<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/NCT03299413</url>
  </required_header>
  <id_info>
    <org_study_id>IBDUJCTC</org_study_id>
    <nct_id>NCT03299413</nct_id>
  </id_info>
  <brief_title>Use of Mesenchymal Stem Cells in Inflammatory Bowel Disease</brief_title>
  <official_title>Ulcerative Colitis Stem Cell Therapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hanan Jafar</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Scientific Research Support fund</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Jordan</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>
      Scientists hypothesize that directly or parentally injecting Mesenchymal stem cells (MSCs) to&#xD;
      affected areas will have a positive impact through reducing or abolishing intestinal&#xD;
      inflammation in part via inhibition of neutrophil Myeloperoxidase (MPOx) activity. Inhibiting&#xD;
      MPOx should modify disease progression as well as reduce colitis associated cancer risk.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Chronic inappropriate mucosal immune activation, due to aberrant host interactions with&#xD;
      intestinal microbiota, is at the heart of inflammatory bowel disease (IBD) pathogenesis.&#xD;
      Currently, there is no cure for IBD and mainstays of therapy are limited to non-cell specific&#xD;
      immunosuppression/immunomodulation, antibiotics and surgery. Advanced ulcerative colitis&#xD;
      patients cost approximately 10,000JD in therapy per year with 12.4% of patients presenting&#xD;
      with rectal bleeding in Jordan being diagnosed with ulcerative colitis. The role of MSCs in&#xD;
      immune modulation is well established in many diseases. However, the therapeutic potential of&#xD;
      MSCs directly injected into the inflamed large intestine or parentally has not been fully&#xD;
      investigated. Injected MSCs may modulate the IBD immune response particularly lymphoid T-cell&#xD;
      and neutrophil activities. While a variety of immune cells contribute to the disease,&#xD;
      increased neutrophil activity is associated with greater frequency and severity of active&#xD;
      inflammation, as well as increased colitis associated cancer risk. MPOx can transform lipids&#xD;
      and polyamines into reactive carbonyl species (RCS) capable of modifying proteins and DNA,&#xD;
      altering cell signalling pathways. Finally, MPOx is reported as a useful tool in screening&#xD;
      and risk stratification of human ulcerative colitis and colorectal cancer. Inhibiting MPOx in&#xD;
      an accelerated preclinical mouse model did reduce incidence and tumor load resulting from gut&#xD;
      inflammation. Additionally, in similar preclinical models others have reported that MSC&#xD;
      transplantation reduces colitis severity and inflammatory markers including MPOx activity.&#xD;
      Even in the absence of the well-known MSC T-cell immune modulation, disease activity indices&#xD;
      and MPOx activity were reduced in these models. In addition to following traditional clinical&#xD;
      outcomes, Reseachers will analyze gut immune responses, specifically neutrophil MPOx activity&#xD;
      along with other IBD immune markers.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">June 5, 2017</start_date>
  <completion_date type="Anticipated">January 2020</completion_date>
  <primary_completion_date type="Anticipated">November 2019</primary_completion_date>
  <phase>Phase 1/Phase 2</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]</measure>
    <time_frame>6 months</time_frame>
    <description>Treatment adverse events are defined by any adverse event leading to hospitalization, organ failure or death</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Evaluation of the efficacy of the injected cells (Change from Baseline in partial mayo score)</measure>
    <time_frame>3 months</time_frame>
    <description>Remission will be considered if reaches 0 points and response if the score diminishes. Endoscopy will be performed at 0 and 12 weeks.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Inflammatory Bowel Diseases</condition>
  <arm_group>
    <arm_group_label>Wharton Jelly Mesenchymal stem cells</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Wharton Jelly Mesenchymal stem cells will be given as a cell suspension in aseptic buffered solution in disposable vials with no preservative agents. The cells will be injected every two weeks at a total of three doses, 120 million cells in 10mls divided on two IV boli for each dose</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Wharton Jelly Mesenchymal stem cells</intervention_name>
    <description>Wharton Jelly Mesenchymal stem cells will be injected intravenously</description>
    <arm_group_label>Wharton Jelly Mesenchymal stem cells</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Single/unmarried females or married females using two modalities of contraception for&#xD;
             six months after completion of the study.&#xD;
&#xD;
          -  Signed informed consent.&#xD;
&#xD;
          -  Patients with previous diagnosis of ulcerative colitis (UC) or newly diagnosed UC&#xD;
             based on endoscopic or histopathologic features&#xD;
&#xD;
          -  Colitis of any activity&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Mental disability that impedes adequate understanding of the study and of the&#xD;
             associated procedures.&#xD;
&#xD;
          -  Extensive severe toxic colitis requiring admission and IV steroids or biological&#xD;
             treatment/surgery.&#xD;
&#xD;
