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/NCT06023927</url>
    </required_header>
    <id_info>
      <org_study_id>21-0958-MEETH</org_study_id>
      <nct_id>NCT06023927</nct_id>
    </id_info>
    <brief_title>Obstructive Sleep Apnea as a Risk Factor for Normal Tension Glaucoma and a Crucial Step in Preventing Blindness</brief_title>
    <official_title>Obstructive Sleep Apnea as a Risk Factor for Normal Tension Glaucoma and a Crucial Step in Preventing Blindness</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Northwell Health</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Northwell Health</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>
        The purpose of this research study is to learn more about the relationship between&#xD;
        Obstructive Sleep Apnea (OSA) and Normal Tension Glaucoma (NTG). OSA is a nighttime disorder&#xD;
        of the upper airway that causes an intermittent lack of oxygen while sleeping. NTG is a type&#xD;
        of glaucoma that occurs despite the normal intraocular pressure levels, making its detection&#xD;
        more difficult. Left untreated, irreversible optic nerve damage and extensive vision loss can&#xD;
        result. Previous research has shown some evidence between OSA and the development of NTG. The&#xD;
        investigators are researching whether undergoing treatment for OSA would help to improve the&#xD;
        vascular health to the retina, and in effect, improve the early signs of visual dysfunction&#xD;
        seen with diagnostic testing.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Glaucoma is a leading cause of irreversible blindness worldwide. Normal tension glaucoma&#xD;
        (NTG) is a challenging subtype in which progressive changes to the optic nerve and retinal&#xD;
        ganglion cell (RGC) function occur despite normal intraocular pressures (IOP). In most types&#xD;
        of glaucoma, elevated IOP is the major risk factor and a key target for medical therapy. The&#xD;
        absence of IOP elevation in NTG poses diagnostic dilemmas and therapeutic challenges. The&#xD;
        disease is often diagnosed late, with irreversible atrophic changes to the optic nerve and&#xD;
        permanent loss of vision. These clinically manifested structural and functional changes seen&#xD;
        on optical coherence tomography (OCT) and visual field (VF) tests are likely preceded by a&#xD;
        subclinical stage at which RGCs become increasingly dysfunctional before dying.&#xD;
  &#xD;
        Obstructive sleep apnea (OSA) is characterized by intermittent nocturnal upper airway&#xD;
        collapse, leading to oxygen deprivation and hypoxemia. It is a common cause of daytime&#xD;
        sleepiness and is associated with an increased likelihood of hypertension, cardiovascular&#xD;
        disease, stroke, and diminished quality of life. Continuous Positive Airway Pressure (CPAP)&#xD;
        therapy is an established treatment for moderate to severe OSA in which patients sleep with a&#xD;
        special mask that helps to regulate inspiratory and expiratory flow, alleviating hypoxia.&#xD;
  &#xD;
        The investigators hypothesize that eliminating the hypoxia induced by OSA could have a&#xD;
        favorable effect on retinal blood flow, thereby reducing the likelihood of progressive RGC&#xD;
        damage and dysfunction in subjects at risk for NTG. The investigators are proposing a&#xD;
        prospective, longitudinal, non-randomized study to evaluate the role of innovative diagnostic&#xD;
        technologies in the early detection of NTG, and to establish its association with OSA.&#xD;
        Additionally, the investigators will monitor the effects of OSA treatment in preventing the&#xD;
        development of the disease, or at least halting its progression. Special attention will be&#xD;
        given to the sex differences in the analysis to recognize the substantial differences in OSA&#xD;
        between men and women, as well as the prevalence of NTG in different OSA severity groups.&#xD;
  &#xD;
        While under the care of a Sleep Medicine physician, newly diagnosed subjects with OSA&#xD;
        interested in participating will be recruited from the Northwell sleep center. Prior to&#xD;
        initiating continuous positive airway pressure therapy (CPAP), consented participants will be&#xD;
        screened to satisfying the eligibility criteria, and undergo a complete ophthalmological&#xD;
        exam. Functional and structural diagnostic testing will be performed to evaluate baseline&#xD;
        measures, including visual field testing, OCT, pattern electroretinography (PERG) and optical&#xD;
        coherence tomography-angiography (OCTA) testing. Using the American Association of sleep&#xD;
        Medicine (AASM) criteria, 3 groups will be formed based on the apnea-hypopnea index (AHI).&#xD;
