<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/NCT03020459</url>
  </required_header>
  <id_info>
    <org_study_id>XH-16-049</org_study_id>
    <nct_id>NCT03020459</nct_id>
  </id_info>
  <brief_title>Internal Limiting Membrane Peeling-reposition to Treat Idiopathic Macular Holes</brief_title>
  <official_title>Comparing the Surgical Outcomes of Internal Limiting Membrane Peeling-reposition Versus Peeling in Idiopathic Macular Holes: A Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Xinhua Hospital, Shanghai Jiao Tong University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Xinhua Hospital, Shanghai Jiao Tong University School of Medicine</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>
      To compare the morphologic and functional outcomes of internal limiting membrane&#xD;
      peeling-reposition versus peeling in idiopathic macular holes&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This randomized clinical trial will be performed at a single center. Eligible patients with&#xD;
      idiopathic macular holes will be equally randomized to internal limiting membrane (ILM)&#xD;
      peeling-reposition group or ILM peeling group through computer-aided random allocation.&#xD;
&#xD;
      A standard 3-port pars plana vitrectomy was performed by a single surgeon using the&#xD;
      Constellation 23 gauge vitrectomy system (Alcon Laboratories Inc, Fort Worth, Texas,&#xD;
      USA).After posterior vitreous detachment was achieved, peeling of the ILM was performed by an&#xD;
      end gripping forceps with the assistance of Brilliant Blue G. In ILM peeling-reposition&#xD;
      group, the peeled ILM flap is flatten back to peeled area with assistance of&#xD;
      perfluoro-n-octane. In ILM peeling group, a round shape with 2.5 to 3.5 disc diameter of ILM&#xD;
      is peeled. This is followed by a complete fluid-gas exchange. Patients are encouraged to&#xD;
      maintain a face-down position for two weeks postoperatively in two groups.&#xD;
&#xD;
      Postoperative measurements of BCVA and spectral domain optical coherence tomography(SD-OCT)&#xD;
      are conducted at 1,3 and 6-month follow-up visits by independent masked observers. Macular&#xD;
      light sensitivity and fixation stability are determined with microperimetry at 1,3, and 6&#xD;
      months of follow-up. Mf-ERG, M-score chart and VFQ-25 chart are performed 1,3, and 6 months&#xD;
      of follow-up.&#xD;
&#xD;
      Comparison of BCVA, anatomical closure were primarily performed between the two groups. Then,&#xD;
      the morphologic changes of inner retina and the functional parameters measured from&#xD;
      microperimetry, Mf-ERG, M-score chart, VFQ-25 chart were analyzed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 1, 2017</start_date>
  <completion_date type="Actual">August 1, 2019</completion_date>
  <primary_completion_date type="Actual">July 30, 2019</primary_completion_date>
  <phase>N/A</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>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Best corrected visual acuity(BCVA)</measure>
    <time_frame>Pre-operation and 6 months after operation</time_frame>
    <description>Change from baseline BCVA at 6 months after operation, examined with snellen chart.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Close rate of macular holes</measure>
    <time_frame>1 month after operation</time_frame>
    <description>Observed from optical coherence tomography</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Morphologic changes of inner retina</measure>
    <time_frame>1，3，6 months after operation</time_frame>
    <description>Dimpling observed from optical coherence tomography</description>
  </other_outcome>
  <other_outcome>
    <measure>Central retinal thickness change</measure>
    <time_frame>Pre-operation and 1，3，6 months after operation</time_frame>
    <description>Measured by software in optical coherence tomography</description>
  </other_outcome>
  <other_outcome>
    <measure>Mean foveal light sensitivity change</measure>
    <time_frame>Pre-operation and 1，3，6 months after operation</time_frame>
    <description>Measured by microperimetry</description>
  </other_outcome>
  <other_outcome>
    <measure>Fixation stability change</measure>
    <time_frame>Pre-operation and 1，3，6 months after operation</time_frame>
    <description>Measured by microperimetry</description>
  </other_outcome>
  <other_outcome>
    <measure>Multifocal electroretinogram(Mf-ERG) change</measure>
