<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/NCT04421300</url>
  </required_header>
  <id_info>
    <org_study_id>2020KYPJ010</org_study_id>
    <nct_id>NCT04421300</nct_id>
  </id_info>
  <brief_title>A Randomized Study of Smile Exercise for Dry Eye</brief_title>
  <official_title>Clinical Efficacy of Smile Exercise Versus 0.1% Hyaluronic Acid Sodium Eye Drops for Dry Eye Symptoms in Patients With Dry Eye Disease: a Randomized, Controlled, Non-inferiority Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Zhongshan Ophthalmic Center, Sun Yat-sen University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Zhongshan Ophthalmic Center, Sun Yat-sen University</source>
  <oversight_info>
    <has_dmc>Yes</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 of the study is to evaluate the effectiveness of laughter therapy in relieving&#xD;
      the symptoms of dry eye disease.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study is designed to: Test the hypothesis that smile exercise is an effective treatment&#xD;
      for Dry Eye Disease (DED) . Better understand the status of emotion, quality of sleep and&#xD;
      life in DED patient by describing and evaluating a comprehensive set of features and&#xD;
      treatment over 2 months of observation in a well-characterized group of patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Enrolling by invitation</last_known_status>
  <start_date type="Actual">July 2, 2020</start_date>
  <completion_date type="Anticipated">March 30, 2021</completion_date>
  <primary_completion_date type="Anticipated">December 30, 2020</primary_completion_date>
  <phase>N/A</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>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change of Ocular Surface Disease Index (OSDI) Score</measure>
    <time_frame>12 weeks</time_frame>
    <description>OSDI scores from 1, 2, 4, 6, 8, 10 and 12 weeks minus values from baseline. OSDI scores range from 0 to 100, score 0 indicating no ocular discomfort and higher scores indicating greater symptom severity. The minimal clinically significant change is 10 points.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion of Participants with 10 Points or More Decreased in OSDI</measure>
    <time_frame>12 weeks</time_frame>
    <description>Proportion of participants with at least 10 points decreased from baseline in Ocular Surface Disease Index (OSDI).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in Lipid layer thickness (LLT)</measure>
    <time_frame>12 weeks</time_frame>
    <description>LLT from 1, 2, 4, 6, 8, 10 and 12 weeks minus values from baseline among eyes that qualified for the study. The interferometer LLT measurement is a non-invasively and objectively method that produces numeric value. The range of the value is 0-100+; lower value indicates thinner lipid layer.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Non-invasive Tear film breakup time (NI-BUT)</measure>
    <time_frame>12 weeks</time_frame>
    <description>In this measurement, NI-BUT is measured using the keratography machine. NI-BUT is recorded as the number of seconds that elapse between the last blink and the appearance of the first dry spot in the tear film. Change is record as the values at 1, 2, 4, 6, 8, 10 and 12 weeks minus values at baseline visit. Possible range of score is 0-&gt;20. Lower values indicate greater severity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Tear Meniscus Height (TMH) by Keratography</measure>
    <time_frame>12 weeks</time_frame>
    <description>Assessment of the tear film meniscus is a quantitative measurement of tear film quantity. In this measurement, TMH is measured using the keratography machine. Change is the values at 1, 2, 4, 6, 8, 10 and 12 weeks minus values at baseline visit.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Corneal Fluorescein Staining Score</measure>
    <time_frame>12 weeks</time_frame>
    <description>Corneal Flourescein Staining Score from 1, 2, 4, 6, 8, 10 and 12 weeks minus values from baseline visit among eyes that quality that qualified for the study. Possible range of scores is 0-15; higher scores indicate more severe.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Self-Rating Anxiety Scale (SAS)</measure>
    <time_frame>12 weeks</time_frame>
    <description>Medical Outcomes from study 20-Item Self-Rating Anxiety Scale. This scale range is 0-100 with lower scores indicating better self-reported mental health. Change is the score at 4, 8 and 12 weeks minus the score at baseline visit.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Self-Rating Depression Scale (SDS)</measure>
    <time_frame>12 weeks</time_frame>
