xml: <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/NCT06023446</url>
    </required_header>
    <id_info>
      <org_study_id>1647468</org_study_id>
      <secondary_id>K08AG080178</secondary_id>
      <nct_id>NCT06023446</nct_id>
    </id_info>
    <brief_title>Can (Optical Coherence Tomography) Pictures of the Retina Detect Alzheimer's Disease at Its Earliest Stages?</brief_title>
    <official_title>Illuminating Glial Dysfunction in Alzheimer's Disease With Optical Coherence Tomography</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of California, Davis</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>National Institute on Aging (NIA)</agency>
        <agency_class>NIH</agency_class>
      </collaborator>
    </sponsors>
    <source>University of California, Davis</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>
        Years before someone experiences the symptoms of Alzheimer's disease, a compound called&#xD;
        amyloid beta (Aβ) builds up in the brain. Excess Aβ - directly or indirectly - causes many of&#xD;
        the symptoms of Alzheimer's dementia. However, recent studies of the FDA-approved drugs&#xD;
        lecanemab (Leqembi®) and aducanumab (Aduhelm®) indicate that removing Aβ from the brain&#xD;
        doesn't stop Alzheimer's. Clearly, there are other problems that need to be fixed. The&#xD;
        investigators are interested in the cause of Aβ buildup.&#xD;
  &#xD;
        Non-neuronal support cells, called glia, keep neurons healthy by regulating water and&#xD;
        nutrient levels for the neurons. They also help clear Aβ away from neurons. Maybe Aβ builds&#xD;
        up when glia are unhealthy.&#xD;
  &#xD;
        Glia are very hard to study in the brain. Luckily, the light-sensing part of the eye - the&#xD;
        retina - is an extension of the brain. The investigators study glia in the retina to learn&#xD;
        about glia in the brain.&#xD;
  &#xD;
        To study retinal glia, the investigators take pictures of the retina with optical coherence&#xD;
        tomography (OCT). OCT is safe, painless, and is used in many eye clinics to look at the&#xD;
        structure of the retina. When the investigators take OCT pictures under a bright light, and&#xD;
        compare those to OCT pictures collected in darkness, it gives the investigators information&#xD;
        about glial function. In a study published in 2020 (&quot;Optical coherence tomography reveals&#xD;
        light-dependent retinal responses in Alzheimer's disease&quot;) the investigators showed that this&#xD;
        functional OCT measurement was different in people with Alzheimer's dementia, compared to&#xD;
        age-matched healthy adults.&#xD;
  &#xD;
        The goal of this observational study is to compare people at a pre-dementia stage of&#xD;
        Alzheimer's disease to people who do not have any signs at all of Alzheimer's disease. By&#xD;
        &quot;pre-dementia stage&quot;, the investigators mean people who are either cognitively normal, or&#xD;
        have mild cognitive impairment, but have had a medical test that shows the chemical&#xD;
        beginnings of Alzheimer's disease. Members of the comparison group will also be cognitively&#xD;
        normal, or have mild cognitive impairment, but had a medical test that shows utterly no signs&#xD;
        of Alzheimer's disease.&#xD;
  &#xD;
        The main question this study, is whether functional OCT can tell these two groups apart. If&#xD;
        so, that would:&#xD;
  &#xD;
          -  Help build the case for glial health being important in the earliest stages of&#xD;
             Alzheimer's, which in turn could lead to new treatment strategies, and&#xD;
  &#xD;
          -  Suggest that functional OCT might be used as an early (pre-dementia) screening test for&#xD;
             Alzheimer's disease&#xD;
  &#xD;
        Participants will:&#xD;
  &#xD;
          -  undergo a brief eye exam (the investigators will not dilate pupils for this study)&#xD;
  &#xD;
          -  undergo a paper-and-pencil cognitive test (to help verify &quot;normal&quot; or &quot;mild cognitive&#xD;
             impairment&quot; status)&#xD;
  &#xD;
          -  take brief one-page survey to collect demographic information (like age)&#xD;
  &#xD;
          -  permit limited access to pre-existing medical or research records (to verify the&#xD;
