<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/NCT03758963</url>
  </required_header>
  <id_info>
    <org_study_id>LTN-02</org_study_id>
    <nct_id>NCT03758963</nct_id>
  </id_info>
  <brief_title>Selective Retina Therapy With 'R:GEN' in Patients With Central Serous Chorioretinopathy</brief_title>
  <official_title>A Prospective, Multi-center, Randomized, Double-blinded (Subject &amp; Independent Efficacy Evaluator), Comparative Clinical Study to Evaluate the Efficacy and Safety of SRT (Selective Retina Therapy) With 'R:GEN' in Patients With Central Serous Chorioretinopathy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>LUTRONIC Corporation</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>LUTRONIC Corporation</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>
      The purpose of this clinical study is to evaluate the efficacy and safety of selective retina&#xD;
      therapy (SRT) using R:GEN, an approved laser device, in patients with central serous&#xD;
      chorioretinopathy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In this study, treatment effect of each group will be evaluated by follow-up once a month of&#xD;
      both study group and control group other than the 2nd month until 6 months following the&#xD;
      first procedure.&#xD;
&#xD;
      For the primary efficacy evaluation, the percentage of subjects who show complete removal of&#xD;
      sub-retinal fluid (SRF) in Optical Coherence Tomography (OCT) results will be evaluated in&#xD;
      the study group, before SRF therapy and at 3 months after therapy, and in control group,&#xD;
      before sham procedure using R:GEN and at 3 months after therapy. In addition, for secondary&#xD;
      efficacy evaluation, major symptoms of central serous chorioretinopathy will be evaluated at&#xD;
      3 and 6 months including changes in best corrected visual acuity (BCVA) on the Early&#xD;
      Treatment Diabetic Retinopathy Study (ETDRS) chart, the degree of retinal functional damage,&#xD;
      and changes in sub-retinal fluid (SRF) and central macula thickness (CMT) on OCT. At 6&#xD;
      months, removal rate of leakage on Fluorescene Angiography (FA) and recurrence of the disease&#xD;
      will be evaluated to compare the recurrence rate of study group and control group undergoing&#xD;
      sham procedure.&#xD;
&#xD;
      The subjects in the study group who only meet the conditions of retreatment at 3 ~ 5 months&#xD;
      after selective retina therapy (SRT) may receive SRT up to twice again.&#xD;
&#xD;
      The subjects in the control group those who have not recovered naturally but have persistent&#xD;
      clinical symptoms at 3 months will undergo SRT. And the subjects in the control group who&#xD;
      only meet the conditions of retreatment at 5 months after SRT at 2 months.&#xD;
&#xD;
      And the subjects in the control group, who have experienced complete disappearance of SRF at&#xD;
      3 months after Sham procedure, but SRF is observed again at 4 or 5 months, may receive SRT up&#xD;
      to twice again.&#xD;
&#xD;
      These subjects will be categorized into a separate subgroup and the efficacy and safety of&#xD;
      SRT will be evaluated every visit.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 30, 2016</start_date>
  <completion_date type="Actual">June 20, 2018</completion_date>
  <primary_completion_date type="Actual">April 2, 2018</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>
    <masking_description>In this study, double-blinding will be applied for subjects and independent efficacy evaluators. It is difficult to apply blinding to the practitioner who handles the products used for therapy because of difference in the procedure of the treatment and sham, but the information related to the medical device shall not be released to subjects and independent efficacy evaluators. For blinding of independent efficacy evaluators, an independent evaluator shall conduct efficacy evaluation tests (OCT, BCVA test, contrast sensitivity test, FA).&#xD;
Subjects and independent efficacy evaluators will not know which group the subjects are assigned to and whether SRT or sham procedure is used. The blinding on the test device will be maintained until the data for statistical analysis are opened.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Sub-retinal Fluid (SRF) Removal Rate</measure>
    <time_frame>3 months</time_frame>
    <description>The percentage of subjects (%) who show complete removal of Sub-retinal Fluid (SRF) on Optical Coherence Tomography (OCT) is compared between study group and control group.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Improvement of Best Corrected Visual Acuity</measure>
    <time_frame>3, 6 months</time_frame>
    <description>The improvement of Best Corrected Visual Acuity is evaluated using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart and is compared between study group and control group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Degree of Retinal Functional Damage</measure>
    <time_frame>3, 6 months</time_frame>
    <description>The degree of retinal functional damage is compared between study group and control group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Sub-retinal Fluid (SRF)</measure>
    <time_frame>3, 6 months</time_frame>
