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

Multiparametric Assessment of Maternal Vascular Function as a New Diagnostic and Prognostic Tool for Hypertensive Disorders of Pregnancy and Preeclampsia - EDIPE Study

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.

Study Overview

• Status: Recruiting
• Conditions: Preeclampsia; Hypertensive Disorder of Pregnancy
• Intervention / Treatment: 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

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 Type: Interventional
• Enrollment (Estimated): 400
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Arrigo Francesco Giuseppe Cicero, MD, PhD; Phone Number: +39 051 214290; Email: arrigo.cicero@unibo.it
• Study Contact Backup: Name: Cristina Scollo, BD; Email: cristina.scollo@aosp.bo.it

Study Locations

• Italy
  • Bologna, Italy, 40124
    • Recruiting
    • Cardiovascular Internal Medicine Unit, IRCCS University Hospital of Bologna, Bologna, Italy
    • Contact: Arrigo Francesco Giuseppe Cicero, MD, PhD; Phone Number: +39051214290; Email: arrigo.cicero@unibo.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Principal arm; 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.

Device: Arterial applanation tonometry; Arterial applanation tonometry will be performed at the carotid and femoral level by the PulsePen device (Software WPulsePen version 2.3.1, DiaTecne, Milan, Italy), while the subject is lying in the horizontal position and after 5 minutes of rest.; Other Names: PulsePen; Arterial stiffness measurement; Pulse wave velocity assessment; Device: In vivo endothelial glycocalyx measurement; The in vivo microscopy (GlycoCheck system) is performed in the sublingual capillaries during the morning, with the participant sitting on a chair. The sublingual capillaries are visualized using an SDF video microscope (Capiscope handheld, KK Research technology Ltd).; Other Names: Glycocheck; Sidestream dark field microscopy; Diagnostic test: Serum markers of angiogenesis and endothelial dysfunction; ELISA assays to measure serum circulating markers of angiogenesis and endothelial dysfunction (ANG-1, ANG-2, ET-1, ICAM-1 and VCAM-1).; Other Names: ET-1; ANG-1; ICAM-1; VCAM-1; ANG-2; Diagnostic test: Blood chemistry test; Immunochemistry analysis of serum levels of uric acid, total cholesterol, LDL-cholesterol, HDL-cholesterol, Triglycerides, Lipoprotein (a); Diagnostic test: Serum xanthine oxidase activity; Serum xanthine oxidase (XO) activity will be assessed in blood samples measuring the ability of XO to produce uric acid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Perfused Boundary Region (PBR)	Micron	Baseline visit (11/13+6 weeks of pregnancy)
Perfused Boundary Region (PBR)	Micron	Follow-up visit (24/27+6 weeks of pregnancy)
Carotid-femoral pulse wave velocity (cf-PWV)	m/s	Baseline visit (11/13+6 weeks of pregnancy)
Carotid-femoral pulse wave velocity (cf-PWV)	m/s	Follow-up visit (24/27+6 weeks of pregnancy)
Number of participants with hypertensive disorders of pregnancy	Number of participants diagnosed during pregnancy with any hypertensive disorder 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 with preeclampsia	Number of participants diagnosed during pregnancy with preeclampsia according to the International Society for the Study of Hypertension in Pregnancy (ISSHP) criteria.	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Angiopoietin 1 (ANG-1)	ng/ml	Baseline visit (11/13+6 weeks of pregnancy)
Serum Angiopoietin 1 (ANG-1)	ng/ml	Follow-up visit (24/27+6 weeks of pregnancy)
Serum Angiopoietin 2 (ANG-2)	ng/ml	Baseline visit (11/13+6 weeks of pregnancy)
Serum Angiopoietin 2 (ANG-2)	ng/ml	Follow-up visit (24/27+6 weeks of pregnancy)
Serum Endothelin-1 (ET-1)	Serum concentration assessed by ELISA (pg/ml)	Baseline visit (11/13+6 weeks of pregnancy)
Serum Endothelin-1 (ET-1)	pg/ml	Follow-up visit (24/27+6 weeks of pregnancy)
Serum Intercellular adhesion molecule-1 (ICAM-1)	ng/ml	Baseline visit (11/13+6 weeks of pregnancy)
Serum Intercellular adhesion molecule-1 (ICAM-1)	ng/ml	Follow-up visit (24/27+6 weeks of pregnancy)
Serum Vascular Cell Adhesion Molecule-1 (VCAM-1)	ng/ml	Baseline visit (11/13+6 weeks of pregnancy)
Serum Vascular Cell Adhesion Molecule-1 (VCAM-1)	ng/ml	Follow-up visit (24/27+6 weeks of pregnancy)
Number of participants with long-term cardiovascular outcomes	Number of participants diagnosed with stroke, myocardial infarction, heart failure or hospitalized for cardiovascular disease in the 5 years after delivery	Interview 5 years after delivery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum uric acid	mg/dl	Baseline visit (11/13+6 weeks of pregnancy)
Serum uric acid	mg/dl	Follow-up visit (24/27+6 weeks of pregnancy)
Serum lipid profile	HDL-cholesterol (mg/dl), LDL-cholesterol (mg/dl), Triglycerides (mg/dl), Lipoprotein (a) (mg/dl)	Baseline visit (11/13+6 weeks of pregnancy)
Serum lipid profile	HDL-cholesterol (mg/dl), LDL-cholesterol (mg/dl), Triglycerides (mg/dl), Lipoprotein (a) (mg/dl)	Follow-up visit (24/27+6 weeks of pregnancy)
Xanthine Oxidase Activity	mU/mL	Baseline visit (11/13+6 weeks of pregnancy)
Xanthine Oxidase Activity	mU/mL	Follow-up visit (24/27+6 weeks of pregnancy)

Collaborators and Investigators

• Sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna
• Collaborators: University of Bologna
• Investigators: Principal Investigator: Arrigo Francesco Giuseppe Cicero, MD, PhD, IRCCS University Hospital of Bologna, Italy. University of Bologna, Italy.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2023
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): September 1, 2031

Study Registration Dates

• First Submitted: June 15, 2023
• First Submitted That Met QC Criteria: August 17, 2023
• First Posted (Actual): August 21, 2023

Study Record Updates

• Last Update Posted (Actual): January 22, 2026
• Last Update Submitted That Met QC Criteria: January 21, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Oxidative stress; Endothelial dysfunction; Hypertension; Arterial Stiffness; Lipids; Preeclampsia; Pregnancy complications; Uric Acid; Hypertensive Disorders of Pregnancy; Cardiovascular outcomes; Xanthine oxidase; Endothelial Glycocalyx; Obstetric Medicine; Cardio-Obstetrics
• Additional Relevant MeSH Terms: Urogenital Diseases; Vascular Diseases; Cardiovascular Diseases; Female Urogenital Diseases and Pregnancy Complications; Infections; Hypertension, Pregnancy-Induced; Pre-Eclampsia; Hypertension; Pregnancy Complications; Toxemia
• Other Study ID Numbers: 346/2023/Oss/AOUBo

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All de-identified IPD that underlie results in a publication for all primary and secondary outcome measures will be shared.
• IPD Sharing Time Frame: Data will be available after the associated manuscript will be published. No ad-interim analysis is planned before enrollment conclusion.
• IPD Sharing Access Criteria: Access to IPD can be requested by qualified researchers engaging in independent scientific research, and provided after review and approval of a research proposal and execution of a Data Sharing Agreement (DSA).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes