<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/NCT02265133</url>
  </required_header>
  <id_info>
    <org_study_id>STU 102011-033</org_study_id>
    <nct_id>NCT02265133</nct_id>
  </id_info>
  <brief_title>Corneal Sensitivity in Patients With Sleep Apnea Syndrome</brief_title>
  <official_title>Corneal Sensitivity and Nerve Fiber Morphology in Patients With Sleep Apnea Syndrome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Texas Southwestern Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Texas Southwestern Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is a prospective, single center clinical trial to assess corneal sensitivity and&#xD;
      nerve fiber morphology in patients with sleep apnea compared to normal controls. Healthy&#xD;
      volunteers with no history of ocular or uncontrollable systemic disease will be encouraged to&#xD;
      participate in the study. After execution and review of the consenting procedures, a detailed&#xD;
      history will be taken and a slit lamp examination performed, verifying ocular health. This&#xD;
      consists of an examination of both eyes including assessments of ocular lids, lashes, cornea&#xD;
      and conjunctival evaluation. Corneal touch thresholds will be tested with a Cochet-Bonnet&#xD;
      aesthesiometer, a standard non-invasive measure of corneal sensitivity. Corneal nerves will&#xD;
      be imaged using a modified HRT in vivo confocal microscope. The in vivo confocal microscope&#xD;
      allows for high resolution imaging of the nerve plexus under the corneal epithelium. This&#xD;
      corneal nerve plexus is responsible for corneal sensitively and changes or loss have been&#xD;
      established as an early, sensitive indicator of corneal neuropathy. The investigators&#xD;
      anticipate that this study will require approximately 30 patients for each group and will&#xD;
      last approximately 12 months for recruitment and completion of subject visit phases. There is&#xD;
      only one clinical visit designed for this project, unscheduled visits may be scheduled in&#xD;
      case of an adverse event.&#xD;
&#xD;
      Patient recruitment will be complete at the one-year time point. At the 14 month time point,&#xD;
      all data points will have been collected and assessment of the outcome measure (corneal&#xD;
      sensitivity in sleep apnea patients versus control patients) will be complete.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Screening Assessment: Following the execution of informed consent, subjects will be carefully&#xD;
      screened for ocular signs and symptoms, consistent with the protocol inclusion and exclusion&#xD;
      criteria. This includes review of ocular and medical history including use of concomitant &amp;&#xD;
      ocular medications and surgeries performed in the past. Researchers will also collect age,&#xD;
      ethnicity, demographics, ophthalmic notes and eye exam history. Upon completion of the&#xD;
      screening exam, subjects will be deemed eligible based on study criteria the testing&#xD;
      procedures will be performed by the investigators.&#xD;
&#xD;
      Testing procedures: The visit will include:&#xD;
&#xD;
      Slit Lamp Microscopy:&#xD;
&#xD;
      An ocular examination of the external (lids, lashes) along with internal (cornea, lens,&#xD;
      retina) structures of the eye can be performed with the aid of a slit lamp. This instruments&#xD;
      uses lenses and an external light source that can be refracted at different angles and&#xD;
      intensities to assess ocular structures for diagnostic purposes.&#xD;
&#xD;
      Corneal sensitivity measurement:&#xD;
&#xD;
        1. Corneal touch sensitivity will be determined using a Cochet-Bonnet aesthesiometer&#xD;
           mounted on a standard slit lamp biomicroscope. The Cochet-Bonnet aesthesiometer is&#xD;
           routinely used for clinical research purposes to investigate corneal touch thresholds.&#xD;
&#xD;
        2. For sensitivity measurements, a 0.12 mm diameter nylon thread will be slowly brought&#xD;
           forward to briefly touch the cornea perpendicularly and then quickly withdrawn.&#xD;
&#xD;
        3. On each occasion, the patient will be asked to respond whenever a stimulus is felt.&#xD;
&#xD;
        4. Thread length is used to quantitatively assess sensitivity. The longest thread length is&#xD;
           used first (6 cm), as this provides the lowest stimulus intensity.&#xD;
&#xD;
        5. If the subject is unable to detect the touch stimulus, the thread will be systematically&#xD;
           shortened in length by 0.5 cm steps until the stimulus is felt.&#xD;
&#xD;
        6. The criterion for the sensitivity threshold will be the filament length which gives a&#xD;
           50% positive response from four stimulus applications.&#xD;
&#xD;
      In Vivo Confocal Microscope&#xD;
&#xD;
        1. Corneal nerves will be imaged using a modified in vivo confocal microscope which is&#xD;
           routinely used in our clinics (HRT Rostock corneal module, Heidelberg Engineering).&#xD;
&#xD;
        2. The HRT In Vivo Confocal microscope was modified by adding a motor to automate the&#xD;
