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/NCT05985447</url>
    </required_header>
    <id_info>
      <org_study_id>Hormone</org_study_id>
      <nct_id>NCT05985447</nct_id>
    </id_info>
    <brief_title>Menopause Related Influences on Leukocyte Distribution, Monocyte Function and Platelet Reactivity</brief_title>
    <official_title>Menopause Related Influences on Leukocyte Distribution, Monocyte Function and Platelet Reactivity</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Heinrich-Heine University, Duesseldorf</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Heinrich-Heine University, Duesseldorf</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Women and men show marked differences in cardiovascular risk profile and outcome. Women&#xD;
        experience fewer cardiovascular events than men before menopause, but this relationship seems&#xD;
        to reverse at menopause. These disparities are probably due to hormonal factors, especially&#xD;
        the female sex hormone estrogen seems to have a protective influence on the development of&#xD;
        atherosclerotic plaques premenopausal.&#xD;
  &#xD;
        The underlying mechanisms of the effect of estrogens on the vessel wall are still&#xD;
        insufficiently investigated. In this study, menopause related effects on leukocyte&#xD;
        distribution and function as well on platelets and their aggregational response will be&#xD;
        evaluated.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Sex-specific differences in the risk profile and outcome of cardiovascular diseases are&#xD;
        evident, which are probably due to hormonal factors. Women suffer significantly fewer&#xD;
        cardiovascular events than men before menopause, after menopause this relationship seems to&#xD;
        reverse. Moreover, outcome is worse in female patients compared to men.&#xD;
  &#xD;
        Platelets and leukocytes play an essential role in cardiovascular risk. Nevertheless, the&#xD;
        underlying mechanisms of the mechanistic effects of the hormone transition in menopause on&#xD;
        leukocytes and platelets have only been insufficiently investigated so far. Moreover, effects&#xD;
        of a possible hormone replacement therapy are insufficiently understood with contradictive&#xD;
        literature concerning cardiovascular effects.&#xD;
  &#xD;
        The aim in this study, is to analyse leukocyte and platelet function in dependence from&#xD;
        menopause related changes in hormone levels of estrogen, testosterone, progesterone, LH and&#xD;
        FSH. Moreover, hormone replacement therapy will be investigated.&#xD;
  &#xD;
        For this purpose, blood samples from male and female patients will be investigated with&#xD;
        regard to age and menopause status. The blood samples are analysed by FACS to differentiate&#xD;
        the leukocytes and test for inflammatory properties and reactive oxygen species. The monocyte&#xD;
        distribution divided according to the surface markers CD14 and CD16 is analysed. In addition,&#xD;
        plasma from the patient samples will be used to assess hormone levels in the blood. In&#xD;
        addition, patient data such as general laboratory parameters, risk and lifestyle factors are&#xD;
        collected and associated with the hormone and lipid levels.&#xD;
  &#xD;
        For platelet function analysis, light-transmittance aggregometry, flow cytometry (platelet&#xD;
        leukocyte crosstalk, investigation of platelet surface markers for platelet activation and&#xD;
        cell-cell-adhesion) will be investigated. Platelets secretory potency will be analysed by&#xD;
        ATP-release. Moreover, platelet adhesion will be investigated by collagen-coated flow&#xD;
        chambers. Platelet proteomics and RNA sequencing will complement the data in an unbiased&#xD;
        approach. In addition in-vitro incubation analyses with estrogen and testosterone will be&#xD;
        conducted to investigate hormone replacement therapy effects.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">March 7, 2022</start_date>
    <completion_date type="Anticipated">December 2026</completion_date>
    <primary_completion_date type="Anticipated">December 2025</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Cohort</observational_model>
      <time_perspective>Prospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Leukocyte distribution measured by flow cytometry</measure>
      <time_frame>single time, up to one day after inclusion</time_frame>
      <description>CD45 (Leukocytes), CD3 (T-cells), CD14 (Monocytes), CD16 (Granulocytes), CD19 (B-cells)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Platelet function</measure>
      <time_frame>single time, up to one day after inclusion</time_frame>
      <description>measured by light transmittance aggregometry (Parameters: Maximum of Aggregation, Slope</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Platelet surface markers, platelet leukocyte crosstalk (CD40, CD40L)</measure>
      <time_frame>single time, up to one day after inclusion</time_frame>
      <description>measured by flow cytometry (FACS)</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Reactive Oxygen Species (ROS) Generation via CellRoxGreen [geometric mean]</measure>