          -  Patients with previous colectomies.&#xD;
&#xD;
          -  History of malignant disease.&#xD;
&#xD;
          -  Pregnant or breastfeeding women.&#xD;
&#xD;
          -  Presence of severe concomitant diseases such as chronic obstructive pulmonary disease,&#xD;
             Diabetes Mellitus, Cardiovascular and other autoimmune diseases.&#xD;
&#xD;
          -  Positive to one or more of the infectious disease panel&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Cell Therapy Center</name>
      <address>
        <city>Amman</city>
        <zip>11942</zip>
        <country>Jordan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Jordan</country>
  </location_countries>
  <verification_date>April 2019</verification_date>
  <study_first_submitted>September 27, 2017</study_first_submitted>
  <study_first_submitted_qc>September 27, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 3, 2017</study_first_posted>
  <last_update_submitted>April 9, 2019</last_update_submitted>
  <last_update_submitted_qc>April 9, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">April 10, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Jordan</investigator_affiliation>
    <investigator_full_name>Hanan Jafar</investigator_full_name>
    <investigator_title>DDS. MSc. PhD</investigator_title>
  </responsible_party>
  <keyword>Inflammatory Bowel Disease</keyword>
  <keyword>Mesenchymal stem cells</keyword>
  <keyword>Ulcerative colitis</keyword>
  <keyword>Neutrophils</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Intestinal Diseases</mesh_term>
    <mesh_term>Inflammatory Bowel Diseases</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03299413
org study id: IBDUJCTC
nct id: NCT03299413
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Scientists hypothesize that directly or parentally injecting Mesenchymal stem cells (MSCs) to
      affected areas will have a positive impact through reducing or abolishing intestinal
      inflammation in part via inhibition of neutrophil Myeloperoxidase (MPOx) activity. Inhibiting
      MPOx should modify disease progression as well as reduce colitis associated cancer risk.
Chronic inappropriate mucosal immune activation, due to aberrant host interactions with
      intestinal microbiota, is at the heart of inflammatory bowel disease (IBD) pathogenesis.
      Currently, there is no cure for IBD and mainstays of therapy are limited to non-cell specific
      immunosuppression/immunomodulation, antibiotics and surgery. Advanced ulcerative colitis
      patients cost approximately 10,000JD in therapy per year with 12.4% of patients presenting
      with rectal bleeding in Jordan being diagnosed with ulcerative colitis. The role of MSCs in
      immune modulation is well established in many diseases. However, the therapeutic potential of
      MSCs directly injected into the inflamed large intestine or parentally has not been fully
      investigated. Injected MSCs may modulate the IBD immune response particularly lymphoid T-cell
      and neutrophil activities. While a variety of immune cells contribute to the disease,
      increased neutrophil activity is associated with greater frequency and severity of active
      inflammation, as well as increased colitis associated cancer risk. MPOx can transform lipids
      and polyamines into reactive carbonyl species (RCS) capable of modifying proteins and DNA,
      altering cell signalling pathways. Finally, MPOx is reported as a useful tool in screening
      and risk stratification of human ulcerative colitis and colorectal cancer. Inhibiting MPOx in
      an accelerated preclinical mouse model did reduce incidence and tumor load resulting from gut
      inflammation. Additionally, in similar preclinical models others have reported that MSC
      transplantation reduces colitis severity and inflammatory markers including MPOx activity.
      Even in the absence of the well-known MSC T-cell immune modulation, disease activity indices
      and MPOx activity were reduced in these models. In addition to following traditional clinical
      outcomes, Reseachers will analyze gut immune responses, specifically neutrophil MPOx activity
      along with other IBD immune markers.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
time frame: 6 months
description: Treatment adverse events are defined by any adverse event leading to hospitalization, organ failure or death
measure: Evaluation of the efficacy of the injected cells (Change from Baseline in partial mayo score)
time frame: 3 months
description: Remission will be considered if reaches 0 points and response if the score diminishes. Endoscopy will be performed at 0 and 12 weeks.
arm group label: Wharton Jelly Mesenchymal stem cells
arm group type: Experimental
description: Wharton Jelly Mesenchymal stem cells will be given as a cell suspension in aseptic buffered solution in disposable vials with no preservative agents. The cells will be injected every two weeks at a total of three doses, 120 million cells in 10mls divided on two IV boli for each dose
intervention type: Biological
intervention name: Wharton Jelly Mesenchymal stem cells
description: Wharton Jelly Mesenchymal stem cells will be injected intravenously
arm group label: Wharton Jelly Mesenchymal stem cells
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
facility: 
country: Jordan
responsible party type: Sponsor-Investigator
investigator affiliation: University of Jordan
investigator full name: Hanan Jafar
investigator title: DDS. MSc. PhD
mesh term: Intestinal Diseases
mesh term: Inflammatory Bowel Diseases
sharing ipd: Undecided