           focus. This does not alter the integrity, the application, the intent or the light&#xD;
           source of the instrument.&#xD;
&#xD;
        3. Corneas will be anesthetized with a topical anesthetic, proparacaine, prior to scanning.&#xD;
&#xD;
        4. The confocal microscope will briefly touch the patient's eye and the images saved for&#xD;
           further analysis.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">July 17, 2015</start_date>
  <completion_date type="Anticipated">December 31, 2024</completion_date>
  <primary_completion_date type="Actual">July 1, 2022</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>Corneal Sensitivity</measure>
    <time_frame>1-Day</time_frame>
    <description>To investigate whether diminished corneal sensitivity contributes to corneal problems commonly reported in patients with sleep apnea. Specifically, this study will correlate changes in corneal touch thresholds with corneal nerve fiber morphology using in vivo confocal microscopy.</description>
  </primary_outcome>
  <enrollment type="Actual">129</enrollment>
  <condition>Sleep Apnea</condition>
  <eligibility>
    <study_pop>
      <textblock>
        Sleep Apnea and normal controls&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Healthy, non-smoking volunteers.&#xD;
&#xD;
          2. Patients with a diagnosis of sleep apnea.&#xD;
&#xD;
          3. Non-contact lens wearers of any gender and race, ages 18 and up.&#xD;
&#xD;
          4. Minority representation will be proactively encouraged.&#xD;
&#xD;
          5. Patients that are willing to review, understand, and sign the written Informed&#xD;
             Consent.&#xD;
&#xD;
          6. Written authorization for use or release of health and research study information.&#xD;
&#xD;
          7. Patients that are willing and able to cooperate with the Investigator and follow all&#xD;
             instructions.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Use of ocular drops including over the counter (OTC) dry eye drops.&#xD;
&#xD;
          2. Previous history of corneal surgery.&#xD;
&#xD;
          3. Previous history of ocular trauma.&#xD;
&#xD;
          4. History of Diabetes Mellitus.&#xD;
&#xD;
          5. Current active or previous history of Herpes virus keratitis.&#xD;
&#xD;
          6. Current or former Contact lens wear.&#xD;
&#xD;
          7. Chronic history of dry eye disease.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Danielle Robertson, O.D, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>UTSW Medical Center at Dallas</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Parkland Hospital</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75235</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aston Ambulatory Care Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>December 21, 2011</study_first_submitted>
  <study_first_submitted_qc>October 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 15, 2014</study_first_posted>
  <last_update_submitted>August 11, 2023</last_update_submitted>
  <last_update_submitted_qc>August 11, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 14, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Texas Southwestern Medical Center</investigator_affiliation>
    <investigator_full_name>Danielle Robertson</investigator_full_name>
    <investigator_title>Associate Professor of Medicine</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Apnea</mesh_term>
    <mesh_term>Sleep Apnea Syndromes</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/NCT02265133
org study id: STU 102011-033
nct id: NCT02265133
lead sponsor: 
has dmc: No
This study is a prospective, single center clinical trial to assess corneal sensitivity and
      nerve fiber morphology in patients with sleep apnea compared to normal controls. Healthy
      volunteers with no history of ocular or uncontrollable systemic disease will be encouraged to
      participate in the study. After execution and review of the consenting procedures, a detailed
      history will be taken and a slit lamp examination performed, verifying ocular health. This
      consists of an examination of both eyes including assessments of ocular lids, lashes, cornea
      and conjunctival evaluation. Corneal touch thresholds will be tested with a Cochet-Bonnet
      aesthesiometer, a standard non-invasive measure of corneal sensitivity. Corneal nerves will
      be imaged using a modified HRT in vivo confocal microscope. The in vivo confocal microscope
      allows for high resolution imaging of the nerve plexus under the corneal epithelium. This
      corneal nerve plexus is responsible for corneal sensitively and changes or loss have been
      established as an early, sensitive indicator of corneal neuropathy. The investigators
      anticipate that this study will require approximately 30 patients for each group and will
      last approximately 12 months for recruitment and completion of subject visit phases. There is
      only one clinical visit designed for this project, unscheduled visits may be scheduled in
      case of an adverse event.

