<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/NCT03233646</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00111831</org_study_id>
    <nct_id>NCT03233646</nct_id>
  </id_info>
  <brief_title>Retinal Imaging in Neurodegenerative Disease</brief_title>
  <official_title>Evaluating the Retinal and Choroidal Microvasculature and Structure Using Multimodal Retinal and Choroidal Imaging in Neurodegenerative Disease: iMIND Research Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Duke University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Edinburgh in Scotland</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Tan Tock Seng Hospital in Singapore</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Queens University of Belfast United Kingdom</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Duke University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study aims to develop and evaluate biomarkers using non-invasive optical coherence&#xD;
      tomography (OCT) and OCT angiography (OCTA) as well as ultra-widefield (UWF) fundus&#xD;
      photography to assess the structure and function of the retinal and choroidal&#xD;
      microvasculature and structure in persons with mild cognitive impairment (MCI) and&#xD;
      Alzheimer's Disease (AD), Parkinson's Disease (PD), or other neurodegenerative disease,&#xD;
      diseases as outlined.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Using a multidisciplinary approach, this study aims to yield new insight into the vascular&#xD;
      and structural pathophysiology of neurodegenerative disease. The investigators propose to&#xD;
      develop and evaluate imaging biomarkers from OCT, OCTA, and UWF fundus photos to assess the&#xD;
      structure and function of the retinal and choroidal microvasculature and structure in these&#xD;
      individuals.&#xD;
&#xD;
      The investigators hypothesize that microvascular and structural network alterations in the&#xD;
      retina and choroid may mirror and possibly precede changes in the cerebral microcirculation&#xD;
      seen in these neurodegenerative diseases. Using advanced image analysis and machine learning&#xD;
      techniques, the investigators aim to evaluate markers of reduced capillary blood flow and&#xD;
      non-perfusion in the superficial retinal vascular plexus and choriocapillaris imaged using&#xD;
      OCT and OCTA, in a resolution not previously possible, that would complement already&#xD;
      established retinal structural markers and increase their sensitivity and specificity in the&#xD;
      earlier detection of these neurodegenerative diseases.&#xD;
&#xD;
      This study looks to provide a proof of concept for retinal and choroidal imaging-based&#xD;
      microvascular and structural biomarkers as an effective screening tool for neurodegenerative&#xD;
      disease, particularly during in cognitive aging.&#xD;
&#xD;
      The protocol for this study was amended and the record was updated accordingly.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 20, 2017</start_date>
  <completion_date type="Anticipated">December 31, 2025</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2025</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>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Change in ganglion cell-inner plexiform layer (GCIPL) thickness</measure>
    <time_frame>Baseline, 1 year</time_frame>
    <description>Ganglion cell inner plexiform layer thickness as measured on optical coherence tomography scan of macula</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in retinal nerve fiber layer (RNFL) thickness</measure>
    <time_frame>Baseline, 1 year</time_frame>
    <description>Retinal nerve fiber layer thickness as measured on optical coherence tomography scan of macula</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in central subfield thickness (CST)</measure>
    <time_frame>Baseline, 1 year</time_frame>
    <description>Central subfield thickness as measured on optical coherence tomography scan of macula</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in choroidal vascularity index (CVI)</measure>
    <time_frame>Baseline, 1 year</time_frame>
    <description>Choroidal vascularity index as measured using the COIN software in 1500 um area centered on the fovea</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in foveal avascular zone (FAZ) area</measure>
    <time_frame>Baseline, 1 year</time_frame>
