<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/NCT03258125</url>
  </required_header>
  <id_info>
    <org_study_id>miR-452PE</org_study_id>
    <nct_id>NCT03258125</nct_id>
  </id_info>
  <brief_title>miRNA-452 in Patients With Preeclampsia and Its Correlation With MMP-9</brief_title>
  <official_title>Expression of miRNA-452 in Patients With Early Onset Preeclampsia and Its Correlation With MMP-9</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assiut University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assiut University</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>
      Preeclampsia is a pregnancy related disease characterized by the new onset of hypertension&#xD;
      and proteinuria after 20 weeks of gestation in previously normotensive women. PE is one of&#xD;
      the most challenging diseases in obstetrics worldwide that affects 2-8 % of pregnancies&#xD;
      causing both morbidity and mortality of both mother and fetus.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The etiology and pathophysiology of preeclampsia are still unclear but the impaired invasive&#xD;
      ability of the trophoblast cells of the placenta and vascular endothelial cell damage are the&#xD;
      main two factors. The invasiveness of trophoblast cells depends on the production of&#xD;
      proteases, particularly matrix metalloproteinases (MMP). MMPs are a family of 24 zinc&#xD;
      dependent endopeptidases capable of degrading extra cellular matrix components. MMP-9 plays&#xD;
      an important role in placental invasion and implantation.&#xD;
&#xD;
      MicroRNAs (miRs) are a class of small (19-24 nucleotides in length), single-stranded,&#xD;
      non-protein-coding RNAs, which suppress translation or promote the degradation of target&#xD;
      messenger RNAs (mRNAs) and thus play an important role in the regulation of cell&#xD;
      proliferation, differentiation, apoptosis and even development of cancer.&#xD;
&#xD;
      The role of miRNA in preeclampsia pathogenesis has been investigated in a number of studies.&#xD;
      One of the target areas of the miRNAs that forms a link with preeclampsia pathogenesis is the&#xD;
      dysregulation of trophoblast differentiation, proliferation, and invasion; this occurs during&#xD;
      early pregnancy and leads to the development of preeclampsia; a range of miRNAs have been&#xD;
      confirmed to play pivotal roles in these processes by targeting a number of different genes.&#xD;
&#xD;
      MiR-452 is a newly discovered cancer related type of miRNA that was shown to be involved in&#xD;
      invasion process where it was upregulated in certain types of cancer such as blad¬der cancer,&#xD;
      urothelial carcinoma, and hepatocellular carcinoma and was found to be significantly&#xD;
      decreased in other types of cancer such as non-small cell lung cancer , glioma, prostate&#xD;
      cancer and Gastric cell cancer.&#xD;
&#xD;
      Based on these previous studies which demonstrate the effect of miR-452 in invasion process&#xD;
      of cancer cells either by stimulation or inhibition and that preeclampsia is a disease of&#xD;
      impaired placental invasion in which MMP-9 play an important role, we will investigate the&#xD;
      placental tissues expression changes of miR-452 which is not studied yet in early onset&#xD;
      preeclampsia patients compared to control and try to find a possible mechanism by which it&#xD;
      act on placental invasion by measuring expression level of MMP-9 and making correlation&#xD;
      between them. The results of this study will provide experimental and theo¬retical basis for&#xD;
      clinical prediction, prevention and treatment of preeclampsia.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 1, 2019</start_date>
  <completion_date type="Actual">June 1, 2020</completion_date>
  <primary_completion_date type="Actual">April 1, 2020</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>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Expression of miRNA-452 and MMP-9.</measure>
    <time_frame>one year</time_frame>
    <description>real time polymerase chain reaction</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Differences in placental and neonatal weight between the two groups</measure>
    <time_frame>one year</time_frame>
    <description>weight the placenta and fetus in kilograms</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">50</enrollment>
  <condition>Preeclampsia</condition>
  <arm_group>
    <arm_group_label>severe EOPE</arm_group_label>
    <description>EOPE: PE starting before 34 weeks gestation Severe PE (Blood pressure more than 160/ 110 mm Hg on 2 occasions 2 hours to 2 weeks apart and proteinuria ( 24-hour urine protein &gt;2000 mg/d).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>control</arm_group_label>
    <description>Healthy Pregnant women who come for termination of pregnancy by vaginal delivery or CS between 28-34 weeks gestational age.</description>
  </arm_group>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>real time PCR (rPCR)</intervention_name>
    <description>A villus tissue (2.5 cm * 2.5 cm * 2.5 cm) will be cut off immediately from the center of placenta, avoiding the area of infarction, bleeding or calcification. After being washed with normal saline, the tissue will be preserved in liquid nitro¬gen at once for subsequent detection of miR-452 and MMP-9 expression by real time PCR (r-PCR). During this procedure total RNA will be extracted including miR-452 and mRNA of MMP-9. Then by reverse transcriptase RNA will be converted into DNA which will be amplification during the PCR, i.e. in real-time, and not at its end, as in conventional PCR. Expression of miR-452 and MMP-9 will be estimated and correlated with each other.</description>
    <arm_group_label>control</arm_group_label>
    <arm_group_label>severe EOPE</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Pregnant women who come for termination of pregnancy by vaginal delivery or CS between&#xD;
        28-34 weaks gestational age in Assiut university maternity hospital in the age range of&#xD;
        18-40 years.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Pregnant women who come for termination of pregnancy by vaginal delivery or CS between&#xD;
             28-34 weaks gestational age in Assiut university maternity hospital in the age range&#xD;
             of 18-40 years.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  1) Diabetes mellitus 2) Chronic hypertension 3) Nephropathy 4) Acute or chronic&#xD;
             infectious diseases or other chronic illness 5) Twins pregnancy 6) Anti phospholipid&#xD;
             antibody syndrome 7) PE complicated with eclampsia, DIC or HELP syndrome&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>pregnant women coming for delivery.</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ahmed Abbas, MD</last_name>
    <role>Study Director</role>
    <affiliation>Assiut University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Faculty of Medicine</name>
      <address>
        <city>Assiut</city>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>August 20, 2017</study_first_submitted>
  <study_first_submitted_qc>August 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 23, 2017</study_first_posted>
  <last_update_submitted>June 23, 2020</last_update_submitted>
  <last_update_submitted_qc>June 23, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 24, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Assiut University</investigator_affiliation>
    <investigator_full_name>FYAli</investigator_full_name>
    <investigator_title>principal investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pre-Eclampsia</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/NCT03258125
org study id: miR-452PE
nct id: NCT03258125
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Preeclampsia is a pregnancy related disease characterized by the new onset of hypertension
      and proteinuria after 20 weeks of gestation in previously normotensive women. PE is one of
      the most challenging diseases in obstetrics worldwide that affects 2-8 % of pregnancies
      causing both morbidity and mortality of both mother and fetus.
The etiology and pathophysiology of preeclampsia are still unclear but the impaired invasive
      ability of the trophoblast cells of the placenta and vascular endothelial cell damage are the
      main two factors. The invasiveness of trophoblast cells depends on the production of
      proteases, particularly matrix metalloproteinases (MMP). MMPs are a family of 24 zinc
      dependent endopeptidases capable of degrading extra cellular matrix components. MMP-9 plays
      an important role in placental invasion and implantation.

