<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/NCT03268330</url>
  </required_header>
  <id_info>
    <org_study_id>ROMMIFISS</org_study_id>
    <nct_id>NCT03268330</nct_id>
  </id_info>
  <brief_title>Role of Macrophage Migratory Inhibitory Factor in Systemic Sclerosis</brief_title>
  <official_title>Role of Macrophage Migratory Inhibitory Factor in Systemic Sclerosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assiut University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assiut 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>
      Migration Inhibitory Factor has proliferative and antiapoptotic actions on fibroblasts which&#xD;
      may be relevant to scleroderma because of the central role of a dysregulated&#xD;
      fibroproliferative response in disease-affected tissues&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      -  Systemic sclerosis (scleroderma) is a disease of unknown etiology characterized by&#xD;
           fibrosis of the skin and internal organs, pronounced vasculopathy, and dysregulated&#xD;
           immune system.&#xD;
&#xD;
        -  Clinically, the disease is divided into 2 major subsets, diffuse cutaneous SSc (dcSSc)&#xD;
           and limited cutaneous SSc (lcSSc). The diffuse cutaneous subtype is generally associated&#xD;
           with significant internal organ involvement, especially renal crisis and diffuse&#xD;
           alveolitis of the lung, along with antitopoisomerase (antitopo) autoantibody. The&#xD;
           limited cutaneous subtype is distinguished by Raynaud's phenomenon, telangiectasias,&#xD;
           pulmonary hypertension, and the presence of anticentromere antibody. However, there is&#xD;
           significant overlap both in the clinical manifestations and in the specific&#xD;
           autoantibodies that occur in these subtypes. It is not known what predisposes a&#xD;
           susceptible individual to develop one subtype versus another, nor is there significant&#xD;
           information about how the 2 disease subtypes may be pathogenically related.&#xD;
&#xD;
        -  Activation of T lymphocytes and macrophages is an early event in the parthenogenesis of&#xD;
           SSc. Activated T cells , macrophages and endothelial cells are important sources of&#xD;
           Macrophage Migration Inhibitory Factor MIF was initially identified as the protein&#xD;
           secreted by activated T lymphocytes capable of inhibiting random migration of&#xD;
           macrophages, concentrating macrophages at inflammation loci, and enhancing their ability&#xD;
           to kill intracellular parasites and tumoral cells.&#xD;
&#xD;
        -  Migration Inhibitory Factor has proliferative and antiapoptotic actions on fibroblasts&#xD;
           which may be relevant to scleroderma because of the central role of a dysregulated&#xD;
           fibroproliferative response in disease-affected tissues.&#xD;
&#xD;
        -  In patients with SSc, elevated serum levels of MIF, increased MIF expression in the skin&#xD;
           and afunctional promoter polymorphism in the MIF gene that might influence clinical&#xD;
           expression have been described therefore MIF might have an important role in the&#xD;
           disease.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Anticipated">September 2021</start_date>
  <completion_date type="Anticipated">November 2021</completion_date>
  <primary_completion_date type="Anticipated">October 2021</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>Correlation between Migration Inhibitory Factor and some of the clinical manifestations of Systemic Sclerosis.</measure>
    <time_frame>1 hour</time_frame>
    <description>Serum levels of Macrophage Migratory Inhibitory Factor will be measured by ELISA</description>
  </primary_outcome>
  <enrollment type="Anticipated">40</enrollment>
  <condition>System; Sclerosis</condition>
  <eligibility>
    <study_pop>
      <textblock>
        -Patients with Systemic Sclerosis diagnosed by Rheumatologists at Department of&#xD;
        Rheumatology, Rehabilitation and Physical Medicine Assiut University.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        -Patients with Systemic Sclerosis .&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with Interstitial Pulmonary Fibrosis caused by causes other than SSc.&#xD;
&#xD;
          -  Other rheumatologic diseases.&#xD;
&#xD;
          -  Overlap or Mixed diseases.&#xD;
&#xD;
          -  Patients with renal disease caused by causes other than SSc.&#xD;
