<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/NCT03275896</url>
  </required_header>
  <id_info>
    <org_study_id>R1366/52/2016</org_study_id>
    <nct_id>NCT03275896</nct_id>
  </id_info>
  <brief_title>Evaluation of the Efficacy of Descemet Membrane Transplantation for the Treatment of Fuchs' Endothelial Dystrophy</brief_title>
  <official_title>Evaluation of the Efficacy of Descemet Membrane Transplantation for the Treatment of Fuchs' Endothelial Dystrophy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Singapore National Eye Centre</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Singapore National Eye Centre</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>
      Fuchs Endothelial Dystrophy (FED) is a degenerative disease affecting the corneal&#xD;
      endothelium. The current gold-standard for treatment of severe FED is endothelial&#xD;
      keratoplasty, wherein a cadaveric Descemet's membrane / endothelium graft is transplanted. In&#xD;
      this study, the investigators hypothesized that the transplantation of an acellular&#xD;
      Descemet's membrane (i.e. Descemet Membrane Transplantation, 'DMT') may be equally&#xD;
      efficacious in promoting recovery of endothelial function in this group of patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Fuchs Endothelial Dystrophy (FED) is a degenerative disease affecting the corneal&#xD;
      endothelium, characterized clinically by guttate excrescences on the posterior corneal&#xD;
      surface and dysfunctional corneal endothelial cells. While patients are commonly asymptomatic&#xD;
      in their early stages, advanced FED can be associated with significant corneal edema,&#xD;
      scarring and impairment of visual function.&#xD;
&#xD;
      Patients with mild FED are usually managed conservatively with the application of topical&#xD;
      hypertonic saline eyedrops. For patients with advanced FED, endothelial keratoplasty may&#xD;
      often be necessary. In 2014, FED represented the most common indication for endothelial&#xD;
      keratoplasty in the United States, accounting for 47.7% (13,817 cases) of all endothelial&#xD;
      keratoplasty procedures performed nationwide. In Singapore, FED was the second most common&#xD;
      indication for corneal transplantation.&#xD;
&#xD;
      Endothelial keratoplasty is associated with endothelial cell attrition in the range of 29.7%&#xD;
      - 47% by the 3rd post-operative year. Additionally, the global demand for corneal graft&#xD;
      material currently still far outstrips supply, critically limiting the number of patients who&#xD;
      can potentially benefit from these surgical interventions. As such, there is a need explore&#xD;
      alternative, sustainable strategies for the management of FED.&#xD;
&#xD;
      In 2009, Shah et al. reported the treatment of a 34 years old patient, with the combined&#xD;
      pathologies of FED and Posterior Polymorphous Corneal Dystrophy (PPMD), by primary stripping&#xD;
      of the central 4-5mm of Descemet's membrane without corneal graft transplantation ('Primary&#xD;
      Descemetorhexis'). Contrary to conventional expectations, there was complete repopulation of&#xD;
      the posterior corneal surface by corneal endothelial cells following the surgery, with&#xD;
      best-corrected-visual-acuity (BCVA) of 6/7.5 achieved by the 6th post-operative month. In&#xD;
      2014, Moloney et al. published a similar report of a 54 years old patient, diagnosed with&#xD;
      FED, successfully treated by Primary Descemetorhexis. Rapid endothelial recovery, as&#xD;
      evidenced by a central endothelial cell count of 620 cells/mm2 and BCVA of 6/6, was achieved&#xD;
      by approximately 6 weeks after the surgery. The success of these cases raised the prospect of&#xD;
      Primary Descemetorhexis as a feasible alternative for the treatment of FED.&#xD;
&#xD;
      To gain a better understanding of the factors which may affect endothelial recovery following&#xD;
      Primary Descemetorhexis, investigators performed an ex vivo human corneal endothelial cell&#xD;
      culture experiment in which Primary Descemetorhexis was performed on cadaveric human cornea&#xD;
      buttons, followed by ex vivo culture for a duration of 2 weeks to allow for endothelial&#xD;
      recovery. A less invasive approach of denuding endothelial cells from the Descemet's membrane&#xD;
      (DM), while maintaining anatomical integrity of the DM, was also assessed. The investigators&#xD;
