xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT05999851</url>
    </required_header>
    <id_info>
      <org_study_id>346/2023/Oss/AOUBo</org_study_id>
      <nct_id>NCT05999851</nct_id>
    </id_info>
    <brief_title>Multiparametric Assessment of Maternal Vascular Function in the Prediction of Hypertensive Disorders of Pregnancy</brief_title>
    <acronym>EDIPE</acronym>
    <official_title>Multiparametric Assessment of Maternal Vascular Function as a New Diagnostic and Prognostic Tool for Hypertensive Disorders of Pregnancy and Preeclampsia - EDIPE Study</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>IRCCS Azienda Ospedaliero-Universitaria di Bologna</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>University of Bologna</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>IRCCS Azienda Ospedaliero-Universitaria di Bologna</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>Yes</is_fda_regulated_device>
      <is_us_export>Yes</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        The present study is a single-centre prospective study that will enrol pregnant women during&#xD;
        their first trimester of pregnancy (11+0 - 13+6 weeks of gestation).&#xD;
  &#xD;
        During pregnancy, women will undergo standard clinical evaluation and management. During the&#xD;
        two study visits (enrollment and 24+0 - 27+6 weeks of gestation) the investigators will&#xD;
        perform arterial tonometry (Pulsepen) and in vivo darkfield microscopy (Glycocheck) to&#xD;
        evaluate endothelial and vascular function. A urine sample and a blood sample for specific&#xD;
        study analyses on metabolic profile, endothelial and angiogenic markers will be collected.&#xD;
        Pregnancy outcomes will be collected at delivery and five years after delivery all the&#xD;
        participants will be interview to collect long-term cardiovascular outcomes. Serum&#xD;
        endothelial and angiogenic markers will be evaluated only in participants who will develop&#xD;
        hypertensive disorders of pregnancy and in an equal number of controls matched for age and&#xD;
        body mass index at the time of conception.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Primary aim:&#xD;
  &#xD;
        To determine the role of the combination of arterial tonometry and endothelial glycocalyx&#xD;
        measurement in predicting the risk of developing hypertensive disorders in pregnancy.&#xD;
  &#xD;
        Secondary aims:&#xD;
  &#xD;
          -  To determine the association between circulating markers of angiogenesis and endothelial&#xD;
             dysfunction (ANG-1, ANG-2, ET-1, ICAM-1 and VCAM-1) and the development of hypertensive&#xD;
             disorders of pregnancy.&#xD;
  &#xD;
          -  To define the trends of serum uric acid, lipids and xanthine oxidase activity in&#xD;
             normotensive and hypertensive pregnancies.&#xD;
  &#xD;
          -  To determine the ability of the combination of arterial tonometry and endothelial&#xD;
             glycocalyx measurement, performed in the two study visits during pregnancy, in&#xD;
             predicting the risk of long-term maternal cardiovascular disease.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">September 2031</completion_date>
    <primary_completion_date type="Anticipated">May 2026</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>N/A</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <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.</intervention_model_description>
      <primary_purpose>Prevention</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Perfused Boundary Region (PBR)</measure>
      <time_frame>Baseline visit (11/13+6 weeks of pregnancy)</time_frame>
      <description>Micron</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Perfused Boundary Region (PBR)</measure>
      <time_frame>Follow-up visit (24/27+6 weeks of pregnancy)</time_frame>
      <description>Micron</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Carotid-femoral pulse wave velocity (cf-PWV)</measure>
      <time_frame>Baseline visit (11/13+6 weeks of pregnancy)</time_frame>
      <description>m/s</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Carotid-femoral pulse wave velocity (cf-PWV)</measure>