    <description>Medical Outcomes from study 20--Item Self-Rating Depression Scale. This scale range is 0-100 with lower scores indicating better self-reported mental health. Change is the score at 4, 8 and 12 weeks minus the score at baseline visit.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Subjective Happiness Scale</measure>
    <time_frame>12 weeks</time_frame>
    <description>A 4-item scale designed to measure subjective happiness. Each of item is completed by choosing one of 7 options that finish a given sentence fragment. Change is the score at 4, 8 and 12 weeks minus the score at baseline visit.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Pittsburgh Sleep Quality Index (PSQI)</measure>
    <time_frame>12 weeks</time_frame>
    <description>Change is the score at 4, 8 and 12 weeks minus the score at the baseline visits. Scores for each question range from 0 to 3, and the total PSQI scores range from 0 to 100.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in SF-36 Physical Health Subscale</measure>
    <time_frame>12 weeks</time_frame>
    <description>Medical Outcomes from study 36-Item Short Form Health Survey (SF-36) Physical Health Subscale. Subscale range is 0-100, with higher scores indicating better self-reported physical health-related quality of life. Change is the score at 4, 8 and 12 weeks minus the score at baseline visit.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in SF-36 Mental Health Subscale</measure>
    <time_frame>12 weeks</time_frame>
    <description>Medical Outcomes from study 36-Item Short Form Health Survey (SF-36) Mental Health Subscale. Change is the score at 4, 8 and 12 weeks minus the score at baseline visit.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Change in Tear Cytokine Level</measure>
    <time_frame>12 weeks</time_frame>
    <description>Change in levels of tear cytokines (mainly in inflammation cytokines, such as iL-17, TNF-alpha, etc.,). Change is the values from 8 and 12 weeks minus the the score at baseline visit.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in Lid Margin Abnormalities</measure>
    <time_frame>12 weeks</time_frame>
    <description>Lid margin abnormalities were scored from 0 to 4 Change in lid margin abnormalities is the score from 4, 8 and 12 weeks minus the score at baseline visit.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in Meibum Quality</measure>
    <time_frame>12 weeks</time_frame>
    <description>To evaluate meibum quality,five glands of the central part of the upper lid were assessed on a scale of 0-3 for each gland (total score range, 0-15).Change is the total score from 4, 8 and 12 weeks minus the score at baseline visit.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in Meibomian Gland Expressibility</measure>
    <time_frame>12 weeks</time_frame>
    <description>The score of meibomian gland expressibility is range from 0-3. Change is the total score from 4, 8 and 12 weeks minus the score at baseline visit.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in Tear Film Break up Time, in Seconds (fluorescein staining)</measure>
    <time_frame>12 weeks</time_frame>
    <description>Tear film break up time from1, 2, 4, 6, 8, 10 and 12 weeks minus values from baseline visit.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in Meibomian gland structure by Keratography</measure>
    <time_frame>12 weeks</time_frame>
    <description>Change in Meibomian gland structure measured using the keratography machine. Change is the score from 8 and 12 weeks minus the values at baseline visit</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">296</enrollment>
  <condition>Dry Eye</condition>
  <condition>Keratoconjunctivitis Sicca</condition>
  <condition>Eye Diseases</condition>
  <condition>Corneal Diseases</condition>
  <condition>Conjunctival Diseases</condition>
  <arm_group>
    <arm_group_label>smile exercise</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>smile exercise, 4 times a day，8 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>0.1% Sodium Hyaluronate Eye Drops</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>0.1% sodium hyaluronate, 4 times a day, 8 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>smile exercise</intervention_name>
    <description>Launch the &quot;smile face recognition&quot; APP on smart phone, after user guidance and pretest, a smile exercise will display on the phone, while facing the front camera on the phone, participant will do an exercise emphasizing facial movements, as exaggerated as possible. The exercise last for 8 weeks and 4 times a day</description>
    <arm_group_label>smile exercise</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>0.1% sodium hyaluronate eye drop</intervention_name>