        The severity of OSA is graded as mild (AHI&lt;15), moderate (15&lt;AHI&lt;30), or severe (AHI&gt;30). The&#xD;
        Epworth questionnaire will be used as part of routine clinical care to monitor improvement or&#xD;
        deterioration after treatment. Once the baseline ophthalmological exam has been performed,&#xD;
        subjects will return to the sleep center to begin CPAP therapy for OSA. Three follow up&#xD;
        ophthalmic exams will be performed at 3, 6, and 9 months after initiating CPA therapy.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 1, 2023</start_date>
    <completion_date type="Anticipated">September 30, 2026</completion_date>
    <primary_completion_date type="Anticipated">September 30, 2025</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Cohort</observational_model>
      <time_perspective>Prospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Prevalence of NTG</measure>
      <time_frame>2 years</time_frame>
      <description>To determine the prevalence of normal tension glaucoma (NTG) in newly-diagnosed subjects with different stages of obstructive sleep apnea (mild, moderate, and severe)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Mean difference in diagnostic parameters at baseline</measure>
      <time_frame>2 years</time_frame>
      <description>Mean difference in pattern electroretinogram (PERG) parameters (in millivolts) and optical coherence tomography angiography (OCTA) Vessel density (VD) measurements at baseline between the 3 OSA study groups (mild, moderate, and severe).Magnitude (mV), MagnitudeD (MagD) (mV), MagD/Mag ratio and VD (%) will be compared across 3 OSA groups</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Mean change in diagnostic parameters at follow up intervals</measure>
      <time_frame>2 years</time_frame>
      <description>Mean change in PERG parameters (in millivolt) and OCTA vessel density measurements (%) in each of the follow up visits compared to baseline</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Two PERG devices will be compared in their ability to detect retinal ganglion cell dysfunction</measure>
      <time_frame>2 years</time_frame>
      <description>Diopsys NOVA PERG parameters will be correlated with PERG SmartEP parameters (in millivolts)</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Incidence of NTG in female subjects</measure>
      <time_frame>2 years</time_frame>
      <description>Incidence of NTG in female subjects</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Correlation of polysomnography and Epworth Sleeping Scale measures with PERG (Mag,MagD in millivolts, MagD/Mag ratio)and OCTA VD (%) measurements</measure>
      <time_frame>2 years</time_frame>
      <description>Correlation of day time sleepiness from the Epworth scale (in points), polysomnography measures (apnea-hypopnea Index, in events/hour, saturation of oxygen, SaO2 in %, ), with PERG Mag, MagD in mV, MagD/Mag ratio and OCTA VD (in %) measurements</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Correlations between PERG parameters, Ocular Perfusion Pressure (OPP) and corneal hysteresis</measure>
      <time_frame>2 years</time_frame>
      <description>Correlations between Mag, magD (in mV) and MagD/Mag ration, OPP measured by Falck device (mm Hg) , and corneal hysteresis (mm Hg), provided by ocular response analyzer, will be assessed</description>
    </secondary_outcome>
    <number_of_groups>3</number_of_groups>
    <enrollment type="Anticipated">100</enrollment>
    <condition>Normal Tension Glaucoma</condition>
    <condition>Obstructive Sleep Apnea</condition>
    <arm_group>
      <arm_group_label>Newly-diagnosed mild OSA - initiating CPAP treatment</arm_group_label>
      <description>Subjects with newly-diagnosed mild obstructive sleep apnea being treated with CPAP undergoing clinical observation/diagnostic evaluation for detection and tracking of NTG.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Newly-diagnosed moderate OSA - initiating CPAP treatment</arm_group_label>
      <description>Subjects with newly-diagnosed moderate obstructive sleep apnea being treated with CPAP undergoing clinical observation/diagnostic evaluation for detection and tracking of NTG.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Newly-diagnosed severe OSA - initiating CPAP treatment</arm_group_label>
      <description>Subjects with newly-diagnosed severe obstructive sleep apnea being treated with CPAP undergoing clinical observation/diagnostic evaluation for detection and tracking of NTG.</description>
    </arm_group>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Clinical observation, diagnostic testing</intervention_name>
      <description>Glaucoma evaluation including structural and functional diagnostic testing at baseline and 3 subsequent follow-up visits over a period of 9 months</description>