      <time_frame>Follow-up visit (24/27+6 weeks of pregnancy)</time_frame>
      <description>m/s</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Number of participants with hypertensive disorders of pregnancy</measure>
      <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</time_frame>
      <description>Number of participants diagnosed during pregnancy with any hypertensive disorder of pregnancy</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Number of participants with preeclampsia</measure>
      <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</time_frame>
      <description>Number of participants diagnosed during pregnancy with preeclampsia according to the International Society for the Study of Hypertension in Pregnancy (ISSHP) criteria.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Serum Angiopoietin 1 (ANG-1)</measure>
      <time_frame>Baseline visit (11/13+6 weeks of pregnancy)</time_frame>
      <description>ng/ml</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Serum Angiopoietin 1 (ANG-1)</measure>
      <time_frame>Follow-up visit (24/27+6 weeks of pregnancy)</time_frame>
      <description>ng/ml</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Serum Angiopoietin 2 (ANG-2)</measure>
      <time_frame>Baseline visit (11/13+6 weeks of pregnancy)</time_frame>
      <description>ng/ml</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Serum Angiopoietin 2 (ANG-2)</measure>
      <time_frame>Follow-up visit (24/27+6 weeks of pregnancy)</time_frame>
      <description>ng/ml</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Serum Endothelin-1 (ET-1)</measure>
      <time_frame>Baseline visit (11/13+6 weeks of pregnancy)</time_frame>
      <description>Serum concentration assessed by ELISA (pg/ml)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Serum Endothelin-1 (ET-1)</measure>
      <time_frame>Follow-up visit (24/27+6 weeks of pregnancy)</time_frame>
      <description>pg/ml</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Serum Intercellular adhesion molecule-1 (ICAM-1)</measure>
      <time_frame>Baseline visit (11/13+6 weeks of pregnancy)</time_frame>
      <description>ng/ml</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Serum Intercellular adhesion molecule-1 (ICAM-1)</measure>
      <time_frame>Follow-up visit (24/27+6 weeks of pregnancy)</time_frame>
      <description>ng/ml</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Serum Vascular Cell Adhesion Molecule-1 (VCAM-1)</measure>
      <time_frame>Baseline visit (11/13+6 weeks of pregnancy)</time_frame>
      <description>ng/ml</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Serum Vascular Cell Adhesion Molecule-1 (VCAM-1)</measure>
      <time_frame>Follow-up visit (24/27+6 weeks of pregnancy)</time_frame>
      <description>ng/ml</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of participants with long-term cardiovascular outcomes</measure>
      <time_frame>Interview 5 years after delivery</time_frame>
      <description>Number of participants diagnosed with stroke, myocardial infarction, heart failure or hospitalized for cardiovascular disease in the 5 years after delivery</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Serum uric acid</measure>
      <time_frame>Baseline visit (11/13+6 weeks of pregnancy)</time_frame>
      <description>mg/dl</description>
    </other_outcome>
    <other_outcome>
      <measure>Serum uric acid</measure>
      <time_frame>Follow-up visit (24/27+6 weeks of pregnancy)</time_frame>
      <description>mg/dl</description>
    </other_outcome>
    <other_outcome>
      <measure>Serum lipid profile</measure>
      <time_frame>Baseline visit (11/13+6 weeks of pregnancy)</time_frame>
      <description>HDL-cholesterol (mg/dl), LDL-cholesterol (mg/dl), Triglycerides (mg/dl), Lipoprotein (a) (mg/dl)</description>
    </other_outcome>
    <other_outcome>
      <measure>Serum lipid profile</measure>
      <time_frame>Follow-up visit (24/27+6 weeks of pregnancy)</time_frame>
      <description>HDL-cholesterol (mg/dl), LDL-cholesterol (mg/dl), Triglycerides (mg/dl), Lipoprotein (a) (mg/dl)</description>
    </other_outcome>
    <other_outcome>
      <measure>Xanthine Oxidase Activity</measure>
