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/NCT05995392</url>
    </required_header>
    <id_info>
      <org_study_id>S2023</org_study_id>
      <nct_id>NCT05995392</nct_id>
    </id_info>
    <brief_title>The Effects and Safety of Topical Spironolactone Ophthalmic Solution, 0.005 mg/cc in Subjects With Dry Eye Disease</brief_title>
    <official_title>A Single-Center, Prospective Randomized, Double-Masked, Placebo-Controlled, Parallel- Group Pilot Study of the Effects and Safety of Topical Spironolactone Ophthalmic Solution, 0.005 mg/cc in Subjects With Dry Eye</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Richard W Yee, MD</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Yee, Richard W., M.D.</source>
    <oversight_info>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
      <is_us_export>Yes</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        The objective of this study is to evaluate the clinical efficacy of topical spironolactone&#xD;
        ophthalmic solution, 0.005 mg/cc in subjects with dry eye disease compared to placebo. The&#xD;
        hypothesis for this study is that topical spironolactone ophthalmic solution will be&#xD;
        beneficial in the management of signs and symptoms of dry eye disease when compared to&#xD;
        placebo.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 2023</start_date>
    <completion_date type="Anticipated">April 2024</completion_date>
    <primary_completion_date type="Anticipated">February 2024</primary_completion_date>
    <phase>Early Phase 1</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Change from Baseline to Week 4 in the Symptom Assessment Questionnaire Dry Eye (SANDE) score.</measure>
      <time_frame>Baseline to Week 4</time_frame>
      <description>The SANDE score is calculated by taking the square root of the product of the severity of symptoms score and the frequency of symptoms score. The SANDE scale ranges from 0 to 100 with 100 being the maximal amount of dry eye symptoms and 0 being the minimal amount or absence of dry eye symptoms.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Change from Baseline to Week 4 in the corneal fluorescein staining</measure>
      <time_frame>Baseline to Week 4</time_frame>
      <description>Corneal fluorescein staining is measured by the 0-3 point National Eye Institute (NEI) grading scale in any one corneal region. 0 represents no staining and 3 represents maximal/severe staining and damages to the cornea. Scores from each of the five corneal regions as defined by the NEI grading scale will be evaluated independently.</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Change from Baseline to Week 4 in SANDE severity sub-score (0-100 point VAS)</measure>
      <time_frame>Baseline to Week 4</time_frame>
      <description>The SANDE severity sub-score ranges from 0 to 100 with 100 being the maximal amount of dry eye severity symptoms and 0 being the minimal amount or absence of dry eye symptoms.</description>
    </other_outcome>
    <other_outcome>
      <measure>Change from Baseline to Week 4 in SANDE frequency sub-score (0-100 point VAS)</measure>
      <time_frame>Baseline to Week 4</time_frame>
      <description>The SANDE frequency sub-score ranges from 0 to 100 with 100 being the maximal amount of dry eye symptoms frequency and 0 being the minimal amount or absence of dry eye symptoms frequency.</description>
    </other_outcome>
    <other_outcome>
      <measure>Change from Baseline to Week 4 in conjunctival lissamine green staining</measure>
      <time_frame>Baseline to Week 4</time_frame>
      <description>Lissamine staining is measured by the 0-5 point Oxford grading scale. 0 represents no staining and 5 represents maximal/severe staining and abnormalities to the conjunctiva. Scores from each of the 3 zones as defined by the Oxford grading scale will be evaluated independently.</description>
    </other_outcome>
    <other_outcome>
      <measure>Change from Baseline to Week 4 in conjunctival injection</measure>
      <time_frame>Baseline to Week 4</time_frame>
      <description>Conjunctival injection is scored on a 0-2 grading scale. 0 represents no conjunctival injection and 2 represents maximal/severe conjunctival injection and redness of the eye.</description>
    </other_outcome>
    <other_outcome>
      <measure>Change from Baseline to Week 4 in tear production as measured by the Schirmer's 1 (unanesthetized) tear secretion test</measure>
      <time_frame>Baseline to Week 4</time_frame>
      <description>The Schirmer strip will be placed into the lower conjunctival sac at the junction of the lateral and middle thirds, avoiding contact with the cornea. The patient will be instructed to close their eyes gently. After 5 minutes have elapsed, the Schirmer test strip will be removed and the length of the tear absorption on the strip will be measured (millimeters/5 minutes).</description>
    </other_outcome>
    <other_outcome>
      <measure>Change from Baseline to Week 4 in lid margin Vascularity (V) score</measure>
      <time_frame>Baseline to Week 4</time_frame>
      <description>The lid margin V score is graded on a scale of 0-4 by the vascularization of the lower lid margin between the anterior and posterior edges of the lid. 0 represents absence/minimal vascularization of the lid margin and 4 represents severe/maximal abnormal vascularization.</description>
