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

• ClinicalTrials.gov Identifier: NCT05999851
• Recruitment Status: Not yet recruiting
• First Posted: August 21, 2023
• Last Update Posted: August 21, 2023
• Sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna
• Collaborator: University of Bologna
• Information provided by (Responsible Party): IRCCS Azienda Ospedaliero-Universitaria di Bologna

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Preeclampsia; Hypertensive Disorder of Pregnancy	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	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 400 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• 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.
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Multiparametric Assessment of Maternal Vascular Function as a New Diagnostic and Prognostic Tool for Hypertensive Disorders of Pregnancy and Preeclampsia - EDIPE Study
• Estimated Study Start Date: September 2023
• Estimated Primary Completion Date: May 2026
• Estimated Study Completion Date: September 2031

Arms and Interventions

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: ANG-1; ET-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

Outcome Measures

Primary Outcome Measures :

1. Perfused Boundary Region (PBR) [ Time Frame: Baseline visit (11/13+6 weeks of pregnancy) ]
   Micron
2. Perfused Boundary Region (PBR) [ Time Frame: Follow-up visit (24/27+6 weeks of pregnancy) ]
   Micron
3. Carotid-femoral pulse wave velocity (cf-PWV) [ Time Frame: Baseline visit (11/13+6 weeks of pregnancy) ]
   m/s
4. Carotid-femoral pulse wave velocity (cf-PWV) [ Time Frame: Follow-up visit (24/27+6 weeks of pregnancy) ]
   m/s
5. Number of participants with hypertensive disorders of pregnancy [ Time Frame: 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
6. Number of participants with preeclampsia [ Time Frame: 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 :

1. Serum Angiopoietin 1 (ANG-1) [ Time Frame: Baseline visit (11/13+6 weeks of pregnancy) ]
   ng/ml
2. Serum Angiopoietin 1 (ANG-1) [ Time Frame: Follow-up visit (24/27+6 weeks of pregnancy) ]
   ng/ml
3. Serum Angiopoietin 2 (ANG-2) [ Time Frame: Baseline visit (11/13+6 weeks of pregnancy) ]
   ng/ml
4. Serum Angiopoietin 2 (ANG-2) [ Time Frame: Follow-up visit (24/27+6 weeks of pregnancy) ]
   ng/ml
5. Serum Endothelin-1 (ET-1) [ Time Frame: Baseline visit (11/13+6 weeks of pregnancy) ]
   Serum concentration assessed by ELISA (pg/ml)
6. Serum Endothelin-1 (ET-1) [ Time Frame: Follow-up visit (24/27+6 weeks of pregnancy) ]
   pg/ml
7. Serum Intercellular adhesion molecule-1 (ICAM-1) [ Time Frame: Baseline visit (11/13+6 weeks of pregnancy) ]
   ng/ml
8. Serum Intercellular adhesion molecule-1 (ICAM-1) [ Time Frame: Follow-up visit (24/27+6 weeks of pregnancy) ]
   ng/ml
9. Serum Vascular Cell Adhesion Molecule-1 (VCAM-1) [ Time Frame: Baseline visit (11/13+6 weeks of pregnancy) ]
   ng/ml
10. Serum Vascular Cell Adhesion Molecule-1 (VCAM-1) [ Time Frame: Follow-up visit (24/27+6 weeks of pregnancy) ]
    ng/ml
11. Number of participants with long-term cardiovascular outcomes [ Time Frame: 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

Other Outcome Measures:

1. Serum uric acid [ Time Frame: Baseline visit (11/13+6 weeks of pregnancy) ]
   mg/dl
2. Serum uric acid [ Time Frame: Follow-up visit (24/27+6 weeks of pregnancy) ]
   mg/dl
3. Serum lipid profile [ Time Frame: Baseline visit (11/13+6 weeks of pregnancy) ]
   HDL-cholesterol (mg/dl), LDL-cholesterol (mg/dl), Triglycerides (mg/dl), Lipoprotein (a) (mg/dl)
4. Serum lipid profile [ Time Frame: Follow-up visit (24/27+6 weeks of pregnancy) ]
   HDL-cholesterol (mg/dl), LDL-cholesterol (mg/dl), Triglycerides (mg/dl), Lipoprotein (a) (mg/dl)
5. Xanthine Oxidase Activity [ Time Frame: Baseline visit (11/13+6 weeks of pregnancy) ]
   mU/mL
6. Xanthine Oxidase Activity [ Time Frame: Follow-up visit (24/27+6 weeks of pregnancy) ]
   mU/mL

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Contacts

Contact: Federica Piani, MD; +390512144291; federica.piani2@unibo.it

Locations

Italy

Cardiovascular Internal Medicine Unit, IRCCS University Hospital of Bologna, Bologna, Italy

Bologna, Italy, 40124

Contact: Federica Piani, MD +390512144291 federica.piani2@unibo.it

Sponsors and Collaborators

IRCCS Azienda Ospedaliero-Universitaria di Bologna

University of Bologna

Investigators

• Study Chair: Federica Piani, MD; IRCCS University Hospital of Bologna, Italy. University of Bologna, Italy.
• Principal Investigator: Claudio Borghi, MD; IRCCS University Hospital of Bologna, Italy. University of Bologna, Italy.

More Information

• Responsible Party: IRCCS Azienda Ospedaliero-Universitaria di Bologna
• ClinicalTrials.gov Identifier: NCT05999851
• Other Study ID Numbers: 346/2023/Oss/AOUBo
• First Posted: August 21, 2023
• Last Update Posted: August 21, 2023
• Last Verified: June 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: All de-identified IPD that underlie results in a publication for all primary and secondary outcome measures will be shared.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP)
• Time Frame: Data will be available after the associated manuscript will be published.
• 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).

• 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

Keywords provided by IRCCS Azienda Ospedaliero-Universitaria di Bologna:

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

Additional relevant MeSH terms:

Toxemia; Pre-Eclampsia; Pregnancy Complications; Hypertension; Hypertension, Pregnancy-Induced; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Vascular Diseases; Cardiovascular Diseases; Infections