<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/NCT03766204</url>
  </required_header>
  <id_info>
    <org_study_id>20181204</org_study_id>
    <nct_id>NCT03766204</nct_id>
  </id_info>
  <brief_title>The Role of Circulating CircRNAs and MicroRNAs in Acute Lung Injury</brief_title>
  <acronym>TRCCMALI</acronym>
  <official_title>Relationship Between Circulating CircRNAs and MicroRNAs and Severity of Experimental and Clinical ALI/ARDS</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Changhai Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Changhai Hospital</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>
      Efforts to identify circulating factors that predict severity of acute lung injury/acute&#xD;
      respiratory distress syndrome（ALI/ARDS）patients is unrevealing. The primary purpose of this&#xD;
      study is to verify circRNAs and microRNAs might be potential novel ALI/ARDS biomarkers and&#xD;
      could play roles in pathogenesis of ALI/ARDS.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a devastating cause&#xD;
      of morbidity and mortality characterized by alveolar epithelial and endothelial injury.&#xD;
      Despite recent advances in pathogenetic mechanisms and therapy strategies of ALI, efforts to&#xD;
      identify circulating factors that predict severity of ALI/ARDS patients have been&#xD;
      unrevealing.&#xD;
&#xD;
      Circular RNAs (circRNAs) are a novel class of endogenous non-coding RNA with a covalently&#xD;
      continuous closed-loop structure. Compared with traditional linear RNAs, circRNAs are more&#xD;
      stable and resistant to RNase R due to the absence of 5' caps and 3' tails, which show clear&#xD;
      advantages in acting as novel molecular biomarkers for many diseases. In addition, many&#xD;
      studies have reported that circRNAs can bind to microRNAs (miRNAs), acting as &quot;miRNA sponges&quot;&#xD;
      which are named competitive endogenous RNAs (ceRNAs), and can regulate gene expression at the&#xD;
      transcriptional or post-transcriptional level. Evidence indicates that circRNAs play&#xD;
      important roles in cancers and other diseases such as tuberculosis and intervertebral disc&#xD;
      degeneration. As no published research has studied the expression and role of circRNAs in the&#xD;
      pathology and pathogenesis of ALI/ARDS, the investigators aimed to validate the aberrant&#xD;
      expression of circRNAs in ALI/ARDS and explore the potential pathological mechanism in which&#xD;
      circRNAs are involved.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 1, 2017</start_date>
  <completion_date type="Anticipated">December 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2023</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants Receiving Mechanical Ventilation</measure>
    <time_frame>up to 28 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Fraction of Inspired Oxygen (FiO2)/Partial Arterial Oxygen Pressure (PO2)</measure>
    <time_frame>up to 28 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Acute Physiology and Chronic Health Evaluation (APACHE) II Scores</measure>
    <time_frame>up to 28 days</time_frame>
    <description>APACHE II scores range from 0 to 71. A higher values represent a worse outcome</description>
  </primary_outcome>
  <primary_outcome>
    <measure>plasma circRNAs</measure>
    <time_frame>Day 3</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>plasma microRNAs</measure>
    <time_frame>Day 3</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Length of Stay in the ICU</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of Hospital Stay</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Days of Unassisted Ventilation</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Death</measure>
    <time_frame>up to 28</time_frame>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">250</enrollment>
  <condition>Acute Lung Injury</condition>
  <condition>Acute Respiratory Distress Syndrome</condition>
  <arm_group>
    <arm_group_label>ARDS patients</arm_group_label>
    <description>137 patients were enrolled consecutively over a two-year time period (2017-2018) and identified as ARDS prospectively according to the Berlin definitions of the European Society of Intensive Care Medicine and American Thoracic Society on ARDS. Exclusion criteria were an age of less than 18 years, pregnancy, chronic obstructive pulmonary disease according to medical history and failure to obtain informed consent.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy volunteers</arm_group_label>
    <description>Forty healthy volunteers recruited from the general population who had no significant medical history and no medications were categorized as control patients.</description>
  </arm_group>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      ARDS patients and healthy volunteers&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with and without ARDS were screened from Changhai Hospital. Patients were enrolled&#xD;
        consecutively over a 2-year time period (2017-2018). All enrolled patients with ALI met the&#xD;
        American-European Consensus Committee criteria.In addition, healthy individuals were&#xD;
        recruited from the general population.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Clinical diagnosis of ALI/ARDS&#xD;
&#xD;
          -  Informed consent was obtained from either the subjects themselves or from designated&#xD;
             surrogates before enrollment in the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who have chronic lung disease before enrollment.&#xD;
&#xD;
          -  Patients who have severe organ dysfunction, autoimmune diseases and tumor.&#xD;
&#xD;
          -  Women who are pregnant or breast-feeding.&#xD;
&#xD;
          -  Patients who, in the opinion of the Investigator, have any other medical condition&#xD;
             which renders the patient unable to complete the study or which would interfere with&#xD;
             optimal participation in the study or produce significant risk to the patient.&#xD;