    <description>Foveal avascular zone area as measured in the superficial capillary plexus on 3mm optical coherence tomography angiography scan of the macula</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in average perfusion density (PD)</measure>
    <time_frame>Baseline, 1 year</time_frame>
    <description>Average perfusion density as measured in the ETDRS 3mm and 6mm circle and rings on optical coherence tomography angiography scan of the macula</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in average vessel density (VD)</measure>
    <time_frame>Baseline, 1 year</time_frame>
    <description>Average vessel density as measured in the ETDRS 3mm and 6mm circle and rings on optical coherence tomography angiography scan of the macula</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in average capillary perfusion density (CPD)</measure>
    <time_frame>Baseline, 1 year</time_frame>
    <description>Capillary perfusion density as measured on peripapillary 4.5mm optical coherence tomography angiography scan</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in average capillary flux index (CFI)</measure>
    <time_frame>Baseline, 1 year</time_frame>
    <description>Capillary flux index as measured on peripapillary 4.5mm optical coherence tomography angiography scan</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in retinal vessel tortuosity</measure>
    <time_frame>Baseline, 1 year</time_frame>
    <description>Retinal vessel tortuosity measured on ultra-widefield scanning laser ophthalmoscopy image using VAMPIRE software</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in retinal vessel width gradient</measure>
    <time_frame>Baseline, 1 year</time_frame>
    <description>Retinal vessel width gradient measured on ultra-widefield scanning laser ophthalmoscopy image using VAMPIRE software</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in retinal vessel fractal dimension</measure>
    <time_frame>Baseline, 1 year</time_frame>
    <description>Retinal vessel fractal dimension measured on ultra-widefield scanning laser ophthalmoscopy image using VAMPIRE software</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">2000</enrollment>
  <condition>Alzheimer's Disease</condition>
  <condition>Mild Cognitive Impairment</condition>
  <condition>Parkinson's Disease</condition>
  <condition>Multiple Sclerosis</condition>
  <condition>Huntington Disease</condition>
  <condition>Lewy Body Dementia</condition>
  <condition>Frontotemporal Dementia</condition>
  <condition>Amyotrophic Lateral Sclerosis (ALS)</condition>
  <condition>APOE-4 Positive</condition>
  <condition>Traumatic Brain Injury</condition>
  <condition>Concussion</condition>
  <condition>Post-Traumatic Stress Disorder</condition>
  <condition>Down Syndrome</condition>
  <condition>Neuro-Degenerative Disease</condition>
  <condition>Normal Cognition</condition>
  <arm_group>
    <arm_group_label>Case</arm_group_label>
    <description>Patients with (MCI, PD, AD, FTD, DLB, ALS, MS, HD, TBI, concussion, PTSD and other neurodegenerations as well as Down Syndrome)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Controls</arm_group_label>
    <description>Controls will be recruited from the relatives/attendants of study participants or will be patients themselves and will not have a neurodegenerative disease diagnosis.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Retinal and Choroidal Imaging</intervention_name>
    <description>Non-invasive OCT, OCTA, and UWF fundus photography of retina</description>
    <arm_group_label>Case</arm_group_label>
    <arm_group_label>Controls</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Neurology Clinics and the community.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adults with neurodegenerative disease ((MCI, PD, AD, FTD, DLB, ALS, MS, HD, TBI,&#xD;
             concussion, PTSD and other neurodegenerations as well as Down Syndrome)&#xD;
&#xD;
          -  Adults without neurodegenerative disease&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Inability to cooperate with or complete testing or other neurologic or age- related&#xD;
             ocular conditions that would impact image acquisition.&#xD;
&#xD;
          -  Eyes that have had intraocular surgery, other than cataract surgery.&#xD;
&#xD;
        If two eyes satisfy the inclusion criteria, both eyes will be included in the study. If one&#xD;
        eye satisfies the inclusion criteria, the eye that qualifies will be included in the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sharon Sharon, MD FACS FASRS</last_name>
