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/NCT06016010</url>
    </required_header>
    <id_info>
      <org_study_id>KIOM_2301_DED_USL</org_study_id>
      <nct_id>NCT06016010</nct_id>
    </id_info>
    <brief_title>Efficacy and Safety of USL for Dry Eye Disease</brief_title>
    <official_title>Efficacy and Safety of USL for Dry Eye Disease (DED): a Randomized, Double-blind, Placebo-controlled, Parallel, Phase 2 Clinical Trial</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Chan-Sik Kim</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Korea Institute of Oriental Medicine</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 objective is to compare the USL and placebo in terms of efficacy and safety, and to&#xD;
        determine the appropriate dosage.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This study is a phase 2, dose-finding, double-blind, randomized placebo-controlled trial of&#xD;
        two different doses of USL compared with placebo. A total of 120 patients, aged over 19&#xD;
        years, with Corneal staining score(Oxford grading) ≥ 2 or TBUT &lt; 10 sec and OSDI ≥ 10 points&#xD;
        will be recruited at Daejeon University Daejeon Korean Medicine Hospital. Patients will take&#xD;
        medications two times daily for 12 weeks, with 5 visiting days(screening, week 0, week 6,&#xD;
        week 12, week 14).&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">January 1, 2024</start_date>
    <completion_date type="Anticipated">December 31, 2025</completion_date>
    <primary_completion_date type="Anticipated">December 31, 2025</primary_completion_date>
    <phase>Phase 2</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>Triple (Participant, Investigator, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>TBUT(Tear break-up time)</measure>
      <time_frame>Screening, 6 week, 12 week, 14 week</time_frame>
      <description>The tear break-up time test measures the time in seconds. The time is from the last blinking to the point of tear layer defect or streak-like defect after blinking the eye with 1% of fluorescein.&#xD;
  10 seconds or more as normal, between 5 and 10 seconds as mild dry eye syndrome, and 5 seconds or less as severe dry eye syndrome.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>OSDI(Ocular Surface Disease Index)</measure>
      <time_frame>Screening, 6 week, 12 week, 14 week</time_frame>
      <description>The Ocular Surface Disease Index consisted of 12 questions each of which included visual symptoms, visual work status, and environmental factors.&#xD;
  The Ocular Surface Disease Index scores are ranged from 0 to 100, and the high score is the more severe the symptoms. The Ocular Surface Disease Index score is calculated as follows.&#xD;
  : (Sum of all items answered × 25) / total number of questions answered</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>VAS(Visual analog scale)</measure>
      <time_frame>0 week, 6 week, 12 week, 14 week</time_frame>
      <description>The Visual Analog Scale(VAS) score is 0 point for no symptom, 10 points for the most severe symptom, and the patient is asked to mark the degree of subjective pain symptoms as an integer.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Schirmer's test</measure>
      <time_frame>0 week, 6 week, 12 week, 14 week</time_frame>
      <description>The eyes were wiped and the Schirmer test paper was inserted into the right eye at 1/3 of the lower eyelid without eye anesthesia and inserted into the left eye. After 5 minutes with the eyes closed, the Schirmer test paper was removed from the right side in the order of insertion and the left side removed. The wet length was measured in millimeters and the length of the midpoint was measured when the wet border was oblique.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Meibomian gland test</measure>
      <time_frame>0 week, 6 week, 12 week, 14 week</time_frame>
      <description>By expression of eyelid, scoring of expressibility and quality of meibum will be tested. Form of secretion predominantly secreted by the eight meibomian glands in the center of the lid was evaluated as follows. grade 0, clear meibum is easily expressed; grade 1, cloudy meibum is expressed with mild pressure; grade 2, cloudy meibum is expressed with more than moderate pressure; and grade 3, meibum cannot be expressed even with the hard pressure. Higher score means a worst outcome.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Fluorescein corneal staining score - Oxford grading</measure>
      <time_frame>Screening, 6 week, 12 week, 14 week</time_frame>
      <description>The degree of corneal inflammation is scored (total of 5 points) according to the Oxford grading scale from 0 (no staining, A) to 5 (severe, confluent staining, &gt;E).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>SPEED-II (Standard Patient Evaluation for Eye Dryness-II)</measure>
