<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/NCT01694095</url>
  </required_header>
  <id_info>
    <org_study_id>GAIN-002-10-2010</org_study_id>
    <nct_id>NCT01694095</nct_id>
  </id_info>
  <brief_title>Evolution and Risk Factors Associated With Geographic Atrophy Progression</brief_title>
  <acronym>GAIN</acronym>
  <official_title>Characterization of Geographic Atrophy Progression in Patients With Age-related Macular Degeneration</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institut de la Macula y la Retina</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Institut de la Macula y la Retina</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Age-related macular degeneration is one of the leading causes of blindness worldwide. The&#xD;
      factors that induce the progression of geographic atrophy, the advanced form of dry&#xD;
      age-related macular degeneration, remain poorly understood. The aims of this study are to&#xD;
      describe the natural history of geographic atrophy and identify potential risk factors&#xD;
      associated with a faster spread of atrophy that may be used to develop rational therapies.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Age-related macular degeneration is the leading cause of blindness in developed countries.&#xD;
      Geographic atrophy is the advanced form of dry age-related macular degeneration, and&#xD;
      currently has no effective therapy. Little is known about the risk factors that drive the&#xD;
      progression of geographic atrophy, and yet they are crucial to understand the mechanisms of&#xD;
      the disease. Therefore, the identification of risk factors associated with a faster spread of&#xD;
      atrophy may help contribute to identify the causes of the disease and, ultimately, to develop&#xD;
      new therapeutic strategies to manage the disorder.&#xD;
&#xD;
      The current prospective, observational, natural history study has the following objectives:&#xD;
&#xD;
        -  Describe the natural history of geographic atrophy in anatomic and visual terms&#xD;
&#xD;
        -  Identify risk factors associated with a faster enlargement of atrophy&#xD;
&#xD;
      The main hypothesis is that lipofuscin accumulation at the borders of atrophy as seen with&#xD;
      fundus autofluorescence imaging is associated with a faster progression of the disease.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>December 2009</start_date>
  <completion_date type="Actual">August 2013</completion_date>
  <primary_completion_date type="Actual">August 2013</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>Median/mean change in area of geographic atrophy as measured in mm2 with fundus autofluorescence on a 30º image centered on field 2</measure>
    <time_frame>From baseline to last follow-up</time_frame>
    <description>For measures related to change in the area of atrophy, a multivariable model will be fit and will include as an independent variable (amongst other presumed risk factors) fundus autofluorescence patterns</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Median change in area of geographic atrophy as measured in square root of mm2 with fundus autofluorescence on a 30º image centered on field 2</measure>
    <time_frame>From baseline to last follow-up</time_frame>
    <description>Exploratory analysis, either in the main publication or in another paper</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Median/mean change in best-corrected visual acuity as measured with an Early Treatment Diabetic Retinopathy Study chart</measure>
    <time_frame>From baseline to last follow-up</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Percentage of eyes developing new choroidal neovascularization in the study eye as evaluated with fluorescein angiography and spectral-domain optical coherence tomography</measure>
    <time_frame>From baseline to last follow-up</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Median/mean change in area of geographic atrophy as measured in mm2 with fundus autofluorescence on a 30º image centered on field 2</measure>
    <time_frame>From baseline to last follow-up</time_frame>
    <description>Principal component analysis will be used to reduce the number of independent variables to increase, if possible, the power of the study to detect an association</description>
  </other_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">96</enrollment>
  <condition>Geographic Atrophy</condition>
  <arm_group>
    <arm_group_label>Patients with geographic atrophy</arm_group_label>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with geographic atrophy&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Both sexes&#xD;