    <time_frame>pre-operation and 1，3，6 months after operation</time_frame>
    <description>An objective measurement of retinal functions</description>
  </other_outcome>
  <other_outcome>
    <measure>M-chart score change</measure>
    <time_frame>Pre-operation and 1，3，6 months after operation</time_frame>
    <description>M-horizontal score and M-vertical score</description>
  </other_outcome>
  <other_outcome>
    <measure>Visual function questionnaire-25(VFQ-25) score change</measure>
    <time_frame>Pre-operation and 1，3，6 months after operation</time_frame>
    <description>A questionnaire consisted of 25 visual function questions concerning life quality</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Macular Hole</condition>
  <condition>Surgery</condition>
  <arm_group>
    <arm_group_label>peeling-reposition</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>After dying with Brilliant Blue G (Brilliant Blue; Gender, Germany) with the help of Constellation 23-gauge vitrectomy system (Alcon Laboratories Inc, Fort Worth, TX), the intervention of &quot;peeling-reposition&quot; was used to peel and unfold the ILM. And the postoperative posture would be prone position in two weeks for all patients after the operation.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>peeling</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>After dying with Brilliant Blue G (Brilliant Blue; Gender, Germany) with the help of Constellation 23-gauge vitrectomy system, the intervention of &quot;peeling&quot; was used to grasped ILM with end-gripping forceps. And the postoperative posture would be prone position in two weeks for all patients after the operation.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>peeling-reposition</intervention_name>
    <description>After dying with Brilliant Blue G (BBG, Brilliant Blue; Gender, Germany), a horizontal ILM strip is peeled off in inferior quadrant of macular area. Then the ILM was peeled from inferior to superior area continuously. The&quot; ILM roll &quot; was unfolded with assistance of perfluoro-n-octane (PFO). Finally, the position of the fixed ILM flap is adjusted under PFO bubble using flute needle or forceps.This was followed by a complete fluid-gas exchange using 14% perfluoropropane gas.Patients are introduced to maintain facedown position for two weeks postoperatively.</description>
    <arm_group_label>peeling-reposition</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>peeling</intervention_name>
    <description>After dying with Brilliant Blue G (Brilliant Blue; Gender, Germany), a horizontal ILM strip is peeled off in inferior quadrant of macular area. Then, the strand of ILM was peeled off radially from the foveal center to vascular arcade. In result, a round -shaped with 2.5-3.5 disc diameter ILM -peeled area was created.This was followed by a complete fluid-gas exchange using 14% perfluoropropane gas. Patients are encourage to maintain facedown position for two weeks postoperatively.</description>
    <arm_group_label>peeling</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Brilliant Blue G</intervention_name>
    <description>We intravitreal injected 0.1ml of Brilliant Blue G (Brilliant Blue; Gender, Germany) to dye ILM before ILM peeling.</description>
    <arm_group_label>peeling</arm_group_label>
    <arm_group_label>peeling-reposition</arm_group_label>
    <other_name>BBG</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>postoperative posture</intervention_name>
    <description>Patients of both two groups need to keep prone position for two weeks after the operation.</description>
    <arm_group_label>peeling</arm_group_label>
    <arm_group_label>peeling-reposition</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Constellation 23-gauge vitrectomy system</intervention_name>
    <description>All surgical procedures are operated on the Constellation 23-gauge vitrectomy system (Alcon Laboratories Inc, Fort Worth, TX).</description>
    <arm_group_label>peeling</arm_group_label>
    <arm_group_label>peeling-reposition</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  The patients are diagnosed as macular hole by optical coherence tomography.&#xD;
&#xD;
          -  Age ranges from 50 to 80 years.&#xD;
&#xD;
          -  The patients have indication for surgery.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Traumatic macular hole.&#xD;
&#xD;
          -  Combined with serious epiretinal membrane.&#xD;
&#xD;
          -  Combined with diabetic retinopathy, hypertensive retinopathy.&#xD;
&#xD;
