<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/NCT01676766</url>
  </required_header>
  <id_info>
    <org_study_id>HUM 64388</org_study_id>
    <nct_id>NCT01676766</nct_id>
  </id_info>
  <brief_title>Novel Quantification Methods for Fluorescence to Detect Progression in Stargardt Disease</brief_title>
  <official_title>Novel Quantification Methods for Fundus Flavoprotein Fluorescence and Lipofuscin Fluorescence to Detect Progression in Stargardt Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Michigan</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Midwest Eye Banks</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Michigan</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to utilize flavoprotein fluorescence and fundus autofluorescence&#xD;
      to detect progression of Stargardt macular dystrophy in a pediatric population over the&#xD;
      course of a year with the hope of aiding future therapeutic risk-benefit decisions and&#xD;
      assessment of outcomes.&#xD;
&#xD;
      Stargardt macular dystrophy is the most common of the juvenile-onset macular dystrophies.&#xD;
      Despite determination of ABCA4 as the causative gene, clinicians have been challenged by&#xD;
      variability in clinical phenotypes. Given the recent initiation of clinical trials to assess&#xD;
      novel treatments (e.g. gene therapy), there is a need to identify patients with the worst&#xD;
      prognosis.&#xD;
&#xD;
      The investigators have observed that pediatric patients lose central visual function faster&#xD;
      than their adult counterparts. Thus, they present an ideal cohort with which to determine the&#xD;
      utility of novel modalities to detect early change. These include flavoprotein fluorescence,&#xD;
      a new imaging technique for detecting mitochondrial dysfunction developed at the University&#xD;
      of Michigan. Fundus autofluorescence (FAF) is another commonly utilized technique of&#xD;
      evaluating hereditary eye diseases. The investigators have developed a novel means of&#xD;
      quantifying FAF signatures that will allow documentation of severity as well as detection of&#xD;
      progression.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will evaluate whether more sophisticated testing and analytic methodologies,&#xD;
      including fundus autofluorescence (FAF) and a novel non-invasive method to measure retinal&#xD;
      flavoprotein fluorescence (FPF) may be used to better predict Stargardt macular dystrophy&#xD;
      progression and monitor treatment effects than conventional modalities such visual acuity and&#xD;
      visual field. This method involves the use of novel statistical methods to assess the&#xD;
      heterogeneity of fundus autofluorescence images.&#xD;
&#xD;
      Participants will complete 3 visits to the University of Michigan Kellogg Eye Center. Each&#xD;
      visit will take approximately 2.5 hours. The initial visit will include a routine clinical&#xD;
      eye examination, measurement of best-corrected visual acuity, indirect ophthalmoscopy,&#xD;
      microperimetry, frequency-domain optical coherence tomography, Goldmann visual fields, fundus&#xD;
      flavoprotein fluorescence (FPF) imaging, and fundus autofluorescence (FAF) and fundus&#xD;
      photography. Patients will return for evaluation at 6 and 12 months after their initial visit&#xD;
      to repeat testing and imaging.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Flavoprotein fluorescence machine for the trial is not working so the trial was terminated. No&#xD;
    study data was collected prior to termination.&#xD;
  </why_stopped>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">October 2016</completion_date>
  <primary_completion_date type="Actual">October 2016</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Change from baseline in pixel intensity quantification of fundus autofluorescence at 6 months</measure>
    <time_frame>0 months, 6 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline in pixel intensity quantification of flavoprotein autofluorescence at 6 months</measure>
    <time_frame>0 months, 6 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in pixel intensity quantification of fundus autofluorescence at 12 months</measure>
    <time_frame>0 months, 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in pixel intensity quantification of flavoprotein autofluorescence at 12 months</measure>
    <time_frame>0 months, 12 months</time_frame>
  </secondary_outcome>
  <enrollment type="Actual">2</enrollment>
  <condition>Stargardt Disease</condition>
  <eligibility>
    <study_pop>
      <textblock>
        We will perform an observational clinical study of 25 pediatric patients with Stargardt&#xD;
        Disease recruited from the retinal degeneration clinic at the University of Michigan who&#xD;
        have two mutations in ABCA4.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Between the age of 5 and 18 years old&#xD;
&#xD;
          -  Clinical diagnosis of Stargardt Disease&#xD;
&#xD;
          -  Molecular confirmation of Stargardt Disease (with 2 identified mutations in ABCA4)&#xD;
&#xD;
          -  Visual acuity better than 20/100&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Limited central vision, defined as visual acuity worse than 20/100&#xD;
&#xD;
          -  A diagnosis of any other retinal degenerative disease&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>5 Years</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>K. Thiran Jayasundera, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Michigan Kellogg Eye Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Kellogg Eye Center</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Elner SG, Elner VM, Field MG, Park S, Heckenlively JR, Petty HR. Retinal flavoprotein autofluorescence as a measure of retinal health. Trans Am Ophthalmol Soc. 2008;106:215-22; discussion 222-4.</citation>
    <PMID>19277237</PMID>
  </reference>
  <reference>
    <citation>Field MG, Elner VM, Park S, Hackel R, Heckenlively JR, Elner SG, Petty HR. Detection of retinal metabolic stress resulting from central serous retinopathy. Retina. 2009 Sep;29(8):1162-6. doi: 10.1097/IAE.0b013e3181a3b923.</citation>
    <PMID>19491721</PMID>
  </reference>
  <reference>
    <citation>Field MG, Elner VM, Puro DG, Feuerman JM, Musch DC, Pop-Busui R, Hackel R, Heckenlively JR, Petty HR. Rapid, noninvasive detection of diabetes-induced retinal metabolic stress. Arch Ophthalmol. 2008 Jul;126(7):934-8. doi: 10.1001/archopht.126.7.934.</citation>
    <PMID>18625939</PMID>
  </reference>
  <reference>
    <citation>Chen B, Tosha C, Gorin MB, Nusinowitz S. Analysis of autofluorescent retinal images and measurement of atrophic lesion growth in Stargardt disease. Exp Eye Res. 2010 Aug;91(2):143-52. doi: 10.1016/j.exer.2010.03.021. Epub 2010 Apr 14.</citation>
    <PMID>20398653</PMID>
  </reference>
  <verification_date>November 2016</verification_date>
  <study_first_submitted>August 23, 2012</study_first_submitted>
  <study_first_submitted_qc>August 28, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 31, 2012</study_first_posted>
  <last_update_submitted>November 4, 2016</last_update_submitted>
  <last_update_submitted_qc>November 4, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 8, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Michigan</investigator_affiliation>
    <investigator_full_name>K. Thiran Jayasundera</investigator_full_name>
    <investigator_title>Assistant Professor, Retina and Uveitis</investigator_title>
  </responsible_party>
  <keyword>Stargardt Disease</keyword>
  <keyword>Macular degeneration</keyword>
  <keyword>Retinal dystrophy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stargardt Disease</mesh_term>
    <mesh_term>Macular Degeneration</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/NCT01676766
org study id: HUM 64388
nct id: NCT01676766
lead sponsor: 
collaborator: 
has dmc: No
The purpose of this study is to utilize flavoprotein fluorescence and fundus autofluorescence
      to detect progression of Stargardt macular dystrophy in a pediatric population over the
      course of a year with the hope of aiding future therapeutic risk-benefit decisions and
      assessment of outcomes.