&#xD;
          -  50 years of age or older&#xD;
&#xD;
          -  Uni or bilateral areas of geographic atrophy in the macula (as defined as areas devoid&#xD;
             of retinal pigment epithelium measuring at least 0.5 disk areas on a 35º fundus&#xD;
             photograph centered on field 2) secondary to age-related macular degeneration&#xD;
&#xD;
          -  Willing to provide Informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Other causes of geographic atrophy aside from age-related macular degeneration (ie,&#xD;
             drug induced, central serous chorioretinopathy)&#xD;
&#xD;
          -  Prior history of wet age-related macular degeneration&#xD;
&#xD;
          -  Other significant concomitant macular diseases (ie, significant epiretinal membrane,&#xD;
             stage II-IV macular hole)&#xD;
&#xD;
          -  Previous treatment with macular laser photocoagulation, photodynamic therapy,&#xD;
             antiangiogenic drugs or other treatments for wet age-related macular degeneration&#xD;
&#xD;
          -  Intraocular surgery aside from phacoemulsification&#xD;
&#xD;
          -  Inability to measure the full extent of the area of atrophy on a 35º fundus&#xD;
             autofluorescence image centered on field 2&#xD;
&#xD;
          -  Areas of geographic atrophy in direct contact with peripapillary areas of atrophy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jordi Monés, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Institut de la màcula i de la retina</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Institut de la màcula i de la retina</name>
      <address>
        <city>Barcelona</city>
        <zip>08017</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <results_reference>
    <citation>Biarnes M, Mones J, Trindade F, Alonso J, Arias L. Intra and interobserver agreement in the classification of fundus autofluorescence patterns in geographic atrophy secondary to age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol. 2012 Apr;250(4):485-90. doi: 10.1007/s00417-011-1846-y. Epub 2011 Oct 28.</citation>
    <PMID>22033626</PMID>
  </results_reference>
  <results_reference>
    <citation>Mones J, Biarnes M, Trindade F. Hyporeflective wedge-shaped band in geographic atrophy secondary to age-related macular degeneration: an underreported finding. Ophthalmology. 2012 Jul;119(7):1412-9. doi: 10.1016/j.ophtha.2012.01.026. Epub 2012 Mar 21.</citation>
    <PMID>22440276</PMID>
  </results_reference>
  <results_reference>
    <citation>Mones J, Biarnes M, Trindade F, Arias L, Alonso J. Optical coherence tomography assessment of apparent foveal swelling in patients with foveal sparing secondary to geographic atrophy. Ophthalmology. 2013 Apr;120(4):829-36. doi: 10.1016/j.ophtha.2012.09.054. Epub 2013 Jan 3.</citation>
    <PMID>23290986</PMID>
  </results_reference>
  <results_reference>
    <citation>Biarnes M, Forero CG, Arias L, Alonso J, Mones J. Reappraisal of geographic atrophy patterns seen on fundus autofluorescence using a latent class analysis approach. Invest Ophthalmol Vis Sci. 2014 Nov 18;55(12):8302-8. doi: 10.1167/iovs.13-13542.</citation>
    <PMID>25406275</PMID>
  </results_reference>
  <verification_date>March 2015</verification_date>
  <study_first_submitted>September 22, 2012</study_first_submitted>
  <study_first_submitted_qc>September 22, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 26, 2012</study_first_posted>
  <last_update_submitted>March 23, 2015</last_update_submitted>
  <last_update_submitted_qc>March 23, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">March 24, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Institut de la Macula y la Retina</investigator_affiliation>
    <investigator_full_name>Jordi Mones</investigator_full_name>
    <investigator_title>MD, PhD</investigator_title>
  </responsible_party>
  <keyword>Geographic atrophy, prognosis, risk factors, natural history</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Geographic Atrophy</mesh_term>
    <mesh_term>Atrophy</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/NCT01694095
org study id: GAIN-002-10-2010
nct id: NCT01694095
lead sponsor: 
has dmc: Yes
Age-related macular degeneration is one of the leading causes of blindness worldwide. The
      factors that induce the progression of geographic atrophy, the advanced form of dry
      age-related macular degeneration, remain poorly understood. The aims of this study are to
      describe the natural history of geographic atrophy and identify potential risk factors
      associated with a faster spread of atrophy that may be used to develop rational therapies.