          -  Combined with other ocular diseases, such as keratitis，uveitis，retinal vasculitis.&#xD;
&#xD;
          -  - 6.0 diopters or more of spherical equivalent, 26mm or more of axial length.&#xD;
&#xD;
          -  History of intraocular surgery.&#xD;
&#xD;
          -  Presence of staphyloma.&#xD;
&#xD;
          -  Other ocular diseases that could influence macular microstructure or visual function&#xD;
&#xD;
        Exit criteria:&#xD;
&#xD;
          -  For reposition group, the patients will exit the research if the peeled ILM cannot&#xD;
             reposition successfully.&#xD;
&#xD;
          -  Due to adverse events, especially severe adverse events, the researchers consider&#xD;
             withdrawal of patients based on concerns of safety and ethics;&#xD;
&#xD;
          -  Drop out;&#xD;
&#xD;
          -  The patients voluntarily withdraw the informed consent;&#xD;
&#xD;
          -  Serious violation of the study protocol due to the subjects or investigators' reasons;&#xD;
&#xD;
          -  Other reasons that the researchers believe for quitting the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Peiquan Zhao, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Xin Hua Hospital Affiliated to Shanghai Jiaotong University School of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine</name>
      <address>
        <city>Shanghai</city>
        <zip>200000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>February 2019</verification_date>
  <study_first_submitted>January 11, 2017</study_first_submitted>
  <study_first_submitted_qc>January 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 13, 2017</study_first_posted>
  <last_update_submitted>May 11, 2021</last_update_submitted>
  <last_update_submitted_qc>May 11, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 13, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>macular holes</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Retinal Perforations</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Individual participant data (IPD) will be shared after the end of this clinical trails.The data included patients' serial number, gender, age, laterality and all outcome measurement</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>After enrollment completed; After the last followup of the last participant.</ipd_time_frame>
  </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/NCT03020459
org study id: XH-16-049
nct id: NCT03020459
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
To compare the morphologic and functional outcomes of internal limiting membrane
      peeling-reposition versus peeling in idiopathic macular holes
This randomized clinical trial will be performed at a single center. Eligible patients with
      idiopathic macular holes will be equally randomized to internal limiting membrane (ILM)
      peeling-reposition group or ILM peeling group through computer-aided random allocation.

      A standard 3-port pars plana vitrectomy was performed by a single surgeon using the
      Constellation 23 gauge vitrectomy system (Alcon Laboratories Inc, Fort Worth, Texas,
      USA).After posterior vitreous detachment was achieved, peeling of the ILM was performed by an
      end gripping forceps with the assistance of Brilliant Blue G. In ILM peeling-reposition
      group, the peeled ILM flap is flatten back to peeled area with assistance of
      perfluoro-n-octane. In ILM peeling group, a round shape with 2.5 to 3.5 disc diameter of ILM
      is peeled. This is followed by a complete fluid-gas exchange. Patients are encouraged to
      maintain a face-down position for two weeks postoperatively in two groups.

      Postoperative measurements of BCVA and spectral domain optical coherence tomography(SD-OCT)
      are conducted at 1,3 and 6-month follow-up visits by independent masked observers. Macular
      light sensitivity and fixation stability are determined with microperimetry at 1,3, and 6
      months of follow-up. Mf-ERG, M-score chart and VFQ-25 chart are performed 1,3, and 6 months
      of follow-up.

      Comparison of BCVA, anatomical closure were primarily performed between the two groups. Then,
      the morphologic changes of inner retina and the functional parameters measured from
      microperimetry, Mf-ERG, M-score chart, VFQ-25 chart were analyzed.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: Best corrected visual acuity(BCVA)
time frame: Pre-operation and 6 months after operation
description: Change from baseline BCVA at 6 months after operation, examined with snellen chart.