    <description>The change in Sub-retinal Fluid (SRF) (μm, mm3) on Optical Coherence Tomography (OCT) is compared between study group and control group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Central Macular Thickness</measure>
    <time_frame>3, 6 months</time_frame>
    <description>The change on Central Macular Thickness (CMT) (μm) based on Optical Coherence Tomography (OCT) results are compared between the study and control group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Removal Rate of Leakage</measure>
    <time_frame>6 months</time_frame>
    <description>The percentage (%) of participants who show complete removal of leakage in Fluorescene Angiography (FA) results is compared between study group and control group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Recurrence Rate</measure>
    <time_frame>6 months</time_frame>
    <description>The percentage (%) of participants who show recurrence is compared between study group and control group</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">63</enrollment>
  <condition>Central Serous Chorioretinopathy</condition>
  <arm_group>
    <arm_group_label>Active Laser</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Once the energy to be applied for the treatment is determined through the laser irradiation testing, conduct laser therapy after selecting &quot;T&quot; corresponding to treatment laser on GUI.&#xD;
At irradiation, excluding the circle area with a 100 μm radius (200 μm diameter) from the center of the fovea, irradiate laser in the form of surrounding the leakage site with an interval of 0.5-1 spot diameter (fovea = 1 spot size). As for the test spots, the serial number needs to be given for each treatment spot with the order of irradiation, as described above.&#xD;
If pigment epithelial detachment (PED) occurs at the leakage site, irradiate laser around the PED (excluding the circle area with a 100 μm radius (200 μm diameter) from the center), not to the leakage site.&#xD;
Within 2 hours after therapy, perform tests for efficacy evaluation (color fundus photography and fluorescein angiography).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham Laser procedure</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Select &quot;C&quot; corresponding to Sham Therapy on GUI of the laser device, and then perform Sham therapy.&#xD;
During Sham therapy, for patient's blinding, both light from the slit lamp and sound from laser oscillation are same as laser irradiation, and no laser oscillation will occur for treatment.&#xD;
Perform subsequent procedures in the same manner as the procedure of study group.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>R:GEN Selective Retina Therapy</intervention_name>
    <description>Selective Retina Therapy (SRT) is the treatment method using innovative laser technology with the wavelength absorbed by melanosomes such as laser photocoagulation, but due to short pulse width (1.7 µs) with 100 Hz repetition rate, Retinal Pigment Epithelium (RPE) cells may be destroyed only through the generation of microbubble around melanosomes (photomechanical action), and no thermal damage of normal cells or tissues may occur in the surrounding tissues. SRT influences the RPE wound healing, including migration and proliferation of RPE cells, which treats CSC in the mechanism of recovering RPE. Once RPE is recovered, the sub-retinal fluid may be pumped out and retinal function again recovered. Moreover, previous studies showed that SRT may stimulate a moderate increase of activated metalloproteinase (MMP), leading to the improvement of Bruch's membrane's transport property.</description>
    <arm_group_label>Active Laser</arm_group_label>
    <arm_group_label>Sham Laser procedure</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male and female adult patients aged 19 or over and less than 55&#xD;
&#xD;
          2. Patients who have had clinical symptoms of central serous chorioretinopathy over 3&#xD;
             months.&#xD;
&#xD;
          3. Patients whose best corrected visual acuity (BCVA) is at least 20/200 based on the&#xD;
             Early Treatment Diabetic Retinopathy Study (ETDRS) chart (BCVA based on the ETDRS&#xD;
             chart will be converted into logMAR)&#xD;
&#xD;
          4. Patients with Sub-Retinal Fluid (SRF) that has been going into the fovea continuously&#xD;
&#xD;
          5. Patients with ≥1 ~ ≤ 3 active leakage sites in Fundus Fluorescein Angiography (FA)&#xD;
&#xD;
          6. Patients who are of child-bearing potential and have agreed to use a medically&#xD;
             acceptable contraceptive method during the study period&#xD;
&#xD;
             ☞Medically acceptable contraceptive method: Condom, oral contraceptive pills that have&#xD;
             been continued for more than three months, contraceptive injection or implants or&#xD;
             intrauterine contraceptive device&#xD;
&#xD;
          7. Patients who voluntarily agree to participate in this study, and are willing to and&#xD;
             able to follow the protocol.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with other retinal diseases such as choroidal neovascularization, polypoidal&#xD;
             choroidal vasculopathy.&#xD;
&#xD;
          2. Patients with the conditions that make laser therapy difficult such as cataract or&#xD;