    <role>Principal Investigator</role>
    <affiliation>Duke University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Dilraj Grewal, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Duke University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Sharon Sharon, MD FACS FASRS</last_name>
    <phone>919-971-1138</phone>
    <email>sharon.fekrat@duke.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27705</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sharon Fekrat, MD FACS FASRS</last_name>
      <phone>919-971-1138</phone>
      <email>sharon.fekrat@duke.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>July 26, 2017</study_first_submitted>
  <study_first_submitted_qc>July 26, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 28, 2017</study_first_posted>
  <last_update_submitted>August 18, 2023</last_update_submitted>
  <last_update_submitted_qc>August 18, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 22, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>OCT angiography (OCTA)</keyword>
  <keyword>Optical Coherence Tomography (OCT)</keyword>
  <keyword>Vessel Density</keyword>
  <keyword>Superficial Capillary Plexus</keyword>
  <keyword>Retinal microvasculature</keyword>
  <keyword>Scanning Laser Ophthalmoscopy</keyword>
  <keyword>Ultra-widefield (UWF) Imaging</keyword>
  <keyword>Perfusion Density</keyword>
  <keyword>Retinal Nerve Fiber Layer</keyword>
  <keyword>Ganglion Cell Inner Plexiform Layer</keyword>
  <keyword>Choroidal Vascularity Index</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Parkinson Disease</mesh_term>
    <mesh_term>Multiple Sclerosis</mesh_term>
    <mesh_term>Alzheimer Disease</mesh_term>
    <mesh_term>Dementia</mesh_term>
    <mesh_term>Brain Injuries</mesh_term>
    <mesh_term>Brain Injuries, Traumatic</mesh_term>
    <mesh_term>Motor Neuron Disease</mesh_term>
    <mesh_term>Amyotrophic Lateral Sclerosis</mesh_term>
    <mesh_term>Down Syndrome</mesh_term>
    <mesh_term>Huntington Disease</mesh_term>
    <mesh_term>Neurodegenerative Diseases</mesh_term>
    <mesh_term>Frontotemporal Dementia</mesh_term>
    <mesh_term>Aphasia, Primary Progressive</mesh_term>
    <mesh_term>Pick Disease of the Brain</mesh_term>
    <mesh_term>Lewy Body Disease</mesh_term>
    <mesh_term>Sclerosis</mesh_term>
    <mesh_term>Cognitive Dysfunction</mesh_term>
    <mesh_term>Stress Disorders, Traumatic</mesh_term>
    <mesh_term>Stress Disorders, Post-Traumatic</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03233646
org study id: Pro00111831
nct id: NCT03233646
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
is us export: No
This study aims to develop and evaluate biomarkers using non-invasive optical coherence
      tomography (OCT) and OCT angiography (OCTA) as well as ultra-widefield (UWF) fundus
      photography to assess the structure and function of the retinal and choroidal
      microvasculature and structure in persons with mild cognitive impairment (MCI) and
      Alzheimer's Disease (AD), Parkinson's Disease (PD), or other neurodegenerative disease,
      diseases as outlined.
Using a multidisciplinary approach, this study aims to yield new insight into the vascular
      and structural pathophysiology of neurodegenerative disease. The investigators propose to
      develop and evaluate imaging biomarkers from OCT, OCTA, and UWF fundus photos to assess the
      structure and function of the retinal and choroidal microvasculature and structure in these
      individuals.

      The investigators hypothesize that microvascular and structural network alterations in the
      retina and choroid may mirror and possibly precede changes in the cerebral microcirculation
      seen in these neurodegenerative diseases. Using advanced image analysis and machine learning
      techniques, the investigators aim to evaluate markers of reduced capillary blood flow and
      non-perfusion in the superficial retinal vascular plexus and choriocapillaris imaged using
      OCT and OCTA, in a resolution not previously possible, that would complement already
      established retinal structural markers and increase their sensitivity and specificity in the
      earlier detection of these neurodegenerative diseases.

      This study looks to provide a proof of concept for retinal and choroidal imaging-based
      microvascular and structural biomarkers as an effective screening tool for neurodegenerative
      disease, particularly during in cognitive aging.

