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/NCT06038968</url>
    </required_header>
    <id_info>
      <org_study_id>MTX DM vitrectomy</org_study_id>
      <nct_id>NCT06038968</nct_id>
    </id_info>
    <brief_title>Methotrexate Infusion and Intrasilicone Injection During Diabetic Vitrectomy</brief_title>
    <official_title>Anatomical and Functional Outcomes of Use of Methotrexate Infusion and Intrasilicone Injection During Diabetic Vitrectomy</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Minia University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Minia University</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The goal of this interventional clinical trial is to assess anatomical and functional&#xD;
        outcomes of methotrexate use in irrigating fluid during parsplana vitrectomy combined with&#xD;
        intrasilicone injection at end of surgery in patients with advanced proliferative diabetic&#xD;
        retinopathy.&#xD;
  &#xD;
        The main questions it aims to answer are:&#xD;
  &#xD;
          1. Does methotrexate use in irrigating fluid during parsplana vitrectomy combined with&#xD;
             intrasilicone injection at end of surgery decrease the post operative vitreoretinal&#xD;
             proliferation after vitrectomy in patients with advanced proliferative diabetic&#xD;
             retinopathy?&#xD;
  &#xD;
          2. Does methotrexate use in irrigating fluid during parsplana vitrectomy combined with&#xD;
             intrasilicone injection at end of surgery improve post operative functional outcome&#xD;
             after vitrectomy in patients with advanced proliferative diabetic retinopathy?&#xD;
  &#xD;
        Researchers will compare the anatomical and functional outcomes after vitrectomy in patients&#xD;
        with advanced proliferative diabetic retinopathy without using methotrexate.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Tractional macular detachment (TMD) or macula threatening tractional retinal detachment (TRD)&#xD;
        and combined tractional-rhegmatogenous retinal detachment (TRD/RRD) are considered as&#xD;
        important indications for vitreoretinal intervention.&#xD;
  &#xD;
        Although a growing number of eyes with TMD and TRD/RRD are successfully treated with a single&#xD;
        procedure, retinal re-detachment associated with fibrovascular proliferation or proliferative&#xD;
        vitreoretinopathy (PVR) is still a major cause of failure of the surgery.&#xD;
  &#xD;
        Previous studies have shown increased expression of inflammatory cytokines and growth factors&#xD;
        in both proliferative diabetic retinopathy (PDR) and PVR.&#xD;
  &#xD;
        Methotrexate (MTX) is an anti-neoplastic and anti-inflammatory agent used to treat a variety&#xD;
        of malignancies and rheumatologic diseases.&#xD;
  &#xD;
        In ophthalmology, systemic and intraocular MTX has been successfully used for indeterminate&#xD;
        uveitis, sarcoid uveitis and intraocular lymphoma.&#xD;
  &#xD;
        MTX has been recently found to inhibit PVR by stopping cellular proliferation and promoting&#xD;
        organized apoptosis. MTX has also been found to be effective in lowering the incidence of PVR&#xD;
        when used as an adjunct in irrigation fluid during vitrectomy for retinal detachment.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">September 1, 2022</start_date>
    <completion_date type="Anticipated">December 1, 2023</completion_date>
    <primary_completion_date type="Anticipated">November 1, 2023</primary_completion_date>
    <phase>Early Phase 1</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Other</primary_purpose>
      <masking>Triple (Participant, Care Provider, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>assess retinal layers by optical coherence tomography</measure>
      <time_frame>one month after pars plana vitrectomy and one month after silicone oil evacuation</time_frame>
      <description>presence of epiretinal membrane, cystic changes in retina, central macular thickens</description>
    </primary_outcome>
    <primary_outcome>
      <measure>assess functional outcomes by multifocal electroretinogram</measure>
      <time_frame>one month after pars plana vitrectomy and one month after silicone oil evacuation</time_frame>
      <description>latency and amplitude of main P wave</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Anterior segment slit lamp biomicroscopic examination</measure>
      <time_frame>one month after pars plana vitrectomy</time_frame>
      <description>assess anterior segment inflammation as iritis or posterior synechia</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>visual acuity</measure>
      <time_frame>one month after pars plana vitrectomy and one month after silicone oil evacuation</time_frame>
      <description>by logMAR (Logarithm of the Minimum Angle of Resolution)</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">60</enrollment>
    <condition>Diabetic Retinopathy</condition>
    <condition>Vitreomacular Traction</condition>
    <arm_group>
      <arm_group_label>Methotrexate group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>methotrexate group will receive 40 mg of MTX in 500 ml of irrigation fluid during vitrectomy and 250 ug intra-silicone oil injection at the end of vitrectomy</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Control group</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>control group will not receive MTX in irrigation fluid during vitrectomy nor intra-silicone at the end of vitrectomy</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Methotrexate 25 MG/ML</intervention_name>
      <description>Methotrexate is a folate derivative that inhibits several enzymes responsible for nucleotide synthesis. This inhibition leads to suppression of inflammation as well as prevention of cell division.</description>
      <arm_group_label>Methotrexate group</arm_group_label>
      <other_name>Methotrexate Mylan 50 mg/2 mL</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>parsplana vitrectomy</intervention_name>
      <description>Pars plana vitrectomy (PPV) is a technique in vitreoretinal surgery that enables access to the posterior segment for treating tractional retinal detachment in advanced proliferative diabetic retinopathy, in a controlled, closed system.</description>