             vitreous cloudiness.&#xD;
&#xD;
          3. Patients who have atrophy (diameter: ≥1000㎛) in the retinal pigment epithelium&#xD;
             including the fovea.&#xD;
&#xD;
          4. Patients who had undergone laser or photodynamic therapy for central serous&#xD;
             chorioretinopathy prior to the study participation.&#xD;
&#xD;
          5. Patients who have received steroid treatment (periocular, subtenon, intraocular)&#xD;
             within the last one year&#xD;
&#xD;
          6. Patients who have received intraocular injection of anti-Vascular Endothelial Growth&#xD;
             Factor (anti-VEGF) agent within the last six months.&#xD;
&#xD;
          7. Patients who have undergone ophthalmological surgery such as intraocular surgery or&#xD;
             vitrectomy within the last six months.&#xD;
&#xD;
          8. Patients who have taken medication for central serous chorioretinopathy such as&#xD;
             acetazolamide, spironolactone, and kalidinogenase [within the last two months].&#xD;
&#xD;
          9. Patients who have a history of allergy to fluorescein used for FA and indocyanine&#xD;
             green used for ICG angiography.&#xD;
&#xD;
         10. Female patients who are pregnant or breastfeeding.&#xD;
&#xD;
         11. Patients with systemic diseases such as Cushing's syndrome, inflammatory diseases,&#xD;
             uncontrolled hypertension and diabetes, liver diseases, kidney diseases.&#xD;
&#xD;
         12. Patients who have pigment epithelial detachment that is directly related to the point&#xD;
             of leakage with a diameter of more than 1000 μm.&#xD;
&#xD;
         13. Patients who are considered ineligible for this study according to the investigator's&#xD;
             judgment.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Oh Woong Kwon, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Nune Eye Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Seoul National University Bundang Hospital</name>
      <address>
        <city>Seongnam-si</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Korea University Anam hospital</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nune Eye Hospital</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seoul National University Hospital</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Catholic University of Korea Seoul ST.Mary's Hospital</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Catholic University of Korea Yeouido St.Mary's Hospital</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>November 2018</verification_date>
  <study_first_submitted>November 28, 2018</study_first_submitted>
  <study_first_submitted_qc>November 28, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 29, 2018</study_first_posted>
  <last_update_submitted>November 28, 2018</last_update_submitted>
  <last_update_submitted_qc>November 28, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">November 29, 2018</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>Central Serous Chorioretinopathy</mesh_term>
  </condition_browse>
  <!-- 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/NCT03758963
org study id: LTN-02
nct id: NCT03758963
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this clinical study is to evaluate the efficacy and safety of selective retina
      therapy (SRT) using R:GEN, an approved laser device, in patients with central serous
      chorioretinopathy.
In this study, treatment effect of each group will be evaluated by follow-up once a month of
      both study group and control group other than the 2nd month until 6 months following the
      first procedure.

      For the primary efficacy evaluation, the percentage of subjects who show complete removal of
      sub-retinal fluid (SRF) in Optical Coherence Tomography (OCT) results will be evaluated in
      the study group, before SRF therapy and at 3 months after therapy, and in control group,
      before sham procedure using R:GEN and at 3 months after therapy. In addition, for secondary
      efficacy evaluation, major symptoms of central serous chorioretinopathy will be evaluated at
      3 and 6 months including changes in best corrected visual acuity (BCVA) on the Early
      Treatment Diabetic Retinopathy Study (ETDRS) chart, the degree of retinal functional damage,
      and changes in sub-retinal fluid (SRF) and central macula thickness (CMT) on OCT. At 6
      months, removal rate of leakage on Fluorescene Angiography (FA) and recurrence of the disease
      will be evaluated to compare the recurrence rate of study group and control group undergoing
      sham procedure.

      The subjects in the study group who only meet the conditions of retreatment at 3 ~ 5 months
      after selective retina therapy (SRT) may receive SRT up to twice again.

      The subjects in the control group those who have not recovered naturally but have persistent
      clinical symptoms at 3 months will undergo SRT. And the subjects in the control group who
      only meet the conditions of retreatment at 5 months after SRT at 2 months.

      And the subjects in the control group, who have experienced complete disappearance of SRF at
      3 months after Sham procedure, but SRF is observed again at 4 or 5 months, may receive SRT up
      to twice again.