             presence/absence of the chemical beginnings of Alzheimer's disease)&#xD;
  &#xD;
          -  take several OCT pictures of both eyes, in light and after 2 minutes of darkness&#xD;
             (several rounds of images are taken)&#xD;
  &#xD;
        The expectation is that all study procedures will fit within 2 hours of one day.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Enrolling by invitation</overall_status>
    <start_date type="Anticipated">September 11, 2023</start_date>
    <completion_date type="Anticipated">February 28, 2028</completion_date>
    <primary_completion_date type="Anticipated">February 28, 2028</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Case-Control</observational_model>
      <time_perspective>Cross-Sectional</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Light-dependent Change in Optical Coherence Tomography Images</measure>
      <time_frame>Day 1 (less than two hours)</time_frame>
      <description>The investigators will obtain OCT B-scans of the span of retina between the center of the optic disc and the fovea. Each B-scan will be spatially normalized and averaged to generate a profile of retinal reflectivity versus depth into the retina. Reflectivities in light will be compared to reflectivities in darkness. In both groups, the investigators expect that (1) over the photoreceptor inner and outer segments, the retina will be more reflective in light then in darkness, (2) in the more vitread portions of the retina (the layers occupied by Müller glia), the retina will be slightly less reflective in light than in darkness.&#xD;
  The investigators expect a group differences in that functional outcome. The largest group difference is expected near the exterior border of the Müller glia, where participants with a pre-dementia stage of Alzheimer's may have an exaggerated light-dependent change in reflectivity.</description>
    </primary_outcome>
    <number_of_groups>2</number_of_groups>
    <enrollment type="Anticipated">100</enrollment>
    <condition>Alzheimer Disease</condition>
    <condition>Mild Cognitive Impairment</condition>
    <arm_group>
      <arm_group_label>Pre-Dementia Alzheimer's</arm_group_label>
      <description>By clinical assessment, these participants will either be cognitively normal, or have mild cognitive impairment. They will enter the study having already completed some biomarker testing for Alzheimer's disease (e.g., amyloid PET, cerebrospinal fluid measurement amyloid and tau). In this group, the biomarker testing is positive/abnormal, indicating a pre-dementia stage of Alzheimer's disease. In the language of the 2018 NIA-AA Research Framework, these participants have A+ in their AT(N) biomarker profile, and are at clinical stage 1-3.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>No Evidence of Alzheimer's</arm_group_label>
      <description>By clinical assessment, these participants will either be cognitively normal, or have mild cognitive impairment. They will enter the study having already completed some biomarker testing for Alzheimer's disease (e.g., amyloid PET, cerebrospinal fluid measurement amyloid and tau). In this group, the biomarker testing is negative/normal. In the language of the 2018 NIA-AA Research Framework, these participants have A- in their AT(N) biomarker profile, and are at clinical stage 1-3.</description>
    </arm_group>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>Optical Coherence Tomography</intervention_name>
      <description>The retina is imaged using infrared light. Images collected in light are compared to those collected in darkness to extract information about function.</description>
      <arm_group_label>No Evidence of Alzheimer's</arm_group_label>
      <arm_group_label>Pre-Dementia Alzheimer's</arm_group_label>
    </intervention>
    <eligibility>
      <study_pop>
        <textblock>
          The investigators plan to recruit participants from:&#xD;
  &#xD;
            -  Participants (or prospective participants) in research on aging and cognition at the&#xD;
               University of California - Davis.&#xD;
  &#xD;
            -  Patients (or prospective patients) of University of California - Davis neurologists.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  By clinician (or prior research) assessment, known to either be cognitively normal, or&#xD;