    </other_outcome>
    <other_outcome>
      <measure>Change from Baseline to Week 4 in Avascular Zone (Zone A) inflammation score</measure>
      <time_frame>Baseline to Week 4</time_frame>
      <description>Zone A will be graded on a scale of 0-4 by the hyperemia and vascularization of the normally avascular region of the palpebral conjunctiva ≤1mm posterior to the posterior tarsal edge. 0 represents absence/minimal hyperemia and vascularization and 4 represents severe/maximal abnormal hyperemia and vascularization.</description>
    </other_outcome>
    <other_outcome>
      <measure>Change from Baseline to Week 4 in Palpebral Conjunctival Redness (PCR) score</measure>
      <time_frame>Baseline to Week 4</time_frame>
      <description>PCR will be graded by the hyperemia of the palpebral conjunctiva of the lower eyelid on a 0-100 Validated Bulbar Redness (VBR) scale. 0 represents minimal/normal redness and 100 represents maximal/severe redness.</description>
    </other_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">30</enrollment>
    <condition>Dry Eye Disease</condition>
    <arm_group>
      <arm_group_label>Treatment</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Subjects receive topical spironolactone ophthalmic solution, 0.005 mg/cc four times a day for 4 weeks.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Subjects receive topical spironolactone vehicle as placebo four times a day for 4 weeks.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Topical spironolactone ophthalmic solution, 0.005 mg/cc</intervention_name>
      <description>Used four times a day in both eyes for 4 weeks.</description>
      <arm_group_label>Treatment</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>Used four times a day in both eyes for 4 weeks.</description>
      <arm_group_label>Placebo</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  SANDE questionnaire ≥30 mm&#xD;
  &#xD;
            -  Schirmer test without anesthesia ≥2 mm/5 minutes&#xD;
  &#xD;
            -  Corneal fluorescein staining score of ≥1 (0-3 point scale) in at least 1 corneal&#xD;
               region of the 5 zones based on the NEI scale, with particular attention paid to the&#xD;
               inferior region&#xD;
  &#xD;
            -  The same eye (eligible eye) must fulfill all the above criteria&#xD;
  &#xD;
            -  No lagophthalmos, entropion, ectropion&#xD;
  &#xD;
            -  No significant conjunctivochalasis (graded &lt;2 on a 0-4 point scale)&#xD;
  &#xD;
            -  Best corrected distance visual acuity (BCDVA) score of +0.7 or better as assessed by&#xD;
               Early Treatment of Diabetic Retinopathy Study (ETDRS) (20/200 Snellen value) in both&#xD;
               eyes at the baseline visit&#xD;
  &#xD;
            -  Intraocular pressure of ≥10 to &lt;21 mmHg&#xD;
  &#xD;
            -  If a female of childbearing potential, have a negative pregnancy test&#xD;
  &#xD;
            -  Only patients who satisfy all Informed Consent requirements may be included in the&#xD;
               study&#xD;
  &#xD;
            -  The patient must read, sign and date the Informed Consent document before any study&#xD;
               related procedures are performed&#xD;
  &#xD;
            -  The Informed Consent form signed by patients must have been approved by the&#xD;
               Institutional Review Board (IRB) / Independent Ethics Committee (IEC) for the current&#xD;
               study&#xD;
  &#xD;
            -  Patients must have the ability and willingness to comply with study procedures&#xD;
  &#xD;
            -  Ability to speak and understand the English language sufficiently to understand the&#xD;
               nature of the study, to provide written informed consent, and to allow the completion&#xD;
               of all study assessments&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Evidence of an active ocular infection, in either eye&#xD;
  &#xD;
            -  Presence of any other ocular disorder or condition requiring topical medication during&#xD;
               the entire duration of study&#xD;
  &#xD;
            -  History of severe systemic allergy or of ocular allergy (including seasonal&#xD;
               conjunctivitis) or chronic conjunctivitis and/or keratitis other than dry eye&#xD;
  &#xD;
            -  Intraocular inflammation defined as Tyndall score &gt;0&#xD;
  &#xD;
            -  Systemic disease not stabilized within 1 month before Visit 1 (e.g. diabetes with&#xD;
               glycemia out of range, thyroid malfunction) or judged by the investigator to be&#xD;
               incompatible with the study (e.g. current systemic infections) or incompatible with&#xD;
               the frequent assessment required by the study&#xD;
  &#xD;
            -  Patient had a serious adverse reaction or significant hypersensitivity to any drug or&#xD;
               chemically related compounds or had a clinically significant allergy to drugs, foods,&#xD;
               amide local anesthetics, or other materials including commercial artificial tears that&#xD;
