<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/NCT04419727</url>
  </required_header>
  <id_info>
    <org_study_id>ER.ALL.2018.31</org_study_id>
    <nct_id>NCT04419727</nct_id>
  </id_info>
  <brief_title>Estrogen Receptors and Peripheral Artery Disease</brief_title>
  <acronym>ESTROPAD</acronym>
  <official_title>Molecular Analysis of Estrogen Receptors in Patients With Peripheral Artery Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Catanzaro</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Catanzaro</source>
  <oversight_info>
    <has_dmc>Yes</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>
      It is estimated that &gt;200 million people have Peripheral artery disease (PAD) worldwide. PAD&#xD;
      is related to increased morbidity or mortality in affected patients. More severe forms of PAD&#xD;
      are surgically managed. Estrogen receptors (ERs) are strictly linked with vascular disease,&#xD;
      and may be involved also in PAD onset and progression. This study will explore the expression&#xD;
      of ERs, (ER-alpha, ER-beta,and a G protein-coupled of estrogen receptor -GPER-) in vessel&#xD;
      wall of arteries of operated PAD patients, through the entire clinical spectrum of PAD.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PAD is the atherosclerotic obstruction of the arteries of the lower extremities and it is&#xD;
      widespread especially in highly developed countries. The most common complication of PAD is&#xD;
      critical limb ischemia with rest pain and leg ulcers. To date the pathophysiology of PAD is&#xD;
      linked to atherosclerosis but other pathways are also under evaluation. A recent study (Serra&#xD;
      et al) investigated the presence of ER-alfa, ER-beta, and GPER in the wall of normal and&#xD;
      varicose veins.&#xD;
&#xD;
      The aim of this observational study is to evaluate the expression and the role of estrogen&#xD;
      receptors in patients with PAD, and undergoing surgical treatment with reconstructive&#xD;
      arterial surgery. Therefore, we will collect tissue samples from diseased arteries that will&#xD;
      be further analyzed for ER expression. We will then correlate the results with the clinical&#xD;
      spectrum of the patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">January 2, 2020</start_date>
  <completion_date type="Anticipated">November 2, 2020</completion_date>
  <primary_completion_date type="Anticipated">September 1, 2020</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>Expression of ER-alpha, ER-beta,and GPER</measure>
    <time_frame>at month 6th</time_frame>
    <description>The expression of ER-alpha, ER-beta,and GPER will be quantified by real-tome PCR using Step One ™ sequence detection system (Applied Biosystems Inc. Milan, Italy) following the manufacturer's instruction</description>
  </primary_outcome>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Estrogen Deficiency</condition>
  <condition>Peripheral Artery Disease</condition>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>arterial reconstructive open surgery</intervention_name>
    <description>Patients with peripheral artery disease (PAD) will undergo arterial reconstructive open surgery. Samples obtained from diseased arteries of lower limbs of patients undergoing arterial reconstructive open surgery will be collected and immediately preserved at -80°. Briefly, the arterial tissues will be excised, homogenized with a motor-driven homogenizer and total RNA will be isolated using Trizol reagent (Invitrogen, Milan Italy), according to the manufacturer's instructions. The expression of ER-alpha, ER-beta,and GPER will be quantified by real-time PCR using the Step One ™ sequence detection system (Applied Biosystems Inc. Milan, Italy), following the manufacturer's instruction</description>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with peripheral artery disease (PAD) eligible to receive arterial reconstructive&#xD;
        open surgery&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with peripheral artery disease (PAD) eligible to receive arterial&#xD;
             reconstructive open surgery.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  malignancy&#xD;
&#xD;
          -  estrogen therapy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Raffaele Serra, M.D., Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Magna Graecia of Catanzaro</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Raffaele Serra, M.D., Ph.D.</last_name>
    <phone>+3909613647380</phone>
    <email>rserra@unicz.it</email>
  </overall_contact>