Age-related macular degeneration is the leading cause of blindness in developed countries.
      Geographic atrophy is the advanced form of dry age-related macular degeneration, and
      currently has no effective therapy. Little is known about the risk factors that drive the
      progression of geographic atrophy, and yet they are crucial to understand the mechanisms of
      the disease. Therefore, the identification of risk factors associated with a faster spread of
      atrophy may help contribute to identify the causes of the disease and, ultimately, to develop
      new therapeutic strategies to manage the disorder.

      The current prospective, observational, natural history study has the following objectives:

        -  Describe the natural history of geographic atrophy in anatomic and visual terms

        -  Identify risk factors associated with a faster enlargement of atrophy

      The main hypothesis is that lipofuscin accumulation at the borders of atrophy as seen with
      fundus autofluorescence imaging is associated with a faster progression of the disease.
observational model: Case-Only
time perspective: Prospective
measure: Median/mean change in area of geographic atrophy as measured in mm2 with fundus autofluorescence on a 30º image centered on field 2
time frame: From baseline to last follow-up
description: For measures related to change in the area of atrophy, a multivariable model will be fit and will include as an independent variable (amongst other presumed risk factors) fundus autofluorescence patterns
measure: Median change in area of geographic atrophy as measured in square root of mm2 with fundus autofluorescence on a 30º image centered on field 2
time frame: From baseline to last follow-up
description: Exploratory analysis, either in the main publication or in another paper
measure: Median/mean change in best-corrected visual acuity as measured with an Early Treatment Diabetic Retinopathy Study chart
time frame: From baseline to last follow-up
measure: Percentage of eyes developing new choroidal neovascularization in the study eye as evaluated with fluorescein angiography and spectral-domain optical coherence tomography
time frame: From baseline to last follow-up
measure: Median/mean change in area of geographic atrophy as measured in mm2 with fundus autofluorescence on a 30º image centered on field 2
time frame: From baseline to last follow-up
description: Principal component analysis will be used to reduce the number of independent variables to increase, if possible, the power of the study to detect an association
arm group label: Patients with geographic atrophy
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 50 Years
maximum age: N/A
healthy volunteers: No
last name: Jordi Monés, MD, PhD
role: Principal Investigator
affiliation: Institut de la màcula i de la retina
facility: 
country: Spain
citation: Biarnes M, Mones J, Trindade F, Alonso J, Arias L. Intra and interobserver agreement in the classification of fundus autofluorescence patterns in geographic atrophy secondary to age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol. 2012 Apr;250(4):485-90. doi: 10.1007/s00417-011-1846-y. Epub 2011 Oct 28.
PMID: 22033626
citation: Mones J, Biarnes M, Trindade F. Hyporeflective wedge-shaped band in geographic atrophy secondary to age-related macular degeneration: an underreported finding. Ophthalmology. 2012 Jul;119(7):1412-9. doi: 10.1016/j.ophtha.2012.01.026. Epub 2012 Mar 21.
PMID: 22440276
citation: Mones J, Biarnes M, Trindade F, Arias L, Alonso J. Optical coherence tomography assessment of apparent foveal swelling in patients with foveal sparing secondary to geographic atrophy. Ophthalmology. 2013 Apr;120(4):829-36. doi: 10.1016/j.ophtha.2012.09.054. Epub 2013 Jan 3.
PMID: 23290986
citation: Biarnes M, Forero CG, Arias L, Alonso J, Mones J. Reappraisal of geographic atrophy patterns seen on fundus autofluorescence using a latent class analysis approach. Invest Ophthalmol Vis Sci. 2014 Nov 18;55(12):8302-8. doi: 10.1167/iovs.13-13542.
PMID: 25406275
responsible party type: Principal Investigator
investigator affiliation: Institut de la Macula y la Retina
investigator full name: Jordi Mones
investigator title: MD, PhD
mesh term: Geographic Atrophy
mesh term: Atrophy