xml: <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/NCT06031714</url>
    </required_header>
    <id_info>
      <org_study_id>APHP230731</org_study_id>
      <secondary_id>2023-A00404-41</secondary_id>
      <nct_id>NCT06031714</nct_id>
    </id_info>
    <brief_title>Fetal Cell Receptors Repertoire</brief_title>
    <acronym>MoreCCR</acronym>
    <official_title>&quot;Study of CCR Receptor Overexpression in Fetal Microchimeric Cells: Proof of Concept Before a Potential Clinical Trial&quot;</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Assistance Publique - Hôpitaux de Paris</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Assistance Publique - Hôpitaux de Paris</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 purpose of this study is to describe the transcriptomic profile of foetal cells in&#xD;
        post-partum and more specifically to determine which chemokine receptors are overexpressed in&#xD;
        foetal cells in post-partum women with wounds To do so, we will isolate foetal cells from the&#xD;
        peripheral blood of healthy controls post partum women as well as from post partum women with&#xD;
        skin ulcers and then perform RNA sequencing.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The aim of regenerative medicine is to repair damaged tissue using different sources of&#xD;
        autologous or heterologous stem cells. These cells are then cultured to achieve amplification&#xD;
        and differentiation adapted to the cell type of the organ to be repaired. These methods are&#xD;
        potentially effective, but involve risks and limitations, in particular the risks of genetic&#xD;
        modifications during culture or contamination by residual ES or iPS cells. Immunosuppressive&#xD;
        treatment is also necessary if the source of stem cells is allogeneic. Finally, implantation&#xD;
        of this type of culture may also be unsuccessful.&#xD;
  &#xD;
        Our team is seeking for an alternative strategy to these methods. This relies on the presence&#xD;
        of a niche of foetal cells transferred during pregnancy that persist after delivery. In fact,&#xD;
        all mammalian pregnancies lead to foetal-maternal cell transfer. The foetal cells&#xD;
        -transferred to the maternal circulation- contain different types of stem cells that will&#xD;
        remain in the maternal bone marrow and persist there for the rest of the mother's life. The&#xD;
        team has shown that in the event of cutaneous wounds in post-gestational mice, a population&#xD;
        of CD11b+ CD34+ CD31+ foetal progenitors was recruited from the maternal bone marrow to the&#xD;
        cutaneous granulation tissue. These cells over-express the chemokine receptor CCR2 compared&#xD;
        with their adult counterparts. Consequently, the injection of low, so-called physiological,&#xD;
        doses of the CCL2 chemokine subcutaneously into wounds accelerates normal wound healing and&#xD;
        restores delayed healing in two pathological models. This pro-healing activity is linked to&#xD;
        the specific recruitment of foetal stem cells to the site of injected wounds. These low doses&#xD;
        of CCL2 never affected wound healing in virgin mice, confirming that this type of treatment&#xD;
        does not alter the homeostasis of adult cells.&#xD;
  &#xD;
        The therapeutic strategy we are proposing, entitled &quot;natural stem therapy&quot;, is based on this&#xD;
        reservoir of foetal stem cells present in every woman who has had at least one pregnancy,&#xD;
        i.e. more than 60% of adult women in western countries. In order to test the validity of this&#xD;
        concept, it is important to ascertain the pathways by which foetal cells are chemoattracted&#xD;
        in the human species, in particular the CCR2/CCL2 pathway.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">November 1, 2023</start_date>
    <completion_date type="Anticipated">November 1, 2026</completion_date>
    <primary_completion_date type="Anticipated">April 1, 2026</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Other</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Transcriptomic analysis by single cell sequencing</measure>
      <time_frame>Month 1 up to month 5</time_frame>
      <description>Transcriptomic analysis by single cell RNA sequencing (Smart-seq3 protocol) of fetal cells sorted from peripheral blood</description>
    </primary_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">130</enrollment>
    <condition>Venous Ulcer</condition>
    <condition>Sickle Cell Ulcer</condition>
    <condition>Diabetic Ulcer</condition>
    <condition>Post-partum Women</condition>
    <arm_group>
      <arm_group_label>Patients</arm_group_label>
      <arm_group_type>Other</arm_group_type>
      <description>Patients who have had at least one pregnancy and have a venous ulcer, diabetic ulcer or sickle cell ulcer</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Patient &quot;Controls group &quot;</arm_group_label>
      <arm_group_type>Other</arm_group_type>
      <description>Post-partum women of the same age but without wounds.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Children</arm_group_label>
      <arm_group_type>Other</arm_group_type>
    </arm_group>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Saliva sampling</intervention_name>