      <arm_group_label>Control group</arm_group_label>
      <arm_group_label>Methotrexate group</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
          - Patients with diabetic tractional macular detachment or combined tractional-&#xD;
          rhegmatogenous retinal detachment&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Previous vitreoretinal surgery.&#xD;
  &#xD;
            -  Pregnant or lactating female.&#xD;
  &#xD;
            -  Co-existing pathology that might induce PVR such as penetrating ocular trauma or&#xD;
               uveitis, co-existing congenital anomalies or hereditary vitreoretinopathies&#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>Rabie MM Hasanin, Professor</last_name>
      <role>Study Chair</role>
      <affiliation>ophthalmology department, faculty of medicine, Minia university hospital</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Khaled MS morad, Professor</last_name>
      <role>Study Director</role>
      <affiliation>ophthalmology department, faculty of medicine, Minia university hospital</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Ahmed MA Shawkat, Professor</last_name>
      <role>Study Director</role>
      <affiliation>ophthalmology department, faculty of medicine, Minia university hospital</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Mohamed Tarek AM Mostafa, Ass. Prof.</last_name>
      <role>Study Director</role>
      <affiliation>ophthalmology department, faculty of medicine, Minia university hospital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Abdallah MM Safwat, ass lecturer</last_name>
      <phone>01092212031</phone>
      <phone_ext>02</phone_ext>
      <email>drabdallahmh@gamil.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>ophthalmology department, Minia university hospital</name>
        <address>
          <city>Minya</city>
          <state>Minia</state>
          <zip>61519</zip>
          <country>Egypt</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>ِAbdallah MM Safwat, Ass Lecturer</last_name>
        <phone>01092212031</phone>
        <phone_ext>01</phone_ext>
        <email>drabdallahmh@gmail.com</email>
      </contact>
    </location>
    <location_countries>
      <country>Egypt</country>
    </location_countries>
    <reference>
      <citation>Newman DK. Surgical management of the late complications of proliferative diabetic retinopathy. Eye (Lond). 2010 Mar;24(3):441-9. doi: 10.1038/eye.2009.325. Epub 2010 Feb 5.</citation>
      <PMID>20139916</PMID>
    </reference>
    <reference>
      <citation>Meleth AD, Carvounis PE. Outcomes of vitrectomy for tractional retinal detachment in diabetic retinopathy. Int Ophthalmol Clin. 2014 Spring;54(2):127-39. doi: 10.1097/IIO.0000000000000021. No abstract available.</citation>
      <PMID>24613889</PMID>
    </reference>
    <reference>
      <citation>Gologorsky D, Thanos A, Vavvas D. Therapeutic interventions against inflammatory and angiogenic mediators in proliferative diabetic retinopathy. Mediators Inflamm. 2012;2012:629452. doi: 10.1155/2012/629452. Epub 2012 Sep 17.</citation>
      <PMID>23028203</PMID>
    </reference>
    <reference>
      <citation>Zhou J, Wang S, Xia X. Role of intravitreal inflammatory cytokines and angiogenic factors in proliferative diabetic retinopathy. Curr Eye Res. 2012 May;37(5):416-20. doi: 10.3109/02713683.2012.661114. Epub 2012 Mar 12.</citation>
      <PMID>22409294</PMID>
    </reference>
    <reference>
      <citation>Ricker LJ, Kijlstra A, Kessels AG, de Jager W, Liem AT, Hendrikse F, La Heij EC. Interleukin and growth factor levels in subretinal fluid in rhegmatogenous retinal detachment: a case-control study. PLoS One. 2011 Apr 27;6(4):e19141. doi: 10.1371/journal.pone.0019141.</citation>
      <PMID>21556354</PMID>
    </reference>
    <reference>
      <citation>Samson CM, Waheed N, Baltatzis S, Foster CS. Methotrexate therapy for chronic noninfectious uveitis: analysis of a case series of 160 patients. Ophthalmology. 2001 Jun;108(6):1134-9. doi: 10.1016/s0161-6420(01)00576-0.</citation>
      <PMID>11382642</PMID>
    </reference>
    <reference>
      <citation>Smith JR, Rosenbaum JT, Wilson DJ, Doolittle ND, Siegal T, Neuwelt EA, Pe'er J. Role of intravitreal methotrexate in the management of primary central nervous system lymphoma with ocular involvement. Ophthalmology. 2002 Sep;109(9):1709-16. doi: 10.1016/s0161-6420(02)01125-9.</citation>
      <PMID>12208721</PMID>
    </reference>
    <reference>
      <citation>Amarnani D, Machuca-Parra AI, Wong LL, Marko CK, Stefater JA, Stryjewski TP, Eliott D, Arboleda-Velasquez JF, Kim LA. Effect of Methotrexate on an In Vitro Patient-Derived Model of Proliferative Vitreoretinopathy. Invest Ophthalmol Vis Sci. 2017 Aug 1;58(10):3940-3949. doi: 10.1167/iovs.16-20912.</citation>
      <PMID>28777835</PMID>
    </reference>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>September 8, 2023</study_first_submitted>
    <study_first_submitted_qc>September 8, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 15, 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 15, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Minia University</investigator_affiliation>
      <investigator_full_name>Abdallah Mohsen Mohamed Safwat</investigator_full_name>
      <investigator_title>assistant lecturer, ophthalmology department, faculty of medicine</investigator_title>
    </responsible_party>
    <keyword>Methotrexate</keyword>
    <keyword>proliferative diabetic retinopathy</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Retinal Diseases</mesh_term>
      <mesh_term>Diabetic Retinopathy</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Methotrexate</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
      <ipd_description>email the main investigator for requested data</ipd_description>
    </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/NCT06038968
  org study id: MTX DM vitrectomy
  nct id: NCT06038968
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  The goal of this interventional clinical trial is to assess anatomical and functional
        outcomes of methotrexate use in irrigating fluid during parsplana vitrectomy combined with
        intrasilicone injection at end of surgery in patients with advanced proliferative diabetic
        retinopathy.
  