      Patient recruitment will be complete at the one-year time point. At the 14 month time point,
      all data points will have been collected and assessment of the outcome measure (corneal
      sensitivity in sleep apnea patients versus control patients) will be complete.
Screening Assessment: Following the execution of informed consent, subjects will be carefully
      screened for ocular signs and symptoms, consistent with the protocol inclusion and exclusion
      criteria. This includes review of ocular and medical history including use of concomitant &
      ocular medications and surgeries performed in the past. Researchers will also collect age,
      ethnicity, demographics, ophthalmic notes and eye exam history. Upon completion of the
      screening exam, subjects will be deemed eligible based on study criteria the testing
      procedures will be performed by the investigators.

      Testing procedures: The visit will include:

      Slit Lamp Microscopy:

      An ocular examination of the external (lids, lashes) along with internal (cornea, lens,
      retina) structures of the eye can be performed with the aid of a slit lamp. This instruments
      uses lenses and an external light source that can be refracted at different angles and
      intensities to assess ocular structures for diagnostic purposes.

      Corneal sensitivity measurement:

        1. Corneal touch sensitivity will be determined using a Cochet-Bonnet aesthesiometer
           mounted on a standard slit lamp biomicroscope. The Cochet-Bonnet aesthesiometer is
           routinely used for clinical research purposes to investigate corneal touch thresholds.

        2. For sensitivity measurements, a 0.12 mm diameter nylon thread will be slowly brought
           forward to briefly touch the cornea perpendicularly and then quickly withdrawn.

        3. On each occasion, the patient will be asked to respond whenever a stimulus is felt.

        4. Thread length is used to quantitatively assess sensitivity. The longest thread length is
           used first (6 cm), as this provides the lowest stimulus intensity.

        5. If the subject is unable to detect the touch stimulus, the thread will be systematically
           shortened in length by 0.5 cm steps until the stimulus is felt.

        6. The criterion for the sensitivity threshold will be the filament length which gives a
           50% positive response from four stimulus applications.

      In Vivo Confocal Microscope

        1. Corneal nerves will be imaged using a modified in vivo confocal microscope which is
           routinely used in our clinics (HRT Rostock corneal module, Heidelberg Engineering).

        2. The HRT In Vivo Confocal microscope was modified by adding a motor to automate the
           focus. This does not alter the integrity, the application, the intent or the light
           source of the instrument.

        3. Corneas will be anesthetized with a topical anesthetic, proparacaine, prior to scanning.

        4. The confocal microscope will briefly touch the patient's eye and the images saved for
           further analysis.
observational model: Case-Control
time perspective: Prospective
measure: Corneal Sensitivity
time frame: 1-Day
description: To investigate whether diminished corneal sensitivity contributes to corneal problems commonly reported in patients with sleep apnea. Specifically, this study will correlate changes in corneal touch thresholds with corneal nerve fiber morphology using in vivo confocal microscopy.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 90 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Danielle Robertson, O.D, PhD
role: Principal Investigator
affiliation: UTSW Medical Center at Dallas
facility: 
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Texas Southwestern Medical Center
investigator full name: Danielle Robertson
investigator title: Associate Professor of Medicine
mesh term: Apnea
mesh term: Sleep Apnea Syndromes
sharing ipd: No