&#xD;
          -  Unwillingness to participate in the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>17 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Doaa K Mohamed, Lectruer</last_name>
    <role>Study Director</role>
    <affiliation>Assiut University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Naima M Omran, Resident</last_name>
    <phone>+01008592039</phone>
    <email>heissa999@yahoo.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Nihal A Fathi, Professor</last_name>
    <phone>01005364739</phone>
    <email>Nfathy@yahoo.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Assiut University Hospital</name>
      <address>
        <city>Assiut</city>
        <country>Egypt</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Naima Omran</last_name>
      <phone>01008592039</phone>
      <email>heissa999@yahoo.com</email>
    </contact>
    <contact_backup>
      <last_name>Nihal Fathi</last_name>
      <phone>01005364739</phone>
      <email>Nfathy@yahoo.com</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Assuit University hospital</name>
      <address>
        <city>Assuit</city>
        <country>Egypt</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Naima Omran</last_name>
      <email>heissa999@yahoo.com</email>
    </contact>
    <contact_backup>
      <last_name>Nihal Fathi</last_name>
      <phone>01005364739</phone>
      <email>Nfathy@yahoo.com</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <reference>
    <citation>Sakkas LI, Chikanza IC, Platsoucas CD. Mechanisms of Disease: the role of immune cells in the pathogenesis of systemic sclerosis. Nat Clin Pract Rheumatol. 2006 Dec;2(12):679-85. doi: 10.1038/ncprheum0346.</citation>
    <PMID>17133253</PMID>
  </reference>
  <reference>
    <citation>Selvi E, Tripodi SA, Catenaccio M, Lorenzini S, Chindamo D, Manganelli S, Romagnoli R, Ietta F, Paulesu L, Miracco C, Cintorino M, Marcolongo R. Expression of macrophage migration inhibitory factor in diffuse systemic sclerosis. Ann Rheum Dis. 2003 May;62(5):460-4. doi: 10.1136/ard.62.5.460.</citation>
    <PMID>12695161</PMID>
  </reference>
  <reference>
    <citation>Wu SP, Leng L, Feng Z, Liu N, Zhao H, McDonald C, Lee A, Arnett FC, Gregersen PK, Mayes MD, Bucala R. Macrophage migration inhibitory factor promoter polymorphisms and the clinical expression of scleroderma. Arthritis Rheum. 2006 Nov;54(11):3661-9. doi: 10.1002/art.22179.</citation>
    <PMID>17075815</PMID>
  </reference>
  <reference>
    <citation>Mitchell RA, Metz CN, Peng T, Bucala R. Sustained mitogen-activated protein kinase (MAPK) and cytoplasmic phospholipase A2 activation by macrophage migration inhibitory factor (MIF). Regulatory role in cell proliferation and glucocorticoid action. J Biol Chem. 1999 Jun 18;274(25):18100-6. doi: 10.1074/jbc.274.25.18100.</citation>
    <PMID>10364264</PMID>
  </reference>
  <reference>
    <citation>Calandra T, Bernhagen J, Mitchell RA, Bucala R. The macrophage is an important and previously unrecognized source of macrophage migration inhibitory factor. J Exp Med. 1994 Jun 1;179(6):1895-902. doi: 10.1084/jem.179.6.1895.</citation>
    <PMID>8195715</PMID>
  </reference>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>August 29, 2017</study_first_submitted>
  <study_first_submitted_qc>August 29, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 31, 2017</study_first_posted>
  <last_update_submitted>January 11, 2021</last_update_submitted>
  <last_update_submitted_qc>January 11, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 12, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Assiut University</investigator_affiliation>
    <investigator_full_name>Naima eid</investigator_full_name>
    <investigator_title>Principal investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Scleroderma, Systemic</mesh_term>
    <mesh_term>Scleroderma, Diffuse</mesh_term>
    <mesh_term>Sclerosis</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/NCT03268330
org study id: ROMMIFISS
nct id: NCT03268330
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Migration Inhibitory Factor has proliferative and antiapoptotic actions on fibroblasts which
      may be relevant to scleroderma because of the central role of a dysregulated
      fibroproliferative response in disease-affected tissues
-  Systemic sclerosis (scleroderma) is a disease of unknown etiology characterized by
           fibrosis of the skin and internal organs, pronounced vasculopathy, and dysregulated
           immune system.