      Stargardt macular dystrophy is the most common of the juvenile-onset macular dystrophies.
      Despite determination of ABCA4 as the causative gene, clinicians have been challenged by
      variability in clinical phenotypes. Given the recent initiation of clinical trials to assess
      novel treatments (e.g. gene therapy), there is a need to identify patients with the worst
      prognosis.

      The investigators have observed that pediatric patients lose central visual function faster
      than their adult counterparts. Thus, they present an ideal cohort with which to determine the
      utility of novel modalities to detect early change. These include flavoprotein fluorescence,
      a new imaging technique for detecting mitochondrial dysfunction developed at the University
      of Michigan. Fundus autofluorescence (FAF) is another commonly utilized technique of
      evaluating hereditary eye diseases. The investigators have developed a novel means of
      quantifying FAF signatures that will allow documentation of severity as well as detection of
      progression.
This study will evaluate whether more sophisticated testing and analytic methodologies,
      including fundus autofluorescence (FAF) and a novel non-invasive method to measure retinal
      flavoprotein fluorescence (FPF) may be used to better predict Stargardt macular dystrophy
      progression and monitor treatment effects than conventional modalities such visual acuity and
      visual field. This method involves the use of novel statistical methods to assess the
      heterogeneity of fundus autofluorescence images.

      Participants will complete 3 visits to the University of Michigan Kellogg Eye Center. Each
      visit will take approximately 2.5 hours. The initial visit will include a routine clinical
      eye examination, measurement of best-corrected visual acuity, indirect ophthalmoscopy,
      microperimetry, frequency-domain optical coherence tomography, Goldmann visual fields, fundus
      flavoprotein fluorescence (FPF) imaging, and fundus autofluorescence (FAF) and fundus
      photography. Patients will return for evaluation at 6 and 12 months after their initial visit
      to repeat testing and imaging.
observational model: Case-Only
time perspective: Prospective
measure: Change from baseline in pixel intensity quantification of fundus autofluorescence at 6 months
time frame: 0 months, 6 months
measure: Change from baseline in pixel intensity quantification of flavoprotein autofluorescence at 6 months
time frame: 0 months, 6 months
measure: Change from baseline in pixel intensity quantification of fundus autofluorescence at 12 months
time frame: 0 months, 12 months
measure: Change from baseline in pixel intensity quantification of flavoprotein autofluorescence at 12 months
time frame: 0 months, 12 months
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 5 Years
maximum age: 18 Years
healthy volunteers: No
last name: K. Thiran Jayasundera, MD
role: Principal Investigator
affiliation: University of Michigan Kellogg Eye Center
facility: 
country: United States
citation: Elner SG, Elner VM, Field MG, Park S, Heckenlively JR, Petty HR. Retinal flavoprotein autofluorescence as a measure of retinal health. Trans Am Ophthalmol Soc. 2008;106:215-22; discussion 222-4.
PMID: 19277237
citation: Field MG, Elner VM, Park S, Hackel R, Heckenlively JR, Elner SG, Petty HR. Detection of retinal metabolic stress resulting from central serous retinopathy. Retina. 2009 Sep;29(8):1162-6. doi: 10.1097/IAE.0b013e3181a3b923.
PMID: 19491721
citation: Field MG, Elner VM, Puro DG, Feuerman JM, Musch DC, Pop-Busui R, Hackel R, Heckenlively JR, Petty HR. Rapid, noninvasive detection of diabetes-induced retinal metabolic stress. Arch Ophthalmol. 2008 Jul;126(7):934-8. doi: 10.1001/archopht.126.7.934.
PMID: 18625939
citation: Chen B, Tosha C, Gorin MB, Nusinowitz S. Analysis of autofluorescent retinal images and measurement of atrophic lesion growth in Stargardt disease. Exp Eye Res. 2010 Aug;91(2):143-52. doi: 10.1016/j.exer.2010.03.021. Epub 2010 Apr 14.
PMID: 20398653
responsible party type: Principal Investigator
investigator affiliation: University of Michigan
investigator full name: K. Thiran Jayasundera
investigator title: Assistant Professor, Retina and Uveitis
mesh term: Stargardt Disease
mesh term: Macular Degeneration