&#xD;
          -  Patients participating in or planning to enroll in another clinical trial during the&#xD;
             time of the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Zhao-fan Xia, MD;PHD</last_name>
    <role>Study Director</role>
    <affiliation>Department of Burn Sugery, Changhai Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Zhao-fan Xia, MD;PHD</last_name>
    <phone>86-21-31161821</phone>
    <email>xiazhaofan@163.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Yong Jiang, MD</last_name>
    <phone>86-15721570244</phone>
    <email>jiangyong233@163.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Department of Burn and Trauma Sugery, Changhai Hospital</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200433</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Zhao-fan Xia, MD;PHD</last_name>
      <phone>+862131161821</phone>
      <email>xiazhaofan@163.com</email>
    </contact>
    <contact_backup>
      <last_name>Yong Jiang, MD</last_name>
      <phone>86-15721570244</phone>
      <email>jiangyong233@163.com</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>December 4, 2018</study_first_submitted>
  <study_first_submitted_qc>December 5, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 6, 2018</study_first_posted>
  <last_update_submitted>December 5, 2018</last_update_submitted>
  <last_update_submitted_qc>December 5, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 6, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Changhai Hospital</investigator_affiliation>
    <investigator_full_name>Zhaofan Xia</investigator_full_name>
    <investigator_title>President</investigator_title>
  </responsible_party>
  <keyword>circRNAs</keyword>
  <keyword>microRNAs</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Respiratory Distress Syndrome</mesh_term>
    <mesh_term>Respiratory Distress Syndrome, Newborn</mesh_term>
    <mesh_term>Acute Lung Injury</mesh_term>
    <mesh_term>Lung Injury</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/NCT03766204
org study id: 20181204
nct id: NCT03766204
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Efforts to identify circulating factors that predict severity of acute lung injury/acute
      respiratory distress syndrome（ALI/ARDS）patients is unrevealing. The primary purpose of this
      study is to verify circRNAs and microRNAs might be potential novel ALI/ARDS biomarkers and
      could play roles in pathogenesis of ALI/ARDS.
Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a devastating cause
      of morbidity and mortality characterized by alveolar epithelial and endothelial injury.
      Despite recent advances in pathogenetic mechanisms and therapy strategies of ALI, efforts to
      identify circulating factors that predict severity of ALI/ARDS patients have been
      unrevealing.

      Circular RNAs (circRNAs) are a novel class of endogenous non-coding RNA with a covalently
      continuous closed-loop structure. Compared with traditional linear RNAs, circRNAs are more
      stable and resistant to RNase R due to the absence of 5' caps and 3' tails, which show clear
      advantages in acting as novel molecular biomarkers for many diseases. In addition, many
      studies have reported that circRNAs can bind to microRNAs (miRNAs), acting as "miRNA sponges"
      which are named competitive endogenous RNAs (ceRNAs), and can regulate gene expression at the
      transcriptional or post-transcriptional level. Evidence indicates that circRNAs play
      important roles in cancers and other diseases such as tuberculosis and intervertebral disc
      degeneration. As no published research has studied the expression and role of circRNAs in the
      pathology and pathogenesis of ALI/ARDS, the investigators aimed to validate the aberrant
      expression of circRNAs in ALI/ARDS and explore the potential pathological mechanism in which
      circRNAs are involved.
observational model: Case-Control
time perspective: Prospective
measure: Number of Participants Receiving Mechanical Ventilation
time frame: up to 28 days
measure: Fraction of Inspired Oxygen (FiO2)/Partial Arterial Oxygen Pressure (PO2)
time frame: up to 28 days
measure: Acute Physiology and Chronic Health Evaluation (APACHE) II Scores
time frame: up to 28 days
description: APACHE II scores range from 0 to 71. A higher values represent a worse outcome
measure: plasma circRNAs
time frame: Day 3
measure: plasma microRNAs
time frame: Day 3
measure: Length of Stay in the ICU
time frame: 1 year
measure: Length of Hospital Stay
time frame: 1 year
measure: Days of Unassisted Ventilation
time frame: 1 year
measure: Death
time frame: up to 28
arm group label: ARDS patients
description: 137 patients were enrolled consecutively over a two-year time period (2017-2018) and identified as ARDS prospectively according to the Berlin definitions of the European Society of Intensive Care Medicine and American Thoracic Society on ARDS. Exclusion criteria were an age of less than 18 years, pregnancy, chronic obstructive pulmonary disease according to medical history and failure to obtain informed consent.
arm group label: Healthy volunteers
description: Forty healthy volunteers recruited from the general population who had no significant medical history and no medications were categorized as control patients.
ARDS patients and healthy volunteers
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 100 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Zhao-fan Xia, MD;PHD
role: Study Director
affiliation: Department of Burn Sugery, Changhai Hospital
last name: Zhao-fan Xia, MD;PHD
phone: 86-21-31161821
email: xiazhaofan@163.com
last name: Yong Jiang, MD
phone: 86-15721570244
email: jiangyong233@163.com
facility: 
status: Recruiting
contact: 
contact backup: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Changhai Hospital
investigator full name: Zhaofan Xia
investigator title: President
mesh term: Respiratory Distress Syndrome
mesh term: Respiratory Distress Syndrome, Newborn
mesh term: Acute Lung Injury
mesh term: Lung Injury
sharing ipd: No