        -  Clinically, the disease is divided into 2 major subsets, diffuse cutaneous SSc (dcSSc)
           and limited cutaneous SSc (lcSSc). The diffuse cutaneous subtype is generally associated
           with significant internal organ involvement, especially renal crisis and diffuse
           alveolitis of the lung, along with antitopoisomerase (antitopo) autoantibody. The
           limited cutaneous subtype is distinguished by Raynaud's phenomenon, telangiectasias,
           pulmonary hypertension, and the presence of anticentromere antibody. However, there is
           significant overlap both in the clinical manifestations and in the specific
           autoantibodies that occur in these subtypes. It is not known what predisposes a
           susceptible individual to develop one subtype versus another, nor is there significant
           information about how the 2 disease subtypes may be pathogenically related.

        -  Activation of T lymphocytes and macrophages is an early event in the parthenogenesis of
           SSc. Activated T cells , macrophages and endothelial cells are important sources of
           Macrophage Migration Inhibitory Factor MIF was initially identified as the protein
           secreted by activated T lymphocytes capable of inhibiting random migration of
           macrophages, concentrating macrophages at inflammation loci, and enhancing their ability
           to kill intracellular parasites and tumoral cells.

        -  Migration Inhibitory Factor has proliferative and antiapoptotic actions on fibroblasts
           which may be relevant to scleroderma because of the central role of a dysregulated
           fibroproliferative response in disease-affected tissues.

        -  In patients with SSc, elevated serum levels of MIF, increased MIF expression in the skin
           and afunctional promoter polymorphism in the MIF gene that might influence clinical
           expression have been described therefore MIF might have an important role in the
           disease.
observational model: Cohort
time perspective: Prospective
measure: Correlation between Migration Inhibitory Factor and some of the clinical manifestations of Systemic Sclerosis.
time frame: 1 hour
description: Serum levels of Macrophage Migratory Inhibitory Factor will be measured by ELISA
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 17 Years
maximum age: 70 Years
healthy volunteers: No
last name: Doaa K Mohamed, Lectruer
role: Study Director
affiliation: Assiut University
last name: Naima M Omran, Resident
phone: +01008592039
email: heissa999@yahoo.com
last name: Nihal A Fathi, Professor
phone: 01005364739
email: Nfathy@yahoo.com
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
contact backup: 
country: Egypt
citation: Sakkas LI, Chikanza IC, Platsoucas CD. Mechanisms of Disease: the role of immune cells in the pathogenesis of systemic sclerosis. Nat Clin Pract Rheumatol. 2006 Dec;2(12):679-85. doi: 10.1038/ncprheum0346.
PMID: 17133253
citation: Selvi E, Tripodi SA, Catenaccio M, Lorenzini S, Chindamo D, Manganelli S, Romagnoli R, Ietta F, Paulesu L, Miracco C, Cintorino M, Marcolongo R. Expression of macrophage migration inhibitory factor in diffuse systemic sclerosis. Ann Rheum Dis. 2003 May;62(5):460-4. doi: 10.1136/ard.62.5.460.
PMID: 12695161
citation: Wu SP, Leng L, Feng Z, Liu N, Zhao H, McDonald C, Lee A, Arnett FC, Gregersen PK, Mayes MD, Bucala R. Macrophage migration inhibitory factor promoter polymorphisms and the clinical expression of scleroderma. Arthritis Rheum. 2006 Nov;54(11):3661-9. doi: 10.1002/art.22179.
PMID: 17075815
citation: Mitchell RA, Metz CN, Peng T, Bucala R. Sustained mitogen-activated protein kinase (MAPK) and cytoplasmic phospholipase A2 activation by macrophage migration inhibitory factor (MIF). Regulatory role in cell proliferation and glucocorticoid action. J Biol Chem. 1999 Jun 18;274(25):18100-6. doi: 10.1074/jbc.274.25.18100.
PMID: 10364264
citation: Calandra T, Bernhagen J, Mitchell RA, Bucala R. The macrophage is an important and previously unrecognized source of macrophage migration inhibitory factor. J Exp Med. 1994 Jun 1;179(6):1895-902. doi: 10.1084/jem.179.6.1895.
PMID: 8195715
responsible party type: Principal Investigator
investigator affiliation: Assiut University
investigator full name: Naima eid
investigator title: Principal investigator
mesh term: Scleroderma, Systemic
mesh term: Scleroderma, Diffuse
mesh term: Sclerosis
sharing ipd: Undecided