<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/NCT03832634</url>
  </required_header>
  <id_info>
    <org_study_id>1703018076</org_study_id>
    <nct_id>NCT03832634</nct_id>
  </id_info>
  <brief_title>Fetal Genome Profiling Via Trophoblast Cells</brief_title>
  <official_title>Fetal Genome Profiling After Non-Invasive Isolation of Trophoblast Cells</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Weill Medical College of Cornell University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Weill Medical College of Cornell 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>
      The objective of this study is to utilize trophoblast cells accumulating in the endocervical&#xD;
      canal at the beginning of pregnancy for non-invasive prenatal testing. If we are able to&#xD;
      validate that trophoblast cells obtained at an early gestational age can be reliably used for&#xD;
      prenatal testing, there is great potential to improve early pregnancy management and&#xD;
      counseling options for potential parents. The target population will be all women between the&#xD;
      age of 18-45 undergoing care at the Center for Reproductive Medicine (CRM) in order to&#xD;
      achieve a pregnancy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The primary purpose of the study is to validate trophoblast retrieval and isolation from the&#xD;
      cervix (TRIC) as a means of reliable non invasive prenatal genetic diagnosis (for both&#xD;
      chromosomal abnormalities, as well as single gene defects).&#xD;
&#xD;
      The study population will be recruited from women, age 18 to 45, presenting to the Center for&#xD;
      Reproductive Medicine (CRM) for medical care with the desire to become pregnant. Patients&#xD;
      that achieve pregnancy will be invited by a physician to participate in the study. If&#xD;
      prospective subjects agree to participate, they will meet with a co-investigator to go&#xD;
      through the informed consent process.&#xD;
&#xD;
      Subjects will undergo a one-time non-invasive collection of trophoblast cells (trophoblast&#xD;
      retrieval and isolation from the cervix, TRIC) at approximately 5-6 weeks of pregnancy as the&#xD;
      experimental procedure for the study. TRIC is performed with ThinPrep kits using a cytobrush,&#xD;
      the same method of Pap smear collection which is a routine part of prenatal care. The fetal&#xD;
      trophoblast cells will then be isolated using immunomagnetic isolation. Once isolated, DNA&#xD;
      fragmentation, fluorescent in situ hybridization (FISH), and single-cell PCR methods will be&#xD;
      utilized to analyze the fetal genome at single nucleotide resolution. Any abnormal results&#xD;
      identified by TRIC will be communicated to the subjects' by their physician in the office who&#xD;
      will counsel them on the potential meaning of the results and recommend follow up testing to&#xD;
      be ordered by their obstetrician to confirm results.&#xD;
&#xD;
      The cellular analysis from TRIC will then be compared to results obtained from CVS,&#xD;
      amniocentesis, preimplantation genetic screening (PGS) and/or preimplantation genetic&#xD;
      diagnosis (PGD) of the transferred embryo(s), or cytogenetic testing of fetal tissue in the&#xD;
      event of miscarriage or pregnancy termination for validation. In the event that a patient&#xD;
      does not undergo any of the aforementioned testing, TRIC results will be compared to birth&#xD;
      outcomes.&#xD;
&#xD;
      Subjects will be followed via medical records through the final outcome of the pregnancy,&#xD;
      whether termination of pregnancy, miscarriage, or live birth. If the pregnancy results in&#xD;
      termination of pregnancy or miscarriage, cytogenetic testing of the fetus will be completed&#xD;
      as standard care with the results compared to those obtained through TRIC testing. If the&#xD;
      pregnancy results in live birth, basic neonatal information will be obtained via medical&#xD;
      records, specifically whether the neonate is diagnosed with a disorder that can be identified&#xD;
      through single gene testing (see attached table).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Lack of personnel and funding resources&#xD;
  </why_stopped>
  <start_date type="Actual">July 2, 2020</start_date>
  <completion_date type="Actual">February 2, 2023</completion_date>
  <primary_completion_date type="Actual">February 14, 2021</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Occurrence of chromosomal anomalies as detected via fetal genome analysis of trophoblast cells</measure>
    <time_frame>6 weeks post pregnancy</time_frame>
    <description>Trophoblast cells isolated from the cervix will be used to detect chromosomal anomalies occurrences as a means of non-invasive prenatal screening.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Occurrence of chromosomal anomalies detected via trophoblast cell analysis as compared to occurrence of chromosomal anomalies detected via preimplantation genetic testing (PGT), chorionic villi sampling (CVS), amniocentesis, or cytogenetic results.</measure>
    <time_frame>16 weeks post pregnancy</time_frame>
    <description>Occurrence of chromosomal anomalies detected via trophoblast cells analysis will be compared to the occurrence of chromosomal anomalies detected via either PGT, CVS, amniocentesis, or cytogenetic which ever is available for validation.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">1</enrollment>
  <condition>Fetal Growth Retardation</condition>
  <arm_group>
    <arm_group_label>Fetal Genome Profiling</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Trophoblast cells will be collected from the cervix approximately 5-6 weeks once pregnancy is achieved.</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Fetal Genome Profiling.</intervention_name>
    <description>Once pregnancy is achieved, patients will undergo non-invasive collection of trophoblast cells (trophoblast retrieval and isolation from the cervix, TRIC) at an early gestational age, approximately 5-6 weeks. The patient will also be screened with blood work for carrier status for genetic conditions.</description>
    <arm_group_label>Fetal Genome Profiling</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Women 18 to 45 who achieve a pregnancy during study time period.&#xD;
&#xD;
          -  If pregnancy result in miscarriage, cytogenetic testing must be completed on the&#xD;
             product of conception.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Women whose cervical sample collection containing inadequate number of trophoblast&#xD;
             cells for analysis.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kangpu Xu, PhD, DVM</last_name>
    <role>Principal Investigator</role>
    <affiliation>Weill Medical College of Cornell University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Weill Cornell Medicine</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>January 9, 2019</study_first_submitted>
  <study_first_submitted_qc>February 5, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 6, 2019</study_first_posted>
  <last_update_submitted>July 31, 2023</last_update_submitted>
  <last_update_submitted_qc>July 31, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fetal Growth Retardation</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/NCT03832634
org study id: 1703018076
nct id: NCT03832634
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The objective of this study is to utilize trophoblast cells accumulating in the endocervical
      canal at the beginning of pregnancy for non-invasive prenatal testing. If we are able to
      validate that trophoblast cells obtained at an early gestational age can be reliably used for
      prenatal testing, there is great potential to improve early pregnancy management and
      counseling options for potential parents. The target population will be all women between the
      age of 18-45 undergoing care at the Center for Reproductive Medicine (CRM) in order to
      achieve a pregnancy.
The primary purpose of the study is to validate trophoblast retrieval and isolation from the
      cervix (TRIC) as a means of reliable non invasive prenatal genetic diagnosis (for both
      chromosomal abnormalities, as well as single gene defects).