    <description>0.1% sodium hyaluronate, 4 times a day, the time is in the morning, lunchtime, afternoon and evening. the interval between two training time is 2 hours, 1 hour before and after can be added or subtracted by users, 8 weeks.</description>
    <arm_group_label>0.1% Sodium Hyaluronate Eye Drops</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Sign the informed consent approved by the Ethics Committee,&#xD;
&#xD;
          2. 18 to 45 years of age,&#xD;
&#xD;
          3. Meetting the dry eye diagnostic criteria of DEWs Ⅱ and demonstrating the following 2&#xD;
             condition in the same eye at screening and baseline visits (Same signs must present at&#xD;
             both in Screening visit and Baseline visit). The same signs must be present in the&#xD;
             same eye on both visits. The following parameters:.&#xD;
&#xD;
               -  Ocular Surface Disease Index (OSDI) score: 18-80 at and baseline visit.&#xD;
&#xD;
               -  Tear film break up time (TFBUT)&lt;8s.&#xD;
&#xD;
          4. Best corrected visual acuity ≥10/20 in each eye&#xD;
&#xD;
          5. Intraocular pressure (IOP) ≥5mmHg and≤21mmHg in each eye&#xD;
&#xD;
          6. Women of child-bearing potential must agree to use a reliable method of contraception&#xD;
             during study participation and must demonstrate a negative urine pregnancy test at the&#xD;
             Screening Visit.&#xD;
&#xD;
          7. Feasible for all visits and willing to follow instructions from the study&#xD;
             investigator.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Corneal fluorescein staining present &gt;5 score.&#xD;
&#xD;
          2. Contact lens wearing history:&#xD;
&#xD;
               -  Used contact lenses within last 14 days prior to the Screening Visit.&#xD;
&#xD;
               -  Unwilling to avoid using contact lenses druing the study.&#xD;
&#xD;
          3. Any corneal surgery within 12 months before Screening Visit .&#xD;
&#xD;
          4. Participation in other medical studies 3 months before screening Visit.&#xD;
&#xD;
          5. Current or previous diagnosis of any following ocular conditions in 3 months:&#xD;
&#xD;
             i). acute allergic conjunctivitis ii). infection (e.g. bacterial, viral, protozoan or&#xD;
             fungal infection of the cornea, conjunctiva, lacrimal gland, lacrimal sac or eyelids)&#xD;
             iii). inflammation (e.g., retinitis, macular inflammation, choroiditis, uveitis,&#xD;
             scleritis, episcleritis, keratitis)&#xD;
&#xD;
          6. Eyelid abnormalities that affect lid function (e.g. lagophthalmos, blepharospasm,&#xD;
             ectropion, entropion, severe trichiasis, etc.)&#xD;
&#xD;
          7. Extensive ocular surface scarring or condition that may compromise ocular surface&#xD;
             integrity such as Stevens-Johnson syndrome, prior chemical burn, recurrent corneal&#xD;
             erosions, persistent corneal epithelial defects, prior ocular trauma, etc.)&#xD;
&#xD;
          8. Currently diagnosis of glaucoma and under glaucoma medication or surgery treatment&#xD;
&#xD;
          9. Currently using, or intent to have any specific treatments for dry eye disease&#xD;
&#xD;
         10. Fluorescein sodium allergy&#xD;
&#xD;
         11. Pregnant, nursing, or lactating&#xD;
&#xD;
         12. Neurological or psychiatric disorders (moderate anxiety, depression and sleep&#xD;
             disorders)&#xD;
&#xD;
         13. Uncontrolled ocular or systemic diseases&#xD;
&#xD;
         14. History of epilepsy .&#xD;
&#xD;
         15. The researchers did not consider the patient is appropriate for inclusion in this&#xD;
             study&#xD;
&#xD;
         16. Cognitive or psychiatric defect that precludes informed consent or ability to perform&#xD;
             requirements in the investigation.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Zhonshan Ophthalmic Centre</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>June 1, 2020</study_first_submitted>
  <study_first_submitted_qc>June 4, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>July 22, 2020</last_update_submitted>
  <last_update_submitted_qc>July 22, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 24, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </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>
    <mesh_term>Keratoconjunctivitis</mesh_term>
    <mesh_term>Corneal Diseases</mesh_term>
    <mesh_term>Conjunctival Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ophthalmic Solutions</mesh_term>
    <mesh_term>Hyaluronic Acid</mesh_term>
  </intervention_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/NCT04421300
org study id: 2020KYPJ010
nct id: NCT04421300
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The objective of the study is to evaluate the effectiveness of laughter therapy in relieving
      the symptoms of dry eye disease.