        The main questions it aims to answer are:
  
          1. Does methotrexate use in irrigating fluid during parsplana vitrectomy combined with
             intrasilicone injection at end of surgery decrease the post operative vitreoretinal
             proliferation after vitrectomy in patients with advanced proliferative diabetic
             retinopathy?
  
          2. Does methotrexate use in irrigating fluid during parsplana vitrectomy combined with
             intrasilicone injection at end of surgery improve post operative functional outcome
             after vitrectomy in patients with advanced proliferative diabetic retinopathy?
  
        Researchers will compare the anatomical and functional outcomes after vitrectomy in patients
        with advanced proliferative diabetic retinopathy without using methotrexate.
  Tractional macular detachment (TMD) or macula threatening tractional retinal detachment (TRD)
        and combined tractional-rhegmatogenous retinal detachment (TRD/RRD) are considered as
        important indications for vitreoretinal intervention.
  
        Although a growing number of eyes with TMD and TRD/RRD are successfully treated with a single
        procedure, retinal re-detachment associated with fibrovascular proliferation or proliferative
        vitreoretinopathy (PVR) is still a major cause of failure of the surgery.
  
        Previous studies have shown increased expression of inflammatory cytokines and growth factors
        in both proliferative diabetic retinopathy (PDR) and PVR.
  
        Methotrexate (MTX) is an anti-neoplastic and anti-inflammatory agent used to treat a variety
        of malignancies and rheumatologic diseases.
  
        In ophthalmology, systemic and intraocular MTX has been successfully used for indeterminate
        uveitis, sarcoid uveitis and intraocular lymphoma.
  