      <time_frame>Baseline visit (11/13+6 weeks of pregnancy)</time_frame>
      <description>mU/mL</description>
    </other_outcome>
    <other_outcome>
      <measure>Xanthine Oxidase Activity</measure>
      <time_frame>Follow-up visit (24/27+6 weeks of pregnancy)</time_frame>
      <description>mU/mL</description>
    </other_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">400</enrollment>
    <condition>Preeclampsia</condition>
    <condition>Hypertensive Disorder of Pregnancy</condition>
    <arm_group>
      <arm_group_label>Principal arm</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>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.</description>
    </arm_group>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>Arterial applanation tonometry</intervention_name>
      <description>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.</description>
      <arm_group_label>Principal arm</arm_group_label>
      <other_name>PulsePen</other_name>
      <other_name>Arterial stiffness measurement</other_name>
      <other_name>Pulse wave velocity assessment</other_name>
    </intervention>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>In vivo endothelial glycocalyx measurement</intervention_name>
      <description>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).</description>
      <arm_group_label>Principal arm</arm_group_label>
      <other_name>Glycocheck</other_name>
      <other_name>Sidestream dark field microscopy</other_name>
    </intervention>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>Serum markers of angiogenesis and endothelial dysfunction</intervention_name>
      <description>ELISA assays to measure serum circulating markers of angiogenesis and endothelial dysfunction (ANG-1, ANG-2, ET-1, ICAM-1 and VCAM-1).</description>
      <arm_group_label>Principal arm</arm_group_label>
      <other_name>ANG-1</other_name>
      <other_name>ET-1</other_name>
      <other_name>ICAM-1</other_name>
      <other_name>VCAM-1</other_name>
      <other_name>ANG-2</other_name>
    </intervention>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>Blood chemistry test</intervention_name>
      <description>Immunochemistry analysis of serum levels of uric acid, total cholesterol, LDL-cholesterol, HDL-cholesterol, Triglycerides, Lipoprotein (a)</description>
      <arm_group_label>Principal arm</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>Serum xanthine oxidase activity</intervention_name>
      <description>Serum xanthine oxidase (XO) activity will be assessed in blood samples measuring the ability of XO to produce uric acid</description>
      <arm_group_label>Principal arm</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Age greater than or equal to 18 years&#xD;
  &#xD;
            -  Single pregnancy&#xD;
  &#xD;
            -  No previous pregnancies lasting more than 12 weeks&#xD;
  &#xD;
            -  Participant willing and able to give informed consent for participation in the study&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Intermediate-high risk of genetic abnormalities and/or need to perform invasive tests&#xD;
               (amniocentesis, villocentesis)&#xD;
  &#xD;
            -  History of solid organ or hematopoietic stem cell transplantation&#xD;
  &#xD;
            -  Chronic renal failure (eGFR≤45ml/min/1.73m2)&#xD;
  &#xD;
            -  Chronic treatment with antihypertensive drugs and/or xanthine oxidase (XO) inhibitors&#xD;
        </textblock>
      </criteria>
      <gender>Female</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>65 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Federica Piani, MD</last_name>
      <role>Study Chair</role>
      <affiliation>IRCCS University Hospital of Bologna, Italy. University of Bologna, Italy.</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Claudio Borghi, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>IRCCS University Hospital of Bologna, Italy. University of Bologna, Italy.</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Federica Piani, MD</last_name>
      <phone>+390512144291</phone>
      <email>federica.piani2@unibo.it</email>
    </overall_contact>
    <location>
      <facility>
        <name>Cardiovascular Internal Medicine Unit, IRCCS University Hospital of Bologna, Bologna, Italy</name>
