NCT05999851

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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
400

participants targeted

Target at P75+ for not_applicable

Timeline
64mo left

Started Sep 2023

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress34%
Sep 2023Sep 2031

First Submitted

Initial submission to the registry

June 15, 2023

Completed
2 months until next milestone

First Posted

Study publicly available on registry

August 21, 2023

Completed
11 days until next milestone

Study Start

First participant enrolled

September 1, 2023

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2026

Completed
5.3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2031

Expected
Last Updated

January 22, 2026

Status Verified

November 1, 2025

Enrollment Period

2.7 years

First QC Date

June 15, 2023

Last Update Submit

January 21, 2026

Conditions

PreeclampsiaHypertensive Disorder of Pregnancy

Keywords

PreeclampsiaHypertensive Disorders of PregnancyHypertensionObstetric MedicineCardio-ObstetricsCardiovascular outcomesPregnancy complicationsArterial StiffnessEndothelial GlycocalyxEndothelial dysfunctionUric AcidOxidative stressXanthine oxidaseLipids

Outcome Measures

Primary Outcomes (6)

  • 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 Outcomes (11)

  • Serum Angiopoietin 1 (ANG-1)

    Baseline visit (11/13+6 weeks of pregnancy)

  • Serum Angiopoietin 1 (ANG-1)

    Follow-up visit (24/27+6 weeks of pregnancy)

  • Serum Angiopoietin 2 (ANG-2)

    Baseline visit (11/13+6 weeks of pregnancy)

  • Serum Angiopoietin 2 (ANG-2)

    Follow-up visit (24/27+6 weeks of pregnancy)

  • Serum Endothelin-1 (ET-1)

    Baseline visit (11/13+6 weeks of pregnancy)

  • +6 more secondary outcomes

Other Outcomes (6)

  • Serum uric acid

    Baseline visit (11/13+6 weeks of pregnancy)

  • Serum uric acid

    Follow-up visit (24/27+6 weeks of pregnancy)

  • Serum lipid profile

    Baseline visit (11/13+6 weeks of pregnancy)

  • +3 more other outcomes

Study Arms (1)

Principal arm

EXPERIMENTAL

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 tonometryDevice: In vivo endothelial glycocalyx measurementDiagnostic Test: Serum markers of angiogenesis and endothelial dysfunctionDiagnostic Test: Blood chemistry testDiagnostic Test: Serum xanthine oxidase activity

Interventions

Arterial applanation tonometryDEVICE

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.

Also known as: PulsePen, Arterial stiffness measurement, Pulse wave velocity assessment
Principal arm
In vivo endothelial glycocalyx measurementDEVICE

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).

Also known as: Glycocheck, Sidestream dark field microscopy
Principal arm
Serum markers of angiogenesis and endothelial dysfunctionDIAGNOSTIC_TEST

ELISA assays to measure serum circulating markers of angiogenesis and endothelial dysfunction (ANG-1, ANG-2, ET-1, ICAM-1 and VCAM-1).

Also known as: ANG-1, ET-1, ICAM-1, VCAM-1, ANG-2
Principal arm
Blood chemistry testDIAGNOSTIC_TEST

Immunochemistry analysis of serum levels of uric acid, total cholesterol, LDL-cholesterol, HDL-cholesterol, Triglycerides, Lipoprotein (a)

Principal arm
Serum xanthine oxidase activityDIAGNOSTIC_TEST

Serum xanthine oxidase (XO) activity will be assessed in blood samples measuring the ability of XO to produce uric acid

Principal arm

Eligibility Criteria

Age18 Years - 65 Years
Sexfemale
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

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

Bologna, 40124, Italy

RECRUITING

MeSH Terms

Conditions

Pre-EclampsiaToxemiaHypertensionPregnancy Complications

Condition Hierarchy (Ancestors)

Hypertension, Pregnancy-InducedFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesInfectionsVascular DiseasesCardiovascular Diseases

Study Officials

  • Arrigo Francesco Giuseppe Cicero, MD, PhD

    IRCCS University Hospital of Bologna, Italy. University of Bologna, Italy.

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Arrigo Francesco Giuseppe Cicero, MD, PhD

CONTACT

+39 051 214290arrigo.cicero@unibo.it

Cristina Scollo, BD

CONTACT

cristina.scollo@aosp.bo.it

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NA
Masking
NONE
Purpose
PREVENTION
Intervention Model
SINGLE GROUP
Model Details: 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.
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 15, 2023

First Posted

August 21, 2023

Study Start

September 1, 2023

Primary Completion

May 1, 2026

Study Completion (Estimated)

September 1, 2031

Last Updated

January 22, 2026

Record last verified: 2025-11

Data Sharing

IPD Sharing
Will share

All de-identified IPD that underlie results in a publication for all primary and secondary outcome measures will be shared.

Shared Documents
STUDY PROTOCOL, SAP
Time Frame
Data will be available after the associated manuscript will be published. No ad-interim analysis is planned before enrollment conclusion.
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).

Locations

IT(1)