<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/NCT03016156</url>
  </required_header>
  <id_info>
    <org_study_id>RBAPP</org_study_id>
    <secondary_id>NCI-2021-05557</secondary_id>
    <nct_id>NCT03016156</nct_id>
  </id_info>
  <brief_title>Determination of the Sensitivity and Specificity of a Smartphone Application to Detect Retinoblastoma</brief_title>
  <official_title>Determination of the Sensitivity and Specificity of a Smartphone Application to Detect Retinoblastoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>St. Jude Children's Research Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>St. Jude Children's Research Hospital</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>
      This study seeks to determine whether a smartphone application called CRADLE (ComputeR&#xD;
      Assisted Detection of LEukocoria) has the potential to improve the detection of leukocoria.&#xD;
      There will be no impact on participants' health outcome.&#xD;
&#xD;
      This study will be performed in two parts, each with a distinct cohort of patients.&#xD;
&#xD;
      Part 1 will assess the feasibility of various techniques/conditions for using CRADLE within&#xD;
      patients known to have leukocoria.&#xD;
&#xD;
      Part 2 will estimate the sensitivity and specificity of CRADLE to detect leukocoria (using&#xD;
      the techniques selected from information gathered in Part 1) as compared to an&#xD;
      ophthalmoscope, within patients referred to the clinic for suspected leukocoria.&#xD;
&#xD;
      PRIMARY OBJECTIVES:&#xD;
&#xD;
        -  To determine the most effective usage of a camera phone application (CRADLE) to maximize&#xD;
           detection of leukocoria in patients with retinoblastoma, congenital cataracts, and&#xD;
           glaucoma.&#xD;
&#xD;
        -  To estimate the sensitivity and specificity of a camera phone application (CRADLE) in&#xD;
           detecting leukocoria.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will utilize three strata called Stratum I, Stratum II and Stratum III.&#xD;
&#xD;
      STRATUM I - Infants and children known to have leukocoria who have been diagnosed with&#xD;
      retinoblastoma, cataracts or glaucoma or other eye conditions.&#xD;
&#xD;
      Participants enrolled on Stratum I of the study will have the CRADLE application used by the&#xD;
      doctor during their appointment.&#xD;
&#xD;
      The participant will look straight forward while the doctor stands about 1-3 feet away&#xD;
      holding the device that has the CRADLE application. He or she will slowly move the device up,&#xD;
      down, middle, right, and left - both in a lit and dimmed room.&#xD;
&#xD;
      The participant will be videotaped and photographed during this appointment. The doctor will&#xD;
      record the results as determined by CRADLE (&quot;normal&quot; or no leukocoria versus &quot;abnormal&quot; or&#xD;
      positive for leukocoria).&#xD;
&#xD;
      STRATUM II - Infants and children who are referred to an eye doctor to evaluate for&#xD;
      leukocoria.&#xD;
&#xD;
      Participants enrolled on Stratum II of the study will be asked to look straight forward while&#xD;
      he or she uses the CRADLE application (using the best method determined from Stratum I). The&#xD;
      doctor will also examine the participant's eyes with the ophthalmoscope method. The results&#xD;
      from both CRADLE and the ophthalmoscope method will be recorded and compared (white eye&#xD;
      present versus absent, and normal versus abnormal as described above).&#xD;
&#xD;
      STRATUM III - Infants and children receiving treatment for retinoblastoma. For participants&#xD;
      enrolled on Stratum III, he or she will have the same procedures as described in Stratum II.&#xD;
&#xD;
      After receiving informed consent, participants will undergo evaluation by ophthalmoscope and&#xD;
      CRADLE on Day 1. Stratum III participants only will also undergo CRADLE evaluation on Days 2,&#xD;
      3, and 4.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 15, 2018</start_date>
  <completion_date type="Anticipated">July 30, 2026</completion_date>
  <primary_completion_date type="Anticipated">July 30, 2025</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Rate of detection of leukocoria using CRADLE</measure>
    <time_frame>Day 1</time_frame>
    <description>This outcome will assess the feasibility of various techniques and conditions for using CRADLE in participants with retinoblastoma, congenital cataracts, and glaucoma. The most effective usage of CRADLE to maximize detection of leukocoria will be determined by review of all images, and the most effective and efficient technique will be selected based on the findings and the clarity of the images. This technique will be used for completion of the subsequent objectives using a new cohort of participants.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Sensitivity of CRADLE versus ophthalmoscope to detect leukocoria</measure>
    <time_frame>Up to Day 4</time_frame>
    <description>The test results obtained by CRADLE will be compared to those obtained by ophthalmoscopic examination to determine the effectiveness of detection of leukocoria by CRADLE. The results will be reported as number of true positive. An ideal test for sensitivity has no false positives.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Specificity of CRADLE versus ophthalmoscope to detect leukocoria</measure>
    <time_frame>Up to Day 4</time_frame>
    <description>The test results obtained by CRADLE will be compared to those obtained by ophthalmoscopic examination to determine the effectiveness of detection of leukocoria by CRADLE. The results will be reported as number of false negatives (specificity). An ideal test for sensitivity has no false negatives.</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">290</enrollment>
  <condition>Retinoblastoma</condition>
  <condition>Cataracts Infantile</condition>