      <description>HLA genotyping. The technique should allow to identify, for children's, a paternal HLA antigen not shared with the mothers.</description>
      <arm_group_label>Children</arm_group_label>
      <arm_group_label>Patient &quot;Controls group &quot;</arm_group_label>
      <arm_group_label>Patients</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Blood sampling</intervention_name>
      <description>Maternal Blood samples will be incubated with the appropriate antibody, targeting the microchimeric fetal cells of each patient, as well as with a cell viability marker (DAPI). The samples were then be processed through the BD FACS Aria III to sort the fetal cells,&#xD;
  The following steps - RNA extraction, quality control, retrotranscription, preparation of the library, sequencing and transcriptomic analysis - will be carried out according to the Smart-seq3 protocol. The data will be sent for in-depth analysis and confirmation of the results. Additional functional experiments may also be carried out.</description>
      <arm_group_label>Patient &quot;Controls group &quot;</arm_group_label>
      <arm_group_label>Patients</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Interviews</intervention_name>
      <description>V2 and/or V3</description>
      <arm_group_label>Patient &quot;Controls group &quot;</arm_group_label>
      <arm_group_label>Patients</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Clinical examination</intervention_name>
      <description>V2 and/or V3</description>
      <arm_group_label>Patient &quot;Controls group &quot;</arm_group_label>
      <arm_group_label>Patients</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
          Common criteria :&#xD;
  &#xD;
            -  Adult women,&#xD;
  &#xD;
            -  Post-partum: having been pregnant for any length of time,&#xD;
  &#xD;
            -  Having signed a free and informed consent form,&#xD;
  &#xD;
            -  Primiparous or multiparous,&#xD;
  &#xD;
            -  Affiliated to a health insurance&#xD;
  &#xD;
          Patients :&#xD;
  &#xD;
          - Patients with venous ulcers, diabetes or sickle cell disease,&#xD;
  &#xD;
          Control group patients :&#xD;
  &#xD;
            -  Volunteers,&#xD;
  &#xD;
            -  Age-matched,&#xD;
  &#xD;
            -  Without skin ulcers.&#xD;
  &#xD;
          There are no specific criteria for children.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Minors (for patients)&#xD;
  &#xD;
            -  Under court protection, curatorship, guardianship (for patients)&#xD;
  &#xD;
            -  Immunocompromised patients for any reason whatsoever&#xD;
  &#xD;
            -  Refusal of consent&#xD;
  &#xD;
            -  Refusal of blood and/or saliva samples for themselves or a member of their family&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>N/A</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Sélim ARACTINGI, MD, PHD</last_name>
      <role>Study Director</role>
      <affiliation>Dermatology unit, Cochin Hospital - APHP</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Sélim ARACTINGI, MD, PHD</last_name>
      <phone>00 33 1 58 41 18 13</phone>
      <email>selim.aractingi@aphp.fr</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Marie Benhammani-Godard</last_name>
      <phone>00 33 1 58 41 11 90</phone>
      <email>marie.godard@aphp.fr</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Dermatology unit - Cochin Hospital - APHP</name>
        <address>
          <city>Paris</city>
          <state>Ile De France</state>
          <zip>75014</zip>
          <country>France</country>
        </address>
      </facility>
      <contact>
        <last_name>Sélim ARACTINGI, MD, PhD</last_name>
        <phone>0033 1 58 41 18 13</phone>
        <email>selim.aractingi@aphp.fr</email>
      </contact>
      <investigator>
        <last_name>Bénédicte OULES, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>France</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>September 4, 2023</study_first_submitted>
    <study_first_submitted_qc>September 8, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 11, 2023</study_first_posted>
    <last_update_submitted>September 8, 2023</last_update_submitted>
    <last_update_submitted_qc>September 8, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 11, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Microchimerism</keyword>
    <keyword>Foetal stem cells</keyword>
    <keyword>Receptors</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Varicose Ulcer</mesh_term>
      <mesh_term>Ulcer</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Undecided</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06031714
  org study id: APHP230731
  secondary id: 2023-A00404-41
  nct id: NCT06031714
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The purpose of this study is to describe the transcriptomic profile of foetal cells in
        post-partum and more specifically to determine which chemokine receptors are overexpressed in
        foetal cells in post-partum women with wounds To do so, we will isolate foetal cells from the
        peripheral blood of healthy controls post partum women as well as from post partum women with
        skin ulcers and then perform RNA sequencing.