The study is designed to: Test the hypothesis that smile exercise is an effective treatment
      for Dry Eye Disease (DED) . Better understand the status of emotion, quality of sleep and
      life in DED patient by describing and evaluating a comprehensive set of features and
      treatment over 2 months of observation in a well-characterized group of patients.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Change of Ocular Surface Disease Index (OSDI) Score
time frame: 12 weeks
description: OSDI scores from 1, 2, 4, 6, 8, 10 and 12 weeks minus values from baseline. OSDI scores range from 0 to 100, score 0 indicating no ocular discomfort and higher scores indicating greater symptom severity. The minimal clinically significant change is 10 points.
measure: Proportion of Participants with 10 Points or More Decreased in OSDI
time frame: 12 weeks
description: Proportion of participants with at least 10 points decreased from baseline in Ocular Surface Disease Index (OSDI).
measure: Change from Baseline in Lipid layer thickness (LLT)
time frame: 12 weeks
description: LLT from 1, 2, 4, 6, 8, 10 and 12 weeks minus values from baseline among eyes that qualified for the study. The interferometer LLT measurement is a non-invasively and objectively method that produces numeric value. The range of the value is 0-100+; lower value indicates thinner lipid layer.
measure: Change in Non-invasive Tear film breakup time (NI-BUT)
time frame: 12 weeks
description: In this measurement, NI-BUT is measured using the keratography machine. NI-BUT is recorded as the number of seconds that elapse between the last blink and the appearance of the first dry spot in the tear film. Change is record as the values at 1, 2, 4, 6, 8, 10 and 12 weeks minus values at baseline visit. Possible range of score is 0->20. Lower values indicate greater severity.
measure: Change in Tear Meniscus Height (TMH) by Keratography
time frame: 12 weeks
description: Assessment of the tear film meniscus is a quantitative measurement of tear film quantity. In this measurement, TMH is measured using the keratography machine. Change is the values at 1, 2, 4, 6, 8, 10 and 12 weeks minus values at baseline visit.
measure: Change in Corneal Fluorescein Staining Score
time frame: 12 weeks
description: Corneal Flourescein Staining Score from 1, 2, 4, 6, 8, 10 and 12 weeks minus values from baseline visit among eyes that quality that qualified for the study. Possible range of scores is 0-15; higher scores indicate more severe.
measure: Change in Self-Rating Anxiety Scale (SAS)
time frame: 12 weeks
description: Medical Outcomes from study 20-Item Self-Rating Anxiety Scale. This scale range is 0-100 with lower scores indicating better self-reported mental health. Change is the score at 4, 8 and 12 weeks minus the score at baseline visit.
measure: Change in Self-Rating Depression Scale (SDS)
time frame: 12 weeks
description: Medical Outcomes from study 20--Item Self-Rating Depression Scale. This scale range is 0-100 with lower scores indicating better self-reported mental health. Change is the score at 4, 8 and 12 weeks minus the score at baseline visit.