  <condition>Glaucoma, Congenital</condition>
  <condition>Leucocoria</condition>
  <arm_group>
    <arm_group_label>Stratum I: Initial Evaluation Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Initially, a small group of patients diagnosed with congenital or infantile cataracts, congenital glaucoma or retinoblastoma and who meet the eligibility criteria will undergo testing with CRADLE on Day 1.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Stratum II: Leukocoria Evaluation Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A separate group of participants who are referred for evaluation of leukocoria or any other eye condition will undergo red reflex testing testing with CRADLE on Day 1.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Stratum III: Retinoblastoma Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A separate group of participants with known retinoblastoma and who are undergoing ocular salvage treatments will be screened with red reflex testing using direct ophthalmoscopy on Day 1. They will also undergo testing with the CRADLE software application defined as the most effect in Stratum I on Day 1 then for three additional consecutive visits which typically occur every 3 to 4 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>CRADLE</intervention_name>
    <description>A smartphone software application designed to detect leukocoria using a sophisticated photoluminic analysis.&#xD;
The investigator or designee will perform tests with CRADLE in separate patient cohorts with known diagnosis of retinoblastoma, congenital glaucoma, or cataracts.</description>
    <arm_group_label>Stratum I: Initial Evaluation Group</arm_group_label>
    <arm_group_label>Stratum II: Leukocoria Evaluation Group</arm_group_label>
    <arm_group_label>Stratum III: Retinoblastoma Group</arm_group_label>
    <other_name>Smartphone application</other_name>
    <other_name>ComputeR Assisted Detection of LEukocoria</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Red reflex testing</intervention_name>
    <description>Traditional red reflex testing for leukocoria using a direct ophthalmoscope on routine eye examination. Red reflex testing via direct ophthalmoscope will be performed before dilation, using the ophthalmoscope held close to the examiner's eye, focused on the pupil, viewed at 12 to 18 inches from the patient's eyes, with the room lights dimmed, in accordance with the American Academy of Pediatrics guidelines.</description>
    <arm_group_label>Stratum II: Leukocoria Evaluation Group</arm_group_label>
    <arm_group_label>Stratum III: Retinoblastoma Group</arm_group_label>
    <other_name>Ophthalmoscopic exam</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria - Stratum I:&#xD;
&#xD;
          -  Patient has been diagnosed with congenital or infantile cataracts, congenital&#xD;
             glaucoma, or retinoblastoma, and is scheduled for a visit with an ophthalmologist at&#xD;
             St. Jude Children's Research Hospital or University of Tennessee Hamilton Eye&#xD;
             Institute.&#xD;
&#xD;
          -  Patient with retinoblastoma is newly diagnosed, or has received &lt; 2 cycles of&#xD;
             chemoreductive therapy, and has not undergone enucleation.&#xD;
&#xD;
          -  Patient with cataracts or glaucoma has not received any prior therapy.&#xD;
&#xD;
        Inclusion Criteria - Stratum II:&#xD;
&#xD;
          -  Patient without prior diagnosis has been referred for ophthalmological evaluation,&#xD;
             including leukocoria or other conditions.&#xD;
&#xD;
        Inclusion Criteria - Stratum III:&#xD;
&#xD;
          -  Patient with retinoblastoma undergoing ocular salvage treatment.&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          -  Prior treatment for cataracts or glaucoma&#xD;
&#xD;
          -  Inability or unwillingness of research participant or legal guardian to consent.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>7 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Carlos Rodriguez-Galindo, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>St. Jude Children's Research Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Carlos Rodriguez-Galindo, MD</last_name>
    <phone>866-278-5833</phone>
    <email>referralinfo@stjude.org</email>
  </overall_contact>
  <location>
    <facility>
      <name>St. Jude Children's Research Hospital</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38105-2794</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Carlos Rodriguez-Galindo</last_name>
      <phone>866-278-5833</phone>
      <email>referralinfo@stjude.org</email>
    </contact>
    <investigator>
      <last_name>Carlos Rodriguez-Galindo, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.stjude.org</url>
    <description>St. Jude Children's Research Hospital</description>
  </link>
  <link>
    <url>http://www.stjude.org/protocols</url>
    <description>Clinical Trials Open at St. Jude</description>
  </link>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>December 28, 2016</study_first_submitted>
  <study_first_submitted_qc>January 6, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 10, 2017</study_first_posted>
  <last_update_submitted>August 14, 2023</last_update_submitted>
  <last_update_submitted_qc>August 14, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 16, 2023</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>Retinoblastoma</mesh_term>
    <mesh_term>Cataract</mesh_term>
    <mesh_term>Hydrophthalmos</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/NCT03016156
org study id: RBAPP
secondary id: NCI-2021-05557
nct id: NCT03016156
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study seeks to determine whether a smartphone application called CRADLE (ComputeR
      Assisted Detection of LEukocoria) has the potential to improve the detection of leukocoria.
      There will be no impact on participants' health outcome.

