<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/NCT01686685</url>
  </required_header>
  <id_info>
    <org_study_id>begin1HMO-CTIL</org_study_id>
    <nct_id>NCT01686685</nct_id>
  </id_info>
  <brief_title>Correlation of CXCR4 Expression in Premature Infants With a Diagnosis of Autism at 24 Months</brief_title>
  <acronym>ASD-CXCR4</acronym>
  <official_title>Study of Correlation Between Expression of Proteins That Are Essential for Embryonic Brain Development and Neurodevelopmental Outcomes at 2 Years of Age in Premature Infants.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hadassah Medical Organization</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hadassah Medical Organization</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Preterm children are at increased risk for autism spectrum disorders, with an estimated rate&#xD;
      of 10%. In the US, about 1 in 8 pregnancies ends with a premature birth. Therefore,&#xD;
      individuals with ASD who were born prematurely form a substantial body of children diagnosed&#xD;
      with ASD.&#xD;
&#xD;
      Premature birth confers an insult to the newborn at a neurologically vulnerable stage.&#xD;
      Prematurity associated changes in oxygen tension can be detrimental to developing organs, the&#xD;
      brain being one of the most rapidly developing organs in the second half of the pregnancy.&#xD;
      Changes in oxygen tension mediate activation of proteins that change the course of cell&#xD;
      development.&#xD;
&#xD;
      In this study, we plan to measure changes in the expression of 3 proteins that may be&#xD;
      affected by changes in oxygen level at birth. We will study the interaction between the&#xD;
      proteins' levels in the first few days after premature birth with a diagnosis of ASD at 2&#xD;
      years of age. The proteins are:&#xD;
&#xD;
        1. VEGF (Vascular Endothelial Growth Factor), a protein that takes part in creating new&#xD;
           blood vessels during embryonic development.&#xD;
&#xD;
        2. Hypoxia-inducible factor -1(HIF-1), a key protein that coordinates expression of&#xD;
           different genes, many with developmentally critical functions.&#xD;
&#xD;
        3. CXCR4, a cell surface protein that is activated by SDF-1. SDF- 1 is a molecule that&#xD;
           regulates migration of cells to their target destination during embryonic life. CXCR4 is&#xD;
           expressed in areas of the brain and on cells that are known to be associated with ASD.&#xD;
&#xD;
      We hypothesis that changes in oxygen tension in premature babies initiates a cascade of&#xD;
      events that lead to changes in cell mobility via abnormal CXCR4 expression. This change leads&#xD;
      to abnormal neurodevelopment.&#xD;
&#xD;
      The investigators' primary aim is to find if there is a correlation between postnatal levels&#xD;
      of expression of HIF-1, CXCR4 and VEGF and a diagnosis of autism at age 24 months. The&#xD;
      investigators' secondary aim is to find if there is a correlation between postnatal levels of&#xD;
      expression of HIF-1, CXCR4 and VEGF and a language or neurocognitive delay.&#xD;
&#xD;
      Methods:&#xD;
&#xD;
        1. Premature babies will be recruited in the first day post delivery.&#xD;
&#xD;
        2. Blood samples will be collected at 3 time points during their hospitalization, and the&#xD;
           expression of HIF-1, CXCR4 and VEGF will be determined.&#xD;
&#xD;
        3. Infants will undergo a complete developmental evaluation at 18-24 months of age .&#xD;
&#xD;
        4. Postnatal levels of HIF, CXCR4 and VEGF will be plotted against the results of the&#xD;
           developmental evaluation.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 2013</start_date>
  <completion_date type="Actual">April 1, 2018</completion_date>
  <primary_completion_date type="Actual">April 2018</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Diagnosis of ASD at 24 months corrected age</measure>
    <time_frame>30 months</time_frame>
    <description>Participants will be screened at 18 and 24 months for autism using the MCHAT questionnaire all positive screens will be referred for a complete developmental evaluation by child psychologist and developmental pediatrician: History, assessment (ADOS) and clinical judgement based on DSM criteria</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Language or cognitive delay at 24 months corrected age</measure>
    <time_frame>30 months</time_frame>
    <description>Participants will be screened by questionnaires at 18 and 24 months. all positive screens will be referred for a full developmental evaluation using the Mullen Scales of Early learning</description>
  </secondary_outcome>
  <enrollment type="Anticipated">400</enrollment>
  <condition>Autism Spectrum Disorder</condition>
  <condition>Complication of Prematurity</condition>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      blood samples. expression of proteins or RNA will be determined from the blood.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        neonatal intensive care units newborn ward&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Parents gave informed consent approved by the Institutional Review Board&#xD;
&#xD;
          -  Gestational week 28-34 as determined by an ultrasound during the first trimester&#xD;
&#xD;
          -  Singleton or twin pregnancy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Major anatomical abnormalities as detected on prenatal US&#xD;
&#xD;
          -  Genetic syndrome as detected by prenatal US, MRI or chorioamniocentesis&#xD;
&#xD;
          -  Obvious anatomical abnormalities or dysmorphic features detected on physical&#xD;
             examination immediately following birth&#xD;
&#xD;
          -  Triplet pregnancy&#xD;
&#xD;
          -  Mother known or suspected to consume alcohol or illegal drugs during pregnancy&#xD;
&#xD;
          -  Mother took medications during pregnancy that are known to have adverse affects on&#xD;
             development (e.g. anti-epileptics)&#xD;
&#xD;
          -  Family history of genetic syndrome related to developmental delays, that was not ruled&#xD;
             out during current pregnancy (e.g. sibling with Tuberous Sclerosis or fragile X)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Hour</minimum_age>
    <maximum_age>1 Day</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michal Begin, MD</last_name>
    <role>Study Director</role>
    <affiliation>Hadassah HMO</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hadassah Medical Center</name>
      <address>
        <city>Jerusalem</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Israel</country>
  </location_countries>
  <verification_date>September 2012</verification_date>
  <study_first_submitted>September 13, 2012</study_first_submitted>
  <study_first_submitted_qc>September 13, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 18, 2012</study_first_posted>
  <last_update_submitted>April 11, 2018</last_update_submitted>
  <last_update_submitted_qc>April 11, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">April 12, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>ASD</keyword>
  <keyword>autism</keyword>
  <keyword>prematurity</keyword>
  <keyword>oxygen-dependant gene activation</keyword>
  <keyword>CXCR4</keyword>
  <keyword>Language delay</keyword>
  <keyword>Cognitive delay</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Premature Birth</mesh_term>
    <mesh_term>Autistic Disorder</mesh_term>
    <mesh_term>Autism Spectrum Disorder</mesh_term>
  </condition_browse>
  <!-- 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/NCT01686685
org study id: begin1HMO-CTIL
nct id: NCT01686685
lead sponsor: 
has dmc: No
Preterm children are at increased risk for autism spectrum disorders, with an estimated rate
      of 10%. In the US, about 1 in 8 pregnancies ends with a premature birth. Therefore,
      individuals with ASD who were born prematurely form a substantial body of children diagnosed
      with ASD.