      <arm_group_label>Newly-diagnosed mild OSA - initiating CPAP treatment</arm_group_label>
      <arm_group_label>Newly-diagnosed moderate OSA - initiating CPAP treatment</arm_group_label>
      <arm_group_label>Newly-diagnosed severe OSA - initiating CPAP treatment</arm_group_label>
    </intervention>
    <eligibility>
      <study_pop>
        <textblock>
          Newly-diagnosed OSA patients that will undergo CPAP treatment&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Newly diagnosed subjects with OSA that will undergo CPAP treatment.&#xD;
  &#xD;
            -  At least 21 years of age&#xD;
  &#xD;
            -  Best corrected vision of 20/40 or better, spherical Rx &lt; ± 6.0 Diopter, and cylinder&#xD;
               &lt;-3.0D&#xD;
  &#xD;
            -  Ability to follow instructions, and intent to complete all study visits&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  High Rx &gt;± 6.0D and cylinder &gt; -3.0D&#xD;
  &#xD;
            -  Narrow angle glaucoma&#xD;
  &#xD;
            -  History of any of the following: severe eye trauma, ocular inflammation, previous&#xD;
               intraocular surgery except for uncomplicated cataract extraction with posterior&#xD;
               chamber intraocular lens implantation.&#xD;
  &#xD;
            -  Any medical or ocular condition which is not appropriate for participation in the&#xD;
               trial (Diabetic retinopathy, and other retinal changes preventing reliable optic disc&#xD;
               evaluation) Hypersensitivity to any component of altafluor benox&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>21 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
    </eligibility>
    <location>
      <facility>
        <name>Manhattan Eye, Ear, &amp; Throat Hospital</name>
        <address>
          <city>New York</city>
          <state>New York</state>
          <zip>10065</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Andrew Tirsi, MD</last_name>
        <phone>201-982-4168</phone>
        <email>atirsi@northwell.edu</email>
      </contact>
      <investigator>
        <last_name>Celso Tello, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
      <investigator>
        <last_name>Stephen Obstbaum, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Sung Chul Park, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Yosef Krespi, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Tirsi Andrew, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Manhattan Eye, Ear, &amp; Throat Hospital</name>
        <address>
          <city>New York</city>
          <state>New York</state>
          <zip>10065</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Andrew Tirsi, MD</last_name>
        <phone>201-982-4168</phone>
        <email>atirsi@northwell.edu</email>
      </contact>
      <contact_backup>
        <last_name>Tirsi</last_name>
        <email>atirsi@northwell.edu</email>
      </contact_backup>
      <investigator>
        <last_name>Celso Tello, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
      <investigator>
        <last_name>Stephen Obstbaum, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Sung Chul Park, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Yosef Krespi, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Tirsi Andrew, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>April 12, 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>August 28, 2023</last_update_submitted>
    <last_update_submitted_qc>August 28, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 5, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Glaucoma, obstructive sleep apnea Syndrome</keyword>
    <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>
      <mesh_term>Sleep Apnea, Obstructive</mesh_term>
      <mesh_term>Blindness</mesh_term>
      <mesh_term>Glaucoma</mesh_term>
      <mesh_term>Low Tension Glaucoma</mesh_term>
    </condition_browse>
    <!-- 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/NCT06023927
  org study id: 21-0958-MEETH
  nct id: NCT06023927
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The purpose of this research study is to learn more about the relationship between
        Obstructive Sleep Apnea (OSA) and Normal Tension Glaucoma (NTG). OSA is a nighttime disorder
        of the upper airway that causes an intermittent lack of oxygen while sleeping. NTG is a type
        of glaucoma that occurs despite the normal intraocular pressure levels, making its detection
        more difficult. Left untreated, irreversible optic nerve damage and extensive vision loss can
        result. Previous research has shown some evidence between OSA and the development of NTG. The
        investigators are researching whether undergoing treatment for OSA would help to improve the
        vascular health to the retina, and in effect, improve the early signs of visual dysfunction
        seen with diagnostic testing.