  <location>
    <facility>
      <name>CIFL- Interuniversity Center of Phlebolymphology</name>
      <address>
        <city>Catanzaro</city>
        <zip>88100</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Raffaele Serra, MD</last_name>
      <phone>+393387078043</phone>
      <email>rserra@unicz.it</email>
    </contact>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <reference>
    <citation>Criqui MH, Aboyans V. Epidemiology of peripheral artery disease. Circ Res. 2015 Apr 24;116(9):1509-26. doi: 10.1161/CIRCRESAHA.116.303849. Erratum In: Circ Res. 2015 Jun 19;117(1):e12.</citation>
    <PMID>25908725</PMID>
  </reference>
  <reference>
    <citation>Serra R, Gallelli L, Perri P, De Francesco EM, Rigiracciolo DC, Mastroroberto P, Maggiolini M, de Franciscis S. Estrogen Receptors and Chronic Venous Disease. Eur J Vasc Endovasc Surg. 2016 Jul;52(1):114-8. doi: 10.1016/j.ejvs.2016.04.020. Epub 2016 May 21.</citation>
    <PMID>27220899</PMID>
  </reference>
  <reference>
    <citation>Barton M, Prossnitz ER. Emerging roles of GPER in diabetes and atherosclerosis. Trends Endocrinol Metab. 2015 Apr;26(4):185-92. doi: 10.1016/j.tem.2015.02.003. Epub 2015 Mar 9.</citation>
    <PMID>25767029</PMID>
  </reference>
  <reference>
    <citation>Boese AC, Kim SC, Yin KJ, Lee JP, Hamblin MH. Sex differences in vascular physiology and pathophysiology: estrogen and androgen signaling in health and disease. Am J Physiol Heart Circ Physiol. 2017 Sep 1;313(3):H524-H545. doi: 10.1152/ajpheart.00217.2016. Epub 2017 Jun 16.</citation>
    <PMID>28626075</PMID>
  </reference>
  <reference>
    <citation>Kublickiene K, Svedas E, Landgren BM, Crisby M, Nahar N, Nisell H, Poston L. Small artery endothelial dysfunction in postmenopausal women: in vitro function, morphology, and modification by estrogen and selective estrogen receptor modulators. J Clin Endocrinol Metab. 2005 Nov;90(11):6113-22. doi: 10.1210/jc.2005-0419. Epub 2005 Aug 30.</citation>
    <PMID>16131583</PMID>
  </reference>
  <reference>
    <citation>Kalicinska E, Wojtas K, Majda J, Zacharski M, Skiba J, Sliwowski J, Banasiak W, Ponikowski P, Jankowska EA. Expression of sex steroid receptors and aromatase in adipose tissue in different body regions in men with coronary artery disease with and without ischemic systolic heart failure. Aging Male. 2020 Jun;23(2):141-153. doi: 10.1080/13685538.2018.1494144. Epub 2018 Sep 7.</citation>
    <PMID>30193537</PMID>
  </reference>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 3, 2020</study_first_submitted>
  <study_first_submitted_qc>June 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 5, 2020</study_first_posted>
  <last_update_submitted>June 3, 2020</last_update_submitted>
  <last_update_submitted_qc>June 3, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 5, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Catanzaro</investigator_affiliation>
    <investigator_full_name>Prof. Raffaele Serra, MD, Ph.D.</investigator_full_name>
    <investigator_title>Associate Professor of Vascular Surgery</investigator_title>
  </responsible_party>
  <keyword>Peripheral artery disease</keyword>
  <keyword>Estrogens receptors</keyword>
  <keyword>GPER</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Peripheral Arterial Disease</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


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/NCT04419727
org study id: ER.ALL.2018.31
nct id: NCT04419727
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
It is estimated that >200 million people have Peripheral artery disease (PAD) worldwide. PAD
      is related to increased morbidity or mortality in affected patients. More severe forms of PAD
      are surgically managed. Estrogen receptors (ERs) are strictly linked with vascular disease,
      and may be involved also in PAD onset and progression. This study will explore the expression
      of ERs, (ER-alpha, ER-beta,and a G protein-coupled of estrogen receptor -GPER-) in vessel
      wall of arteries of operated PAD patients, through the entire clinical spectrum of PAD.
PAD is the atherosclerotic obstruction of the arteries of the lower extremities and it is
      widespread especially in highly developed countries. The most common complication of PAD is
      critical limb ischemia with rest pain and leg ulcers. To date the pathophysiology of PAD is
      linked to atherosclerosis but other pathways are also under evaluation. A recent study (Serra
      et al) investigated the presence of ER-alfa, ER-beta, and GPER in the wall of normal and
      varicose veins.