        <address>
          <city>Bologna</city>
          <zip>40124</zip>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Federica Piani, MD</last_name>
        <phone>+390512144291</phone>
        <email>federica.piani2@unibo.it</email>
      </contact>
    </location>
    <location_countries>
      <country>Italy</country>
    </location_countries>
    <verification_date>June 2023</verification_date>
    <study_first_submitted>June 15, 2023</study_first_submitted>
    <study_first_submitted_qc>August 17, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 21, 2023</study_first_posted>
    <last_update_submitted>August 17, 2023</last_update_submitted>
    <last_update_submitted_qc>August 17, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 21, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Preeclampsia</keyword>
    <keyword>Hypertensive Disorders of Pregnancy</keyword>
    <keyword>Hypertension</keyword>
    <keyword>Obstetric Medicine</keyword>
    <keyword>Cardio-Obstetrics</keyword>
    <keyword>Cardiovascular outcomes</keyword>
    <keyword>Pregnancy complications</keyword>
    <keyword>Arterial Stiffness</keyword>
    <keyword>Endothelial Glycocalyx</keyword>
    <keyword>Endothelial dysfunction</keyword>
    <keyword>Uric Acid</keyword>
    <keyword>Oxidative stress</keyword>
    <keyword>Xanthine oxidase</keyword>
    <keyword>Lipids</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Toxemia</mesh_term>
      <mesh_term>Pre-Eclampsia</mesh_term>
      <mesh_term>Pregnancy Complications</mesh_term>
      <mesh_term>Hypertension</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>All de-identified IPD that underlie results in a publication for all primary and secondary outcome measures will be shared.</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
      <ipd_time_frame>Data will be available after the associated manuscript will be published.</ipd_time_frame>
      <ipd_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_access_criteria>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT05999851
  org study id: 346/2023/Oss/AOUBo
  nct id: NCT05999851
  lead sponsor: 
  collaborator: 
  is fda regulated drug: No
  is fda regulated device: Yes
  is us export: Yes
  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.
  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.
  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.
  primary purpose: Prevention
  masking: None (Open Label)
  measure: Perfused Boundary Region (PBR)
  time frame: Baseline visit (11/13+6 weeks of pregnancy)
  description: Micron
  measure: Perfused Boundary Region (PBR)
  time frame: Follow-up visit (24/27+6 weeks of pregnancy)
  description: Micron
  measure: Carotid-femoral pulse wave velocity (cf-PWV)
  time frame: Baseline visit (11/13+6 weeks of pregnancy)
  description: m/s
  measure: Carotid-femoral pulse wave velocity (cf-PWV)
  time frame: Follow-up visit (24/27+6 weeks of pregnancy)
  description: m/s
  measure: 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
  description: Number of participants diagnosed during pregnancy with any hypertensive disorder of pregnancy
  measure: 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
  description: Number of participants diagnosed during pregnancy with preeclampsia according to the International Society for the Study of Hypertension in Pregnancy (ISSHP) criteria.
  measure: Serum Angiopoietin 1 (ANG-1)
  time frame: Baseline visit (11/13+6 weeks of pregnancy)
  description: ng/ml
  measure: Serum Angiopoietin 1 (ANG-1)
  time frame: Follow-up visit (24/27+6 weeks of pregnancy)
  description: ng/ml
  measure: Serum Angiopoietin 2 (ANG-2)
  time frame: Baseline visit (11/13+6 weeks of pregnancy)
  description: ng/ml
  measure: Serum Angiopoietin 2 (ANG-2)
  time frame: Follow-up visit (24/27+6 weeks of pregnancy)
  description: ng/ml
  measure: Serum Endothelin-1 (ET-1)
  time frame: Baseline visit (11/13+6 weeks of pregnancy)
  description: Serum concentration assessed by ELISA (pg/ml)
  measure: Serum Endothelin-1 (ET-1)
  time frame: Follow-up visit (24/27+6 weeks of pregnancy)
  description: pg/ml
  measure: Serum Intercellular adhesion molecule-1 (ICAM-1)
  time frame: Baseline visit (11/13+6 weeks of pregnancy)