               have mild cognitive impairment&#xD;
  &#xD;
            -  Known Alzheimer's biomarker status. As of 2023-JUL, this must either be an amyloid PET&#xD;
               scan, or cerebrospinal fluid measurement of amyloid and tau levels.&#xD;
  &#xD;
            -  NOTE: Although this is a study of the eyes, age-typical ocular/vision complaints are&#xD;
               permissible, so long as the the retina is thought to be healthy. This list of&#xD;
               acceptable conditions includes most people who:&#xD;
  &#xD;
                 -  wear glasses&#xD;
  &#xD;
                 -  wear contacts&#xD;
  &#xD;
                 -  use over-the-counter eye drops&#xD;
  &#xD;
                 -  have mild cataracts (no surgery scheduled)&#xD;
  &#xD;
                 -  had cataracts removed&#xD;
  &#xD;
                 -  had eye muscle surgery (e.g., to correct eye misalignment)&#xD;
  &#xD;
                 -  had eyelid surgery (blepharoplasty)&#xD;
  &#xD;
                 -  are monitored by an ophthalmologist in case a problem with the retina develops&#xD;
                    (this is sometimes suggested for people with diabetes), but one or both retinas&#xD;
                    is/are thought to be completely healthy&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Pregnant women&#xD;
  &#xD;
            -  Prisoners&#xD;
  &#xD;
            -  Known *for both eyes* to have ocular health or vision abnormalities that are not&#xD;
               age-typical. The list of unacceptable conditions includes most people who:&#xD;
  &#xD;
                 -  have a special corrective lens (glasses or contact lens) prescription with a&#xD;
                    sphere greater than seven&#xD;
  &#xD;
                 -  currently use prescription eye drops (e.g., for glaucoma)&#xD;
  &#xD;
                 -  have/had prior surgical treatment for a retinal problem (e.g., retinal detachment&#xD;
                    that required surgery)&#xD;
  &#xD;
                 -  have/had eye injections for age-related macular degeneration&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>50 Years</minimum_age>
      <maximum_age>89 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <location>
      <facility>
        <name>University of California - Davis</name>
        <address>
          <city>Sacramento</city>
          <state>California</state>
          <zip>95816</zip>
          <country>United States</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <reference>
      <citation>Bissig D, Zhou CG, Le V, Bernard JT. Optical coherence tomography reveals light-dependent retinal responses in Alzheimer's disease. Neuroimage. 2020 Oct 1;219:117022. doi: 10.1016/j.neuroimage.2020.117022. Epub 2020 Jun 5.</citation>
      <PMID>32512126</PMID>
    </reference>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>July 21, 2023</study_first_submitted>
    <study_first_submitted_qc>August 28, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 5, 2023</study_first_posted>
    <last_update_submitted>September 5, 2023</last_update_submitted>
    <last_update_submitted_qc>September 5, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 8, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Amyloid</keyword>
    <keyword>Retinal Muller Glial Cells</keyword>
    <keyword>Optical Coherence Tomography</keyword>
    <keyword>Glia</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Alzheimer Disease</mesh_term>
      <mesh_term>Cognitive Dysfunction</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>De-identified OCT data will be posted to a data repository.</ipd_description>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06023446
  org study id: 1647468
  secondary id: K08AG080178
  nct id: NCT06023446
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Years before someone experiences the symptoms of Alzheimer's disease, a compound called
        amyloid beta (Aβ) builds up in the brain. Excess Aβ - directly or indirectly - causes many of
        the symptoms of Alzheimer's dementia. However, recent studies of the FDA-approved drugs
        lecanemab (Leqembi®) and aducanumab (Aduhelm®) indicate that removing Aβ from the brain
        doesn't stop Alzheimer's. Clearly, there are other problems that need to be fixed. The
        investigators are interested in the cause of Aβ buildup.
  
