<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/NCT04453267</url>
  </required_header>
  <id_info>
    <org_study_id>CAR0566</org_study_id>
    <nct_id>NCT04453267</nct_id>
  </id_info>
  <brief_title>DNA Repair in Patients With Stable Angina.</brief_title>
  <acronym>DECODE II</acronym>
  <official_title>DNA Repair in Patients With Stable Angina.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital Southampton NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital Southampton NHS Foundation Trust</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>
      Markers of DNA damage and repair are present in both atherosclerotic plaques and peripheral&#xD;
      blood mononuclear cells of patients with coronary artery disease. A positive correlation has&#xD;
      been observed between the level of DNA damage and the severity of atherosclerotic lesions, as&#xD;
      well as atherogenic risk factors such as smoking, hypertension and hyperlipidaemia. A number&#xD;
      of in-vitro studies have implicated defective DNA repair in the development and progression&#xD;
      of atherosclerotic lesions. In mouse models of atherosclerosis, the DNA repair signalling&#xD;
      cascade has been shown to be amenable to pharmacological intervention and overexpression of&#xD;
      specific repair proteins attenuate the development of atherosclerotic plaques. However, data&#xD;
      regarding the role of DNA repair in the pathogenesis of atherosclerosis in humans are&#xD;
      lacking. We have preliminary data indicating reduced DNA repair activity in patients with&#xD;
      stable angina. This study will determine the molecular basis and the biological consequences&#xD;
      of this observation.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">February 5, 2020</start_date>
  <completion_date type="Anticipated">August 1, 2024</completion_date>
  <primary_completion_date type="Anticipated">August 1, 2023</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Other</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Association between monocytes exhibiting reduced base excision repair and/or double strand break repair activity in patients with stable angina as compared to patients without coronary artery disease.</measure>
    <time_frame>Blood will be collected at the time of hospital admission for index procedure. No follow-up of patients will be required.</time_frame>
    <description>This will be assessed using real-time polymerase chain reaction, western blotting and proteosomal degradation assay.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Reduced DNA repair activity is associated with impaired response to oxidative stress in human monocytes in patients with stable angina in comparison to an age and gender matched control.</measure>
    <time_frame>Blood will be collected at the time of hospital admission for index procedure. No follow-up of patients will be required.</time_frame>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">172</enrollment>
  <condition>Coronary Artery Disease</condition>
  <condition>Coronary Arteriosclerosis</condition>
  <condition>DNA Damage</condition>
  <condition>DNA Repair Abnormality</condition>
  <arm_group>
    <arm_group_label>Patient Arm.</arm_group_label>
    <description>Consecutive patients undergoing elective percutaneous coronary intervention (PCI) or isolated coronary artery bypass grafting (CABG) for symptomatic stable angina (SA) despite optimal medical therapy at the University Hospital Southampton NHS Foundation Trust will be prospectively enrolled (n=86).&#xD;
No interventions administered. 40ml of whole blood in EDTA vials to be taken for cellular separation and analysis.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Age and gender matched controls</arm_group_label>
    <description>Age and gender-matched patients being investigated for chest pain with unobstructed coronary arteries, defined as coronary stenosis ≤ 30% in any major epicardial vessel on CT or invasive coronary angiography, will also be recruited as controls (n=86).&#xD;
40ml of whole blood in EDTA vials to be taken for cellular separation and analysis.</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Stored samples of isolated T-Cells and Monocytes.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients undergoing an assessment of thier coronary anatomy either by computerised&#xD;
        tomography coronary angiogram or invasive coroanry angiogram at a large university teaching&#xD;
        hospital performed as part of thier routine care.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥18 years&#xD;
&#xD;
          -  Ability to provide written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 80 years&#xD;
&#xD;
          -  Inability to provide written informed consent&#xD;
&#xD;
          -  Presentation with an acute coronary syndrome&#xD;
&#xD;
          -  Severe valvular heart disease&#xD;
&#xD;
          -  Hypertrophic cardiomyopathy&#xD;
&#xD;
          -  Left ventricular ejection fraction ≤ 35%&#xD;
&#xD;
          -  Prior coronary revascularisation (surgical or percutaneous)&#xD;
&#xD;
          -  Diabetes Mellitus&#xD;
&#xD;
          -  Clinical evidence of peripheral vascular disease&#xD;
&#xD;
          -  Prior history of cerebrovascular disease&#xD;
&#xD;
          -  Malignancy&#xD;
&#xD;