      <time_frame>single time, up to one day after inclusion</time_frame>
      <description>measured by Flow Cytometry (FACS)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Hormone levels of estrogen</measure>
      <time_frame>single time, up to one day after inclusion</time_frame>
      <description>measured by ELISA [ng/l]</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Hormone levels of testosterone measured by ELISA</measure>
      <time_frame>single time, up to one day after inclusion</time_frame>
      <description>measured by ELISA [ng/l]</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Hormone levels of progesterone</measure>
      <time_frame>single time, up to one day after inclusion</time_frame>
      <description>measured by ELISA [µg/l]</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Hormone levels of follicle stimulating hormone</measure>
      <time_frame>single time, up to one day after inclusion</time_frame>
      <description>measured by ELISA [µg/l]</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Hormone levels of luteinizing hormone</measure>
      <time_frame>single time, up to one day after inclusion</time_frame>
      <description>measured by ELISA [µg/l]</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Questionnaire including lifestyle factors, cardiovascular risk factors</measure>
      <time_frame>single time, up to one day after inclusion</time_frame>
    </secondary_outcome>
    <enrollment type="Anticipated">180</enrollment>
    <condition>Arteriosclerosis</condition>
    <condition>Acute Myocardial Infarction</condition>
    <condition>Cardiovascular Events</condition>
    <condition>Menopause</condition>
    <biospec_retention>Samples With DNA</biospec_retention>
    <biospec_descr>
      <textblock>
        prospectively defined blood sampling protocol&#xD;
      </textblock>
    </biospec_descr>
    <eligibility>
      <study_pop>
        <textblock>
          Male and female Patients with and without cardiovascular disease&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Age &gt; 18 years&#xD;
  &#xD;
            -  Male, female, diverse patients with current treatment in the Department of Cardiology,&#xD;
               Pneumology and Angiology.&#xD;
  &#xD;
            -  Persons who are able to understand and follow the instructions of the study staff&#xD;
  &#xD;
            -  Written informed consent&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Age &lt; 18 years&#xD;
  &#xD;
            -  Lack of written consent to participate in the study&#xD;
  &#xD;
            -  coagulation disorders&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Malte Kelm, Prof.</last_name>
      <role>Study Chair</role>
      <affiliation>Clinic for Cardiology, Pneumology and Angiology at University Hospital Düsseldorf</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Lisa Dannenberg, MD</last_name>
      <phone>+492118105315</phone>
      <email>lisa.dannenberg@med.uni-duesseldorf.de</email>
    </overall_contact>
    <location>
      <facility>
        <name>University-Hospital Düsseldorf Division of Cardiology, Pulmonary Disease and Vascular Medicine</name>
        <address>
          <city>Düsseldorf</city>
          <zip>40225</zip>
          <country>Germany</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Lisa Dannenberg, MD</last_name>
        <phone>+492118105315</phone>
        <email>lisa.dannenberg@med.uni-duesseldorf.de</email>
      </contact>
      <contact_backup>
        <last_name>Clinical Trial Unit</last_name>
        <phone>+4921181105315</phone>
        <email>ctu@med.uni-duesseldorf.de</email>
      </contact_backup>
      <investigator>
        <last_name>Lisa Dannenberg, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>Germany</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>April 14, 2023</study_first_submitted>
    <study_first_submitted_qc>August 2, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 14, 2023</study_first_posted>
    <last_update_submitted>August 2, 2023</last_update_submitted>
    <last_update_submitted_qc>August 2, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 14, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>sex</keyword>
    <keyword>gender</keyword>
    <keyword>female</keyword>
    <keyword>male</keyword>
    <keyword>menopause</keyword>
    <keyword>hormone replacement therapy</keyword>
    <keyword>Atherosclerosis</keyword>
    <keyword>cardiovascular events</keyword>
    <keyword>cardiovascular risk</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Myocardial Infarction</mesh_term>
      <mesh_term>Arteriosclerosis</mesh_term>
      <mesh_term>Infarction</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </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/NCT05985447
  org study id: Hormone
  nct id: NCT05985447
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Women and men show marked differences in cardiovascular risk profile and outcome. Women
        experience fewer cardiovascular events than men before menopause, but this relationship seems
        to reverse at menopause. These disparities are probably due to hormonal factors, especially
        the female sex hormone estrogen seems to have a protective influence on the development of
        atherosclerotic plaques premenopausal.
  