      Premature birth confers an insult to the newborn at a neurologically vulnerable stage.
      Prematurity associated changes in oxygen tension can be detrimental to developing organs, the
      brain being one of the most rapidly developing organs in the second half of the pregnancy.
      Changes in oxygen tension mediate activation of proteins that change the course of cell
      development.

      In this study, we plan to measure changes in the expression of 3 proteins that may be
      affected by changes in oxygen level at birth. We will study the interaction between the
      proteins' levels in the first few days after premature birth with a diagnosis of ASD at 2
      years of age. The proteins are:

        1. VEGF (Vascular Endothelial Growth Factor), a protein that takes part in creating new
           blood vessels during embryonic development.

        2. Hypoxia-inducible factor -1(HIF-1), a key protein that coordinates expression of
           different genes, many with developmentally critical functions.

        3. CXCR4, a cell surface protein that is activated by SDF-1. SDF- 1 is a molecule that
           regulates migration of cells to their target destination during embryonic life. CXCR4 is
           expressed in areas of the brain and on cells that are known to be associated with ASD.

      We hypothesis that changes in oxygen tension in premature babies initiates a cascade of
      events that lead to changes in cell mobility via abnormal CXCR4 expression. This change leads
      to abnormal neurodevelopment.

      The investigators' primary aim is to find if there is a correlation between postnatal levels
      of expression of HIF-1, CXCR4 and VEGF and a diagnosis of autism at age 24 months. The
      investigators' secondary aim is to find if there is a correlation between postnatal levels of
      expression of HIF-1, CXCR4 and VEGF and a language or neurocognitive delay.

      Methods:

        1. Premature babies will be recruited in the first day post delivery.

        2. Blood samples will be collected at 3 time points during their hospitalization, and the
           expression of HIF-1, CXCR4 and VEGF will be determined.

        3. Infants will undergo a complete developmental evaluation at 18-24 months of age .

        4. Postnatal levels of HIF, CXCR4 and VEGF will be plotted against the results of the
           developmental evaluation.
observational model: Cohort
time perspective: Prospective
measure: Diagnosis of ASD at 24 months corrected age
time frame: 30 months
description: Participants will be screened at 18 and 24 months for autism using the MCHAT questionnaire all positive screens will be referred for a complete developmental evaluation by child psychologist and developmental pediatrician: History, assessment (ADOS) and clinical judgement based on DSM criteria
measure: Language or cognitive delay at 24 months corrected age
time frame: 30 months
description: Participants will be screened by questionnaires at 18 and 24 months. all positive screens will be referred for a full developmental evaluation using the Mullen Scales of Early learning
blood samples. expression of proteins or RNA will be determined from the blood.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 1 Hour
maximum age: 1 Day
healthy volunteers: Accepts Healthy Volunteers
last name: Michal Begin, MD
role: Study Director
affiliation: Hadassah HMO
facility: 
country: Israel
responsible party type: Sponsor
mesh term: Premature Birth
mesh term: Autistic Disorder
mesh term: Autism Spectrum Disorder