          -  Active inflammatory disorders (e.g. rheumatoid arthritis/connective tissue disorder)&#xD;
&#xD;
          -  Renal impairment eGFR &lt;60ml/min/1.73m2&#xD;
&#xD;
          -  Anaemia (Hb &lt;100g/dL)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michael Mahmoudi, MD,PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital Southampton NHS Foundation Trust</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Thomas R Gilpin, MBBCh</last_name>
    <phone>0044 (0)2380777222</phone>
    <phone_ext>3912</phone_ext>
    <email>thomas.gilpin@uhs.nhs.uk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Zoe Nicholas, BSc</last_name>
    <phone>0044 (0)2380777222</phone>
    <phone_ext>8538</phone_ext>
    <email>zoe.nicholas@uhs.nhs.uk</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University Hospital Southampton NHS Foundation Trust</name>
      <address>
        <city>Southampton</city>
        <state>Hampshire</state>
        <zip>SO16 6YD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Michael Mahmoudi, MD,PhD</last_name>
      <phone>0044 (0)23801208538</phone>
      <phone_ext>8538</phone_ext>
      <email>michael.mahmoudi@uhs.nhs.uk</email>
    </contact>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>June 26, 2020</study_first_submitted>
  <study_first_submitted_qc>June 26, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 1, 2020</study_first_posted>
  <last_update_submitted>October 27, 2022</last_update_submitted>
  <last_update_submitted_qc>October 27, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 28, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Coronary Artery Disease</mesh_term>
    <mesh_term>Myocardial Ischemia</mesh_term>
    <mesh_term>Angina, Stable</mesh_term>
    <mesh_term>Arteriosclerosis</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/NCT04453267
org study id: CAR0566
nct id: NCT04453267
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Markers of DNA damage and repair are present in both atherosclerotic plaques and peripheral
      blood mononuclear cells of patients with coronary artery disease. A positive correlation has
      been observed between the level of DNA damage and the severity of atherosclerotic lesions, as
      well as atherogenic risk factors such as smoking, hypertension and hyperlipidaemia. A number
      of in-vitro studies have implicated defective DNA repair in the development and progression
      of atherosclerotic lesions. In mouse models of atherosclerosis, the DNA repair signalling
      cascade has been shown to be amenable to pharmacological intervention and overexpression of
      specific repair proteins attenuate the development of atherosclerotic plaques. However, data
      regarding the role of DNA repair in the pathogenesis of atherosclerosis in humans are
      lacking. We have preliminary data indicating reduced DNA repair activity in patients with
      stable angina. This study will determine the molecular basis and the biological consequences
      of this observation.
observational model: Other
time perspective: Prospective
measure: Association between monocytes exhibiting reduced base excision repair and/or double strand break repair activity in patients with stable angina as compared to patients without coronary artery disease.
time frame: Blood will be collected at the time of hospital admission for index procedure. No follow-up of patients will be required.
description: This will be assessed using real-time polymerase chain reaction, western blotting and proteosomal degradation assay.
measure: Reduced DNA repair activity is associated with impaired response to oxidative stress in human monocytes in patients with stable angina in comparison to an age and gender matched control.
time frame: Blood will be collected at the time of hospital admission for index procedure. No follow-up of patients will be required.
arm group label: Patient Arm.
description: Consecutive patients undergoing elective percutaneous coronary intervention (PCI) or isolated coronary artery bypass grafting (CABG) for symptomatic stable angina (SA) despite optimal medical therapy at the University Hospital Southampton NHS Foundation Trust will be prospectively enrolled (n=86).
No interventions administered. 40ml of whole blood in EDTA vials to be taken for cellular separation and analysis.
arm group label: Age and gender matched controls
description: Age and gender-matched patients being investigated for chest pain with unobstructed coronary arteries, defined as coronary stenosis ≤ 30% in any major epicardial vessel on CT or invasive coronary angiography, will also be recruited as controls (n=86).
40ml of whole blood in EDTA vials to be taken for cellular separation and analysis.
Stored samples of isolated T-Cells and Monocytes.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Michael Mahmoudi, MD,PhD
role: Principal Investigator
affiliation: University Hospital Southampton NHS Foundation Trust
last name: Thomas R Gilpin, MBBCh
phone: 0044 (0)2380777222
phone ext: 3912
email: thomas.gilpin@uhs.nhs.uk
last name: Zoe Nicholas, BSc
phone: 0044 (0)2380777222
phone ext: 8538
email: zoe.nicholas@uhs.nhs.uk
facility: 
status: Recruiting
contact: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Coronary Artery Disease
mesh term: Myocardial Ischemia
mesh term: Angina, Stable
mesh term: Arteriosclerosis
sharing ipd: No