      found that advanced patient age and the absence of DM were significantly associated with&#xD;
      slower endothelial recovery.&#xD;
&#xD;
      As such, the investigators hypothesized that the outcomes of Primary Descemetorhexis for the&#xD;
      treatment of FED may be improved by DM transplantation following Primary Descemetorhexis ('DM&#xD;
      Transplantation'). The main difference between the proposed technique of DM transplantation&#xD;
      and conventional endothelial keratoplasty is that the DM transplant does not require the&#xD;
      presence of a functional corneal endothelial monolayer on the graft. If successful, the&#xD;
      greatest advantage of this approach would be to greatly expand the pool of donors who are&#xD;
      eligible to provide cadaveric corneal graft tissue for transplantation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">September 2016</start_date>
  <completion_date type="Anticipated">December 2020</completion_date>
  <primary_completion_date type="Anticipated">December 2020</primary_completion_date>
  <phase>Early Phase 1</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>Central Endothelial Cell Density</measure>
    <time_frame>Measured monthly, for the first 6 post-operative months</time_frame>
    <description>Central endothelial cell density will be determined using a specular microscope (Konan Medical), measured as number of cells per square millimetre, using the automated cell counting algorithm.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Visual acuity</measure>
    <time_frame>Measured monthly, for the first 6 post-operative months</time_frame>
    <description>The visual acuity will be measured using the Snellen visual acuity scale, performed in a standardized room using a 6-metre visual acuity lane, by a fully qualified optometrist.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Fuchs' Endothelial Dystrophy</condition>
  <arm_group>
    <arm_group_label>Descemet Membrane Transplantation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with severe, symptomatic Fuch's Endothelial Dystrophy (FED) will be offered Descemet Membrane Transplantation (DMT) for their condition.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Descemet Membrane Transplantation</intervention_name>
    <description>The diseased host Descemet membrane will first be stripped, as per a standard Descemet Stripping Automated Endothelial Keratoplasty surgery. A cadaveric, acellular Descemet membrane graft will then be harvested and transplanted onto the host.</description>
    <arm_group_label>Descemet Membrane Transplantation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Fuchs' Endothelial Dystrophy (FED) as defined by any of the following criteria:&#xD;
&#xD;
               1. FED of at least Grade 4 on the Krachmer grading scale (i.e. greater than 5mm of&#xD;
                  confluent central corneal guttata)&#xD;
&#xD;
               2. Best-corrected-visual-acuity of less than 6/12 in a patient clinically diagnosed&#xD;
                  with FED of any grade, in which poor visual acuity cannot be accounted by any&#xD;
                  other significant ophthalmic disease (e.g. cataracts, age-related macular&#xD;
                  degeneration, glaucoma, optic neuropathies)&#xD;
&#xD;
          2. Patients in the range of &lt;85 years old will be recruited for this study&#xD;
&#xD;
          3. Only individuals with the mental capacity to provide informed consent will be&#xD;
             included.&#xD;
&#xD;
          4. Patients who are willing and able to sign a written Informed Consent Form prior to any&#xD;
             study-specific procedures will be included&#xD;
&#xD;
          5. Patients who are willing and able to return for scheduled follow-up examinations for&#xD;
             up to 12 months after the surgery will be included&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Subjects that meet any of the following criteria will be excluded from participation:&#xD;
&#xD;
          1. Eyes which have previously been subject to any form of keratoplasty&#xD;
&#xD;
          2. An only-functioning eye in a patient who has lost visual potential in the&#xD;
             contralateral eye&#xD;
&#xD;
          3. Patients with chronic, advanced FED who meet the above mentioned inclusion criteria,&#xD;
             but whose disease is associated with significant stromal scarring to such an extent&#xD;
             that will predictably impair post-operative visual recovery after DSAEK or DM&#xD;