      This study will be performed in two parts, each with a distinct cohort of patients.

      Part 1 will assess the feasibility of various techniques/conditions for using CRADLE within
      patients known to have leukocoria.

      Part 2 will estimate the sensitivity and specificity of CRADLE to detect leukocoria (using
      the techniques selected from information gathered in Part 1) as compared to an
      ophthalmoscope, within patients referred to the clinic for suspected leukocoria.

      PRIMARY OBJECTIVES:

        -  To determine the most effective usage of a camera phone application (CRADLE) to maximize
           detection of leukocoria in patients with retinoblastoma, congenital cataracts, and
           glaucoma.

        -  To estimate the sensitivity and specificity of a camera phone application (CRADLE) in
           detecting leukocoria.
This study will utilize three strata called Stratum I, Stratum II and Stratum III.

      STRATUM I - Infants and children known to have leukocoria who have been diagnosed with
      retinoblastoma, cataracts or glaucoma or other eye conditions.

      Participants enrolled on Stratum I of the study will have the CRADLE application used by the
      doctor during their appointment.

      The participant will look straight forward while the doctor stands about 1-3 feet away
      holding the device that has the CRADLE application. He or she will slowly move the device up,
      down, middle, right, and left - both in a lit and dimmed room.

      The participant will be videotaped and photographed during this appointment. The doctor will
      record the results as determined by CRADLE ("normal" or no leukocoria versus "abnormal" or
      positive for leukocoria).

      STRATUM II - Infants and children who are referred to an eye doctor to evaluate for
      leukocoria.

      Participants enrolled on Stratum II of the study will be asked to look straight forward while
      he or she uses the CRADLE application (using the best method determined from Stratum I). The
      doctor will also examine the participant's eyes with the ophthalmoscope method. The results
      from both CRADLE and the ophthalmoscope method will be recorded and compared (white eye
      present versus absent, and normal versus abnormal as described above).

      STRATUM III - Infants and children receiving treatment for retinoblastoma. For participants
      enrolled on Stratum III, he or she will have the same procedures as described in Stratum II.