      MicroRNAs (miRs) are a class of small (19-24 nucleotides in length), single-stranded,
      non-protein-coding RNAs, which suppress translation or promote the degradation of target
      messenger RNAs (mRNAs) and thus play an important role in the regulation of cell
      proliferation, differentiation, apoptosis and even development of cancer.

      The role of miRNA in preeclampsia pathogenesis has been investigated in a number of studies.
      One of the target areas of the miRNAs that forms a link with preeclampsia pathogenesis is the
      dysregulation of trophoblast differentiation, proliferation, and invasion; this occurs during
      early pregnancy and leads to the development of preeclampsia; a range of miRNAs have been
      confirmed to play pivotal roles in these processes by targeting a number of different genes.

      MiR-452 is a newly discovered cancer related type of miRNA that was shown to be involved in
      invasion process where it was upregulated in certain types of cancer such as blad¬der cancer,
      urothelial carcinoma, and hepatocellular carcinoma and was found to be significantly
      decreased in other types of cancer such as non-small cell lung cancer , glioma, prostate
      cancer and Gastric cell cancer.

      Based on these previous studies which demonstrate the effect of miR-452 in invasion process
      of cancer cells either by stimulation or inhibition and that preeclampsia is a disease of
      impaired placental invasion in which MMP-9 play an important role, we will investigate the
      placental tissues expression changes of miR-452 which is not studied yet in early onset
      preeclampsia patients compared to control and try to find a possible mechanism by which it
      act on placental invasion by measuring expression level of MMP-9 and making correlation
      between them. The results of this study will provide experimental and theo¬retical basis for
      clinical prediction, prevention and treatment of preeclampsia.
observational model: Case-Control
time perspective: Retrospective
measure: Expression of miRNA-452 and MMP-9.
time frame: one year
description: real time polymerase chain reaction
measure: Differences in placental and neonatal weight between the two groups
time frame: one year
description: weight the placenta and fetus in kilograms
arm group label: severe EOPE
description: EOPE: PE starting before 34 weeks gestation Severe PE (Blood pressure more than 160/ 110 mm Hg on 2 occasions 2 hours to 2 weeks apart and proteinuria ( 24-hour urine protein >2000 mg/d).
arm group label: control
description: Healthy Pregnant women who come for termination of pregnancy by vaginal delivery or CS between 28-34 weeks gestational age.
intervention type: Genetic
intervention name: real time PCR (rPCR)
description: A villus tissue (2.5 cm * 2.5 cm * 2.5 cm) will be cut off immediately from the center of placenta, avoiding the area of infarction, bleeding or calcification. After being washed with normal saline, the tissue will be preserved in liquid nitro¬gen at once for subsequent detection of miR-452 and MMP-9 expression by real time PCR (r-PCR). During this procedure total RNA will be extracted including miR-452 and mRNA of MMP-9. Then by reverse transcriptase RNA will be converted into DNA which will be amplification during the PCR, i.e. in real-time, and not at its end, as in conventional PCR. Expression of miR-452 and MMP-9 will be estimated and correlated with each other.
arm group label: control
arm group label: severe EOPE
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Female
gender based: Yes
gender description: pregnant women coming for delivery.
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Ahmed Abbas, MD
role: Study Director
affiliation: Assiut University
facility: 
country: Egypt
responsible party type: Principal Investigator
investigator affiliation: Assiut University
investigator full name: FYAli
investigator title: principal investigator
mesh term: Pre-Eclampsia
sharing ipd: No