             transplant&#xD;
&#xD;
          4. Patients whose corneal endothelial disease may possibly be attributed to pathologies&#xD;
             other than FED, including but not limited to pseudophakic bullous keratopathy,&#xD;
             laser-peripheral-iridotomy induced bullous keratopathy, iridocorneal endothelial&#xD;
             syndrome, Axenfeld Rieger syndrome, congenital hereditary endothelial dystrophy and&#xD;
             any other anterior segment developmental anomalies&#xD;
&#xD;
          5. Patients with visually significant cataracts&#xD;
&#xD;
          6. Patients with diagnosed with visually significant retinal disease, including but not&#xD;
             limited to age-related macular degeneration, myopic macular degeneration, diabetic&#xD;
             retinopathy, diabetes related maculopathy, retinal vein occlusion related maculpathy,&#xD;
             retinal dystrophies and previous retinal detachments.&#xD;
&#xD;
          7. Patients with any form of glaucoma&#xD;
&#xD;
          8. Patients diagnosed with visually significant, non-glaucomatous optic neuropathies,&#xD;
             including but not limited to those related to ischemic (both arteritic and&#xD;
             non-arteritic), toxic, nutritional, myopic, compression, infective and inflammatory&#xD;
             causes&#xD;
&#xD;
          9. Patients who are pregnant, lactating, of child-bearing potential and not practising a&#xD;
             medically approved method of birth control, or planning to become pregnant during the&#xD;
             course of the trial, and patients with other conditions associated with fluctuation of&#xD;
             hormones that could lead to refractive changes.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jodhbir Mehta, FRCS</last_name>
    <role>Principal Investigator</role>
    <affiliation>Singapore National Eye Centre</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Yu Qiang Soh, MBBS</last_name>
    <email>yuqiang.soh@mohh.com.sg</email>
  </overall_contact>
  <location>
    <facility>
      <name>Singapore National Eye Centre</name>
      <address>
        <city>Singapore</city>
        <zip>168751</zip>
        <country>Singapore</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yu Qiang Soh, MBBS</last_name>
    </contact>
    <investigator>
      <last_name>Jodhbir Mehta, FRCS</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Singapore</country>
  </location_countries>
  <reference>
    <citation>Soh YQ, Peh G, George BL, Seah XY, Primalani NK, Adnan K, Mehta JS. Predicative Factors for Corneal Endothelial Cell Migration. Invest Ophthalmol Vis Sci. 2016 Feb;57(2):338-48. doi: 10.1167/iovs.15-18300.</citation>
    <PMID>26842752</PMID>
  </reference>
  <reference>
    <citation>Arbelaez JG, Price MO, Price FW Jr. Long-term follow-up and complications of stripping descemet membrane without placement of graft in eyes with Fuchs endothelial dystrophy. Cornea. 2014 Dec;33(12):1295-9. doi: 10.1097/ICO.0000000000000270.</citation>
    <PMID>25299425</PMID>
  </reference>
  <reference>
    <citation>Bleyen I, Saelens IE, van Dooren BT, van Rij G. Spontaneous corneal clearing after Descemet's stripping. Ophthalmology. 2013 Jan;120(1):215. doi: 10.1016/j.ophtha.2012.08.037. No abstract available.</citation>
    <PMID>23283191</PMID>
  </reference>
  <reference>
    <citation>Moloney G, Chan UT, Hamilton A, Zahidin AM, Grigg JR, Devasahayam RN. Descemetorhexis for Fuchs' dystrophy. Can J Ophthalmol. 2015 Feb;50(1):68-72. doi: 10.1016/j.jcjo.2014.10.014. Epub 2014 Oct 31.</citation>
    <PMID>25677286</PMID>
  </reference>
  <reference>
    <citation>Shah RD, Randleman JB, Grossniklaus HE. Spontaneous corneal clearing after Descemet's stripping without endothelial replacement. Ophthalmology. 2012 Feb;119(2):256-60. doi: 10.1016/j.ophtha.2011.07.032. Epub 2011 Oct 7.</citation>
    <PMID>21982414</PMID>
  </reference>
  <reference>
    <citation>Kitagawa K, Kojima M, Sasaki H, Shui YB, Chew SJ, Cheng HM, Ono M, Morikawa Y, Sasaki K. Prevalence of primary cornea guttata and morphology of corneal endothelium in aging Japanese and Singaporean subjects. Ophthalmic Res. 2002 May-Jun;34(3):135-8. doi: 10.1159/000063656.</citation>
    <PMID>12097795</PMID>
  </reference>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>September 4, 2017</study_first_submitted>
  <study_first_submitted_qc>September 6, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 8, 2017</study_first_posted>