      The aim of this observational study is to evaluate the expression and the role of estrogen
      receptors in patients with PAD, and undergoing surgical treatment with reconstructive
      arterial surgery. Therefore, we will collect tissue samples from diseased arteries that will
      be further analyzed for ER expression. We will then correlate the results with the clinical
      spectrum of the patients.
observational model: Cohort
time perspective: Prospective
measure: Expression of ER-alpha, ER-beta,and GPER
time frame: at month 6th
description: The expression of ER-alpha, ER-beta,and GPER will be quantified by real-tome PCR using Step One ™ sequence detection system (Applied Biosystems Inc. Milan, Italy) following the manufacturer's instruction
intervention type: Procedure
intervention name: arterial reconstructive open surgery
description: Patients with peripheral artery disease (PAD) will undergo arterial reconstructive open surgery. Samples obtained from diseased arteries of lower limbs of patients undergoing arterial reconstructive open surgery will be collected and immediately preserved at -80°. Briefly, the arterial tissues will be excised, homogenized with a motor-driven homogenizer and total RNA will be isolated using Trizol reagent (Invitrogen, Milan Italy), according to the manufacturer's instructions. The expression of ER-alpha, ER-beta,and GPER will be quantified by real-time PCR using the Step One ™ sequence detection system (Applied Biosystems Inc. Milan, Italy), following the manufacturer's instruction
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Raffaele Serra, M.D., Ph.D.
role: Principal Investigator
affiliation: University Magna Graecia of Catanzaro
last name: Raffaele Serra, M.D., Ph.D.
phone: +3909613647380
email: rserra@unicz.it
facility: 
status: Recruiting
contact: 
country: Italy
citation: Criqui MH, Aboyans V. Epidemiology of peripheral artery disease. Circ Res. 2015 Apr 24;116(9):1509-26. doi: 10.1161/CIRCRESAHA.116.303849. Erratum In: Circ Res. 2015 Jun 19;117(1):e12.
PMID: 25908725
citation: Serra R, Gallelli L, Perri P, De Francesco EM, Rigiracciolo DC, Mastroroberto P, Maggiolini M, de Franciscis S. Estrogen Receptors and Chronic Venous Disease. Eur J Vasc Endovasc Surg. 2016 Jul;52(1):114-8. doi: 10.1016/j.ejvs.2016.04.020. Epub 2016 May 21.
PMID: 27220899
citation: Barton M, Prossnitz ER. Emerging roles of GPER in diabetes and atherosclerosis. Trends Endocrinol Metab. 2015 Apr;26(4):185-92. doi: 10.1016/j.tem.2015.02.003. Epub 2015 Mar 9.
PMID: 25767029
citation: Boese AC, Kim SC, Yin KJ, Lee JP, Hamblin MH. Sex differences in vascular physiology and pathophysiology: estrogen and androgen signaling in health and disease. Am J Physiol Heart Circ Physiol. 2017 Sep 1;313(3):H524-H545. doi: 10.1152/ajpheart.00217.2016. Epub 2017 Jun 16.
PMID: 28626075
citation: Kublickiene K, Svedas E, Landgren BM, Crisby M, Nahar N, Nisell H, Poston L. Small artery endothelial dysfunction in postmenopausal women: in vitro function, morphology, and modification by estrogen and selective estrogen receptor modulators. J Clin Endocrinol Metab. 2005 Nov;90(11):6113-22. doi: 10.1210/jc.2005-0419. Epub 2005 Aug 30.
PMID: 16131583
citation: Kalicinska E, Wojtas K, Majda J, Zacharski M, Skiba J, Sliwowski J, Banasiak W, Ponikowski P, Jankowska EA. Expression of sex steroid receptors and aromatase in adipose tissue in different body regions in men with coronary artery disease with and without ischemic systolic heart failure. Aging Male. 2020 Jun;23(2):141-153. doi: 10.1080/13685538.2018.1494144. Epub 2018 Sep 7.
PMID: 30193537
responsible party type: Principal Investigator
investigator affiliation: University of Catanzaro
investigator full name: Prof. Raffaele Serra, MD, Ph.D.
investigator title: Associate Professor of Vascular Surgery
mesh term: Peripheral Arterial Disease
sharing ipd: No