measure: Change in Subjective Happiness Scale
time frame: 12 weeks
description: A 4-item scale designed to measure subjective happiness. Each of item is completed by choosing one of 7 options that finish a given sentence fragment. Change is the score at 4, 8 and 12 weeks minus the score at baseline visit.
measure: Change in Pittsburgh Sleep Quality Index (PSQI)
time frame: 12 weeks
description: Change is the score at 4, 8 and 12 weeks minus the score at the baseline visits. Scores for each question range from 0 to 3, and the total PSQI scores range from 0 to 100.
measure: Change in SF-36 Physical Health Subscale
time frame: 12 weeks
description: Medical Outcomes from study 36-Item Short Form Health Survey (SF-36) Physical Health Subscale. Subscale range is 0-100, with higher scores indicating better self-reported physical health-related quality of life. Change is the score at 4, 8 and 12 weeks minus the score at baseline visit.
measure: Change in SF-36 Mental Health Subscale
time frame: 12 weeks
description: Medical Outcomes from study 36-Item Short Form Health Survey (SF-36) Mental Health Subscale. Change is the score at 4, 8 and 12 weeks minus the score at baseline visit.
measure: Change in Tear Cytokine Level
time frame: 12 weeks
description: Change in levels of tear cytokines (mainly in inflammation cytokines, such as iL-17, TNF-alpha, etc.,). Change is the values from 8 and 12 weeks minus the the score at baseline visit.
measure: Change in Lid Margin Abnormalities
time frame: 12 weeks
description: Lid margin abnormalities were scored from 0 to 4 Change in lid margin abnormalities is the score from 4, 8 and 12 weeks minus the score at baseline visit.
measure: Change in Meibum Quality
time frame: 12 weeks
description: To evaluate meibum quality,five glands of the central part of the upper lid were assessed on a scale of 0-3 for each gland (total score range, 0-15).Change is the total score from 4, 8 and 12 weeks minus the score at baseline visit.
measure: Change in Meibomian Gland Expressibility
time frame: 12 weeks
description: The score of meibomian gland expressibility is range from 0-3. Change is the total score from 4, 8 and 12 weeks minus the score at baseline visit.
measure: Change in Tear Film Break up Time, in Seconds (fluorescein staining)
time frame: 12 weeks
description: Tear film break up time from1, 2, 4, 6, 8, 10 and 12 weeks minus values from baseline visit.
measure: Change in Meibomian gland structure by Keratography
time frame: 12 weeks
description: Change in Meibomian gland structure measured using the keratography machine. Change is the score from 8 and 12 weeks minus the values at baseline visit
arm group label: smile exercise
arm group type: Experimental
description: smile exercise, 4 times a day，8 weeks
arm group label: 0.1% Sodium Hyaluronate Eye Drops
arm group type: Active Comparator
description: 0.1% sodium hyaluronate, 4 times a day, 8 weeks.
intervention type: Behavioral
intervention name: smile exercise
description: Launch the "smile face recognition" APP on smart phone, after user guidance and pretest, a smile exercise will display on the phone, while facing the front camera on the phone, participant will do an exercise emphasizing facial movements, as exaggerated as possible. The exercise last for 8 weeks and 4 times a day
arm group label: smile exercise
intervention type: Drug
intervention name: 0.1% sodium hyaluronate eye drop
description: 0.1% sodium hyaluronate, 4 times a day, the time is in the morning, lunchtime, afternoon and evening. the interval between two training time is 2 hours, 1 hour before and after can be added or subtracted by users, 8 weeks.
arm group label: 0.1% Sodium Hyaluronate Eye Drops
criteria: 
gender: All
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: China
responsible party type: Sponsor
mesh term: Dry Eye Syndromes
mesh term: Keratoconjunctivitis Sicca
mesh term: Eye Diseases
mesh term: Keratoconjunctivitis
mesh term: Corneal Diseases
mesh term: Conjunctival Diseases
mesh term: Ophthalmic Solutions
mesh term: Hyaluronic Acid
sharing ipd: No