      <time_frame>0 week, 6 week, 12 week, 14 week</time_frame>
      <description>The SPEED questionnaire was designed in order to quickly track the progression of dry eye symptoms over time. This questionnaire gives a score from 0 to 28 that is the result of 8 items that assess frequency and severity of symptoms. The symptoms assessed include dryness, grittiness, scratchiness, irritation, burning, watering, soreness, and eye fatigue. The questionnaire further assesses whether these symptoms were not problematic, tolerable, uncomfortable, bothersome, or intolerable.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Biomarkers</measure>
      <time_frame>0 week, 12 week</time_frame>
      <description>The levels of IL-1β, IFN-γ, TNF-α</description>
    </secondary_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">120</enrollment>
    <condition>Dry Eye Disease</condition>
    <arm_group>
      <arm_group_label>Standard-dose USL group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>2 tablets(1 USL, 1 placebo) b.i.d for 12 weeks</description>
    </arm_group>
    <arm_group>
      <arm_group_label>High-dose USL group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>2 tablets(2 USL) b.i.d for 12 weeks</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo group</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>2 tablets(2 placebo) b.i.d for 12 weeks</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>USL</intervention_name>
      <description>500mg of Achyranthis Radix Extract</description>
      <arm_group_label>High-dose USL group</arm_group_label>
      <arm_group_label>Standard-dose USL group</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>USL Placebo</intervention_name>
      <description>USL Placebo</description>
      <arm_group_label>Placebo group</arm_group_label>
      <arm_group_label>Standard-dose USL group</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Aged over 19&#xD;
  &#xD;
            -  Screening both eyes, the corrected visual acuity is 0.2 or more&#xD;
  &#xD;
            -  Subjects with Fluorescein Corneal Staining score (Oxford grading) ≥ 2 or TBUT test ≤10&#xD;
               at screening&#xD;
  &#xD;
            -  Subjects with OSDI ≥ 13&#xD;
  &#xD;
            -  Subjects who voluntarily agreed to participate in this clinical study in written form&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Current or history of ocular disorders possibly affecting the study results (ocular&#xD;
               surgery, trauma, diseases) as followings within 2 months:&#xD;
  &#xD;
                 1. Abnormal eyelid function: disorders of the eyelids or eyelashes&#xD;
  &#xD;
                 2. Ocular allergies or currently under the treatment of allergic diseases of the eye&#xD;
                    (topical ocular mast cell stabilizer, antihistamine use, etc.)&#xD;
  &#xD;
                 3. Cicatricial keratoconjunctivitis caused by herpetic keratopathy, conjunctival&#xD;
                    scarring (alkali damage, Steven-Johnson syndrome, cicatricial pemphigoid),&#xD;
                    pterygium, pinguecula, lack of congenital lacrimal, neurogenic keratitis,&#xD;
                    keratoconus, corneal transplantation&#xD;
  &#xD;
            -  Those with acute eye inflammation/infection within 1 month&#xD;
  &#xD;
            -  Those who have undergone eye surgery (including LASIK/LASIK) within 3 months&#xD;
  &#xD;
            -  Those who had taken lacrimal punctal occlusion, cauterization of the punctum, or&#xD;
               intense pulsed light procedure within 3 months&#xD;
  &#xD;
            -  Those who wear contact lenses within 72 hours of screening or plan to wear contact&#xD;
               lens during the study period&#xD;
  &#xD;
            -  Intraocular pressure (IOP)&gt; 25 mmHg in more than one side&#xD;
  &#xD;
            -  Autoimmune disease (e.g., Sjogren's syndrome, Rheumatoid arthritis, systemic lupus&#xD;
               erythematosus, Graves' disease)&#xD;
  &#xD;
            -  Those who have used cyclosporine or diquafosol use in any form (systemic, topical)&#xD;
               within 1 month&#xD;
  &#xD;
            -  Medical condition or history within 1 month to be treated with topical agents besides&#xD;
               artificial tears (glaucoma, ocular allergy, ocular inflammation/infectious disease,&#xD;
               etc.)&#xD;
  &#xD;
            -  Those who have taken or are taking steroid drugs or immunosuppressants (Azathioprine,&#xD;
               Tacrolimus, Cyclosporin, Mycophenolate mofetil etc.) that may affect immune function&#xD;
               within 3 months prior to screening&#xD;
  &#xD;
            -  Those who had taken antihypertensive drugs such as antihistamine and beta blockers,&#xD;
               diuretics, antidepressants (especially tricyclic antidepressants, Parkinson's&#xD;