        MTX has been recently found to inhibit PVR by stopping cellular proliferation and promoting
        organized apoptosis. MTX has also been found to be effective in lowering the incidence of PVR
        when used as an adjunct in irrigation fluid during vitrectomy for retinal detachment.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Other
  masking: Triple (Participant, Care Provider, Outcomes Assessor)
  measure: assess retinal layers by optical coherence tomography
  time frame: one month after pars plana vitrectomy and one month after silicone oil evacuation
  description: presence of epiretinal membrane, cystic changes in retina, central macular thickens
  measure: assess functional outcomes by multifocal electroretinogram
  time frame: one month after pars plana vitrectomy and one month after silicone oil evacuation
  description: latency and amplitude of main P wave
  measure: Anterior segment slit lamp biomicroscopic examination
  time frame: one month after pars plana vitrectomy
  description: assess anterior segment inflammation as iritis or posterior synechia
  measure: visual acuity
  time frame: one month after pars plana vitrectomy and one month after silicone oil evacuation
  description: by logMAR (Logarithm of the Minimum Angle of Resolution)
  arm group label: Methotrexate group
  arm group type: Experimental
  description: methotrexate group will receive 40 mg of MTX in 500 ml of irrigation fluid during vitrectomy and 250 ug intra-silicone oil injection at the end of vitrectomy
  arm group label: Control group
  arm group type: Placebo Comparator
  description: control group will not receive MTX in irrigation fluid during vitrectomy nor intra-silicone at the end of vitrectomy
  intervention type: Drug
  intervention name: Methotrexate 25 MG/ML
  description: Methotrexate is a folate derivative that inhibits several enzymes responsible for nucleotide synthesis. This inhibition leads to suppression of inflammation as well as prevention of cell division.
  arm group label: Methotrexate group
  other name: Methotrexate Mylan 50 mg/2 mL
  intervention type: Procedure
  intervention name: parsplana vitrectomy
  description: Pars plana vitrectomy (PPV) is a technique in vitreoretinal surgery that enables access to the posterior segment for treating tractional retinal detachment in advanced proliferative diabetic retinopathy, in a controlled, closed system.
  arm group label: Control group
  arm group label: Methotrexate group
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Rabie MM Hasanin, Professor
  role: Study Chair
  affiliation: ophthalmology department, faculty of medicine, Minia university hospital
  last name: Khaled MS morad, Professor
  role: Study Director
  affiliation: ophthalmology department, faculty of medicine, Minia university hospital
  last name: Ahmed MA Shawkat, Professor
  role: Study Director
  affiliation: ophthalmology department, faculty of medicine, Minia university hospital
  last name: Mohamed Tarek AM Mostafa, Ass. Prof.
  role: Study Director
  affiliation: ophthalmology department, faculty of medicine, Minia university hospital
  last name: Abdallah MM Safwat, ass lecturer
  phone: 01092212031
  phone ext: 02
  email: drabdallahmh@gamil.com
  facility: 
  status: Recruiting
  contact: 
  country: Egypt
  citation: Newman DK. Surgical management of the late complications of proliferative diabetic retinopathy. Eye (Lond). 2010 Mar;24(3):441-9. doi: 10.1038/eye.2009.325. Epub 2010 Feb 5.
  PMID: 20139916
  citation: Meleth AD, Carvounis PE. Outcomes of vitrectomy for tractional retinal detachment in diabetic retinopathy. Int Ophthalmol Clin. 2014 Spring;54(2):127-39. doi: 10.1097/IIO.0000000000000021. No abstract available.
  PMID: 24613889
  citation: Gologorsky D, Thanos A, Vavvas D. Therapeutic interventions against inflammatory and angiogenic mediators in proliferative diabetic retinopathy. Mediators Inflamm. 2012;2012:629452. doi: 10.1155/2012/629452. Epub 2012 Sep 17.
  PMID: 23028203
  citation: Zhou J, Wang S, Xia X. Role of intravitreal inflammatory cytokines and angiogenic factors in proliferative diabetic retinopathy. Curr Eye Res. 2012 May;37(5):416-20. doi: 10.3109/02713683.2012.661114. Epub 2012 Mar 12.
  PMID: 22409294
  citation: Ricker LJ, Kijlstra A, Kessels AG, de Jager W, Liem AT, Hendrikse F, La Heij EC. Interleukin and growth factor levels in subretinal fluid in rhegmatogenous retinal detachment: a case-control study. PLoS One. 2011 Apr 27;6(4):e19141. doi: 10.1371/journal.pone.0019141.
  PMID: 21556354
  citation: Samson CM, Waheed N, Baltatzis S, Foster CS. Methotrexate therapy for chronic noninfectious uveitis: analysis of a case series of 160 patients. Ophthalmology. 2001 Jun;108(6):1134-9. doi: 10.1016/s0161-6420(01)00576-0.
  PMID: 11382642
  citation: Smith JR, Rosenbaum JT, Wilson DJ, Doolittle ND, Siegal T, Neuwelt EA, Pe'er J. Role of intravitreal methotrexate in the management of primary central nervous system lymphoma with ocular involvement. Ophthalmology. 2002 Sep;109(9):1709-16. doi: 10.1016/s0161-6420(02)01125-9.
  PMID: 12208721
  citation: Amarnani D, Machuca-Parra AI, Wong LL, Marko CK, Stefater JA, Stryjewski TP, Eliott D, Arboleda-Velasquez JF, Kim LA. Effect of Methotrexate on an In Vitro Patient-Derived Model of Proliferative Vitreoretinopathy. Invest Ophthalmol Vis Sci. 2017 Aug 1;58(10):3940-3949. doi: 10.1167/iovs.16-20912.
  PMID: 28777835
  responsible party type: Principal Investigator
  investigator affiliation: Minia University
  investigator full name: Abdallah Mohsen Mohamed Safwat
  investigator title: assistant lecturer, ophthalmology department, faculty of medicine
  mesh term: Retinal Diseases
  mesh term: Diabetic Retinopathy
  mesh term: Methotrexate
  sharing ipd: No
  ipd description: email the main investigator for requested data