  <last_update_submitted>September 6, 2017</last_update_submitted>
  <last_update_submitted_qc>September 6, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 8, 2017</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>Fuchs' Endothelial Dystrophy</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>No sharing of OPD with other researchers</ipd_description>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>August 28, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/96/NCT03275896/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>June 27, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/96/NCT03275896/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03275896
org study id: R1366/52/2016
nct id: NCT03275896
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Fuchs Endothelial Dystrophy (FED) is a degenerative disease affecting the corneal
      endothelium. The current gold-standard for treatment of severe FED is endothelial
      keratoplasty, wherein a cadaveric Descemet's membrane / endothelium graft is transplanted. In
      this study, the investigators hypothesized that the transplantation of an acellular
      Descemet's membrane (i.e. Descemet Membrane Transplantation, 'DMT') may be equally
      efficacious in promoting recovery of endothelial function in this group of patients.
Fuchs Endothelial Dystrophy (FED) is a degenerative disease affecting the corneal
      endothelium, characterized clinically by guttate excrescences on the posterior corneal
      surface and dysfunctional corneal endothelial cells. While patients are commonly asymptomatic
      in their early stages, advanced FED can be associated with significant corneal edema,
      scarring and impairment of visual function.

      Patients with mild FED are usually managed conservatively with the application of topical
      hypertonic saline eyedrops. For patients with advanced FED, endothelial keratoplasty may
      often be necessary. In 2014, FED represented the most common indication for endothelial
      keratoplasty in the United States, accounting for 47.7% (13,817 cases) of all endothelial
      keratoplasty procedures performed nationwide. In Singapore, FED was the second most common
      indication for corneal transplantation.

      Endothelial keratoplasty is associated with endothelial cell attrition in the range of 29.7%
      - 47% by the 3rd post-operative year. Additionally, the global demand for corneal graft
      material currently still far outstrips supply, critically limiting the number of patients who
      can potentially benefit from these surgical interventions. As such, there is a need explore
      alternative, sustainable strategies for the management of FED.

      In 2009, Shah et al. reported the treatment of a 34 years old patient, with the combined
      pathologies of FED and Posterior Polymorphous Corneal Dystrophy (PPMD), by primary stripping
      of the central 4-5mm of Descemet's membrane without corneal graft transplantation ('Primary
      Descemetorhexis'). Contrary to conventional expectations, there was complete repopulation of
      the posterior corneal surface by corneal endothelial cells following the surgery, with
      best-corrected-visual-acuity (BCVA) of 6/7.5 achieved by the 6th post-operative month. In
      2014, Moloney et al. published a similar report of a 54 years old patient, diagnosed with
      FED, successfully treated by Primary Descemetorhexis. Rapid endothelial recovery, as
      evidenced by a central endothelial cell count of 620 cells/mm2 and BCVA of 6/6, was achieved
      by approximately 6 weeks after the surgery. The success of these cases raised the prospect of
      Primary Descemetorhexis as a feasible alternative for the treatment of FED.

      To gain a better understanding of the factors which may affect endothelial recovery following
      Primary Descemetorhexis, investigators performed an ex vivo human corneal endothelial cell
      culture experiment in which Primary Descemetorhexis was performed on cadaveric human cornea
      buttons, followed by ex vivo culture for a duration of 2 weeks to allow for endothelial
      recovery. A less invasive approach of denuding endothelial cells from the Descemet's membrane
      (DM), while maintaining anatomical integrity of the DM, was also assessed. The investigators
      found that advanced patient age and the absence of DM were significantly associated with
      slower endothelial recovery.

