<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/NCT03306719</url>
  </required_header>
  <id_info>
    <org_study_id>1115/2017</org_study_id>
    <nct_id>NCT03306719</nct_id>
  </id_info>
  <brief_title>mtDNA as Novel Biomarker for Intra-amniotic Infection</brief_title>
  <acronym>mtDNA</acronym>
  <official_title>Circulating Cell-free Mitochondrial as a Novel Biomarker for Intra-amniotic Infection in Obstetrics</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University of Vienna</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Medical University of Vienna</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>
      Finding a predictive biomarker for IAI could improve the clinical outcome for the mother and&#xD;
      the neonate. The aim of this study is to quantify the copy number of circulating cell-free&#xD;
      mitochondrial DNA in maternal serum and the placenta compared to controls.the investigators&#xD;
      hypothesise that circulating cell-free mitochondrial DNA levels could help predict the&#xD;
      likelihood of early inflammation in IAI. In addition, mitochondrial DNA could be a promotor&#xD;
      triggering the pathogenesis of systemic inflammation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background: Intra-amniotic infection (IAI) or chorioamnionitis is a common condition seen in&#xD;
      obstetrics leading to labor abnormalities such as uterine atony, postpartum bleeding and&#xD;
      preterm labor (Schrag et al., 2006). Further adverse effects such as perinatal death,&#xD;
      asphyxia, sepsis, pneumonia, respiratory distress and especially neurodevelopmental delay and&#xD;
      cerebral palsy are associated with IAI (Buhimschi et al., 2009; Holzman, Lin, Senagore, &amp;&#xD;
      Chung, 2007). Diagnosing IAI can be challenging due to its very heterogeneous clinical signs,&#xD;
      which are often very insensitive for this condition. Clinical findings such as fever,&#xD;
      tachycardia and maternal leukocytosis leave room for multiple differential diagnoses. During&#xD;
      apoptosis (due to hypoxia, cell damage or infection) the cell membrane integrity is&#xD;
      disturbed, releasing the cytoplasm into the blood circulation. Circulating cell-free&#xD;
      mitochondrial DNA acts as a damage associated molecular pattern (DAMP) by activating the&#xD;
      innate immune system leading to inflammation (Matzinger, 1994). These DAMPs are evolutionary&#xD;
      conserved and have structural similarity to their bacterial ancestor (Zhang et al., 2010).&#xD;
      Therefore, cell-free mitochondria can act as a potent agent triggering the immune system in&#xD;
      an autoimmune manner as well as a biomarker for cell damage due to infection.&#xD;
&#xD;
      Objective: Finding a predictive biomarker for IAI could improve the clinical outcome for the&#xD;
      mother and the neonate. The aim of this study is to quantify the copy number of circulating&#xD;
      cell-free mitochondrial DNA in maternal serum and the placenta compared to controls.&#xD;
      Investigators hypothesize that circulating cell-free mitochondrial DNA levels could help&#xD;
      predict the likelihood of early inflammation in IAI. In addition, mitochondrial DNA could be&#xD;
      a promotor triggering the pathogenesis of systemic inflammation.&#xD;
&#xD;
      Methods: For this study the investiagtors planned 2 groups each consisting of 30 patients.&#xD;
      The control group are pregnant women without IAI. The intervention group will be women with&#xD;
      premature preterm rupture of membranes (pProm), suffering from IAI (meeting the diagnostic&#xD;
      criteria for IAI suggested by the National Institute of Child Health and Human Development&#xD;
      Workshop). 12ml of venous blood will be drawn from a peripheral venous line in addition to&#xD;
      routine blood tests, when the patient arrives at the ward (2 weeks before delivery). A&#xD;
      further 12ml of venous blood will be taken from the peripheral venous line, during delivery&#xD;
      (during delivery). In addition, 12ml of venous blood will be drawn from the placenta&#xD;
      postpartum. In total, 36 ml of blood will be withdrawn in each patient. Circulating cell-free&#xD;
      mitochondrial DNA will be quantified in maternal and placental serum by real time&#xD;
      quantitative PCR and statistical analysis will be performed by non-parametric tests.&#xD;
&#xD;
      Design: Single center, prospective, observational pilot trial.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">April 5, 2017</start_date>
  <completion_date type="Anticipated">December 31, 2018</completion_date>
  <primary_completion_date type="Anticipated">June 30, 2018</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>mtDNA in Plasma</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Preterm Premature Rupture of Membrane</condition>
  <arm_group>
    <arm_group_label>Study Group</arm_group_label>
    <description>The intervention group will be women with premature preterm rupture of membranes (pProm), suffering from IAI</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Group</arm_group_label>
    <description>Pregnant women without IAI</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Blood sampling</intervention_name>
    <description>Serial blood sampling</description>
    <arm_group_label>Control Group</arm_group_label>
    <arm_group_label>Study Group</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Venous blood samples and placental blood samples&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Pregnant women&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Pregnant women 2 weeks before scheduled elective caesarian section at term (control&#xD;
             group)&#xD;
&#xD;
          -  Pregnant women in week 22+0 until week 28+0 who are admitted because of pPROM&#xD;
             (intervention group)&#xD;
&#xD;
          -  aged between 18 and 45 years&#xD;
&#xD;
          -  Provide signed and dated informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Women younger than 18 years&#xD;
&#xD;
          -  No written consent&#xD;
&#xD;
          -  Patients suffering from any autoimmune disease&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Herbert Kiss, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medical University of Vienna</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Herbert Kiss, MD, PhD</last_name>
    <phone>+43140400</phone>
    <email>herbert.kiss@meduniwien.ac.at</email>
  </overall_contact>
  <location>
    <facility>
      <name>Medical University of Vienna</name>
      <address>
        <city>Vienna</city>
        <zip>1090</zip>
        <country>Austria</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Herbert Kiss, MD, PhD</last_name>
      <phone>+43140400</phone>
    </contact>
  </location>
  <location_countries>
    <country>Austria</country>
  </location_countries>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>October 1, 2017</study_first_submitted>
  <study_first_submitted_qc>October 10, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 11, 2017</study_first_posted>
  <last_update_submitted>October 10, 2017</last_update_submitted>
  <last_update_submitted_qc>October 10, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 11, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Medical University of Vienna</investigator_affiliation>
    <investigator_full_name>Herbert Kiss</investigator_full_name>
    <investigator_title>MD, PhD</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fetal Membranes, Premature Rupture</mesh_term>
    <mesh_term>Rupture</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Biomarker pilot trial</ipd_description>
  </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/NCT03306719
org study id: 1115/2017
nct id: NCT03306719
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Finding a predictive biomarker for IAI could improve the clinical outcome for the mother and
      the neonate. The aim of this study is to quantify the copy number of circulating cell-free
      mitochondrial DNA in maternal serum and the placenta compared to controls.the investigators
      hypothesise that circulating cell-free mitochondrial DNA levels could help predict the
      likelihood of early inflammation in IAI. In addition, mitochondrial DNA could be a promotor
      triggering the pathogenesis of systemic inflammation.
Background: Intra-amniotic infection (IAI) or chorioamnionitis is a common condition seen in
      obstetrics leading to labor abnormalities such as uterine atony, postpartum bleeding and
      preterm labor (Schrag et al., 2006). Further adverse effects such as perinatal death,
      asphyxia, sepsis, pneumonia, respiratory distress and especially neurodevelopmental delay and
      cerebral palsy are associated with IAI (Buhimschi et al., 2009; Holzman, Lin, Senagore, &
      Chung, 2007). Diagnosing IAI can be challenging due to its very heterogeneous clinical signs,
      which are often very insensitive for this condition. Clinical findings such as fever,
      tachycardia and maternal leukocytosis leave room for multiple differential diagnoses. During
      apoptosis (due to hypoxia, cell damage or infection) the cell membrane integrity is
      disturbed, releasing the cytoplasm into the blood circulation. Circulating cell-free
      mitochondrial DNA acts as a damage associated molecular pattern (DAMP) by activating the
      innate immune system leading to inflammation (Matzinger, 1994). These DAMPs are evolutionary
      conserved and have structural similarity to their bacterial ancestor (Zhang et al., 2010).
      Therefore, cell-free mitochondria can act as a potent agent triggering the immune system in
      an autoimmune manner as well as a biomarker for cell damage due to infection.

