponsor class: OTHER
Collaborators: name: University of Bologna
First posted: 2023-08-21
Enrollment: 400
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: The study is a single group study (Principal Arm) with a sub-group of participants undergoing additional experimental analyses. The additional analyses will be performed in participants who will develop hypertensive disorders of pregnancy and matched (age and body mass index before conception) controls with healthy pregnancies.
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Perfused Boundary Region (PBR)
timeFrame: Baseline visit (11/13+6 weeks of pregnancy)
measure: Perfused Boundary Region (PBR)
timeFrame: Follow-up visit (24/27+6 weeks of pregnancy)
measure: Carotid-femoral pulse wave velocity (cf-PWV)
timeFrame: Baseline visit (11/13+6 weeks of pregnancy)
measure: Carotid-femoral pulse wave velocity (cf-PWV)
timeFrame: Follow-up visit (24/27+6 weeks of pregnancy)
measure: Number of participants with hypertensive disorders of pregnancy
timeFrame: 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
measure: Number of participants with preeclampsia
timeFrame: 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
Secondary outcomes:
measure: Serum Angiopoietin 1 (ANG-1)
timeFrame: Baseline visit (11/13+6 weeks of pregnancy)
measure: Serum Angiopoietin 1 (ANG-1)
timeFrame: Follow-up visit (24/27+6 weeks of pregnancy)
measure: Serum Angiopoietin 2 (ANG-2)
timeFrame: Baseline visit (11/13+6 weeks of pregnancy)
measure: Serum Angiopoietin 2 (ANG-2)
timeFrame: Follow-up visit (24/27+6 weeks of pregnancy)
measure: Serum Endothelin-1 (ET-1)
timeFrame: Baseline visit (11/13+6 weeks of pregnancy)
measure: Serum Endothelin-1 (ET-1)
timeFrame: Follow-up visit (24/27+6 weeks of pregnancy)
measure: Serum Intercellular adhesion molecule-1 (ICAM-1)
timeFrame: Baseline visit (11/13+6 weeks of pregnancy)
measure: Serum Intercellular adhesion molecule-1 (ICAM-1)
timeFrame: Follow-up visit (24/27+6 weeks of pregnancy)
measure: Serum Vascular Cell Adhesion Molecule-1 (VCAM-1)
timeFrame: Baseline visit (11/13+6 weeks of pregnancy)
measure: Serum Vascular Cell Adhesion Molecule-1 (VCAM-1)
timeFrame: Follow-up visit (24/27+6 weeks of pregnancy)
measure: Number of participants with long-term cardiovascular outcomes
timeFrame: Interview 5 years after delivery
Other outcomes:
measure: Serum uric acid
timeFrame: Baseline visit (11/13+6 weeks of pregnancy)
measure: Serum uric acid
timeFrame: Follow-up visit (24/27+6 weeks of pregnancy)
measure: Serum lipid profile
timeFrame: Baseline visit (11/13+6 weeks of pregnancy)
measure: Serum lipid profile
timeFrame: Follow-up visit (24/27+6 weeks of pregnancy)
measure: Xanthine Oxidase Activity
timeFrame: Baseline visit (11/13+6 weeks of pregnancy)
measure: Xanthine Oxidase Activity
timeFrame: Follow-up visit (24/27+6 weeks of pregnancy)
Locations:
city: Bologna
country: Italy
facility: Cardiovascular Internal Medicine Unit, IRCCS University Hospital of Bologna, Bologna, Italy
Study officials:
affiliation: IRCCS University Hospital of Bologna, Italy. University of Bologna, Italy.
name: Federica Piani, MD
role: STUDY_CHAIR
affiliation: IRCCS University Hospital of Bologna, Italy. University of Bologna, Italy.
name: Claudio Borghi, MD
role: PRINCIPAL_INVESTIGATOR
References: