<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/NCT03302390</url>
  </required_header>
  <id_info>
    <org_study_id>1015909</org_study_id>
    <secondary_id>5R01AR063091</secondary_id>
    <nct_id>NCT03302390</nct_id>
  </id_info>
  <brief_title>Role of Chemokine and Chemokine Receptor in Psoriasis</brief_title>
  <official_title>Role of Chemokine and Chemokine Receptor in Psoriasis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, Davis</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institutes of Health (NIH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of California, Davis</source>
  <oversight_info>
    <has_dmc>Yes</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>
      This study aims to elucidate the role of Chemokine and chemokine receptor in the pathogenesis&#xD;
      of Psoriasis by using human psoriasis skin xenograft SCID mouse model. The hypothesis is that&#xD;
      chemokine and chemokine receptor play important roles in psoriasis and establishment of human&#xD;
      skin xenograft mouse model provide excellent platform to test the hypothesis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Chemokines belongs to a large group of small chemotactic proteins (8-11 kilodaltons in size).&#xD;
      Upon engagement of chemokine, chemokine receptor can activate downstream intracellular&#xD;
      signaling pathways and results in diverse cellular processing such as cytoskeleton&#xD;
      reorganization and cell locomotion. Chemokines are chemoattractant factors and can stimulate&#xD;
      directional migration of all classes of leukocytes such as T cells. Epidermal keratinocytes&#xD;
      in the skin are able to express multiple chemokines that can attract certain leukocytes, such&#xD;
      as T cells or dendritic cells (DCs), to migrate to the epidermis. Psoriasis is a type of skin&#xD;
      inflammatory diseases that results in misregulated immune system including immune cell&#xD;
      infiltration. Keratinocyte secreted chemokine and chemokine receptor on leukocytes have been&#xD;
      known to involve in the pathogenesis of psoriasis. However, it is not very clear how&#xD;
      chemokines are regulated in keratinocytes and the binding of chemokine to receptor on&#xD;
      leukocytes controls the pathogenesis of psoriasis. To better understand the immune regulation&#xD;
      of chemokine and chemokine receptor in the molecular mechanism and pathogenesis of psoriasis,&#xD;
      the investigators plan to establish human psoriasis skin xenograft mouse model that involves&#xD;
      graft of human skin onto immune deficient mice. The human skin, including lesional and&#xD;
      non-lesional skins, has been proven to be acceptable to the SCID mice and the phenotype can&#xD;
      maintain for a number of months. The advantage of the xenograft model is to that it can&#xD;
      preserve the full complexity of human diseases and thus resembles the pathogenesis of human&#xD;
      diseases. This model has also been shown with constant efficacy of anti-psoriasis drug in&#xD;
      comparison with clinical practice. Thus, this mouse model has great value to help the&#xD;
      investigators understand how chemokine and immune cells are regulated in psoriasis. Of&#xD;
      particular note is that this model can be used to test therapeutic drug before introduce them&#xD;
      into clinical trial.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    PI failed to submit study for continuing review by IRB&#xD;
  </why_stopped>
  <start_date type="Actual">April 17, 2017</start_date>
  <completion_date type="Actual">April 13, 2018</completion_date>
  <primary_completion_date type="Actual">April 13, 2018</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Other</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Acquisition of psoriatic skin from patient to transfer to immunocompromised mice</measure>
    <time_frame>Five years</time_frame>
    <description>The purpose of this human clinical trial is to harvest psoriatic skin for engraftment onto immunocompromised mice. The primary outcome measure is to identify a 0.75 x 0.75 square inch piece of skin with psoriasis on study subjects to be biopsied. specific outcome measure that will be obtained in the patients other than ensuring that their graft sites heal appropriately. Their skin, once placed on immunocompromised mice, will be used to test new therapeutic drugs which might have a beneficial outcome in psoriasis, as measured in this mouse model.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Observe Appropriate Healing in Subject Biopsy sites</measure>
