<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/NCT03279770</url>
  </required_header>
  <id_info>
    <org_study_id>201505165RINC</org_study_id>
    <nct_id>NCT03279770</nct_id>
  </id_info>
  <brief_title>Circulating Non-coding RNAs and Cardiovascular Outcomes in Patients With Dyslipidemia and Atherosclerosis</brief_title>
  <official_title>Circulating Non-coding RNAs and Cardiovascular Outcomes in Patients With Dyslipidemia and Atherosclerosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Taiwan University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Taiwan University Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Cardiovascular diseases and stroke are the major causes of morbidity and death in Taiwan.&#xD;
      There is a clear need to identify novel mediators of atherosclerosis in dyslipidemic patients&#xD;
      to provide insights into the pathogenesis, to tailor clinical care based on cardiovascular&#xD;
      risks, and to develop new therapeutic strategies.&#xD;
&#xD;
      While the roles of lncRNAs in human diseases including cancer and neurodegenerative disorders&#xD;
      are beginning to emerge, it remains unclear how lncRNA regulation contributes to&#xD;
      atherosclerotic vascular diseases in patients with dyslipidemia. In this proposal, we seek to&#xD;
      apply next-generation sequencing technology to investigate circulating (plasma and peripheral&#xD;
      blood mononuclear cells [PBMC]) lncRNA expression in control subjects and in dyslipidemic&#xD;
      patients with and without atherosclerotic vascular diseases (CAD, ischemic stroke and PAOD).&#xD;
      The results from these experiments will lead to better understanding of how circulating&#xD;
      lncRNAs contribute to atherosclerotic cardiovascular complications.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Cardiovascular diseases and stroke are the major causes of morbidity and death in Taiwan.&#xD;
      Patients with dyslipidemia are prone to atherosclerosis, which predispose to various&#xD;
      cardiovascular pathology including coronary artery disease (CAD), ischemic stroke and&#xD;
      peripheral artery occlusive disease (PAOD). There are, however, no reliable biomarkers to&#xD;
      detect atherosclerotic vascular diseases among dyslipidemic patients or to predict the risks&#xD;
      of cardiovascular morbidities and mortality among patients with atherosclerosis. There is a&#xD;
      clear need to identify novel mediators of atherosclerosis in dyslipidemic patients to provide&#xD;
      insights into the pathogenesis, to tailor clinical care based on cardiovascular risks, and to&#xD;
      develop new therapeutic strategies.&#xD;
&#xD;
      It has become increasingly clear that the transcription of the eukaryotic genome is far more&#xD;
      pervasive and complex than previously appreciated. While the expression of messenger RNAs&#xD;
      (mRNAs) and microRNAs (miRNAs) account for only ~1% of all transcribed species, up to 90% of&#xD;
      the mammalian genome is transcribed as long non-coding RNAs (lncRNAs), a heterogeneous group&#xD;
      of non-coding transcripts longer than 200 nucleotides. LncRNAs have been shown to be&#xD;
      functional and involved in specific physiological and pathological processes through&#xD;
      epigenetic, transcriptional and post-transcriptional mechanisms. While the roles of lncRNAs&#xD;
      in human diseases including cancer and neurodegenerative disorders are beginning to emerge,&#xD;
      it remains unclear how lncRNA regulation contributes to atherosclerotic vascular diseases in&#xD;
      patients with dyslipidemia.&#xD;
&#xD;
      In this proposal, we seek to apply next-generation sequencing technology to investigate&#xD;
      circulating (plasma and peripheral blood mononuclear cells [PBMC]) lncRNA expression in&#xD;
      control subjects and in dyslipidemic patients with and without atherosclerotic vascular&#xD;
      diseases (CAD, ischemic stroke and PAOD). We will test the hypothesis that circulating lncRNA&#xD;
      expression signature can reflect the atherosclerotic disease states in patients with&#xD;
      dyslipidemia. A gene co-expression network analysis will be conducted to identify lncRNAs&#xD;
      that are functionally involved in the pathogenesis of atherosclerosis. With the experimental&#xD;
      results from an initial dyslipidemic cohort, we will establish an atherosclerosis scoring&#xD;
      model on the basis of circulating lncRNA expression signature to facilitate the detection of&#xD;
      atherosclerotic vascular diseases in patients with dyslipidemia. The accuracy, sensitivity&#xD;
      and specificity of the lncRNA-based atherosclerosis scoring system will then be tested in an&#xD;
      independent, large validation cohort. Next, we propose to test the hypothesis that&#xD;
      circulating lncRNAs can be novel prognostic biomarkers to predict atherosclerosis progression&#xD;
      and cardiovascular outcomes in dyslipidemic patients. The results from these experiments will&#xD;
      lead to better understanding of how circulating lncRNAs contribute to atherosclerotic&#xD;
