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

Preeclampsia Clinical Trial

— EDIPE  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05999851
• Other study ID #: 346/2023/Oss/AOUBo
• Status: Not yet recruiting
• Phase: N/A
• Start date: September 2023
• Est. completion date: September 2031

Study information

• Verified date: June 2023
• Source: IRCCS Azienda Ospedaliero-Universitaria di Bologna
• Contact: Federica Piani, MD
• Phone: +390512144291
• Email: federica.piani2[@]unibo.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 400
• Est. completion date: September 2031
• Est. primary completion date: May 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Hypertension
• Hypertensive Disorder of Pregnancy
• Pre-Eclampsia
• Preeclampsia
• Pregnancy Complications
• Toxemia

Intervention

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.
• 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).

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).
• Blood chemistry test
Immunochemistry analysis of serum levels of uric acid, total cholesterol, LDL-cholesterol, HDL-cholesterol, Triglycerides, Lipoprotein (a)
• Serum xanthine oxidase activity
Serum xanthine oxidase (XO) activity will be assessed in blood samples measuring the ability of XO to produce uric acid

Locations

Country	Name	City	State
Italy	Cardiovascular Internal Medicine Unit, IRCCS University Hospital of Bologna, Bologna, Italy	Bologna

Sponsors (2)

Lead Sponsor	Collaborator
IRCCS Azienda Ospedaliero-Universitaria di Bologna	University of Bologna

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Serum uric acid	mg/dl	Baseline visit (11/13+6 weeks of pregnancy)
Other	Serum uric acid	mg/dl	Follow-up visit (24/27+6 weeks of pregnancy)
Other	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)
Other	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)
Other	Xanthine Oxidase Activity	mU/mL	Baseline visit (11/13+6 weeks of pregnancy)
Other	Xanthine Oxidase Activity	mU/mL	Follow-up visit (24/27+6 weeks of pregnancy)
Primary	Perfused Boundary Region (PBR)	Micron	Baseline visit (11/13+6 weeks of pregnancy)
Primary	Perfused Boundary Region (PBR)	Micron	Follow-up visit (24/27+6 weeks of pregnancy)
Primary	Carotid-femoral pulse wave velocity (cf-PWV)	m/s	Baseline visit (11/13+6 weeks of pregnancy)
Primary	Carotid-femoral pulse wave velocity (cf-PWV)	m/s	Follow-up visit (24/27+6 weeks of pregnancy)
Primary	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
Primary	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	Serum Angiopoietin 1 (ANG-1)	ng/ml	Baseline visit (11/13+6 weeks of pregnancy)
Secondary	Serum Angiopoietin 1 (ANG-1)	ng/ml	Follow-up visit (24/27+6 weeks of pregnancy)
Secondary	Serum Angiopoietin 2 (ANG-2)	ng/ml	Baseline visit (11/13+6 weeks of pregnancy)
Secondary	Serum Angiopoietin 2 (ANG-2)	ng/ml	Follow-up visit (24/27+6 weeks of pregnancy)
Secondary	Serum Endothelin-1 (ET-1)	Serum concentration assessed by ELISA (pg/ml)	Baseline visit (11/13+6 weeks of pregnancy)
Secondary	Serum Endothelin-1 (ET-1)	pg/ml	Follow-up visit (24/27+6 weeks of pregnancy)
Secondary	Serum Intercellular adhesion molecule-1 (ICAM-1)	ng/ml	Baseline visit (11/13+6 weeks of pregnancy)
Secondary	Serum Intercellular adhesion molecule-1 (ICAM-1)	ng/ml	Follow-up visit (24/27+6 weeks of pregnancy)
Secondary	Serum Vascular Cell Adhesion Molecule-1 (VCAM-1)	ng/ml	Baseline visit (11/13+6 weeks of pregnancy)
Secondary	Serum Vascular Cell Adhesion Molecule-1 (VCAM-1)	ng/ml	Follow-up visit (24/27+6 weeks of pregnancy)
Secondary	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