    <time_frame>Five years</time_frame>
    <description>The secondary outcome measure is to observe that study subjects' graft sites heal appropriately.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">0</enrollment>
  <condition>Psoriasis</condition>
  <arm_group>
    <arm_group_label>Biopsy of Skin with Psoriasis</arm_group_label>
    <description>Shave biopsy of psoriasis lesion</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Shave Biopsy of Psoriasis Lesion</intervention_name>
    <description>The investigator will take about 0.5x0.5 inch square section of skin from the psoriasis lesion. To numb the skin, the subject will receive a small injection of 0.5% lidocaine HCl 5mg/mL with 1:200,000 mcg/mL epinephrine solution as per standard shave biopsy protocol. The shaving instrument has a blade that will shave off a superficial piece of skin that is less than &lt;3mm in thickness. After 14 days, the subject will return to make sure that the skin biopsy site has healed properly. The piece of skin that is removed will be grafted onto the back of an immunocompromised SCID mouse. An approved IACUC protocol covering this procedure will be in place prior to engraftment.</description>
    <arm_group_label>Biopsy of Skin with Psoriasis</arm_group_label>
    <other_name>shave biopsy</other_name>
    <other_name>biopsy</other_name>
    <other_name>injection, lidocaine HCl with epinephrine</other_name>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Subjects 18 years of age or greater will be recruited for this study. The study population&#xD;
        will include patients at UC Davis Dermatology with diagnostic evidence for psoriasis who do&#xD;
        not have coexisting inflammatory diseases.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects 18 years of age or greater&#xD;
&#xD;
          -  Subjects need to fulfill the diagnostic evidence of psoriasis with or without&#xD;
             psoriatic arthritis&#xD;
&#xD;
          -  Subject may take the following medicines: NSAID, hydroxychloroquine, sulfasalazine,&#xD;
             prednisone (&lt;10 mg/day), Methotrexate (10 mg/week)&#xD;
&#xD;
          -  Subject needs to stop topical skin preparations other than emollients in one small&#xD;
             plaque of psoriasis for 3-4 wks from where the shave biopsy will be taken&#xD;
&#xD;
          -  Willing and able to provide informed consent in English&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects less than 18 years old&#xD;
&#xD;
          -  no clinical evidence of psoriatic skin&#xD;
&#xD;
          -  Subjects with contraindications for biopsy, and patients receiving anticoagulants&#xD;
&#xD;
          -  Subjects with active hepatitis B or Hepatitis C infection&#xD;
&#xD;
          -  Subjects with concomitant inflammatory diseases such as inflammatory bowel disease,&#xD;
             gout&#xD;
&#xD;
          -  Subjects who are taking the following systemic biological therapies for psoriasis:&#xD;
             cyclosporine, methotrexate, prednisone, acitretin, sulfasalazine, certolizumab,&#xD;
             etanercept, adalimumab, infliximab, golimumab, secukinumab, ustekinumab, and&#xD;
             apremilast. Other systemic medications may exclude the subject from the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Samuel Hwang, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, Davis</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UC Davis</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2018</verification_date>
  <study_first_submitted>July 8, 2017</study_first_submitted>
  <study_first_submitted_qc>September 29, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 5, 2017</study_first_posted>
  <last_update_submitted>October 15, 2018</last_update_submitted>
  <last_update_submitted_qc>October 15, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">October 17, 2018</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>Psoriasis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lidocaine</mesh_term>
    <mesh_term>Epinephrine</mesh_term>
  </intervention_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/NCT03302390
org study id: 1015909
secondary id: 5R01AR063091
nct id: NCT03302390
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study aims to elucidate the role of Chemokine and chemokine receptor in the pathogenesis
      of Psoriasis by using human psoriasis skin xenograft SCID mouse model. The hypothesis is that
      chemokine and chemokine receptor play important roles in psoriasis and establishment of human
      skin xenograft mouse model provide excellent platform to test the hypothesis.