      The study population will be recruited from women, age 18 to 45, presenting to the Center for
      Reproductive Medicine (CRM) for medical care with the desire to become pregnant. Patients
      that achieve pregnancy will be invited by a physician to participate in the study. If
      prospective subjects agree to participate, they will meet with a co-investigator to go
      through the informed consent process.

      Subjects will undergo a one-time non-invasive collection of trophoblast cells (trophoblast
      retrieval and isolation from the cervix, TRIC) at approximately 5-6 weeks of pregnancy as the
      experimental procedure for the study. TRIC is performed with ThinPrep kits using a cytobrush,
      the same method of Pap smear collection which is a routine part of prenatal care. The fetal
      trophoblast cells will then be isolated using immunomagnetic isolation. Once isolated, DNA
      fragmentation, fluorescent in situ hybridization (FISH), and single-cell PCR methods will be
      utilized to analyze the fetal genome at single nucleotide resolution. Any abnormal results
      identified by TRIC will be communicated to the subjects' by their physician in the office who
      will counsel them on the potential meaning of the results and recommend follow up testing to
      be ordered by their obstetrician to confirm results.

      The cellular analysis from TRIC will then be compared to results obtained from CVS,
      amniocentesis, preimplantation genetic screening (PGS) and/or preimplantation genetic
      diagnosis (PGD) of the transferred embryo(s), or cytogenetic testing of fetal tissue in the
      event of miscarriage or pregnancy termination for validation. In the event that a patient
      does not undergo any of the aforementioned testing, TRIC results will be compared to birth
      outcomes.

      Subjects will be followed via medical records through the final outcome of the pregnancy,
      whether termination of pregnancy, miscarriage, or live birth. If the pregnancy results in
      termination of pregnancy or miscarriage, cytogenetic testing of the fetus will be completed
      as standard care with the results compared to those obtained through TRIC testing. If the
      pregnancy results in live birth, basic neonatal information will be obtained via medical
      records, specifically whether the neonate is diagnosed with a disorder that can be identified
      through single gene testing (see attached table).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Occurrence of chromosomal anomalies as detected via fetal genome analysis of trophoblast cells
time frame: 6 weeks post pregnancy
description: Trophoblast cells isolated from the cervix will be used to detect chromosomal anomalies occurrences as a means of non-invasive prenatal screening.
measure: Occurrence of chromosomal anomalies detected via trophoblast cell analysis as compared to occurrence of chromosomal anomalies detected via preimplantation genetic testing (PGT), chorionic villi sampling (CVS), amniocentesis, or cytogenetic results.
time frame: 16 weeks post pregnancy
description: Occurrence of chromosomal anomalies detected via trophoblast cells analysis will be compared to the occurrence of chromosomal anomalies detected via either PGT, CVS, amniocentesis, or cytogenetic which ever is available for validation.
arm group label: Fetal Genome Profiling
arm group type: Other
description: Trophoblast cells will be collected from the cervix approximately 5-6 weeks once pregnancy is achieved.
intervention type: Diagnostic Test
intervention name: Fetal Genome Profiling.
description: Once pregnancy is achieved, patients will undergo non-invasive collection of trophoblast cells (trophoblast retrieval and isolation from the cervix, TRIC) at an early gestational age, approximately 5-6 weeks. The patient will also be screened with blood work for carrier status for genetic conditions.
arm group label: Fetal Genome Profiling
criteria: 
gender: Female
gender based: Yes
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Kangpu Xu, PhD, DVM
role: Principal Investigator
affiliation: Weill Medical College of Cornell University
facility: 
country: United States
responsible party type: Sponsor
mesh term: Fetal Growth Retardation
sharing ipd: No