  Glaucoma is a leading cause of irreversible blindness worldwide. Normal tension glaucoma
        (NTG) is a challenging subtype in which progressive changes to the optic nerve and retinal
        ganglion cell (RGC) function occur despite normal intraocular pressures (IOP). In most types
        of glaucoma, elevated IOP is the major risk factor and a key target for medical therapy. The
        absence of IOP elevation in NTG poses diagnostic dilemmas and therapeutic challenges. The
        disease is often diagnosed late, with irreversible atrophic changes to the optic nerve and
        permanent loss of vision. These clinically manifested structural and functional changes seen
        on optical coherence tomography (OCT) and visual field (VF) tests are likely preceded by a
        subclinical stage at which RGCs become increasingly dysfunctional before dying.
  
        Obstructive sleep apnea (OSA) is characterized by intermittent nocturnal upper airway
        collapse, leading to oxygen deprivation and hypoxemia. It is a common cause of daytime
        sleepiness and is associated with an increased likelihood of hypertension, cardiovascular
        disease, stroke, and diminished quality of life. Continuous Positive Airway Pressure (CPAP)
        therapy is an established treatment for moderate to severe OSA in which patients sleep with a
        special mask that helps to regulate inspiratory and expiratory flow, alleviating hypoxia.
  
        The investigators hypothesize that eliminating the hypoxia induced by OSA could have a
        favorable effect on retinal blood flow, thereby reducing the likelihood of progressive RGC
        damage and dysfunction in subjects at risk for NTG. The investigators are proposing a
        prospective, longitudinal, non-randomized study to evaluate the role of innovative diagnostic
        technologies in the early detection of NTG, and to establish its association with OSA.
        Additionally, the investigators will monitor the effects of OSA treatment in preventing the
        development of the disease, or at least halting its progression. Special attention will be
        given to the sex differences in the analysis to recognize the substantial differences in OSA
        between men and women, as well as the prevalence of NTG in different OSA severity groups.
  
        While under the care of a Sleep Medicine physician, newly diagnosed subjects with OSA
        interested in participating will be recruited from the Northwell sleep center. Prior to
        initiating continuous positive airway pressure therapy (CPAP), consented participants will be
        screened to satisfying the eligibility criteria, and undergo a complete ophthalmological
        exam. Functional and structural diagnostic testing will be performed to evaluate baseline
        measures, including visual field testing, OCT, pattern electroretinography (PERG) and optical
        coherence tomography-angiography (OCTA) testing. Using the American Association of sleep
        Medicine (AASM) criteria, 3 groups will be formed based on the apnea-hypopnea index (AHI).