      cardiovascular complications. These studies will also establish a set of novel, lncRNA-based&#xD;
      diagnostic and prognostic biomarker in dyslipidemic patients to improve clinical preventive&#xD;
      and therapeutic care. In addition, the findings from these studies will help to develop novel&#xD;
      therapeutic strategies to treat or prevent atherosclerotic vascular diseases in patients with&#xD;
      dyslipidemia.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">June 2015</start_date>
  <completion_date type="Anticipated">December 2020</completion_date>
  <primary_completion_date type="Anticipated">June 2020</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Composite cardiovascular outcome</measure>
    <time_frame>up to 5 years</time_frame>
    <description>The composite cardiovascular (CV) outcome will be any CV events (coronary, cerebral, or peripheral vascular diseases)</description>
  </primary_outcome>
  <enrollment type="Anticipated">1000</enrollment>
  <condition>Cardiovascular Diseases</condition>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Plasma and serum Non-coding RNAs&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        patients with dyslipidemia, atherosclerotic vascular diseases, or at least one CV risk&#xD;
        factors&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Dyslipidemia: Total cholesterol (TC) &gt;200 mg/dL; LDL-C &gt; 130 mg/dL ; TG &gt; 200 mg/dL;&#xD;
             male HDL-C &lt; 40 mg/dL, female HDL-C &lt; 50 mg/dL, or under lipid lowering therapy&#xD;
&#xD;
          2. Atherosclerotic vascular disease:&#xD;
&#xD;
               1. Coronary atherosclerosis as evidenced by cardiac catheterization examination,&#xD;
                  having history of myocardial infarction as evidenced by ECG or hospitalization,&#xD;
                  angina patient showing ischemic ECG changes or positive response to stress test;&#xD;
&#xD;
               2. Cerebral vascular disease, cerebral infarction, intracerebral hemorrhage&#xD;
                  (excluding intracerebral hemorrhage associated with other diseases); transient&#xD;
                  ischemic attack (TIA) with carotid artery ultrasound confirming atheromatous&#xD;
                  change with more than 70% blockage;&#xD;
&#xD;
               3. Peripheral atherosclerosis with symptoms of ischemia and confirmed by Doppler&#xD;
                  ultrasound or angiography in history.&#xD;
&#xD;
          3. Control subjects: Age, gender-matched healthy adults without dyslipidemia and&#xD;
             atherosclerotic diseases will be recruited as control subjects.&#xD;
&#xD;
        Exclusion Criteria The main exclusion criteria will be hemodynamically significant valvular&#xD;
        or congenital heart disease, life-threatening malignancy, treatment with immunosuppressive&#xD;
        agents, or any condition or situation which, in the opinion of the investigator, might be&#xD;
        not suitable for this registration.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Chau-Chung Wu, M.D., Ph. D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Taiwan University Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Chau-Chung Wu, M.D.,Ph.D.</last_name>
    <phone>02-23123456</phone>
    <phone_ext>88560</phone_ext>
    <email>chauchungwu@ntu.edu.tw</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Peo-Chun Cheng, BS</last_name>
    <phone>02-23123456</phone>
    <phone_ext>88558</phone_ext>
    <email>ntuh204@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>National Taiwan University Hospital</name>
      <address>
        <city>Taipei</city>
        <zip>100</zip>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kai-Chien Yang, M.D. Ph.D.</last_name>
      <phone>+886223123456</phone>
      <phone_ext>88327</phone_ext>
      <email>kcyang@ntu.edu.tw</email>
    </contact>
    <investigator>
      <last_name>Chau-Chung Wu, M.D. Ph.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>May 11, 2017</study_first_submitted>
  <study_first_submitted_qc>September 10, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 12, 2017</study_first_posted>
  <last_update_submitted>September 13, 2017</last_update_submitted>
  <last_update_submitted_qc>September 13, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 15, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>lnRNA</keyword>
  <keyword>CV disease</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cardiovascular Diseases</mesh_term>
    <mesh_term>Atherosclerosis</mesh_term>
    <mesh_term>Dyslipidemias</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</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/NCT03279770
org study id: 201505165RINC
nct id: NCT03279770
lead sponsor: 
has dmc: Yes
Cardiovascular diseases and stroke are the major causes of morbidity and death in Taiwan.
      There is a clear need to identify novel mediators of atherosclerosis in dyslipidemic patients
      to provide insights into the pathogenesis, to tailor clinical care based on cardiovascular
      risks, and to develop new therapeutic strategies.