      The protocol for this study was amended and the record was updated accordingly.
observational model: Case-Control
time perspective: Prospective
measure: Change in ganglion cell-inner plexiform layer (GCIPL) thickness
time frame: Baseline, 1 year
description: Ganglion cell inner plexiform layer thickness as measured on optical coherence tomography scan of macula
measure: Change in retinal nerve fiber layer (RNFL) thickness
time frame: Baseline, 1 year
description: Retinal nerve fiber layer thickness as measured on optical coherence tomography scan of macula
measure: Change in central subfield thickness (CST)
time frame: Baseline, 1 year
description: Central subfield thickness as measured on optical coherence tomography scan of macula
measure: Change in choroidal vascularity index (CVI)
time frame: Baseline, 1 year
description: Choroidal vascularity index as measured using the COIN software in 1500 um area centered on the fovea
measure: Change in foveal avascular zone (FAZ) area
time frame: Baseline, 1 year
description: Foveal avascular zone area as measured in the superficial capillary plexus on 3mm optical coherence tomography angiography scan of the macula
measure: Change in average perfusion density (PD)
time frame: Baseline, 1 year
description: Average perfusion density as measured in the ETDRS 3mm and 6mm circle and rings on optical coherence tomography angiography scan of the macula
measure: Change in average vessel density (VD)
time frame: Baseline, 1 year
description: Average vessel density as measured in the ETDRS 3mm and 6mm circle and rings on optical coherence tomography angiography scan of the macula
measure: Change in average capillary perfusion density (CPD)
time frame: Baseline, 1 year
description: Capillary perfusion density as measured on peripapillary 4.5mm optical coherence tomography angiography scan
measure: Change in average capillary flux index (CFI)
time frame: Baseline, 1 year
description: Capillary flux index as measured on peripapillary 4.5mm optical coherence tomography angiography scan
measure: Change in retinal vessel tortuosity
time frame: Baseline, 1 year
description: Retinal vessel tortuosity measured on ultra-widefield scanning laser ophthalmoscopy image using VAMPIRE software
measure: Change in retinal vessel width gradient
time frame: Baseline, 1 year
description: Retinal vessel width gradient measured on ultra-widefield scanning laser ophthalmoscopy image using VAMPIRE software
measure: Change in retinal vessel fractal dimension
time frame: Baseline, 1 year
description: Retinal vessel fractal dimension measured on ultra-widefield scanning laser ophthalmoscopy image using VAMPIRE software
arm group label: Case
description: Patients with (MCI, PD, AD, FTD, DLB, ALS, MS, HD, TBI, concussion, PTSD and other neurodegenerations as well as Down Syndrome)
arm group label: Controls
description: Controls will be recruited from the relatives/attendants of study participants or will be patients themselves and will not have a neurodegenerative disease diagnosis.
intervention type: Device
intervention name: Retinal and Choroidal Imaging
description: Non-invasive OCT, OCTA, and UWF fundus photography of retina
arm group label: Case
arm group label: Controls
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Sharon Sharon, MD FACS FASRS
role: Principal Investigator
affiliation: Duke University
last name: Dilraj Grewal, MD
role: Principal Investigator
affiliation: Duke University
last name: Sharon Sharon, MD FACS FASRS
phone: 919-971-1138
email: sharon.fekrat@duke.edu
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Sponsor
mesh term: Parkinson Disease
mesh term: Multiple Sclerosis
mesh term: Alzheimer Disease
mesh term: Dementia
mesh term: Brain Injuries
mesh term: Brain Injuries, Traumatic
mesh term: Motor Neuron Disease
mesh term: Amyotrophic Lateral Sclerosis
mesh term: Down Syndrome
mesh term: Huntington Disease
mesh term: Neurodegenerative Diseases
mesh term: Frontotemporal Dementia
mesh term: Aphasia, Primary Progressive
mesh term: Pick Disease of the Brain
mesh term: Lewy Body Disease
mesh term: Sclerosis
mesh term: Cognitive Dysfunction
mesh term: Stress Disorders, Traumatic
mesh term: Stress Disorders, Post-Traumatic
sharing ipd: No