      After receiving informed consent, participants will undergo evaluation by ophthalmoscope and
      CRADLE on Day 1. Stratum III participants only will also undergo CRADLE evaluation on Days 2,
      3, and 4.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Diagnostic
masking: Single (Outcomes Assessor)
measure: Rate of detection of leukocoria using CRADLE
time frame: Day 1
description: This outcome will assess the feasibility of various techniques and conditions for using CRADLE in participants with retinoblastoma, congenital cataracts, and glaucoma. The most effective usage of CRADLE to maximize detection of leukocoria will be determined by review of all images, and the most effective and efficient technique will be selected based on the findings and the clarity of the images. This technique will be used for completion of the subsequent objectives using a new cohort of participants.
measure: Sensitivity of CRADLE versus ophthalmoscope to detect leukocoria
time frame: Up to Day 4
description: The test results obtained by CRADLE will be compared to those obtained by ophthalmoscopic examination to determine the effectiveness of detection of leukocoria by CRADLE. The results will be reported as number of true positive. An ideal test for sensitivity has no false positives.
measure: Specificity of CRADLE versus ophthalmoscope to detect leukocoria
time frame: Up to Day 4
description: The test results obtained by CRADLE will be compared to those obtained by ophthalmoscopic examination to determine the effectiveness of detection of leukocoria by CRADLE. The results will be reported as number of false negatives (specificity). An ideal test for sensitivity has no false negatives.
arm group label: Stratum I: Initial Evaluation Group
arm group type: Experimental
description: Initially, a small group of patients diagnosed with congenital or infantile cataracts, congenital glaucoma or retinoblastoma and who meet the eligibility criteria will undergo testing with CRADLE on Day 1.
arm group label: Stratum II: Leukocoria Evaluation Group
arm group type: Experimental
description: A separate group of participants who are referred for evaluation of leukocoria or any other eye condition will undergo red reflex testing testing with CRADLE on Day 1.
arm group label: Stratum III: Retinoblastoma Group
arm group type: Experimental
description: A separate group of participants with known retinoblastoma and who are undergoing ocular salvage treatments will be screened with red reflex testing using direct ophthalmoscopy on Day 1. They will also undergo testing with the CRADLE software application defined as the most effect in Stratum I on Day 1 then for three additional consecutive visits which typically occur every 3 to 4 weeks.
intervention type: Other
intervention name: CRADLE
description: A smartphone software application designed to detect leukocoria using a sophisticated photoluminic analysis.
The investigator or designee will perform tests with CRADLE in separate patient cohorts with known diagnosis of retinoblastoma, congenital glaucoma, or cataracts.
arm group label: Stratum I: Initial Evaluation Group
arm group label: Stratum II: Leukocoria Evaluation Group
arm group label: Stratum III: Retinoblastoma Group
other name: Smartphone application
other name: ComputeR Assisted Detection of LEukocoria
intervention type: Other
intervention name: Red reflex testing
description: Traditional red reflex testing for leukocoria using a direct ophthalmoscope on routine eye examination. Red reflex testing via direct ophthalmoscope will be performed before dilation, using the ophthalmoscope held close to the examiner's eye, focused on the pupil, viewed at 12 to 18 inches from the patient's eyes, with the room lights dimmed, in accordance with the American Academy of Pediatrics guidelines.
arm group label: Stratum II: Leukocoria Evaluation Group
arm group label: Stratum III: Retinoblastoma Group
other name: Ophthalmoscopic exam
criteria: 
gender: All
minimum age: N/A
maximum age: 7 Years
healthy volunteers: No
last name: Carlos Rodriguez-Galindo, MD
role: Principal Investigator
affiliation: St. Jude Children's Research Hospital
last name: Carlos Rodriguez-Galindo, MD
phone: 866-278-5833
email: referralinfo@stjude.org
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
url: http://www.stjude.org
description: St. Jude Children's Research Hospital
url: http://www.stjude.org/protocols
description: Clinical Trials Open at St. Jude
responsible party type: Sponsor
mesh term: Retinoblastoma
mesh term: Cataract
mesh term: Hydrophthalmos