        The underlying mechanisms of the effect of estrogens on the vessel wall are still
        insufficiently investigated. In this study, menopause related effects on leukocyte
        distribution and function as well on platelets and their aggregational response will be
        evaluated.
  Sex-specific differences in the risk profile and outcome of cardiovascular diseases are
        evident, which are probably due to hormonal factors. Women suffer significantly fewer
        cardiovascular events than men before menopause, after menopause this relationship seems to
        reverse. Moreover, outcome is worse in female patients compared to men.
  
        Platelets and leukocytes play an essential role in cardiovascular risk. Nevertheless, the
        underlying mechanisms of the mechanistic effects of the hormone transition in menopause on
        leukocytes and platelets have only been insufficiently investigated so far. Moreover, effects
        of a possible hormone replacement therapy are insufficiently understood with contradictive
        literature concerning cardiovascular effects.
  
        The aim in this study, is to analyse leukocyte and platelet function in dependence from
        menopause related changes in hormone levels of estrogen, testosterone, progesterone, LH and
        FSH. Moreover, hormone replacement therapy will be investigated.
  
        For this purpose, blood samples from male and female patients will be investigated with
        regard to age and menopause status. The blood samples are analysed by FACS to differentiate
        the leukocytes and test for inflammatory properties and reactive oxygen species. The monocyte
        distribution divided according to the surface markers CD14 and CD16 is analysed. In addition,
        plasma from the patient samples will be used to assess hormone levels in the blood. In
        addition, patient data such as general laboratory parameters, risk and lifestyle factors are
        collected and associated with the hormone and lipid levels.
  
        For platelet function analysis, light-transmittance aggregometry, flow cytometry (platelet
        leukocyte crosstalk, investigation of platelet surface markers for platelet activation and
        cell-cell-adhesion) will be investigated. Platelets secretory potency will be analysed by
        ATP-release. Moreover, platelet adhesion will be investigated by collagen-coated flow
        chambers. Platelet proteomics and RNA sequencing will complement the data in an unbiased
        approach. In addition in-vitro incubation analyses with estrogen and testosterone will be
        conducted to investigate hormone replacement therapy effects.
  observational model: Cohort
  time perspective: Prospective
  measure: Leukocyte distribution measured by flow cytometry
  time frame: single time, up to one day after inclusion
  description: CD45 (Leukocytes), CD3 (T-cells), CD14 (Monocytes), CD16 (Granulocytes), CD19 (B-cells)
  measure: Platelet function
  time frame: single time, up to one day after inclusion
  description: measured by light transmittance aggregometry (Parameters: Maximum of Aggregation, Slope
  measure: Platelet surface markers, platelet leukocyte crosstalk (CD40, CD40L)
  time frame: single time, up to one day after inclusion
  description: measured by flow cytometry (FACS)
  measure: Reactive Oxygen Species (ROS) Generation via CellRoxGreen [geometric mean]
  time frame: single time, up to one day after inclusion
  description: measured by Flow Cytometry (FACS)
  measure: Hormone levels of estrogen
  time frame: single time, up to one day after inclusion
  description: measured by ELISA [ng/l]
  measure: Hormone levels of testosterone measured by ELISA
  time frame: single time, up to one day after inclusion
  description: measured by ELISA [ng/l]
  measure: Hormone levels of progesterone
  time frame: single time, up to one day after inclusion
  description: measured by ELISA [µg/l]
  measure: Hormone levels of follicle stimulating hormone
  time frame: single time, up to one day after inclusion
  description: measured by ELISA [µg/l]
  measure: Hormone levels of luteinizing hormone
  time frame: single time, up to one day after inclusion
  description: measured by ELISA [µg/l]
  measure: Questionnaire including lifestyle factors, cardiovascular risk factors
  time frame: single time, up to one day after inclusion
  prospectively defined blood sampling protocol
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: Accepts Healthy Volunteers
  last name: Malte Kelm, Prof.
  role: Study Chair
  affiliation: Clinic for Cardiology, Pneumology and Angiology at University Hospital Düsseldorf
  last name: Lisa Dannenberg, MD
  phone: +492118105315
  email: lisa.dannenberg@med.uni-duesseldorf.de
  facility: 
  status: Recruiting
  contact: 
  contact backup: 
  investigator: 
  country: Germany
  responsible party type: Sponsor
  mesh term: Myocardial Infarction
  mesh term: Arteriosclerosis
  mesh term: Infarction
  sharing ipd: No