      These subjects will be categorized into a separate subgroup and the efficacy and safety of
      SRT will be evaluated every visit.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
masking description: In this study, double-blinding will be applied for subjects and independent efficacy evaluators. It is difficult to apply blinding to the practitioner who handles the products used for therapy because of difference in the procedure of the treatment and sham, but the information related to the medical device shall not be released to subjects and independent efficacy evaluators. For blinding of independent efficacy evaluators, an independent evaluator shall conduct efficacy evaluation tests (OCT, BCVA test, contrast sensitivity test, FA).
Subjects and independent efficacy evaluators will not know which group the subjects are assigned to and whether SRT or sham procedure is used. The blinding on the test device will be maintained until the data for statistical analysis are opened.
measure: Sub-retinal Fluid (SRF) Removal Rate
time frame: 3 months
description: The percentage of subjects (%) who show complete removal of Sub-retinal Fluid (SRF) on Optical Coherence Tomography (OCT) is compared between study group and control group.
measure: Improvement of Best Corrected Visual Acuity
time frame: 3, 6 months
description: The improvement of Best Corrected Visual Acuity is evaluated using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart and is compared between study group and control group.
measure: Degree of Retinal Functional Damage
time frame: 3, 6 months
description: The degree of retinal functional damage is compared between study group and control group.
measure: Change in Sub-retinal Fluid (SRF)
time frame: 3, 6 months
description: The change in Sub-retinal Fluid (SRF) (μm, mm3) on Optical Coherence Tomography (OCT) is compared between study group and control group.
measure: Change in Central Macular Thickness
time frame: 3, 6 months
description: The change on Central Macular Thickness (CMT) (μm) based on Optical Coherence Tomography (OCT) results are compared between the study and control group.
measure: Removal Rate of Leakage
time frame: 6 months
description: The percentage (%) of participants who show complete removal of leakage in Fluorescene Angiography (FA) results is compared between study group and control group.
measure: Recurrence Rate
time frame: 6 months
description: The percentage (%) of participants who show recurrence is compared between study group and control group
arm group label: Active Laser
arm group type: Experimental
description: Once the energy to be applied for the treatment is determined through the laser irradiation testing, conduct laser therapy after selecting "T" corresponding to treatment laser on GUI.
At irradiation, excluding the circle area with a 100 μm radius (200 μm diameter) from the center of the fovea, irradiate laser in the form of surrounding the leakage site with an interval of 0.5-1 spot diameter (fovea = 1 spot size). As for the test spots, the serial number needs to be given for each treatment spot with the order of irradiation, as described above.
If pigment epithelial detachment (PED) occurs at the leakage site, irradiate laser around the PED (excluding the circle area with a 100 μm radius (200 μm diameter) from the center), not to the leakage site.
Within 2 hours after therapy, perform tests for efficacy evaluation (color fundus photography and fluorescein angiography).
arm group label: Sham Laser procedure
arm group type: Sham Comparator
description: Select "C" corresponding to Sham Therapy on GUI of the laser device, and then perform Sham therapy.
During Sham therapy, for patient's blinding, both light from the slit lamp and sound from laser oscillation are same as laser irradiation, and no laser oscillation will occur for treatment.
Perform subsequent procedures in the same manner as the procedure of study group.
intervention type: Device
intervention name: R:GEN Selective Retina Therapy
description: Selective Retina Therapy (SRT) is the treatment method using innovative laser technology with the wavelength absorbed by melanosomes such as laser photocoagulation, but due to short pulse width (1.7 µs) with 100 Hz repetition rate, Retinal Pigment Epithelium (RPE) cells may be destroyed only through the generation of microbubble around melanosomes (photomechanical action), and no thermal damage of normal cells or tissues may occur in the surrounding tissues. SRT influences the RPE wound healing, including migration and proliferation of RPE cells, which treats CSC in the mechanism of recovering RPE. Once RPE is recovered, the sub-retinal fluid may be pumped out and retinal function again recovered. Moreover, previous studies showed that SRT may stimulate a moderate increase of activated metalloproteinase (MMP), leading to the improvement of Bruch's membrane's transport property.
arm group label: Active Laser
arm group label: Sham Laser procedure
criteria: 
gender: All
minimum age: 19 Years
maximum age: 55 Years
healthy volunteers: No
last name: Oh Woong Kwon, PhD
role: Principal Investigator
affiliation: Nune Eye Hospital
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Korea, Republic of
responsible party type: Sponsor
mesh term: Central Serous Chorioretinopathy