      As such, the investigators hypothesized that the outcomes of Primary Descemetorhexis for the
      treatment of FED may be improved by DM transplantation following Primary Descemetorhexis ('DM
      Transplantation'). The main difference between the proposed technique of DM transplantation
      and conventional endothelial keratoplasty is that the DM transplant does not require the
      presence of a functional corneal endothelial monolayer on the graft. If successful, the
      greatest advantage of this approach would be to greatly expand the pool of donors who are
      eligible to provide cadaveric corneal graft tissue for transplantation.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Central Endothelial Cell Density
time frame: Measured monthly, for the first 6 post-operative months
description: Central endothelial cell density will be determined using a specular microscope (Konan Medical), measured as number of cells per square millimetre, using the automated cell counting algorithm.
measure: Visual acuity
time frame: Measured monthly, for the first 6 post-operative months
description: The visual acuity will be measured using the Snellen visual acuity scale, performed in a standardized room using a 6-metre visual acuity lane, by a fully qualified optometrist.
arm group label: Descemet Membrane Transplantation
arm group type: Experimental
description: Patients with severe, symptomatic Fuch's Endothelial Dystrophy (FED) will be offered Descemet Membrane Transplantation (DMT) for their condition.
intervention type: Other
intervention name: Descemet Membrane Transplantation
description: The diseased host Descemet membrane will first be stripped, as per a standard Descemet Stripping Automated Endothelial Keratoplasty surgery. A cadaveric, acellular Descemet membrane graft will then be harvested and transplanted onto the host.
arm group label: Descemet Membrane Transplantation
criteria: 
gender: All
minimum age: 21 Years
maximum age: 85 Years
healthy volunteers: No
last name: Jodhbir Mehta, FRCS
role: Principal Investigator
affiliation: Singapore National Eye Centre
last name: Yu Qiang Soh, MBBS
email: yuqiang.soh@mohh.com.sg
facility: 
status: Recruiting
contact: 
investigator: 
country: Singapore
citation: Soh YQ, Peh G, George BL, Seah XY, Primalani NK, Adnan K, Mehta JS. Predicative Factors for Corneal Endothelial Cell Migration. Invest Ophthalmol Vis Sci. 2016 Feb;57(2):338-48. doi: 10.1167/iovs.15-18300.
PMID: 26842752
citation: Arbelaez JG, Price MO, Price FW Jr. Long-term follow-up and complications of stripping descemet membrane without placement of graft in eyes with Fuchs endothelial dystrophy. Cornea. 2014 Dec;33(12):1295-9. doi: 10.1097/ICO.0000000000000270.
PMID: 25299425
citation: Bleyen I, Saelens IE, van Dooren BT, van Rij G. Spontaneous corneal clearing after Descemet's stripping. Ophthalmology. 2013 Jan;120(1):215. doi: 10.1016/j.ophtha.2012.08.037. No abstract available.
PMID: 23283191
citation: Moloney G, Chan UT, Hamilton A, Zahidin AM, Grigg JR, Devasahayam RN. Descemetorhexis for Fuchs' dystrophy. Can J Ophthalmol. 2015 Feb;50(1):68-72. doi: 10.1016/j.jcjo.2014.10.014. Epub 2014 Oct 31.
PMID: 25677286
citation: Shah RD, Randleman JB, Grossniklaus HE. Spontaneous corneal clearing after Descemet's stripping without endothelial replacement. Ophthalmology. 2012 Feb;119(2):256-60. doi: 10.1016/j.ophtha.2011.07.032. Epub 2011 Oct 7.
PMID: 21982414
citation: Kitagawa K, Kojima M, Sasaki H, Shui YB, Chew SJ, Cheng HM, Ono M, Morikawa Y, Sasaki K. Prevalence of primary cornea guttata and morphology of corneal endothelium in aging Japanese and Singaporean subjects. Ophthalmic Res. 2002 May-Jun;34(3):135-8. doi: 10.1159/000063656.
PMID: 12097795
responsible party type: Sponsor
mesh term: Fuchs' Endothelial Dystrophy
sharing ipd: No
ipd description: No sharing of OPD with other researchers
provided document: 
provided document: 