  The aim of regenerative medicine is to repair damaged tissue using different sources of
        autologous or heterologous stem cells. These cells are then cultured to achieve amplification
        and differentiation adapted to the cell type of the organ to be repaired. These methods are
        potentially effective, but involve risks and limitations, in particular the risks of genetic
        modifications during culture or contamination by residual ES or iPS cells. Immunosuppressive
        treatment is also necessary if the source of stem cells is allogeneic. Finally, implantation
        of this type of culture may also be unsuccessful.
  
        Our team is seeking for an alternative strategy to these methods. This relies on the presence
        of a niche of foetal cells transferred during pregnancy that persist after delivery. In fact,
        all mammalian pregnancies lead to foetal-maternal cell transfer. The foetal cells
        -transferred to the maternal circulation- contain different types of stem cells that will
        remain in the maternal bone marrow and persist there for the rest of the mother's life. The
        team has shown that in the event of cutaneous wounds in post-gestational mice, a population
        of CD11b+ CD34+ CD31+ foetal progenitors was recruited from the maternal bone marrow to the
        cutaneous granulation tissue. These cells over-express the chemokine receptor CCR2 compared
        with their adult counterparts. Consequently, the injection of low, so-called physiological,
        doses of the CCL2 chemokine subcutaneously into wounds accelerates normal wound healing and
        restores delayed healing in two pathological models. This pro-healing activity is linked to
        the specific recruitment of foetal stem cells to the site of injected wounds. These low doses
        of CCL2 never affected wound healing in virgin mice, confirming that this type of treatment
        does not alter the homeostasis of adult cells.
  
        The therapeutic strategy we are proposing, entitled "natural stem therapy", is based on this
        reservoir of foetal stem cells present in every woman who has had at least one pregnancy,
        i.e. more than 60% of adult women in western countries. In order to test the validity of this
        concept, it is important to ascertain the pathways by which foetal cells are chemoattracted
        in the human species, in particular the CCR2/CCL2 pathway.
  allocation: Non-Randomized
  intervention model: Parallel Assignment
  primary purpose: Other
  masking: None (Open Label)
  measure: Transcriptomic analysis by single cell sequencing
  time frame: Month 1 up to month 5
  description: Transcriptomic analysis by single cell RNA sequencing (Smart-seq3 protocol) of fetal cells sorted from peripheral blood
  arm group label: Patients
  arm group type: Other
  description: Patients who have had at least one pregnancy and have a venous ulcer, diabetic ulcer or sickle cell ulcer
  arm group label: Patient "Controls group "
  arm group type: Other
  description: Post-partum women of the same age but without wounds.
  arm group label: Children
  arm group type: Other
  intervention type: Other
  intervention name: Saliva sampling
  description: HLA genotyping. The technique should allow to identify, for children's, a paternal HLA antigen not shared with the mothers.
  arm group label: Children
  arm group label: Patient "Controls group "
  arm group label: Patients
  intervention type: Other
  intervention name: Blood sampling
  description: Maternal Blood samples will be incubated with the appropriate antibody, targeting the microchimeric fetal cells of each patient, as well as with a cell viability marker (DAPI). The samples were then be processed through the BD FACS Aria III to sort the fetal cells,
  The following steps - RNA extraction, quality control, retrotranscription, preparation of the library, sequencing and transcriptomic analysis - will be carried out according to the Smart-seq3 protocol. The data will be sent for in-depth analysis and confirmation of the results. Additional functional experiments may also be carried out.
  arm group label: Patient "Controls group "
  arm group label: Patients
  intervention type: Other
  intervention name: Interviews
  description: V2 and/or V3
  arm group label: Patient "Controls group "
  arm group label: Patients
  intervention type: Other
  intervention name: Clinical examination
  description: V2 and/or V3
  arm group label: Patient "Controls group "
  arm group label: Patients
  criteria: 
  gender: All
  minimum age: N/A
  maximum age: N/A
  healthy volunteers: Accepts Healthy Volunteers
  last name: Sélim ARACTINGI, MD, PHD
  role: Study Director
  affiliation: Dermatology unit, Cochin Hospital - APHP
  last name: Sélim ARACTINGI, MD, PHD
  phone: 00 33 1 58 41 18 13
  email: selim.aractingi@aphp.fr
  last name: Marie Benhammani-Godard
  phone: 00 33 1 58 41 11 90
  email: marie.godard@aphp.fr
  facility: 
  contact: 
  investigator: 
  country: France
  responsible party type: Sponsor
  mesh term: Varicose Ulcer
  mesh term: Ulcer
  sharing ipd: Undecided