               treatment drugs, etc.) that can worsen dry eye cannot participate in this study&#xD;
  &#xD;
            -  Severe abnormal liver function tests (Alanine transaminase (ALT) or Aspartate&#xD;
               transaminase (AST) values ≥ 2 times the upper limit of normal) and abnormal renal&#xD;
               function (Creatinine values ≥ 2 times the upper limit of normal)&#xD;
  &#xD;
            -  Genetic disorders, such as galactose intolerance, Lapp lactase deficiency, or&#xD;
               glucose-galactose malabsorption&#xD;
  &#xD;
            -  Comorbidities that may interrupt the treatment of cancers or clinically significant&#xD;
               disorders of the kidney, liver, psychiatric system, cardiovascular system, respiratory&#xD;
               system, endocrine system, and central nervous system, the safety assessment, or&#xD;
               completion of this clinical study&#xD;
  &#xD;
            -  Unregulated hypertension (high blood pressure of 160 mmHg in the condenser or high&#xD;
               blood pressure exceeding 100 mmHg in the relaxation period)&#xD;
  &#xD;
            -  Unregulated diabetes (fasting blood sugar (FBS) exceeding 180 mg/dL)&#xD;
  &#xD;
            -  Hepatitis A (active) or hepatitis B (active) or hepatitis C&#xD;
  &#xD;
            -  History of hypersensitivity reaction to active ingredients or excipients of the&#xD;
               investigational product&#xD;
  &#xD;
            -  History of excessive alcohol use or drug addiction&#xD;
  &#xD;
            -  Pregnant or lactating women&#xD;
  &#xD;
            -  Those who did not agree to use contraception by medically permitted methods (e.g.,&#xD;
               surgical treatment of infertility, intrauterine device, condom or diaphragm, and&#xD;
               injectable or insertable contraceptives) during the period from dosing of the&#xD;
               investigational product to 90 days after the clinical study, among female subjects of&#xD;
               childbearing potential and male subjects with the female partner&#xD;
  &#xD;
            -  Those who had experience of participating in a different clinical study within 4 weeks&#xD;
               prior to participation in this clinical study&#xD;
  &#xD;
            -  Subjects who were determined to be ineligible to participate in this study&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>19 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Chan-Sik Kim, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Korea Institute of Oriental Medicine</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Yee Ran Lyu, PhD</last_name>
      <phone>82-10-9904-8049</phone>
      <email>onedoctor2ran@kiom.re.kr</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Chan-Sik Kim, PhD</last_name>
      <phone>82-10-3018-0213</phone>
      <email>chskim@kiom.re.kr</email>
    </overall_contact_backup>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 23, 2023</study_first_submitted>
    <study_first_submitted_qc>August 23, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 29, 2023</study_first_posted>
    <last_update_submitted>September 7, 2023</last_update_submitted>
    <last_update_submitted_qc>September 7, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 11, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor-Investigator</responsible_party_type>
      <investigator_affiliation>Korea Institute of Oriental Medicine</investigator_affiliation>
      <investigator_full_name>Chan-Sik Kim</investigator_full_name>
      <investigator_title>Principal 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>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </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/NCT06016010
  org study id: KIOM_2301_DED_USL
  nct id: NCT06016010
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The objective is to compare the USL and placebo in terms of efficacy and safety, and to
        determine the appropriate dosage.
  This study is a phase 2, dose-finding, double-blind, randomized placebo-controlled trial of
        two different doses of USL compared with placebo. A total of 120 patients, aged over 19
        years, with Corneal staining score(Oxford grading) ≥ 2 or TBUT < 10 sec and OSDI ≥ 10 points
        will be recruited at Daejeon University Daejeon Korean Medicine Hospital. Patients will take
        medications two times daily for 12 weeks, with 5 visiting days(screening, week 0, week 6,
        week 12, week 14).
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Triple (Participant, Investigator, Outcomes Assessor)
  measure: TBUT(Tear break-up time)
  time frame: Screening, 6 week, 12 week, 14 week
  description: The tear break-up time test measures the time in seconds. The time is from the last blinking to the point of tear layer defect or streak-like defect after blinking the eye with 1% of fluorescein.