               is judged by the investigator to be incompatible with the study&#xD;
  &#xD;
            -  Females of childbearing potential (those who are not surgically sterilized or post-&#xD;
               menopausal for at least 1 year) are excluded from participation in the study if they&#xD;
               meet any one of the following conditions:&#xD;
  &#xD;
                 1. are currently pregnant&#xD;
  &#xD;
                 2. have a positive result at the urine pregnancy test (Baseline/Day 0)&#xD;
  &#xD;
                 3. intend to become pregnant during the study treatment period&#xD;
  &#xD;
                 4. are breast-feeding&#xD;
  &#xD;
                 5. are not willing to use highly effective birth control measures, such as: hormonal&#xD;
                    contraceptives - oral, implanted, transdermal, or injected - and/or mechanical&#xD;
                    barrier methods - spermicide in conjunction with a barrier such as a condom or&#xD;
                    diaphragm or Intra Uterine Device (IUD) - during the entire course of and 30 days&#xD;
                    after the study treatment period ends&#xD;
  &#xD;
            -  Any concurrent medical condition, that in the judgment of the PI, might interfere with&#xD;
               the conduct of the study, confound the interpretation of the study results, or&#xD;
               endanger the patient's well-being&#xD;
  &#xD;
            -  Use of topical, nasal, or oral antihistamine within 24 hours prior to or during study&#xD;
               enrollment&#xD;
  &#xD;
            -  Use of oral spironolactone within 6 months prior to or during study enrollment&#xD;
  &#xD;
            -  Previous use of topical spironolactone ophthalmic solution&#xD;
  &#xD;
            -  Unstable use of topical cyclosporine, topical corticosteroids, artificial tears, lid&#xD;
               scrubs, or any other topical drug for the treatment of dry eye in either eye prior to&#xD;
               and during study enrollment&#xD;
  &#xD;
            -  Contact lenses use at any time 30 days prior or during study enrollment&#xD;
  &#xD;
            -  Cauterization of the punctum or punctal plugs placed within 14 days prior or during&#xD;
               study enrollment&#xD;
  &#xD;
            -  Any prior ocular surgery (including refractive palpebral and cataract surgery) within&#xD;
               90 days of study enrollment&#xD;
  &#xD;
            -  History of drug addiction or alcohol abuse&#xD;
  &#xD;
            -  Participation in a trial with a new active substance during the past 6 months&#xD;
  &#xD;
            -  Participation in another trial study at the same time as the present study&#xD;
  &#xD;
            -  Have been exposed to any investigational drug within the preceding 30 days&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Richard W Yee, MD</last_name>
      <phone>7133063051</phone>
      <email>drrichardyee@gmail.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Richard W Yee, MD PLLC</name>
        <address>
          <city>Bellaire</city>
          <state>Texas</state>
          <zip>77401</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <phone>832-289-2020</phone>
      </contact>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 9, 2023</study_first_submitted>
    <study_first_submitted_qc>August 9, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 16, 2023</study_first_posted>
    <last_update_submitted>August 16, 2023</last_update_submitted>
    <last_update_submitted_qc>August 16, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 21, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor-Investigator</responsible_party_type>
      <investigator_affiliation>Yee, Richard W., M.D.</investigator_affiliation>
      <investigator_full_name>Richard W Yee, MD</investigator_full_name>
      <investigator_title>Sponsor-Investigator</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Dry Eye Syndromes</mesh_term>
      <mesh_term>Keratoconjunctivitis Sicca</mesh_term>
      <mesh_term>Eye Diseases</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Spironolactone</mesh_term>
      <mesh_term>Ophthalmic Solutions</mesh_term>
    </intervention_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/NCT05995392
  org study id: S2023
  nct id: NCT05995392
  lead sponsor: 
  is fda regulated drug: Yes
  is fda regulated device: No
  is us export: Yes
  The objective of this study is to evaluate the clinical efficacy of topical spironolactone
        ophthalmic solution, 0.005 mg/cc in subjects with dry eye disease compared to placebo. The
        hypothesis for this study is that topical spironolactone ophthalmic solution will be
        beneficial in the management of signs and symptoms of dry eye disease when compared to
        placebo.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  measure: Change from Baseline to Week 4 in the Symptom Assessment Questionnaire Dry Eye (SANDE) score.
  time frame: Baseline to Week 4
  description: The SANDE score is calculated by taking the square root of the product of the severity of symptoms score and the frequency of symptoms score. The SANDE scale ranges from 0 to 100 with 100 being the maximal amount of dry eye symptoms and 0 being the minimal amount or absence of dry eye symptoms.