      While the roles of lncRNAs in human diseases including cancer and neurodegenerative disorders
      are beginning to emerge, it remains unclear how lncRNA regulation contributes to
      atherosclerotic vascular diseases in patients with dyslipidemia. In this proposal, we seek to
      apply next-generation sequencing technology to investigate circulating (plasma and peripheral
      blood mononuclear cells [PBMC]) lncRNA expression in control subjects and in dyslipidemic
      patients with and without atherosclerotic vascular diseases (CAD, ischemic stroke and PAOD).
      The results from these experiments will lead to better understanding of how circulating
      lncRNAs contribute to atherosclerotic cardiovascular complications.
Cardiovascular diseases and stroke are the major causes of morbidity and death in Taiwan.
      Patients with dyslipidemia are prone to atherosclerosis, which predispose to various
      cardiovascular pathology including coronary artery disease (CAD), ischemic stroke and
      peripheral artery occlusive disease (PAOD). There are, however, no reliable biomarkers to
      detect atherosclerotic vascular diseases among dyslipidemic patients or to predict the risks
      of cardiovascular morbidities and mortality among patients with atherosclerosis. There is a
      clear need to identify novel mediators of atherosclerosis in dyslipidemic patients to provide
      insights into the pathogenesis, to tailor clinical care based on cardiovascular risks, and to
      develop new therapeutic strategies.

      It has become increasingly clear that the transcription of the eukaryotic genome is far more
      pervasive and complex than previously appreciated. While the expression of messenger RNAs
      (mRNAs) and microRNAs (miRNAs) account for only ~1% of all transcribed species, up to 90% of
      the mammalian genome is transcribed as long non-coding RNAs (lncRNAs), a heterogeneous group
      of non-coding transcripts longer than 200 nucleotides. LncRNAs have been shown to be
      functional and involved in specific physiological and pathological processes through
      epigenetic, transcriptional and post-transcriptional mechanisms. While the roles of lncRNAs
      in human diseases including cancer and neurodegenerative disorders are beginning to emerge,
      it remains unclear how lncRNA regulation contributes to atherosclerotic vascular diseases in
      patients with dyslipidemia.

      In this proposal, we seek to apply next-generation sequencing technology to investigate
      circulating (plasma and peripheral blood mononuclear cells [PBMC]) lncRNA expression in
      control subjects and in dyslipidemic patients with and without atherosclerotic vascular
      diseases (CAD, ischemic stroke and PAOD). We will test the hypothesis that circulating lncRNA
      expression signature can reflect the atherosclerotic disease states in patients with
      dyslipidemia. A gene co-expression network analysis will be conducted to identify lncRNAs
      that are functionally involved in the pathogenesis of atherosclerosis. With the experimental
      results from an initial dyslipidemic cohort, we will establish an atherosclerosis scoring
      model on the basis of circulating lncRNA expression signature to facilitate the detection of
      atherosclerotic vascular diseases in patients with dyslipidemia. The accuracy, sensitivity
      and specificity of the lncRNA-based atherosclerosis scoring system will then be tested in an
      independent, large validation cohort. Next, we propose to test the hypothesis that
      circulating lncRNAs can be novel prognostic biomarkers to predict atherosclerosis progression
      and cardiovascular outcomes in dyslipidemic patients. The results from these experiments will
      lead to better understanding of how circulating lncRNAs contribute to atherosclerotic
      cardiovascular complications. These studies will also establish a set of novel, lncRNA-based
      diagnostic and prognostic biomarker in dyslipidemic patients to improve clinical preventive
      and therapeutic care. In addition, the findings from these studies will help to develop novel
      therapeutic strategies to treat or prevent atherosclerotic vascular diseases in patients with
      dyslipidemia.
observational model: Case-Only
time perspective: Retrospective
measure: Composite cardiovascular outcome
time frame: up to 5 years
description: The composite cardiovascular (CV) outcome will be any CV events (coronary, cerebral, or peripheral vascular diseases)
Plasma and serum Non-coding RNAs
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Chau-Chung Wu, M.D., Ph. D.
role: Principal Investigator
affiliation: National Taiwan University Hospital
last name: Chau-Chung Wu, M.D.,Ph.D.
phone: 02-23123456
phone ext: 88560
email: chauchungwu@ntu.edu.tw
last name: Peo-Chun Cheng, BS
phone: 02-23123456
phone ext: 88558
email: ntuh204@gmail.com
facility: 
status: Recruiting
contact: 
investigator: 
country: Taiwan
responsible party type: Sponsor
mesh term: Cardiovascular Diseases
mesh term: Atherosclerosis
mesh term: Dyslipidemias
sharing ipd: Yes