        Non-neuronal support cells, called glia, keep neurons healthy by regulating water and
        nutrient levels for the neurons. They also help clear Aβ away from neurons. Maybe Aβ builds
        up when glia are unhealthy.
  
        Glia are very hard to study in the brain. Luckily, the light-sensing part of the eye - the
        retina - is an extension of the brain. The investigators study glia in the retina to learn
        about glia in the brain.
  
        To study retinal glia, the investigators take pictures of the retina with optical coherence
        tomography (OCT). OCT is safe, painless, and is used in many eye clinics to look at the
        structure of the retina. When the investigators take OCT pictures under a bright light, and
        compare those to OCT pictures collected in darkness, it gives the investigators information
        about glial function. In a study published in 2020 ("Optical coherence tomography reveals
        light-dependent retinal responses in Alzheimer's disease") the investigators showed that this
        functional OCT measurement was different in people with Alzheimer's dementia, compared to
        age-matched healthy adults.
  
        The goal of this observational study is to compare people at a pre-dementia stage of
        Alzheimer's disease to people who do not have any signs at all of Alzheimer's disease. By
        "pre-dementia stage", the investigators mean people who are either cognitively normal, or
        have mild cognitive impairment, but have had a medical test that shows the chemical
        beginnings of Alzheimer's disease. Members of the comparison group will also be cognitively
        normal, or have mild cognitive impairment, but had a medical test that shows utterly no signs
        of Alzheimer's disease.
  
        The main question this study, is whether functional OCT can tell these two groups apart. If
        so, that would:
  
          -  Help build the case for glial health being important in the earliest stages of
             Alzheimer's, which in turn could lead to new treatment strategies, and
  
          -  Suggest that functional OCT might be used as an early (pre-dementia) screening test for
             Alzheimer's disease
  
        Participants will:
  
          -  undergo a brief eye exam (the investigators will not dilate pupils for this study)
  
          -  undergo a paper-and-pencil cognitive test (to help verify "normal" or "mild cognitive
             impairment" status)
  
          -  take brief one-page survey to collect demographic information (like age)
  
          -  permit limited access to pre-existing medical or research records (to verify the
             presence/absence of the chemical beginnings of Alzheimer's disease)
  
          -  take several OCT pictures of both eyes, in light and after 2 minutes of darkness
             (several rounds of images are taken)
  
        The expectation is that all study procedures will fit within 2 hours of one day.
  observational model: Case-Control
  time perspective: Cross-Sectional
  measure: Light-dependent Change in Optical Coherence Tomography Images
  time frame: Day 1 (less than two hours)
  description: The investigators will obtain OCT B-scans of the span of retina between the center of the optic disc and the fovea. Each B-scan will be spatially normalized and averaged to generate a profile of retinal reflectivity versus depth into the retina. Reflectivities in light will be compared to reflectivities in darkness. In both groups, the investigators expect that (1) over the photoreceptor inner and outer segments, the retina will be more reflective in light then in darkness, (2) in the more vitread portions of the retina (the layers occupied by Müller glia), the retina will be slightly less reflective in light than in darkness.
  The investigators expect a group differences in that functional outcome. The largest group difference is expected near the exterior border of the Müller glia, where participants with a pre-dementia stage of Alzheimer's may have an exaggerated light-dependent change in reflectivity.
  arm group label: Pre-Dementia Alzheimer's
  description: By clinical assessment, these participants will either be cognitively normal, or have mild cognitive impairment. They will enter the study having already completed some biomarker testing for Alzheimer's disease (e.g., amyloid PET, cerebrospinal fluid measurement amyloid and tau). In this group, the biomarker testing is positive/abnormal, indicating a pre-dementia stage of Alzheimer's disease. In the language of the 2018 NIA-AA Research Framework, these participants have A+ in their AT(N) biomarker profile, and are at clinical stage 1-3.
  arm group label: No Evidence of Alzheimer's
  description: By clinical assessment, these participants will either be cognitively normal, or have mild cognitive impairment. They will enter the study having already completed some biomarker testing for Alzheimer's disease (e.g., amyloid PET, cerebrospinal fluid measurement amyloid and tau). In this group, the biomarker testing is negative/normal. In the language of the 2018 NIA-AA Research Framework, these participants have A- in their AT(N) biomarker profile, and are at clinical stage 1-3.
  intervention type: Diagnostic Test
  intervention name: Optical Coherence Tomography
  description: The retina is imaged using infrared light. Images collected in light are compared to those collected in darkness to extract information about function.
  arm group label: No Evidence of Alzheimer's
  arm group label: Pre-Dementia Alzheimer's
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 50 Years
  maximum age: 89 Years
  healthy volunteers: Accepts Healthy Volunteers
  facility: 
  country: United States
  citation: Bissig D, Zhou CG, Le V, Bernard JT. Optical coherence tomography reveals light-dependent retinal responses in Alzheimer's disease. Neuroimage. 2020 Oct 1;219:117022. doi: 10.1016/j.neuroimage.2020.117022. Epub 2020 Jun 5.
  PMID: 32512126
  responsible party type: Sponsor
  mesh term: Alzheimer Disease
  mesh term: Cognitive Dysfunction
  sharing ipd: Yes
  ipd description: De-identified OCT data will be posted to a data repository.