  measure: Change from Baseline to Week 4 in the corneal fluorescein staining
  time frame: Baseline to Week 4
  description: Corneal fluorescein staining is measured by the 0-3 point National Eye Institute (NEI) grading scale in any one corneal region. 0 represents no staining and 3 represents maximal/severe staining and damages to the cornea. Scores from each of the five corneal regions as defined by the NEI grading scale will be evaluated independently.
  measure: Change from Baseline to Week 4 in SANDE severity sub-score (0-100 point VAS)
  time frame: Baseline to Week 4
  description: The SANDE severity sub-score ranges from 0 to 100 with 100 being the maximal amount of dry eye severity symptoms and 0 being the minimal amount or absence of dry eye symptoms.
  measure: Change from Baseline to Week 4 in SANDE frequency sub-score (0-100 point VAS)
  time frame: Baseline to Week 4
  description: The SANDE frequency sub-score ranges from 0 to 100 with 100 being the maximal amount of dry eye symptoms frequency and 0 being the minimal amount or absence of dry eye symptoms frequency.
  measure: Change from Baseline to Week 4 in conjunctival lissamine green staining
  time frame: Baseline to Week 4
  description: Lissamine staining is measured by the 0-5 point Oxford grading scale. 0 represents no staining and 5 represents maximal/severe staining and abnormalities to the conjunctiva. Scores from each of the 3 zones as defined by the Oxford grading scale will be evaluated independently.
  measure: Change from Baseline to Week 4 in conjunctival injection
  time frame: Baseline to Week 4
  description: Conjunctival injection is scored on a 0-2 grading scale. 0 represents no conjunctival injection and 2 represents maximal/severe conjunctival injection and redness of the eye.
  measure: Change from Baseline to Week 4 in tear production as measured by the Schirmer's 1 (unanesthetized) tear secretion test
  time frame: Baseline to Week 4
  description: The Schirmer strip will be placed into the lower conjunctival sac at the junction of the lateral and middle thirds, avoiding contact with the cornea. The patient will be instructed to close their eyes gently. After 5 minutes have elapsed, the Schirmer test strip will be removed and the length of the tear absorption on the strip will be measured (millimeters/5 minutes).
  measure: Change from Baseline to Week 4 in lid margin Vascularity (V) score
  time frame: Baseline to Week 4
  description: The lid margin V score is graded on a scale of 0-4 by the vascularization of the lower lid margin between the anterior and posterior edges of the lid. 0 represents absence/minimal vascularization of the lid margin and 4 represents severe/maximal abnormal vascularization.
  measure: Change from Baseline to Week 4 in Avascular Zone (Zone A) inflammation score
  time frame: Baseline to Week 4
  description: Zone A will be graded on a scale of 0-4 by the hyperemia and vascularization of the normally avascular region of the palpebral conjunctiva ≤1mm posterior to the posterior tarsal edge. 0 represents absence/minimal hyperemia and vascularization and 4 represents severe/maximal abnormal hyperemia and vascularization.
  measure: Change from Baseline to Week 4 in Palpebral Conjunctival Redness (PCR) score
  time frame: Baseline to Week 4
  description: PCR will be graded by the hyperemia of the palpebral conjunctiva of the lower eyelid on a 0-100 Validated Bulbar Redness (VBR) scale. 0 represents minimal/normal redness and 100 represents maximal/severe redness.
  arm group label: Treatment
  arm group type: Experimental
  description: Subjects receive topical spironolactone ophthalmic solution, 0.005 mg/cc four times a day for 4 weeks.
  arm group label: Placebo
  arm group type: Placebo Comparator
  description: Subjects receive topical spironolactone vehicle as placebo four times a day for 4 weeks.
  intervention type: Drug
  intervention name: Topical spironolactone ophthalmic solution, 0.005 mg/cc
  description: Used four times a day in both eyes for 4 weeks.
  arm group label: Treatment
  intervention type: Drug
  intervention name: Placebo
  description: Used four times a day in both eyes for 4 weeks.
  arm group label: Placebo
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Richard W Yee, MD
  phone: 7133063051
  email: drrichardyee@gmail.com
  facility: 
  contact: 
  country: United States
  responsible party type: Sponsor-Investigator
  investigator affiliation: Yee, Richard W., M.D.
  investigator full name: Richard W Yee, MD
  investigator title: Sponsor-Investigator
  mesh term: Dry Eye Syndromes
  mesh term: Keratoconjunctivitis Sicca
  mesh term: Eye Diseases
  mesh term: Spironolactone
  mesh term: Ophthalmic Solutions