        The severity of OSA is graded as mild (AHI<15), moderate (15<AHI<30), or severe (AHI>30). The
        Epworth questionnaire will be used as part of routine clinical care to monitor improvement or
        deterioration after treatment. Once the baseline ophthalmological exam has been performed,
        subjects will return to the sleep center to begin CPAP therapy for OSA. Three follow up
        ophthalmic exams will be performed at 3, 6, and 9 months after initiating CPA therapy.
  observational model: Cohort
  time perspective: Prospective
  measure: Prevalence of NTG
  time frame: 2 years
  description: To determine the prevalence of normal tension glaucoma (NTG) in newly-diagnosed subjects with different stages of obstructive sleep apnea (mild, moderate, and severe)
  measure: Mean difference in diagnostic parameters at baseline
  time frame: 2 years
  description: Mean difference in pattern electroretinogram (PERG) parameters (in millivolts) and optical coherence tomography angiography (OCTA) Vessel density (VD) measurements at baseline between the 3 OSA study groups (mild, moderate, and severe).Magnitude (mV), MagnitudeD (MagD) (mV), MagD/Mag ratio and VD (%) will be compared across 3 OSA groups
  measure: Mean change in diagnostic parameters at follow up intervals
  time frame: 2 years
  description: Mean change in PERG parameters (in millivolt) and OCTA vessel density measurements (%) in each of the follow up visits compared to baseline
  measure: Two PERG devices will be compared in their ability to detect retinal ganglion cell dysfunction
  time frame: 2 years
  description: Diopsys NOVA PERG parameters will be correlated with PERG SmartEP parameters (in millivolts)
  measure: Incidence of NTG in female subjects
  time frame: 2 years
  description: Incidence of NTG in female subjects
  measure: Correlation of polysomnography and Epworth Sleeping Scale measures with PERG (Mag,MagD in millivolts, MagD/Mag ratio)and OCTA VD (%) measurements
  time frame: 2 years
  description: Correlation of day time sleepiness from the Epworth scale (in points), polysomnography measures (apnea-hypopnea Index, in events/hour, saturation of oxygen, SaO2 in %, ), with PERG Mag, MagD in mV, MagD/Mag ratio and OCTA VD (in %) measurements
  measure: Correlations between PERG parameters, Ocular Perfusion Pressure (OPP) and corneal hysteresis
  time frame: 2 years
  description: Correlations between Mag, magD (in mV) and MagD/Mag ration, OPP measured by Falck device (mm Hg) , and corneal hysteresis (mm Hg), provided by ocular response analyzer, will be assessed
  arm group label: Newly-diagnosed mild OSA - initiating CPAP treatment
  description: Subjects with newly-diagnosed mild obstructive sleep apnea being treated with CPAP undergoing clinical observation/diagnostic evaluation for detection and tracking of NTG.
  arm group label: Newly-diagnosed moderate OSA - initiating CPAP treatment
  description: Subjects with newly-diagnosed moderate obstructive sleep apnea being treated with CPAP undergoing clinical observation/diagnostic evaluation for detection and tracking of NTG.
  arm group label: Newly-diagnosed severe OSA - initiating CPAP treatment
  description: Subjects with newly-diagnosed severe obstructive sleep apnea being treated with CPAP undergoing clinical observation/diagnostic evaluation for detection and tracking of NTG.
  intervention type: Other
  intervention name: Clinical observation, diagnostic testing
  description: Glaucoma evaluation including structural and functional diagnostic testing at baseline and 3 subsequent follow-up visits over a period of 9 months
  arm group label: Newly-diagnosed mild OSA - initiating CPAP treatment
  arm group label: Newly-diagnosed moderate OSA - initiating CPAP treatment
  arm group label: Newly-diagnosed severe OSA - initiating CPAP treatment
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 21 Years
  maximum age: N/A
  facility: 
  contact: 
  investigator: 
  investigator: 
  investigator: 
  investigator: 
  investigator: 
  facility: 
  contact: 
  contact backup: 
  investigator: 
  investigator: 
  investigator: 
  investigator: 
  investigator: 
  country: United States
  responsible party type: Sponsor
  mesh term: Apnea
  mesh term: Sleep Apnea Syndromes
  mesh term: Sleep Apnea, Obstructive
  mesh term: Blindness
  mesh term: Glaucoma
  mesh term: Low Tension Glaucoma