measure: Close rate of macular holes
time frame: 1 month after operation
description: Observed from optical coherence tomography
measure: Morphologic changes of inner retina
time frame: 1，3，6 months after operation
description: Dimpling observed from optical coherence tomography
measure: Central retinal thickness change
time frame: Pre-operation and 1，3，6 months after operation
description: Measured by software in optical coherence tomography
measure: Mean foveal light sensitivity change
time frame: Pre-operation and 1，3，6 months after operation
description: Measured by microperimetry
measure: Fixation stability change
time frame: Pre-operation and 1，3，6 months after operation
description: Measured by microperimetry
measure: Multifocal electroretinogram(Mf-ERG) change
time frame: pre-operation and 1，3，6 months after operation
description: An objective measurement of retinal functions
measure: M-chart score change
time frame: Pre-operation and 1，3，6 months after operation
description: M-horizontal score and M-vertical score
measure: Visual function questionnaire-25(VFQ-25) score change
time frame: Pre-operation and 1，3，6 months after operation
description: A questionnaire consisted of 25 visual function questions concerning life quality
arm group label: peeling-reposition
arm group type: Experimental
description: After dying with Brilliant Blue G (Brilliant Blue; Gender, Germany) with the help of Constellation 23-gauge vitrectomy system (Alcon Laboratories Inc, Fort Worth, TX), the intervention of "peeling-reposition" was used to peel and unfold the ILM. And the postoperative posture would be prone position in two weeks for all patients after the operation.
arm group label: peeling
arm group type: Active Comparator
description: After dying with Brilliant Blue G (Brilliant Blue; Gender, Germany) with the help of Constellation 23-gauge vitrectomy system, the intervention of "peeling" was used to grasped ILM with end-gripping forceps. And the postoperative posture would be prone position in two weeks for all patients after the operation.
intervention type: Procedure
intervention name: peeling-reposition
description: After dying with Brilliant Blue G (BBG, Brilliant Blue; Gender, Germany), a horizontal ILM strip is peeled off in inferior quadrant of macular area. Then the ILM was peeled from inferior to superior area continuously. The" ILM roll " was unfolded with assistance of perfluoro-n-octane (PFO). Finally, the position of the fixed ILM flap is adjusted under PFO bubble using flute needle or forceps.This was followed by a complete fluid-gas exchange using 14% perfluoropropane gas.Patients are introduced to maintain facedown position for two weeks postoperatively.
arm group label: peeling-reposition
intervention type: Procedure
intervention name: peeling
description: After dying with Brilliant Blue G (Brilliant Blue; Gender, Germany), a horizontal ILM strip is peeled off in inferior quadrant of macular area. Then, the strand of ILM was peeled off radially from the foveal center to vascular arcade. In result, a round -shaped with 2.5-3.5 disc diameter ILM -peeled area was created.This was followed by a complete fluid-gas exchange using 14% perfluoropropane gas. Patients are encourage to maintain facedown position for two weeks postoperatively.
arm group label: peeling
intervention type: Drug
intervention name: Brilliant Blue G
description: We intravitreal injected 0.1ml of Brilliant Blue G (Brilliant Blue; Gender, Germany) to dye ILM before ILM peeling.
arm group label: peeling
arm group label: peeling-reposition
other name: BBG
intervention type: Other
intervention name: postoperative posture
description: Patients of both two groups need to keep prone position for two weeks after the operation.
arm group label: peeling
arm group label: peeling-reposition
intervention type: Device
intervention name: Constellation 23-gauge vitrectomy system
description: All surgical procedures are operated on the Constellation 23-gauge vitrectomy system (Alcon Laboratories Inc, Fort Worth, TX).
arm group label: peeling
arm group label: peeling-reposition
criteria: 
gender: All
minimum age: 50 Years
maximum age: 80 Years
healthy volunteers: No
last name: Peiquan Zhao, PhD
role: Principal Investigator
affiliation: Xin Hua Hospital Affiliated to Shanghai Jiaotong University School of Medicine
facility: 
country: China
responsible party type: Sponsor
mesh term: Retinal Perforations
sharing ipd: Yes
ipd description: Individual participant data (IPD) will be shared after the end of this clinical trails.The data included patients' serial number, gender, age, laterality and all outcome measurement
ipd info type: Study Protocol
ipd info type: Informed Consent Form (ICF)
ipd time frame: After enrollment completed; After the last followup of the last participant.