  10 seconds or more as normal, between 5 and 10 seconds as mild dry eye syndrome, and 5 seconds or less as severe dry eye syndrome.
  measure: OSDI(Ocular Surface Disease Index)
  time frame: Screening, 6 week, 12 week, 14 week
  description: The Ocular Surface Disease Index consisted of 12 questions each of which included visual symptoms, visual work status, and environmental factors.
  The Ocular Surface Disease Index scores are ranged from 0 to 100, and the high score is the more severe the symptoms. The Ocular Surface Disease Index score is calculated as follows.
  : (Sum of all items answered × 25) / total number of questions answered
  measure: VAS(Visual analog scale)
  time frame: 0 week, 6 week, 12 week, 14 week
  description: The Visual Analog Scale(VAS) score is 0 point for no symptom, 10 points for the most severe symptom, and the patient is asked to mark the degree of subjective pain symptoms as an integer.
  measure: Schirmer's test
  time frame: 0 week, 6 week, 12 week, 14 week
  description: The eyes were wiped and the Schirmer test paper was inserted into the right eye at 1/3 of the lower eyelid without eye anesthesia and inserted into the left eye. After 5 minutes with the eyes closed, the Schirmer test paper was removed from the right side in the order of insertion and the left side removed. The wet length was measured in millimeters and the length of the midpoint was measured when the wet border was oblique.
  measure: Meibomian gland test
  time frame: 0 week, 6 week, 12 week, 14 week
  description: By expression of eyelid, scoring of expressibility and quality of meibum will be tested. Form of secretion predominantly secreted by the eight meibomian glands in the center of the lid was evaluated as follows. grade 0, clear meibum is easily expressed; grade 1, cloudy meibum is expressed with mild pressure; grade 2, cloudy meibum is expressed with more than moderate pressure; and grade 3, meibum cannot be expressed even with the hard pressure. Higher score means a worst outcome.
  measure: Fluorescein corneal staining score - Oxford grading
  time frame: Screening, 6 week, 12 week, 14 week
  description: The degree of corneal inflammation is scored (total of 5 points) according to the Oxford grading scale from 0 (no staining, A) to 5 (severe, confluent staining, >E).
  measure: SPEED-II (Standard Patient Evaluation for Eye Dryness-II)
  time frame: 0 week, 6 week, 12 week, 14 week
  description: The SPEED questionnaire was designed in order to quickly track the progression of dry eye symptoms over time. This questionnaire gives a score from 0 to 28 that is the result of 8 items that assess frequency and severity of symptoms. The symptoms assessed include dryness, grittiness, scratchiness, irritation, burning, watering, soreness, and eye fatigue. The questionnaire further assesses whether these symptoms were not problematic, tolerable, uncomfortable, bothersome, or intolerable.
  measure: Biomarkers
  time frame: 0 week, 12 week
  description: The levels of IL-1β, IFN-γ, TNF-α
  arm group label: Standard-dose USL group
  arm group type: Experimental
  description: 2 tablets(1 USL, 1 placebo) b.i.d for 12 weeks
  arm group label: High-dose USL group
  arm group type: Experimental
  description: 2 tablets(2 USL) b.i.d for 12 weeks
  arm group label: Placebo group
  arm group type: Placebo Comparator
  description: 2 tablets(2 placebo) b.i.d for 12 weeks
  intervention type: Drug
  intervention name: USL
  description: 500mg of Achyranthis Radix Extract
  arm group label: High-dose USL group
  arm group label: Standard-dose USL group
  intervention type: Drug
  intervention name: USL Placebo
  description: USL Placebo
  arm group label: Placebo group
  arm group label: Standard-dose USL group
  criteria: 
  gender: All
  minimum age: 19 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Chan-Sik Kim, PhD
  role: Principal Investigator
  affiliation: Korea Institute of Oriental Medicine
  last name: Yee Ran Lyu, PhD
  phone: 82-10-9904-8049
  email: onedoctor2ran@kiom.re.kr
  last name: Chan-Sik Kim, PhD
  phone: 82-10-3018-0213
  email: chskim@kiom.re.kr
  responsible party type: Sponsor-Investigator
  investigator affiliation: Korea Institute of Oriental Medicine
  investigator full name: Chan-Sik Kim
  investigator title: Principal Investigator
  mesh term: Dry Eye Syndromes
  mesh term: Keratoconjunctivitis Sicca
  mesh term: Eye Diseases
  sharing ipd: No