  description: ng/ml
  measure: Serum Intercellular adhesion molecule-1 (ICAM-1)
  time frame: Follow-up visit (24/27+6 weeks of pregnancy)
  description: ng/ml
  measure: Serum Vascular Cell Adhesion Molecule-1 (VCAM-1)
  time frame: Baseline visit (11/13+6 weeks of pregnancy)
  description: ng/ml
  measure: Serum Vascular Cell Adhesion Molecule-1 (VCAM-1)
  time frame: Follow-up visit (24/27+6 weeks of pregnancy)
  description: ng/ml
  measure: Number of participants with long-term cardiovascular outcomes
  time frame: Interview 5 years after delivery
  description: Number of participants diagnosed with stroke, myocardial infarction, heart failure or hospitalized for cardiovascular disease in the 5 years after delivery
  measure: Serum uric acid
  time frame: Baseline visit (11/13+6 weeks of pregnancy)
  description: mg/dl
  measure: Serum uric acid
  time frame: Follow-up visit (24/27+6 weeks of pregnancy)
  description: mg/dl
  measure: Serum lipid profile
  time frame: Baseline visit (11/13+6 weeks of pregnancy)
  description: HDL-cholesterol (mg/dl), LDL-cholesterol (mg/dl), Triglycerides (mg/dl), Lipoprotein (a) (mg/dl)
  measure: Serum lipid profile
  time frame: Follow-up visit (24/27+6 weeks of pregnancy)
  description: HDL-cholesterol (mg/dl), LDL-cholesterol (mg/dl), Triglycerides (mg/dl), Lipoprotein (a) (mg/dl)
  measure: Xanthine Oxidase Activity
  time frame: Baseline visit (11/13+6 weeks of pregnancy)
  description: mU/mL
  measure: Xanthine Oxidase Activity
  time frame: Follow-up visit (24/27+6 weeks of pregnancy)
  description: mU/mL
  arm group label: Principal arm
  arm group type: Experimental
  description: 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.
  intervention type: Device
  intervention name: Arterial applanation tonometry
  description: 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.
  arm group label: Principal arm
  other name: PulsePen
  other name: Arterial stiffness measurement
  other name: Pulse wave velocity assessment
  intervention type: Device
  intervention name: In vivo endothelial glycocalyx measurement
  description: 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).
  arm group label: Principal arm
  other name: Glycocheck
  other name: Sidestream dark field microscopy
  intervention type: Diagnostic Test
  intervention name: Serum markers of angiogenesis and endothelial dysfunction
  description: ELISA assays to measure serum circulating markers of angiogenesis and endothelial dysfunction (ANG-1, ANG-2, ET-1, ICAM-1 and VCAM-1).
  arm group label: Principal arm
  other name: ANG-1
  other name: ET-1
  other name: ICAM-1
  other name: VCAM-1
  other name: ANG-2
  intervention type: Diagnostic Test
  intervention name: Blood chemistry test
  description: Immunochemistry analysis of serum levels of uric acid, total cholesterol, LDL-cholesterol, HDL-cholesterol, Triglycerides, Lipoprotein (a)
  arm group label: Principal arm
  intervention type: Diagnostic Test
  intervention name: Serum xanthine oxidase activity
  description: Serum xanthine oxidase (XO) activity will be assessed in blood samples measuring the ability of XO to produce uric acid
  arm group label: Principal arm
  criteria: 
  gender: Female
  minimum age: 18 Years
  maximum age: 65 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Federica Piani, MD
  role: Study Chair
  affiliation: IRCCS University Hospital of Bologna, Italy. University of Bologna, Italy.
  last name: Claudio Borghi, MD
  role: Principal Investigator
  affiliation: IRCCS University Hospital of Bologna, Italy. University of Bologna, Italy.
  last name: Federica Piani, MD
  phone: +390512144291
  email: federica.piani2@unibo.it
  facility: 
  contact: 
  country: Italy
  responsible party type: Sponsor
  mesh term: Toxemia
  mesh term: Pre-Eclampsia
  mesh term: Pregnancy Complications
  mesh term: Hypertension
  sharing ipd: Yes
  ipd description: All de-identified IPD that underlie results in a publication for all primary and secondary outcome measures will be shared.
  ipd info type: Study Protocol
  ipd info type: Statistical Analysis Plan (SAP)
  ipd time frame: Data will be available after the associated manuscript will be published.
  ipd 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).