Chemokines belongs to a large group of small chemotactic proteins (8-11 kilodaltons in size).
      Upon engagement of chemokine, chemokine receptor can activate downstream intracellular
      signaling pathways and results in diverse cellular processing such as cytoskeleton
      reorganization and cell locomotion. Chemokines are chemoattractant factors and can stimulate
      directional migration of all classes of leukocytes such as T cells. Epidermal keratinocytes
      in the skin are able to express multiple chemokines that can attract certain leukocytes, such
      as T cells or dendritic cells (DCs), to migrate to the epidermis. Psoriasis is a type of skin
      inflammatory diseases that results in misregulated immune system including immune cell
      infiltration. Keratinocyte secreted chemokine and chemokine receptor on leukocytes have been
      known to involve in the pathogenesis of psoriasis. However, it is not very clear how
      chemokines are regulated in keratinocytes and the binding of chemokine to receptor on
      leukocytes controls the pathogenesis of psoriasis. To better understand the immune regulation
      of chemokine and chemokine receptor in the molecular mechanism and pathogenesis of psoriasis,
      the investigators plan to establish human psoriasis skin xenograft mouse model that involves
      graft of human skin onto immune deficient mice. The human skin, including lesional and
      non-lesional skins, has been proven to be acceptable to the SCID mice and the phenotype can
      maintain for a number of months. The advantage of the xenograft model is to that it can
      preserve the full complexity of human diseases and thus resembles the pathogenesis of human
      diseases. This model has also been shown with constant efficacy of anti-psoriasis drug in
      comparison with clinical practice. Thus, this mouse model has great value to help the
      investigators understand how chemokine and immune cells are regulated in psoriasis. Of
      particular note is that this model can be used to test therapeutic drug before introduce them
      into clinical trial.
observational model: Other
time perspective: Prospective
measure: Acquisition of psoriatic skin from patient to transfer to immunocompromised mice
time frame: Five years
description: The purpose of this human clinical trial is to harvest psoriatic skin for engraftment onto immunocompromised mice. The primary outcome measure is to identify a 0.75 x 0.75 square inch piece of skin with psoriasis on study subjects to be biopsied. specific outcome measure that will be obtained in the patients other than ensuring that their graft sites heal appropriately. Their skin, once placed on immunocompromised mice, will be used to test new therapeutic drugs which might have a beneficial outcome in psoriasis, as measured in this mouse model.
measure: Observe Appropriate Healing in Subject Biopsy sites
time frame: Five years
description: The secondary outcome measure is to observe that study subjects' graft sites heal appropriately.
arm group label: Biopsy of Skin with Psoriasis
description: Shave biopsy of psoriasis lesion
intervention type: Procedure
intervention name: Shave Biopsy of Psoriasis Lesion
description: The investigator will take about 0.5x0.5 inch square section of skin from the psoriasis lesion. To numb the skin, the subject will receive a small injection of 0.5% lidocaine HCl 5mg/mL with 1:200,000 mcg/mL epinephrine solution as per standard shave biopsy protocol. The shaving instrument has a blade that will shave off a superficial piece of skin that is less than <3mm in thickness. After 14 days, the subject will return to make sure that the skin biopsy site has healed properly. The piece of skin that is removed will be grafted onto the back of an immunocompromised SCID mouse. An approved IACUC protocol covering this procedure will be in place prior to engraftment.
arm group label: Biopsy of Skin with Psoriasis
other name: shave biopsy
other name: biopsy
other name: injection, lidocaine HCl with epinephrine
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Samuel Hwang, M.D.
role: Principal Investigator
affiliation: University of California, Davis
facility: 
country: United States
responsible party type: Sponsor
mesh term: Psoriasis
mesh term: Lidocaine
mesh term: Epinephrine
sharing ipd: No