      Objective: Finding a predictive biomarker for IAI could improve the clinical outcome for the
      mother and the neonate. The aim of this study is to quantify the copy number of circulating
      cell-free mitochondrial DNA in maternal serum and the placenta compared to controls.
      Investigators hypothesize that circulating cell-free mitochondrial DNA levels could help
      predict the likelihood of early inflammation in IAI. In addition, mitochondrial DNA could be
      a promotor triggering the pathogenesis of systemic inflammation.

      Methods: For this study the investiagtors planned 2 groups each consisting of 30 patients.
      The control group are pregnant women without IAI. The intervention group will be women with
      premature preterm rupture of membranes (pProm), suffering from IAI (meeting the diagnostic
      criteria for IAI suggested by the National Institute of Child Health and Human Development
      Workshop). 12ml of venous blood will be drawn from a peripheral venous line in addition to
      routine blood tests, when the patient arrives at the ward (2 weeks before delivery). A
      further 12ml of venous blood will be taken from the peripheral venous line, during delivery
      (during delivery). In addition, 12ml of venous blood will be drawn from the placenta
      postpartum. In total, 36 ml of blood will be withdrawn in each patient. Circulating cell-free
      mitochondrial DNA will be quantified in maternal and placental serum by real time
      quantitative PCR and statistical analysis will be performed by non-parametric tests.

      Design: Single center, prospective, observational pilot trial.
observational model: Case-Control
time perspective: Prospective
measure: mtDNA in Plasma
time frame: through study completion, an average of 1 year
arm group label: Study Group
description: The intervention group will be women with premature preterm rupture of membranes (pProm), suffering from IAI
arm group label: Control Group
description: Pregnant women without IAI
intervention type: Biological
intervention name: Blood sampling
description: Serial blood sampling
arm group label: Control Group
arm group label: Study Group
Venous blood samples and placental blood samples
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: No
last name: Herbert Kiss, MD, PhD
role: Principal Investigator
affiliation: Medical University of Vienna
last name: Herbert Kiss, MD, PhD
phone: +43140400
email: herbert.kiss@meduniwien.ac.at
facility: 
status: Recruiting
contact: 
country: Austria
responsible party type: Principal Investigator
investigator affiliation: Medical University of Vienna
investigator full name: Herbert Kiss
investigator title: MD, PhD
mesh term: Fetal Membranes, Premature Rupture
mesh term: Rupture
sharing ipd: No
ipd description: Biomarker pilot trial